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NEET
Concepts
Volume 01 Anatomy Physiology Biochemistry DADH
HUMAN ANATOMY Scalp
SCALP
Soft tissues covering cranial vault EXTENT Lateral: temporal lines Anterior: eyebrows-superior orbital margins Posterior: superior nuchal line Layers S: Skin C: (dense) Connective tissue A: Aponeurosis/ Glea aponeurtica L: Loose areolar connective tissue Thin skin Contents with sweat and Sebaceous cysts sebaceous glands Thin layer of fat and fibrous tissue in form of locules with blood vessels and nerves (with its walls attached to its fibrous walls) Aponeurosis tendon of epicranial is fleshly muscle membranous, bellies (formed of by Injury (horizontal) leads to gapping of wound by contraction of fronto-occipitalis Injury blood vessels walls non-collapsible very painful Applied anatomy
severe bleeding, inflammation
occipitalis and frontalis muscles, each with two bellies) Layer provides an easy plane of separation between the upper three layers and the Pericranium "Danger Zone" because of the ease by which infectious agents can spread through it to emissary veins which then drain into the cranium. It contains the major blood vessels of the scalp. Safety-valve hematoma-fracture of the skull with tear of dura, signs of cerebral compression do not develop until this space is filled with blood.
P: Pericranium
Periosteum of the skull bones (continuous with endocranium at sutural lines)
Cephalohaematoma / traumatic cephalohydrocele takes shape of related bone
BLOOD SUPPLY
Location
Arteries Supratrochlear Artery
Branches of INTERNAL CAROTID
Anterior to auricle
Supraorbital Artery Superficial Temporal Artery Posterior Auricular Artery EXTERNAL CAROTID
Posterior to auricle Occipital Artery
BRIHASPATHI ACADEMY SUBSCRIBERS COPY NOT FOR SALE
HUMAN ANATOMY Scalp VENOUS DRAINAGE Location Veins Supratrochlear vein Supraorbital Superficial Temporal vein; join Drain into Join to form Angular vein, continue as Facial with anterior division of Retromandibular vein Internal jugular vein Join Join Posterior Auricular Posterior to auricle Occipital vein with with maxillary posterior vein, division forms of Retromandibular vein Retromandibular vein Sub clavian vein External jugular common facial vein
Anterior to auricle
Joins Sub-occipital venous plexus
NERVE SUPPLY - "Z-GLASS" Location Nature Nerves Supratrochlear Ophthalmic division of the Trigeminal nerve Anterior to auricle Supraorbital Sensory Zygomatico temporal Auriculo temporal Motor Temporal Greater Auricular Posterior to auricle Lesser occipital Sensory Greater occipital Third occipital Motor LYMPHATIC DRAINAGE Anterior to Auricle: Pre-auricular/Superficial parotid node Posterior to Auricle: Post auricular/Mastoid and Occipital nodes Posterior auricular C2-Cervical Plexus C3-Cervical Plexus Facial Maxillary division of the Trigeminal nerve Mandibular division of the Trigeminal nerve Facial nerve C2, C3-Cervical Plexus C2 -Cervical Plexus Branches of
PHYSIOLOGY General Physiology
GENERAL PHYSIOLOGY
INTRODUCTION The cell is the smallest structural and functional unit of the body Integrated functioning of about 100 trillion cells forms human body These cells are organized into different organs which in turn are combined to form system. For better understanding human body can be considered to be functionally organized into various systems like: 1. 2. 3. 4. Skin and its appendages: Skin, Hair, Nails, Sebaceous glands, Sweat glands Skeletal system: Bone, Cartilage, Joints, Ligaments Muscular system: Skeletal muscles, Smooth muscles, Cardiac muscles Nervous system: Central Nervous system Brain Spinal Cord
5.
Cardiovascular system: Heart Arteries Arterioles Capillaries Blood Vessels Veins Small venules Sinusoids
6.
Respiratory system: Lungs Airway: Nasal cavity Pharynx Bronchioles Trachea Alveoli Larynx Bronchi
7.
Digestive system: Starts at mouth and ends at anus Oral cavity, pharynx, esophagus, stomach, intestine Also includes liver and gall bladder and pancreas small intestine, large
8.
Excretory system: Excretion is not egestion Involves kidney, ureter, bladder and urethra
Peripheral Nervous system
9.
Reproductive system: Male reproductive system Epididymis, Seminal urethra, Penis Female reproductive system Right and left ovaries, Uterine tubules, Uterus, Vagina, External genitalia, Mammary glands Ductus vesicles, Prostate, Testis, deferens, Male
Cerebrospinal Nerves Supplies Body wall and Limbs
Autonomic Nervous System
10. Endocrine system: Pituitary Sympathetic Parasympathetic Suprarenal glands, Pineal glands, of Thyroid glands, Parathyroid glands, glands, Islet Langerhans, Interstitial cells of the Supplies Viscera (Organs) testis, Follicles and corpora lutea of the ovaries, Some cells of the kidneys, thymus and the placenta 11. Blood and Immune system
PHYSIOLOGY General Physiology BODY COMPOSITION In an average adult male Water (60%) Minerals (7%) Proteins and related substances (18%) Fat (15%) Measurement of body fluid volumes
Theoretically measured using formula A1 A2 = V = Volume of fluid compartment A1 = Area of indicator injected in the fluid A2 = Area of indicator and removed by excretion of metabolism C = Concentration of indicators in the fluid Most abundant Cation Most abundant Anion Na+ K+ (Mg2+) Cl- (HCO3-) Proteins (PO3-4)
Total Body Water TBW (60 % of body weight) Intracellular fluid (2/3rd of TBW) 40% of body wt Extracellular fluid (1/3rd of TBW) 20% of body wt Interstitial fluid (5% of body wt) (25% of ECF) Plasma (75% of body wt) (15% of ECF) Lymph CSF ECF ICF
+ = +
VOLUMES TBW
MEASUREMENT By dilution principle; used to measure other body spaces D2O (heavy water) is most frequently used Tritium oxide and amino pyrine are also used (Mn: DAT) Most accurate method is by using Inulin, Mannitol and sucrose have also been used TBW ECF (Mn: SIM) ECF Plasma volume By dyes that become bound to plasma protein Ex: Evan blue (T-1824) Serum Albumin labeled with radioactive iodine, I126, Na22, Thio sulfate
ECF ICF (cannot be measured directly) Interstitial fluid volume (can not be measured) Plasma Volume Mn: PEA Total blood volume (TBV)
Plasma Vol Pl. V x
TBV Pl. V Red cell volume Measured by injecting tagged RBCs and measuring the fraction of red cells that is tagged. Commonly used tag is Ca51 and Fe59, P32
PHYSIOLOGY General Physiology BODY ELECTROLYTES 7% of total body weight Ionic concentration in ECF and ICF
Total percentage ION ICF (mMol/L) ECF (mMol/L) available exchange cell membrane Na+ K+ H+ ClHCO3Anions (proteins) PO4 12 155 13 x 10 -5 3.8 8 155 145 4 3.8 x 10 -5 120 27 0 Non exchangeable 65 70% 100% for across
because all the body cells depends on ECF for maintenance of cellular life. Homeostasis is a term introduced by W.B Cannon, refers to the mechanism by which the constancy of the internal environment is maintained and ensured. Cell membrane and vascular endothelium with varying permeability play an important role in maintenance of homeostasis. Factors involved in the maintenance of Internal Environment 1. 2. 3. 4. 5. Maintenance of pH of ECF (acid-base balance) Regulation of temperature Maintenance balance Supply of nutrients, oxygen, enzymes and hormones Removal of metabolic and other waste products All systems of the body play vital role in an integrated manner for the maintenance of internal environment Mode of action of Homeostatic control system of water and electrolytic
K+ Na+
Efflux Influx
along concentration and electrical gradient
High proteins in plasma than in interstitial fluid plays important role in maintaining fluid balance.
Ca2+
(predominant
in
ECF)
and
Mg2+
(predominant in ICF) are non exchangeable. Only exchangeable solutes are osmotically active. Functions of Electrolytes Electrolytes are main solutes in the body fluids for maintenance of acid base balance Electrolytes maintain the proper Adaptive control system osmolarity and volume of body fluids The concentration of certain electrolytes determines their specific physiological functions. Eg: The effect of calcium ions on neuromuscular excitability INTERNAL ENVIRONMENT AND HOMEOSTASIS Claude Bernarde (1949), the great French Physiologist, introduced the term Internal environment of the body or the Milieu interiew for the extra cellular fluid (ECF) of the body Feedback Mechanism 1. Negative feedback mechanism Most control systems of body act by this mechanism That is, in general if the activity of a particular system is increased or decreased a control system initiates a series of changes that returns the activity towards normal. Stabilizes homeostatic mechanism Is through Negative Positive Feedback mechanism
PHYSIOLOGY General Physiology Ex: 1. When the blood pressure suddenly rises or lowers, it initiates a series of reactions that tries to bring the BP to normal levels. 2. Other examples: ACTH secretion, aldosterone K+ glucose regulation, GH secretion. 2. Positive feedback mechanism It is better known as a Vicious circle Usually it is harmful and in some instances even death can occur due to positive feedback Destabilizes homeostatic mechanism Ex: 1. When a person has suddenly bled 2 liters of blood, a vicious circle of progressively weakening of the heart is set which ultimately cause death. If it of mild degree can be overcome by negative feedback mechanism. 2. Sometimes positive feedback can serve useful purposes. Ex: child birth (parturition) facilitated during by labour is progressively Ratio of proteins to lipids in CELL MEMBRANE CELL STRUCTURE
A typical cell as seen by the light microscope consists of three basic components Cell membrane Cytoplasm Nucleus
Cell membrane/plasma membrane is the protective sheath, enveloping the cell body It separates ECF from ICF It is a unit membrane consisting of two electron dense layers separated by an electro lucent layer Biochemically, cell membrane is mainly made up of Lipids (40%) Proteins (55 %) Carbohydrates (5 %) different
membranes Inner mitochondrial membrane 3.2 (max) Sarcoplasmic reticulum 2.0 Outer mitochondrial membrane Myelin 0.23 In almost all the membrane of the body proteins are equal or exceed the quantity of lipid. The only exception is Myelin (high lipid content provide good insulation) Two types of proteins are recognized 1. 2. Lipoproteins enzymes, ion channels Glycoproteins neurotransmitters receptors, 1.1
increasing uterine contractions due to positive feedback from stretching of cervix by head of the body. 3. Other examples: Clotting blood, Ca
2+
entry into sarcoplasmic reticulum, LH surge during ovulation, Milk ejection Shock Adaptive Control System This refers to a delayed type of negative feedback mechanism Seen in nervous system reflex, Action potential,
PHOSPHOLIPIDS
Along with Cholesterol Maintains membrane As membrane fluidity its permeability to water and small hydrophilic molecules increases fluidity of
Lipid rafts Dynamic exoplasmic cholesterol phospholipid Involved transduction in signal areas leaflets of of and Lipid
Caveolae rafts + specific in protein Cavedin-I Proteins detected of Caveolae form various components signal transduction system
lipid bilayer enriched in
PROTEINS
Integral/Transmembrane proteins They interact with the phospholipids and requires the use of detergents for their solubilisaiton Generally span the lipid bilayer Distributed asymmetrically across the lipid bilayer Are usually globular proteins On the basis of function they have been described as Channel proteins Carries proteins Receptor proteins Antigen Pumps
Peripheral proteins Are present embedded in either the inner or outer leaflet of the lipid bilayer and are respectively called as Intrinsic proteins or Extrinsic/Surface proteins They do not interact directly with the phospholipids in the bilayer and do not require use of detergents for their release They are weakly bound to the hydrophilic region of specific integral proteins
PHYSIOLOGY General Physiology Properties of Cell Membrane Membranes are asymmetrical shut like enclosed structures with distinct out and inner surface. This asymmetry is attributed to Irregular distribution of protein within the cell membrane External location of carbohydrate 3. attached to membrane protein Specific enzymes are located exclusively on the outside or inside of membranes Gap junction, synapses and tight local 2. Functions 1. Being negatively charged of
the cell
carbohydrate
molecules
the
membrane do not allow the negatively charged particles to move out of the cell The glycocalyx helps in tight fixation of the cells with one another Some of carbohydrates molecules also serve as receptors Arrangement of Lipid bilayer of the cell membrane Each lipid molecule in the lipid bilayer of the cell membrane consists of phospholipids, cholesterol and glycolipids. The lipid molecules are cloth pin shape and consists of a head and a tail end The head end/globular end of the molecules contains phosphate moiety radical of of phospholipid/hydroxyl water soluble (hydrophilic) The tail end consists of two chain of fatty acids/steroid radical of cholesterol. It is water insoluble and is hydrophobic These lipid molecules are arranged as bilayer in such a way that their non polar hydrophobic tail ends are directed towards the centre of membrane, where as their polar hydrophilic head ends are directed outwards on either sides of the membrane Functional significance of the Lipid bilayer 1. It is the major barrier for the water soluble molecules like electrolytes, urea and glucose 2. Fat soluble substance like O2 fatty acids and alcohol can pass through the membrane with ease
junctions occupy only smaller regions of membrane asymmetry The choline containing phospholipids (phosphotidylcholine and sphinomyelin) are located mainly in the outer molecular layer; The amino phospholipids (phosphotidyl serine and phosphotidylethanolamine) are preferentially located in inner leaflet Membranes are dynamic structures Major lipids in mammalian membranes are phospholipids, glycolipids and cholesterol. Membrane lipids are amphipathic i.e., contain both hydrophobic and hydrophilic regions Membrane lipids are bilayered Proteins are associated with lipid bilayer and may be integral or peripheral in location Ion channels are transmembrane proteins that allow selective entry of various ions; ionophores membrane are molecules for that various act as shuttle ions; and generate
cholesterol. It is positively charged and quite
aquaporins are proteins that form water channels in certain molecules. Arrangement of Carbohydrates in the cell membrane The carbohydrates are attached either to the proteins (glycoproteins) the cell or the lipids (glycolipids). Throughout membrane, carbohydrate molecules form a thin layer of loose covering called Glycocalyx
PHYSIOLOGY General Physiology CYTOPLASM An aqueous substance containing a variety of cell organelles and other structures In Eukaryotic cell, Nucleus and Cytoplasm together form Protoplasm Cytoplasm contains, 1. 2. 3. Organelles Inclusion bodies Cytoskeleton 1. enzymes Sl. No. 1 Mitochondria Endoplasmic reticulum 1. Rough ER/Granular ER 2 2. Characterized by presence of a number of ribosomes on its surface Ex: Russells bodies of plasma cells, Nissl granules of nerve cells and Acinar cells of pancreas Smooth endoplasmic reticulum/ Agranular ER Is devoid of ribosomes on its surface. In skeletal and cardiac muscle, it is modified as sarcoplasmic reticulum Golgi Apparatus 3 It is particularly well developed in exocrine glandular cells It is collection of membranous vesicles, sacs or tubules which is generally located close to nucleus Organelle Function Plays role as power generating unit ORGANELLES
Are permanent components of the cells, participates in cellular metabolic activity as they contain
May have role in synthesizing membrane bound proteins
It transports proteins made by the ribosomes through the cisternae
It is site of lipid and steroid synthesis found in abundance with Leydig cells and cells of adrenal cortex Synthesis of carbohydrates Packaging of proteins synthesized in the rough ER into vesicles Site of formation of lysosomal enzymes Transport of the material to the other parts of cell or to cell surface membrane and secretion Glycolysation glycoproteins of proteins to form
Ribosomes 4 Spherical particles with 80 to 85 % of cells RNA
The sites of protein synthesis They synthesize all transmembrane proteins, secreted proteins and most proteins are stored in Golgi apparatus, lysosomes and endosomes
PHYSIOLOGY General Physiology Sl. No. Lysosomes Are membrane bound organelles containing powerful lysosomal digestive enzymes They are formed by Golgi apparatus There are three forms of lysosomes 1. Primary lysosomes/storage vacuoles Formed various hydrolytic enzymes synthesized by rough 5 2. ER and packaged in the Golgi apparatus Secondary vacuoles Are formed by fusion of primary lysosomes components 3. Residual bodies Are undigestible materials in the lysosomes Peroxisome 6 Are known as microbodies Are predominantly present in 2. hepatocytes and tubular epithelial cells Centrosome 7 Consists of two 2. short cylindrical structures called centrioles These are temporary components of certain cells These may or may not be enclosed in the membrane Ex: Lipid droplets: seen in cells of adipose tissue, liver and adrenal cortex Glycogen: seen in the cells of liver and skeletal muscles Melanin pigment: seen in the cells of epidermis, retina and basal ganglia with parts out of cell damaged/worn lysosomes/autophagic Organelle Function
They essentially contain two types of enzymes 1. Oxidases: which are active in oxidation of lipids Catalases: which act on hydrogen peroxide to liberate oxygen
They are responsible in movement of chromosomes during cell division
CYTOPLASMIC INCLUSIONS
3. shape and move
CYTOSKELETON
This is a complex network of fibres that maintains the structures of the cell and allows it to change It primarily consists of microtubules, intermediate filaments and micro-filaments along with proteins which anchor and tie them together
Microtubules Are long hollow tubular structures with limiting membrane and are about 25 nm in diameter Kinesis and dynein known as molecular motors help in the movement of molecules through the microtubules The cilia and flagella which projects from surface of certain cells are also composed of microtubules enclosed in the plasma membrane and are active in the locomotion of the cells. Intermediate filaments Is about 10 nm diametric filamentous structures Main function of intermediate filament is to mechanically integrate the cell organelles within the cytoplasm In their absence, cell ruptures more easily When they are abnormal in human., blistering of the skin is common Microfilaments Are long solid filamentous structures of 6-8 nm diameter These are made up of contractile proteins actin and myosin Actin is the most abundant protein in the Mammalian cell Extension of microfilament along with plasma membrane on the surface of the cells form microvilli which increases the absorptive surface of the cells In skeletal muscle, are of contractile function
NUCLEUS Nucleus is present in all the eukaryotic cells It controls all the cellular activities including reproduction of the cell DNA replication occurs in nucleus Most are uninucleated cells except few like skeletal It muscle of cells Nuclear which are multinucleated cells consists Membrane, Nucleoplasm and Nucleolus 1. Nuclear membrane Double layered structure with 40-70 nm wide space in between called perinuclear cistern, which is continuous with the lumen of ER 2. Nucleoplasm Is Matrix gel like ground substances with large quantity of genetic material in the form of Deoxyribose Nucleic Acid (DNA) When cell is not dividing, nuceloplasm contains dark staining thread like material called chromatin, while cell division it is converted to rod shape structures, the chromosomes. All somatic cells contains 23 pairs/46 chromosomes while gamete cells (sex Exchange Nucleoplasm of and materials cytoplasm between occurs
through this membrane
PHYSIOLOGY General Physiology cells) contains only 23 (haploid) number of chromosomes Chromosomes composed of two G1 S G2 chromatids connected at the centre to form X configuration by centromere Chromosomes are composed of three components - DNA, RNA and Nuclear proteins 3. Nucleolus Nucleus may contain one or more nucleoli. They are the sites of synthesis of ribosomal RNA (r RNA). These are present mainly in cells activity synthesizing proteins and in growing cells CELL CYCLE The sequence of cell cycle is G0 phase quiescent cells are in Go phase or resting phase G1 phase (2 - 12 hrs): Presynthetic phase, Maximum part of cell cycle remain in G1 S phase (6-8 hrs): DNA synthesis phase G2 phase (4 - 5 hrs): Premitotic phase, Cytoplasmic enlargement; preparation for cell division, DNA repair can occur. M Phase (2 hrs): Mitotic phase, Stages of mitosis are Prophase Anaphase Telophase Metaphase Interphase Radiation injury to the cell If cells are irradiated in G1
10
Cells cycle arrest due to P53 occurs in late G2 phase Site a M G1 G0 Site b
Cell cycle regulators in cell growth: cyclins and kinases In block prior to G2 phase (Site a) by TGF will lead to increase in cell size (and thus cell hypertrophy). In block after mitosis (Site b) if cell not enters quiescent phase it leads to increase in number of cells (i.e., cell hyperplasia) Growth factors are most effective in G1 phase In Mitosis spindles are formed in late Prophase and chromosomes are attached to spindles in Metaphase In Meiosis crossing over and chiasmata formation in Pachytene stage of 1st meiotic division; Genetic shuffling occurs in 2nd meiotic division
phase,
chromosomal abnormally may result It cells are irradiated in G2 phase, chromatid aberration may result Cells are most radiosensitive in G2 - M interface and most resistant towards the end of S phase. Series of radio sensitivity M > G2 > G1 > S
The duration of cell cycle and its stages varies greatly between cell types The time taken for S, G2 and M phases are similar for most cell types, whereas the duration of G1 shows considerable variations
Drugs acting in various phases of cell cycle G1 Vinblastine S Doxorubicin, Methotrexate, Cytarabine, 6-TG, 6-MP, Hydroxyurea, Mitomycin C G2 Bleomycin, Etoposide, Daunorubicin, Topotecan M Vincristine and Vinblastine (breaks microtubules), Paclitaxel (stabilizes microtubules), Colchicines
Because
in
this
phase,
cells
are
not
committed to DNA replication, can enter resting state or progress to next cell division In mammals, because of the time required for a cell to progress of S-phase through mitosis from beginning is typically 12-24 hrs irrespective of duration of G1 phase; almost all the variation in proliferation rates are attributable to the amount of time spent in G1/G0 state.
PHYSIOLOGY General Physiology TRANSPORT ACROSS CELL MEMBRANE The physiological activity of a cell depends on the substances like nutrients, oxygen and water which must be transported into the cell and at the same time metabolic waste must be transported out of the cells 1. Various process of transport across 1. the gradient without membranes are Passive transport Is along expenditure of any energy It depends on physical factors like concentration gradient, electrical 2. gradient and pressure gradient Transport occurs along the gradient (down hill movement) Types i. Diffusion a. b. Simple diffusion Facilitated diffusion o o ii. 2. Osmosis Carrier mediated Uniport, Symport and Antiport 3. Vesicular transport 4. 3. 2. Types of Secondary Active Transport 1.
11
Co-transport carrier protein transports secondary substances in the direction of primary substances Counter transport carrier protein transports secondary substances in the opposite direction of primary substances
Examples Sodium Co-transport: substances carried are like glucose, aminoacids, chloride and iodine. Carrier protein acts as symport Sodium Counter transport: sodium ion is exchanged for some other substances like calcium, hydrogen, potassium, magnesium. Carrier protein acts as antiport. Calcium - Magnesium counter transport system Chloride - Bicarbonate counter transport system
This mechanism is involved in the Active transport Is transport of substances against the chemical and or electrical gradient with the expenditure of energy which is liberated by breakdown of high energy compounds like ATP Types i. Primary active transport o Energy is derived of directly by breakdown o Ex: pump ii. Secondary active transport o Energy is derived secondarily from the energy which has been stored in the form of ionic concentration difference between two sides of membranes, created in the first place by primary active transport sodium, high energy pump, i. transport of macromolecules such as large protein molecules which can neither pass through the cell membrane by diffusion nor by active transport mechanism Types Endocytosis o Process by which the substances is transported into the cell by in folding of cell membrane around the substances and internalizing it Sub Types Pinocytosis cell drinking for liquid substances. Ex: reabsorption by renal tubular epithelial cells Phagocytosis substances. mechanism Receptor cells mediated endocytosis. Ex: transport of iron and cholesterol into the cell eating Ex: In cell for solid defense
compounds (ATP) potassium calcium pump, potassium- hydrogen
PHYSIOLOGY General Physiology ii. Exocytosis o o Reverse of endocytosis. Ex: Release of hormones and = 61 log enzymes by secretory cells of the body occurs by exocytosis. o This process of exocytosis requires Ca2+ and energy along with docking proteins iii. Transcytosis o o Is vesicular transport within the cell Is also called cytopemisis Transport membrane o Ex: Ultra filtration MEMBRANE POTENTIAL Potential difference across the cell membrane of all living cells with the inside being negative in relation to the outside is named Membrane Potential Membrane potential is basically due to unequal distribution of ions across the cell membrane Factors involved in the genesis of membrane potential are Selective membrane Gibbs Donnan Equilibrium Nernst equation Constant field Goldman equation Sodium Potassium ATPase pump Equilibrium Potential Equilibrium potential of an ion is defined by Nernst equation. It is the membrane potential at which efflux and influx of the ions are equal Formula Ln Em = Equilibrium potential = R = Gas constant 8.316 Joules/degree T = Absolute temperature F = Faraday constant = 96,500 coulomb/mole Z = Valency of the ion
12
Ln = Logarithm symbol
Equilibrium potential for important ions in a mammalian spinal motor neuron Concentration Ion (in mmol/L of H2O) Outside cell 150 5.5 125 Inside cell 15 150 9
Equilibrium potential (in MV) + 60 - 90 - 70
iv. Other transport process o across epithelial Na+ K

+ -
Cl
permeability
of
the
cell
BIOCHEMISTRY Carbohydrates
CHEMISTRY OF CARBOHYDRATES
DEFINITION Carbohydrates are polyhydroxy aldehydes or polyhydroxy ketones or compounds that can be hydrolyzed into these compounds. General formula is CnH2nOn.. FUNCTIONS 1. 2. 3. 4. 5. Major source of energy in most organisms Serve as metabolic intermediates Constituents of nucleotides that form DNA & RNA Give structure to cell membranes & cell walls Play a role in immunity, joint lubrication & cell to cell communications
COMMON DISEASES associated with carbohydrates include diabetes mellitus, galactosemia, glycogen storage diseases and lactose intolerance. CLASSIFICATION OF CARBOHYDRATES A. SIMPLE ONLY CARBOHYDRATE MOIETY 1. Monosaccharides i. 2. 3. 4. Aldoses [glucose (6C), glycerose (3C), erythrose (4C), ribose (5C)] ii. Ketoses [fructose (6C), dihydroxyacetone (3C), erythrulose (4C), ribulose (5C)] Disaccharides (sucrose, maltose, lactose) Oligosaccharides (3-9 residues; Eg. raffinose, stachyose) Polysaccharides (>/= 10 residues; Homopolysaccharidesstarch, inulin, cellulose and Heteropolysaccharides- heparin, chondroitin sulphate) B. COMPLEX SUGAR + LIPID or PROTEIN MOIETY proteoglycan, glycoprotein, glycolipid
CARBON NUMBERING SYSTEM
BIOCHEMISTRY Carbohydrates HAWORTH (OPEN CHAIN) STRUCTURE OF CARBOHYDRATES
PYRANOSE RING STRUCTURES
FRUCTOSE STRUCTURE
ISOMERISM Same molecular formula but different physical or chemical properties 1. 2. 3. Optical Functional Stereoisomerism i. ii. iii. iv. Anomerism Epimerism Enantiomerism Diastereoisomerism Types
Optical isomerism Same molecular formula but differs in their physical property of turning the plane polarized light. d / + : dextrorotatory l / - : laevorotatory.
Stereoisomerism Same molecular formula but differs in spatial configuration of H & OH groups at penultima penultimate carbon atoms. OH on the right side- D form. EgEg D-glucose & OH on left side- L form. Eg- L-glucose. glucose.
Asymmetric carbon atom- C atom with 4 different groups attached to it.
No of isomers = 2n (n = no of asymmetric carbon atoms).
Epimerism Differ in orientation of H & OH groups around single C atom. Eg- Glu & Gal at C4, Glu & Mannose at C2. Anomerism Differ in orientation of H & OH groups around first C atom. Eg- - OH to the right of 1st C., glucose - OH to the right of 1st C., -glucose. GLYCOSIDES Sugar + Aglycone Phlorhizin- glucose + phloretin; renal damage Digitonin- glucose+ digitogenin; cardiac stimulant Ouabain- Na+-K+ ATPase inhibitor Amino sugars Glucosamine- in hyaluronic acid, heparin & blood group substances Galactosamine- in chondroitin of cartilage, bone & tendons Mannosamine, N-acetylated glucosamine & N-acetylated galactosamine- in glycoproteins Erythromycin- Diethyl amino sugar; antibiotic Deoxysugars L-fucose- 6-deoxy L-galactose - in blood group antigens Deoxyribose- in nucleic acid. Feulgen staining is specific for DNA PENTOSES D-Ribose- constituent of RNA, ATP & NAD Deoxyribose- in DNA D-Ribulose- in HMP shunt D-Xylose- in proteoglycans D-Lyxose- in heart muscle
KEY POINTS ABOUT GLUCOSE Aldo-sugar with 6 membered pyranose ring -D glucopyranose is the most common form C1 carbon is the anomeric carbon Ring closure occurs between C1 & C5 D-glucose is dextrorotatory Forms 16 stereoisomers Glucose is oxidized to gluconic acid, glucuronic acid & glucosaccharic acid Reduced to sorbitol (mechanism in diabetic cataract)
BIOCHEMISTRY Carbohydrates KEY POINTS ABOUT FRUCTOSE Keto-sugar with predominant furanose ring structure C2 carbon is the anomeric carbon. D-fructose is laevorotatory Forms 4 isomers It is a major constituent of honey Component of inulin
KEY POINTS ABOUT GALACTOSE Component of lactose Epimer of glucose at C4 Constituent of glycolipids & glycoproteins Oxidized to galactonic acid, galacturonic acid & mucic acid Reduced to dulcitol
KEY POINTS ABOUT MANNOSE Occurs in glycoproteins Epimer of glucose at C2
IMPORTANT POINTS ABOUT DISACCHARIDES Sucrose Lactose (1, 4) is sugar present in milk. Contains glucose & galactose Hedgehog or powder puff appearance of lactosazone crystals Digested by separate enzyme, lactase HOMOPOLYSACCHARIDES Structural Homopolysaccharides Cellulose made up of glucose residues linked by (1,4) linkages., so its not digestible in humans Inulin is a fructosan Chitin- the constituent of exoskeleton of crustaceans is made up of amino sugar N-acetyl glucosamine Storage Homopolysaccharides Starch- 2 components- amylose, unbranched form with (1, 4) linkages [300-400 glucose units] and amylopectin, highly branched with (1, 4) along straight lines and (1, 6) along branch points [each branch at interval of 24-30 glucose units]
(1, 2) is not reducing since both anomeric carbons of glucose & fructose are involved in glycosidic linkage It is called invert sugar as sucrose being dextrorotatory (+66.50) becomes laevorotatory (- 19.50 ) on hydrolysis Honey contains invert sugar (1, 4) contains 2 glucose units Forms sunflower shaped crystals of maltosazone (1, 6) contains 2 glucose units produced by partial digestion of glycogen and starch
Maltose
Isomaltose
BIOCHEMISTRY Carbohydrates Glycogen highly branched, formed on a protein core- glycogenin to which glucose molecules are attached with (1, 4) linkages along straight line & (1, 6) along branch points [each branch at interval of 12-18 glucose units]. Each branch has 11 residues & the whole molecule is arranged in 12 concentric circles. HETEROPOLYSACCHARIDES Mucopolysaccharides Features of glycosaminoglycans (GAG)GAG / Proteoglycans are composed of an uronic acid & amino sugar. Exception keratan sulphate doesnt have uronic acid, instead it has galactose. Normally, they prefer to have glucuronic acid & N-acetyl glucosamine. Exception- Iduronic acid in Heparin & Dermatan sulphates. Galactosamine in chondroitin & dermatan sulphate. COMPLEX POLYSACCHARIDES Proteoglycans It has a core protein, to which the GAGs (unbranched, repetitive units) are linked by O linkage. Exception is keratan sulfate type 1, which is N-linked and, hyaluronic acid is not linked to the core protein directly at all. All GAGs are sulfated so that they get a negative charge, but hyaluronic acid is not sulfated. Constituents of extracellular matrix providing negative charge which is important for basement membranes charge selectivity for proteins. Helps in morphogenesis and metastasis in cancer. Keratan sulfate is responsible for corneal transparency. Dermatan sulfate is responsible for shape of the cornea. Glycoproteins Glycosylated protein but the side chains are branched, non repetitive carbohydrate moietiescarbohydrates less than proteoglycans Eg- plasma proteins, Igs, hormones, enzymes, transport proteins etc It helps in maintaining receptor function, protein folding, determining protein solubility.\ Types- N-linked, O-linked & GPI anchored. GPI anchored glycoprotein- carboxy terminal of amino acid is linked to the carbohydrate chain, ethanolamine & inositol. Eg- Decay acceleration factor is a GPI anchored protein which prevents RBC lysis by complement pathway product, mutation of which causes PNH. BIOCHEMICAL TESTS 1. 2. 3. 4. 5. Molisch test- for carbohydrates Benedicts test- for reducing sugars Barfoeds test- for distinguishing between monosaccharides & disaccharides Bials test- for pentoses Seliwanoffs test- for distinguishing between aldoses & ketoses. Functions
METABOLISM OF CARBOHYDRATES
DEFINITIONS Metabolism- process by which we assimilate energy from the food we intake (Catabolism) (Catabolism) & utilize the same for building up macromolecules (Anabolism). Oxidative Phosphorylation- The energy obtained by oxidation of substrates is trapped in the f form of reducing equivalents NADH or FADH2 which passes thro mitochondria to generate ATP. Substrate Level Phosphorylation ATP is generated directly from the substrate. EgPhosphoglycerate kinase Pyruvate kinase Succinyl thiokinase Creatine kinase EXAMPLES OF Catabolic Pathways- Glycolysis, glycogenolysis, fatty acid oxidation, amino acid oxidation Anabolic Pathways- Glycogen synthesis, FFA synthesis, protein synthesis Amphibolic Pathways- TCA cycle KEY POINTS IN GLYCOLYSIS
Irreversible Steps Hexokinase or glucokinase Phosphofructokinase Pyruvate kinase Phosphofructokinase Phosphoglycerate kinase Pyruvate kinase Pyruvate Lactate- For the regeneration of NAD- NAD is required for the G3PDH step when itll be converted to NADH. In aerobic glycolysis, NADH will enter into respiratory chain & we get back the NAD, but if its happening anerobically, LDH step converts it back to NAD to convert pyruvate to lactate. ANAEROBIC GLYCOLYSIS- occurs in RBC, white muscle fibres, lens, retina, brain, renal medulla. Only 2 ATP is produced. RBC- glycolysis is the only energy generating pathway as it lacks mitochondria & hence dependent on anaerobic pathway. RAPPAPORT LUEBERIN CYCLE- a deviation of the normal glycolysis whereby phosphoglycerate kinase step is bypassed & phosphoglycerate mutase generates 2, 3-DPG which is essential for decreasing the affinity of RBC for oxygen, thereby facilitating unloading in tissues. PASTEUR EFFECT- Body attempts to prevent anaerobic glycolysis whenever there is high ATP level, which is obtained by lipolysis & fatty acid oxidation. FATES OF PYRUVATE Aerobic Condition- forms acetyl Co A Anaerobic Condition- forms lactate Well Fed State- forms alanine by transaminase Starvation- forms oxaloacetate for gluconeogenesis
Rate Limiting Step Substrate Level Phosphorylation Steps
Products
PYRUVATE DEHYDROGENASE COMPLEX (PDH) Multi enzyme complex, mitochondrial enzyme with PDH, dihydrolipoyl tranacetylase, dihydrolipoyl DH & coenzymes: TPP, CoA, Lipoic acid, NAD, FAD Generates 3 ATP.
REGULATION Allosteric inhibition by acetyl Co A(glucose sparing effect), NADH, ATP COVALENT MODIFICATION-activated by phosphorylation & vice versa. Activated by insulin.
BIOCHEMISTRY Carbohydrates KEY POINTS IN GLUCONEOGENESIS Formation of glucose e from non carbohydrate sources ORGANS INVOLVED- liver & kidney Conversion of pyruvate to phosphoenolpyruvate consumes CO2 & ATP generating inorg inorganic phosphate. Enzymes Involved Pyruvate carboxylase PEPCK Fructose 1,6 bis phosphatase (rate limiting step) Glucose-6-phosphatase Glucogenic amino acids, lactates, glycerol & propionate Regulated by PFK-2 PFK-2 2 on phosphorylation acts like fructose 2, 6 bisphosphatase (glucagon) & when it gets dephosphorylated, it behaves like PFK PFK-2 synthesizing fructose 2,6 bisphosphate. Fructose 2,6 bisphosphate is an allosteric activator of PFK-1 PFK (glycolysis)
Substrates Regulation
TCA CYCLE
Occurs in mitochondria Only aerobic pathway Amphibolic
Catabolic- generates 12 ATP from acetyl Co A Anabolic- forms various intermediates like glutamate from alpha-KG, aspartate from oxaloacetate, fatty acids from acetyl Co A. Regulation of TCA Cycle Depends on the type of the cell In skeletal muscle- main purpose is energy production, the cycle generates ATP. The dehydrogenases are all activated by calcium ions & the ATP/ADP ratio will be very low: inhibition on PDH is overcome. In Liver- cycle is anabolic. Citrate synthase is inhibited by high energy level, so oxaloacetate accumulates, which can be utilized for aspartate synthesis. Similarly ATP allosterically inhibits DH to help in glutamate & other synthesis. Succinyl CoA is used in heme synthesis. In adipose tissue- aconitase inhibited-citrate accumulates & helps in FA synthesis. Inhibitors of TCA cycle Fluoroacetate- inhibits aconitase Malonate- inhibits succinate dehydrogenase
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ENERGY YIELD (NO OF ATP GENERATED) PER MOLECULE OF GLUCOSE THROUGH GLYCOLYSIS PLUS CITRIC ACID CYCLE, UNDER AEROBIC CONDITIONS PATHWAY GLYCOLYSIS Hexokinase Phosphofructokinase Glyceraldehyde-3-P-DH 1, 3-BPG Kinase Pyruvate kinase PYRUVATE TO ACETYL CO A Pyruvate dehydrogenase TCA CYCLE Isocitrate dehydrogenase Alpha-KG DH Succinate thiokinase Succinate DH Malate DH Net generation in Glycolysis Generation in PDH reaction Generation in TCA cycle Net generation of ATP from 1 molecule of glucose NADH NADH GTP FADH2 NADH 3X2=6 3X2=6 1X2=2 2X2=4 3X2=6 10 - 2 = 8 =6 = 24 = 38 NADH 3X2=6 NADH ATP ATP - Minus 1 - Minus 1 3X2=6 1X2=2 1X2=2 SOURCE NO OF ATPs GAINED
BIOCHEMISTRY Carbohydrates KEY POINTS IN GLYCOGEN METABOLISM Occurs in 2 tissues- liver & muscle Total glycogen is higher in muscle than liver Liver glycogen gives rise to plasma glucose whereas muscle glycogen does not since glucose-6phosphatase is absent in muscle Key enzyme for glycogen synthesis- glycogen synthetase Key enzyme for glycogenolysis- glycogen phosphorylase Regulation of glycogen metabolism- by cyclic AMP Total ATP utilized in glycogen synthesis- 2
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KEY POINTS IN GLYCOGEN SYNTHESIS Enzymes Hexokinase in skeletal muscle & glucokinase in liver Glucokinase has got high Km & low affinity for glucose UDP glucose pyrophosphorylase Glycogen synthase adds glucose subunits in straight chains until 11 residues are attached Branching enzyme (1->4)->(1->6) transferase
GLYCOGENOLYSIS KEY POINTS IN GLYCOGENOLYSIS Enzymes involved are phosphorylase & debranching enzyme (amylo 1, 6 glucosidase) Rate limiting step is phosphorylase- pyridoxine dependent enzyme Gives rise to glucose-1-phosphate Energy from glucose obtained by glycogenolysis- 9 ATP Liver glycogen phosphorylase is activated by glucagon & epinephrine, whereas muscle GP is only by epinephrine & not glucagon
BIOCHEMISTRY Carbohydrates HEXOSE MONO-PHOSPHATE SHUNT
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KEY POINTS IN HEXOSE MONOPHOSPHATE SHUNT Occurs in cytosol of liver, mammary glands, adipose tissue & fetal heart 2 PHASESOxidative- production of NADPH (used for reductive synthesis of lipid derivatives) Non oxidative- production of ribose-5-phosphate (used for purine biosynthesis, nucleoside synthesis) No ATP is generated Prevents RBC hemolysis by assisting glutathione peroxidase G6PD deficiency causes drug (antimalarial) induced hemolytic anemia
BIOCHEMISTRY Carbohydrates GALACTOSE METABOLISM
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GALACTOSEMIA Defect in the following enzymes enzymesGalactose-1-P- uridyl transferase : classical type Galactokinase : minor type Epimerase : rare Clinically manifest with failure to thrive, lethargy, hypoglycemia, hepatomegaly, cataract, cata mental retardation. Biochemically- increased blood galactose, decreased blood glucose, galactosuria, galactosu albuminuria, aminoaciduria FRUCTOSE METABOLISM
Fructose intoleranceintolerance Aldolase B deficiency Clinically- hypoglycemia, liver damage, hyperuricemia, lactate acidosis.
___THE END___
DADH Oral Mucous Membrane
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ORAL MUCOUS MEMBRANE

Definition The moist lining of the oral cavity that is in continuation with the exterior surface of skin on one end and esophagus on the other end is called Oral Mucous Membrane Origin and Development The mouth is derived partly from the stomatodaeum and partly from the foregut; hence its epithelial lining is partly ectodermal and endodermal.
The lamina propria is thick, tightly bound to the underlying bone and does not stretch It bears the masticatory forces
LINING OR REFLECTING MUCOSA It is distensible over the musculature and covers adapting itself to the contraction and relaxation of cheeks, lips and tongue It makes up all the surfaces of the mouth except the dorsum of the tongue and the masticatory mucosa is not subjected to high levels of friction and must be mobile and distensible It is nonkeratinised and has loose lamina propria It is not exposed so much to masticatory forces Mucosa covering the lip cheek vestibule, alveolar mucosa, floor of the mouth and soft palate SPECIALIZED MUCOSA Dorsum of the tongue has gustatory type of specialised mucosa It is so called because it bears the taste buds which have a special sensory function in addition to general sensory function GENERAL FEATURES Oral mucosa is situated anatomically between the skin and intestinal mucosa. Hence it shows some properties of both The oral mucosa like skin and intestinal mucosa consists of two separate tissues competent A covering epithelium An underlying connective tissue It is considered an organ Oral cavity is divided into Oral cavity proper Oral vestibule Different from skin Moist surface Absence of appendages present in skin ORAL EPITHELIUM Oral mucosa is made up of stratified squamous epithelium derived from embryonic ectoderm Stratification occurs as a result of cell
Functions 1. 2. 3. 4. 5. 6. 7. Protection Sensation Thermal regulation Secretion Absorption Excretion Aesthetics
CLASSIFICATION Based on the functional criteria 1. 2. Masticatory mucosa lining the gingiva and hard palate Lining or reflecting mucosa lining the cheek, vestibular fornix, alveolar mucosa, floor of mouth and soft palate 3. Specialized mucosa Dorsum of the tongue, taste buds and vermillion border of lip Based on structure of surface layers 1. 2. Keratinized mucosa Hard palate and gingiva (COMEDK-05) Nonkeratinised mucosa Cheek, soft palate, vestibule, floor of mouth Based on location 1. 2. 3. 4. 5. 6. Buccal mucosa Palatal mucosa Lingual mucosa Labial mucosa Alveolar mucosa Gingival mucosa
MASTICATORY MUCOSA It is present in the areas of high compression and friction and characterized by keratinized and parakeratinised epithelium (AP-05)
proliferation and sequential differentiation

The cells vary from cuboidal or low columnar at the base of flat squamous cells in the superficial layers The surface of the stratified squamous epithelium depending on the location and functional requirements has a layer that is keratinized, nonkeratinised or parakeratinised The oral epithelium maintains its structural integrity by a system of continuous cell renewal in which the cells produced by mitosis in the deeper layers of epithelium migrate to the surface and are eventually shed off The cells in the basal layer are of 2 types: Progenitor cell which proliferates to give rise to new cell Keratinocyte/maturing cell which migrates and matures and is eventually shed off The keratinizing oral epithelium has 4 layers 1. 2. 3. 4. 1. Stratum basale Stratum spinosum Stratum granulosum Stratum corneum 3. Stratum basale Layer of cuboidal or columnar epithelium cells adjacent to the basement membrane. As the stratum basale undergoes the most mitotic activity this layer is called stratum germinativum The cells of basal layer have specialized structure called hemidesmosomes which rest on the basal lamina The basal lamina has 2 zones o A clear zone called Lamina lucidum containing pemphigoid o laminin antigen. and bullous just Found Stratum Granulosum
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These intercellular bridges are packed with tonofibrils which are called desmosomes This arrangement of cells as a network is believed to give tensile support for the epithelium The intercellular space is rich in glycoprotein and glycosaminoglycans and fibronectin In the upper layers of stratum spinosum the cells contain cytoplasmic inclusions called keratinosomes or Odland bodies or membrane coating granules Expression of K5 and K14 decreases but that of K1 and K10 increases which are early markers of keratinocyte differentiation Acanthosis increase in thickness of prickle cell layer in pathologic conditions Acantholysis separation of cells due to loss of intercellular bridges
The cells are flat, wide and are stacked in a layer that is 3 5 cells deep This layer is prominent in keratinized epithelium but is deficient or absent in non keratinized epithelium The cells show pyknotic nuclei and are packed with tonofilaments The cells of this layer have numerous dense, large basophilic keratohyaline granules (AIPG-02, COMEDK-04, 07) They are 0.5 nm to 1nm, associated with tonofibrils; facilitate formation and aggregation of cross links Odland bodies are also found in cells of this layer The intercellular space is rich in glycolipids and the inner layer of cell membrane is thickened to form a cornified cell envelope Synthesis of K1 and K10 declines, mRNAs for filaggrin, loricrin and involucrin and precursors of the cell envelope increase in amounts which are late markers of keratinocyte differentiation Involucrin is a sulfur rich protein present in the upper of stratum spinosum that forms a highly resistant cornified cell envelope
below the epithelium A second dark layer called lamina densa is found below the lamina lucida. This zone contains type IV collagen Filaments comprising K5 and K14 keratin chains are present in the cytoplasm 2. Stratum Spinosum (MAHE-01) This layer is made up of 12 to 22 layers of polyhedral cells. It is also called prickle cell layer as the cells exhibit short cytoplasmic processes which meet similar processes from adjacent cells

4. Stratum Corneum It is the surface layer of oral mucosa containing flat cells devoid of nuclei and other cytoplasmic organelles packed with keratin filaments The cells of the stratum corneum are continually shed off and are replaced by migrating cells from the underlying layers The cells of this layer are compact dehydrated and packed close to one another Such keratinization with absence of nucleus is termed as orthokeratinization If cells retain shrunken or pyknotic nuclei until they desquamate - parakeratinization Odland Body / Keratinosome They are also called membrane coating 1. granules They are formed in the upper spinous and granular cell layers They are glycolipids having an internal lamellated structure Keratinosomes discharge their contents into inter cellular space forming an intercellular lamellar material It contributes to form a permeability barrier between stratum corneum and granulosum Keratinization The process of formation of insoluble protein keratin by epithelial cells is called as keratinization The events that occur are Gradual flattening of cells Disappearance of nucleus The prevalence of tonofilaments The prevalence of keratohyaline granules The surface epithelium can be ortho, para or nonkeratinised in nature Orthokeratinization Superficial cells form scales of keratin and loss their nuclei Cytoplasm is packed with keratin filaments The gingiva and palate are usually orthokeratinized as they are associated with masticatory function Stratum granulosum is present Keratinizing Epithelium Four layers 1. Stratum basale 2. Stratum spinosum 3. Stratum granulosum 4. Stratum corneum Intercellular space is more
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Parakeratinization This is a type of epithelium in which superficial cells retain pyknotic nuclei and shows some signs of being keratinized Cytoplasm contains little keratin filaments Stratum granulosum is absent Gingival tissue may be parakeratinised
NON KERATINIZED EPITHELIUM Surface cells are nucleated and shows no signs of keratinization Cytoplasm does not contain keratin filaments It consists of 3 layers 1. 2. 3. Stratum basale Stratum intermedium Stratum superficiale
Stratum granulosum and stratum corneum are absent (AIPG-02) Stratum Basale Similar to basal cell layer of keratinized epithelium
2.
Stratum Intermedium Large cells that do not exhibit the prickle cell appearance as in stratum spinosum The cells are closely arranged and attached to one another by desmosomes Keratohyaline granules are rare and if present they appear as regular spherical structure tonofilaments Loricrin is present not associated with
Stratum Superficiale Also called stratum distendum, reflecting its mechanical flexibility Cells are flatter and nucleated with no signs of keratinization Decrease in cell organelles and increase in the dispersed tonofilaments Cells are not dehydrated thus form a surface that is flexible & tolerant to compression & distention Non Keratinizing Epithelium Three layers 1. Stratum basale 2. Stratum intermedium 3. Stratum superficiale Intercellular space is less

Cells of stratum spinosum show prickly appearance Cornified surface layer, They dont show prickly appearance Does deeply eosinophilic Superficial layer contains extremely flattened cells without nucleus or pyknotic nuclei Turnover and mitotic rate is low Present in gingiva and hard palate (KCET-01) Do not not stain produce intensely cornified surface layer eosinophilic Superficial layer contains big and plump cells with nuclei Turnover and mitotic rate is high Present in cheeks and floor of mouth (AIIMS-99, AP01, COMEDK-09) 2. Non Keratinocytes
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The epithelium contains a small number of cells that do not possess cytokeratin filaments; hence they do not have the ability to keratinize. These groups of cells are termed as non keratinocytes They do not show mitotic activity, or undergo desquamate They are not arranged in layers They are usually dendritic and appear clear in the routine H & E stains They are identified by special stains or immune histochemical methods The cells migrate to the oral epithelium from neural crest or from bone marrow Melanocytes, Langerhans cells, Merkel cells and lymphocytes are considered as the non keratinocytes of the oral cavity maturative changes
Factors affecting keratinization Linea Alba Keratinized area in the cheek opposite the occlusal plane, gets keratinized due to continuous stress of friction during occlusion Palate of smokers becomes hyperkeratotic Mild inflammation Severe inflammation Keratosis: s keratinization s keratinization
Melanocytes They are the melanin producing cells present in the basal layer Derived from neural crest cells Each melanocyte establishes contact with 30 40 keratinocytes through their dendritic processes The melanin from these cells are transferred to the adjacent basal keratinocytes which store the pigment
when keratinization occurs in a
normally non keratinized tissue Parakeratosis: When normally keratinized tissue such as epidermis becomes parakeratinised CELLS The cells of the epithelium can be of two types 1. 2. 1. Keratinocytes Non keratinocytes
in the form of melanosomes Melanin dopa producing cells which contain tyrosinase stain positively for They can be stained by silver stains or Mosan Fontana stain Melanocytes appear as clear cells in Haematoxyline sections Silver stains reveal a spiderlike Hence (dendritic) appearance.
Keratinocytes Epithelial cells that ultimately keratinize are called keratinocytes (MAHE-2K) They show cell division, undergo maturation and finally desquamate Keratinocytes increase in volume in each successive layer form basal to granular Keratohyaline granules are absent The cells are extremely flattened and dehydrated All the organelles are lost and cells are packed with keratin They are acidophilic in nature
referred to as dendritic cells Melanin pigment dispersed in the connective tissue will be phagocytosed by the macrophages termed as melanophages Keratinocytes essential function for release normal mediators melanocyte

Langerhans Cells They layer are of dendritic and the to cells of hematopoietic origin found in upper skin mucosal areas of 1. Lamina Propria epithelium confined CONNECTIVE TISSUE It is made up of 1. 2. Lamina Propria Sub mucosa
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orthokeratinization It has a convoluted nucleus and characteristic rod like granules in the cytoplasm termed as Birbeck granules It stains with gold chloride, ATPase and immunofluorescent markers It is free of melanin and does not give a DOPA reaction Langerhans They are cells penetrates in the epithelium from lamina propria involved immune response (MAHE-01) They migrate into the epithelium in response to chemotactic factors released by keratinocytes They contain la antigens which they present to primed T cells (thymocytes) Merkel cells They are specialized neural pressure sensitive receptor cells with nerve tissue lying just below then They are found among basal cells and respond to touch sensation They are commonly seen in masticatory mucosa and absent in lining mucosa They are not dendritic Slow acting, have neuro secretory activity and migrate from neural crest cells Lymphocytes They are found at various levels of epithelium These cells are transients and can pass through the epithelium to the surface Keratinocytes IL1 but they can may also activate inhibit produce lymphocytes through production of
Lamina propria is also called as corium It is a connective tissue of variable thickness supporting the oral epithelium It is made up of 2 layers: Superficial papillary layer Deep reticular layer Papillary layer consists of finger like projection of connective tissue that inter lock with similar epithelium projection Epithelium has no blood supply and depends for its nutrition on lamina propria Basement membrane can be distinguished from lamina propria as it takes sliver stain Significance arrangement o o Helps to increase the attachment area Increases between propria o Facilitates exchange between the epithelium and blood vessels 2. Sub Mucosa It is a connective tissue layer that attaches the lamina propria to the underlying bone or muscle It is of variable thickness and density Glands, blood vessels, nerves, lymph vessels and adipose tissue are present in submucosa Gingiva and certain parts of hard palate do not have a submucosa SUB DIVISIONS OF ORAL MUCOSA 1. Keratinized areas 2. Masticatory mucosa Hard palate Gingiva Lining mucosa Soft palate Ventral surface of tongue Floor of oral cavity Lips and cheek the strength of bond lamina epithelium and of ridge and papillary
Nonkeratinised areas
lymphocyte proliferation Stimulated lymphocytes gamma-interferon which stimulates Keratinocytes to express HLA DR antigen

3. Vestibular mucosa Specialized mucosa Dorsal lingual mucosa Taste buds Palatine raphe formix and alveolar and
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process and horizontal plate of hard palate
Palatine raphe extends from the incisive or palatine papilla posteriorly Thick, ortho or parakeratinised epithelium is seen Lamina propria shows long, narrow papillae and rete ridges with dense connective tissue These do not have sub mucous layer beneath the lamina propria and are directly attached to the bone
MASTICATORY MUCOSA The areas that bear masticatory force and compression forms the masticatory mucosa It is a keratinized mucosa, generally ortho or parakeratinised Epithelium in this region is thicker than other regions Has the greatest number of papillae per unit area HARD PALATE It is antero laterally thrown into transverse palatine ridges or rugae Histologically the masticatory mucosa of hard palate is divided into 3 parts 1. Epithelium It is thickly orthokeratinized (some places parakeratinised) Stratified squamous epithelium 2. Lamina propria May show long narrow papillae Dense network of thick collagen tissue especially under rugae Blood supply is moderated by short capillary loops 3. Submucosa It is pale pink in colour The thick submucosa in the palatal region is immovably attached to the periosteum through collagen fibres Except over neurovascular bundles in posterior lateral region and minor salivary glands It is divided into irregular
The thick layers of submucosa are present in a wide region extending between the palatine gingiva and palatine raphe
Incisive Papilla In the midline of the hard palate, immediately posterior to the maxillary central incisor is a dense elevation called the incisive papilla This small project of tissue is composed of dense connective tissue It overlies the oral opening of the incisive canal. It contains remnants of oral part of nasopalatine duct, nasopalatine nerve and vessels Nasopalatine ducts are vestigial in humans In lower mammals it is functional as a part of Jacobsons organ of olfaction Sometimes cyst Palatine Rugae Mucosa of the anterior 1/3rd of hard palate is formed into elevated and irregular transverse folds of the palatine rugae The rugae are laterally supported by a sub mucous cushion of fat The core of the rugae is made up of dense connective making it immovable Epithelial Pearls These are circular or concentrically arranged keratinized epithelial cells They are remnants of epithelium formed in the line of fusion of palatine processes These are found in the lamina propria, mostly in the region of incisive papillae the nasopalatine duct gets pathologically involved to form nasopalatine
compartments filled with adipose tissue in the anterior part and with glands in the posterior part of the hard palate The glandular zone extends on to the soft palate The mucosa of hard palate contains the anterior palatinate nerves and blood vessels that pass and course through the junction of the alveolar

GINGIVA Those parts of the masticatory mucosa which cover the alveolar process and surround the cervical portion of teeth The color of normal gingiva is coral pink. (AP-99)
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Width of the keratinized gingiva width of attached gingiva + marginal gingiva Width of attached gingiva varies in different parts of the mouth Between Right and Left sides Between different people Increases with age (AP-2K) Increases in supra erupted teeth
Anatomical Divisions 1. Free/Marginal/Unattached gingiva (AIIMS-06) Terminal edge or border of the gingiva surrounding the teeth in collar like fashion Demarcated from the adjacent attached gingiva by a shallow linear depression free gingival groove. It represents the histologic depth of the gingival sulcus. (AIIMS-89) Usually about 1mm wide Forms the soft tissue wall of the gingival sulcus Can be separated from the tooth surface by a probe Gingival Sulcus Shallow crevice or space around the tooth bounded by the surface of the tooth on one side and the lining epithelium of the free gingiva on the other side (KAR-PGET-02) V shaped and barely permits for a probe Depth of Gingival Sulcus o Under absolute normal or ideal conditions: 0 mm or close to 0 mm o Clinically healthy gingiva: 1.8 mm, varies from 0 to 6 mm (other studies reported 1.5 mm and 0.69 mm) histologic depth o 2. Probing depth: 2 to 3 mm (PGI-03, AIPG-05) Attached gingiva (COMEDK-05) Extends from free gingival groove to mucogingival junction Firm, resilient and tightly attached to 3.
Greatest width in Incisor region (Maxilla: 3.5 - 4.5 mm; Mandible: 3.3 3.9 mm) Least width in First Premolar region (Maxilla: 1.9 mm; Mandible: 1.8 mm) (PGI-01) Biological width is defined as the physiologic dimension of the functional epithelium and connective tissue attachment. This is approximately found to be 2 mm. (KAR-08)
Interdental gingiva Also called Interdental papilla Portion of the gingiva present in the interproximal space beneath the area of the tooth contact Shape is determined by Contact relationship b/w teeth Width of proximal surfaces Shape of the CEJ Anterior: Pyramidal Molars: flattened in a bucco lingual direction Between buccal and lingual papillae Gingival Col is non-keratinized (KAR99). The area most prone to infection is the Interdental col. (PGI-02)
Gingival Epithelium General Features Composed of overlying Stratified squamous epithelium and underlying central core of Connective tissue The principal cell type of the gingival epithelium and other stratified squamous epithelia is Keratinocyte. (AIPG-96) Other cells found in the epithelium are the clear cells or non keratinocytes Langerhans cells, Merkel cells and Melanocytes Main function of the gingival epithelium is to protect the deeper structures and a selective interchange with the oral environment. This is by Proliferation and Differentiation of keratinocytes
underlying bone (KAR-PGET-02) Stippling is seen in the attached gingiva and central core of interdental papilla (AIPG-95, MAHE-02, COMEDK-10). It is absent in infancy, appears in children at about the age of 5, increases until adulthood and begins to disappear in old age. (AIPG-96, specialization (MCET-07) Gingiva in children is more keratinized and less stippled (PGI-99) Width of attached gingiva the distance between the mucogingival junction and the projection on the external surface of the bottom of the gingival sulcus or the periodontal pocket 97) or It is a form of for adaptive function. reinforcement

Proliferation by mitosis in basal layer and to a lesser extent in supra basal layers Differentiation process of keratinization, that involves progressions of biochemical and morphologic events that occur in the cell as they migrate from the basal layer The main morphological events that take place are progressive flattening of the cell with an increasing intercellular production prevalence junctions of of tonofilaments, to the granules, coupled
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Melanocytes are dendritic cells located in basal and spinous layers of gingival epithelium. They synthesize melanin in organelles called premelanosomes or melanosomes. (AIPG-07, 10) Langerhans cells are dendritic cells located at suprabasal layers derived from the bone marrow. Considered as the macrophages with possible antigenic properties. (KAR-PGET-04, COMEDK-05). They are antigen presenting cells for lymphocytes. They contain g-specific granules (Birbecks granules) and have marked adenosine triphosphatase activity. They are absent from the junctional epithelium of normal gingiva
keratohyaline
disappearance of the nucleus A complete keratinization process leads to the production of either orthokeratinized or parakeratinised epithelia Keratin proteins are composed of different polypeptide subunits characterized by their isoelectric points and molecular weights Basal cells synthesize low molecular weight keratins like K19 and express higher molecular weight keratins as they migrate to the surface K1 is the main component of the stratum corneum Keratolinin, Involucrin and Flaggrin form the keratohyaline granules Flaggrin forms the matrix of the Corneocyte the most differentiated epithelial cell Keratinocytes Desmosomes Desmosomes consists of two dense attachment plaques into which tonofibrils insert and intermediate, electron-dense line in the extracellular compartment Tonofilaments are the morphologic expression of the cytoskeleton of keratin proteins, radiate in brush like fashion from the attachment plaques into the cytoplasm of the cells Mitochondria are more numerous in deeper strata and decrease toward the surface Enzyme activity of succinic dehydrogenase, nicotinamide-adenine dinucelotide, cytochrome oxidase and other mitochondrial enzyme activity is more in basal and para basal cells Enzymes of the pentose shunt like glucose-6phosphatase increase their activity toward the surface Upper most cells contain numerous dense granules like keratnisomes or Odland bodies, which are modified lysosomes. Contain high amounts of acid phosphatase are interconnected by
Merkel cells are located in the deep layers of the epithelium. Contain nerve endings and connected to adjacent cells by desmosomes. They serve as tactile receptors
Features of Different Areas of Gingival Epithelium Epithelium is divided into three histological distinct areas 1. Oral or Outer Epithelium (OE) Covers the crest and outer surface of the marginal gingiva and the surface of the attached gingiva Average thickness: 0.2 to 0.3 mm Keratinized presents or parakeratinised combinations or of various
these conditions. The prevalent surface is Para keratinized Responsible for the stippled structure Turnover rate: 10 12 days With increase of age, keratinization of gingiva decreases. (MAHE-02) The degree of gingival keratinization diminishes with age and the onset of menopause The color of gingiva is due to - capillaries, thickness of the epithelium and thickness of keratinization and pigmentation. (MAHE-99, KAR-PGET-01) Order of Keratinization: Palate (most keratinized), Gingiva, Ventral Aspect of Tongue and Cheek (least keratinized) Keratins K1, K2 and K10 to KI2 are specific to epidermal-type are immune differentiation,
histochemically expressed with high intensity in orthokeratinized areas

and with less intensity in
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Act as a semi permeable membrane through which injurious bacterial products pass into the gingiva and tissue fluid from the gingiva seeps into the sulcus 3. Junctional Epithelium (JE) Consists of a collar-like band of stratified squamous non keratinizing epithelium 3 - 4 layers thick in early life, but the number of layers increases with age to 10 or even 20 layers Also, it may taper from its coronal end, which may be 10 to 29 cells wide to one or two cells at its apical termination These cells can be grouped into 2 strata: Basal and Supra basal The length of the junctional epithelium ranges from 0.25 to 1.35 mm (PGI-99, COMEDK-06) Derived from confluence of epithelium and reduced oral enamel
parakeratinised areas K6 and K16, characteristic of highly proliferative epithelia and K5 and K14 are stratification-specific cytokeratins Parakeratinised areas express K19 which is usually absent from orthokeratinized normal epithelia In keeping with complete or almost complete maturation, histoenzyme reactions for Acid phosphatase and pentose - shunt enzymes are very strong Glycogen can accumulate intra cellularly when it is not completely degraded by any of the glycolytic pathways. Thus, its concentration in normal gingiva is inversely related to the degree of inflammation 2. Sulcular Epithelium (SE) Lines the gingival sulcus It is a thin, non keratinized stratified squamous epithelium without retepegs (PGI-05) Extends from the coronal limit of the junctional epithelium to the crest of the gingival margin Usually shows numerous cells with hydropic degeneration It lacks granulosum, corneum strata and K1, K2 and K10 to KI2 cytokeratins But contains K4 and K13 (esophageal type cytokeratins). It also expresses K19 Normally does not contain Merkel cells Enzymes have lower degree of activity than in the outer epithelium particularly in the case of enzymes related to keratinization Glucose-6-phosphate dehydrogenase has faint and homogeneous expression Acid phosphatase staining is negative Sulcular epithelium has the potential to keratinize if o It is reflected and exposed to the oral cavity or the bacterial flora of the sulcus is totally eliminated o Local irritation prevents sulcular keratinization keratinization and
epithelium during tooth eruption (But reduced enamel epithelium is not essential for its formation) Attached by one broad surface to the tooth and by the other to the gingival connective tissue (AIPG-93) Has two basal laminas, one that faces the tooth (internal basal lamina) (MAHE-01) and one that faces the connective tissue (external basal lamina) Desquamative (shedding) surface of the JE is located at its coronal end, which also forms the bottom of the gingival sulcus JE is more permeable than the Oral or Sulcular epithelium. Serves as the preferential route for the passage of bacterial products from the sulcus into the connective tissue and for fluid and cells from the connective tissue into the sulcus (AIIMS-93, MAHE-94) In disease, migration of JE occurs, along with the tissue degeneration under in the connective
attachment; as the JE proliferates along the root surface (gets longer) the coronal portion detaches

JE expresses KI9 (which is absent from keratinized epithelia) and the stratification-specific cytokeratins K5 and K14 (COMEDK-10) It lacks the expression of K6 and K16 (proliferation-specific very high Similar to Sulcular epithelium, 2. junctional epithelium exhibits less glycolytic enzyme activity than outer epithelium and lacks Acid Phosphatase activity Langerhans cells are absent in JE Epithelial attachment: special part of JE that actually provides the attachment. Consists of lamina lucida, lamina densa and hemidesmosomes. JE is attached to the enamel (AIPG-97, by 99, Differences between Gingival epithelia 1. adhesive in 2. 3. present hemidesmosomes COMEDK-10) The transmembrane molecules keratins), although the turnover of the cells is Cuticular structures on the tooth
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Cuticle a thin, Acellular structure with a homogeneous matrix, enclosed within clearly demarcated, linear borders
Listgarten Classification 1. Developmental formed as a part of tooth development. Ex: REE, Coronal cementum, dental cuticle Acquired exogenous origin. Ex: saliva, bacteria, calculus and surface stains Cuticle consists of a layer of
Dental
homogeneous organic material of variable thickness (approx. 0.25m) overlying the enamel surface. Non mineralized, not always present. May be present between the junctional epithelium and the tooth. Proteinacious in nature and formed by accumulation of tissue fluid components
Cell size/tissue volume in JE is > than in OE Intercellular spaces in JE are > than in OE Number of desmosomes in JE > than in OE
hemidesmosomes which specifically binds to basal lamina are integrin 6 4. (COMEDK-10) Dentogingival 03) The abundant glycoprotein in the basement membrane and has binding domain to both ECM and cell surface receptor is Laminin (COMEDK-10) Renewal of Gingival Epithelium unit: Junctional epithelium + Gingival fibers (AP-99, Gingival Connective Tissue Composition: collagen fibers (60%), fibroblasts (5%), vessels, nerves and matrix (35%) Connective tissue of the gingiva is known as lamina propria (KCET-97, 98) and has two layers papillary layer subjacent to the epithelium and a reticular layer that continues with the periosteum of alveolar bone
Ground substance fills the space between fibers and cells, has a high content of water. Composed of proteoglycans (mainly hyaluronic acid and chondroitin sulfate) and glycoproteins (mainly fibronectin)
Mitotic activity exhibits a 24 hour periodicity with the highest and lowest rates occurring in the morning and evening respectively
Three types of connective tissue fibers are collagen, reticular and elastic Type I collagen forms the bulk of the lamina propria and provides the tensile strength to the gingival tissue (COMEDK-04)
Mitotic rate higher in nonkeratinised areas and is increased in gingivitis Order of Mitotic rate: buccal mucosa > hard palate > sulcular epithelium > junctional epithelium > outer surface of marginal gingiva > attached gingiva
Type IV collagen branches between the type I collagen bundles and continues with fibers of the basement membrane and blood vessel walls (MAHE-01)
Turnover rate Junctional epithelium: 1 to 6 days Palate, tongue & cheek: 5 to 6 days Gingiva: 10 to 12 days
Elastic fibers are composed of Oxytalan, Eluanin and Elastin Densely packed collagen bundles that are anchored into the acellular extrinsic fiber

cementum just below the terminal point of the junctional epithelium form the connective tissue attachment. The stability of this Page Classification 1. attachment is a key factor in limiting the migration of junctional epithelium Gingival Fibers Connective tissue of the marginal gingiva is densely collagenous, containing a prominent system of collagen fiber bundles called the Gingival Fibers Composed of type I collagen Also known as Supracrestal connective tissue fibers Functions 1. 2. 3. Types o Arranged in three groups gingivodental, circular and transseptal 1. Gingivodental group present on facial, lingual and interproximal surfaces. Embedded in the cementum just beneath the epithelium at the base of the gingival sulcus. On the facial and lingual surfaces, they project from the cementum in fan like shape towards the crest and outer surface of the marginal gingiva, terminating short of the epithelium. Also extend externally to the periosteum of the facial and lingual alveolar bones, terminating in the attached gingiva or blending with the periosteum of the bone. Interproximally, extend toward the crest of the interdental gingiva 2. Circular group course through the connective tissue of the marginal and interdental gingivae and encircle the tooth in ring like fashion 3. Transseptal group Form located horizontal interproximally. Nerve supply Lymphatic drainage Drain into sub maxillary lymphnodes Blood supply Brace the marginal gingiva firmly against the tooth Provides rigidity to withstand masticatory forces Unites the free marginal gingiva with cementum and attached gingiva Cellular Elements 2.
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the base of the gingival sulcus and the crest of the interdental bone
Semicircular fibers attach at the proximal surface of a tooth, immediately below the CEJ. Run around the facial or lingual marginal gingiva of the tooth and attach on the other proximal surface of the same tooth Transgingival fibers attach in the proximal surface of the tooth, traverse interdental space diagonally, run around the facial or lingual surface of the adjacent tooth, again traverse diagonally the interdental space and attach in the proximal surface on the next tooth
Preponderant cellular element in the gingival connective tissue is fibroblast Other cells mast cells, histiocytes (fixed macrophages), adipose cells, eosinophils, small foci of plasma cells & lymphocytes Neutrophils are more in gingival connective tissue and sulcus
Gingiva is supplied by the supra periosteal arterioles, vessels of the periodontal ligament and the arterioles that emerge from the crest of the interdental septa (AIPG-00)
Gingival innervation is derived from fibers arising from nerves in the PDL and from the labial, buccal and palatal nerves Nerve structures present in connective tissue Meshwork of terminal argyrophilic fibers Meissners-type tactile corpuscles Krause-type end bulbs for temperature receptors Encapsulated spindles
bundles that extend between the cementum of approximating teeth into which they are embedded. Present in between the epithelium at Correlation of Clinical and Microscopic Features Color Coral pink color of attached and marginal gingiva is determined by vascular supply,

degree and thickness of keratinization and presence of pigmentation (melanin) Alveolar mucosa is red, smooth and shiny, thinner, non keratinized, no rete pegs, and more blood vessels In some patients the basal layer of the gingiva contains melanocytes - pigment containing cells which give a brownish hue to portions of the gingiva There are also a few cells in the connective tissue which have taken up melanin granules melanophores Oral repigmentation refers to the clinical appearance of melanin pigment after a period of clinical depigmentation of the oral mucosa resulting from chemical, thermal, surgical, pharmacologic or idiopathic factors Age Changes in Gingiva Size Its the sum total of the bulk of cellular and intercellular supply Contour Depends on The shape of teeth Alignment in the arch Location and size of the area of proximal contact Dimensions of the facial and lingual gingival embrasure Lips and Cheek Shape Of the interdental gingiva is related with the contour of the proximal tooth The height of the papilla varies with the location of the proximal contact Consistency Gingiva is firm and resilient Stratified epithelium squamous non LINING MUCOSA Its a common appearance of gingival disease elements and their vascular Miscellaneous Position Level of the gingival margin Actual Apparent
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Stippling is a form of adaptive specialization or reinforcement for function Stippling is a feature of healthy gingiva Stippled - best viewed by drying tissue
The oxygen consumption of normal gingiva is 1.6 0.3 (AIPG-05) After tooth emerges to the occlusal plane the clinical crown height increases by passive eruption (AIPG-01)
Apical migration of dentogingival junction occurs Histologically, epithelium becomes thinner and friable Flattening of the epithelium and connective tissue junction occurs
Constitutes the covering epithelia of lips, soft palate, cheeks, floor of mouth and vestibular fornix It is loosely textured allowing easy movement of lip, cheek and tongue
keratinized
Submucosal layer consists of strands of densely grouped collagen fibres Loose connective tissue containing fat and few mixed minor salivary glands Buccinator muscle forms the major portion of cheek with serous or mucous salivary glands between them
Surface texture Stippling is absent in infancy, appears at about 5 years of age, increases until adulthood and begins to disappear in old age The attached gingiva is stippled The marginal gingiva is not stippled Produced by rete pegs Fordyce Spots Ectopic sebaceous glands found within the oral mucosa of cheek opposite to the molars and lateral to the corner of the mouth The glands are pale yellowish in appearance They are a normal anatomic feature found in 75% adults

Vestibular Fornix and Alveolar Mucosa Vestibular fornix mucosa is then non keratinized and loosely textured allowing free movement of cheek and lips The distinction between alveolar mucosa and gingiva is made by mucogingival junction Alveolar mucosa is red, smooth and shiny rather than pink and stippled Epithelium is thin, non keratinized stratified squamous and contains no rete pegs Mucosa is loosely attached to connective tissue with numerous blood vessels Floor of the Oral Cavity The mucous membrane is thin and loosely adherent to the underlying structures to allow for free mobility of tongue (KCET-2K, AIPG05) Epithelium is thin non keratinized and the papillae of lamina propria are short Sub mucosa contains adipose tissue o o o o Anterior papillary part or body o
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Comprises the anterior two thirds of the tongue It contains fine pointed cone shaped papillae giving a velvety appearance Supplied by the lingual branch of trigeminal nerve
Posterior lymphatic part or base Comprises of the posterior two thirds of the tongue Supplied by the glossopharyngeal nerve Note: These two parts develop embryologically from two different arches which accounts for two different nerves supplying the general senses It is covered by 4 types of papillae of which some show specialized sensory function of taste 1. Filiform Papillae Epithelial structures bearing conical epithelial caps having a core of connective tissue papillae The conical covering epithelium is keratinized (COMEDK-04) It is not associated with taste perception and does not contain taste buds These cover the entire anterior surface of tongue 2. Fungiform Papillae Mushroom shaped papillae found interspersed between filiform papillae highly chiefly at the side and tip of tongue These are round, elevated and reddish prominences The surface is covered by thin non keratinized epithelium bearing 1 3 taste buds only on the dorsal surface 3. Circumvallate Papillae Are 8 12 in number, larger in size and situated in front of the dividing V shaped terminal sulcus They do not protrude above the surface of the tongue Numerous taste buds are found lining the lateral walls of the papillae which is non keratinized (MAHE-94, KCET99) stratified
Ventral Surface of Tongue Epithelium is thin non keratinized and loosely textured Lamina propria is thick having short papillae with a rich capillary network Sub mucosa is thin and irregular
Mucosa of Soft Palate The mucous membrane is highly vascularized and reddish in colour Epithelium is thin non keratinized stratified squamous epithelium with taste buds Lamina propria is thick and vascularized being red in color shows few short papillae, this layer is rich in elastic fibres Submucosa contains a continuous layer of mucous glands, taste buds and minor salivary glands SPECIALISED MUCOSA Dorsal Lingual Mucosa Covers the dorsum of tongue Covering epithelium of tongue is non keratinized or parakeratinised squamous epithelium Tongue is divided into 2 parts by a V shaped terminal sulcus, sulcus terminalis which runs laterally and forward from a median pit named foramen caecum (remnant of thyroglossal duct)

Free surface shows numerous
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Taste buds are more in no in infants than in adults because with increasing age atrophy occurs
secondary papillae covered by a thin smooth epithelium Ducts from underlying serous salivary glands (Von Ebner glands) are seen open into the trough surrounding the papilla (AP-06) These secretions serve to wash out soluble elements of food and are main source of salivary lipase The taste buds help in perception of bitter and sweet They 05, PGI-05) 4. Foliate Papillae Rows of large papillae found on posterior side of tongue Normally 4 10 vertical furrows containing these papillae are seen lined by stratified squamous epithelium Taste buds are seen in the epithelium of the lateral wall or folds They are more frequently seen in mammals other than humans Taste Buds Taste buds / Gustatory organs are small ovoid or barrel shaped intra epithelial organs about 80 m high and 40 m thick They extend from basal lamina to the surface of the epithelium Their outer surface is covered by a few flat epithelial cells which surrounds a small opening, the taste pore It leads into a narrow space lined by supporting cells or sustenticular cells (COMEDK-04, 05) The receptors for taste are found in between inner supporting cell The base of each taste bud is penetrated by a group of gustatory nerve fibres Taste buds are found in tongue, soft palate, epiglottis and posterior wall of oral part of pharynx They are most numerous on circumvallate papillae of tongue are supplied by
The mid dorsal region of oral part of tongue contains no taste buds Primary taste sensations are perceived in different regions of tongue and soft palate Sweet tip of tongue Salty Lateral borders of tongue Bitter middle of the tongue (KCET-2K) Sour lateral areas of tongue
VERMILION BORDER OF LIP It is a transition zone between the skin of lip and the mucous membrane of the oral cavity It is found only in humans Connective tissue papillae are few and short This is a zone where keratinization ends, as skin of the lip is keratinized and the mucous membrane of lip is non keratinized The transitional region is characterized by a thicker but mildly keratinized epithelium and numerous long papillae in the lamina propria The blood vessels are very near to the epithelial surface giving a red colour to the lips The skin contains appendages such as hair follicles, sweat glands and sebaceous glands, while in oral mucosa there is lack of appendages (AIIMS-90) As this transitional zone contains only occasional glands, it tends to become dry, often becoming cracked and sore in cold weather Between the vermillion border and the thicker non keratinized labial mucosa, is an intermediate zone covered by parakeratinised oral epithelium In infants this region is thickened as an adaptation to, suckling and is called suckling pad BLOOD SUPPLY OF ORAL MUCOSA Upper lip Superior labial artery, buccal artery Upper gingiva Anterior superior alveolar artery, Posterior superior alveolar artery, Greater palatine artery Hard palate Greater palatine artery, Sphenopalatine artery, Nasopalatine artery Soft palate Lesser palatine artery Cheek Buccal artery, Posterior superior alveolar artery, Terminal branches of facial artery
glossopharyngeal nerve. (COMEDK-

Lower lip Inferior labial artery, Mental artery, Inferior alveolar artery branch Lower gingiva Mental artery, Incisive artery, Sublingual artery, Inferior alveolar artery Floor of the mouth Lingual and sublingual artery Tongue Deep lingual artery, Dorsal lingual artery AGE CHANGES IN ORAL MUCOSA With age, the oral mucosa becomes smooth and dry Epithelium becomes thin due to reduction in thickness of epithelial ridges and decrease in salivary secretion Filiform papillae are reduced Tongue appears smooth due to reduction in thickness deficiencies Varicose veins on the ventral aspect of tongue (lingual varices) Ectopic sebaceous glands are commonly seen in old people ATTACHMENT EPITHELIUM It is an organic attachment between epithelium and tooth Mechanism of epithelial attachment was given by Orban and Gottlieb Primary Attachment Epithelium Attachment of the junctional epithelium onto the tooth surface is called the attachment epithelium During eruption, the tip of the tooth approaches oral mucosa As a result the reduced epithelium and oral epithelium meet and fuse The epithelium covering the tip of the crown degenerates allowing crown to emerge into the oral cavity On eruption, the reduced enamel epithelium which is attached to the enamel before eruption is called the primary attachment epithelium With the eruption of tooth, the reduced enamel epithelium moves apically, reducing in length Secondary Attachment Epithelium When reduced enamel epithelium has disappeared, primary enamel epithelium is DENTOGINGIVAL JUNCTION Stage 3 This is a pathological condition of epithelium or nutritional Stage 2
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replaced by a secondary attachment epithelium derived from gingival epithelium Crown exposure which involves passive eruption and further recession consists of 4 stages that may be physiologic or pathologic Stage 1 This is a physiologic stage usually present upto one year before shedding in primary teeth and upto 20 30 years of age in permanent dentition In this stage, the bottom of gingival sulcus remains on enamel and the apical end of the epithelial attachment lies at CEJ
This is also a physiologic stage present usually upto 40 years In this, the bottom of the gingival sulcus lies on the enamel but the apical end of attachment epithelium is shifted to the cementum
The anatomical crown is fully exposed in the oral cavity Bottom of gingival sulcus shifts to the CEJ and the epithelial attachment entirely shift to cementum Stage 4 or gingival recession Is a pathologic condition Gingival recession can be defined as an exposure of root surface by an apical shift in the position of gingiva In this stage both gingival sulcus and epithelium attachment are on cementum It may occur early in life but generally gingival recession increases with age
The junction of the gingiva and tooth formed by junctional epithelium and gingival fibres is known as dentogingival junction It may be a point of reduced resistance to mechanical forces and bacterial attack The integrity of the dentogingival junction is maintains by epithelium and connective tissue which are attached to tooth Any condition that causes breakdown of collagen weakens the dentogingival junction

Shifting of Dentogingival Junction With time the position of gingiva on tooth surface changes When the tooth tip of enamel emerges into oral cavity, almost the entire enamel is covered by the epithelium As the crown erupts into the oral cavity, the attachment of epithelium separates from the enamel surface gradually A very slow exposure of the crown is followed by Preclinical/Active eruption The actual movement of teeth towards the occlusal plane Passive eruption separation of primary attachment epithelium form the enamel surface During the first 2 stages, clinical crown is smaller than anatomic crown CUTICLE The primary and secondary cuticle is formed on the enamel When the epithelium proliferates beyond the CEJ, the cuticle extends along the cementum The cemental cuticle and secondary enamel cuticle is called the dental cuticle Cuticles exist as amorphous materials between attachment epithelium and tooth
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*****
NEET
Concepts
Volume 02 General Pathology Microbiology Pharmacology Dental Materials
GENERAL PATHOLOGY Hemodynamic Pathology
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HEMODYNAMIC PATHOLOGY
INTRODUCTION Normal fluid homeostasis encompasses
Oncotic Edema Oncotic pressure of plasma Albumin Decreased synthesis in the liver Liver disease Increased loss in the urine Nephrotic syndrome Inadequate intake - Kwashiorkar Lymphedema Obstruction of lymphatics Elephantiasis Edema of breast Edema of arm post radiation Pitting Edema Heart failure THAT GOVERN MOVEMENT OF
maintenance of vessel wall integrity as well as intravascular pressure and osmolarity within certain physiologic ranges Changes in vascular volume, pressure, or protein content, or alterations in endothelial function, all affect the net movement of water across the vascular wall. Such water extravasation into the interstitial spaces is called edema and has different manifestations depending on its location. In the lower extremities, edema mainly causes swelling; in the lungs, edema causes water to fill alveoli, leading to difficulty in breathing. Normal fluid homeostasis also means maintaining blood as a liquid until such time as injury necessitates clot formation. Clotting at inappropriate sites (thrombosis) or migration of clots (embolism) obstructs blood flow to tissues and leads to cell death (infarction). Conversely, inability to clot after vascular injury results in hemorrhage; local bleeding can compromise regional tissue perfusion, while more extensive hemorrhage can result in hypotension (shock) and death Major factor keeping fluid in vessel Oncotic (albumin) Major factor pushing fluid out of vessel Hydrostatic pressure FACTORS
FLUID BETWEEN INRA AND EXTRA-VASCULAR COMPARTMENTS: Under normal conditions, fluid passes out into the interstitial tissue from the arteriolar end of the capillaries and re-enters the circulation at their venular end. This is governed by The capillary hydrostatic pressure which tends to expel fluid into the interstitial tissue The colloidal osmotic pressure of the plasma which tends to retain fluid within the intra-vascular compartment. Also, a small amount of fluid is drained by lymphatics.
EDEMA
CAUSES DEFINITIONS Edema: Increased fluid in interstitial tissue Hydrothorax (pleural effusion): Collection of fluid in pleural cavity Hydropericardium (pericardial effusion): Collection of fluid in pericardial cavity Ascitis (hydroperitoneum): Collection of fluid in peritoneal cavity Anasarca: severe generalized edema Effusion: fluid within the body cavities II. Reduced Hydrostatic Edema Impaired venous return Heart failure Increased influx of arterial blood Edema 1. 2. 3. Plasma Osmotic Pressure (Hypoproteinemia) Nephrotic-syndrome Cirrhosis of liver (ascites) Malnutrition I. Increased hydrostatic pressure Impaired venous return 1. 2. 3. 4. Congestive heart failure Constrictive pericarditis Cirrhosis of liver Obstruction of narrowing vein Heat Neurohumoral dysregulation
Arteriolar dilatation

4. Protein-losing gastroenteropathy PATHOLOGICAL FEATURES III. Lymphatic obstruction (lymph edema) 1. 2. 3. 4. Inflammatory Neoplastic Postsurgical Postirradiation
18
Microscopically, edematous tissue appears pale with widening of extra-cellular matrix Cardiac edema is influenced by gravity and, therefore, scrotum, appears where first and is most is prominent in dependant parts e.g. legs, hydrostatic pressure highest (dependant edema)
IV. Sodium retention 1. 2. 3. 4. Excessiv salt intake with reduced renal function Increased sodium Renal hypoperfusion Increased renin-angiotensin-aldosterone secretion tubular reabsorption of
Edema resulting from hypoproteinemia (e.g. nephrotic edema) is more severe than cardiac edema and affects all parts of the body but appears early in sites with loose connective tissue e.g. eyelids (periorbital edema)
Nephritic edema is a mild form of generalized edema and is most prominent in the eyelids and face
V. Inflammation 1. 2. 3. Acute inflammation Chronic inflammation Angiogenesis
Markedly edematous subcutaneous tissue may pit under pressure (pitting edema) Lymphatic overgrowth edema of is associated tissue with and, connective
therefore, the edematous area becomes firm and does not pit on pressure The edema fluid associated with hemodynamic derangements is poor in protein (less than 1 g %), contains few or no cells and has a specific gravity below 1.020 (transudate) The edema fluid associated with inflammation (increased vascular permeability) is rich in protein (more than 4 g %), contains many cells and has a specific gravity over 1.020 (exudate) CLINICAL EFFECTS Range from only annoying to fatal Subcutaneous edema may impair wound healing or clearance of infection Pulmonary edema may lead to death by interfering with normal ventilation (fluid in alveolar septa) or predisposing to infection (fluid in alveolar spaces) Brain edema may kill due to brain herniation or by compressing vascular supply of the brain stem to lymphatic
TYPES OF EDEMA FLUID 1. Transudate 2. Edema fluid with low protein content Clear fluid Specific gravity < 1.020 Proteins < 1.5 g/dL
Exudate Edema fluid with high protein content and cells Turbid fluid Specific gravity > 1.020 Proteins > 3 g/dL Types of exudates Purulent (pus) Fibrinous Eosinophilic Hemorrhagic
3.
Lymphedema obstruction
related
Protein-rich fluid produces non-pitting edema
4.
Glycosaminoglycan-rich edema fluid In creased hyaluronic acid and chondroitin sulfate causes myxedema
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HYPEREMIA AND CONGESTION

HYPEREMIA (ACTIVE HYPEREMIA) Increased blood in a tissue resulting from arteriolar dilatation with accumulation of blood in arterioles and capillaries It is an active process in which affected tissues appear red due to engorgement with oxygenated blood Causes 1. Physiologic Conditions Exercise in which hyperemia occurs in skeletal and cardiac muscles Digestion in which hyperemia occurs in the splanchnic area 3.
ventricular failure and systemic venous congestion Local venous congestion Due to impaired venous outflow from an area or part as a result of, o o o o Mechanical obstruction of vein e.g. by ligature or twisting Venous thrombosis Pressure on vein e.g. by tumor Constriction of vein by scar tissue e.g. portal fibrosis area of congestion of resulting liver from (in
schistosomiasis or cirrhosis) PATHOLOGICAL CHANGES IN CHRONIC
2.
Acute Inflammation
VENOUS CONGESTION (CVC) 1. Liver Grossly, the liver is enlarged, firm and its cut surface shows a nutmeg appearance of fatty change Microscopically, the central veins and the sinusoids in the central zones of the hepatic lobules are dilated and engorged with blood. The hepatocytes between the dilated sinusoids show fatty change. With advance of the condition, the sinusoidal dilatation extends peripherally and the hepatocytes in the central zones become necrotic, while those in the mid zones develop fatty change. In old cases, centrilobular fibrosis occurs and regenerative nodules venous of hepatic parenchyma develop (cardiac cirrhosis) 2. Spleen Grossly, the spleen is moderately enlarged, firm and its cut surface is dark red and may show scattered brownish plaques (fibrosiderotic nodules or due to with dark areas of congestion alternating with yellow areas
Mechanism Vasodilatation mediated by Vasoactive mediators Hormones Neurogenic reflexes CONGESTION (PASSIVE HYPEREMIA) Increased blood in a tissue resulting from impaired venous outflow with accumulation of blood in veins and capillaries It is a passive process in which affected tissues appear blue-red (cyanosed) engorgement with deoxygenated blood Types and Causes There are three types of congestion, each of which may be acute or chronic 1. Systemic congestion In which blood accumulates in veins all over the body except pulmonary veins It is caused by right sided heart failure 2. Pulmonary venous congestion In which blood accumulates in the pulmonary veins and their tributaries within the lung It is caused by mitral stenosis or left sided heart failure It may be complicated by pulmonary hypertension which may lead to right (generalized)
Gamna-Gandi bodies). Microscopically, the red pulp sinusoids are dilated and engorged with blood and their walls are thickened due to fibrosis. The fibrosiderotic nodules are composed of fibrous tissue They entrapping result from hemosiderin.

hemorrhage from engorged veins, with the hemosiderin liberated from the broken RBCs inducing the fibrosis 3. Lungs Grossly, the lungs are enlarged, heavy, firm and deep red in color (brown induration). The cut surface may ooze frothy blood on squeezing Microscopically, the pulmonary venules and alveolar capillaries are dilated and engorged with blood. The alveolar walls are thickened due to edema and later due to fibrosis. The alveolar spaces contain RBCs and many large macrophages with brownish hemosiderin pigment granules (heart failure cells). They may also contain edema fluid. The pulmonary veins show medial hypertrophy and intimal fibrosis. If pulmonary arterial hypertension changes of Blood include Hemothorax (pleura) Hemopericardium Hemoperitoneum Hemoarthrosis (joints) accumulations in body develops, structural CLASSIFICATION Hemorrhage may be
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External in which blood escapes outside the body Internal in which blood accumulates within a tissue or in body cavities Blood accumulations in tissues are classified according to size into Petechiae: measuring 0.1 0.2 cm (1-2 mm) and usually encountered in skin, mucous membranes and serosal surfaces Purpura: measuring 0.3 1 cm. and usually occurring in the skin Ecchymoses: measuring 1 2cm and usually occurring in the skin Hematoma: accumulation which in is soft a large tissues blood e.g.
mediastinum or retroperitoneum cavities
hypertension occur in the pulmonary arterial tree (elastic hyperplasia of arteries and hyaline thickening of arterioles)
HAEMORRHAGE
Escape of blood outside the CVS
CLINICAL EFFECTS Depend on Volume of blood loss Rate of blood loss Site of bleeding Rapid loss of more than 20% of blood volume leads to hemorrhagic (hypovolemic) shock while slow losses or smaller rapid losses may have little effect. Also relatively mild bleeding in the brain may cause death
TERMINOLOGY Hematuria Blood in urine Hematemesis Vomiting o.Lf blood Hematochezia Bleeding through rectum Melena Coffee-ground material in stool (upper GIT) Epistaxis Bleeding from nose Hemoptysis Bleeding from lungs Menorrhagia Heavy menstrual bleeding Metrorrhagia Occurs at any time
CAUSES Rupture of an artery or vein due to Trauma Atherosclerosis Inflammation Neoplasia Capillary bleeding due to minor trauma in Chronic congestion Hemorrhagic diathesis
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THROMBOSIS
DEFINITIONS Thrombosis: The vital process by which a thrombus is formed. Thrombus: A solid mass made up of blood elements that develop within the cardiovascular system during life Clotting: The transformation of soluble fibrinogen into a fibrin network. It occurs outside the cardiovascular system or within the cardiovascular system after death PATHOGENESIS (Virchows triad)
3.
Hypercoagulability of the blood due to genetic (primary) or acquired (secondary) causes
CAUSES OF THROMBI T Tissue damage (trauma, (t burns, fractures, surgery) H Hereditary conditions (protein C or S, Antithrombin III, factor V Leiden) R Rest (prolonged bed rest after surgery or old age) Obstetrics (normal normal pregnancy, pregnancy eclampsia, abruptio placenta) M Malignancy B Blood flow disturbances (MI, varicose veins, aneurysms) I Immune mechanisms (SLE, PAN)
MECHANISM OF THROMBUS FORMATION Platelets deposit and adhere to the endothelium where they become activated with initiation of the intrinsic coagulation sequence Concomitantly, the release of tissue factors from injured cells participates in the activation of the extrinsic coagulation sequence 1. Endothelial Injury This is particularly important in thrombus formation in the heart and arterial circulation It is mainly caused by: atherosclerosis, infarction of the heart, inflammation, and trauma It leads to: exposure of sub endothelial collagen, adherence of platelets, release of tissue factor, and local depletion of prostacyclin clin and plasminogen activators 2. Alterations in normal blood flow Turbulence over atherosclerotic plaques or at t sites of vascular bifurcation Stasis in varicose veins, aneurysms, dilated cardiac chambers (e.g (e.g. dilated left atrium in mitral stenosis), myocardial infarcts, and small vessels in polcythemia (hyperviscosity) and sic sickle cell anemia (deformed RBCs) Stasis and turbulence disrupt normal laminar blood flow bringing platelets in contact with the endothelium MORPHOLOGY OF THROMBI Structural Features A thrombus forming in rapidly flowing blood e.g. in an artery consists mainly of platelets and is firm and pale reddish-grey reddish (pale thrombus) A thrombus forming in stagnant blood (e.g. adjacent to a complete vascular occlusion) is indistinguishable in appearance from a blood clot, i.e. soft, dark red and gelatinous with a smooth outer surface, and consists mainly of fibrin and RBCs, along with leucocytes l and few platelets (red thrombus) Between the two extremes are mixed thrombi which form in slowly flowing blood, usually in veins and consist of alternating layers of pale and red thrombi or, alternatively, a red thrombus interrupted by pale thrombi at points of vascular anastomosis
The deposited platelets form ridges known as the lines of Zahn. The spaces between the lines of Zahn contain fibrin, RBCs and leucocytes The lines of Zahn appear homogeneous, hyaline and basophilic under the microscope

SITES OF THROMBOSIS Thrombosis in the heart Thrombi may develop, In the dilated left atrium in mitral stenosis, where they may be attached to the wall (mural thrombus) or are free in the atrial lumen and may plug the mitral valve (ball-valve thrombus) On the endocardium lining a ventricular myocardial infarct (mural thrombus) On the cardiac valves (vegetations) in various forms of endocarditis and 3. 4. hypercoagulability states Thrombosis in arteries Develops at sites of endothelial injury (most commonly due to atheroma), turbulence (arterial bifurcation) or stasis (aneurysms) In small arteries e.g. coronary, cerebral, thrombi may occlude the arterial lumen (occluding thrombi) Venous thrombosis Superficial venous thrombosis usually develops in the saphenous system in the presence of varicosities. Deep venous thrombosis usually develops in popleteal, femoral or iliac veins following congestive heart failure, trauma, surgery or burns, peurperal and postpartum states, tumors, bed rest and immobilization Thrombophlebitis This is venous thrombosis resulting from damage of the either endothelium bacterial by inflammation, (septic COMPLICATIONS OF THROMBI 1. 2. 3. 4. 5. Infarction Edema & obstruction of venous flow Emboli Infection Inflammation of vessel wall 2. FATE OF THROMBUS 1. Capillary thrombosis
22
May develop in acute inflammation, some forms of vasculitis and DIC
Dissolution by fibrinolytic activity: This leads to rapid shrinkage and even lysis of recent thrombi. Polymerization of fibrin in old thrombi renders them more resistant to lysis Propagation, mainly in venous thrombi which propagate in the direction of blood flow i.e. towards the heart Embolization following dislodgement or fragmentation of the thrombus Organization and Recanalization Organization refers to replacement of the thrombus by granulation tissue from the vessel wall. The granulation tissue is then replaced by fibrous tissue which contracts. This may lead to restoration of the previously interrupted blood flow in case of occluding thrombi Restoration of blood flow may also be achieved by persistence of one or more capillary thrombus channels which in the fibrosed the communicates
blood columns on either side of the thrombus (organization with canalization)
thrombophlebitis) or, less commonly, due to ionizing radiation or chemicals In septic thrombophlebitis, the thrombus is invaded by micro-organisms from the vessel wall, and then becomes softened and broken into fragments that circulate in the blood as septic emboli Migratory syndrome) Recurrent attacks of multiple venous thromboses at changing sites, that occur in association with various forms of cancer especially cancer pancreas. It is probably due to release of procoagulant substances by cancer cells thrombophlebitis (Trousseaus
DIFFERENCES BETWEEN THROMBUS & CLOT Thrombus Forms during life inside the CVS Forms in flowing blood Adherent to underlying vessel or heart wall Firm and friable Surface rough Gelatinous Surface smooth Clot Forms after death or outside the CVS Forms blood Not adherent in stagnant
23
EMBOLISM
DEFINITIONS Embolism: Impaction of an embolus in a blood vessel (artery or portal venous radicle) which is too small to allow its further progress Embolus: Any solid, liquid or gaseous mass that is carried by the blood stream to a site distant to its point of origin in the CVS 3. 2.
limbs, brain, intestines, kidneys, spleen Tumor emboli Composed of malignant cells, lead to secondary tumors (metastases) wherever they settle. Parasitic emboli Composed of parasitic elements e.g. ova of S. mansoni, larvae of E. granulosus and vegetative forms of E. hystolytica
TYPES AND EFFECTS OF EMBOLI 1. Thrombotic Emboli Constitute 99% of emboli and are derived from dislodgement or fragmentation of a thrombus. Their effects depend on whether they are infected (septic emboli) or bland (aseptic emboli), the size of the embolus and the organ embolized Septic emboli lead to pyemic abscesses wherever they settle. Aseptic emboli o A large embolus derived from a venous thrombus impacts in the main trunk of the pulmonary artery, across its bifurcation (saddle thrombus) or in one of its major branches leading to sudden death due to acute right ventricular failure (because of sudden obstruction of 60% or more of the pulmonary outflow) with a consequent pronounced reduction in left ventricular cardiac output and cardiogenic o shock (massive pulmonary embolism) Smaller emboli derived from a venous thrombus or a thrombus or vegetation in the right side of the heart impact in smaller branches of the pulmonary lung infarcts artery producing o 5. 4.
lead to parasitic lesions wherever they settle Fat emboli Consisting of fat globules which may enter the circulation from the bone marrow following fractures of long bones or, less commonly, from the subcutaneous tissue following trauma or burns Air emboli Air may enter the circulation through wounds involving the large veins of the neck, during obstetric procedures (e.g. tubal insufflations) or following chest wall injury Decompression sickness When air is breathed at high pressure e.g. during a deep see dive, increased (particularly amounts nitrogen) of gas become
dissolved in blood and tissues. If the diver ascends (depressurizes) too rapidly, gases come out of solution and form bubbles in the blood (gas emboli) and tissues, leading to various clinical effects involving muscles and joints, CNS, CVS and respiratory system. Caissons disease A more chronic form of with decompression sickness
only in the presence of CVC. Emboli derived from the left side of the heart, aorta or large arteries leads to infarcts in organs occluded supplied vessel by e.g. the lower
persistence of gas emboli in bones leading to multiple foci of ischemic necrosis

6. Amniotic fluid embolism A rare maternal complication of childbirth which is often fatal It results from introduction of amniotic fluid into the maternal circulation via tears in the placental membranes and uterine veins. Amniotic fluid produces disseminated intravascular clotting (DIC) because of its high thromboplastic activity. DIC results in marked hypofibrinogenemia (consumptive coagulopathy) that leads to fatal uterine hemorrhage (amniotic fluid infusion) o o Infection of the infarcted tissue
24
In these cases the infarct changes into an abscess
Infarcts are often wedge-shaped, with the base of the wedge directed towards the surface of the organ and its apex (occluded vessel) towards the hilum. When the base of the infarct is a serosal surface, there is often an overlying fibrinous inflammation Infarcts are often surrounded by a narrow rim of hyperemia (congestion). This results from acute inflammation at the margin of the lesion, induced by the necrotic tissue, with congestion and infiltration by neutrophils and macrophages The inflammatory response is eventually followed by gradual removal of the necrotic tissue by macrophages and replacement of the infarct by granulation tissue then fibrous tissue (healed infarct)
INFARCTION
It is Ischemic necrosis resulting from occlusion of the arterial blood supply or, much less commonly, the venous drainage (in organs with a single venous outflow e.g. testis, ovary) The area of necrosis so produced is called an infarct MORPHOLOGY OF INFARCTS Infarcts may be red (hemorrhagic) or pale (white, anemic) depending on the vascularity, blood content and texture of the tissue in which the infarct develops Thus, red infarcts occur in, o Tissues with a dual circulation e.g. lung permitting blood flow from the patent vessels into the infarcted area o o o Previously congested tissues Venous torsion Loose tissues that allow blood to collect in the infarcted area e.g. small intestine, lung Pale infarcts occur with arterial occlusion in solid organs e.g. heart, spleen, kidney, where the solidity of the tissue limits the amount of hemorrhage from the necrotic capillaries in the infarcted area Infarcts may be septic or bland depending on the presence or absence of infection. Septic infarcts develop as a result of either: o Impaction of septic emboli derived from an infected thrombus or vegetation 5. 4. 3. 2. occlusions e.g. ovarian
The necrosis of the infarct is of the coagulative type in all infarcts except those of the CNS in which the necrosis is of the liquefactive type where the necrotic area undergoes rapid liquefaction and eventually appears as a cavity filled with clear fluid and surrounded by a layer of gliosis resulting from proliferation of astrocytes
CLINICAL SIGNIFICANCE OF INFARCTION 1. Myocardial infarction may lead to: Death, mainly due to arrhythmias or acute left ventricular heart failure failure and cardiogenic shock Congestive tissue Cerebral infarction often leads to hemiplegia due to destruction of the pyramidal tract in the internal capsule Infarction of the intestine leads to, Acute intestinal obstruction (affected loop ceases to contract) Severe toxemia (gangrene) Hemoptysis (hemorrhage into alveolar spaces) Chest pain and friction rub (pleurisy) Hematuria Infarction of the kidney may lead to, Infarction of the lung may lead to, following replacement of the infarct by fibrous

Senile or atherosclerotic kidney if the infarction is repeated over a prolonged period MORPHOLOGY OF SHOCK
25
Shock of any form is associated with morphologic changes of hypoxic injury in a number of organs particularly the brain, heart, lungs, kidney, adrenals and GIT.
SHOCK (CARDIOVASCULAR COLLAPSE)

It is Failure of the circulatory system to maintain adequate perfusion and oxygenation of vital organs due to sudden severe reduction of cardiac output or circulating blood volume TYPES & CAUSES OF SHOCK 1. Cardiogenic shock Results from reduction of cardiac (left ventricular) output and may be caused by: Large myocardial infarction Ventricular arrhythmias Cardiac Massive (acute failure) 2. Hypovolemic shock Results from reduction of blood or plasma volume and may be caused by: Severe hemorrhage Fluid loss from severe burns or trauma 3. Septic shock Results from systemic microbial infection, most commonly infections by Gram -ve bacilli (endotoxic shock) 4. Neurogenic shock Results from loss of vascular tone and peripheral pooling of blood and may be caused by: An anesthetic complication Spinal cord injury 5. Anaphylactic shock Results from generalized vasodilatation and increased by vascular an IgE permeability mediated caused tamponade pulmonary right (extrinsic embolism ventricular compression)
With the exception of neuronal and myocyte loss, all tissues may recover if the patient survives
The brain is swollen with widened gyri and narrowed sulci. Microscopically, early cases show acute neuronal change or red neurones (vacuolation, then eosinophilia of neuronal cytoplasm, followed by nuclear pyknosis and karyorrhexis). Later on, there is tissue necrosis with infiltration by macrophages. Finally, the necrotic tissue is removed and replaced by gliosis (hypoxic encephalopathy).
The kidneys are swollen and congested with pooling of blood in the outer medulla. Microscopically, there is extensive acute tubular necrosis (shock kidney)
The
lungs
are
heavy, they
firm
and
red.
Microscopically,
show
congestion,
edema, inflammation and diffuse alveolar damage (shock lung, ARDS) The adrenals show depletion of lipids in cortical cells (lipids utilized in synthesis of steroids). There may be also focal hemorrhage or rarely, massive hemorrhagic necrosis (as in Waterhouse- Friderichsen syndrome of meningococcal septicemia). CLINICAL MANIFESTATIONS Unless rapidly fatal, shock passes through three stages: 1. An initial non-progressive stage during which compensatory neuro-hormonal mechanisms are activated and perfusion of vital organs is maintained. 2. A progressive stage characterized by tissue hypoperfusion and hypoxia, metabolic imbalances including acidosis (anerobic glycolysis and renal failure) and progressively decreasing cardiac output and increasing endothelial injury. 3. An irreversible stage after severe tissue injury has developed, so severe that even if the hemodynamic defects are corrected, survival is not possible
hypersensitivity response

The most common manifestations of shock are, Pale, cool, clammy skin Subnormal temperature Tachycardia and weak pulse Hypotension Air hunger Oliguria which may progress to anuria
26
*****
MICROBIOLOGY Introduction & History
INTRODUCTION
Micros (small) + bio (life) + logos (study of) = Microbiology Father of Cell theory Robert Hooke Father of Microbiology Louis Pasteur; developed rabies vaccine Father of Anti septic surgery Joseph Lister Father of Immunology Edward Jenner Father of Mycology Raymond Sabouraud Paul Ehrlich coined the term Chemotherapy; made the first synthetic chemotherapeutic drug (salvarsan) Spontaneous generation hypothesis that some forms of life could arise spontaneously from non-living matter HISTORICAL TIME LINE 1677 First Observed "little animals" (Antony Leeuwenhoek) 1796 First scientific Small pox vaccination (Edward Jenner) 1850 Advocated washing hands to stop the spread of disease (Ignaz Semmelweis) 1861 Disproved spontaneous generation (Louis Pasteur) 1862 Supported Germ Theory of Disease (Louis Pasteur) 1867 Practiced antiseptic surgery (Joseph Lister) 1876 First proof of Germ Theory of Disease with B. anthracis discovery (Robert Koch) 1881 Growth of Bacteria on solid media (Robert Koch) 1882 Outlined Kochs postulates (Robert Koch) 1882 Developed acid-fast Stain (Paul Ehrlich) 1884 Developed Gram Stain (Christian Gram) 1885 First Rabies vaccination (Louis Pasteur) 1887 Invented Petri Dish (R.J. Petri) 1892 Discovered viruses (Dmitri Iosifovich Ivanovski) 1899 Recognized viral dependence on cells for reproduction (Martinus Beijerinck) 1900 Proved mosquitoes carried the yellow fever agent (Walter Reed) 1910 Discovered cure for syphilis (Paul Ehrlich) 1928 Discovered Penicillin (Alexander Fleming) 1952 Hershey & Chase Experiments identified that DNA was the genetic material of Bacteriophages
1977 Developed a method to sequence DNA (W. Gilbert & F. Sanger) 1983 Polymerase Chain Reaction invented (Kary Mullis) 1995 - First microbial genomic sequence published (H. influenzae) (TIGR)
DEVELOPMENT OF MICROSCOPY 384-322: Aristotle and others believed that living organisms could develop from nonliving materials. 1590: Hans and Zacharias Janssen (Dutch lens grinders) mounted two lenses in a tube to produce the first compound microscope. 1660: Robert Hooke (1635-1703) published and "Micrographia", containing drawings
detailed observations of biological materials made with the best compound microscope and illumination system of the time. 1676: Anton van Leeuwenhoek (1632-1723) was the first person to observe microorganisms. 1883: Carl Zeiss and Ernst Abbe pioneered developments in microscopy (such as immersion lenses and apochromatic lenses which reduce chromatic aberration) which perist until the present day. 1931: Ernst Ruska constructed the first electron microscope. Robert Koch (1843-1910) German bacteriologist was the first to cultivate anthrax bacteria outside the body using blood serum at body temperature Building on Pasteurs "germ theory", he subsequently published "Koch's postulates" (1884), the critical test for the involvement of a microorganism in a disease: 1. 2. 3. The agent must be present in every case of the disease. The agent must be isolated and cultured in vitro. The disease must be reproduced when a pure culture of the agent is inoculated into a susceptible host. 4. The agent must be recoverable from the experimentally-infected host. Diseases caused by Bacteria 1. 2. 3. Acne Anthrax Cholera
MICROBIOLOGY Introduction & History

4. 5. 6. 7. 8. 9. Dental caries Diphtheria Gangrene Gonorrhea Leprosy Leptospirosis
*****
10. Meningitis 11. Plague 12. Pneumonia 13. Staphylococcal food poisoning 14. Tetanus 15. Tuberculosis 16. Typhoid fever Diseases caused by Fungi 1. 2. 3. 4. 5. 6. Aflatoxin poisoning Candidiasis Dandruff Ergot poisoning Meningitis Ringworm of the feet (athletes foot)
Diseases caused by Protozoans 1. 2. 3. 4. 5. Malaria Amoebiasis Giardiasis African sleeping sickness Chagas disease
Diseases caused by Helminthes 1. 2. 3. 4. 5. 6. Schistosomiasis Ascariasis Trichinosis Tapeworm infestations Pinworms Hookworms
Diseases caused by Viruses 1. 2. 3. 4. 5. 6. 7. 8. 9. AIDS Warts Small pox Chicken pox Measles Poliomyelitis Rabies Encephalitis Yellow fever
10. Dengue influenza 11. Mumps 12. Hepatitis
MICROBIOLOGY Bacterial Morphology
BACTERIAL MORPHOLOGY
Only two types of cells are produced by all living organisms on earth. 1. Prokaryotes (pro. or primitive nucleus) do not have a membrane bound nucleus i. ii. 2. Eubacteria (true bacteria) Archaebacteria (ancient bacteria)
Lysosomes Ribosomes
Absent 70s free in the cytoplasm
present 80s in the and the endoplasmic reticulum free in
cytoplasm; 70 s in organelles Plasma membrane sterols absent except mycoplasma; no CHO Cell wall chemically complex; mucopeptides containing chemically simple; if consists of polysaccrides or inorganic substances(cellul ose and chitin) Capsule Double membrane Frequently present Absent Mitochondria, chloroplasts chlorobium; vesicles organelles chromatophores, thylakoids Locomotion flagella rotate; motion Flagella submicroscopic; each to equivalent a that gliding Golgi membranes; lysosomes; endoplasmic reticulum; vacuoles flagella and cilia that undulate; ameboid motion microscopic, contain 20 fibrils (nine pairs surrounding two single fibrils) complex; consists consists of two protein of multiple microtubules Absent simple present, in usually contains sterols; CHO serve as receptors
Eukaryotes (eu, or true nucleus) have a membrane bound nucleus i. ii. Algae fungi
iii. protozoa iv. plants v. animals
Prokaryotes Size of cell typically 0.20 -2 m in diameter
Eukaryotes typically 10-100 m in diameter usually >10 m in diameter DNA true nucleus within a membrane
muramic acid and DAP or lysine
usually < 5 m in diameter Nucleus a single molecule not bounded by a membrane
divide by mitosis DNA replicate and two bodies single chromosome, circular, naked DNA complexed with histones Cytoplasm no or cytoskeleton cytoplasmic cytoskeleton; cytoplasmic streaming not separate always more than one chromosome DNA with histones complexed nuclear producing chains
organelles Simple membrane organelles
single eukaryotic fibril
streaming Cytoplasmic structures Endoplasmic reticulum Golgi apparatus Mitochondria Absent Absent Absent
present Present present
building blocks
MICROBIOLOGY Bacterial Morphology BACTERIAL CELL

1. Most bacteria produce a layered cell envelope that includes the plasma membrane, cell wall and associated proteins and polysaccharides. 2. 3. 4. Some bacteria produce capsules or slimes. External filamentous Appendages ( (flagella and pili) may also occur. The cell wall is a rigid structure that enclose encloses and protects the protoplast from physical damage and conditions of low external osmotic pressure. 5. 6. 7. 8. The cell wall also generally all allows bacteria to tolerate a wide range of environmental conditions. The protoplast comprises the naked cytoplasmic membrane and its contents. Internally, bacteria are relatively simple cells. Major cytoplasmic structures include a central fibrillar chromatin network surround surrounded by an amorphous cytoplasm that contains ribosomes. 9. Cytoplasmic inclusion bodies or e energy storage granules vary in chemical nature accordin according to species and in amounts depending on growth phase and environment. 10. Some cytoplasmic structures, s, such as endospores, are limited to only a few bacteria. 11. Typical gram positive and gram negative bacterial cells differ primarily in cell envelope organization. Size of bacteria Units of microbial measurement 1. micrometers (m) 1 m being 10-6 m(1/25,000 inch) 2. nanometers 1 nm being 10-9 or r 0.000000001 m Pathogenic bacteria species vary from Chemical Composition of Bacteria 1. 2. approximately 0.4 to 2 m m in size Water - 70% Dry weight - 30% composed of: i. ii. DNA - 5% MW 2,000,000,000 RNA - 12% a. b. c. d. v. Ribosomes(10,000) rna Protein particles - mw 3,000,000 Enzymes Surface structures m or 0.000001
iii. Protein - 70% found in
iv. Polysaccharides - 5% Lipids - 6% vi. Phospholipids - 4% Components of the Bacterial Cell A. Structures external to the cell wall 1. Glycocalyx i. ii. Capsules Slime layer

2. 3. 4. B. C. Flagella Axial filaments Pili or fimbriae 2. Quellung Reaction o Homologous capsule o o
Bacterial cells appear to lie in lacunae
Cell Wall Structures internal to the cell wall 1. 2. 3. 4. 5. Plasma membrane or cytoplasmic membrane Cytoplasm Nuclear area Ribosomes Inclusions a. b. c. d. e. f. 6. 7. Metachromatic granules or Babes Ernst granules Polysaccharide granules Lipid inclusions Sulphur granules Carboxysomes Gas vacuoles
antibody
is
added to a preparation of Micro precipitation at the periphery of the capsule altering its refractive index rendering the capsule to be visible Functions of the Capsule 1. 2. 3. 4. 5. Protection Identification Vaccine preparation Tissue attachment Antibiotic barrier
Endospores Mesosomes
GLYCOCALYX A viscous (sticky), gelatinous polymer that is external to the cell wall Composed of polysaccharide and polypeptide or both Produced inside the cell and excreted on the cell surface 1. 2. Slime layer - if the substance is unorganized and only loosely attached to the cell wall Capsule If the substance is organized and is firmly attached to the cell wall Found in both gram positive and gram negative cells Presence denotes virulence Encapsulated cells form smooth or mucoid colonies Non encapsulated cells form rough colonies Not seen in the usual stained smear because of their failure to retain the dye Capsular functioning substance largely is as antigenic a partial 2. FLAGELLA
Medical Importance o Rapid serological identification of: 1. 2. 3. 4. 5. 6. Several groups of streptococci Meningococcus Hemophilus influenzae Klebsiella pneumoniae Some of the coli forms Yersinia and Bacillus specie
Organ of locomotion Long filamentous appendage originating in a spherical body or basal granules Occur most commonly although not exclusively among the rod-shaped bacteria
Morphological Regions 1. Helical filament Long outermost region; composes up to 90% of its length Contains the globular (roughly spherical) protein flagellin, arranged in several chains that intertwine and form a helix around a hollow core Hooked or curved area Filament is attached; consists of a different protein 3. Basal body Terminal portion of the flagellum Anchors the flagellum to the cell wall and plasma membrane
antigen or hapten Methods to distinguish the capsule 1. India Ink Technique o o Most satisfactory method of demonstrating the capsule Bacteria are suspended in diluted India ink

Composed of a central rod inserted into a series of rings o Gram negative - 2 pairs of rings i. Outer pair - anchored to the outer membrane ii. o (L ring) and Antigenicity peptidoglycan layer (P ring) Inner pair - anchored to the plasma membrane (SM ring) Gram positive - only inner pair is present Types of arrangement of flagella 1. 2. 3. 4. 5. Motility Presumptive evidence that bacteria possesses flagella although it gives no indication of the number or rearrangement of the flagella Types of bacterial motility Stately motility: Bacillus sps Active motility: Pseudomonas sps Darting motility: Vibrio cholerae Tumbling motility: Listeria monocytogens Corkscrew, Spirochetes Examples of non-motile bacteria: Most cocci, Shigella, Klebsiella Demonstration of motility 1. Direct or Microscopic Hanging drop preparation or wet mount preparation Distinguishes, i. Brownian movement when the bacteria show molecular movement with no apparent effort to change their position and direction to the field ii. True motility - if a bacterium describes a rotatory, undulatory or sinuous movement 2. Indirect or Macroscopic Stab inoculation of the semisolid media i. Non motile - growth is limited at the point of inoculation Functions of Pili 1. 2. 2. Types 1. Pili extension-flexion motility: Fimbriae FIMBRIAE AND PILI Hair like appendages that are Atrichous - no flagella Monotrichous - one polar flagellum Lophotrichous - tuft of several polar flagella Amphitrichous - flagella at both poles Peritrichous - flagella over the entire cell surface AXIAL FILAMENTS ii.
Motile - growth is diffuse or moves away from the line of inoculation; turbidity of the medium
Flagellar or H antigen - useful in the serological identification organisms of serotypes of Salmonella
Bundles of fibrils that arise at the ends of the cell beneath the outer sheath and spiral around the cell Rotation moves an opposing movement of the outer sheath that propels the spirochetes by causing them to move like corkscrews Found in Spirochetes and are similar to flagella, but are located between the cell wall and an outer sheath, and are attached to one end of the organism.
shorter,
straighter and thinner than flagella Used for attachment rather than for motility Consist of a protein called pilin arranged helically around a central core
Can occur at the poles of the bacterial cell or they can be evenly distributed over the entire surface of the cell Allow a cell to adhere to surfaces
Usually longer than fimbriae and number only one or two per cell Genetically determined by a fertility factor called F factor which is carried on an Episome (sex or F pilus)
Sex or conjugation pili for the transfer of extra chromosomal recipient Attachment pili or fimbriae: There are many and are used for attachment to surfaces DNA between donor and
Sites of adsorption for RNA and DNA viruses Act as a means of genetic transfer between

similar or related Gram negative enteric species 3. Provide the channel through which DNA from the donor (male) cell is transferred to the recipient (female cell) CELL WALL The layers of cell envelope lying between the cytoplasmic membrane and the capsule are referred to collectively as cell wall In gram positive bacteria, the cell wall mainly consists of peptidoglycan and teichoic acid while the cell wall in gram negative bacteria includes peptidoglycan, lipoprotein, outer membrane and lipopolysaccharide layers Cell wall does not take up any stain and hence are not seen by light microscope Most bacteria have a complex cell wall consisting of peptidoglycan (also called Demonstration of cell wall murein, mucopeptide) This complex polymer consists of three parts, A backbone consisting of alternating units of NAG (N-acetyl glucosamine) and NAM (N-acetyl muramic acid) Tetrapeptide side chain attached to NAM Peptide cross-bridges, which are short chains of amino acids that crosslink the backbone Differences between cell walls of Gram positive and Gram negative organisms Feature Thickness Amino acids Aromatic & sulphur Containing Amino acid Lipids Teichoic acid Peptidoglycan Absent Absent Present More Present Present Absent Less Gram Positive Thicker Few Gram Negative Thinner Several Atypical cell walls 1. Gram Negative Substances acting against cell wall
Bacteria may attach to surface, produce slime, divide and produce microcolonies within the slime layer and construct a biofilm. E.g. formation of dental plaque mediated by the bacterium Streptococcus mutans. Confer specific antigenicity to a strain/species that can be exploited to detect and identify an isolate.
Lysozyme, an enzyme found in tears and saliva breaks down a component of cell walls Antibiotics that inhibits cell wall synthesis such as Penicillins and cephalosporins Autolytic enzymes produced by some bacteria such as Streptococcus pneumoniae
Since cell wall does not take up stain, they cant be demonstrated by light microscopy Their presence can be demonstrated by placing a cell in hypertonic solution, where they undergo plasmolysis. The cytoplasm shrinks as the water is lost by osmosis but the cell wall retains its original shape (due to its rigidity). This is described as "bacterial ghost" The cell wall may also be demonstrated by micro-dissection, electron microscopy and immunological reactivity
Naturally occurring wall less microorganisms Genus Mycoplasma and related organism Smallest known bacteria that can grow and cells Pass through most bacterial filters and were first mistaken for viruses Require cholesterol or sterols for growth Cultivated in the laboratory only in hypertonic media 2. Archaebacteria Lack walls or may have unusual walls composed of polysaccharides and proteins but not peptidoglycan Walls contain n-acetylalosaminuronic acid but lacks the d amino acids found in the bacterial cell walls reproduce outside living host
Significance of cell wall Maintains cell shape, any cell that loses its cell wall, loses its shape as well. Protects bacteria from osmotic lysis Acts as a barrier, protects cell contents from external environment Determines reactivity to Gram stain, cells become gram negative if they lose cell wall Attachment site for flagella Site of action of certain antimicrobial agents (E.g. Penicillins, Cephalosporins)

PLASMA MEMBRANE (CYTOPLASMIC 4. cell wall and cell membrane synthesis
MEMBRANE/INNER MEMBRANE) A thin structure lying inside the cell wall and enclosing the cytoplasm of the cell Consists primarily of phospholipids which are the most abundant in the membrane and proteins Structure Electron microscopy - two layered structure; phospholipid bilayer Phospholipid parallel rows 1. Phospholipid molecule Polar head - composed of a phosphate group in water Non polar tail - composed of fatty acids that are hydrophobic (water fearing) and are insoluble in water; lies in the interior of the bilayer 2. Protein molecule Peripheral proteins o o o Easily removed from the membrane by mild treatment Lie at the inner or outer surface of the membrane Functions i. ii. Act as enzymes that catalyze chemical reactions Act as a scaffold for support in membrane shape during movement Integral proteins o Can be removed from the membrane only after disrupting the bilayer o o Penetrate completely Contain channels through which substances enter and exit the cell Functions 1. 2. Holds the intracellular contents within the cytoplasm and prevents their leakage Concentrates nutrients by effecting their transport from the external environment of the cell to the cytoplasm of the cell 3. Provides the enzymes necessary for capsules, the membrane and glycerol that is hydrophilic(water loving) and soluble molecules arranged in two
Serves as the site for enzymes involved in electron transport and energy metabolism
Associated structures 1. Chromatophores or thylakoids Infolding of the plasma membrane that extend into the cytoplasm Contains 2. Mesosomes One or more large, irregular folds in the plasma membrane; believed to be artefacts Functions of Mesosomes i. ii. Site Site for for energy metabolism of DNA and to respiration attachment membrane and are the site of growing septum formation iii. Contain enzymes instrumental in the synthesis of the cell wall, cell membrane and other components external to the cytoplasmic membrane iv. Site of exoenyzme synthesis and secretion for penicillinase CYTOPLASM The internal matrix of the cell contained inside the plasma membrane Thick, aqueous, semitransparent and elastic the pigments and enzymes involved in photosynthesis
Composition 1. 2. 3. 4. 5. 6. Water - 80% Proteins (enzymes) Carbohydrates Lipids Inorganic ions Low molecular weight compounds
iii. Act as mediators of changes
Major Structures 1. 2. 3. DNA Ribosomes Inclusions
Nuclear area or Nucleoid A. Bacterial chromosomes Single long, circular molecules of double stranded DNA Carries all the information required for the cell structures and functions Bacterial chromosomes do not include histones

and are not surrounded by a nuclear envelope (membrane) Attached to plasma membrane, the proteins of which are responsible for the replication of DNA and segregation of the new chromosomes to daughter cells in cell division B. Plasmids Small, circular, double stranded DNA 3. Lipid inclusions Appear Spirillum in various Bacillus, molecules Extra chromosomal genetic elements Replicate independently of chromosomal DNA Associated with plasma membranes Usually contain from five to 100 genes Maybe gained or lost without harming the cell May carry genes for such activities as o o o o antibiotic resistance tolerance to toxic metals production of toxins synthesis of enzymes 5. Carboxysomes 4. Sulphur granules 2. Polysaccharide granules
Not usually enclosed by a membrane Consist of glycogen and starch Glycogen granules - reddish brown with iodine Starch granules - blue with iodine
species
of
Mycobacterium,
Azobacter,
Polymer polybetahydroxybutyric acid storage material
Sulphur bacteria (Genus Thiobacillus) deposit sulphur granules in the cell, where they serve as an energy reserve
Can be transferred from one bacterium to another Ribosomes Sites for protein synthesis Composed of two subunits, each subunit being composed of protein and a type of RNA called ribosomal RNA (r RNA) Prokaryotic ribosomes are called 70s ribosomes MA: inhibition of protein synthesis on the ribosomes Ex. Streptomycin, Tetracyclines Inclusions 1. Reserve deposits Metachromatic granules or volutin or Babes Ernst granules Spherical granules that are not membrane bound Contains relatively large amounts or or of trichloroacetic acid polymetaphosphate phosphoric acid insoluble polymerized polymerized
Polyhedral and hexagonal inclusions Contain the enzyme ribulose 1,5 diphosphate carboxylase Required by bacteria for carbon dioxide fixation during photosynthesis Ex. Nitrifying bacteria, cyanobacteria, thiobacilli 6. Gas vacuoles Hollow cavities found in many aquatic prokaryotes Consist of rows of several individual gas vesicles which are hollow cylinders covered by protein Function: maintain buoyancy so that the cells can remain at the depth in the water appropriate for them to receive sufficient amounts of oxygen, light and nutrients ENDOSPORES A refractile oval body formed within the bacterial cell found intracellularly and extracellularly in the usual stained smear Found in all species of Family Bacillaceae Genus Bacillus - aerobic spore forming rods Genus Clostridium - anaerobic spore forming rods of Corynebacterium Found also in Sporosarcinae - Gram positive coccus Coxiella Burneti
polymetaphosphate or volutin Generally formed by cells that grow in phosphate rich well as bacteria Stain red with certain blue dyes such as Methylene blue Characteristic diphtheria environments Found in algae, fungi and protozoans as

Structure 1. Core or spore protoplast Contains o o o Complete nucleus All of the components of the protein synthesizing apparatus Energy generating system on Respiratory organisms Zoonoitic organisms glycolysis - energy for germination stored as 3 phosphoglycerate 2. Spore wall o o o 3. Innermost layer surrounding the inner spore membrane Contains the normal peptidoglycan Becomes the cell wall of the germinating vegetative cell Cortex o Thickest layer of the spore envelope with many fewer cross links than are found in cell wall peptidoglycan o o Cortex peptidoglycan is extremely Curved Aerobic Anaerobic 3. B. sensitive to lysozyme Contains dipicolinic acid, mucopeptide and calcium, all of which are significant in spore 4. containing disulfide bonds 5. Exosporium lipoprotein membrane containing some carbohydrate CLASSIFICATION OF MEDICALLY IMPORTANT BACTERIA I. Rigid, thick walled cells A. Free living (extracellular) 1. Cocci Spore forming rods Aerobic Anaerobic Non spore forming rods Non filamentous Filamentous Corynebacterium Listeria Actinomyces Nocardia Bacillus Clostridium Gram positive Streptococcus Staphylococcus resistance many intra molecular Coat - composed of keratin like portion Enteric & related organisms Rods Facultative Straight Haemophilus Bordetella Leigionella Brucella Francisella Pasteurella Escherichia Serratia Klebsiella Salmonella Shigella Proteus 2. Cocci Gram negative Neisseria
Camphylobacter Vibrio Pseudomonas Bacteroides
Acid fast - Mycobacteria living (Obligate intracellular
Non-free parasites) 1. 2.
Rickettsia Chlamydia
II. Flexible, thin walled cells (Spirochetes) 1. 2. 3. Treponema Borellia Leptospira
III. Wall-less cells 1. Mycoplasma

BACTERIAL GROWTH CURVE When bacteria is seeded into suitable liquid medium and incubated, its growth follows a definite course. If it is plotted on a graph it shows 4 stages as follows 3. Stationary phase Rate e of multiplication multipl decreases
This is due to depletion of nutrients and accumulation of toxic products equilibrium exists between the dying dyi cells and newly formed cells
4.
Phase of decline In this phase the liable count decreases due to nutritional exhaustion and autolysis of cells by toxic substances produced during multiplication But no change in total count
1.
Lag phase In this period there is n no appreciable multiplication of cells but increase in the size of the cell This is an adaptation time for new environment during which the necessary enzymes and metabolic intermediates for multiplication to proceed.
2.
Log phase In this stage cell starts to divide and then number increases exponentially Curve shows a liner relationship bet between number of cells and time This growth rate depends on generation time and environmental factors.
MICROBIOLOGY Culture Methods
15
CULTURE METHODS
INDICATIONS FOR CULTURE 1. 2. 3. 4. 5. 6. 7. 8. Isolate Bacteria in pure form Demonstrate their properties Preparation of Antigens & other tests Typing of Isolates for Epidemiological purpose Antibiogram demonstration Estimate viable counts Maintain stock cultures Diagnosis of infection
Appropriate Dilutions of inoculums are added incubated at 37C Colonies distributed in depth of medium Used to Estimate viable count of Bacteria & Quantitative urine cultures
Liquid culture In Tubes, flasks, Bottles Employed for Blood culture & Sterility tests Preferred when large amounts of organism are required Growth is demonstrated by General Turbidity Surface pellicle formation Gas production Hemolysis in the Blood culture Broth Disadvantages Doesnt yield pure growth from mixed growth Cannot demonstrate colony Morphology
METHODS OF CULTURE 1. 2. 3. 4. 5. 6. Streak culture Lawn culture Stroke culture Stab culture Pour plate culture Liquid culture
Streak culture (surface plating) Employed for isolation of bacteria from Other methods 1. Sweep plate method Edges of Petri dishes are swept over the surface of fabric, surface, floor etc On incubation colonies Develop and Estimated 2. uniform surface Growth of Cough plate method In Whopping cough patients, for isolation of Bordetella Plate placed in front of mouth & coughed incubated for growth of organism INCUBATION OF CULTURE MEDIA Stroke culture Done on a Agar slant For providing pure growth of organism for slide agglutination Stab culture Puncturing suitable medium by charged straight wire E.g.: Gelatin agar or nutrient agar Used for Demonstrating Gelatin liquefaction, 4. 5. Pour plate culture Tubes containing 15 ml of agar medium melted and kept in a water bath at 45C
mixed organisms (in pure culture) Inoculation by Platinum / Nichrome loop (24 SWG) Growth is confluent at primary site, separated colonies at final series of streaks
Lawn / Carpet culture Provides Bacterium Used for Bacteriophage typing & Antibiotic Sensitivity testing (Disk Diffusion method) Used for preparation of Bacterial vaccines & Antigens
At 37C inside the incubator for 18 -24 hours Blood culture bottles are declared negative after 7 days incubation. E.g.: In Brucellosis
ANAEROBIC CULTURE METHODS 1. using 2. 3. Production desiccators) Displacement of Oxygen (Candle jar method) Displacement and combustion of O2 (McIntosh - Fildes anaerobic jar) Absorption of O2 by or chemical or biological methods (Gas pak system) Using reducing agents in medium Anaerobic chamber 6. of vacuum (E.g. Vacuum
Motility & Maintenance of stock cultures

1. Production of vacuum E.g.: Vacuum desiccators method Cultivating in vacuum Disadvantages O2 always left behind Media gets detached from surface of plate 2. Displacement of Oxygen (Candle jar method) Displacement of O2 by Hydrogen, Nitrogen, CO2 or Helium E.g. Candle jar method Disadvantages O2 cannot be completely removed by this method Not able to cultivate strict anaerobes 3. Displacement and combustion of O2 (Mc Intosh & Fields anaerobic jar) 4. Metal / glass jar with metal lid clamped air tight LID: Two tubes inlet & outlet, two electric terminals Lid underside - Small grooved porcelain pool with a layer of wrapped palladinised asbestos Plates placed inside Outlet to vacuum pump, then inlet to hydrogen supply Reduced Methylene blue is used as indicator Risk of explosion which may rarely occur 3. 2. 5. By reducing substances 1% glucose, 1% thioglycollate 0.1%Ascorbicacid 0.05% cysteine and cooked meat pieces 1. Thioglycollate broth Biological Method Incubation along with Aerobic
16
bacteria,
germinating seeds, chopped vegetables Slow & ineffective
Nutrient broth + 1% thioglycollate. Added Vitamin K + Haemin improves growth of Anaerobic & microaerophilic bacteria Robertsons Cooked meat broth Nutrient broth + Pieces of fat free minced cooked meat of ox heart (+ a layer of liquid paraffin) Smith - Noguchis medium Broth with fresh animal tissues that supports the growth of anaerobes It contain Unsaturated fatty acids use O2 for auto oxidation Glutathione and cysteine (both are reducing agents) Sulphydryl compounds also reduce O2. Interpretation Sacharolytic organisms turn the meat colour to red Asacharolytic organisms turn the meat colour to black 6. Glove Box Air tight, glass inert gas hands Used for Quantitative cultures of fastidious Anaerobes METHODS OF ISOLATING PURE CULTURES Surface plating Inoculating Cultivation environments Incubating optimums Heating at 80oC separates vegetative & spore stages under different temperature into under selective, aerobic & Enrichment, anaerobic Indicator media fronted cabinet filled with with an entry lock & gloves for
Absorption of O2 by or chemical and biological methods Chemical Methods 1. Pyrogallol Alkaline Pyrogallol can absorb O2 (A large tube containing NaOH and pyrogallic acid is placed inside the test tube.) 2. Chromium and sulphuric acid Chromium + Sulphuric acid (in presence of O2) Chromous sulphate 3. Gas Pak system Containing disposable envelope: Sodium borohydride, Cobalt chloride, citric acid and sodium bicarbonate These chemicals generate hydrogen and CO2 when water is added Widely used method Indicator used is reduced Methylene blue Colorless anaerobically, turns blue on exposure to O2

Motile from non motile by inoculation under Craiges tube Pathogenic from non pathogenic by Animal inoculation Bacteria of different size by passing through Filters
17
MICROBIOLOGY Bacterial Genetics
18
BACTERIAL GENETICS
BACTERIAL DNA A single circular double stranded DNA Length 1000 micrometer or 1m When straightened (expressed as kilo base, around 4000 kb) Super coiled like a thread to accommodate within the bacterial cell Replication starts at a certain point (origin of replication) Replicates in a semi-conserved manner (one of the original strands is retained in the new double strands) Most bacterial genes code for proteins Introns are absent (non-coding interposed sequences) Operons are DNA sequences arranged sequentially at specific locations and code for functionally related proteins CHARACTERISTICSProkaryotic (Bacterial) Chromosome Replicates just prior to binary fission Single molecule of DNA per genetic trait (haploid) Closed loop Histones absent No No dominance organization as or a PROKARYOTIC AND
conservative rolling occurs circle
method, method
conservative method. No evidence of rolling circle method
EXTRA CHROMOSOMAL GENETIC ELEMENTS Plasmid Autonomous DNA molecules present in the cytoplasm of bacteria Small & closed loops of DNA Number of copies varies from1-2 to100 per cell depending upon the size Can multiply independent of the chromosome Transferred easily between bacteria Many carry genes that code for certain characteristics Eg: R Plasmids code for drug resistance, F plasmids code for sex pili, Virulence plasmids code for toxin production like entero toxin TRANSPOSONS Genetically discrete segments of DNA Can move in a cut and paste manner between chromosomal DNA & extra chromosomal DNA elements like plasmids within the cell (called jumping genes) Insertion of transposon leads to acquisition of new characteristics by the DNA molecule. Eg. drug resistance to beta lactam by Tn3 transposon Not self replicating & depend upon chromosomal or plasmid DNA for replication GENOTYPE Sum total of the genes that make up the genetic apparatus of a cell (genome) It is the hereditary constitution of the cell It is transmitted to its progeny Includes complete genetic potential of the cell All the genetic potential may or may not be expressed in a given environment PHENOTYPE It is the physical expression of the genotype in a given environment Exhibit different phenotypic appearances in different situations Eg. Synthesis of enzyme beta galactosidase by E.coli only in the presence of lactose
EUKARYOTIC CHROMOSOMES Eukaryotic Chromosome Replicates just prior to mitosis Two molecules of DNA per genetic trait (diploid) some haploid Linear Histones present Genes may be dominant or recessive Organized in the nucleus with a nuclear membrane Introns present DNA DNA also in plasmids chloroplasts Mutations occur in DNA Genetic occur 4000 genes in E.coli DNA About 1.5mm in length Replication by semirecombination Mutations occur in DNA Genetic occur 35,000 genes in total of human chromosome Ten or hundreds of mm in length Replication by semirecombination also in and
Recessive genes nucleus No introns present
mitochondria

Genotypic Alteration in the genome Stable Heritable Not influenced by the environment Phenotypic Alteration expression Unstable Not heritable Influenced environment by in the GENETIC TRANSFER MECHANISMS Transformation
19
Process in which a live bacterium acquires DNA fragments from the environment Fragments of DNA (composed of 10-20 genes) obtained from naturally dying& lysing bacteria in the environment
OCCURRENCE OF GENOTYPIC VARIATION By mutation By mechanisms of genetic transfer or exchange 1. 2. 3. MUTATION It is a random, undirected, heritable variation caused by an alteration in the nucleotide sequence at some point of the DNA of the cell Occurrence Spontaneous Induced by external agents like chemicals, radiation Point Mutation Affects one point (base pair) in a gene May change to or substitution of a different base pair Or Result in the deletion or addition of a base pair Mutation Rate Frequency of mutations expressed as mutation rate Mutation rate is the probability of mutation per gene per cell division In bacteria the rate ranges from 10 to 10 per bacterium per division Consequences of Mutations May be lethal or may affect some minor functions that may not be expressed It is of vital importance when it confers a survival advantage. Eg-if a streptomycin resistant mutant of the tubercle bacillus develops in a patient under treatment with the drug, it multiplies selectively and ultimately replaces the original drug sensitive bacteria Practical importance of mutation is the development of drug resistance
4 9
Mechanism Binding of DNA fragment to recipient bacteria Passage of single stranded DNA into the recipient Incorporation of DNA fragment into the recipient chromosome Significance Acquisition of virulence genes Drug resistance genes Eg. Streptococcus pneumoniae, Haemophilus influenza Transduction A process where bacterial virus called bacteriophage carries the DNA fragment from donor to recipient cell Bacteriophages are viruses that parasitize bacteria and consist of a nucleic acid core & a protein coat After replication inside bacteria, phage assembly occurs When this particle infects another bacterium it acquires the new donor DNA & new characteristics Types 1. Generalized Any segment of donor DNA is transduced at random 2. Restricted/Specialized When a specific phage transduces only a particular genetic trait Sometimes apart from bacterial DNA plasmid can also be transduced Eg. Plasmids determining penicillin resistance in Staphylococcus aureus is transferred from one bacterium to another by transduction Lysogenic conversion A process where phage infecting the bacterium gets incorporated in the bacterial chromosome (such a phage is called prophage)
Transformation Transduction Conjugation

Prophage multiplies synchronously with the host DNA and passed on to daughter cells The prophage confers genetic information to bacteria and is called lysogenic conversion Eg. Prophage in Corynebacterium diphtheriae confers the property of toxin production Conjugation A process where a donor bacterium (F+) makes physical contact with recipient (F-) bacterium and transfers genetic elements into it Donor status is determined by the presence of a plasmid which Codes for the sex pilus forming the conjugation tube Plasmid DNA replicates and a copy of it passes into the recipient Along with the plasmid DNA sometimes host DNA is also transferred Recipient becomes F+ and can in turn conjugate with another F- bacterium Importance
20
Transfer of multi drug resistance through R factor R factor-A plasmid with 2 components (rtf+ r determinants) RTF R is responsible for conjugational for drug transfer determinant responsible resistance Resistance to as many as 8 or more drugs is possible simultaneously Commonly bacteria This transfer of drug resistance is also called transferable or infectious drug resistance Wide spread resistance has considerably diminished the clinical efficacy of antibiotics occurs among gram negative

F-FACTOR Plasmid contains genetic information for synthesis of sex pilus & self transfer Does not carry drug resistance markers Some times when integrated with the host chromosome is called as Episome Such cells are able to transfer high host chromosomal genes with frequency
21
Hence called as Hfr cells COL FACTOR A plasmid carries genes for production of bacteriocins called colicins Colicins are antibiotic like substances produced by intestinal bacteria called coli forms which are selectively and specifically lethal to other bacteria Col factor is capable of self transfer to other bacteria COMPARISON OF MUTATIONAL Transferable Drug Resistance Multiple drug resistance High degree resistance High dose ineffective Combinations prevent does not Spreads to same or different species Not defective Virulence not decreased cannot &
TRANSFERABLE DRUG RESISTANCE Mutational Drug Resistance One drug resistance at a time Low degree resistance Can overcome by high drug dose Drug combinations can prevent Resistance spread Mutants may be defective Virulence may be low
MICROBIOLOGY Sterilization
23
STERILIZATION, DISINFECTTION & ANTISEPSIS

Sterilization: Process by which an article, surface or medium is freed of all organisms Disinfection: Destruction of all pathogenic organisms or organisms capable of giving rise to infection Antisepsis: Prevention of infection usually by inhibiting growth of bacteria CLASSIFICATION Physical Sunlight Drying Heat Dry Moist Filtration UV & Sonic waves Radiations Heavy Metal Salts Halogens Dyes Surfactants Phenols HEAT 3. Gases 2. Chemical Alcohols Aldehydes
Uses: Metal, Glass articles, Fats, Oils Greases, Talc & Sulpha powders Not Sterilized: Glass + Metal articles, Culture media Precautions: Ensure load dried, No overloading, proper packing, Open only after cooling Moist Heat Latent heat makes all the difference! Latent Heat: 1600 ml of steam condenses to one ml of water releasing 518 calories of heat Classification 1. Temperature below 100C Pasteurization Vaccine bath Inspissation Temperature at 100C Boiling Kochs steam sterilizer Temperature above 100C Autoclave Temperature below 100C Pasteurization Holder: 63C x Vaccine bath For cultures only 60C x 30 minutes pure Inspissation 85C x 30 min x 3 successive days Egg & Serum containing media
The most reliable method of choice, unless contraindicated!
30 min Flash: 72C x 20 sec followed by For rapid milk &
Factors influencing 1. 2. Nature of heat dry or moist Temperature & time Lower temp with longer duration or repeat cycle 3. 4. 5. No. of microbes present Types of microbes Type of material to be sterilized
cooling to 12C milk products Temperature at 100C Boiling Best method of
Kochs steam sterilizer 100C x 20 minutes x 3 successive days For sterilization of sugar containing media
Dry Heat Dry heat maintains sterility longer!! Mechanism: Oxidative destruction Methods 1. 2. 3. 4. Flaming: Slides, Scalpels, Needles, Cover-slips Red Heat: Inoculating Loops, Points of Forceps Incineration: Rapid & terminal destruction of soiled material Hot Air Oven
disinfection For instruments used on body surface Temperature above 100C Autoclave Problems
Steam under pressure 15 pound per sq inch 121C x 20 min
Inefficient air discharge system Load remains moist at the end
Hot Air Oven Holding Time: 160C X 60 Min
Types Non jacketed Jacketed takes care of both the problems Precautions for autoclaving Do not forget to put water in the first place! Keep space for free circulation of steam Lid should be screwed air tight Keep the discharge tap open Allow all air to escape before applying pressure Ensure safety valve is functional & adjust to desired level Open discharge valve only after pressure has come to atmospheric level Dyes Uses Articles sterilized Gowns, Towels, dressings, linen Glass or metal instruments Articles with glass & metal components Rubber & plastic articles Culture media, pharmaceutical products Articles not sterilized Fats, oils, greases Talc & other powders Egg & serum containing media Heat labile sugars FILTRATION Basically used for heat labile liquids Halogens Phenols Candle filters Unglazed ceramic. Ex: Chamberland Diatomaceous earth. Ex: Berkfield Asbestos filter Seitz filter Sintered glass filter Membrane filters Cellulose acetate Cellulose nitrate RADIATION 1. Ionizing X-rays Gamma rays Cosmic rays Metallic salts Copper Fungicide Silver Credes prophylaxis Gases Ethylene oxide (ETO or EO) Formaldehyde Betapropiolactone Carbolic acids Chlorphenols Chloroxyphenols Hexachlorphene Chlorhexidine Iodine Chlorine & its compounds Aniline dyes Brilliant green Malachite green Crystal violet Acridine dyes Acriflavin Proflavin Euflavin Aminacrine Aldehydes Formaldehyde Glutaraldehyde 2. Non-ionizing Infra red UV light CHEMICALS ANTISEPTICS Alcohols Ethyl alcohol Isopropyl alcohol Methyl alcohol USED AS
24
DISINFECTANTS
Surface active agents Anionic common soaps Cationic Cetrimide, Benzylcolium chloride Non-ionic Amphoteric
Mercury CONCENTRATIONS OF THE
25
WORKING 1. 2. 3. 4.
COMMONLY USED DISINFECTANTS Ethanol 70% Methylated spirit 70% Glutaraldehyde 2 Bleaching powder i. ii. 5. 6. 7. 8. 9. Calcium hypochlorite 1.4% Sodium hypochlorite 0.1 to 1%
Hydrogen peroxide 3% Savlon 2%, 5% Dettol 4% Betadine 2% Ethylene oxide 10%
TESTING OF DISINFECTANTS Rideal Walker test Phenol coefficient taken as 1 Comparison made of new agent with phenol Test carried out in lab conditions
Chick Martin Test Similar to Rideal Walker test but in presence of 3% dried human faeces Indicates effectivity in field conditions
MICROBIOLOGY Infection
INFECTION
Infection: Lodgement & multiplication of parasite in or on host tissues of a host BACTERIAL ZOONOSES Infectious diseases which are primarily affect the animal and capable of transferring from animals to human beings are called Zoonoses. Based on the type of etiological agent, Zoonoses are classified as 1. 2. 3. 4. Bacterial Viral Fungal Parasitic i. ii. Examples Name of the Bacteria Bacillus anthraces Yersinia pestis Brucella spp E.g: abortus Lepto spira Campylo bacter jejuni Brucella Agent transmitting Infection Cattle, sheep etc Rats Goats Sheep Cattle Buffalos Rodents, etc Domestic animals,(Poultry) Leptospirosis Gastro enteritis Brucellosis 2. Anthrax Plague Diseases Protozoal Helminthic
Still birth NOSOCOMIAL INFECTIONS Any clinically recognizable disease that affects a patient as a consequence of admission into the hospital or from the hospital staff as a consequence of their work is called as hospital acquired infection (Nosocomial infections) The term is derived from the Greek word Nosos meaning Disease and Koneo meaning to take care of. Nosocomial infections are largely a product of advances in medical treatment like Intravenous catheters Urinary and other catheters Invasive diagnostic tests, Complex surgical procedures Intensive use of antibiotics contributes to the development of resistant strains of pathogens. METHODS OF TRANSMISSION OF INFECTION 1. Contact i. ii. Direct: ex: STDs are transmitted by this method. Indirect: Through contaminated Fomites like Toys, Pencils, and clothing. Ex: Diphtheria, Trachoma are transmitted. Inhalation Usually respiratory tract transmitted by this route. Secretions are released from the patient during Sneezing, Speaking and Coughing and converted into droplet nuclei and aerosols which contain the microbial agent. Ex: H. influenza, Tubercle bacilli, Many viral infections 3. Ingestion Through contaminated food & water microbes are ingested. Ex: Cholera, Dysentery, Food poisoning with B. cereus, Staphylococci. 4. Inoculation Pathogenic their forms are tissues. Ex: Tetanus spores. Arboviruses through the insects. injected into infections are
CONGENITAL INFECTIONS (TRANSPLACENTAL INFECTIONS) Most infections do not result in bacteremia or viremia and fetal involvement. However, if the pathogen crosses the placenta and infection occurs In utero, results in serious damage to the fetus. Fetal infection results in Malformations like cardiac anomalies, Microcephaly Infected fetus with or without disease: Mental deafness Spontaneous Abortion Fetal death retardation, Cataract, Sensory
MICROBIOLOGY Infection
5. Congenital transmission (Trans placental,
Vertical transmission) Placental defects results in congenital transformation of microbes from the infected mother and may results in congenital infections or severe congenital malformations (Teratogenic infections). Ex: To R C H complex, HIV, HCV, HBV, Chicken pox. 6. Iatrogenic infections Some of the therapeutic or investigative procedures are responsible for the transmission of the infectious agents. Procedures like Dialysis, Transfusions, Heart Surgery, of Transplant injections, Surgery, Lumbar administration
puncture, Catheterization. MICROBIOL CARRIER A carrier is a person who harbors the pathogenic microorganism with or without suffering from any ill effects because of it. Types of Carrier 1. Healthy carrier is one who harbors the pathogen but has never suffered from the disease caused by pathogen. 2. Convalescent carrier is one who has recovered from the disease and continues to harbor pathogen in his body. 3. 4. Temporary carrier: Who harbors the pathogen for not more than 6-9 months duration Chronic carrier: causative agent may persist for several years and sometimes even for the rest of ones life. 5. 6. Contact carrier: is applied to a person who acquires the pathogen from the patient Paradoxical carrier: Refers to a carrier who acquires the pathogen from another carrier the
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PHARMACOLOGY General Pharmacology
GENERAL PHARMACOLOGY
Important Terms and Scientists Allopathy Homeopathy Principle of Homeopathy Rudolf Buchheim Oswald Schmiedeberg P Ehrlich Definitions The other suffering The similar suffering (Hannemann) Like cures like Dilution potentiates the actions of drugs
Founded First Institute of Pharmacology Father of Pharmacology Father of Chemotherapy
Pharmacognosy Pharmacoeconomics Pharmaco epidemiology Pharmaco vigilance Pharmacogenetics Pharmacogenomics
Science of identification of drugs from natural sources Analysis of the cost of drug therapy to the health care system and the society The study of use and effects of drugs in large number of people Science and activities related to detection, evaluation, understanding and prevention of adverse effects or any other drug related problems The study of genetically mediated variation/differences in drug metabolism and response in humans The use of genetic information to guide the choice of drug and dose on an individual basis Official code containing selected list of the established drugs and medicinal preparations with descriptions of their physical properties and tests for their identity, purity and potency Book which provides the subscriber with information about the available
Pharmacopoeia
Formulary
drugs, based on original and reputed drug information sources as well as experts recommendation Drugs those satisfy the priority health care need of the population and hence should be available at all times and in adequate amounts, appropriate dosage forms with assured quality and adequate information Drugs or biological products for diagnosis/treatment/prevention of rare disease or condition, or a more common disease for which there is no reasonable expectation that the cost of developing and marketing it will be recovered from the sales of that drug
Essential drugs (Medicine)
Orphan Drugs
PHARMACOLOGY General Pharmacology Words and their Derivations Word Pharmacology Pharmacovigilance Pharmacopoeia Placebo Teratogenicity Iatrogenecity Derived from Pharmacon Drug (in Greek) Logos Discourse Vigilare to watch to make Placere to please Taros (monster) Iatros (physician)
Sources of Drugs Minerals Animals Plant Microorganisms Synthetic Genetic engineering (Recombinant DNA Technology) Hybridoma technique Monoclonal antibodies Ex: Abciximab, Infliximab, Rituximab, Basiliximab Insulin, GH, Interleukins, Interferons, Alteplase, Erythropoietin Liquid paraffin, Magnesium sulphate, Magnesium trisilicate, Silver nitrate, Iron salts Insulin, Heparin, Thyroid Hormone, Gonadotropins, Antitoxin Sera Morphine, Digoxin, Quinine, Atropine, Pilocarpine, Physostigmine, Salicylic acid, Reserpine, Vinca Alkaloids Antibiotics, Streptokinase, L-Asparaginase Analgesic, Anticancer drugs, Antimicrobial agents
Drugs active principles (Nature of Sources) Alkaloid Glycosides Resins Oleoresins Gums Tannins Water Soluble salts of water, insoluble nitrogenous compounds Ether like combinations of sugar with other organic structures Oxidized or polymerized volatile oils Mixture of volatile oils and resins Secretory products of plants which form thick, mucilaginous colloids with water Non nitrogenous constituents or Astringents
Iontophoresis: In this procedure, galvanic current allows penetration of drugs applied to skin into deeper tissues Anode Iontophoresis: For compounds having positive charge, force of repulsion drives the drug into deeper tissues. Ex: Salicylates, Fluoride Iontophoresis for dental hypersensitivity Special Drug Delivery Systems Ocusert Ex: Pilocarpine Placed under eyelid; drug remains round the clock up to 7 days
PHARMACOLOGY General Pharmacology Progestasert Drug Eluting stents (DES) Ex: Sirolimus, Paclitaxel Targeted delivery Liposomes Ex: Anticancer drugs (Daunorubicin and Doxorubicin), Amphoterecin B, Gentamicin, Insulin (tried) Osmotic drug delivery system or GITS (Gastro Intestinal Therapeutic Systems) Soft contact lens Ex: Pilocarpine Ex: Prazosin, Nifedipine Intrauterine contraceptive device releases drug for up to 1year
Metallic stent backbone covered with a polymer Drug gradually released over 14 - 30 days and modifies local healing response with the stented artery (tried in coronary angioplasty) For anticancer drugs using monoclonal antibodies against cancer cell antigens Vehicles for targeted drug delivery are concentric, spherical shells of phospholipids in watery medium into which drugs are incorporated
CHIRALITY: (word comes from Cheir Hand in Greek) Many commonly used drugs exists as race mates i.e. 50:50 mixture of non super imposable right handed and left handed mirror image stereo isomers (enantiomers). The two molecules may differ in pharmacokinetics or toxicity. Several drugs are now developed as single enantiomers to provide uniform action and reduce adverse effects. Ex: S-Atenolol, R-Salbutamol, cis Atracurium, S-Omeprazole, levo Cetrizine
ABSORPTION Definition: Movement of drug from site of administration into systemic circulation. Drug may cross biological membrane (100A thick) by 1. 2. 3. Passive diffusion (commonest mode) Carrier mediated transport Pinocytosis and filtration Active transport occur against concentration gradient (requires energy ATP) occurs along concentration gradient (no energy required) (diffusion) Facilitated transport Names of Transporter Proteins 1. 2. 3. 4. 5. SLC transporters solute carrier transporters for facilitated diffusion for primary active transport for P. glycoprotein, ATP binding cassette transporters secondary active transport Pinocytosis only for larger molecules (MW>1000), engulfment. Ex: Proteins Filtration Occurs through pores or paracellular spaces. Mostly occurs through capillaries (have large paracellular spaces)
Organic Anion Transporting Polypeptide (OATP), Organic Cationic Transporter (OCT)
General principles of absorption Weak acids are better absorbed in acidic environment; weak bases in basic environment Strong acid/alkalies are always ionized so above principle do not apply Basic drugs are always concentrated intra cellularly For easy penetration or diffusion, molecule should be unionized Phagocytosis (cell eating) Pinocytosis (cell drinking)
Factors affecting Drug Absorption 1. Physical properties Physical State, Lipid and Water Solubility Particle Size, Disintegration Time, Dissolution Time, Formulations 2. Nature of dosage forms Micro fining of drug particles to improve absorption dose for drugs like Aspirin, Griseofulvin, Spironolactone Some drugs are purposely made of larger size to decrease systemic absorption and toxicity. Ex: Bephenium hydroxynaphthoate Ionization, pH of GI fluids and blood GI transit time, Enterohepatic circulation 3. Physiological factors Area of absorbing surface, vascularity of absorbing area First pass metabolism Presence of other drugs 4. 5. Pharmocogenetic factors Diseases Ex: Malabsorption, Thyrotoxicosis, Cirrhosis, Achlorhydria
Ion Trapping When acidic drug comes in contact with acidic pH of stomach, it remains in unionised form. But when it penetrates the gastric mucosal cell, it gets ionized since intracellular pH is alkaline. Hence acidic drug can get stored within the cell in ionized state. The process is called Ion Trapping. Ex: Aspirin To facilitate drug absorption by oral route, micro fining of drug particles are done. Ex: aspirin, Griseofulvin, Spironolactone Certain dugs particle size is purposely made larger to slow the absorption by oral route. Ex: Bephenium hydroxynaphthoate Bioavailability Fraction of administered dose of the drug that reaches the systemic circulation in unchanged form following non-vascular administration It is the measure of rate and extent of drug absorption. Denoted by F When drug is administered IV, bioavailability is 100 % Plasma concentration time curve denote bioavailability of drug by different routes. The graph obtained is called Area Under Curve (AUC) F can be calculated by comparing AUC of a drug by any route to IV route
AUC by oral route x 100 AUC by IV route
Pharmaceutical Equivalence
If drug formulations are identical in strength, concentration and dosage forms, they are said to be pharmaceutically equivalent
Bioequivalence
When the rates and extent of bioavailability of the active ingredients in the two formulations which are pharmaceutically equivalent do not differ significantly under standard condition, they are termed as bioequivalent preparations
Usually bioavailability by IV Route is 100 % except for few drugs like Chloramphenicol succinate since there is renal excretion of ester before hydrolysis Some drugs have almost 100 % bioavailability by oral route like warfarin, clonidine, levofloxacin etc BA/BE studies are very important for drugs having narrow margin of safety and during antimicrobial therapy failure
DISTRIBUTION Apparent volume of distribution (Vd): Volume that would accommodate all the drug in the body, if the concentration throughout was the same as the plasma
= Factors governing (Vd) 1. 2. 3. 4. 5. Plasma protein binding Affinity for different tissues
Lipid water partition coefficient of drug pKa, Fat lean body mass ratio Diseases like CHF, uraemia, cirrhosis, edema
Redistribution Common with highly lipid soluble drugs Initially, they get distributed to organs with high blood flow. Ex: Brain Later, less vascular more bulky tissues take the drug. Ex: Adipose tissue results in termination of action of certain drugs. Ex: Thiopentone Na, Diazepam Blood Brain Barrier (BBB) Deficient in 1. 2. 3. 4. CTZ (Medulla Oblongata) Pineal body Anterior hypothalamus Anterior and lateral commisures
PHARMACOLOGY General Pharmacology Drugs which DO NOT cross BBB 1. 2. 3. 4. Streptomycin Dopamine Neostigmine Domperidone
Some drugs usually do not cross BBB, but in presence of inflammation of meninges, they can cross easily. Ex: Penicillin G
Plasma Proteins Acidic drugs Albumin Ex: NSAIDs, Barbiturates, Benzodiazepines, Penicillins, Tetracyclines Basic drugs 1 acid glycoprotein 1. 2. 3. 4. Highly bound drugs have restriction to vascular compartment, hence low Vd Only free (unbound) drug is available for action Highly bound drugs have longer duration of action Highly bound drugs show drug displacement reactions Ex: -blockers, Lignocaine, Verapamil, Prazosin, Impramine Highly plasma protein bound drugs Drugs which are 0 % bound Sulfonamides, Methotrexate, Indomethacin, and Warfarin Ethosuccimide, Lithium
BIOTRANSFORMATION (METABOLISM) Definition Sites Liver (commonest), others kidney, intestine, lungs, plasma Streptomycin, Neostigmine, Mannitol Drugs which are not biotransformed 1. 2. 3. Prodrug: Inactive form of drug which gets converted into the body into one or more active metabolites Advantages of Prodrug more stable, better bioavailability, less side effects or toxicity Active drug Morphine Diazepam Digitoxin Active metabolite Morphine-6-Glucuronide Oxazepam Digoxin Inactivation Active drug Prodrug active metabolite active metabolite(s) Chemical alteration of drug in the body To facilitate easy excretion/elimination of drug Lipid soluble (non polar) lipid insoluble (polar) which is excreted Purpose
Three major types of processes involved
Substances metabolized in lungs - Prostaglandins
PHARMACOLOGY General Pharmacology Spironolactone Imipramine Desipramine Canrenone Amitryptyline Nortryptyline
Prodrug Levodopa Enalapril Bacampicillin Omeprazole Dipivefrin (in Glaucoma)
Active drug Dopamine Enalaprilate Ampicillin Sulphenic acid + Sulphenamide configuration Adrenaline
REACTIONS Phase I (Non synthetic/Functionalisation)
Produces active or inactive metabolites 1. 2. 3. 4. 5. Oxidation (commonest) Enzyme mostly involved (CYP3A4) Reduction Ex: Chloramphenicol, Warfarin, Halothane Hydrolysis Ex: Choline esters, Pethidine, Lignocaine, Aspirin, Oxytocin Cyclization Ex: Proguanil, Methadone Decyclization Ex: Barbiturates, Phenytoin
Phase II (Synthetic/Conjugation)
Produces mostly inactive metabolites 1. 2. 3. 4. 5. 6. 7. Glucuronide conjugation (commonest) Acetylation Ex: Sulfonamides, INH, Hydralazine, PAS Methylation Ex: Adrenaline, Histamine, Methyl dopa, Captopril Sulfation Ex: Chloramphenicol, Steroids Glycine conjugation Ex: Salicylates Glutathione conjugation Ex: Paracetamol Ribonucleoside/nucleotide synthesis Ex: Purine & Pyrimidine metabolites
Microsomal enzymes
Present in microtubules (smooth ER) They are inducible Ex: Monooxygenases, Cytochrome P450, glucuronyl transferase
Non Microsomal enzymes
Present in cytoplasm and mitochondria Non inducible Ex: flavoprotein oxidases, esterases, amidases, conjugases
Hofmann elimination
Inactivation of drug in the body fluids by spontaneous molecular rearrangement without using any enzymes Ex: Atracurium
First pass metabolism (pre systemic)
Refers to metabolism of drug during its passage from the site of absorption into systemic circulation Site: intestinal wall, liver, skin, lungs First pass metabolism is inversely proportional to oral bioavailability There is marked inter individual variation in 1st pass metabolism Drugs with high first pass metabolism: Lignocaine, Morphine, Propranolol, and Hydrocortisone Drugs with low first pass metabolism: Phenobarbitone, Tolbutamide, Theophylline, and Isosorbide Mononitrate
Microsomal Enzyme inducers
Phenobarbitone, Rifampicin, Phenytoin, Carbamazepine, INH, Griseofulvin, Chronic alcohol, Smoking, DDT
Enzyme inhibitors
Omeprazole, Erythromycin, Cimetidine, Ketoconazole
EXCRETION After biotransformation, drug is ready to pass out through various routes given below 1. 2. 3. 4. 5. 1. 2. 3. Kidney (urine) Commonest Faeces (bile) Purgatives, Heavy Metals, Rifampicin, Ampicillin, Tetracycline Exhaled air Inhaled anaesthetics, Alcohol Saliva, sweat Lithium, KI, Rifampicin, Heavy metals Milk Usually basic drugs are concentrated in milk
Routes
Glomerular filtration depends upon plasma protein binding & renal blood flow Tubular reabsorption depends upon lipid solubility & ionization of drugs at given urinary pH. Hence Acidic drugs better excreted in alkaline urine & vice versa Tubular secretion Bidirectional process. Probenecid prolongs duration of Penicillin G by blocking its tubular secretion
Clearance (CL)
Theoretical volume of plasma from which drug is completely removed in unit time CL =

First order kinetics (Exponential)
Constant FRACTION of drug is eliminated in unit time. Thus CL remains constant.
Zero order kinetics (Linear)

Constant AMOUNT of drug is eliminated in unit time Thus CL decreases with increase in concentration. Ex: Ethyl alcohol Some drug kinetics changes from first order to zero order at higher doses. Ex: Phenytoin, Tolbutamide, Theophylline, Warfarin
Saturation kinetics
Plasma half life
The time taken for the plasma concentration of drug to be reduced to half of its original value 2 phases distribution & elimination Formula: t = 0.693

(t =
K = elimination rate constant)
Complete drug elimination occurs in approx. 4 5 half lives Steady state concentration (CPSS) is achieved in 4 5 half lives CPSS =

Loading dose =
Hit & Run Drugs
Drugs whose effect lasts much longer even if drug is not present in the body Ex: Omeprazole, MAO Inhibitors
Methods of prolonging Drug Action 1. Prolonging absorption from site of administration 2. 3. 4. Orally sustained release tablets (timesules), spansules, controlled release tablets oily solutions, adding proteins (using Poly Ethylene Glycol (PEG), Protamine), Parenteral
pellet implantation, using vasoconstrictor Transdermal route Increasing plasma protein binding Ex: Sulfonamides Ex: addition of chemical groups like ethinyl, estradiol; inhibition of enzymes Ex: Probenecid+ Penicillin Retarding rate of metabolism (inhibition of enzymes) Retarding Renal excretions
Therapeutic Drug monitoring (TDM) Done in cases like 1. 2. 3. 4. 5. Drug with low therapeutic Index (low safety margin). Ex. Digoxin, Lithium, Theophylline, Antidepressants Inter individual variations are large Toxic drugs used in renal failure Poisoning To check patient compliance. Ex: drugs used in psychiatry
Principles of Drug Action 1. 2. 3. Stimulation Depression Irritation

PHARMACOLOGY General Pharmacology 4. 5. 6. Replacement Cytotoxic action Modification of immune status
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Mechanisms of Drug Action 1. 2. 3. 4. 5. 6. Physical property. Ex: Mass of drug, Radio opacity, Radioactivity, Osmotic property Chemical property. Ex: Acid neutralisation, Oxidising agents, Chelating agents Through Enzymes Ion channels Transporters Receptors
Agonist: agent which activates a receptor to produce an effect (maximal) Antagonist: agent which activates a receptor to produce an effect in the opposite direction to that of the agonist Partial Agonist: agent which activates a receptor to produce sub maximal effect but antagonises the effect of a full agonist Inverse Agonist: agent which activates a receptor to produce an effect in the opposite direction to that of agonist. Ex: DMCM on Benzodiazepine receptor Ligand: Any molecule which attaches selectively to particular receptors or sites Affinity: Ability of a drug to bind to receptor Intrinsic Activity (IA) / Efficacy: Capacity to induce functional change in the receptor Agonist Affinity +, IA Antagonist Affinity +, IA Partial Agonist Affinity +, IA Inverse Agonist Affinity +, IA neurotransmitters. Silent Receptors: those sites which bind specific drugs but no pharmacological response is elicited. Also called drug acceptors/sites of loss. Ex: Plasma proteins Drug action: Refers to initial combination of drug to receptor resulting in conformational change in the latter Drug effect: It is the ultimate change in biological function brought about as consequences of drug action through source of transducer mechanism Receptors located in nucleus: Thyroid hormones, Vitamin A Receptors located in cytoplasm: Glucocorticoids, Androgens, Estrogens, Progesterone Transducer mechanisms 1. G. protein coupled receptors i. Adenylylcyclase cAMP pathway ii. Phospholipase IP3/DAG pathway iii. Channel regulation 2. 3. 4. Receptors with intrinsic ion channel Enzyme-linked receptors Insulin, ANP Receptors regulating gene expression (transcription factors) Steroids, Sex hormones, Vitamin A & D 1 0 01 01
Auto Receptors: usually present pre synaptically. Ex: 2, M2, 5HT1A. They decrease the action of
Therapeutic Window Phenomenon
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Optimal therapeutic effect is exerted only over a narrow range of plasma drug concentration both below and above this range, beneficial effects are sub optimal Ex: Tricyclic antidepressants, Clonidine, Glipizide
Drug Potency: amount of drug needed to produce a certain response Drug Efficacy: Maximal response that can be elicited by a drug Therapeutic Index (TI) Refers to margin of safety of drug TI = or Drugs with Low TI - Antiepileptics like Phenytoin, Carbamazepine, Valproate, Antiarrhythmics, Digoxin, Lithium, Theophylline, Barbiturates, and Antidepressants Drugs with High TI = Benzodiazepines, Penicillin G, Chlorpromazine

Drug Synergism: when action of one drug is increased/facilitated by other 1. 2. Additive: Ex: Combination of analgesics, GAs, Bronchodilators Supra additive (potentiation): Ex: Sulfamethoxazole + Trimethoprim; Acetylcholine + Physostigmine; Levodopa + Carbidopa; Amphoterecin B + 5-Flucytosine Drug Antagonism: when one drug decreases or abolishes the action of another 1. 2. 3. 4. Physical Charcoal adsorbs alkalies Chemical KMnO4 oxidises alkaloids, chelating agents, complex heavy metals Physiological/functional Histamine or Adrenaline on bronchial smooth muscles, insulin glucagon on blood sugar level Receptor antagonism Competitive, Non competitive Diazepam Bicuculline
Equilibrium Ex: ACh, Atropine, Morphine, Naloxone Drug Dosage 1. 2. 3. 4.
Non Equilibrium Ex: Adrenaline, Phenoxybenzamine
Standard dose Ex: Penicillin, Chloroquine, Mebendazole Regulated dose Ex: Hypoglycemics, Antihypertensives, Anticoagulants Target level dose Ex: Antiepileptics, Antidepressants, Digoxin, Lithium Titrated dose Ex: Anticancer drugs, Corticosteroids.
Factors Modifying Drug Action = Body size BSA m x Average adult dose 1.7 Youngs Formula: = x Adult dose =
BW Kg x Average adult dose 70
Age
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Dillings Formula: = Clarks Formula: =
x Adult dose
x Adult dose
Frieds Formula: =
x Adult dose
Cowlings Formula: = Sex Species and Race Genetics Routes of Administration Environmental factors, Time of administration Psychological factors Disease Presence of other Drugs Cumulation
x Adult dose
Dose is less in females than males Antihypertensives interfere with sexual function in males Rabbits resistant to Atropine (develop Atropinase enzyme) Rats/mice resistant to Digoxin Indians tolerate Thiacetazone Quinidochlor is better to foreigners Atypical pseudocholinesterase Succinylcholine apnoea G6PD deficiency Haemolysis due to Primaquine Malignant hyperthermia Halothane Acute intermittent porphyria Barbiturates MgSO4 different actions by different routes * Insecticides, Carcinogens, Tobacco smoke Diazepam (sedatives) act better at night Steroids less HPA axis suppression if given in morning Simvastatin Maximum action at night (cholesterol reduction)
Placebo, Nocebo Diseases of Liver, Kidney, Heart, Thyroid etc Drug interactions Occurs if rate of admission is more than rate of elimination Ex: Chloroquine causing retinal damage, Digoxin causing renal damage Natural, Acquired Ex: Barbiturates, Opioids, Ethyl alcohol, Antipsychotics Tachyphylaxis Rapid development of tolerance. Ex: Tyramine, Ephedrine, Nicotine Tachy Fast, Phylaxis Protection Barbiturates tolerance by both pharmacokinetic and pharmacodynamic mechanism Cross tolerance: Development of tolerance to pharmacologically related drugs. Ex: Alcohol, Barbiturates, GA
Tolerance
* Magnesium Sulphate
PHARMACOLOGY General Pharmacology 1. 2. 3. 4. Orally (Epsom salt) act as purgative When applied over skin relieves cellular edema due to its hygroscopic property Rectally relieves cerebral edema IV Antiarrhythmic, Anticonvulsant, uterine relaxant
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Adverse Drug effects Side effect Toxic effect Secondary effect Intolerance Idiosyncrasy Unwanted and unavoidable pharmacodynamic effects which occur at therapeutic doses Excessive pharmacological actions of drug due to over dosage or prolonged use Indirect consequences of a primary action of drug Appearing of characteristic toxic effect of a drug in an individual at therapeutic dose (indicates low threshold of individual) Genetically determined abnormal reactivity to a chemical Immunologically mediated reaction which is unrelated to pharmacological profile of drug and independent of dose. Always needs prior sensitization Drug allergy Type I (Anaphylactic/IgE mediated) itching, urticaria anaphylaxis Type II (Cytotoxic/IgG, IgM) cell destruction Type III (Arthus/IgG) serum sickness Type IV (Delayed) Cell mediated, T lymphocytes Contact dermatitis Type I H1 antihistamines (itching, urticaria) Treatment of allergy Adrenaline IM (Anaphylactic shock) Steroids: effective for all hypersensitivity reactions (I to IV) inflammatory response on blood vessels; Humoral
Skin test- detects only type I reaction Cutaneous reaction from drug induced sensitization of skin to UV radiation Photosensitivity Phototoxic toxicity: UV-B (290-320 nm) UV-A (320-400 nm) erythema, Ex: edema, blistering, hyper pigmentation, Sulphonamide, Fluroquinolone, Sulfones, Photo allergic
Photo
desquamation. Phenothiazines
Photo allergic: cell mediated response like Contact dermatitis Use of drug for personal satisfaction where drug alters mood and feelings Psychological mild Physical severe
Drug dependence
Physical dependence leads to withdrawal symptoms. Ex: Opioids, Cocaine, Alcohol, Barbiturates Drug addiction: pattern of compulsive drug use characterized by over whelming involvement with use of drug
PHARMACOLOGY General Pharmacology Drug withdrawal reactions Abrupt withdrawal Ex: steroids acute adrenal insufficiency - blockers worsening of angina, MI Antiepileptics frequency of seizures increased Teratogenicity Ability of drug to induce foetal abnormalities when administered to pregnant mother. First case: Thalidomide Drugs affect in 3 stages 1. 2. 3. Carcinogenicity Mutagenecity Fertilization and implantation: conception to 17 days, failure of pregnancy Organogenesis: 18 55 days deformities predicted Growth and development: 56 day onwards development and functional abnormalities Ex: Phenytoin, Warfarin, Tetracycline, Lithium, Valproate, Steroids Capacity of drug to induce cancer. Ex: Anticancer drugs, Estrogens, Radioisotopes Capacity of drug to induce genetic defects. Ex: Metronidazole, Radioisotopes Iatrogenecity Drug Interactions In Vitro: some drugs react chemically in syringes Ex: Succinylcholine + Thiopentone Penicillin + Gentamicin In Vivo: in the body Pharmacokinetic, Pharmacodynamic Pharmacokinetic: Ex: Rifampicin + OCs tubular secretion Harmful Salicylates displace Methotrexate from ppb sites Pharmacodynamic: Ex: Drug Synergism/Autogonosim failure of OCs due to fast metabolism Physician induced diseases due to drugs Diseases persist even if drug is withdrawn Ex: Peptic ulcer by NSAIDS, Hepatitis by Rifampicin/INH Parkinsons disease by Phenothiazines (antipsychotics) Phocomelia (seal like limbs, Birth defect) in 1958
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Favourable - Penicillin + Probenecid Penicillin duration of action is increased due to blockade of
Dosage Forms Dusting powders Insufflations Meant for external use. Ex: Boric acid powder, Talc Fine dusting powders which are blown with the help of insufflators into nose/ear
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Lozenges Vitrellae Suppository Pessary Bougies Mixture Elixir Linctuses
Solid preparations made of sugar & gum, used for local action in mouth and throat. Ex: Cough remedies Thin walled glass capsules containing volatile substances. Ex: Amyl Nitrite Ovoid shaped solid preparations meant for insertion into rectum Ex: LA for piles, Bisacodyl for constipation Cone shaped rolled dosage forms meant for insertion into vagina Long cylindrical (thin) dosage form for introduction into urethra Liquid preparation containing two or more substances meant for oral use Clear, palatable, flavoured liquid preparation for oral use Sweet viscous liquids containing syrup with glycerine Ex: Cough remedies Liquid preparation meant for introduction into rectum Retention enema Steroids Evacuant enema soap + glycerine water purgation Hydro alcoholic preparation of vegetable drugs Ex: Tincture benzoin, Tincture iodine Liquid/semi liquid preparation meant for skin application with friction Ex: Turpentine liniment Liquid/semi liquid preparation meant for skin application without friction Ex: Calamine lotion Semisolid preparation for external application, contain a greasy base Ex: Conite fields ointment Same as ointment but contain water soluble base (cleansed easily) Same as ointment but contain a non greasy base
Enema
Tincture Liniment Lotion Ointment Cream Paste
Routes of Drug Administration 1. 2. 3. 4. 5. 6. 7. 8. 9. Sublingual Nitroglycerine, Nifedipine, Isoprenaline, Clonidine, Ergotamine, Buprenorphine Rectal injection Diazepine, Paracetamol, Indomethacin, Ergotamine Transdermal patch Nitroglycerine, Nicotine, Hyoscine, Clonidine, Estradiol, Fentanyl, Bupropion Inhalation N2O, Ether, Halothane, O2, Amyl Nitrate, Insulin Nasal Oxytocin, Desmopressin, Calcitonin, Azelastine, Sodium Cromoglycate, Budesonide Intra dermal BCG vaccine, Sensitivity testing (Penicillin, vitamin B12) Subcutaneous Insulin, Adrenaline, Salbutamol, Heparin, Morphine, Bethanechol Intra muscular Analgesics, Antibiotics Intra articular Steroids (for arthritis)
10. Intra arterial Dyes for angiography, Anticancer drugs 11. Intra cardiac Adrenaline DRUGS GIVEN ONLY INTRA VENOUS Blood, Dopamine, Adenosine, Esmolol, Plasma Expanders DRUGS NOT TO BE GIVEN INTRA MUSCULARLY Heparin, Diazepam, Phenytoin Drugs given through endotracheal tube in emergencies Adrenaline, Atropine
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NEW DRUG DEVELOPMENT STAGES 1. 2. 3. 4. 5. 6. 7. Synthesis/Isolation of Compound 1-2 years 2-4 years 3-6 months 1 year Animal studies (screening, short term toxicity) Scrutiny & grant of permission for clinical trials Clinical trials (Phase I, II and III) 3-10 years 0.5-2 years
Pharmaceutical formulation/Standardisation of drug Review & grant of marketing permission Post marketing surveillance (Phase IV)
PHASES OF CLINICAL TRIALS I. Human Pharmacology and Safety Carried out by qualified clinical pharmacologist or trained physicians Mostly healthy volunteers are selected Drugs are given with lowest dose and stepwise increase in dose in 20-40 healthy volunteers and safety and tolerability is checked No blinding is done
II. Therapeutic exploration and dose ranging Done by trained clinical investigators on 100-400 patients Aim is to study therapeutic efficacy, dose range and ceiling effect in controlled setting Blinding is done
III. Therapeutic confirmation/comparison Carried over 500-3000 patients by several physicians at many centres Aim is to establish safety, tolerability, drug interactions, additional pharmacokinetic data After this phase, New Drug Application (NDA) is submitted to Licensing Authority for obtaining marketing permission IV. Post marketing surveillance/studies Practicing physicians are identified and data collected from them regarding efficacy, acceptability and adverse effects of the drug Uncommon/idiosyncratic adverse effects and long term side effects and uncommon drug interactions are deleted in this phase Toxicity studies Usually done in animals like rat, mice, guinea pig, dog, rabbit 1. Acute toxicity Single toxic dose is given in group of animals and observed for organ damage and mortality over 1-3 days 2. Subacute toxicity Repeated doses are given for 2-12 weeks
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Animals are examined for overt effects, food intake, body weight, haematology, organ toxicity 3. Chronic toxicity Drug is given for 6-12 months and same effects like sub acute toxicity are studied
TRANSDUCER MECHANISMS 1. G-Protein Coupled Receptors (GPCR) Commonest mechanisms for various receptors like adrenergic, muscarinic, dopaminergic, histaminergic, purinergic, opioid, GABA, prostaglandins, leukotriene, angiotensin, bradykinin, FSH, LH, ACTH, TSH etc 2. 3. Receptors with intrinsic ion channel 4. Nicotinic, GABA, Glycine, 5HT3, Kainate Insulin, epidermal growth factor, nerve growth factor atrial natriuretic peptide, cytokines, interleukins, growth hormone, interferons Receptors regulating gene expression Steroids, androgens, estrogens, progesterone, thyroxin, Vitamin A and Vitamin D Enzyme linked receptors
P- Drug (Personal drug) concept P-drugs refer to those drugs which a physician chooses for prescribing regularly and with which he becomes familiar. Since varieties of drugs are available from different companies, it is difficult for a practicing physician to remember about their brand names, dose, cost, tolerability. Hence a physician selects few drugs to prescribe and those drugs he makes an attempt to remember all the properties. Now with the inflow of increasing number of drugs, it is essential to prepare ones own pocket pdrug formulary. Drug expiry and shelf life On an average, expiry date of any formulation is between 2-3 years from the date of manufacture. Shelf life of a drug is the time where a given product stored under reasonable conditions is expected to remain stable. During the shelf life, the product should have potency in excess of 90%.
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DENTAL MATERIALS Nature of Metals and Alloys
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NATURE OF METALS AND ALLOYS

Metals represent one of the four major groups of dental materials. The Metals Handbook (1992) defines a Metal as "an opaque lustrous chemical substance that is a good conductor of heat and electricity and, when polished, is a good reflector of light." An Alloy is a substance with metallic properties that consists of two or more chemical elements, at least one of which is a metal. The study of metals and alloys is called as Metallurgy Gallium and Mercury, elements commonly used in dental alloys, are liquid at body temperature A unique characteristic of metals is that they are good thermal and electrical conductors. Compared with ceramics, polymers, and composites, metals have high fracture toughness (KIc), i.e. the ability to absorb energy and inhibit crack propagation under increasing tensile stress. This property is a measure of the resistance of a material to clack propagation Noble metals (gold, iridium, osmium, and palladium, platinum, rhodium,
Sag: deformation of a metal or alloy; for our discussion, this occurs at high temperatures such as during porcelain firing.
Generally, alloys are used in dentistry because alloying strengthens a metal. Pure metals such as gold are not used because their relatively poor physical properties make them a poor choice for intraoral use. For example, pure cast gold is only 1/5th as strong and 1/6th as hard as a typical gold-based casting alloy.
During solidification (i.e., when a metal or alloy goes from liquid to solid), the following process occurs: random atoms to embryos (temporary nuclei) to nuclei to dendrites to grains
As the grains grow, they contact each other. The border between them is called a grain boundary.
Generally, a metal to be used under intraoral conditions should have a fine grained structure because it tends to be more resistant to permanent deformation.
BONDING OF METALS Apart from ionic and covalent bonding a solid can be held together by metallic bonds. Metallic bonds are formed between the free moving valence electrons and the positively charged ionic cores. Outer shell valence electrons can be removed easily from atoms in metals, thus the nuclei contains the balance of the bound electrons forming a positively charged ionic core. The electrons from these metal atoms flow freely to form a sea of electrons or cloud or gas Often called delocalized electrons Since the electrons are negatively charged and ionic cores are positively charged, electrostatic attraction force results giving rise to metallic bonds which holds the particles in the atom together ATOMIC STRUCTURE Atomic level, pure metals exist as crystalline arrays.
ruthenium) are highly resistant to corrosion and oxidation and do not require alloying elements for this purpose TERMINOLOGY Liquidus: the temperature below which a metal is completely solid (i.e., the temperature at which it begins to melt). Solidus: the temperature above which a metal is completely melted. Grain: a single crystal of metal as seen in the metals microstructure. Grain refiner: a metal such as iridium that is added to a metal or alloy because of its high melting temperature. Since it remains solid while the rest of the metal is molten, its small particles act as seeds around which grains of the solidifying metal form. This enhances the physical properties of the solid metal.

In these arrays, the nuclei and core electrons occupy the atomic centers, whereas the free electrons float among the atomic positions There here are six crystal systems that occur and these can further be divided into 14 crystalline arrays. Within each array, the smallest repeating unit that captures all of the relationships among atomic centres is called a unit cell.
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Hexagonal - atoms are equidistant from each other in the horizontal plane but not in the vertical direction
PROPERTIES OF METALS All properties are a result from its structure and metallic bonds. Higher density due to efficient packing of atomic centres in the crystal lattice. Good electrical and thermal conductivity due to mobility of valence electrons which transfers energy by moving readily from areas of higher energy to those of lower energy under the influence or a thermal gradient or an electrical field. The unit cells for the most common arrays in dental metals are body centred cubic, face centred cubic and hexagonal. Body centred cubic metallic atoms are located at the corners of the unit cell, and one atom is at the centre of the unit cell. Face centred has 90 degree angles and atomic centres that are equidistant horizontally and vertically but atoms are located at the centres of the faces but none in the centre of the unit cell Opacity and nd reflective nature of metals ability of free electrons to absorb and re - emit light. Melting Point occur as metallic bonds are overcome by the applied heat. The more valence electrons to an atomic centre, the higher the melting point. Corrosion depend on how the valence electrons are held. The weaker the metallic bond, the higher the corrosion. Good ductility and malleability result from the ability of the atomic centres to slide against each other into new positions. Crystals have dislocation that allows the atomic centres to slide past each other one plane at a time. Force required is less to move

one plane at a time than trying to overcome to move all planes simultaneously. Hence dislocations allow relatively easy deformation of metals. Strength of metals are increased by impeding the movement of dislocations. Fracture of metals occurs when atoms are unable to slide past one another. This occurs when there are impurities which block the dislocations. Emits a metallic sound Appear white except for gold and copper. Grains and Crystal Structure in Alloys
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When cooling continues, nuclei grow into crystals grains Grains enlarge until all of the liquid is gone and the grains meet and form boundaries grain boundaries
Size of grains depends on the cooling rate, alloy composition, presence of grain refiners. Small grain size is generally desirable as it has better properties. Grain size influences an alloys strength, workability and even susceptibility to corrosion Grain refiners are added to decrease grain size. Such as metals are iridium and ruthenium. Grain boundaries are important as they contain impurities such as oxides that are sites of corrosive attack. Grain boundary regions are the final sites to undergo freezing for a molten metal that forms an equiaxed grain structure Dendrites result from grains that grow along the major axes of the crystal lattice early in the freezing process. Dendritic skeleton structure persists to room temperature if the cooling rate is too fast. Alloys that are predominantly base metal have larger grain size and cannot use grain refiners such as iridium. Equiaxed means that the three dimensions of each grain are similar, in contrast to the elongated morphology of the dendrites Most noble metal casting alloys solidify with an equiaxed polycrystalline microstructure Cold-worked (wrought) microstructure When the metal is to be used for wires, bands, bars, or other types of wrought structures, it is first cast into ingots that are then subjected to rolling, swaging, or wire-drawing operations that produce severe mechanical deformation of the metal. Such operations are described as hot or cold working of the metal,
ALLOYS Use of pure metals is limited in dentistry as they are soft and some like iron tend to corrode easily. It has been seen that metals maintain metallic behavior even when they are not pure and therefore can accept to a certain extent of addition of other elements when they solidify from liquid to solid state. To optimize properties, most metals are mixtures of two or more metallic elements or in some case one or more metals and/or nonmetals. Normally prepared by fusion of the elements above their melting points. Categorizing Alloys Based on either being noble or non noble Noble alloys have noble metals as the majority of the components whereas non noble alloys have a greater percentage of base metals American Dental Association has three categories high-noble, noble and predominantly base metals. Based on the basis of their most common metal For instance if the alloy contains mainly gold, then it will be called gold based Microstructure of Alloys As the molten alloy is cooled, the first solid alloy particles form as the temperature reaches the Liquidus this process is called nucleation

depending on the temperature at which the operation is performed. Many dental structures, such as orthodontic wires and bands, are formed by cold working operations. The finished product is often described as a wrought structure to denote that it has been formed by severe working or shaping operations. The microscopic appearance of a cast metal is crystalline and sometimes has dendritic structure, when this metal is subjected to cold-working operations, such as drawing into a wire; the grains are broken down, entangled in each other, and elongated to develop a fibrous structure change in or appearance internal that is is characteristic of wrought forms. This appearance accompanied by a change in mechanical properties. In general, mechanical properties of the wrought structure are superior to those of a casting prepared from the same melt or alloy Recrystallization and Grain Growth Metals or alloys that have been cold worked in the process of forming wires or bands change their internal structure and properties when heated or annealed. The characteristic fibrous structure of the wrought mass is gradually lost, and the grain or crystalline structure reappears. The process is known as recrystallization or alloy during grain growth. The and but degree of recrystallization is related not only to the composition fabrication, mechanical also to the treatment or strain hardening received temperature and the duration of the heating operation. High temperatures and long heating periods produce the greatest amount of recrystallization. Because the strength is usually reduced in recrystallized wrought structure (ductility often increases), it is necessary to guard SOLIDIFICATION OF METALS
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against excessive heating during the assembly of a wrought metal appliance. Within practical limits of operation, this characteristic structures. of recrystallization and grain growth is limited to wrought
If a pure metal is melted and allowed to cool to room temperature in a clean (and inert) container and if its temperature during cooling is plotted as a function of time, the following graph results
The following observations can be made from the above graph From point A to point B steady decrease in temperature From point B to point B increase in temperature. Here time temperature remains constant until point C From point C steady decrease in temperature Temperature Tf indicted by straight or plateau portion of the curve at BC. It is the freezing point or solidification temperature of the pure metal and also the melting point or fusion temperature All temperatures above Tf (plateau BC) are associated with molten metal

All temperatures below Tf (plateau BC) are associated with solid metal The initial cooling of the liquid metal from Tf to point B' is termed super cooling. During melting, temperature remains constant During freezing or solidification, heat is released as the metal changes from the higher-energy liquid state to the lower-energy solid state. This energy difference is the latent heat of solidification and is equal to the heat of fusion During the Super cooling process, crystallization begins for the pure metal. Once the crystals begin to form, release of the latent heat of fusion causes the temperature to rise to Tf, where it remains until crystallization is completed at point C. Super cooling of pure metals occurs only in clean and inert containers Nucleus formation As the molten metal approaches its freezing temperature, its energy relationships change Solidification begins with the formation of embryos in the molten metal (embryo is a small cluster of atoms that has the same arrangement as the long-range atomic order found in the solidified metal) At temperatures above Tf, such embryos will also form spontaneously in the molten metal, but they are unstable since the liquid state has a lower free energy than the solid state Free energy is of two types surface free energy and volume free energy Surface free energy (FS) = 4 . It increases as the square of the embryo radius Volume of free energy (FV) the difference in the free energies of the solid and liquid states. It is given by FV becomes

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Overall or Resultant free energy of an embryo (R) is the sum of the surface free energy (positive) and the volume free energy change (negative) contributions
Observations from the above graph are as follows At small values of embryo radius, FS is dominant and the overall free energy for the formation of the embryo is positive (energetically unfavorable) At larger values of the embryo radius, FV become dominant and the overall free energy of the embryo is negative (energetically favourable) Critical nucleus size (ro) is the maximum point in the total free energy of the embryos as a function of radius For an embryo of radius (ro), the overall flee energy (R) decreases with the addition of another atom and continues to decrease as the embryo grows. Hence, embryos with radii smaller than ro, are unstable and spontaneously form and disappear in the liquid metal, whereas embryos with radii larger than ro, are stable nuclei and continue to grow during the solidification process
. It varies as the third negative (more
power of the spherical embryo radius increasingly energetically favourable) as the temperature of the super cooled liquid is decreased below Tf
Greater the amount of super cooling, the greater the rate of temperature reduction below Tf, the smaller is the critical radius ro,

because the value of FV for a given embryo size becomes increasingly negative Hence, an increasing number of embryos become stable as the super cooling is increased, and these embryos have reduced surface energy because of their decreased radii. If the molten metal is cooled so rapidly that solidification must occur at a much lower temperature than Tf, there is a tendency for many, very small, stable nuclei or solidification centers to form. If a single crystal is desired, little super cooling is needed, and the molten metal must be cooled very slowly Homogeneous Nucleation It occurs when there are no special objects inside a phase which can cause nucleation For instance, when a pure liquid metal is slowly cooled below its equilibrium freezing are temperature by to a sufficient atoms degree, numerous homogeneous nuclei created slow-moving bonding together in a crystalline form It is a random process, having equal probability of occurring at any point in the molten metal Heterogeneous Nucleation Occurs when there are special objects inside a phase which can cause nucleation The mold walls or particles of dust and other impurities in the molten metal may produce heterogeneous nucleation Super cooling is not required for heterogeneous nucleation Solidification modes & Effects on properties Characteristically, a pure metal crystallizes from nuclei in a pattern that often resembles the branches of a tree yielding elongated crystals that are called dendrites. After their nucleation, typically at mold walls for castings, dendrites grow during the solidification of pure metals by the mechanism of thermal super cooling. Implications of Dendrites in Cast Alloys Dendritic microstructures Extensions or elevated areas
117
called
protuberances form spontaneously on the advancing front of the solidifying metal and grow into regions of negative temperature gradient In these regions of negative temperature gradient, the temperature is higher in the liquid adjacent to the frozen metal because of the latent heat of fusion released during freezing. The protuberances rapidly grow in the adjacent super cooled regions that lie farther away in the molten metal; growth is along specific crystallographic directions. The latent heat released by the solidifying metal also lowers the amount of super cooling at the liquid-solid interface, hindering growth in regions adjacent to the protuberances and resulting in separated, and highly elongated crystals. A similar growth mechanism subsequently occurs at lateral sites along the protuberances and later at lateral sites along the secondary branches, resulting in the three-dimensional dendritic structure.
are
not
generally desirable for cast dental alloys, since the inter dendritic regions can serve as sites for facile crack propagation Hot tears (micro cracks) can form at elevated temperatures in thin areas of castings prepared from these alloys, where there is insufficient bulk metal to resist the stresses imposed by the stronger casting investment, and these cracks will degrade the mechanical properties of the restorations. To avoid hot tears, castings need to have adequate thickness, and an alloy should be selected that has an equiaxed grain structure rather than a dendritic structure along with a lower burnout temperature

PHASE DIAGRAMS
118
A phase is a state of matter that is distinct in some way from the matter around it. In a mixture of ice and water there are two phases because although ice and water are the same chemically, they each have distinct arrangements of atoms. Ice has the crystalline arrangement of a solid whereas water h has the random atomic arrangement of a liquid.
A solid dental alloy may also have one phase if the composition of the alloy is essentially homogeneous throughout.
If the alloy has areas where compositions are different, it is called a multiple multiple-phase alloy. Phase diagrams are "maps" of the phases that occur when metals are mixed together. If there are two metals in an alloy, a binary phase diagram is used. If three metals are in the alloy, a ternary phase diagram may be used.
EQUILIBRIUM PHASES IN CAST ALLOYS

An alloy phase is any homogeneous, physically distinct, and mechanically separable portion of the microstructure CLASSIFICATION OF CAST DENTAL ALLOYS Classification I 1. Use (all metal inlays, crown and bridges, bridge metal-ceramic ceramic prostheses, posts and cores, RPD and implants) 2. Major elements (gold based, palladium based, silver based, nickel based, cobalt based and titanium based) 3. 4. 5. Nobility (high noble, noble and predominantly base metal) Principal three elements (Au-Pd-Ag Ag, Pd-Ag-Sn, Ni-Cr-Be, Co-Cr-Mo, Ti-Al-V V and Fe-Ni-Cr) Fe Dominant phase system eutectic, (single peritectic phase and [isomorphous], intermetallic) Classification II 1. 2. 3. Binary alloy two metals are present Ternary alloy three metals are present Quaternary alloy four metals are present
Phase diagrams describing alloys with more than three metals are not used because they are too complex; the vast majority of phase diagrams describe only binary alloys.
A typical phase diagram for a theoretical binary alloy AB is shown in above figure. The x-axis describes the composition of the elements in either weight percent or atomic percent. The y-axis axis is the temperature of the alloy system. It is important to remember that a phase diagram shows the composition and types of phases at a given temperatur temperature and at equilibrium. Every phase diagram divides an alloy system into at least three areas: the liquid phase, the liquid + solid phases, and the solid
Classification III 1. Solid solution atoms of two metals are located 2. 3. in the same crystal structure, structure intimately combined Eutectic alloys limited solid solubility Peritectic alloys -

phase. For example, everything above the temperatures shown by line ACB is liquid. This line is therefore e called the Liquidus. Everything below line ADB is solid. This line is thus called the solidus. The area between these two lines contains some liquid and some solid. At 0% B, a single phase exists (100% A) that has a single melting point (800 (800C). At 100% B, a single phase exists that has a melting point (210C). At any composition between these extremes, the melting range is defined as the temperature difference between the liquidus (ACB) and solidus (ADB). When metals are mixed together in the molten state, e, then cooled to the solid state, there are several outcomes depending on the solubility of the metals in each other. If the metals remain soluble in one another, the result is a solid solution. If the metals are not soluble in the solid state, then a eutectic may form. Sometimes, the elements react to form a specific compound, called an intermetallic compound. SOLID SOLUTIONS By far the greatest number r of alloys that are useful ul for dental restorations are ar based on solid solutions Types 1. Substitutional solid solution he atoms of the solute metal occupy the The positions in the crystal structu cture that are normally occupied ed by the solvent atoms in the pure metal For a palladium silver alloy in which palladium is the solvent metal, the silver atoms replace the palladium atoms randomly in the crystal structure Another example include gold gold-copper alloy which is a disorded solid solution at high temperatures 3. Super lattice/ordered structure 2. Interstitial solid solution
119
The solute atoms are present in random positions (interstices) between the atoms in the crystal structure of the solvent metal This type of solid solution ordinarily requires that hat the solute atoms should be much smaller in diameter than the solvent atoms, and these soli solid solutions usually are limited to relatively small concentrations of solute Examples are carbon in iron i.e. carbon steel and commercially pure (CP) Titanium alloys
If an alloy containing ing 50.2wt% gold and 43.8 wt% copper is allowed lowed to cool slowly below 400C (752F), the AuCu3 structure forms, in which the gold atoms are located at the corners of the face-centered cubic (fcc) unit cells and the coppe copper atoms are located at the centers of the faces faces. This unit cell is equ equivalent to AuCu3, since two adjacent uni unit cells share each of the six copper atoms at the centers of each of the six faces s of the cube and eight unit cells share each of the he e eight gold corner atoms. This ordered structure is called super lattice Ordered solution impart higher hardness and strengths to alloys

EUTECTIC ALLOYS
120
lower than either of the pure components. The eutectic system of Pb-Sn uses the eutectic alloy composition as plumber's solder because of its low melting point. Hypo-eutectic alloys: If an alloy composition C is lower, than eutectic composition CE, solidification of the alloy starts from formation of the primary crystals of -phase according to the left branch of the liquidus curve. These alloys are called hypo-eutectic. Hyper-eutectic alloys: If an alloy composition C is higher, than eutectic composition CE, solidification of the alloy starts from formation of the primary crystals of -phase according to the right branch of the liquidus curve. These alloys are called hyper-eutectic. PERITECTIC ALLOYS Sometimes a solid solution phase, which has already been formed, and the residual liquid phase react and form another solid solution phase or intermetallic compound, having a composition between the compositions of the liquid and the first solid. This is peritectic transformation (peritectic reaction). INTERMETALLIC COMPOUNDS If two metals react to form a new compound with Ag3Sn a specific is a composition, fundamentally the phase diagram reflects an intermetallic compound. important intermetallic compound in dental amalgam. TERNARY PHASE DIAGRAMS These phase diagrams are three-dimensional. Two dimensional representations in the shape of an equilateral triangle are also used to represent the three-dimensional structure.
Above graph shows a series of binary Ag-Cu alloys. In this phase diagram, the liquidus and solidus meet at a mid-range composition and the solidus is lower (at 779.4C) than either pure Ag (960.5C) or Cu (1083C). This liquidus-solidus configuration is characteristic of an eutectic alloy system. The Ag-Cu system is especially important in high-Cu dental amalgam, but is also important in the formulation of some dental casting alloys.
The eutectic system shown in above figure contains a pure solid solution below 400C only at either extreme of composition (4% Ag or 4 % Cu) because the Ag and Cu are essentially insoluble in one another in the solid state. At all other equilibrium conditions below the solidus, a mixture of a solid solution (either or ) and the eutectic composition occurs. The eutectic composition is 28.1% Cu (and 71.9% Ag) and has a layered appearance under a light microscope. If the alloy is at the eutectic composition, all of the alloy will be in the eutectic phase at room temperature (see the dotted line in figure). If the composition is other than this, then the alloy will be some combination of the solid solution and eutectic phases. The exact proportions of eutectic and solid solution can also be determined from the phase diagram.
A pure eutectic composition has a melting point (vs, a melting range) that is substantially

The vertical axis represents increasing Hardening
121
temperature (T). The AB, AC, and BC axes reflect concentrations of the components. The three-dimensional surface that is visible represents the liquidus for this system. Other features of the phase diagram below the liquidus require a two-dimensional cross section parallel to the ABC plane. The shape of the liquidus indicates that this is a eutectic system. ALLOY STRENGTHENING MECHANISMS Precipitation hardening is used to strengthen dental alloys. By heating some cast alloys carefully, a second phase can be made to appear in the body of the alloy. The new phase blocks the movement of dislocations, thereby increasing strength and hardness. The effectiveness of precipitation hardening is greater if the precipitate is still part of the normal crystal lattice. This type of precipitation is called coherent precipitation. Overheating may reduce alloy properties by allowing the second phase to grow outside of the original lattice structure. Grain refiners such as Ir, Rh, and Ru improve the strength of alloys by several times. Moreover, generally ductility. Cold working an alloy will significantly further strengthen it. Cold working works out the dislocations, thereby making deformation more difficult. BASIC PRINCIPLES OF HEAT TREATMENT Heat treatment of a metal or alloy is a technological procedure, including controlled heating and cooling operations, conducted for the purpose of changing the alloy microstructure and resulting in achieving required properties. There are two general objectives of heat treatment: hardening and annealing. strength improved and hardness are without sacrificing
Hardening is a process of increasing the metal hardness, resistance. Strain hardening (work hardening) strengthening by cold-work (cold plastic deformation) Cold plastic deformation causes increase of concentration of dislocations, which mutually entangle one another, making further dislocation motion difficult and therefore resisting the deformation or increasing the metal strength. Grain size strengthening (hardening) strengthening by grain refining. Grain boundaries serve as barriers to dislocations, raising the stress required to cause plastic deformation. Solid solution hardening strengthening by dissolving an alloying element. Atoms of solute element distort the crystal lattice, resisting solid the solution dislocations hardening, motion. than Interstitial elements are more effective in substitution elements. Dispersion strengthening strengthening by addition of second phase into metal matrix. The second phase boundaries resist the dislocations motions, increasing the material strength. The strengthening effect may be significant if fine hard particles are added to a soft ductile matrix (composite materials). Precipitation hardening (age hardening) strengthening by precipitation of fine particles of a second phase from a supersaturated solid solution. The second phase boundaries resist the dislocations motions, increasing the material strength. strength, toughness, fatigue
Annealing Annealing is a heat treatment procedure involving heating the alloy and holding it at a certain temperature (annealing temperature), followed by controlled cooling. Annealing results in relief of internal stresses, softening, chemical homogenizing and

transformation of the grain structure into more stable state. It takes place in three successive stages i.e. recovery, recrystallization and grain growth
122
*****
NEET
Concepts
Volume 03 General Medicine General Surgery Oral Pathology
ORAL PATHOLOGY Cysts of Oral Region
CYSTS
Cyst A pathologic cavity having fluid, semi fluid or gaseous contents and which is not created by accumulation of pus Derived from Greek word Kystis Sac
Cysts associated with the Maxillary Antrum 1. 2. 3. 4. Mucocele Retention cyst Pseudo cyst Post operative maxillary cyst
Cysts of the soft tissues of Mouth, Face and Neck 1. Dermoid and epidermoid cyst Lymphoepithelial (bronchial) cyst Thyroglossal duct cyst Anterior median lingual cyst (intra lingual cyst of foregut origin) 5. 6. 7. 8. 9. Oral cysts with gastric or intestinal epithelium (oral alimentary tract) Cystic hygroma Nasopharyngeal cyst Thymic cyst Cysts of the salivary glands: Mucous extravasation cyst, Mucous retention cyst, Ranula, Polycystic (dysgenetic) disease of parotid 10. Parasitic cysts: Hydatid cyst, Cysticercus cellulosae, Trichinosis CLASSIFICATION BY TISSUE OF ORIGIN Derived from Rests of Malassez 1. 2. Periapical cyst Residual cyst 2. 3. 4.
Cyst Parts 1. 2. 3. Cyst lumen/central cavity Cyst lining epithelium Cyst capsule at periphery connective tissue wall CLASSIFICATION Presence/absence of Epithelial lining 1. 2. True cyst Pseudocyst/false cyst Pathologic cavities not lined by epithelium CLASSIFICATION (SHEARS) Cysts of the Jaw A. Epithelium Lined Cysts I. Developmental origin 1. Odontogenic i. ii. Gingival cysts of infant Gingival cysts of adult
iii. Odontogenic keratocyst iv. Dentigerous cyst v. Eruption cyst lateral periodontal cyst vii. Botryoid odontogenic cyst viii. Glandular odontogenic cyst ix. Calcifying odontogenic cyst 2. Non-odontogenic i. ii. Mid palatal raphe cyst of infants Nasopalatine duct cyst
Derived from Reduced Enamel Epithelium 1. 2. Dentigerous cyst Eruption cyst
vi. Developmental
Derived from dental lamina (Rests of Serre) 1. 2. 3. 4. 5. Odontogenic keratocyst Gingival cyst of new born Gingival cyst of adult Lateral periodontal cyst Glandular odontogenic cyst
iii. Nasolabial cyst II. Inflammatory origin i. ii. Radicular cyst, apical and lateral Residual cyst cyst and Juvenile Paradental cyst iv. Inflammatory collateral cyst B. Non-Epithelial Cysts 1. 2. Solitary bone cyst Aneurismal bone cyst MECHANISM OF CYST DEVELOPMENT The common feature of all cysts is the stimulation of residual developmental epithelial cells, leading to proliferation but not invasion of adjacent tissues. The epithelial rests proliferate into a solid mass of epithelial cells. As the mass enlarges, the epithelial cells in the center become positioned further from the blood supply at the periphery of the mass. At some point, the cells at the center become too far removed from the nearest blood vessel
iii. Paradental

to survive by nutritional diffusion. They die, creating a lumen. Their intracellular products make the lumen hypertonic, which transudates fluid into the lumen. This in turn creates a hydrostatic pressure, producing bone resorption, clinical expansion, and sometimes mild paresthesia or pain. As additional epithelial cells die off and are sloughed into the lumen, their contents perpetuate the hypertonic state and the hydrostatic pressure. The cell membranes and nuclear membranes of these sloughed cells are high in cholesterol, hence the common finding of cholesterol clefts in the lumen or even in the walls of many cysts. As the cyst enlarges, it tissue compresses into a surrounding connective Accumulation of cellular contents Accumulation Cyst volume of mural o o o o o o Highest for OKC 8 Least for DC 0.6 Radicular cyst 4.6 Nasopalatine cyst 2.3
Inflammatory collateral cyst 2 Residual cyst 1
Mitotic activity not equated to the number of mitotic figs Hence other factors play a major role rather than the mitotic activity alone
keratin by
squames in lumen
enlargement increases
proliferation of cyst lining at active cellular sites & shedding of cells into lumen Local areas of increased cell division finger like epithelial projections in turn CT proliferation expansion of cyst Growth of cyst due to this factor occurs mainly along medullary bone with little cortical expansion 2. Hydrostatic enlargement Distension of cyst wall by fluid that accumulates by one / more processes Distension depends on Vascular pressure Collagen fibers Average intra luminal pressure Radicular cyst 70 cm of water Dentigerous cyst 65 cm Anterior developmental cysts 87.5 cm Mechanisms Secretion Transudation & exudation Dialysis
connective tissue wall. The epithelial lining matures and develops a basement membrane. The cyst lining continues to proliferate, thus causing the cyst to enlarge until it is removed (enucleation); the proliferating cells are communicated into the oral cavity or an external surface so as to break the proliferationhydrostatic pressure cycle (marsupialization), or the inciting cytokines are removed (via tooth removal or root canal therapy in radicular cysts) FACTORS ASSOCIATED WITH GROWTH OF A CYST 3 mechanisms 1. Mural growth 2. Hydrostatic enlargement 3. Bone resorbing factors 1. Mural growth Growth occurring in the wall of cyst Occurs by peripheral cell division/ accumulation of cellular contents Peripheral cell division Stimulus acts as an irritant to lining epithelium active cell division inductive CT peripheral growth of cyst Proliferating epithelium influence on underlying 1.
Secretion Very few secretory products Active secretion by secretory cells in epithelium is very less 40% of DC Goblet cells mucous High molecular weight GAGs o Products metabolic of normal / turnover
proliferation & expansion of CT Mitotic values of epithelial lining reflect cyst growth Higher mitotic value = greater growth potential of cyst & vice versa

inflammatory products of CT o Enter lumen via of altered lining permeability epithelia 2% DC epithelial lining cells keratinizing contributes Plasma cells o o Secrete immunoglobulins Reach the cyst lumen via epithelial lining 2. Transudation & exudation Cysts grow by accumulation of inflammatory transudates & exudates proven by examining the protein content & specific gravity Total soluble Protein levels o Radicular cyst: 6.3 7.5 gms100 ml (rich in gamma globulins) High mol wt substances enter via altered : globulin vascular permeability suggest that they are inflammatory exudates o Dentigerous cyst 5.5 6.8 gms/100 ml Albumin similar to serum IgA local synthesis by plasma o cells inflammatory exudate Apart from these proteins other high mol wt substances fibrin & cholesterol also found o in cyst fluid PSEUDOCYSTS products of haemorrhage Growth of both Dentigerous cyst forces 3. Dialysis Refers to accumulation of fluid in the cyst lumen due to difference in the osmolarity of the cyst fluid and serum with cyst fluid having a higher osmolarity Aneurysmal bone cyst / cavity Solitary bone cyst Antral Pseudocyst & Radicular cyst Unicentric due to hydrostatic BIOCHEMICAL EVALUATION OF FLUID Levels of soluble metaplasia to keratin degradative
Osmolarity refers to the number of dissolved particles in a solution and it is directly related to osmotic pressure Different particles in the cyst fluid o o o o o o attributing to its high osmolarity Desquamated epithelial cells Fibrin Cholesterol Serum proteins Mucus Keratin
accumulation in cyst lumen
ASPIRATION FINDINGS Confirms the cystic nature Wide bore needle with 5-10ml syringe Clear pale straw colored fluid periodontal & periapical cyst Glistening crystals (cholesterol crystals) periapical cyst Cheesy creamy white material masses of desquamated keratocyst Golden yellow fluid clots on standing Solitary bone cyst Fresh blood solitary bone cyst / ABC / Haemorrhage in Cyst vascular tumours?? / AV aneurysms?? Opaque dark brown (pus) Infected cyst solid tumour Greenish thick, viscous fluid with foul odor Failure to aspirate keratin Odontogenic Dentigerous,
proteins estimated
by
electrophoresis > 4.89/100ml Inflammatory / non keratinizing cyst < 4.89/100ml Keratinizing Cyst
Pseudocysts are pathological cavity or an abnormal or dilated space, resembling a cyst but not lined by epithelium. They may contain fluid or sometimes tissue.
Pseudocysts of jaws
Pseudocysts of soft tissue
Mucous extravasation cyst

Stafnes bone cavity Focal osteoporotic Intra-oral lymphothelial cyst Parasitic cysts Hydatid cyst Cysticercus cellulosae ---
bone marrow defect Ganglion cyst
Common features of jaw Pseudocysts Largely asymptomatic Demarcated radiolucent appearance Diagnosed incidentally on radiographs Unclarified etiology/ pathogenesis

PATHOGENESIS C/F R/F
H/P
ADDITIONAL NOTES
DENTIGEROUS CYST (Follicular cyst) (DC) Develops due to the fluid Young adult predilection M>F Most common sites: Mandibular and maxillary third molars, maxillary cuspids Mandibular 3rd molar involvement may result in hollowing-out of ramus May resemble an acute sinusitis or cellulites as it involves maxillary cuspid Mostly unilocular 3 types 1. Central Type: Crown is enveloped symmetrically. 2. Lateral Type: Dilatation of the follicle on one aspect of crown (common in mesioangular impaction of third molar) 3. Circumferential type: Entire tooth appears to be enveloped by cyst. Should be D/D from envelopmental variety of OKC. In DC definite attachment at CEJ Central type is most common Normal follicular space is 3-4 mm Suspicion arises when the follicular space is > 5 mm Aspirate Yellowish colored fluid Cholesterol crystals Soluble gms/dl Potential Complications 1. Development of an Ameloblastoma either from the lining epithelium or from rests of odontogenic epithelium in the protein level: 5-7 Thin connective tissue wall with a thin layer of stratified squamous epithelial lining (2-4 cell thick) Presence of Rushton bodies (linear, curved, Presence hyaline of bodies, of hematogenous origin) islands odontogenic epithelium Metaplasia mucous and ciliated cells Sebaceous cells in connective tissue & lymphoid follicles with germinal centers Dentigerous means tooth bearing. (by Browne) Most common type of developmental odontogenic cyst Second most common cyst Initially associated with crown of an impacted, embedded or unerupted tooth May enclose complex compound odontome May involve supernumerary tooth Multiple or associated dysplasia, syndrome Complications of incomplete removal: development of Ameloblastoma, Squamous cell carcinoma and Mucoepidermoid carcinoma Bilateral cysts are with Maroteaux Cleidocranial Lamy accumulation surface Encloses the crown of unerupted tooth at CEJ between reduced
enamel epithelium and the enamel
wall of the cyst 2. Development of squamous cell carcinoma form the same to sources 3. Development of Mucoepidermoid carcinoma form the lining epithelium of dentigerous cyst which contains mucous secreting cells or cells with this potential 4. Squamous cell carcinoma ERUPTION CYST (Eruption Hematoma) Result of separation of dental follicle from around the crown of an erupting tooth that is within Usually the soft tissues with overlying the alveolar bone associated Children predilection M>F Most common site: anterior to first permanent molar Soft, translucent swelling on gingiva Surface purple hematoma trauma color blood blue or Eruption accumulation Soft tissue shadow Keratinized stratified squamous epithelium gingiva Dense connective tissue with inflammation of the overlying Soft tissue analogue of Dentigerous cyst
erupting succedaneous tooth / deciduous tooth Arises in an extra alveolar location Lies just beneath alveolar mucosa
GINGIVAL (ALVEOLAR) CYST OF NEW BORN Arise from remnants of dental More common in infants lamina Bohns nodules odontogenic origin Epsteins pearls non Maxillary alveolus is more common than mandible Multiple raised nodules / small discrete white or cream colored of them under go involution and disappear, or rupture through the surface epithelium and exfoliates surface of NA Thin, flattened epithelial lining with a parakeratotic luminal surface Synonyms 1. 2. 3. Dental lamina cyst of New born Bohns nodules Epsteins pearls
odontogenic origin (epithelial Most inclusions in the fusion line between the palatal shelves & nasal processes)
Both have similar clinical & Buccal/lingual

histopathological features alveolar ridge Bohns nodules Junction of hard & soft palate Epsteins pearls
GINGIVAL CYST OF ADULT Sources: Heterotopic tissue Degenerative changes in proliferating epithelium Epithelial islands of periodontal membrane Traumatic implantation of epithelium Remnants of dental lamina or enamel organ LATERAL PERIODONTAL CYST Arise from remnants of dental lamina 5 6 decade
th th
glandular
5th 6th decade More common in mandibular canine & pre molar area Always found on f facial NA gingiva or alveolar mucosa Painless, dome like swelling May cupping cause out superficial of alveolar
Similar
features
to
Lateral
Soft tissue analogue of Lateral Periodontal Cyst (as it derives from Cell Rests of Serre)
Periodontal Cyst Thin, flattened epithelial lining with or without focal plaques that contain glycogen rich clear cells
bone (seen on excision only)
Round or tear drop shaped well circumscribed radiolucencies with a sclerotic margin, and measuring < 1 cm in diameter
thelium & CT Junction b/w epithelium flat / may show reteridges Nonkeratinised, 2-5 cell layers thick Clear cells with pyknotic nuclei rich in glycogen (originates from DL) Epithelial proliferation in localized areas areas Plaques overlying islands epithelial project into thickening off & cuboidal/ cuboidal squamoid stratified epithelium
Botryoid Odontogenic Cyst Uncommon, multilocular polycystic by They because Weathers variant and grossly (Botryoid), of
M>F More common in Mandibular premolar-canine-lateral lateral area incisor
odontogenic cyst, first described Waldron the term cyst" (1973) as a type of LPC proposed the gross "Botryoid odontogenic
Asymptomatic Associated tooth vital
Located between the alveolar crest and the apex of the tooth
Botryoid Odontogenic Cyst Variant of LPC Multilocular pattern
specimen
lumen / underlying CT focal epithelial plaques pinch from lie epithelium
resembled a cluster of grapes
separately in CT
multiple
cystic degeneration
multiple cysts / daughter cysts
GLANDULAR ODONTOGENIC CYST Arise from remnants of dental lamina Oder adults M>F Mandible > Maxilla Ant. region > Post. Region Asymptomatic Lateral periodontal multilocular radiolucency with sclerotic rim Epithelium pseudo has glandular or Synonyms 1. 2. 3. Sialo-odontogenic (Padayachee and Van Wyk) Mucoepidermoid odontogenic cyst (Sadeghi) Polymorphous odontogenic cyst cyst
glandular
structure,
goblet cells and intra epithelial cysts or micro cysts containing mucous Diagnostically superficial layer of epithelium containing columnar or cuboidal cells (referred as hob nail) occasionally with cilia or filiform cytoplasm extensions of the
KERATINIZING/CALCIFYING EPITHELIAL ODONTOGENIC CYST Central variety more common Peripheral variety rare 2nd or 3rd decade Maxilla = Mandible Ant. region > Post. region Central Usually unilocular, well defined radiolucency Calcifications or tooth like densities are seen in few cases May common 2 4 cm radiolucency Root resorption of or divergence teeth is seen Peripheral localized superficial bone resorption or saucer shaped radiolucency adjacent associate with unerupted tooth canine is Central Fibrous capsule with 4-10 cell thick odontogenic epithelium Superficial cells resemble stellate reticulum Basal cells look similar to ameloblasts Presence of Ghost cells Presence of dysplastic dentin May associate with odontomas Peripheral Islands of odontogenic epithelium in fibrous stroma resembling Ameloblastoma Nests of ghost cells & juxta epithelial dentinoid Types 1. Cystic 2. Neoplastic (solid) Synonyms 1. Calcifying Odontogenic Cyst 2. Gorlin cyst 3. Dentinogenic Ghost Cell Tumor 4. Calcifying Ghost Cell Odontogenic Cyst 5. Cystic Keratinizing Tumor

PATHOGENESIS C/F R/F ANEURYSMAL BONE CYST (ABC) 2 forms 1. 2. Primary Secondary bone form: no prewell are existing lesion identified form: lesions recognized pre-disposing recognized 4 phases 1. 2. 3. 4. Osteolytic initial phase Active growth phase Mature stage/stage of stabilization Healing phase Any age M>F For maxillary cases, F > M Seen in shaft of long bones and vertebral column Oral cavity: Mandible > common clinical Maxilla Most common in ramus region Most manifestation is swelling with rapid rate of enlargement H/O trauma Expansion or perforation of cortex and the lesion may exhibit egg shell crackling 3 theories 1. 2. 3. Traumatic origin Altered state Secondary phenomenon hemodynamic when covered by periosteum or thin shell of bone. Tooth is vital Aspirate: dark red or brownish hemorrhagic fluid Characteristic radiolucent area ballooning with During surgery, welling up of blood within tissue is encountered which is described as blood soaked sponge with large pores Lesion consists of capillaries & blood filled spaces Multinucleate cells, scattered osteoid & woven bone are found In solid areas: sheets of vascular tissue with giant cells, fibroblasts & haemosiderin are present The blood filled spaces have no elastic tissue or smooth muscle around them H/P
ADDITIONAL NOTES
ABC first recognized as a distinct entity by Jaffe & Lichtenstein in 1942 to describe the characteristic blown out contour of bone seen in radiograph of the lesion. It is an intra osseous osteolytic lesion mainly affecting the metaphyseal regions of long bone & vertebrae Philipsen termed it as Aneurysmal Bone Cavity First case of jaw reported by Bernier & Bhaskar in 1958 WHO definition: Benign intraosseous lesion characterized by blood filled spaces of varying size associated tissue with giant a cells, fibroblastic containing
growth pattern resulting in a elevation of the periosteum to produce an ovoid or fusiform expansion of the bone. Usually unilocular
multinucleated
osteoid & woven bone Old Terminologies 1. 2. 3. 4. 5. Ossifying hematoma Hemorrhagic osteomyelitis Osteitis fibrosa cystica Expansile hemangioma Aneurysmal tumors giant cell

PATHOGENESIS C/F R/F SIMPLE BONE CYST (SBC) Trauma Failure of differentiation of osteogenic cells Venous obstruction Osteoclasis due to disturbed circulation Origin from bone tumors Result Local growth End result of low grade infection Unidentified small aneurysm or vascular defect of faulty calcium in bone metabolism disturbance Any age, peak in 2nd decade M>F Mandible > Maxilla Most common in premolar area Asymptomatic incidental finding Occasional pain, swelling & paresthesia may be present H/O trauma Occasional buccal & lingual cortical plate expansion Vital tooth 3. 2. usually an Well defined unilocular, oval radiolucency 3 distinctive features (Lucas) 1. Area of radiolucency larger than the size of swelling suggests Cavity arch between the roots of the teeth Outline typically irregular SBC often located above and in front of the mandibular canal Scalloping feature 4 shapes of the lesion was identified tracings border 1. Cone i. Typical cone ii. Double cone iii. Half cone iv. Cone & a half cone 2. 3. 4. Oval Irregular Round Rushtons Cyst of based the on the peripheral is a prominent Loose vascular fibrous tissue membrane of variable thickness C.T lining overlies zone of reactive bone that exhibits an extensive osteophytic reaction on outer cortical plate Hemorrhage, Areas necrotic of haemosiderin, hemorrhage tissue & with myxoid Synonyms 1. 2. 3. 4. 5. small multinucleate cells H/P
ADDITIONAL NOTES
First described by Lucas 1929 Resembles of long bone WHO definition: Solitary bone cyst is an intra-osseous cyst having a tenuous tissue lining with of no connective unicameral bone cavity which is analogous lesion
epithelial lining
degeneration
Solitary bone cyst Traumatic bone cyst Hemorrhagic bone cyst Unicameral bone cyst Idiopathic bone cavity (1949) should be criteria single, for no
diagnosing SBC epithelial lining, no evidence of acute or prolonged infection Principally contain fluid & not soft tissue Walls should be hard bone, which may be thin in parts Pathological & chemical findings do not exclude a diagnosis of SBC
PATHOGENESIS
C/F
R/F STAFNES BONE CAVITY
H/P
ADDITIONAL NOTES
Glandular Hypothesis Hyperplastic/hypertrophic or aberrant lobe of salivary gland Pressure resorption
Any age, peak in 5th & 6th decade M>F Mandible > Maxilla Most common in angle of mandible & 1st molar below inferior alveolar canal
Round or ovoid radiolucency with radiopaque borders Submandibular salivary gland tissue may extend into lingual bone depression
Surface
of
depressions
show
The term first coined by Stafne in 1942 Also (LMBD) 1. Lingual localized posterior in variant: posterior called as Lingual Depression Mandibular Bone
osteoclastic activity May contain normal, hyperplastic or hypertrophic salivary gland tissue
Typically asymptomatic Not palpable Routinely radiographs detected on 2.
lingual mandible in area of angle `1& below inferior alveolar canal Anterior LMBD: localized in mandibular incisor-caninepremolar area above the mylohyoid muscle. 3. Ascending lingual mandibular ramus (MRBD): to just localized lingual below the posterior foramen, 4.
neck of condyle Buccal aspect of ascending mandibular ramus Other Synonyms 1. 2. 3. 4. 5.

Mandibular defect
embryonic
Latent bone cavity Idiopathic bone cavity Lingual mandibular SG depression Latent hemorrhagic cyst of
the mandible 6. Aberrant salivary gland tissue in the mandible FOCAL OSTEOPOROTIC BONE MARROW DEFECT Aberrant form of bone healing with focal formation of hematopoietic bone marrow Persistence of fetal marrow Peak in 4th & 5th decade F>M Mandible > Maxilla Most common in molar-ramus area, premolar region of mandible, maxillary tuberosity Generally asymptomatic Occurs at sites of recent surgical interventions 3. Irregular round or oval Tissue may be either normal red marrow, fatty marrow or both Lymphoid aggregates may be present Trabeculae: thin, irregular & 2. devoid of osteoblastic layer Synonyms 1. Osteoporotic marrow defect of jaw Hematopoietic defect of the jaw Focal marrow containing jaw cavity (FMJC) and may be First described by Cahn in 1954
radiolucency Anterior border may be well delineated sclerotic
ANTRAL PSEUDOCYST H/O previous infection Focal accumulation of inflammatory exudate Lifting of antral mucosa from underlying bone M>F Most common in antral floor Generally asymptomatic Well defined radioopacities, spherical, ovoid or dome shaped lesion with a smooth uniform outline Pools of mucoid material lined by inflamed fibrous C.T Mucoid infiltrate Mucin stains negative infiltrate appears 2. 3. 4. primarily to be an inflammatory Synonyms 1. Benign mucosal cyst of maxillary antrum Mucosal cyst Serous cyst Non-secreting cyst

DIFFERENCES BETWEEN ANTRAL PSEUDOCYST AND POLYP Pseudocyst May be single or multiple Fluid accumulates beneath the periosteum Not observed Dome shaped swelling Less fibrous C.T Impossible to remove the lesion intact Found in otherwise healthy sinus Multiple Fluid accumulates in the loose C.T of lamina propria of lining of sino nasal tract Sinus mucosa adjacent to polyps thickened by edema Pendulous or irregularly shaped More than Pseudocyst Possible to remove intact Seen in inflamed edematous mucosa Antral polyp
PATHOGENESIS
C/F
R/F MUCOCELE (Extravasation type)
H/P
ADDITIONAL NOTES
Traumatic severance of salivary duct Spillage of mucin into surrounding tissue
Peak in 4th & 5th decade M=F Mandible > Maxilla Most common in lower lip lateral to midline Painless, H/O raised domed & shaped vesicles rupture, collapse refilling Two types: Depending on location 1. Superficial lesions Presents with bluish translucent cast The blue color imparted by the spilled mucin __
Wall
of
circumscribed
cavity __
made of a lining of compressed fibrous connective tissue and fibroblasts Dense infiltration of PML, lymphocytes and plasma cells Lumen filled with spilled mucin containing chiefly leukocytes & foamy histiocytes Salivary gland acini adjacent to area of mucocele may consist of interstitial inflammation or sialadenitis, dilatation of intra lobular & interlobular ducts with collection of mucus & breakdown of individual acinar cells

below surface Commonly seen in soft palate, retromolar area and posterior buccal mucosa Present as either single or multiple which tense often vesicles the mucosal
rupture leaving shallow painful ulcers that heal within few days 2. Deeper lesions Color of normal mucosa and are firmer May be confused with a fibro-epithelial polyp ORAL LYMPHOEPITHELIAL CYST Some arise from epithelial oral dilatation of Peak in 3rd & 4h decade M=F Mandible > Maxilla Most common in floor of the mouth; other sites include ventral surface & posterior lateral border of tongue, painless, nodule with palatine tonsil & soft palate Movable, submucosal __ Atrophic and often degenerated stratified squamous epithelium usually lacking rete process and demonstrating minimal granular layer Keratin may fill the lumen and sometimes undergo dystrophic calcification Lumen may communicate with the oral cavity through an epithelial lined tract Epithelium closely enveloped by lymphoid tissue may contain Germinal centers Hyperplastic lymphoid aggregate __
inclusions
within
lymphoid tissue Others are pseudocysts, arising from cystic tonsillar crypts or superficial ducts of minor salivary glands
yellow or yellowish white discoloration, less than 1 cm in diameter The lesion creamy or cheesy keratinous

material in the lumen
PARASITIC CYSTS Most of the reported parasitic cysts of the oral cavity have been caused by two groups, Echinococcus granulosus Taenia solium Hydatid cyst Cysticercus cellulosae
Hydatid cyst Causative organism: E. granulosus Humans: Intermediate host Life Cycle Ingested ova Hatch in upper GIT Permeate intestinal mucosa Dispersed through blood vessels & lymphatics Causative organism: T. solium
Cysticercus cellulosae
Ingested by humans in inadequately heated or frozen pork; fecal-oral route Life Cycle Ingested eggs Pass to stomach Covering digested, larval forms hatched Penetrate intestinal mucosa Blood vessels & lymphatics
Common sites: Salivary gland, pterygo-palatine & infratemporal fossa Macroscopy: Presence of brood capsules Microscopy: 3 layers Outer host layer 2 inner parasitic layers
Common sites: Tongue, buccal mucosa & lips Common sites: Intact cystic masses, clear watery fluid & a coiled white structure attached to inner aspect of cyst Microscopy Dense fibrous outer capsule- host tissue Inner aspect: dense aggregate of eosinophils & neutrophils Double layered membrane in the fibrous capsule Cyst lies within this membrane
GANGLION CYST
Pseudocyst with fibrous C.T wall that lacks a synovial cell lining Located near a joint capsule or tendon sheath Common sites: joint of wrist Etiology: Myxoid degeneration Softens collagenous joint capsule wall Filled with viscoid or gelatinous material Focus of myxoid degeneration starts in C.T adjacent to synovial cells
Rarely a large cyst produce through and through fluctuant expansion involving anterior palate and labial alveolar mucosa
Can go upto 30 mm diameters Rarely NPDC may develop in soft tissues of incisive papilla area without bony involvement cysts of the incisive papilla / cysts of the palatine papilla (soft tissue counterpart)
Appear bluish in color Soft & fluctuating
Radiographic Features
NASOPALATINE DUCT/ INCISIVE CANAL CYST

First described by Meyer in 1941 as a supernumerary nasal sinus Most common nonodontogenic cyst of the oral cavity Prevalence 1% of population Arises from the embryonal remnants of the nasopalatine ducts retained in the nasopalatine canal Trigger for proliferation Trauma Infection Mucous retention Spontaneous cystic degeneration of epithelial remnants Racial or genetic factors
Well circumscribed radiolucency Occurring in or near the midline of anterior maxilla, between and apical to central incisor teeth
Often round or oval with sclerotic / corticated border Some times may have inverted pear or heart shape Notched expansion Superimposition by nasal spine If bilateral cysts by nasal septum during
Nasal spine radio-opaque line Roots of maxillary incisors displaced distally Lamina dura is intact Root resorption and bony expansion rare Radiographic diameter ranges from 1 2.5 cm Difficult to distinguish small NPDC from large incisive foramen (radiolucency 6mm or smaller usually considered normal foramen RoperHall)
Clinical Features Develop at any age most common in 4th 5th decade Rarely seen in first decade Shows slight male predilection Slow growing lesion Many are asymptomatic discovered on routine radiographs Symptoms do occur most common symptoms include Occurs between roots of max incisors Swelling in the midline of anterior palate with a bulge in the floor of the nose Drainage through tiny fistula - Salty discharge if infected discharge Pain due to secondary infection or pressure on the nerves Displacement of teeth foul smelling
Location is important with regard to early diagnosis More inferiorly localized NPDC seem to give earlier swelling of the palatal gingiva than the superficial ones
Histopathology Epithelial lining highly variable composed of Stratified squamous Pseudo stratified columnar Simple columnar Simple cuboidal Combination of more than one type also seen Most commonly stratified squamous followed by ciliated pseudo - stratified columnar Type of epithelium related to vertical position
Cyst developing near nasal cavity more likely to develop respiratory epithelium PSCCE with mucous / goblet cells
Histopathology Lined by stratified squamous epithelium Sometimes ciliated pseudo stratified epithelium also seen Chronic inflammatory cells seen in the cyst wall
More inferior stratified squamous epithelium CT Nerves, blood vessels / neurovascular bundles terminal branches of sphenopalatine vessels & nerves Seromucous glands can also be seen Remnants of hyaline cartilage remnants of Jacobsons organ
GLOBULOMAXILLARY CYST
Controversial existence Thought to be a fissural cyst that arise from the epithelium entrapped during fusion of the globular portion of the medial nasal process with the maxillary process Current theory most cysts that develop in the Globulomaxillary area are actually of odontogenic origin Clinical and Radiographic Features Occurs between maxillary lateral and cuspid teeth Radiographically Well circumscribed Unilocular radiolucency between and apical to the teeth Inverted pear shape As lesion expands tipping of the roots may occur Histopathology Explained on odontogenic basis Lined by inflamed stratified squamous epithelium periapical cyst Some exhibit features of OKC Some have features of lateral periodontal cyst Rarely lined by pseudo stratified or ciliated columnar epithelium explained by the close proximity of sinus lining
Inflammatory infiltrate ranges from mild to severe
MEDIAN PALATAL CYST

Rare fissural cyst Occurs anywhere along the mid-palatine raphe Develops from Epithelium entrapped along the embryonic line of fusion of lateral palatal shelves of the maxilla If between junction of hard & soft palate Remnants of dental lamina If diffusely distributed multiple cysts Remnants of embryonic salivary gland tissue If anterior portion of palate Posterior extension of NPDC - Difficult to distinguish from NPDC Cause of proliferation unknown
Clinical Features Present as a firm or fluctuant swelling Occur in the midline of hard palate posterior to incisive papilla Most frequent in young adults Often asymptomatic some patients complain of pain or expansion Enlargement of palate Average size 2x2 cm
MEDIAN MANDIBULAR CYST

Radiographic Features Well circumscribed radiolucency in the midline of the hard palate (opposite to bicuspid and molars) May have a sclerotic border Occasionally produce divergence of roots Occlusal radiographs helpful in diagnosis True MPC should exhibit clinical evidence of palatal enlargement
Extremely rare lesion occurring in the midline of the mandible Lesion of questionable existence Some suggest it as a fissural cyst Now it is considered that most of these midline cysts are of odontogenic origin
Clinical and Radiographic Features Asymptomatic discovered during routine RG examination Midline radiolucency between or apical to the mandibular central incisor teeth Cortical as well as teeth displacement may be noted in some cases Associated teeth may or may not be vital
Squamous metaplasia rare Apocrine changes seen in some cases Cyst wall composed of a fibrous con tissue with adjacent skeletal muscle Inflammation seen if infected
THYROGLOSSAL DUCT CYST

Uncommon developmental cyst arising from the remnants of embryonic TGD epithelium Trigger for proliferation is unknown Inflammation the most commonly suggested stimulus from adjacent lymphoid tissue that may react to draining infections in head and neck Retention of secretion within the duct Familial occurrence Clinical Features Classically in the midline may occur anywhere between foramen caecum and suprasternal notch Infrahyoid 65-85% Suprahyoid 8% Suprasternal 5% Intra lingual 1-2% Develop at any age Most common in first 2 decades No sex predilection Usually painless, fluctuant, mobile Pain if it is secondarily infected Lesions develop at the base of the tongue may cause laryngeal obstruction Mostly smaller than 3cm Occasionally 10cm in size Move with deglutition or protrusion when attached to hyoid or tongue Fistulous tract may occur as sequelae of infection or surgery Histopathology Lined by columnar or stratified squamous epithelium Occasionally cuboidal or intestinal epithelium may be seen Thyroid tissue may be seen in the cyst wall
Histopathology Variation in the type of lining Most common is stratified squamous Few cases lined by pseudo stratified columnar epithelium
NASOALVEOLAR CYST
First described by Zuckerkandl in 1982 Rare developmental cyst Occur in the lip beneath the ala of the nose Pathogenesis uncertain 2 theories Klestadt develops from entrapped embryonic epithelium at the junction of medial nasal, lateral nasal, and maxillary process Bruggemann arise from remnants of nasolacrimal duct, because of their similar location and histology Clinical and Radiographic Features More common in females than males Peak prevalence in 4th or 5th decade 10% - bilateral Mostly asymptomatic Pain if secondarily infected Cyst is fluctuant and obliterates the nasal fold Occasionally expansion may produce nasal obstruction and difficulty in wearing denture Some times may rupture spontaneously and drain into the oral cavity or nose As it arises from soft tissues in most cases, no radiographic changes seen Occasionally pressure resorption of underlying bone may occur Precise extension best appreciated by CT
Histopathology Most frequently lined by pseudo stratified columnar or cuboidal epithelium Stratified squamous epithelium also seen in some cases Between the cells, numerous goblet cells can be seen
CERVICAL LYMPHOEPITHELIAL CYST (BRANCHIAL CLEFT CYST)

Located on the lateral aspect of the neck Described classically as originating from remnants of branchial arches or pharyngeal pouches Another theory considers that it arises from cystic changes in the parotid gland epithelium that becomes entrapped in the upper cervical nodes during embryonic life (Elliot Oestal) Recent IHC evidence supports the classic theory 95% from secondary branchial arches 5% from the remaining arches Clinical Features Most commonly in upper lateral neck, along the anterior border of sternomastoid Young adults between 20-40 yrs Soft fluctuant mass ranging 1-10 cm in size Tenderness and pain associated with sec.inf Some lesions become evident after upper respiratory tract infection or trauma May appear as a sinus or a fistula with a mucous discharge on the skin Increased incidence of parotid LEC have been reported in HIV pts related to intra parotid lymphadenopathy Intra nodal proliferation with cyst formation originates from the activity of the included parotid gland epithelium Histopathology 90 % lined by stratified squamous epithelium Some demonstrate respiratory epithelium Cyst wall typically contains lymphoid tissue, often demonstrating germinal centre formation Variable amount of con tissue in the wall Cyst may contain thin watery fluid or thick gelatinous mucoid material
Teratoid cyst a cystic form of teratoma that contain skin appendages, muscle, blood vessels, bone, GIT lining
Etiopathogenesis Results from entrapped midline ectodermal tissue during fusion of the mandibular and hyoid arches (3rd and 4th weeks in utero) Most accepted theory Classification Histology 1. 2. 3. Location 1. 2. 3. Median dermoid Lateral sublingual True lateral Epidermoid Dermoid Teratoid
Clinical Features Most commonly occurs in the floor of the mouth Midline. Above Geniohyoid Sublingual swelling Displace the tongue towards palate Difficulty in eating Below Geniohyoid Sub-mental swelling Double chin appearance Sometimes penetrate sub mental and sub lingual space Dumb-bell shaped Highest incidence between 15 35 yrs Equal age distribution Size few mm 12 cm Slow growing Painless Well encapsulated Doughy or rubbery mass pitting on pressure Sec infection drain Intraorally or onto the skin CT, MRI contrast medium radiographs helpful in delineation Histopathology Lined by orthokeratinized stratified squamous epithelium Abundant keratin cyst lumen Rarely respiratory epithelium
DERMOID AND EPIDERMOID CYSTS

Uncommon developmental cystic malformation Forms of teratoid spectrum Cyst lined by epidermis like epithelium and contain dermal adnexal structures in the cyst wall dermoid cysts Cyst lined by epidermis like epithelium without dermal appendages in the cyst wall epidermoid cysts
Cyst wall fibrous connective tissue that contains one or more skin appendages in dermoid & no skin appendages in epidermoid cyst 2. 3. 1.
INFLAMMATORY CYSTS
Radicular Cyst (Periapical Cyst, Apical Periodontal Cyst) and Lateral Radicular Cyst Residual Cyst remains of radicular cyst Paradental Lateral cyst/Inflammatory aspect of root collateral of cyst/ inflammatory periodontal cyst partially impacted/erupted mandibular 3rd molars (vital teeth) with H/O pericoronitis 4. Adults Main (1970, 1985) & Craig (1976) infected buccal cyst/Juvenile
HETEROTROPHIC ORAL GIT CYST

Rare lesion that occur in oral cavity lined by gastric or intestinal epithelium Etiopathogenesis different theories From misplaced embryonic gastric remnants entrapped in the midline of the tongue (Gorlin and Jirasek et al) From islands of endoderm that lined the primitive stomodeum and trapped during the fusion of the embryonic process (Daley and Wysoki et al) Entrapped undifferentiated endoderm cells (Wooglar and Smith) Clinical Features Occur at any age mostly in infants and young children More common in males Small nodule or large swelling Most common location in the anterior two thirds of tongue followed by floor of the mouth Asymptomatic or may cause difficulty in eating or speaking Some may communicate with the surface by a duct like structure Histopathology Lined partly by gastric epithelium and partly by stratified squamous epithelium Some may also exhibit the features of dermoid cysts
Mandibular Paradental cyst
Similar lesion on buccal surfaces of partially erupted / fully erupted I & II mandibular molars at root bifurcation
ORIGIN
Pericoronitis Young children Stoneman & Worth (1983)
Source of the epithelium Usually rests of Malassez RC & PDC Reduced enamel epithelium Paradental cyst (PDC) May be crevicular epithelium, sinus lining or lining of fistulous tracts
Hence only Radicular & residual cysts are definitely of Odontogenic origin Others may not all be of odontogenic origin Source / site of inflammatory stimulus Necrotic pulps at apex of a non vital tooth, or adjacent to a lateral canal of non vital tooth Radicular & Residual Periodontal pocket/Paradental follicular tissue Inflammatory collateral / periodontal cyst / Paradental cyst & Mandibular infected buccal cyst
RADICULAR CYST (PERIAPICAL CYST, APICAL PERIODONTAL CYST)

Most common cyst Both radicular & residual 60.3% of odontogenic cysts Age III, IV & V decades Rarely in I decade - though dentigerous cyst is common in children radicular cyst are not often assoc with deciduous teeth
PATHOGENESIS OF CYST FORMATION 1. 2. 3. Phase of initiation Phase of cyst formation Phase of expansion
Not to rely on the radiographic size of a periapical radiolucency to establish the diagnosis of either cyst or granuloma, unless the lesion is larger than 2 cm in diameter
10%
of
periapical treated
radiolucencies teeth are cysts
in -
endodontically
remaining either a residual granulomatous tissue, a collagenous scar as a consequence to the endodontic treatment HISTOPATHOLOGY Lumen is filled with fluid and cellular debris. Lined by non keratinized stratified squamous epithelium which may show hyperplasia ( (1-50 cell layers) & spongiosis CLINICAL FEATURES M>F 60% - maxilla anteriors 40% mandible Presence of non-vital tooth Generally asymptomatic unless they are secondarily infected Discovered on routine radiographs Vary in size from 1/2 to 2 centimeters or more in diameter Maxilla buccal / palatal enlargement, mandible labial/ / buccal rarely lingual If infected - Accompanied by pain and the other signs and symptoms of inflammatoryinflammatory infectious processes sinus formation Large sized cysts intraoral or facial asymmetry and even paresthesia due to compression of nerves, may erode the bone cortical plate or invade the maxillary sinus or the nasal fossae Extremely large radicular cysts - risk of accidental secondary fractures of bone RADIOLOGICAL FEATURES Peri- or para-apical, apical, round or oval radiolucency of variable size Generally well delineated Most likely with a marked radiopaque rim Rarely resorption of the root of the affected tooth Similar periapical radiolucent appearance some diseases of bone granulomas, neoplasms of various origin and Discontinuous in areas Arcading pattern of proliferation with intense assoc acute inflammatory ammatory process early stages With cyst enlargement - quiescent & fairly regular simple st stratified squamous epithelium The wall consists of dense fibrous connective tissue with a predominant chronic inflammatory infiltrate many plasma cells with Russell ell bodies (collections of Igs), mast cells Rushtons hyaline bodies May be present within the lining / occasionally capsule 10% of cysts 0.1 mm Linear/st/curved /curved structures Concentrically laminated Brittle & fracture Odontogenic origin gin - ?? Some form of keratin - Ker sec enamel cuticle Rushton, Takeda Wertheimer Hematogenous origin derived from thrombi in venules of CT which were varicose & strangled by epi epithelial cuffs Recent secretory product of odontogenic epithelium Dystrophic calcification, cholesterol clefts surrounded rounded by dense aggregates of foreign body multi nucleate giant cells (mural nodules which eventually are extruded out) Haemorrhage and hemosiderin pigmentation may be seen some capsules markedly vascular hairpin like calcified
Epithelium can become Orthokeratinsed 2% cysts & part of the lining Metaplastic changes mucous cells & ciliated cells frequently found Islands of squamous epithelium developed from rests of Malassez in a periapical granuloma without cystic transformation referred as "bay cyst
RESIDUAL CYST
Arises as a consequence of an improper surgical elimination of a radicular cyst Identical clinical and histological characteristics to those of a radicular cyst Become less inflamed tissue Thin & regular epithelium lining similar to DC / LPC Radiologically - radiolucency of variable size at the site of a previous tooth extraction cause removed Cyst wall uninflammed collagenous fibrous
FNAC Straw colored fluid Cholesterol crystals Protein levels- 5-11g/dl Smear -Inflammatory cells
Paradental cyst / Inflammatory collateral cyst / inflammatory periodontal cyst 60% of PD cysts Main (1970, 1985) & Craig (1976) Adults, III decade III molars (vital teeth) Partially erupted Lateral aspect (distal / distobuccal surface) of root H/O pericoronitis Cyst continuous with pericoronal / PDD pocket Associated with buccal enamel spur projecting towards furcation Discovered accidentally Occasional swelling Well demarcated distal / distobuccal RL superimposed over roots Distal follicular space preserved Lamina dura intact / no widening of PDL space apical region
Mandibular infected buccal cyst / Juvenile Paradental cyst 36% of PD cysts Stoneman & Worth (1983) Young children8 & 9 yrs & 13 &19 yrs I & II mandibular molars & premolars (vital teeth) Partially / fully erupted Buccal surfaces of root bifurcation inv H/O Pericoronitis More severe clinical signs & symptoms related to anatomical diff in mandible Swelling, pain, tenderness & suppuration Tooth tipped buccally Painful occlusion Facial swelling with pointing abscess Deep PD pockets continuous with cyst lumen Well demarcated RL over buccal aspect of roots Buccal expansion with corticated outline /Loss of buccal cortex Tooth buccally tilted roots close to lingual cortex Cyst large displace adjacent tooth crypt Furcation inv loss of inter-radicular bone Lamina dura intact / no widening of PDL space
PATHOGENESIS Origin REE / rests of M / non-odontogenic epi (sinus / crevicular epithelium) REE Extended portion of REE over enamel spur Unilateral expansion of dental follicle sec to inflammatory destruction of PDL & bone Rests of Malassez Inflammatory originpericoronitis stimulated rests of M Demonstrated continuity b/w cyst epithelium & REE / Pericoronal / PDD pocket PDC dilated follicle lined by hyperplastic REE eruption pocket cysts / inflammatory pocket cysts
*****
GENERAL MEDICINE Cardiology
GENERAL PHYSICAL EXAMINATION

General examination of a pt with suspected heart disease should include vital signs (respiratory rate, pulse, blood pressure), skin color (e.g., cyanosis, pallor), clubbing, edema, evidence of decreased perfusion (cool and sweaty skin), and hypertensive changes in optic fundi. Examine aneurysm. An ankle-brachial brachial index (systolic BP at ankle divided by arm systolic BP) < 0.9 indicates lower extremity arterial obstructive disease. Jugular Venous Pressure Jugular venous pressure indicates the pressure of the right atrium The jugular venous pressure is normally 6 to 8 cm H2O (1 mm Hg is equal to 1.36 cm H2O) and is best evaluated d with the patient supine su at an angle of 45 or more The normal waves profile contains an a deflection, which reflects atrial contraction; c deflection, closure of tricuspid valve; followed by the x descent, downward motion of right ventricle; and v deflection, atrial filling deflection while the tricuspid valve is closed followed by the y descent, representing ventricular filling as the tricuspid valve opens abdomen for evidence of hepatomegaly, ascites, or abdominal aortic
atrioventricular dissociation)
valve
(atrioventricular
Rapid x + y descent: constrictive pericarditis Kussmaul sign: venous filling increase with in inspiration, pericardial tamponade, or constriction. Paradoxical venous pressure with inspiration occurs in pericardial tamponade, constriction, and right ventricular failure Large, fused cv wave: tricuspid regurgitation Arterial Pulse Palpation of the radial pulse is useful for rate; the brachial or carotid pulse is checked for contour Tardus is the timing and rate of rise of upstroke, and parvus is the volume. Abnormalities of the arterial pulse and their indicated conditions are as follows Pulsus tardus: aortic stenosis Pulsus parvus: hypovolemia, LV failure, aortic or mitral stenosis Bounding (hyperkinetic): aortic regurgitation or atrioventricular fistulas Bifid (2 systolic peaks): hypertrophic obstructive cardiomyopathy (from mid systolic obstruction) Bisferiens (2 systolic peaks, occurs when a large volume is ejected rapidly, and a distinct systolic dip): aortic regurgitation Dicrotic (a systolic peak followed by diastolic pulse wave): left ventricular failure with hypotension, low output, and increased peripheral resistance Pulsus paradoxus (exaggerated inspiratory decrease [>10 mm Hg] in pulse pressure): suggestive of tamponade Pulsus alternans (alternating strong and
Abnormalities of the waves indicate various conditions, as follows: Increased jugular venous ous pressure, increased pressure failure Large a wave: tricuspid stenosis, right ventricular hypertension Cannon a hypertrophy, (i.e., e., wave: pulmonary right increased atria indicating possible fluid overload. Common in congestive heart
weak pulse): severe depression of left ventricular function
ventricular end-diastolic diastolic pressure) contracting a closed intermittently against

Thrills Thrills indicate turbulent flow (such as aortic stenosis, ventricular septal defect) AUSCULTATION (MAHE-95) The bell of the stethoscope is used for lowpitched sounds (heart sounds and middiastolic (MAHE-94) The diaphragm is used for high-pitched sounds (systolic murmurs, aortic regurgitation, ejection clicks and opening snaps). Ascultatory Areas Mitral area Pulmonary area First Aortic area Second Aortic area Tricuspid area murmur in mitral stenosis).
The intensity of S2 is decreased with heavily calcified valves Physiologic splitting of S2 occurs in inspiration as a result of increased blood return to the right side of the heart Abnormalities include, Widened splitting: Right bundle branch block, pulmonic stenosis, mitral regurgitation Fixed splitting (no respiratory change in splitting): Atrial septal defect Narrow splitting: Pulmonary hypertension Paradoxical splitting (splitting narrows with inspiration): Aortic stenosis, left bundle branch block, CHF Loud A2: Systemic hypertension Soft A2: Aortic stenosis (AS) Loud P2: Pulmonary arterial hypertension Soft P2: Pulmonic stenosis (PS)
Third heart sound (S3) Low-pitched, heard best with bell of stethoscope at apex, following S2 Normal in children S3 in adults is associated with volume load on the left ventricle (aortic regurgitation, mitral regurgitation, cardiomyopathy) Fourth heart sound (S4) First heart sound (S1) This is due to mitral and tricuspid valve closure A loud S1 occurs in thin people, hyper dynamic circulation, tachycardias, short PR interval and mildmoderate mitral stenosis (Delhi-92) A soft S1 occurs in obesity, emphysema, pericardial effusion, severe calcific mitral stenosis, mitral or tricuspid regurgitation, heart failure, shock, bradycardias, long PR interval and first-degree block Second heart sound (S2) This is due to aortic and pulmonary valve closure. This is best heard in the left second intercostal space with the patient seated. The intensity of S2 is increased by hypertension Opening Snap (OS) High-pitched Follows S2 (by 0.060.12 s) Heard at lower left sternal border and apex in mitral stenosis (MS) Gallop rhythm It is hearing of 3 sounds (1st, 2nd, and extra sound) in the presence of tachycardia (like galloping horse) Types 1. 2. 3. Diastolic gallop (S1, S2, S3 ) Presystolic gallop (S1, S2, S3 ) Summation gallop (S1, S2, S3, S4 ) Low-pitched, heard best with bell at apex, preceding S1 Reflects atrial contraction into a noncompliant ventricle Found in AS, hypertension, hypertrophic cardiomyopathy, and coronary artery disease (CAD)

The more severe the MS, the shorter the S2OS interval Ejection Clicks High-pitched sounds following S1 Observed in dilatation of aortic root or pulmonary artery, congenital AS (loudest at apex) or PS (upper left sternal border); the latter decreases with inspiration Mid systolic Clicks At lower left sternal border and apex, often followed by late systolic murmur in mitral valve prolapse HEART MURMURS Audible vibration produced by turbulent flow of blood from a narrow to a wide channel through large blood vessels or valves during the cardiac cycle Heard best over point where channel widens or beyond narrowing in the direction in which blood is flowing Exercise or severe anemia (increases blood flow) may cause murmurs to appear Polcythemia (thickening of blood) may cause murmur to disappear Pathological heart murmur is one associated with a structural or functional abnormality of the heart Describing a heart murmur 1. Timing Murmurs are longer than heart sounds can distinguished by simultaneous palpation of the carotid pulse systolic, diastolic, continuous 2. Shape/Configuration 3. Crescendo, decrescendo, crescendo3. decrescendo, plateau Location of maximum intensity 4. 5. Determined by the site where the murmur originates E.g. A, P, T, M areas Reflects the intensity of the murmur and the direction of blood flow Intensity Graded on a 6 point scale Grade 1 = very faint Grade 2 = quiet but heard immediately 2. Diastolic Murmurs 1. Early diastolic Aortic valve regurgitation Pulmonic valve regurgitation Mitral or tricuspid stenosis Radiation 2. Systolic Murmurs 1. Ejection-type Aortic outflow tract Aortic valve stenosis Hypertrophic cardiomyopathy Aortic flow murmur Pulmonary outflow tract Pulmonic valve stenosis Pulmonic flow murmur Holosystolic Mitral regurgitation Tricuspid regurgitation Ventricular septal defect Mitral or tricuspid valve prolapse 7. 6. Pitch Grade 3 = moderately loud Grade 4 = loud with thrill
Grade 5 = heard with stethoscope partly off the chest with thrill Grade 6 = audible without stethoscope with thrill High (MR, TR, AR) best heard by diaphragm Low (TS, MS) best heard by bell Blowing (MR, AR), harsh (AS, PS, VSD) & rumbling, and musical Others Variation with respiration Left heart murmurs (AR, MR) are accentuated in expiration Right heart murmur (PR, TR, TS) in inspiration Variation with position of the patient Variation with special maneuvers Valsalva/Standing Murmurs decrease in length and intensity Except Hypertrophic cardiomyopathy and Mitral valve prolapse Quality
obstructive
Late-systolic
Mid-to-late diastolic Flow murmur across mitral or tricuspid valves

3. Continuous Patent ductus arteriosus Coronary AV fistula Ruptured sinus of Valsalva aneurysm Functional Murmurs These are murmurs which arise in absence of organic heart disease at their site of origin. They are mostly systolic, soft, of low intensity, not accompanied with thrill and change with change of posture of patient. Examples 1. Pulmonary and aortic ejection systolic murmur, in hyperdynamic circulatory states 2. Ejection systolic m. at pulmonary area in ASD Pericardial Rub Scratching sound like friction between rough surfaces and has a superficial to and fro quality. Best heard to the left of the lower sternum It is accentuated when patient leans forward and by pressure with stethoscope Cause: Acute retardates hypertension cardiomyopathy and
hypertrophic
A double pulsation may occur in hypertrophic cardiomyopathy A sustained left parasternal heave occurs with right ventricular hypertrophy or left atrial enlargement A palpable thrill may be felt overlying an abnormal cardiac valve, e.g. systolic thrill with aortic stenosis Forceful apical thrust: Left ventricular hypertrophy Lateral and downward displacement of apex impulse: Left ventricular dilatation Prominent presystolic impulse: Hypertension, aortic stenosis, hypertrophic cardiomyopathy Double systolic apical impulse: Hypertrophic cardiomyopathy Sustained lift at lower left sternal border: Right ventricular hypertrophy Dyskinetic (outward bulge) impulse: Ventricular aneurysm, large dyskinetic area post MI, cardiomyopathy
RHEUMATIC FEVER
An acute inflammatory complication of group A streptococcal infection, with a possibility of residual heart disease as a result of carditis It occurs most often in children (streptococcal sore throat is common), the peak age-related incidence is between 5 and 15 years in The disease is more common among population with low social and economic standards, due to overcrowding PATHOGENESIS Rheumatic fever follows acute beta-hemolytic streptococcal infection (group A) of the pharynx (KAR-2000, 01) The mechanism of development of rheumatic fever after infection is still unknown The hypothesis of "antigenic mimicry" between heart valves and myocardial cells with bacterial antigens was suggested, abnormal immune response by the human host to these antigens, will result in damage to the cardiac tissue. Genetic predisposition may be involved Crunch
Exocardiac Noises These are sounds recurring with each heartbeat but originate outside the heart. Examples: 1. 2. 3. Pericardial rubs Clicking sound of small pneumothorax Mediastinal pneumomediastinal: systolic EXAMINATION OF THE PRECORDIUM With the patient at 45, the cardiac apex is located in the 5
th
sounds like a loud
intercostal space mid-
clavicular line. Left ventricular dilatation will displace the apex downwards and laterally. It may be impalpable in patients with emphysema, obesity, pericardial or pleural effusions A tapping apex is a palpable first sound and occurs in mitral stenosis A vigorous apex may be present in diseases with volume overload, e.g. aortic regurgitation A heaving apex may occur with left ventricular hypertrophy aortic stenosis, systemic

Diagnosis of Rheumatic Fever Clinical diagnosis is the main method of diagnosis supported by laboratory evidence of streptococcal infection (KCET-2000, 01). o Laboratory tests may help in the diagnosis of RF but all of them are non-specific. 2. CRITERIA OF DIAGNOSIS (Updated Jones criteria) (MAHE-01, KCET-03, PGI-95) Major Criteria: 5 Criteria 1. 2. 3. 4. 5. Carditis Migratory polyarthritis Sydenhams chorea (Rheumatic chorea) Subcutaneous nodules Erythema marginatum 3. Migratory Polyarthritis o
The mitral valve is involved most frequently, followed by the aortic valve. Diseased valve is susceptible to bacterial endocarditis.
Found in 75 percent of cases. Most often affecting large joints like ankles, wrists, knees, and elbows over a period of days. It does not affect small joints of the hands or feet and seldom involves the hip joints. It is extremely painful, leaving one joint to start inflammation in the other joint (migratory), causing pain and swelling. Sydenham's chorea (Rheumatic chorea) Occurs in less than 10 % of patients with rheumatic fever. The latent period between the onset of the initiating streptococcal infection and the onset of Sydenham's chorea may be as long as several months. Clinically the patient shows involuntary rapid, jerky, irregular movements that tends to occur in the limbs or the face, these movements may cause falling of things from the patient's hand. 4. Subcutaneous nodules Present in less than 10 % of cases. They are found over extensor surfaces of the joints, most often in patients with long-standing rheumatic heart disease.
Minor Criteria 1. 2. 3. 4. 5. Fever Arthralgia Elevated acute phase reactants ( c- reactive proteins) Prolonged P-R interval in ECG Evidence of a recent streptococcal infection (ASOT, Throat culture) At least 80% of patients with acute RF have an elevated anti-streptolysin-O titer at presentation To diagnose Rheumatic fever: According to Jones criteria, Either 2 major criteria one major + two minor criteria Plus evidence of an recent streptococcal infection for both 1. Carditis Pancarditis involving the pericardium, myocardium, and endocardium. Clinical manifestations includes: Sinus tachycardia, the murmur of mitral regurgitation, an S3 gallop, a pericardial friction rub, and cardiomegaly, and may be evidence of heart failure. ECG may show prolonged PR interval. Outcome of Rheumatic carditis o Healing of the rheumatic valvulitis may cause fibrous complication of the valve. of thickening and rheumatic fever, adhesion, resulting in the most serious valvular stenosis and/or regurgitation
5.
Erythema marginatum An uncommon manifestation. It is an evanescent the trunk. macular eruption with rounded borders, usually concentrated on
TREATMENT 1. Antibiotics Therapy immediately: a complete 10-day course in adults Oral penicillin V (500 mg twice daily). Erythromycin (250 mg four times daily) for those with penicillin allergy. Benzathine penicillin G (a single intramuscular injection of 1.2 million units) may be used to prevent colonization in the throat.

2. Salicylates for rheumatic arthritis: Given in excitement, fever, anemia,
paroxysmal
increasing doses up to 2 g four times daily. For 4 to 6 weeks and gradually tapered to prevent rebound. 3. Prednisone ( Corticosteroids) for rheumatic carditis in doses up to 30 mg four times daily in severe cases, as the patient improves, salicylates can be added during the tapering of the steroid dose; this may require 4 to 6 weeks. Secondary Prophylaxis: (According to American Heart Association and of the World Health Organization) To prevent subsequent colonization of the upper respiratory tract with group A streptococci, and prevent recurrence of rheumatic fever. Benzathine penicillin G (Intramuscular), 1.2 million units every 4 weeks Penicillin V (250 mg twice daily) orally Sulfadiazine (1.0 g daily) orally Duration of prophylactic treatment: Should be individualized but at least for 5 years. High risk group may be for life (patients with rheumatic heart disease). OUTCOME OF RHEUMATIC FEVER Complete healing. Residual damage to the heart valves. The heart may escape the first attack of rheumatic fever without residual damage, but rarely escape the second attack, so prophylactic treatment is mandatory after the first attack. Rx
tachycardia, pregnancy etc. Signs (MAHE-01) Right ventricular lift Loud S1 Opening snap (OS) follows A2 by 0.060.12 s Diastolic rumbling murmur with presystolic accentuation in sinus rhythm Duration of murmur correlates with severity of obstruction Diagnosis ECG Typically shows atrial fibrillation (AF) or left atrial (LA) enlargement when sinus rhythm is present. Right-axis deviation and RV hypertrophy in the presence of pulmonary hypertension. CXR Shows LA and RV enlargement and Kerley B lines. Echocardiogram: Most useful non invasive test; shows inadequate separation, calcification and thickening of valve leaflets and sub valvular apparatus, and LA enlargement. Complications Hemoptysis, pulmonary embolism, pulmonary infection, systemic embolization; endocarditis is uncommon in pure MS.
Pts should receive prophylaxis for recurrent rheumatic fever (penicillin V 250500 mg PO bid or benzathine penicillin G 12 M units IM monthly) In the presence of dyspnea, sodium restriction and oral diuretic therapy; beta blockers; digitalis, or rate-limiting calcium channel antagonists (i.e., verapamil or diltiazem) to slow ventricular rate in AF
VALVULAR HEART DISEASES

MITRAL STENOSIS (MS) Etiology Most commonly rheumatic, although history of acute rheumatic fever is now uncommon Observed primarily in infants Symptoms (MAHE-94) Symptoms most commonly begin in the fourth decade, but MS often causes severe disability at earlier ages in developing nations Principal symptoms are dyspnoea and pulmonary edema precipitated by exertion,
Warfarin (with target INR 2.03.0) for pts with AF and/or history of systemic and pulmonic emboli For AF of recent onset, consider reversion (chemical or electrical) to sinus rhythm, ideally after 3 weeks of anticoagulation Mitral valvotomy in the presence of symptoms and mitral orifice ~1.5 cm2 In uncomplicated MS, percutaneous balloon valvuloplasty is the procedure of choice; if not feasible, then open surgical valvotomy

MITRAL REGURGITATION (MR) Etiology Rheumatic heart disease in ~33% of patients with chronic MR Other causes: mitral valve prolapse, ischemic heart annular congenital Symptoms Signs Sharp upstroke of arterial pulse LV lift S1 diminished Wide splitting of S2; S3 Loud holosystolic murmur and often a brief early-mid-diastolic murmur Echocardiogram Rx For severe/decompensated MR, treat as for heart failure, including vasodilators diuretics, (e.g., ACE IV inhibitors, beta blockers, and digoxin Intravenous MR Anticoagulation is indicated in the presence of atrial fibrillation Surgical treatment, either valve repair or replacement, dysfunction MITRAL VALVE PROLAPSE (MVP) Etiology Most commonly idiopathic; may accompany rheumatic fever, ischemic heart disease, atrial septal defect, the Marfan syndrome. Pathology Redundant mitral valve tissue with myxedematous degeneration and elongated chordae tendineae is indicated if patient has symptoms or evidence of progressive LV Symptoms nitroprusside) are beneficial for acute, severe AORTIC STENOSIS (AS) Etiology Enlarged LA Hyperdynamic LV Rx Asymptomatic pts should be reassured Fatigue, weakness, and exertional dyspnea Echocardiogram disease with papillary muscle dysfunction, LV dilatation of any cause, mitral calcification, infective hypertrophic endocarditis, Signs (MAHE-94, 01) cardiomyopathy, Symptoms More common in female Most pts are asymptomatic
Most common symptoms are atypical chest pain and a variety of supraventricular and ventricular arrhythmias
Mid or late systolic click(s) followed by late systolic murmur at the apex Exaggeration by Valsalva maneuver, reduced by squatting and isometric exercise (Chap. 117)
Shows posterior displacement of one or both mitral leaflets late in systole.
Beta blockers may lessen chest discomfort and palpitations Prophylaxis for infective endocarditis is indicated only if prior history of endocarditis Valve repair or replacement for pts with severe mitral regurgitation; aspirin or anticoagulants for pts with history of TIA or embolization
Most common cause in adults is age-related degenerative calcific AS and is usually mild Other causes are congenital (bicuspid valves) or rheumatic (almost always associated with rheumatic mitral valve disease)
Dyspnea, angina, and syncope are cardinal symptoms; they occur late, after years of obstruction.
Signs (AIIMS-02) Weak and delayed arterial pulses with carotid thrill Double apical impulse A2 soft or absent S4 common Diamond-shaped systolic murmur grade 3/6, often with systolic thrill Murmur is typically loudest at 2nd right intercostal space, with radiation to carotids

Echocardiogram Shows thickening of LV wall, calcification and thickening of aortic valve cusps with reduced systolic opening Rx Avoid strenuous activity in severe AS, even in asymptomatic phase Valve replacement is indicated in adults with symptoms resulting from AS and hemodynamic evidence of severe obstruction Operation should be carried out before frank failure has developed AORTIC REGURGITATION (AR) Etiology Rheumatic etiology is common, especially if rheumatic mitral disease present May also be due to infective endocarditis, syphilis, aortic dissection, or aortic dilatation due to cystic medial necrosis Signs and Symptoms Exertional failure Wide pulse pressure, water hammer pulse, capillary pulsations (Quincke s sign) A2 soft or absent S3 common Blowing, decrescendo diastolic murmur along left sternal border (along right sternal border with aortic dilatation) Echocardiogram LA enlargement, LV enlargement, high frequency diastolic fluttering of mitral valve Failure of coaptation of aortic valve leaflets may be present Rx Standard therapy for LV failure Vasodilators (long-acting nifedipine or ACE inhibitors) are recommended as Rx dyspnea and awareness of heartbeat, angina pectoris, and signs of LV Clinical Manifestations TRICUSPID REGURGITATION (TR) Etiology Rx TRICUSPID STENOSIS (TS) Etiology
Usually rheumatic; most common in females; almost invariably associated with MS
Clinical Manifestations Hepatomegaly, ascites, edema, jaundice, jugular venous distention with slow y descent Diastolic rumbling murmur along left sternal border increased by inspiration with loud presystolic component Right atrial and superior vena caval enlargement on chest x-ray
In severe TS, surgical relief is indicated, with valvular repair or replacement
Usually functional and secondary to marked RV dilatation of any cause and often associated with pulmonary hypertension
Severe RV failure, with edema, hepatomegaly, and prominent v waves in jugular venous pulse with rapid y descent Systolic murmur along lower left sternal edge is increased by inspiration
Intensive diuretic therapy when right-sided heart failure signs are present In severe cases (in absence of severe pulmonary hypertension), surgical treatment consists of tricuspid annuloplasty or valve replacement
INFECTIVE ENDOCARDITIS (IE)

A serious complication to valvular heart disease either rheumatic or congenital. The most common organism causing IE is streptococcus viridans and secondly S. fecalis. Which are normal commensals in the oral cavity. (PGI-98, AIPG-03) Minor procedures (dental extraction) may result in bactremia, settling on the valve and cause endocarditis.
antihypertensive agents Surgical valve replacement should be carried out in pts with severe AR when symptoms develop or in asymptomatic pts with LV dysfunction (LVEF < 50%, LV end systolic volume > 55 mL/m2, end-systolic diameter > 55 mm or LV diastolic dimension > 75 mm) by echocardiography

PATHOLOGY (AIPG-96, 03, PGI-98, AIIMS-04) Vegetations are formed over the valvular & mural endocardium organism causing in the valvular center Sub acute IE: most common & requires combinations of the 2 factors (infection & cardiac lesion). Acute IE: affecting the healthy endocardium ,usually occurs in the right side of the heart in addicts. CLINICAL PICTURE Manifestations of the disease are due to, Toxemia Embolization Immune complexes Extra cardiac manifestations Face Fever (usually low grade & prolonged) Pallor & toxic facies Eye Subcojuctival hemorrhage (Toxemia) Roth spots (area of retinal hemorrhage with pale center) Sudden blindness : due to embolism of the central retinal artery Upper & lower limbs (KCET-01) Clubbing: It occurs with long standing cases . Splinter hemorrhage: longitudinal hemorrhage under the nails due to rupture capillaries (toxemia) Oslers nodule: Small, painful, intra cutaneous in the pulps of fingers & toes. (Due to toxic endothelial hyperplasia of the capillary Janeways nodule : Small painless patches on the palms Abnormalities of the radial pulse Tachycardia: due to fever Absent pulse: due to embolization of brachial artery Investigations Blood culture: for organism (the most important investigation) (KCET-04) It is +ve in most cases (90 %)
At least 3 samples are taken during fever & cultured under aerobic & anaerobic conditions. The results are observed from 3 days up to 3 weeks. Negative culture may be seen in Antibiotic treatment before taking the blood sample Some organisms e.g. fungi
damage.(The
surrounded by fibrin & platelets) may detach leading to embolization. TYPES
Vegetation
Echo: for vegetations Small vegetations can detected by trans esophageal echo. Blood picture Anemia Leukocytosis ESR
TREATMENT OF IE For streptococcus viridans Penicillin G 23 million units IV / 4h for 4 weeks OR Penicillin G 23 million units IV / 4h + Gentamicin 1 mg/kg IM or IV / 8h, both for 2 Weeks Prophylaxis of IE (MAHE-02,98, KCET-03, AIIMS-99) Should be given for any patient with rheumatic or congenital valvular lesions before any surgical procedure especially in the mouth. For oral cavity, respiratory tract, or esophageal procedures: Standard regimen: Amoxicillin 2 g orally 1 hour before procedure Inability to take oral medication: Ampicillin 2 g IV or IM within 30 min of procedure Penicillin allergy: Clarithromycin 500 mg orally 1 h before procedure Cephalexin or Cefadroxil 2.0 g orally 1 h before procedure Penicillin allergy + Inability to take oral medication: Cefazolin 1 g IV or IM 30 min before procedure
10
ACUTE MYOCARDIAL INFARCTION

MI occurs if sudden decrease in coronary blood flow following a thrombotic occlusion of a coronary artery previously narrowed by atherosclerosis. (AIIMS-93, MAHE-94) CLINICAL PRESENTATION In about 50% of patients there is a precipitating factor as vigorous physical exercise, emotional stress, or a medical or surgical illness. Severe chest pain described as heavy, squeezing, and crushing is the most common symptom. Site is central chest and/or the epigastrium, sometimes it radiates to the arms. (AIPG-97) Less common sites of radiation include the abdomen, back, lower jaw, and neck. Usually accompanied by weakness, sweating, nausea, vomiting, anxiety, and a sense of impending death. EXAMINATION Patients are anxious and restless, trying to relieve the pain by moving about in bed, altering their position, and stretching. Pallor is associated with perspiration and coolness of the extremities. May be changes in blood pressure, and pulse.
TREATMENT (KCET-08) Pre-hospital care: rapid transfer to the hospital with a trained team capable of resuscitative maneuvers, including defibrillation. Hospital management: Emergency treatment: Aspirin, oxygen inhalation, SL nitrates, Intravenous beta blockers and morphine to control pain. Decrease infarct size: o Thrompolysis: plasminogen o Using activator tissue (tPA), or
streptokinase intravenously. Percutaneous Transluminal Coronary Angioplasty Drug therapy: o o Heparin: anticoagulant. Beta-blockers. (PTCA): Can also decrease infarcted area.
HYPERTENSION
Arterial hypertension Elevation of systolic and/or diastolic blood pressure, either primary or secondary. Borderline isolated systolic hypertension Diastolic BP is < 90 mmHg, between 140 and 159. systolic BP
INVESTIGATIONS (AIIMS-92, AIPG-95, KCET-02) ECG: Typical changes in ST segment and QRS complex. Serum cardiac markers: Creatine phosphokinase (CK): rises within 4 to 8 h and generally returns to normal by 48 to 72 h. (CKMB: specific for myocardial muscle). Cardiac-specific troponins: Proteins found in cardiac muscle, normally undetectable but rises over 20 times in MI. (KAR-02) Other non-specific markers: Raised white cell count, ESR, SGOT, LDH. Two-dimensional Abnormal wall motion. Myocardial perfusion imaging with thallium 201 or technetium 99m: Reveal a cold spot. echocardiography: Malignant hypertension Blood pressure above 200/140, the condition is defined by the presence of papilledema, usually accompanied by retinal hemorrhages and exudates, rather than by the absolute pressure level. Labile hypertension Patients who are sometimes, but not always, have arterial pressures in the hypertensive range. They are considered to have borderline BP. Isolated systolic hypertension Diastolic BP is < 90 mmHg, Systolic BP is 160 mmHg.

AJC 7 Classification
11
when there is increased cardiac sympathetic nerve activity (cardioselective B1 blocker:atenolol ), ( Propranolol: non non-selective). Vasodilators: Arteriolar vasodilators: Reduce peripheral resistance (Hydralazine). ACE inhibitors: 2 Prevent (potent production of angiotensin vaso vaso-constrictor),
preserve bradykinin (vaso (vaso-dilator), (Captopril). Calcium channel antagonists: modify Ca intry into the cells, cause peripheral vasodilation (nifedipine).
HEART FAILURE
Primary or essential hypertension (EH) Patients with arterial hypertension with no definable cause are said to have primary, essential, or idiopathic hypertension. It is the most common cause of hypertension. There is a familial tendency for hypertension. Invironmental factors involved in the disease: salt intake, obesity, occupation, alcohol intake, family size, and crowding. These factors have all been assumed to be important in the increase in blood pressure with age. TREATMENT General measures Relief of stress Dietary management: reduce sodi sodium, calory , and saturated fats Regular aerobic exercise Weight reduction (if needed) Control of other risk factors contributing to the development of arteriosclerosis Drug therapy Diuretics: Acts through depletion of plasma volume ( Thiazides, spironolactone). Antiadrenergic agents: alpha-receptor receptor agonists. Stimulation vasomotor sympathetic methyldopa). Alpha-Adrenergic Adrenergic Receptor Blockers: blocking sympathetic receptors 1 and 2 in the CNS( prazocin). Beta-Adrenergic Adrenergic Receptor Blockers: block sympathetic effects on the heart , reducing cardiac rdiac output, lowering arterial pressure SYMPTOMS (TNPSC-99) Due to inadequate perfusion of peripheral tissues (fatigue, dyspnea) and elevated intra cardiac filling pressures (orthopnea, of alpha2 of receptors the he brain agents in the centers reduces ACUTE PRECIPITATING FACTORS (AP-04) Include (1) increased Na intake, (2) noncompliance with anti anti-CHF medications, (3) acute MI (may be silent), (4) exacerbation of hypertension, infections (5) acute fever, arrhythmias, (7) (6) and/or pulmonary UNDERLYING CARDIAC DISEASE Includes: (1) states that depress systolic ventricular function (coronary artery disease, hypertension, dilated cardiomyopathy, valvular disease, congenital heart disease); and (2) states of heart failure w with preserved ejection fraction (e.g., restrictive hypertrophic fibrosis, endomyocardial cardiomyopathies, cardiomyopathy, DEFINITION Condition in which heart is unable to pump sufficient blood for metabolizing tissues or can do so only from an abnormally elevated fil filling pressure It is important to identify the underlying nature of the cardiac disease and the factors that precipitate ecipitate acute CHF.
disorders), also termed diastolic failure.
embolism, (8) anemia, (9) thyrotoxicosis, (10) pregnancy, (11) acute myocarditis or infective endocarditis, and (12) certain drugs (e.g., non steroidal anti inflammatory agents, verapamil).
outflow
(clonidine,

paroxysmal nocturnal dyspnea, peripheral edema) SIGNS Jugular venous distention, S3, pulmonary congestion ascites) Sinus tachycardia is common. In patients with diastolic dysfunction, an S4 is often present. CXR Can reveal cardiomegaly, pulmonary vascular redistribution, Kerley B lines, pleural effusions. Left ventricular contraction and diastolic dysfunction can be assessed by echocardiography with Doppler recordings. In addition, echo can identify underlying valvular, pericardial, or congenital heart disease, as well as regional wall motion abnormalities typical of coronary artery disease. Measurement of brain 5. Digitalis natriuretic peptide (BNP) differentiates cardiac from pulmonary causes of dyspnea (>100 pg/mL in heart failure). CONDITIONS THAT MIMIC CHF Pulmonary Disease Chronic bronchitis, 6. Other measures emphysema, and asthma; look for sputum production and abnormalities on CXR and pulmonary function tests Other Causes of Peripheral Edema Liver disease, varicose veins, and cyclic edema, none of which results in jugular venous distention. Edema due to renal dysfunction is often accompanied by elevated serum creatinine and abnormal urinalysis Rx 1. General measures Restrict salt intake Avoid anti arrhythmics for asymptomatic arrhythmias Avoid NSAIDs Immunize against influenza and 4. Beta blockers (rales, dullness over pleural 3. ACE inhibitors effusion, peripheral edema, hepatomegaly, and
12
For diuretic resistance, administer IV or use 2 diuretics in combination (e.g., furosemide plus metolazone) Low-dose dopamine to enhance renal flow
For all patients with LV systolic heart failure or asymptomatic LV dysfunction Contraindications: Serum K+ > 5.5, advanced renal failure (e.g., creatinine > 3 mg/dL), bilateral renal artery stenosis, pregnancy
For patients with class IIIII heart failure, combined diuretics Contraindications: Bronchospasm, symptomatic bradycardia or advanced heart block, unstable heart failure or class IV symptoms with ACE inhibitor and
For persistently symptomatic pts with systolic heart failure (especially if atrial fibrillation present) added to ACE inhibitor, diuretics, beta blocker
Consider angiotensin receptor blocker or combination of hydralazine and oral nitrate if not tolerant of ACE inhibitor Consider spironolactone in class IIIIV heart failure Consider ventricular resynchronization in pts with class III or IV heart failure and QRS > 120 ms Consider implantable cardioverterdefibrillator in pts with class III heart failure and ejection fraction <30%
COR PULMONALE
RV enlargement resulting from primary lung disease; leads to RV hypertrophy and eventually to RV failure. (AIPG-96, 2000)
pneumococcal pneumonia 2. Diuretics Use in volume-overloaded pts to achieve normal JVP and relief of edema Weigh daily to adjust dose
ETIOLOGY Pulmonary parenchymal or airway disease. Chronic obstructive lung disease (COPD),

interstitial lung diseases, bronchiectasis, cystic fibrosis Pulmonary pulmonary vascular emboli, disease. primary Recurrent pulmonary Rx
13
Aimed at underlying pulmonary disease and may include bronchodilators, antibiotics, and oxygen administration If RV failure is present, treat as CHF, instituting low-sodium diet and diuretics; digoxin must be administered cautiously (toxicity increased due to hypoxemia, hypercapnia, acidosis)
hypertension (PHT) (Chap. 134), vasculitis, sickle cell anemia Inadequate Kyphoscoliosis, mechanical neuromuscular ventilation. disorders,
marked obesity, sleep apnea. SYMPTOMS Depend on underlying disorder but include dyspnea, cough, fatigue, and sputum production (in parenchymal diseases). SIGNS Tachypnea, cyanosis, clubbing are common RV impulse along left sternal border, loud P2, right-sided S4 If RV failure develops, elevated jugular venous pressure, hepatomegaly with ascites, pedal edema. Murmur of tricuspid regurgitation may appear. ECG RV hypertrophy and RA enlargement; tachyarrhythmias are common. CXR Shows RV and pulmonary artery enlargement; if PHT present, tapering of the pulmonary artery branches. CHEST CT (APPSC-99) Identifies emphysema, interstitial lung disease, and acute pulmonary embolism; V/Q scan more reliable for diagnosis tests of and chronic ABGs thromboemboli. Pulmonary function characterize intrinsic pulmonary disease. ECHOCARDIOGRAM RV hypertrophy; LV function typically normal. RV systolic pressure can be estimated from Doppler measurement of tricuspid regurgitant flow. If imaging is difficult because of air in distended lungs, RV volume and wall thickness can be evaluated by MRI
Loop diuretics must also be used with care to prevent significant metabolic alkalosis that blunts respiratory drive. Supraventricular tachyarrhythmias are common and treated with digoxin or verapamil (should typically avoid beta blockers). Chronic anticoagulation with warfarin is indicated when pulmonary hypertension is accompanied by RV failure
*****
14
General Surgery Thyroid Diseases
THYROID DISEASES
EMBRYOLOGY The gland is derived from Median bud of the pharynx (thyroglossal duct) which passes from the foramen caecum at the base of the tongue forming the ishmus. The 2 lobes derive from the ultimobranchial body from the fourth pharyngeal pouch. Para-follicular cells (C-cells )are derived from the neural crest. ANATOMY The gland lies at the front of the lower part of the neck Located in the anterior compartment of the neck It weights 20 - 25 gram, pinkish in colour Consists of two lobes, isthmus and Its upper pole reaches the oblique line of the thyroid cartilage Its lower pole reaches the sixth tracheal ring Isthmus lies in front of 2, 3 & 4 tracheal rings Part of the deep fascia of the neck, investing layer of deep fascia (pretracheal fascia) encloses the thyroid gland & is attached to the cricoid cartilage & oblique line of the thyroid cartilage So It moves up & down with deglutition. Medial relations Larynx and pharynx above, and the trachea, esophagus below and RLN in between Antero-lateral relations Strap muscles
Plus branches from tracheal and esophageal arteries.
Venous drainage Superior thyroid Vein drains to internal Jugular vein Middle thyroid vein drains to internal jugular vein. Inferior thyroid vein drains to innominate veins Multiple thyroid veins
Lymphatics Pretracheal (Delphic) and prelaryngeal then to the deep cervical, supracalvicular & mediastinal lymph nodes Nerve supply of the gland Sympathetic innervations from the cervical plexus Parasympathetic supply from the vagus nerve
Nerves related to the thyroid gland Recurrent laryngeal nerve runs from below the gland in between branches of inferior thyroid artery and passes in a tracheo-oesophageal groove to enter the larynx and supply all muscles of the larynx Superior laryngeal nerve runs at the upper pole of the gland with superior thyroid artery PHYSIOLOGY OF THE GLAND Iodide Trapping Iodide oxidation to iodine Binding to tyrosine to form mono & Di iodotyrosine Coupling to form tri-iodothyronine (T3) or T4. Stored in the colloid .with thyroglobulin Release occurs after separation from TG In blood mostly carried with TBG and the rest as free T3 & T4
Postero-lateral relations The carotid sheath
Posterior relations The parathyroid glands Physiological effects of thyroxin hormone Arterial Supply Superior thyroid artery branch of external carotid artery. Inferior thyroid arteries branch of thyro-cervical trunk branch of the first part of subclavian artery. Some times thyroidea ima artery branch from Arch of aorta.
Increased basal metabolic rate due to increased absorption of carbohydrates Increase mobilization & metabolism of lipids from stores Increased protein breakdown in the tissue
Increases heart rate due to affection of the sinus rhythm and increased conduction of excitation wave

Increased motility of the GIT due to increased smooth muscle tone Weakness of skeletal muscles due to protein breakdown & decreasing muscle myoglobin Excessive sweating due to stimulation of adrenergic nerve fibers to sweat glands Neuritis leading to nervous irritability Clinical Examination Loss of hair Muscles fatigue
Look at the whole patient for agitation nervousness or lethargy Examine the hands for sweating, tremor, tachycardia Examine the eyes for exophthalmos, lid
EVALUATION OF THE THYROID History The thyroid gland can cause two groups of symptoms 1. 2. Those connected with the swelling in the neck Those related to the endocrine activity of the thyroid gland Neck Symptoms H/O a lump in the neck H/O discomfort during swallowing H/O dyspnoea H/O pain H/O change in the voice (Hoarseness) Eye Symptoms The patient may complain of staring of protruding of the eyes H/O difficulty in closing eyelids H/O double vision H/O pain in the eyes Symptoms of Thyrotoxicosis Nervous irritability, Cardiovascular dyspnoea on symptoms: Nervousness, nervous insomnia,
lag, ophthalmoplegia, chemosis Examine the neck always; check that the lump moves with swallowing Palpate the cervical lymph nodes
Investigations 1. Synthesis and liberation of thyroid hormones is controlled by TSH from the anterior pituitary Measurements of thyroid hormones in blood Total serum thyroxin (T4) (55-150 mmol/l) Total serum tri-iodothyronin (T3) (1.2-3.1 mmol/l) Free serum thyroxin (T4) (8-26 pmol/l) Free serum tri-iodothyronine (T3) (3-9 pmol/l) Estimation of free hormone level is more accurate as total serum level is under the influence of carrying proteins: o False False elevated low level accompanies occur with pregnancy & CP o results hypoprotinaemia syndrome & cirrhosis) 2. Estimation of serum TSH This test is routinely done with estimation of thyroxin as it is, o o 3. Elevated in hypothyroidism Below normal in thyrotoxicosis ( nephrotic
instability, tremor of the hands systems: Palpitations, exertion, swelling
of the ankles and chest pain Metabolic & GIT symptoms: High in appetite but loss of weight, change in bowel habit usually diarrhea, preference of cold weather With excessive sweating and intolerance of hot weather. Changes in menstruation usually amenurrhoea. Symptoms of Myxoedema Increased weight with deposition of fat across the back of the neck Slow thought, speech and action Intolerance of cold weather
Tests using radioactive iodine I123 Radioactive iodine uptake Thyroid scanning o o Hot nodule or warm Cold nodule uptake uptake
Some times technetium 99 perchlorate (Tc99m ) is used if patient is sensitive to iodine

DISEASES OF THE THYROID Goiter (Gutter throat) is the word used to describe enlargement of part or all of the thyroid gland I. A. Goiter may be classified clinically as follows Treatment Conservative treatment Diffuse Euthyroid types 1. 2. 3. 4. B. Endemic goiter Physiological goiter Simple goiter Thyroiditis Euthyroid 3. 4. 5. Adenoma Carcinoma (papillary or follicular)
Enlargement of the whole of one lobe (Usually Hashimotos thyroiditis)
indicated
in
patient with multinodular goiters and Hashimotos thyroiditis. Indicators for surgery are, 1. 2. 3. 4. 5. 6. 7. Suspicious of cancer Symptoms of pressure Hyperthyroidism Substernal extension Cosmetic deformity Patient expose to radiation Family history
Nodular Euthyroid types 1. 2. Single Nodular Multi Nodular
II. Hyperthyroid A. B. Diffuse (Graves Disease) Nodular (Hyperthyroid) 1. 2. Single Nodular Multi Nodular
Multinodular Goiter The aetiology of this common type of thyroid swelling is unclear. Often the disease is sequel to previous simple or endemic goiter. Goiter may occur early in the life as
III. Other classifications according to toxicosity A. Thyroiditis 1. 2. 3. Subacute Disease) Hashimotos Disease Riedels Disease Thyroiditis (De Quervains
consequence of congenital defect in thyroid hormones product. Symptoms are usually awareness of neck mass, dyspnoea, dysphagia or symptoms caused by interference with venus return. Thyroid function studies (T4, T3) normal TSH increased and thyroid antibodies normal. Radioactive iodine uptake on scanning, may be increased. Pathological Complications Cyst formation Haemorrhage into cystadenoma may lead to compression of the trachea Calcification Infection Intrathoracic extension Toxicity (secondary thyrotoxicosis) common at the age of 30 years Pressure effects Malignancy may develop in at least 10% of long standing cases Treatment If there are no clinical signs of malignancy and the gland is not symptomatic, as thyroxine
NODULAR ENLARGEMENT (Euthyroid) The Solitary Nodule (SN) S.N. is the common clinical problem and significant percentage of cases represent some form of cancer. Clinical History and Examination Age, sex, place of birth, family history and H/O radiation H/O: Showed specifically emphasize the duration of the swelling, recent growth and local symptoms (dysphagia, pain, changes of voice) O/E: The clinician must systemically palpate the thyroid to determine whether there is solitary nodule or mulitnodular goiter and whether there are palpable lymph nodes Causes of solitary nodule in the thyroid gland 1. 2. Multinodular goiter Haemorrhage into nodule
conservative
treatment

therapy and simple observation is Skeletal Effects Muscular weakness Bone pain
appropriate Surgery, if there is any above complication (Subtotal Thyroidectomy)
Eye Signs TOXIC GOITER (Diffuse) (Primary Thyrotoxicosis or Graves Disease) Graves Disease is thought to be autoimmune disease resulting from defect in cell mediated immunity especially in view of, The presence of circulating thyroglobulin and microsomal antibodies in many patients with Graves Disease Lymphocytic infiltration of the gland There is often increase in IgG and the substance known long-acting thyroid stimulators (LATS) Graves Disease usually occurs in the twenties and thirties and affects females more often than males Clinical Presentation Since the excess thyroxine affects all the cells of the body, the symptoms are varied. General Symptoms The increased metabolism causes, Loss of weight with increased appetite Intolerance of warm weather with excess sweating Warm sweating hands Nervous Symptoms Nervousness disturbance Fine tremors and irritability with Radioactive Iodine Therapy
131
Lid retraction Protussion of the eye ball (exopthalmos)
Management Medical Treatment The preferred method of treatment is medical since the disease has tendency to remit spontaneously after 1-2 years in adults or 3-6 months in children Antithyroid drugs altering various stages of iodine metabolism:Propylthiouracil and methimazole Iodine in high concentration (Lugols Iodine) Propranalol o Prolonged therapy is required otherwise, stopped incidence of recurrence is high if drugs are
I may be given safely after othe patient
has been treated with antithyroid drugs and has become Euthyroid Radioactive Iodine is indicated in elderly or poor risk for surgery patient or patient with recurrence Contraindication: Children and pregnant women should not be treated with radioactive iodine Surgery (Sub total Thyroidectomy) Indications 1. 2. 3. 4. 5. 6. Failed medical treatment Very severe disease Large goiter with pressure symptoms Ophthalmic complication Compensated thyrocardiac fibrillation Social and economic circumstances
Cardiovascular Systems Palpitation and tachycardia Elevation of the pulse rate of the sleeping patient Atrial fibrillation
Gastrointestinal Disturbances Increased appetite for food and drink Loose stools with diarrhoea and distention
Pre-operative Preparation Genitourinary Symptoms Polyuria Menstrual disturbances Infertility with impotence o For at least 2 weeks; it consists , o Complete physical and mental rest Sedation

o Lugols Iodine ten drops TDS in milk or orange juice for 10-15 days before surgery o Antithyroid drugs in severe cases should be stopped 2 weeks before surgery o Propranalol (Inderal) 10-40 mgms TDS for 4 days before surgery and one day after surgery Postoperative Complications Immediate 1. 2. 3. 4. Haemorrhage Recurrent laryngeal nerve damage Thyroid crisis Parathyroid tetany Late Complications 1. 2. 3. PLUMMERS Hypothyroidism Recurrent thyrotoxicosis Keloid scars Myxoedema DISEASE (Toxic Nodular Goiter/ Cretinism HYPOTHYROIDISM
Deficiency of thyroid hormones in infancy leads to cretinism where as in adult, it leads to myxoedema
Cretinism is congenital deficiency of thyroid function which may be associated with aplasia of the thyroid or with goitrous gland (Cretinoid Goiter) Clinically the child is sluggish constipated and post-bellied with pale puffy face, protruding tongue, thick lips, flattered nose, short neck and thick short hands In adolescence, the patient is dwarfed and mentally retarded with dry wrinkled skin The thyroid gland may or may not be palpable Treatment: Thyroid extract should be daily for life. given
This common disease is important to the surgeon because there are other causes than surgery can cause it like Hashimotos Disease, De Quervains Thyroiditis, Iodine deficiency and Irradiation
Secondary Thyrotoxicosis) Secondary thyrotoxicosis differs from primary thyrotoxicosis in the following: Diffuse Graves disease Nodular Plummers disease Age Onset Course Young age Abrupt Remissions & exacerbations Nervous symptoms Metabolic manifestations Eye signs CV manifestations Thyroid gland +++ Elderly Gradual Steady course
Most patients are women and the commonest age at menopause
Clinical Symptoms Voice: Deepening CVS: Slow pulse, cardiomegaly Neurological: Mental slowness o o Delayed reflex relaxation Carpal tunnel syndromes
Skin: Dry , Coarse, loss of hair; Periorbital swelling Genital symptoms: Menorrhagia
+++ +++ + Diffuse
+ + false +++ Nodular
GIT: Increased weight and constipation Medical Treatment Thyroxine - the initial dose should be 0.05 mg daily; increased gradually until the serum thyroxine level is stabilized THYROIDITIS Diseases in which circulating thyroid antibodies can be demonstrated with common features such as lymphocytic infiltration of the gland.

The macroscopic appearance of the thyroid in autoimmune disease is hard and pale and microscopically. Most of the gland may be replaced by sheets of lymphocytic cells. 1. De Quervains Disease Virus infections which usually affect middle age women, often in course of influenza or mumps The gland became enlarged and painful with fever, pain on swallowing and radiating to the ears. The onset is sudden but the condition subsides months Most cases required no treatment apart from analgesics in severe cases giving short course of steroids for about a month. 2. Hashimotos Disease The etiology of this disease is not known and the most common form of thyroiditis. It is characterized by enlargement of the thyroid with or without pain and ACUTE SUPPURATIVE THYROIDITIS tenderness It is common in women and in most often seen at the time of the menopause. Hashimotos thyroiditis is believed to be autoimmune disease in which patients became sensitized against their own thyroid tissues and form antithyroid antibodies The relationship to thyroid function is variable but in the early stages of the disease. Some patients pass through brief hyperthyroid state while later in the disease hypothyroidism become more common Treatment appropriate for most patients consists of giving suppressive doses of thyroid hormones. Operation is indicated for marked pressure symptoms, suspected malignancy and for cosmetic reason. Benign Tumours of the Thyroid 3. Riedels Thyroiditis This very rare disease is grouped with the autoimmune thyroid diseases only because of tradition and for convenience THYROID CANCER spontaneously in about 3-6
Thyroid antibodies are not present in the blood and histological examination of the gland shows dense fibrosis and no lymphatic infiltration Clinical presentation usually occurs in middle age and common in men than women and may related to other ill understood diseases such as mediastinal fibrosis and sclerosis, cholangitis and may cause pressure symptoms such as cough, dyspnoea or dysphagia The gland is usually stony hard The condition is difficult to distinguish from thyroid malignancy and is only differentiated by biopsy. Treatment indicated if replacement there is therapy evidence is of
hypofunction of the thyroid. Steroids may arrest fibrosis in the early stages of the disease Surgery resection of the isthmus is needed both to confirm the diagnosis and relieved symptoms.
Uncommon; caused by haematogenous spread of microorgansims into the thyroid Clinical presentations: Characterized by sudden pain, accompanied by dysphagia, fever, and chills and swelling and redness area one or both lobes. Usually follow upper respiratory tract infection Organisms: Most of them are streptococci and staphylococci. It may be associated with piriform fistulae. recommended Diagnosis by needle aspiration with appropriate bacteriological studies Treatment is by open drainage or localized resection with administration of antibiotics Barium swallow
Thyroid cancer can be primary or secondary. The primary divided into benign and malignant tumours
Mostly are adenomas, usually solitary and encapsulated thyroid The major reasons for removal are and compress the adjacent

Suspicious of cancer Functional overactivity Cosmetic disfigurement Malignant Tumours Primary Tumours 1. 2. 3. 4. 5. Papillary Follicular Medullary Anaplastic Lymphoma MEDULLARY CARCINOMA
The rarest variety 2-5% of the thyroid tumour It has the following characteristics It arises from the para-follicular (C) cells which is derived from the ultimobranchial body which secrete calcitonin It is tumour which tend to present in young adult as autosomal dominant in some families May be associated with and known can be as bilateral hyper Sipple by pheochromocytoma parathyroidism
Secondary Tumours These are rare and usually come from adjacent structures PAPILLARY CARCINOMA This is the commonest type of tumour seen in children and in young adult and usually arises in solitary adenoma or cystadenoma It grows slowly but usually attains a large size forming soft cystic mass This type is relatively less malignant than other variety The tumour has special tendency to invade the lymph nodes and the patient may present with enlarged LN while the primary growth is still impalpable Operation of choice is total thyroidectomy with removal of involved lymph node The patient is treated by thyroxine as maintenance secretion FOLLICULAR CARCINOMA This tends to occurs in middle age and two types are recognized Encapsulated Invasive Are common in endemic goitre regions The invasive type characteristically spread by blood stream to bone and ultimately to the lungs. Typically the tumour presents either as solitary lump in the thyroid gland or as pathological fracture, it take up radioactive do its metastasis The prognosis is not as good as with the papillary type Treatment by total thyroidectomy. This is followed by ablation dose of radioactive iodine Iodine as Treatment and suppression TSH
syndrome or (Type II MEA). The diagnosis made demonstration of raised serum calcitonin level and serum calcium level normal. Doesnt respond to the treatment by radioactive Clinical Features Swelling: The thyroid enlarges rapidly with short duration Pain is common with pressure symptoms with dyspnoea, dysphagia and changes in voice On Examination The thyroid swelling feels hard irregular and does not move freely on deglutition; late cases the skin becomes fixed Glandular metastasis occurs 1st in the prelaryngeal, pretracheal LN later in the deep cervical and mediastinal glands Distant metastasis are common in the bone Eg: Vertebrae, skull and long bones the
By total thyroidectomy with modified neck dissection External beam radiotherapy is useful when it is impossible to hormones remove fully the tumour thyroid Maintenance therapy for life with
ANAPLASTIC CARCINOMA This is the rarest variety usually affect elderly people and carried extremely poor prognosis The tumour grow rapidly and characteistic features are the early invasion of the adjacent structures with early distant metastasis by blood and lymphatics

Treatment Partial removal of the gland or splits the isthmus, if there is airway compression. Radiotherapy is the treatment of relieving the distress MALIGNANT LYMPHOMA Non Hodgkins lymphoma of the thyroid is unusual disease which predominates in women and is more common in middle age It presents with swelling of the thyroid gland usually in association with involved regional lymph node There is evidence that Hashimotos thyroiditis is sometimes precursor of this type of thyroid tumour Treatment The treatment of choice Chemotherapy The prognosis is poor is - Radiotherapy or choice for
Comparison of Malignant varieties

Type Papillary Follicular % of Total 60% 25% Cell Origin Epithelial Epithelial of Differentiation Well Well Spread Lymphatic Haematog enous Direct, lymphatic Anaplastic 10% Epithelial Poor and haematog enous Lymphatic Medullary 5% Para follicular Moderate and haematog enous
*****
NEET
Concepts
Volume 04 Oral Medicine Orthodontics Pedodontics
Community Dentistry
ORAL RADIOLOGY Radiology
X-RAY PROPERTIES AND PRODUCTION

HISTORICAL ASPECTS Discovery of X-Rays Sir Wilhelm Conrad Roentgen, 8, November, 1895 (MAHE-1995, KAR-2002) 1896, Otto Walkhoff, German dentist first dental Koenig) 1901, William H. Rollins, a Boston dentist first dental x-ray unit Frank Van Woert, a New York dentist, first intraoral radiograph 1913, William D. Coolidge, an electrical engineer first x-ray tube (prototype) Intraoral 1904, Weston. A. Price introduction of bisecting technique 1925, Howard Riley Raper introduction of bite-wing technique 1896, C. Edmund Kells introduction of paralleling technique 1947, F. Gordon Fitzgerald, the father of modern dental radiography introduction of long cone paralleling technique Extraoral 1933, Hisatugu Numata of Japan concept of rotational panoramics proposed Yrjo Paatero of Finland the father of panoramic radiography experimented with slit beam of radiography, In 1913, Neils mechanical model SUBATOMIC PARTICLES Nucleus Protons (positive charge) Neutrons (no charge) Electrons (negative charge) Mass of Electron at rest 9.110-28gms Proton 1.6710-24gms(1838 more than electron)
LET Mass
Neutron - 1.6810-24gms(1841 more than electron) Size of nucleus 1/100,000 in atom
IONIZATION Process of converting atoms to ion When an electrically neutral atom loses electron either by heating or interacting with high energy particles, it becomes +ve ion and the free electron a -ve ion(ion pair) Ionizing radiation can be classified into 1. 2. Particulate radiation Electromagnetic radiation
radiograph
on
himself
(Wilhelm
The capacity of particulate radiation to ionize atoms depends on its mass, velocity & charge.
Particulate Radiation (AIIMS-2001, AIPG-2002, 2006, KAR-2004)) Atomic nuclei or subatomic particles moving at high velocity in straight line E.g: Electrons - Beta particles, Cathode rays Alpha particles Protons Neutrons
Character Alpha EmittedCharge Nuclei of Heavy metals Double + ve Heavy Few microns Penetration of tissue Least Ionization Velocity Is more than B Least Highest More damaging to tissue Lesser Alpha More Lower radiation therapy for Least treatment of skin lesions than Least More Beta than body Max of 1.5cm in tissue Beta Radioactive Nuclei Single - ve Less Alpha than Cathode Originate Neutral Least in
an x-ray tube.
intensifying Bohr
screens,
and
rotational techniques proposed Quantum

Linear Energy Transfer (LET) is the rate of loss of energy from a particle as it moves along its track through matter. When physical size and charge of a particle is greater, the velocity is low, and greater is its LET and vice versa. Electromagnetic Radiation It is the movement of energy (without mass) through space as a combination of electric and magnetic fields. Generated when the velocity of an electrically charged particle is altered E.g.: gamma rays, x-rays, UV rays, visible light, infrared radiation, microwave, and radio waves (MCET-2010) High energy radiations like cosmic rays, gamma rays, and x-rays are capable of ionizing. These radiations require a dualistic theory. Quantum theory or particle concept Wave theory or wave concept (Best expressed) PROPERTIES OF X-RAYS 1. 2. 3. 4. 5. 6. 7. Appearance: Invisible and cannot be detected by any of the senses Mass: no mass or weight Charge: no charge Speed: travel at the speed of light. 3 x10 m/sec; 1, 86,000 miles/sec; 2, 97,600 km Wave length: travel in waves and have short wave length with a high frequency Path of travel: travel in straight line Focusing capability: cannot be focused to a point and always diverge from a point. Cannot be reflected, refracted (MAHE-95) 8. Penetrating power: penetrate liquids, solids, and gases. The composition of the substance determines whether x-rays penetrate or pass through or are absorbed 9. Absorption: absorbed by matter. The absorption depends on the atomic structure of matter and the wave length of the x-ray 10. Ionization capability: interact with materials they penetrate and cause ionization (AIPG-06) Anode Stationary Insulating oil. Focusing cup (COMEDK-2009)
8
11. Fluorescence capability: cause certain substances (Phosphors) to fluoresce or emit radiation in larger wave length (Eg: visible & UV light) 12. Effect on film: produce an image on photographic film 13. Effect on living substances: cause biologic change in living cells 14. They cast shadows of the objects in their paths 15. Effected by magnetic and electric fields X-RAY MACHINE 1. Component parts i. Control panel ii. 2. 3. Extension arm iii. Tube head X-ray tube X-ray generating apparatus
X-RAY TUBE Cathode Filament Source of electrons coil of Tungsten 2 mm in diameter 1 cm or less in length Hot filament emits electrons from tungsten at a rate proportional to the temperature of the filament by a process called thermionic emission Also called Coolidge tube Evacuated to prevent collision of the moving electrons with gas molecules Composed of Cathode and Anode
-ve charged molybdenum concave reflector
Rotational beveled target, rotor, stator; drive the rotor at 3000 rpm Tungsten target embedded in copper stem Tungsten Ideal target material o o o o High atomic number (74) High melting point (33700c) Low vapor pressure High thermal conductivity

Tungsten converts kinetic energy of electrons into x-ray photons Copper o o Focal spot The electrons travel towards a small rectangular area on anode called focal spot. Focal spot - sharpness of image & vice versa (COMEDK-2008) Large - no sharp image (BHU-2007, MCET2010) Small - heat on target (AIIMS-2000) Placed at an angle of 200 to the electron beam Projection of the focal spot perpendicular to the electron beam (effective focal spot) is smaller than the actual size of the focal spot. Actual focal spot 1 x 3mm reduced to 1 x 1mm (COMEDK-06) The two methods of dissipating heat from focal spot are: Line focus principle: The target is inclined about 20 degrees in relation to central xray beam thus decreasing the actual focal spot size of 1x3mm to the effective focal spot size of 1x1mm(MAHE-2000, COMEDK-2008) By using a rotating anode, the tungsten target is in form of a beveled disk that rotates when the tube is in operation. (APPG-2005) Heel effect (MAHE-2K) When cathode rays strike anode target, x-rays with high intensity are found towards cathode side of central ray & x-rays with low intensity are found towards anode. Due to this effect, the target should not be inclined more than 20 degrees in relation to central ray. Functions of power supply of x-ray machine Transformer Increase or decrease the voltage in an electric circuit Tube rating Timer Tube current Thermal conductor Reducing the risk of target melting
Autotransformer: minor fluctuations in line voltage Step-up transformer: 00,000 V Step-down transformer: 110 V to 3-5 V Provide a low-voltage current to heat the xray tube filament by use of a step-down transformer Generate a high-potential difference between cathode &anode by use of a high-voltage transformer. To accelerate the electrons from cathode to anode & generate x-rays. Quality of X-ray beam depends on Autotransformer X-ray transformer is an example for Step-up Filament transformer - Step-down (Coolidge) 110 V to 65,000-1,
Flow of electrons through the tube step-down transformer Regulated by filament current control (mA switch) Regulates the temperature of filament, thus the number of electrons emitted Rectification: Self or half wave rectified (All conventional). X-ray tube: 60 cycles AC duration of 1/120 sec. 60 x-rays generate each second. Each having
Timer controls the length of time high voltage applied & time during which tube current flows & produces x-rays. Failure of the filament (burn out) is a common source of malfunction of x-ray tube. To minimize burn out the timing circuit first sends a current through the filament for half second to bring it to proper operating temperature. After the filament is heated, the timer then applies power to high-voltage circuit.
Maximum exposure time the tube can be energized without risk of damage to the target from overheating.

Intra-oral radiography: no specific tube rating. Extra-oral radiography: tube rating chart for easy reference. Primary Radiation or Useful beam Duty cycle Frequency with which successive exposures can be made Heat at anode is measured in heat units (HU) = kVp x mA x seconds For dental x-ray tubes heat storage capacity 20 kHU Position Indicating device (PID) or Cone Open ended Lead lined cylinder Aims & shapes the x-ray beam 0.2 -0.8% of cathode rays transformed into Xrays after striking the anode. Hard X-rays (strong) PRODUCTION OF X-RAYS Bremsstrahlung Radiation Sudden stopping or breaking of high speed electrons at target 70% of x-ray energy is at anode is this radiation When electron hits nucleus of tungsten atom, all its kinetic energy converted to high energy x-ray photons Energy of resultant photon is numerically equal to the kilo voltage applied across the x-ray tube at the time of passage Generate photons having a continuous spectrum of energy Consists of different energies & wavelengths Stray radiation Grenz rays Soft 2 AU Soft X-rays (Weak) Therapeutics or Braking Radiation: Primary Short W.L High penetration Diagnostic radiology Secondary Radiation
difference in two orbital binding energies (AIPG1989, AIIMS-2000)
Penetrating x-ray beam that is produced at the target of anode & that exits the tube head
X-radiations that is created when the primary beam interacts with matter Less penetrating than primary radiation
Scatter Radiation Form of secondary radiation that deflected to all directions from its path by the interaction with matter Detrimental to both the patient & operator
Produced from the other than the focal spot So KVp controls the W.L & Penetration power
Factors controlling x-ray beam X-ray beam quality Quality is mean energy or penetrating ability of the x-ray beam. Wave length determines energy and
Characteristic Radiation (AIIMS-07) Discrete radiation Electrons pass near the nucleus of target and deflected causing this radiation. Minor source Dislodges ionization Occurs at 70 KVp Displaces electron from outer to inner shell, photon is emitted with an energy equivalent to the inner shell electron causes
penetrating power of radiation (KAR-01) Quality or wave length and energy of x-ray beam are controlled by kilovoltage. Dental radiography requires 65-100 KV (MAHE-95, 97, KAR-2K, 03) KV more penetrating rays with greater energy and short wave length to examine dense areas. Kilovoltage controlled by KVp adjustment in control panel.

Film density & KVp Density is overall darkness or blackness of a film (AIIMS-06) Increased KVp increased density and appears dark (KAR-97, AIIMS-06) Density range Film contrast & KVp Contrast is how sharply dark & light areas are differentiated on the film Low KVp high contrast (many black & white areas & few shades of grey), Incipient caries (KAR-2000) High KVp low contrast (many shades of grey) low contrast is useful for periodontal and periapical diseases (AIPG-2002) Exposure time & KVp (KAR-1998) Exposure time is the interval of time during which x-rays are produced Measured in impulses 1 impulse 1/60 seconds, 60 impulse 1 second When KVp is changed adjustment in exposure time to compensate for the penetrating power. E.g.: 90 KVp for 0.5 seconds; 75 KVp for 1 second for proper film density and contrast X-ray beam quantity Quantity is the number of x-rays produced in the x-ray unit Quantity of x-rays is controlled by mill amperage (KCET-2008) Ampere (A) is the unit of measure used to describe the number of electrons, or current flow through the cathode filament Dental radiography requires 7-15mA Increase in mA more electrons more x-rays (PGI-2003) Film density & mA Increase mA - increase density darker image X-ray beam intensity 0 1 2 Density increase 2007) % of light transmitted through film 100% 10% 1% In dental x-rays, 0.3 2
Density is in direct proportion to milli amperage & kilovoltage & is inversely proportional to focal spot (target)-film distance (AIPG-99, AIIMS-92, KAR-03) d= mA x KVp / Fsfd x filtration x collimation
film fog increase (KCET-
Exposure time is inversely proportional to mA & KVp & directly proportional to square of the focal spot film distance (AIPG-1989) T = (Fsfd)2 / KVp x mA
Intensity is the product of the quantity (number of x-ray photons) & quality (energy of each photon) per unit of area per unit of time of exposure Intensity = (no of photons) x (energy of each photon) / (area) x (exposure rate) Intensity affected by KVp, mA, exposure time & distance Increase KVp high intensity of x-ray beam Increase mA high intensity Increase Exposure time high intensity Increase distance low intensity
Inverse square law: The intensity of radiation is inversely proportional to the square of the distance from the source of radiation X-ray beam spreads out as it moves from the source E.g. Sourcefilm distance is doubled as intense Distance reduced by half 4 times as intense
Exposure time & m Inversely related Increase mA decrease exposure time to maintain the density of film
Formula to calculate inverse square law, (MAHE-2000, KAR-2003) I1 / I2= (D2)2 / (D1)2
ORTHODONTICS Introduction
GROWTH & DEVELOPMENT

GROWTH Growth is an increase in size Growth may also be defined as normal changes in the amount of living substance. Growth is a quantitative aspect of biologic development and is measured in units of increase per unit time. E.g. Cm per years, gm per day Generally growth is equated with increase in size, but there are instances in which results in decrease of size. E.g. Thymus gland after puberty DEVELOPMENT Development is progress towards maturity. Development may also be defined as all the natural sequential series of events between fertilization of ovum and the adult size. The important aspects of development are increase in size (growth), cellular differentiation and morphogenesis. MATURATION The stabilization of the adult stage brought about by the growth and development is called Maturation. The changes associated with aging i.e degeneration and senility are considered by some as part of maturation, while other consider as a part of development METHODS OF STUDYING PHYSICAL GROWTH Opinion Opinion can be considered as a calculated guess based on once experience. E.g. One may be able to guess which one of the two siblings may be taller by assessing their previous growth. Observation Observations are useful for studying all or none phenomenon. E.g. During a survey of school children of a particular class, it was observed that class II div. I malocclusion was common. Rating Rating makes use of comparisons with conventional scales or classification. As in all 1. Ranking
biologic sciences normal values ranges between two extreme ends, the average of which is considered as a guideline or norm. Each individual can be compared with these norms.
It is the method of arranging the data in an orderly sequence according to its value. E.g. the ranks of children were determined on the basis of their performance in the annual examination.
Quantitative Examination Direct data Direct growth data are measurements taken on the living individual or cadaver by means of calipers, scales, measurement tapes etc. Indirect data Indirect data are growth measurements taken from the images or reproductions of the individual E.g. Measurements made from photograph dental casts or cephalograms Derived Data These data are obtained by comparing two measurements E.g. the mandible of a child grew 2 mm between 7 and 8 years of age METHODS OF GATHERING GROWTH DATA 1. 2. 3. Longitudinal Cross sectional Semi longitudinal Longitudinal Measurements of a particular person or group of persons made at regular intervals through the passage of time are considered as longitudinal method of gathering the growth data. Advantages 1. 2. 3. Specific pattern of an individual as he develops can be studied Variability in development among individuals Temporary temporal problems in sampling are smoothed out with time
Disadvantages 1. 2. 3. 2. Time Expenses Attrition METHODS OF STUDYING BONE GROWTH 1. 2. Cross Sectional A different individual or a different sample is studied at the different periods at a particular time to derive at the data. Collecting the data by measuring the height of a group of 7 years old boys and on the same day, at the same school, measure the height of another group of 8 years old boys. Changes in the height of the boys between the ages of 7 and 8 years can be assessed immediately from the data collected. Advantages 1. Speed: Unlike the longitudinal study, the data required for the study can be collected immediately. 2. Cost: As the study can be completed in a short period of time, it is less expensive. 3. Sample size: It is much easier to get larger sample and there is not attrition in the size of the sample. 3. Disadvantages 1. It must always be assumed that the groups 2. being measured and compared are similar. Cross-sectional group averages tend to obscure individual variations. This is particularly true when studying the timing of developmental events. E.g. The onset of pubescence or the adolescent growth spurt. 3. Semi Longitudinal The two methods are combined by some workers to seek advantages of each. In this way, one might compress 15 years of study into 3 years of gathering data, each sub sample including children studied for the same number of years, but started at different ages. E.g. 1. 2. Sub sample A: 3-6 yrs Sub sample B: 4-7 yrs 4. Comparative Anatomy Implants 2. Radioisotopes 1. Vital Staining 3. 4. 5. 6. Vital staining Radioisotopes Implants Comparative Anatomy X ray Cephalometrics Natural Makers 3. Sub sample C: 5-8 yrs
In 1736, Beclhier reported that the bones of animals which have eaten the madder plant were studied with red color. The bones contained a band of red color followed by an unstained band. Alizarin, Procion, Tetracycline dyes were subsequently to study the bone growth.
Radioisotopes are elements which are used as in vivo markers for studying growth. Such materials are injected and then after some time are located within the growing bones by means of Geiger counter or the use of Auto radiographic techniques. E.g. Ca 45 and P32
Bjork devised an ingenious method of implanting tiny bits of tantalum or biologically inert reference markers for serial cephalometric analysis. This method allows precise orientation of serial cephalometric and information on the amount and sites of bone growth. This method is the most useful because bone does not grow interstitially and therefore implants placed inside a bone are stable
Comparative anatomy is the study of evolutionary concepts leading to higher forms. Basic principles common to growth in all species are first recognized and defined by studies in comparative anatomy This knowledge of comparative anatomy helps us in carrying out most of the experiments of growth and development.
5. Roentgenographic Cephalometrics Cephalometrics contributes to the major role in the study of craniofacial growth. Serial cephalometrics of the same patient over a period of time gives the direction and amount of growth. 6. Natural Makers The persistence of certain developments features of bone has led to their use as natural makers. By means of serial radiography, trabeculae, , nutrient canals and lines of arrested growth can be used for ref. To study the deposition, resorption res or the remodeling changes. MECHANISMS OF BONE GROWTH Deposition & Resorption On one side of bony cortex new bone is added on other side, bone is taken away. Deposition occurs on the side facing the direction of growth Resorption is seen on the surface facing away from the direction of bone growth Uniform growth is impossible and differential growth is a necessity The best example is the expanding V principle. Remodeling Growth site Vs Growth Centre
The determinants of growth reside in the outer muscles, integument, mucosa, bloo blood vessels, nerves, connective tissue and the brain. The varying activities and rate of growth of the fields are the basis for the differential growth processes that produce bones or irregular shape.
Some growth fields have particular roles in the growth of bones they are called growth sites. E.g. the condyle, maxillary tuberosity, the synchondrosis of basicra basicranium, the sutures, and the alveolar bone. These special growth sites do not cause all of the growth rowth in their bone, for all other inside and outside surfaces must actively participate in the overall growth Some growth sites have been called growth centres a term which implies that a special area somehow controls the overall growth of the bone. The growth centre also implies that the force, energy, or the motor for a bone resides primarily or solely with in its growth center. E.g. the epiphyseal plates of long bones
Facial bones are not enlarged by generalized surface accretion that merely follows existing contours they do not get bigger as a balloon enlarges, for their shape changes.
Remodeling involves simultaneous deposition and resorption on all inner and outer surfaces of the entire bone.
Remodeling a basic part of the growth process not only provides regional changes in shape, dimensions and proportions it also produces regional adjustments that adapt to the developing function of the bone and its various growing soft tissues.
Growth Fields All surfaces, inside and outside of every bone are covered by an irregular pattern of growth fields comprised of various soft tissue osteogenic ic membranes or cartilages. Bone does not grow itself; it is grown by the environment of soft tissue growth fields. The genetic program is not contained within the hard bone Growth Movements Two kinds of growth movements are seen during the enlargement of craniofacial bones: Cortical Drift, Displacement . Drift: Combination of deposition and resorption result in growth movement toward the depository surface. E.g. if an Implant is placed on the surface bone it gradually gets embedded in the bone.
PEDODONTICS Child Psychology
17
CHILD PSYCHOLOGY
Psychology science dealing with human nature, function and phenomenon of his soul in the main
Proposed by Sigmund Freud Freud thought the personality to originate as a result of satisfaction of sets of instincts of which sexual instinct was most important
Importance Helps to understand the child better To establish effective communication with child so as to deliver dental services in a meaningful and effective manner To produce a comfortable environment for dental team to work on the patients THEORIES OF CHILD PSYCHOLOGY I. Psychodynamic theories 1. 2. 3. Psychoanalytical/Psychosexual theory Freud (1905) Psychosocial theory Eric Erickson (1963) Cognitive theory Piaget (1952) (MAHE01) II. Behavioral theories 1. 2. 3. 4. Hierarchy of needs Maslow (1954) Social learning theory Bandura (1963) Classical conditioning Pavlov (1927) Operant conditioning Skinner (1938) (MAHE-2K)
5 psychosexual stages (oral / anal / phallic / latency / genital) called as erogenous zone
Components of Psychic structure Id at birth, pleasure principle Ego 2nd to 6th month of life, reality principle Super Ego censor of acceptability of thoughts, feelings & behavior Oedipus complex Young boys have a natural tendency to be attached to the mother and they consider their father as their enemy The name of the oedipal complex comes from Greek mythology Oedipus the king of Thebe, unwittingly slewed his father and married his mother Electra complex Similarly young girls develop an attraction towards their father and they resent the mother being close to the father Castration Anxiety Unconscious fear of loss of genitals Fear of powerful people overcoming them Fear of revenge of the powerful people
Oral stage Birth

st
Anal stage (1.5 to 3 years) Control over anal sphincter results increased voluntary activity in It
(birth to 1.5 years) In site needs. Serves as a erogenous zone infants for
Urethral stage is a
Phallic (3 to 5 years) The

rd
Latency (5 to 11 years) Resolution of any phase. The ends puberty phase in defects occurs in this
Genital (11 to 13 years) Psychosexual development extends from 11 13 yrs to young adult hood.
Is
the
stage
experience to effect Introduction personality development
oral cavity is identifying
transition between anal phallic stage. and
begin during the 3 year of life till the 5 year

th
Abrupt change birth in Characteristics physiological emergency reaction. at results
This stage
is
Development of autonomy and independence
Child derives pleasure from exercising control over urinary sphincter
Characterized by Oedipus complex & Electra complex
child gain a sense starts adapting adverse environment to of initiative and
Realize goals for reproduction and survival
dependent since the infant in dependent on adult for getting oral his needs
fulfilled PSYCHOANALYTICAL THEORY BRIHASPATHI ACADEMY SUBSCRIBERS COPY NOT FOR SALE

Limitations Pessimistic and deterministic approach to personality Over emphasis on infantile sexuality Overemphasis on differences between men and women No controlled studies-poor poor research It is unconcerned with interpersonal relations, individual identity and adaptation over ones lifetime PSYCHOSOCIAL THEORY Proposed by Eric Erickson Erickson concentrated on childs development covering the entire span of life cycle from infancy to childhood through old age Erickson described 8 stages of life cycle which are marked by internal crisis defined as the turning points Stage 2: Autonomy v/s s Shame and Doubt (1-3 (1 yrs)
18
The balance of trust with mistrust depends largely on the quality of maternal relationship. Such patients are highly uncooperative & frightened
Moves es away from mother and develops a sense of individual identity Toddler learns to talk, walk, use toilets (control over sphincters) and do things for thems themselves self control, confidence Says no to every parental wishes Parents must not overprotective Reassurance develops confidence If denied autonomy, the child will turn angry and shamed Parental over control control---muscular and anal impotencedoubt Separation threatened Dental visit provide options to the child & make him feel more important, let mother be with of mother leaves the child
Stage 3: Initiative v/s Guilt (3-6 6 yrs) Greater autonomy, increased physical activities Initiates motor and intellectual activities, planning, and undertaking tasks. Imitates the people he likes / respects Depends on how much freedom child will get & intellectual curiosity is satisfied Play with peers and learn to interact with environment Feels guilt over failure to attain goals, which makes the child feel unable to be independent Develops sibling rivalry The castration complex occurring in this stage is due to the child's erotic fantasies. Dental visit - more curious about dentists office, they will tolerate being separated from mother Stage 1: Basic Trust v/s Mistrust (0-1 yrs) Dependency on mother Strong bond between mother & child Developing basic trust in the world Positive outcome - secure attachment with parents and environment Negative outcome: inattentive mother maternal deprivation syndrome Stage ge 4: Industry v/s Inferiority (6-11 yrs) Achieves mastery on skills Enters School - organized program of learning, ability to work Sets up competition in the competitive world The fundamentals of technology are developed Learns the pleasure of work completion

Failure results in isolated, less conscious, inferiority - if discriminated, compared in schools Dental visit: try to please dentist and parents & are easy to treat Decrease in influence of parents as role models with simultaneous increase in peer group influence Beginning of orthodontic treatment. Wear appliance regularly Stage 5: Identity v/s Role Confusion (or Diffusion") (12-21 yrs) Development of personnel identity The adolescent is newly concerned with how they appear to others. Ego identity (confidence that the inner sameness and continuity) as evidenced in the promise of a career. Preoccupation with appearance Easily influenced by people considered as idols Increased Group identity and peer group influence Inability to separate from peers results in confusion, inability to make decision & choices. Most orthodontic treatments carried out in this age more conscious about appearance Stage 6: Intimacy v/s Isolation (21-40 yrs) Development of intimacy (attain intimate relationship with others) Involved in intense and long term relations Loves to work Tries to achieve goals The avoidance of these experiences leads to isolation and self-absorption. Now true genitality can fully develop. The counterpart of intimacy is dinstantiation, which is the readiness to isolate and destroy forces and people considered as competitors Inability to develop identity---fear to form a committed relationship The danger at this stage is isolation which can lead to severe character problems. Stage 7: Generativity v/s Stagnation (40-65 yrs) Generativity is the concern in establishing and guiding the next generation. Fruitful parenting Look outside one & care for others Generativity cant be achieved by simply having or wanting children.
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Erickson stated that adults need children as much as children need adults Generativity is expressed through Sociallyvalued work and disciples Creation of living legacy If not - self concerned people, isolation, and absence of intimacy all of which results in stagnation
Stage 8: Ego Integrity v/s Despair (>65yrs) Ego integrity is the ego's accumulated assurance of his capacity for order and meaning. It is the sense of satisfaction of achieving goals or success Despair is a loss of hope producing misanthropy and disgust Signified by a fear of one's own death, as well as the loss of self-sufficiency, and of loved partners and friends Erikson: Healthy children won't fear life if their elders have integrity enough not to fear death.
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Age (years)
Ericksons Psychological Stages (Psychosocial)
Freuds Psychological Stages (Psychosexual)
Developmental Characteristics (significant relations) Attachment
01
Basic Trust v/s Basic Mistrust
Oral phase (Infancy)
Sensomotoric intelligence Motor functions Continuity of existence Parents Language development Self control Motor function Play and imagination Parents Creativity Self awareness
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Autonomy v/s Shame and doubt
Anal stage (early childhood)
Phallic Stage 45 Initiative v/s guilt (Oedipal phase, late childhood)
Moral development Problem solving/activity Gender identification Play in groups Parents and peers Practical / Problem solving Learning skills
6 12
Industry v/s Inferiority
Latency Stage (early school age)
Learning knowledge working together Self evaluation family of origin / School Peers, others Self image / identity Abilities / possibilities Formal operational thought Group activity / identity Gender activity / identity Gender role / relation with the opposite sex Physical maturity Family of origin / peer group Married life Relation to children working relation Relation to values of life Own family / colleagues, friends Family structure / function Child rearing Working situation involvements in society Own family / colleagues / groups of interests Reflection
13 18
Identity v/s Role confusion
Genital Stage (teens)
19 25
Intimacy v/s Isolation
26 50
Generativity v/s Stagnation
50 +
Ego Integrity v/s Despair
Winding up Own family

COGNITIVE THEORY (KCET-99) Proposed by Jean Piaget in 1952 According to Piaget, the environment does not shape child behavior but the child and adult actively seek to understand the environment This process of adaptation is made up of 3 functional Piaget 1. variants 4 stages Assimilation, in cognitive Accommodation and Equilibration describes development Sensory motor stage (0-2 years) Reconstructs objects Memory by mental images Develops rudimentary concepts of objects Objects in the environment are permanent; do not disappear when the child is not looking at them. Communication between a child at this stage and an adult is extremely limited because of the childs simple concepts and lack of language capabilities. Little ability to interpret sensory data and a limited ability to project forward or backward in time. CLASSICAL CONDITIONING THEORY 2. Preoperational (3-6 years) Good language development Capacity to form mental symbols represent things and events Children learn to use words to symbolize the objects. Understand the world in the way they sense it through its primary senses: sense of vision, hearing, smell, taste or feel Child learns to classify things Solves problem, but cannot explain how it solved Characteristics o Egocentrism child is incapable of assuming another persons point of view. o Animism investing used to the by inanimate teams dental objects with life. Animism can be dental giving advantage 1. 2. 3. 4. 5. By Ivan Pavlov 4. Formal operation stage (12-15 years) Good communication skill 3. Concrete operation (6-12 years) Logical capacity grows o
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Constructivism child acquires reality by touching, exploring, observing
Good answering / reasoning capacity Decline of egocentrism Decline of animism Thinks much more like adults Easy to treat Making operation in ones head out from perceived reality (COMEDK-08)
Ability to deal with abstract concepts & reasoning Child is a teenager & should be treated as adult Concept of imaginary audience constantly on stage Easy to treat if interested Orthodontic treatment and concept of imaginary audience
Classical conditioning operates by a simple process of association of one stimulus with other Learning by association Experiment: Presentation of food to a hungry dog Three steps Conditioning Stimulus generalization Extinction Stimuli Neutral stimulus (NS) Unconditional stimulus (US) Unconditional response (UR) Conditional stimulus (CS) Conditional response (CR)
instruments and equipment life like names and qualities.


Before conditioning FIRST VISIT White Coat (Neutral stimulus) Pain of Injection (Unconditioned stimulus)
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No Response (No response) Fear and Crying (Unconditioned response)
Conditioning process
SECOND VISIT Sight of White Coat (Conditioned stimulus) Fear and Crying (Conditioned response)
OPERANT CONDITIONING After conditioning Proposed by B.F Skinner Extension of Classical Conditioning Theory Complicated theory Related to trial and error learning A person attempts to solve a problem by trying different actions ons until one proves successful Instrumental conditioning
The Basic Principles 1. 2. Extinction Before extinction Classical conditioning - a stimulus leads to a response Operant conditioning - a response becomes a further stimulus. Types 1. Positive reinforcement If a pleasant consequence follows a response Ex. reward for co-operation 2. After extinction 3. Negative reinforcement Withdrawal of an unpleasant stimulus after a response Ex. Stopping treatment if crying Omission (time out) Removal of a pleasant stimulus after a particular response Ex. Taking out of favorite toy 4. Punishment When an unpleasant stimulus is presented after a response Ex. Sending mother out of operatory 3. Operant behaviors are voluntary The consequence of a behavior is in itself a stimulus that hat can affect future behavior Teach new behaviours (behaviour shaping)
Extinction process

1 & 2 are more suitable for dental office 1. Positive Reinforcers - immediate Presenting food, candy, toys Activity which the child likes (permission to leave the dental chair) Social reinforcer (giv (giving attention, praise, smiling) 2. Negative reinforcers Halting treatment because of SOCIAL LEARNING THEORY Proposed by Bandura (1963) behavioral resistance is likely to reinforce undesirable behavior 3 & 4 should be used sparingly with some caution (Aversive learning) Punishers Voice control and HOME are mild forms of punishments Physical restraints HIERARCHY OF NEEDS Abraham individuals. He believed that violence exists to fulfill the basic needs
Self actualization Self esteem
23
People who have everything can maximize their potential. They can seek knowledge, peace, self selffulfillment, oneness with God etc. They are reality respect centered, self and problem others centered,
accompanied with strong ethics.
The learning of behavior is affected by 4 principal elements 1. Antecedent determinant conditioning is affected if the person is aware of what is occurring 2. Consequent perception determinant and persons (cognitive expectancy
factors) determine behavior Maslow established 3. Modeling learning through observation eliminates the trial trial-error search. It is not an automatic process, proces but requires cognitive factors 4. Self regulation this system involves a process of self regulation, judgment and evaluation of individuals response to his own behavior EMOTIONAL DEVELOPMENT
Security
Harold old
Hierarchy of needs by observing basic needs of
Social
Characteristics of commonly seen Emotions in Child Distress or Cry Anger Fear Anxiety
Physiological needs
Physiological Needs: basic needs - air, water, food, sleep, sex, etc. When not satisfied - feel sickness, irritation, pain, discomfort
Phobia Types of Cry (Elsbach, 1963) (KCET-04) (KCET Frightened cry - Usually accompanied by torrent of tears, breath-catching catching sobs Hurt cry - Initially a child in discomfort, shows a single tear filling from corner of the eye Obstinate cry - characterized by siren-like siren wail Compensatory cry - is a sort of coping mechanism Fear Fear is a reaction to a known danger (MAHE(MAHE 94) At birth - is a primary response acquired soon after birth such as startle response
Safety needs: stability & constancy in a chaotic world. Ex. security of home & family, insurance policies etc
Social needs/Love & belonging needs: Loving and caring partners, children, friends, frien society Esteem needs: Self esteem by mastery of tasks, tasks respect from others. The negative version of these needs is low self-esteem esteem and inferiority complexes.
Self actualization The need for self-actualization actualization is "the desire to become more and more what one is capable of becoming"

Pre-schooler (2-5 yrs) - Fear of animals or being left alone or abandoned (AIIMS-91, AIPG-98, COMEDK-10) Early schooler - Fear of dark, staying alone. Shows fear of supernatural powers like ghosts and witches Late schooler - Fear of failure, not being liked, competition, and fear of punishment Adolescent - Fear of social rejection and fear of performance (peer group pressures, academic pursuits). 03) Innate fear Without stimuli or previous experience Subjective fear Fears transmitted to 2. individual are termed as subjective fears. Objective fear Fears due to events, objects or specific conditioning, previous experience 3. (dental trauma) or generalization (medial experience). 4. Fear evoking dental stimuli The most feared events in dental clinic can be ranked as Anesthetic administration by injection Extraction Sound of drill Anxiety Emotion arising without any source of danger It is a learned process being in response to ones environment Maternal anxiety plays an important role in childs anxiety level determinant Factors influencing child behavior Growth & development Family & Peer influence Past medical/dental history Dental office environment Maternal attitude & Childs behavior Mothers behavior Overprotective dominant Over indulgent Under affectionate Rejecting Authoritarian Childs behavior Shy, submissive Aggressive, demanding Wrights Classification Cooperative behavior Lacking behavior Potentially cooperative Cooperative Wilsons Classification 1. 2. 3. 4. Normal / Bold Timid Hysterical Nervous / Fearful (KCET-01, AIPGFrankels Behavior Rating Scale 1. Rating I Definitely negative -Negative Positive + Definitely positive ++ Lampshires Classification 1. 2. 3. 4. 5. 6. 7. 8. Cooperative Tensely cooperative Outwardly apprehensive Fearful Stubborn Hyper motive Handicapped Emotionally immature
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Rating II
Rating III
Rating IV
Uncooperative behavior Hysterical Defiant/obstinate behavior Tense cooperative Timid / shy Whining type Stoic behavior
Dental team requirements (AIPG-91, 98) Positive approach Team attitude Organization Truthfulness Tolerance Flexibility
Usually well behaved, shy, may cry easily Aggressive, over active Evasive & dawdling
*****
COMMUNITY DENTISTRY Biostatistics
14
BIOSTATISTICS
INTRODUCTION Statistics is a field of study concerned with Collection, organization, summarization and analysis of data Drawing of inferences about a body of data when only a part of the data is observed Statisticians try to interpret and communicate the results to others The term statistics is said to be derived from statista or statistic. Italian word statista means statesman German word statistic means political state John Graunt Father of Health Statistics (MAHE-01) Vital statistics is the branch of biostatistics which deals with the births, deaths and marriage (KAR-04) DEFINITIONS Statistics can be defined as, Principles collection, and methods for the and presentation, analysis
USES OF STATISTICS IN DENTISTRY 1. To assess the state of oral health in the community and to determine the availability and utilization of dental care facilities. 2. To indicate the basic factors underlying the state of oral health by diagnosing the community problems. 3. To determine success or failure of specific oral health care programs or to evaluate the program action. 4. To promote health legislation and in creating administrative standards for oral health COMMON STATISTICAL TERMS Constant - Quantities that do not vary e.g. in biostatistics, mean, standard deviation are considered constant for a population Variable - Characteristics which takes different values for different person, place or thing such as height, weight, blood pressure 1. Quantitative Variables It can be measured in the usual sense. Ex: 1. 2. 3. The heights of adult males The weights of preschool children The ages of patients seen in a dental clinic i. Discrete Variable o Characterized can assume o Ex: 1. The number of daily admissions to a general hospital 2. The decayed, number missing of or by gaps or interruptions in the values that it and find solutions to such
interpretation of numerical data or The science and art of dealing with variation in such a way as to obtain reliable results Biostatistics is application of statistics to health problems GENERAL APPLICATIONS OF BIOSTATISTICS 1. 2. To define what is normal or healthy in a population. Ex: pulse rate/ min. Statistical difference between means of two variables. Ex: mean plaque scores for two groups. 3. Co-relation between two variables. Ex: sugar intake & Dental caries; Fluoride concentration in drinking water & Fluorosis. 4. Usefulness of sera & vaccines in the field. % of deaths among vaccinated compared to % of deaths among unvaccinated. 5. To test the efficacy of different treatments. Ex: Surgical management vs. medical management of angina patients ii.
filled teeth per child in an elementary school Continuous Variable o Can assume any value within a specified relevant interval of values assumed by the variable

o For example: 1. 2. 3. 2. Height Weight Skull circumference Population and Sample
15
Population: The whole collection of individuals that one intends to study. Sample: A representative part of the population.
Qualitative Variables Many characteristics are not capable of being measured. Some of them can be ordered (called ordinal) and some of them cant be ordered (called nominal) Ex: 1. Classification of people into socio-economic (ordinal) 2. Hair color (nominal) groups
Randomization: An important way to make the sample representative.
Random By chance!
Random event The event may occur or may not occur in one experiment. Before one experiment, nobody is sure whether the event occurs or not Probability Measure the possibility of occurrence of a random event. A random event P(A): Probability of the random event A P(A)=1 , if an event always occurs P(A)=0, if an event never occurs
Population - Population includes all persons, events and objects under study. It may be finite or infinite.
Sample - Defined as a part of a population generally selected so as to be representative of the population whose variables are under study
Parameter - It is a constant that describes a population e.g. in a college there are 40% girls. This describes the population, hence it is a parameter. Parameter and Statistic Parameter: A measure of population or a measure of the distribution of population. Parameter is usually presented by Greek letter such as , -- Parameters are unknown usually. To know the parameter of a population, we need a sample Statistic: A measure of sample or a measure of the distribution of sample. Statistic is usually presented by Latin letter such as s and p. Sampling Error The difference between observed value and true value Three kinds of error 1. 2. 3. Systematic error (fixed) Measurement error (random) Sampling error (random)
Statistic - Statistic is a constant that describes the sample e.g. out of 200 students of the same college 45% girls. This 45% will be statistic as it describes the sample
Attribute - A characteristic based on which the population can be described into categories or class. Ex. gender, caste, religion
BASIC CONCEPTS Homogeneity and Variation Homogeneity: All individuals have similar values or belong to same category. Ex: all individuals are Indians, women, middle age (30~40 years old), work in a textile mill homogeneity in nationality, gender, age and occupation. Variation: the differences in height, weight etc

MEASUREMENT SCALES Different measurement scales allow for different levels of exactness, depending upon the characteristics of the variables being measured. The four types of scales available in statistical analysis are Nominal A scale that measures data by name only For and example, xample, so forth), religious political affiliation affiliation DATA (measured as Jewish, Christian, Buddhist, (measured as Democratic, Republican, Libertarian, and so forth), or style of automobile (measured as sedan, sports car, station wagon, van, and so forth).
16
placed, which makes the interval scale different from ratio.
4.
Ratio Similar to an interval scale, a ratio scale includes a 0 measurement that signifies the point at which the characteristic being measured vanishes (absolute 0). For example, income (measured in dollars, with 0 equal to no income at all), years of formal education, items sold, and so forth, are all ratio scales.
1.
A collective recording of observations either numeric or otherwise is called Data Understanding the he data is crucial in bio statistics, since the type of data determines the selection of appropriate test of significance
2.
Ordinal Measures by rank order only. Other than rough order, no precise measurement is possible. For example, medical condition (measured as satisfactory, fair, poor, guarded, serious, and critical); socialsocial economic status (measured as lower class, lower-middle middle class, middle class, upper uppermiddle class, upper class); or military officer rank (measured as lieutenant, captain, major, lieutenant colonel, colonel, general). Such rankings are not absolute but rather relative to each other: Major is higher than captain, but we cannot measure the exact difference in numerical terms. I.
Nomina l
Types of Data
Data Qualitative Ordinal Dichotomou s Quantitative Discrete Continuous
Qualitative Data or Categorical Data or Discrete Data This data exists in mutually exclusive categories It deals with attributes or qualities of sampling units 1. Nominal Data The categories are not ordered but simply have names. variables have neither measurement scales nor direction Examples include blood group (A, B, AB, and O) and marital status (married/widowed/single etc.)
3.
Interval Measures by using equal intervals. Here The as is you can compare differences scale, The between pairs of values. Fahrenheit the temperature scale. measured in degrees, is an interval inte scale, centigrade temperature difference between 50 and 60 degrees centigrade (10 degrees) equals the temperature difference between 80 and 90 degrees centigrade (10 degrees). Note that the 0 in each of these scales is arbitrarily

2. Ordinal (Ranked) Data The categories are ordered in some way. Characterized in terms of more than two variables and have a clearly implied direction but the data are not measured on a measurement scale (KCET-09) Examples include disease staging systems (advanced, moderate, mild, none), students degree and of pain (severe, medals. 3. moderate, mild, none) ranking of Olympic (MAHE-97) 3. Dichotomous data (Binary variables) The variable can have only two values Examples Dead/Alive disease/Patient disease II. Quantitative Data or Continuous Data or include or does Yes/No, has have Methods of Collecting Data 1. Census not Patient Sources of Data 2. Primary data Obtained directly from the source It is first hand information 2. Continuous Data
17
Occur when there is no limitation on the values that the variable can take. Ex: weight or height
Data can be obtained by means of questionnaires, interviews, or clinical examinations Secondary data Obtained from pre-existing records It is Second hand information Data can be obtained from govt. records, hospital records etc.
Defined as the total process of collecting, compiling and publishing demographic, economic and social data pertaining at a specified time or times, to all persons in a country or a delimited territory The first regular census in India was recorded in 1881. Census is conducted for every 10 years in India (MAHE-99) Recent census in India was recorded in February, 2011. Census act was passed by the parliament of India in1948. Census Commissioner of India is the chief officer for census enumeration.
Numerical Data These occur when the variable takes some numerical value The observations follow a direction and are quantified on a scale of measurement. Continuous data not only show the position of the different observations relative to each other but also show the extent to which one observation differs from another. It enables the investigators to make more detailed inferences than do nominal or ordinal data 1. Discrete Data Occur when the variable can only take certain whole numbers but not fractions These are often counts of numbers of events, such as the number of visits to a hospital in a year or the number of episodes of illness in an individual over the last five years.
Advantages o Complete information
Disadvantages o Expensive, time consuming, needs more man-power, lesser accuracy.

2. Sampling Sample is a portion of a population, selected from the population in some manner A Sampling unit is defined as representing every member of sample. (AIPG-09) Importance of Sampling The physical all impossibility the items of in of the checking population Adequate results Cost of study in the entire population Saving the time Types 1. Purposive Sampling i. Judgment Sampling Selection of samples is left to the Judgment of investigator. In this sampling technique, the accuracy of results 2. Indications o Employed mainly when population is small o Employed to conduct pilot study Limitations o Accuracy depends knowledge investigator. o If investigator is biased, it affects the acceptance or rejection of a hypothesis ii. Convenience Chunk selected Sampling is a (Chunk of is is of upon of results the the depends upon investigator. Random Sampling accuracy sampling iii. Quota Sampling
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conveniently available for investigator. Ex: In order to estimate oral hygiene status of school children few work. in a city, the his this rarely investigator may select a schools nearby of are Results
sampling
representative because they are generally biased.
Each investigator is allotted quota of persons which are to be interviewed. Investigators instructions with to are given interview specified
persons within the quota some characteristics. Ex: Persons within the quota of 10 house wives, 6 professionals.
The sample is selected using random techniques. Selection bias is avoided. i. Simple Random Sampling (unrestricted random sampling ) The procedure of selecting a sample in which, every item in a population has an equal chance of being included in the sample. (MAHE-97) Applicable when population is very small, homogeneous and readily available Lottery method Advantages o Eliminates bias selection
Sampling/ incidental sampling ) fraction which it population,
because

Disadvantages o Selection of sample is costly and time consuming Limitation o Difficult to collect data for large samples ii. Systematic Random Sampling By selecting one unit at random and then selecting additional units at evenly spaced required formed It is applied to field studies when large, the population scattered is & Advantages o There is a intervals size (sample been interval) till the sample of has
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iii. Stratified Random Sampling (KAR99) If population is heterogeneous, the simple random sampling is not effective. Purpose of this sampling is to increase the efficiency of sampling population homogenous Ex: Areas, groups classes, by dividing sample into are age heterogeneous
homogenous groups. These termed as strata. groups, sexes etc.
greater
homogenous. Sample interval is calculated by the following formula K = N/n Where, or K - sample interval ratio, N o sample o
precision of results It gives better results when More representativeness accuracy Disadvantages o It is too technical Time method and & population is scattered
population size and n Sample size Ex: If 150 patients are to be included in the sample from a population of 3000, K = 3000/150 = 20 Advantages o Systematic adopt o The time & labor in collection of sample is relatively small o It gives accurate results when large population is design is simple, convenient to
consuming. iv. Cluster Sampling In this sampling are selected the by required no of groups or clusters simple random sampling. Then all the individuals present in those clusters are included (KAR-04) Advantages in the sample
Limitation o Requires a pre-formed list

o o
Simpler Involves less time and cost

PRESENTATION OF DATA Indication o When wide population area and is the vast & scattered over a population clusters), forms cluster
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Statistical data once collected should be systematically arranged and presented, To arouse interest of readers For data reduction To bring out important points clearly and strikingly For easy grasp and meaningful conclusions To facilitate further analysis To facilitate communication
natural groups (called sampling is applicable. v. Multistage Sampling As the name implies this method sampling using random refers to the procedures sampling I.
Two main types of data presentation are I. II. Tabulation Graphic representation with charts and diagrams Tabulation It is the most common method Data presentation is in the form of columns and rows It can be of the following types
carried out in several stages technique. Indication o When involves the very study large like
population, nationwide surveys vi. Multiphase Sampling
1. 2. 1.
Simple tables Frequency distribution tables Simple Table Year Jan 06 Feb 06 March 06 Number of in patients 2,800 1,900 1,750
In this method, part of the information is collected from the whole sample & part from the sub sample. Advantages o Economic, purposeful o Saves time and manpower Errors in Sampling Sampling Errors Faulty sampling design Small sample size yet
2.
Frequency distribution table In a frequency distribution table, the data is first split into (class convenient groups
interval) and the number of items (frequency) which occurs in each group is shown in adjacent column. Number Cavities 0 to 3 3 to 6 6 to 9 9 and above of Number of Patients 78 67 32 16
Non sampling Errors Coverage error Observational error Processing error

II. Charts and diagrams Ideal requirements of Charts and diagrams Self explanatory Simple and consistent with the d data Values of the variables should be shown on horizontal or X-axis X and the frequency ency on vertical line or Y Yaxis No too many lines on the graph Should not look clumsy The scale of presentation should be indicated at the right hand top corner of the graph The scale of division of the two axes should be proportional The details of the variables and frequencies presented on the axes should be mentioned Types of Diagrams 1. Simple Bar Represent qualitative data Only one variable can be represented using one diagram Width of the bar remains the same &has no meaning The length varies according to the frequency Bars can be oriented vertically or horizontally Limitation o It represents only one classification, thus cannot be used for comparison. 4.
300 250 200 150 100 50 0 1st Qtr 2nd Qtr 3rd Qtr 4th Qtr
Number of CD Patients
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2.
Multiple Bar It is used to compare qualitative data with respect to a single variable. Eg: with respect to sex, time or region. Each category of the variable have a set of bars of the same width corresponding to the different sections without any gap in between the width and the length corresponds to the frequency.
400 300 200 100 0
370 320 250 180 45 1st Qtr 80 95
390 280 290 220 CD Patient s
40 2nd Qtr 3rd Qtr 4th Qtr
3.
Component Bar It represents qualitative data. We can represent the number of cases in major groups as well as the subgroups First, simultaneously, are using drawn, component bar diagram. rectangles proportional to the number of cases of the major group. Then, each rectangle components, is divided proportional roportional in to to the
numbers in the subgroups. Histogram (AP-01, 03, , KAR KAR-10) Most widely used to represent quantitative data of continuous type. It is a bar diagram without gap between the bars. It represents a frequency distribution. X-axis: the size of an observation is marked. Starting from 0, the limit of each class interval is marked. The width of each bar corresponds to the width of the class interval in the frequency distribution.

Y-axis: the frequencies are marked. A rectangle is drawn above each class interval with height proportional to the frequency of that class interval.
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40,000 35,000 30,000 25,000 20,000 15,000 10,000 5,000 0 males females total
98
99
00
01
02
95
96
97
03 20
19
19
19
19
19
20
20
20
7.
Pie Chart/Sector Diagram Used to present data, expressed in percentages (KAR-04, 04, COMEDK COMEDK-10) The frequency of the group is shown in a circle. Degree of angle denotes the frequency.
5.
Frequency Polygon It represents frequency distribution of quantitative data It facilitates comparison of two or more frequency distributions. A point is marked over the mid-point mid of the class interval, corresponding to the frequency. The first point and last point of each class interval are joined to the midpoint of previous and d next class respectively. All the points are connected by straight lines. To compare two or more frequency distributions, lines of different types are drawn on the same graph.
Instead of comparing the length of bar, the areas of segments are compared.
8.
Scatter/Dot Diagram It is used to show the association between two quantitative uantitative variables. The imaginary line drawn through the center of the scatter shows the association.
6.
Line Diagram It is useful to study the changes of values in the variables over time. . (AIIMS-01) (AIIMS Time is represented on X axis and frequency of the variable on Y axis. Facilitates comparison of data among different groups in a simple way
20
04
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MEASURES OF STATISTICAL AVERAGES OR CENTRAL TENDENCY Single estimate of a series of data that summarizes the data is known as the parameter and one such parameter is the measure of central tendency. Objective: to condense the entire mass of data to facilitate comparison with other data measured on the same grounds. Ideal Properties of Central Tendency 9. Cartograms or Spot Map It shows geographical distribution of frequencies of a characteristic. Easy to understand and condenses a lot of information in to a simple picture. Should be easy to understand and compute Should be based on each and every item in the series Should values) Should be capable of further computations It should have sampling stability. i..e, if different samples of same siz size, say 10% are picked up from the same population and the measure of central tendency is calculated, they should not differ from each other markedly Types statistical not be affected by extreme observations (Either too small or too large
1. 2. 3.
1.
Arithmetic mean mathematical estimate Median positional estimate Mode based on frequency Arithmetic Mean/Mean (MAHE-95, (MAHE 98, 99, 2K, AIIMS-01, PGI-02) The simplest est measure of central tendency
10. Pictogram The pictures representing the value of items are called pictograms. It is most useful way of representing data to lay groups.
It is the summation of all the observations divided by the total number of observations (n) Denoted by X for sample and for population Mean = Sum of all the observations of the data Number of observations in the data X = Xi n : sigma means the sum of. Xi: is the value of each observation in the data, n: is the number of observations in the data.
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Properties of the Median Properties of the Mean Uniqueness For a given set of data there is one and only one mean Simplicity It is easy to understand and to compute Affected by extreme values. Since all values enter into the computation 2. Median (UPSC-01, KAR-02, AIIMS-04) When ordering the data, it is the observation that divides the set of observations into two equal parts such that half of the data are before it and the other are after it. If n is odd, the median will be the middle of observations. It will be the (n+1)/2th ordered observation. When n = 11, then the median is the 6th observation. If n is even, there are two middle observations. The median will be the mean of these two middle observations. It will be the mean of the [(n/2)th, (n/2 +1)th] ordered observation. When n = 12, then the median is the 6.5th observation, which is an observation halfway between the 6th and 7th ordered observation. Calculation of Median o Observations are arranged in the ascending or descending order of magnitude & then the middle value of the observations is Median. o In case of even number of observations, the average of the two middle values is Median TYPES OF VARIABILITY There are three types of variability Properties of the Mode Sometimes, it is not unique. It may be used for describing qualitative data. 3. Uniqueness For a given set of data there is one and only one median Simplicity It is easy to calculate It is not affected by extreme values as is the mean Mode (KAR-03, AIIMS-08) The value in a series of observations, which occurs with the greatest frequency Example o Number of decayed teeth in 10 children: 2, 2, 4, 1, 3, 0, 10, 2, 3, 8 Mean = 34 / 10 = 3.4 Median = (0,1,2,2,2,3,3,4,8,10) = 2+3 /2 = 2.5 Mode = 2 (3 Times)
1. 2. 3.
Biological variability Real variability Experimental variability i. ii. Observer Error Instrumental Error
iii. Sampling Error


1. Biological Variability It is the natural difference which occurs in individuals due to age, gender and other attributes which are inherent This difference is small and occurs by chance and is within certain accepted biological limits Ex: vertical dimension may vary from patient to patient 2. Real Variability Such variability is more than the normal biological limits The cause of difference is not inherent or natural and is due to some external factors Ex: Difference in incidence of cancer among smokers and non smokers may be due to excessive smoking and not due to chance only 3. Experimental Variability It occurs due to the experimental study i. Observer Error o The investigator may alter some information or not record the measurement correctly ii. Instrumental Error o This is due to defects in the measuring instrument o Both the observer and the instrument error are called non sampling error iii. Sampling Error or Errors of Bias o This is the error which occurs when the samples are not chosen at random from population. o Thus the sample does not truly represent the population MEASURES OF VARIATION OR DISPERSION (KAR-98, MAHE-98, AIPG-10) A measure that describes the spread or variation of the observations is referred to as a Measure of Dispersion. The various measures of variation or dispersion are
25
1. 2. 3. 4.
1. Range
Range Mean or average deviation Standard deviation Co efficient of variation
It is the simplest Defined as the difference between the highest and the lowest figures in a sample Defines the normal limits of a biological characteristic e.g. freeway space ranges between 2-4 mm Not satisfactory as based on two extreme values only Let the range be denoted by R, and X1, X2, , Xn be n observations. Then the range is given by R = Xmax Xmin. Disadvantages 1. The sampling stability (variability from one sample to the next) of the range is very poor. 2. It depends on the sample size. The more samples we have, the more likely we are to observe greater extreme values. Therefore, the larger range will likely be observed as we increase the sample size. 3. It is very sensitive to the two extreme values and ignores the rest of the observations. 4. It is not meaningful for unordered qualitative data. 2. Mean deviation It is the summation of difference or deviations from the mean in any distribution ignoring the + or sign Denoted by MD MD = x = mean n = no of observation
( )
X = observation

3. Standard deviation (KAR-03) Also called root mean square deviation It is an improvement over mean deviation used most commonly in statistical Characteristics Bell shaped Bilaterally symmetrical analysis Denoted by SD or s for sample and for a population Denoted by the formula SD =
()
26
NORMAL DISTRIBUTION OR NORMAL CURVE Also called Gaussian curve, after Gauss, who observed it. (KAR-03)
Frequency increases from one side reaches its highest and decreases exactly the way it had increased The highest point denotes mean, median and mode which coincide Mean 1 SD includes 68.27% of all observations. Such observations are fairly common Mean 2 SD includes 95.45% of all observations i.e. by convention values beyond this range are uncommon or rare. Their chances of being normal is 100 95.45 % i.e. only 4.55%. Mean 3 SD includes 99.73%. Such values are very rare. There chance of being normal is 0.27% only These limits on either side of measurement are called Confidence Limits The look of frequency distribution curve may vary depending on mean and SD. Thus it becomes necessary to standardize it. Eg- One study has SD as 3 and other has SD as 2, thus it becomes difficult to compare them Thus normal curve is standardized by using the unit of standard deviation to place any measurement with reference to mean. The curve that emerges through this procedure is called Standard Normal Curve
Greater the standard deviation, greater will be the magnitude of dispersion from mean Small standard deviation means a high degree of uniformity of the observations Usually measurement beyond the range of 2 SD are considered rare or unusual in any distribution Uses o It summarizes the deviation of a large distribution from its mean. o It helps in finding the suitable size larger o It helps of sample sample in e.g. to greater draw of the deviation indicates the need for meaningful conclusions calculation whether standard error which helps us to determine difference between two samples is by chance or real 4. Coefficient of variation It is used to compare attributes having two different units of measurement Ex. height and weight Denoted by CV CV =

It is expressed as percentage
27
Mean median mode coincide (KAR-99, AIPG09) The unit of SD here is relative or standard normal deviate and is denoted by Z Z=

With the help of Z value we can find the area under the curve from a table This area helps to give the P value MEASURES OF THE SHAPE OF A DISTRIBUTION The measures of the shape of a distribution are the coefficients of skewness and kurtosis. Skewness (sk) A measure of asymmetry of a frequency distribution It shows if deviations from the mean are larger on one side than the other side of the distribution For a symmetric distribution skewness is equal to zero.
The direction of the tail of the curve indicates the direction of the skewed distribution. If the tail of the curve is toward the right, the distribution is said to be positively skewed. Mean is greater than Median
Properties of Standard Normal Curve Smooth bell shaped Perfectly symmetrical Based on infinite number of observations thus curve does not touch x axis Mean is zero SD is always 1 Total area under the curve is 1

If the tail of the curve is toward the left, the distribution is negatively skewed. Mean is less than Median MEASURES OF RELATIVE POSITION Measures of relative position
28
include
percentiles and z-value. Percentile value (p) It is of an observation yi, in a data set has 100p% of observations smaller than yi and has 100(1-p) % of observations greater than yi.
In a skewed distribution, the mean always follows the tail of the curve. From the tail of the curve to the apex (mode), the mean, median, and mode are always in alphabetical order.
A lower quartile is the 25th percentile, an upper quartile is 75th percentile, and the median is the 50th percentile. (AIPG03,AIIMS-06)
Kurtosis (kt) A measure of flatness or steepness of a distribution, or a measure of the heaviness of the tails of a distribution. If observations follow a normal distribution then kurtosis is equal to zero. A distribution with positive kurtosis has a large frequency of observations close to the mean and thin tails.
z-value The deviation of an observation from the mean in standard deviation units CORRELATION COEFFICIENT (r) The quantity r, called the linear correlation coefficient, measures the strength and the direction of a linear relationship between two variables. The linear correlation coefficient is sometimes referred to as the Pearson product moment correlation coefficient in honor of its developer Karl Pearson. The mathematical formula for computing r is
A distribution with a negative kurtosis has thicker tails and a lower frequency of observations close to the mean than does the normal distribution Where n is the number of pairs of data. The value of r is such that -1 < r < +1. The + and signs are used for positive linear correlations and negative linear correlations, respectively. Positive correlation: If x and y have a strong positive linear correlation, r is close to +1. An r value of exactly +1 indicates a perfect positive fit. Positive values indicate a relationship between x and y variables such that as values for x increase, values for y also increase.

Negative correlation: If x and y have a strong negative linear correlation, r is close to -1. An r value of exactly -1 indicates a perfect negative fit. Negative values indicate a relationship between x and y such that as values for x increase, values for y decrease. No correlation: If there is no linear correlation or a weak linear correlation, r is close to 0. A value near zero means that there is a random, nonlinear variables Note that r is a dimensionless quantity; that is; it does not depend on the units employed. A perfect correlation of 1 occurs only when the data points all lie exactly on a straight line. If r = +1, the slope of this line is positive. If r = -1, the slope of this line is negative. A correlation greater than 0.8 is generally described as strong, whereas a correlation less than 0.5 is generally described as weak. COEFFICIENT OF REGRESSION Regression, sciences, is as often practiced to in earth the attempt establish a relationship between the two SAMPLING
29
Regression or correlation can be bivariate (between 2 variables, x and y) or multivariate, between greater than two variables. Regression is interested in the form of the relationship, whereas correlation is more focused simply on the strength of a relationship.
It is not possible to include each and every member of population as it will be time consuming, costly, laborious, therefore sampling is done
Sampling is a process by which some unit of a population or universe are selected for the study and by subjecting it to statistical computation, conclusions are drawn about the population from which these units are drawn
The sample will be a representative of entire population only It is sufficiently large It is unbiased Such sample will have its statistics almost equal to parameters of entire population Two main characteristics of a representative sample are
mathematical relationship between variables. This can be used to extrapolate or to predict one variable given the other. For example, a relationship exists between the frequency of occurrence of a given size flood or earthquake, and the size of the event. Given flood data, and assuming constancy of system operation then one can predict how big a size of a certain frequency will be, i.e. how big the 100 year flood will be. A linear relationship between two variables is captured by the formula y = b + m x, where b is the y intercept and m is the slope. It is significant which variable is y and which is x Correlation measures the dependability of the relationship (the goodness of fit of the data to that). It is a measure of how well one variable can predict the other (given the context of the data), and determines the precision you can assign to a relationship. 2. 1.
1. 2.
Precision Unbiased character
Precision Precision depends on a sample size Ordinarily sample size should not be less than 30 Precision = Precision is n/s directly proportional to n = sample size , s = standard deviation square root of sample size, greater the sample size greater the precision Also greater the SD, less will be the precision Thus in such cases to obtain precision, sample size needs to be increased Unbiased character The sample should be unbiased i.e. every individual should have an equal chance to be selected in the sample.

Thus a standard random sampling PROBABILITY or p VALUE Using standardized instruments and criteria o o By single, double, triple blind trials Use of a control group
30
method should be used Non sampling errors can be taken care of by o
Concept of probability is very important in statistics Probability is the chance of occurrence of any event or permutation combination. It is denoted by p for sample and P for population In various tests of significance we are often interested to know whether the observed difference between two samples is by chance or due to sampling variation. There probability or p value is used
Determination of Sample Size 1. For Quantitative Data The investigator needs to decide how large an error due to sampling defect is allowable i.e. allowable error L Either the investigator should start with assumed SD or do a pilot study to estimate SD Sample size = 4 SD2 / L2 Mean pulse rate of population is 70 beats per min with standard deviation of 8 beats. What will be the sample size if allowable error is 1 n = 4 X 8 X 8 / 1 X 1 = 256 If L is less n will be more i.e. larger the sample size lesser is the error. 2. For Qualitative Data In such data we deal with proportion Sample size = n = 4 p q L2 o o o p = proportion of positive character q = proportion of negative character q = 1-p or (100-p if expressed in percent) o L = allowable error usually 10% of p (AIPG-10) Ex: incidence rate in last influenza was found to be 5% of the population exposed. What should be the size of the sample to find incidence rate in current epidemic if allowable error is 10%? p = 5% q = 95% l = 10 % of p = 0.5% n= 4 X 5 X 95 / 0.5 X 0.5 = 7600
P ranges from 0 to 1 0 = there is no chance that the observed difference could not be due to sampling variation 1 = it is absolutely certain that observed difference between two samples is due to sampling variation However such extreme values are rare. If P = 0.4 Chances that the difference is due to sampling variation is 4 in 10 Obviously the chances that it is not due to sampling variation will be 6 in 10 The essence of any test of significance is to find out p value and draw inference If p value is 0.05 or more It is customary to accept that difference is due to chance (sampling variation) The observed difference is said to be statistically not significant If p value is less than 0.05 Observed difference is not due chance but due to role of some external factors The observed difference here is said to be statistically significant.
From Shape of Normal Curve We know that 95% observation lie within mean 2 SD. Thus probability of value more or less than this range is 5% From Probability Tables p value is also determined by probability tables in case of student t test or chi square test
31
Since these test make assumptions about By Area Under Normal Curve Here Z = standard normal deviate is calculated Corresponding to Z values. the area under the curve is determined (A) Probability is given by 2 (0.5 - A) the population parameters hence they are called parametric tests These are usually used to test the difference They are, o Student t test (paired or unpaired) (COMEDK-10) TESTS OF SIGNIFICANCE Whatever be the sampling procedure or the care taken while selecting sample, the sample statistics will differ from the population parameters Also variations between 2 samples drawn from the same population may also occur i.e. differences in the results between two research workers for the same investigation may be observed (AIIMS-99) Thus it becomes important to find out the significance of this observed variation i.e. whether it is due to Chance or biological variation (statistically not significant) or Due to influence of some external factors (statistically significant) To test whether the variation observed is of significance, the various tests of significance are done. The Tests of Significance can be broadly classified as 1. 2. 1. Parametric tests Non parametric tests 1. Parametric Tests Parametric tests are those tests in which certain assumptions are made about the population o Population from which sample is drawn has normal distribution o The variances of sample do not differ significantly o The observations found are truly numerical thus arithmetic procedure such as addition, division, and multiplication can be used One tailed test In the test of significance when one wants to specifically know if the difference between the two groups is higher or lower i.e. the direction plus or minus side is specified. Then one end or tail of the distribution is excluded Ex: if one wants to know if malnourished children have less mean IQ than well nourished then higher side of the distribution will be excluded Such test of significance is called one tailed test Tests of Significance can also be divided into one tailed or two tailed test 2. Non Parametric Tests In many biological investigations, the research worker may not know the nature of distribution or other required values of the population. Also some biological measurements may not be true numerical values hence arithmetic procedures are not possible in such cases. In such cases distribution free or non parametric tests are used in which no assumption population Whitney are Chi made square about Ex: test, the Mann Phi parameters. o o ANOVA Test of significance between two means
test,
coefficient test, Fischers Exact test, Sign Test, Freidmans Test

2. Two tailed test This test determines between if there two is a difference the groups
32
Null hypothesis of no difference is rejected accepted This area of normal curve is called zone of rejection for null hypothesis 4. Finally determine the p value p value is determined using any of the previously mentioned methods If p > 0.05 the difference is due to chance and not statistically different but if p < 0.05 the difference is due to (AIIMS-2004) TYPES OF ERROR While drawing conclusions in a study we are likely to commit two types of error. some external factor and statistically significant and alternate hypothesis
without specifying whether difference is higher or lower It includes both ends or tails of the normal distribution Such test is called Two tailed test Ex: when one wants to know if mean IQ in malnourished children is different from well nourished children but does not specify if it is more or less Stages in performing Tests of Significance
1. 2. 3. 4.
1.
State the Null Hypothesis State the Alternative Hypothesis Accept or reject the null hypothesis Finally determine the p value State the Null Hypothesis Null Hypothesis o It is a hypothesis of no difference between statistics of a sample and parameter o It nullifies of the population or the claim that the between statistics of two samples experimental result is different from or better than the one observed already 2. Type II Error/False Negative Error/ Error This type of error occurs When we say that the difference is not significant when in fact there is a real difference between the populations i.e. the null hypothesis is not rejected when it is actually false (KAR-03, COMEDK08) It is denoted by TESTS OF SIGNIFICANCE FOR LARGE SAMPLES These tests are used for sample size greater than 30 The test used is Z test Z is standard normal derivative and has been discussed under normal distribution Z = observation mean / SD 1. Type I Error/False Positive Error/ Error This type of error occurs When we conclude that the difference is significant when in fact there is no real difference in the population i.e. we reject the null hypothesis when it is true Denoted by
1. 2.
Type I error Type II error
2.
State the Alternative hypothesis It is hypothesis stating that the sample result is different ie larger or smaller than the value of population or statistics of one sample is different from the other
3.
Accept or reject the Null Hypothesis Null Hypothesis is accepted or rejected depending on whether the result falls in zone of acceptance or zone of rejection If the result of a sample falls in the area of mean 2 SE the null hypothesis is accepted This area of normal curve is called zone of acceptance for null hypothesis If the result of sample falls beyond the area of mean 2 SE

However in Z test, standard deviation is replaced by standard error In Z test, Z = observed difference / standard error We know that standard deviation measure the variation within a sample Standard error is the measure of difference in values occurring between a sample and population between two samples of the same population Standard error used in Z test can be
33
In a random sample of 100 the mean blood sugar is 80 mg % with SD 6 mg%. Within what limits the population mean will be? What can be said about another sample whose mean is 82% SE = 6 / 100 0.6 = 78.8 to 81.2 A sample with 82% mean is not within limits of population mean thus it does not seem to be drawn from the same population 2. Standard Error of Difference between 2 Means Used for quantitative data It is the difference between means of two samples drawn from the same population It helps to know what is the significance of difference obtained by 2 research workers for the same investigation SE (X1 X2) = SD12 / n1 + SD22 / n2 Ex: Find the significance of difference in mean heights of 50 girls and 50 boys with following values Mean Girls Boys SE 147.4 151.6 SD 6.6 6.3 = 6 / 10 = 0.6 Thus the population mean will be 80 2 X
1. 2. 3. 4.
Standard error of mean Standard error of proportion Standard error of difference between 2 means Standard error of difference between 2 proportions
If in the Z test the Z > 2 i.e. if the observed difference between the 2 means or proportion is greater than 2 times the standard error of difference
p < 0.05 according to the given table Z p 1.6 0.1 2.0 0.05 2.3 0.02 2.6 0.01
Thus the difference is not due to chance and may be due to influence of some external factor i.e. the difference is statistically significant
= (6.6)2 / 50 + (6.3)2 / 50 = 1.29
Z = observed difference / SE 1. Standard Error of Mean Used for quantitative data Standard error of mean is the difference between sample mean and population mean given by SE x = SD of Sample / n (AIIMS-08) 3. Also population mean will be sample mean 2 standard error of mean This will enable us to know whether the sample mean is within the limits of population mean Here Z = sample mean population mean / SE of mean Standard Error of Proportion In case of qualitative data where character remains same but its frequency varies we express it in proportion instead of mean Proportion of individual having special character p Z = 151.6 147.4 / 1.29 = 3.26 Since Z value is more than 2 ,p will be less than 0.05 Thus difference is statistically significant and it can be concluded that boys are taller than girls

q is number of individual not having the character P + q =1 or 100 if expressed in % Standard error of proportion is the unit which measures variation in proportion of a character from sample to population SE of proportion = p X q / n (AIPG-06, AIIMS-07) P = proportion of positive character q = proportion of negative character n = sample size Also proportion of population = proportion of sample 2 SEP Thus one can determine whether the proportion of sample is within limits of population proportion Ex: Proportion of blood group B among Indians is 30%. If in a sample of 100 individuals it is 25% what is your conclusion about the group SEP = p X q / n = 4.33 = 1.15 Since Z is < 2, p will be more than 0.05 thus the difference is not significant. 4. Standard Error of Difference between 2 Proportions Measures the difference in proportion of a character from sample to sample SE (p1-p2) = p1 q1 / n1 + p2 q2 / n2 If typhoid mortality in a sample of 100 is 20 % and other sample of 100 is 30% then is this difference in mortality rate significant? p1 = 20 : q1 = 80 : n1 = 100 p2 = 30 : q2 = 70 : n2 = 100 SE (p1-p2) = 6.08 Z = 30 20 / 6.08 = 1.64 Z < 2, p<.05 thus difference observed is not significant TESTS OF SIGNIFICANCE FOR SMALL SAMPLES In case of samples less than 30 the Z value will not follow the normal distribution Hence Z test will not give the correct level of significance o 25 X 75 / 100 = 4.33 Z = observed difference / SE = 30 - 25 / 1. Unpaired t Test Students t Test In such cases Students t test is used
34
It was given by WS Gossett whose pen name was student The student's t test is used to compare the means of two small (n < 30) independent samples for the purpose of determining the statistical significance (p value) of the observed findings (as opposed to the F test, which compares three or more means). (AIIMS-95, 01) The p value represents the probability that the results occurred purely by chance, rather than as a result of the variable under study. There are two types of Student t Test 1. 2. Unpaired t Test Paired t Test
Applied to unpaired data of observation made on individuals of 2 separate groups to find the significance of difference between 2 means (AIIMS-03) Sample size is less than 30 Ex: difference in accuracy two in an impression using different
impression materials Steps in unpaired t Test are o o Calculate the mean of two samples Calculate deviation Calculate the Standard Error of Mean (SEM) which is given by SEM = SD means X1 X2 Calculate t value = observed difference / Standard error of mean Determine the degree of freedom which is one less than no of observation in a sample (n -1) (KAR-03) Here combined degree of freedom will be = (n1 1) + (n2 1) Refer to table and find the probability of the t value corresponding to degree of freedom P < 0.05 states difference is significant 1/n1 + 1/n2 Calculate observed difference between combined standard

P > 0.05 states difference is not significant Ex: In a nutritional study 13 children in group A are given usual diet along with vitamin A and vitamin D while 12 children in group B take the usual diet. The gain in weight in pounds for both groups after 12 months is shown in the table. Is vitamin A and D responsible for gain in weight? Mean of group A = 4 Mean of group B = 2.5 Total SD = 1.37 Total SE = 0.548 t = Observed difference / SE t = 4 2.5 / 0.548 = 2.74 Combined degree of freedom = n1 + n2 2 = 12 +13 - 2 p value is checked corresponding to the t value at 23 degree of freedom (d.f) from the t table It is < 0.02 Thus difference is statistically BP before X1 122 121 120 115 126 130 120 125 128 BP after X2 120 118 115 110 122 130 116 124 125 giving drug giving drug
35
P < 0.05 states difference is significant P > 0.05 states difference is not significant Ex: Systolic BP of a normal individual before and after injection of hypotensive drug is given in the table. Does the drug lower the BP?
Difference X1X2 = y 2 3 5 5 4 0 4 1 3
Mean of difference y = y / n = 27 / 9=3 SD = ( y - y )2 /n-1 = 1.73 SE = SD / n = 1.73 / 9 = 0.58 t = y / SE = 3 / 0.58 = 5.17 Degree of freedom to n 1 = 9 1 = 8 p value corresponding to t = 5.17 and d.f. 8 is < 0.001 Thus highly significant Thus decrease in BP is due to the Drug Chi Square Test Chi square test unlike z and t test is a non parametric test The test involves calculation of a quantity called chi square Chi square is denoted by X2 (AIPG-2000, AIIMS-01, COMEDK-06, 07, 08) It was developed by Karl Pearson The most important application of chi square test in medical statistics are o o o Test of proportion Test of association Test of goodness of fit
significant And accounted to role of vitamins A &D 2. Paired t test (AIPG-02) (COMEDK-06) It is applied to paired data of observation from one sample only Used in sample less than 30 The individual gives a pair of observation i.e. observation before and after taking a drug The steps involved are o Calculate the difference in paired observation i.e. before and after = x1 x2 = y o Calculate the mean of this difference =y o o o o Calculate SD Calculate SE = SD / n Determine t = y / SE Determine the degree of freedom
Since there is one sample df = n-1 Refer to table and find the probability of the t value corresponding to degree of freedom
Test of proportion

o Used as an alternate test to find the significance of difference in 2 or more than 2 proportions Test of association o To measure the probability of association between 2 discreet attributes e.g. smoking and cancer Test of goodness of fit o Tests whether the observed values of a character differ from the expected value by chance or due to play of some external factor X2 = (O E) 2 / E X2 denotes Chi square O = Observed Value E = Expected Value Steps in Chi Square Test State the null hypothesis Determine the Chi square value Find the degree of freedom Refer the Chi square table to find the probability value corresponding to the degree of freedom Let us consider the following example o o We are making a field trial of 2 vaccines The results of field trial are Vaccine Attacked Not Attacked A B Total o o 22 14 36 68 72 140 Total 90 86 176 Attack Rate 24.4% 16.2% X2 = (O E) 2 / E = (3.64)2 /18.36 + (3.55)
2
36
Vaccine
Attacked O = 22
Not Attacked O = 68 E = 0.795 X 90 = 71.55 O - E = - 3.55
A (n=90)
E = 0.204 X 90 =18.36 O - E = + 3.64
O = 14 B (n=86) E = 0.204 X 86 = 17.54 O - E = -3.54
O = 72 E = 0.795 X 86 = 68.37 O - E = + 3.63
/ 71.55 +
(3.54) 2/ 17.54 + (3.63) 2 / 68.37 = 0.72 + 0.17 + 0.71 + 0.19 = 1.79 Find the Degree of Freedom = (c-1) (r-1) c = number of Columns r = number of Rows d.f. = (2-1)(2-1) = 1 Find the p value On referring to Chi square table with one degree of freedom the p value was more than 0.05. Hence the difference is not statistically significant and the null hypothesis of no difference between vaccines is accepted. ANOVA Analysis of Variance Investigations may not always be confined to comparison of 2 samples only (AIIMS-03) Ex: we might like to compare the difference in vertical dimension obtained using 3 or more methods like phonetics, swallowing, Niswongers method In such cases where more than 2 samples are used ANOVA can be used Also when measurements are influenced by several factors playing their role Ex; factors affecting retention of a denture, ANOVA can = be used.
Vaccine B seems to be superior to Vaccine A We perform Chi Square test to verify if the vaccine B is superior to vaccine A or is it merely due to chance
State the null hypothesis o It states that the vaccines have equal efficacy
Determining the Chi Square Value o o o Find total attack and non attack rates Total Attack rate = 36 / 176 = Total Non Attack Rate = 0.795 0.204 140 / 176

ANOVA helps to decide which factors are more important Requirements Data for each group are assumed to be independent and normally distributed Sampling should be at random One way ANOVA Where only one factor will affect the result between 2 groups Two way ANOVA Where we have 2 factors that affect the result or outcome Multi way ANOVA Three or more factors affect the result or outcomes between groups F test F = Mean Square between Samples / Mean Square within Samples F = variance ratio The values of Mean square are seen from the analysis of variance table if we have the values of sum of squares and degree of freedom ( which are calculated ) Mean Square between Samples o It denotes the difference between the sample mean of all groups involved in the study (A, B, C etc) with the mean of the population Mean Square within Samples o it denotes the difference between the means in between different samples The greater both these value more is the difference between the samples The F value observed from the study is compared to the theoretical F value obtained from the Tables at 1% and 5% confidence limits. The results are then interpreted. If the observed value is more than theoretical value at 1%, the relation is highly significant. If the observed value is less than the theoretical value at 5% it is not significant. If the observed value is between 1 and 5% of theoretical value it is statistically significant.
37
MISCELLANEOUS Friedmans test nonparametric equivalent of analysis of variance (COMEDK-10) Kruskal Wallis test to compare medians of several independent samples equivalent of one way analysis of variance Mann Whitney U test compares medians of two independent samples. Equivalent of t test McNemars test variant of chi squared test, used when data is paired Wilcoxons Sign rank test paired data Spearmans coefficient The Fisher's exact test procedure calculates an exact probability value for the relationship between two dichotomous variables, as found in a two by two cross table. The program calculates the difference between the data observed and the data expected, considering the given marginal and the assumptions of the model of independence. It works in exactly the same way as the Chi-square test for independence; however, the Chi-square gives only an estimate of the true probability value, an estimate which might not be very accurate if the marginal is very uneven or if there is a small value (less than five) in one of the cells. In such cases the Fisher exact test is a better choice than the Chi-square. However, in many cases the Chi-square is preferred because the Fisher exact test is difficult to calculate. rank correlation correlation

Appropriate Tests of Significance to be used in Bivariate Analysis First variable Quantitative Quantitative Water F levels and mean DMFT Second variable Example Tests of significance
38
Pearson correlation coefficient (r) Linear regression Spearman correlation coefficient (rho) Possibly use ANOVA or F test Students t- test or Z- test
Quantitative
Ordinal
Water
levels
and
esthetic
concerns Tooth displacement in mm in males and females Difference LA Mean DMFT in four areas in systolic blood
Quantitative
Dichotomous unpaired Dichotomous paired Nominal
Quantitative
pressure before and after injecting
Paired t- test or Z- test ANOVA (F- test) Spearman correlation coefficient
Quantitative
Ordinal
Ordinal
Esthetic concerns and TSIF scores
(rho) Kendall correlation coefficient
Ordinal
Dichotomous unpaired Dichotomous paired Nominal Dichotomous unpaired Dichotomous paired
Esthetic concerns of males and females Esthetic concerns of children
Mann- Whitney u test Wilcoxon matched- pairs signedranks test Kruskal- Wallis test Chi- square test; Fisher exact probability test Mc Nemar Chi- square test
Ordinal Ordinal Dichotomous
before and after bleaching Esthetic concerns and ethnicity Success / Failure in treated / untreated groups Change in success / failure before and after treatment Retention of different pit and
Dichotomous
Dichotomous
Nominal
fissure sealants two years after application
Chi- square test
Nominal
Nominal
Sterilizing equipment used by doctors of different specialties
Chi- square test

Appropriate Tests of Significance to be used in Multivariate Analysis Dependent Variable Independent Variables
39
Example Prevalence of dental caries -
Tests of Significance
Quantitative
All are categorical
frequency of sugar intake, water fluoride level, socio economic status Blood pressure- body mass index,
ANOVA
Quantitative
All are quantitative
age, amount of fat intake, salt intake
Multiple linear regression
There is no formal multi variable procedure for ordinal dependent Ordinal variables. Either analysis Dichotomous All are categorical Happiness with tooth colourseverity of fluorosis, SES, locality Logistic analysis Logistic regression * Diabetic statusoccupation, *
If the outcome is a time related
treat
the
variables
as
continuous or perform log- linear
regression;
log linear
Some are categorical Dichotomous Some continuous are
family history, BMI, age
dichotomous variable (such as live/die), proportional hazards (Cox) models are suitable
Diabetic status-body mass index, Dichotomous All are continuous age, amount of fat intake, salt intake Longitudinal study Nominal All are categorical Diseases- occupation, education, area of residence Some are categorical Nominal Some are continuous Longitudinal study Diseasesoccupation, education, age, BMI Longitudinal study Nominal All are continuous DiseasesMean no. of cigarettes per day, age, BMI
Logistic regression; discriminant function analysis
Log linear analysis
Group the continuous variables and perform log linear analysis
Discriminant function analysis; Group the continuous variables and perform log linear analysis
*****
NEET
Concepts
Volume 05 Prosthodontics Cons & Endo Periodontics Oral surgery
PROSTHODONTICS (RPD) Direct Retainers
21
DIRECT RETAINERS
DEFINITIONS Retention is resistance to movement of a denture away from the teeth and/or tissues along the path of placement of the prosthesis. Most retention of RPDs is provided by Direct Retainers which are clasp assemblies or attachments applied to an abutment tooth to retain an RPD in position Some retention of tooth-tissue supported RPDs may be obtained from those factors which provide retention in complete dentures. This will be called Denture Type Retention A Clasp Assembly is the part of an RPD that acts as a direct retainer and/or stabilizer for the prosthesis by partially encompassing or contacting an abutment tooth The Clasp is the component of the clasp assembly that engages a portion of the tooth surface and either enters an undercut for retention or remains entirely above the height of contour to act as a reciprocating element The part of the clasp assembly that enters an undercut for retention is frequently called the Retentive Clasp Arm An Attachment is a mechanical device for the fixation, prosthesis REQUIREMENTS OF A DIRECT RETAINER All direct retainers, clasp assemblies or retention, and stabilization of
2.
Retention Retention of a clasp assembly is provided by the resistance to flexure of the retentive clasp arm as it engages the height of contour of the tooth as the RPD moves occlusally/incisally. Some retention of a clasp assembly may also be provided by frictional contact of rigid portions of the clasp assembly, such as the proximal minor connector and reciprocal component, with surfaces of the tooth which are parallel to the path of placement of the RPD. Retention of an attachment may be provided by frictional contact of the long parallel walls of the attachment, mechanical locking devices, resistance to deformation of resilient locking materials, and other such imaginative systems. Retention of attachments is frequently provided, or supplemented, by a retentive clasp arm on the lingual surface of the abutment.
3.
Cross-Tooth Reciprocation Reciprocation is the mechanism by which lateral forces generated by a retentive clasp passing over a height of contour are counterbalanced, counteracted or negated by a reciprocal component passing along reciprocal guiding plane. Cross-tooth reciprocation of a clasp
attachments, must
provide the
following
assembly is provided by the Reciprocal Component which may be a clasp arm, plate or minor connector. The reciprocal component contacts the tooth on the side opposite the retentive clasp arm as the retentive clasp arm flexes over the height of contour of the tooth. The reciprocal component stabilizes the tooth and counterbalances, counteracts, negates or "reciprocates" the force applied by the retentive component. Cross-tooth reciprocation of an attachment is provided by the precise fit of the long parallel walls of the component parts, or by supplemental reciprocal components on the framework
functions in order to be effective and not do harm to the abutment teeth or tissues of the denture foundation area 1. 2. 3. 4. 5. 1. Support Retention Cross-tooth reciprocation Fixation Passivity
Support Support of a clasp assembly is provided by positive contact of the rest of the clasp assembly with the rest preparation of the abutment tooth Support of an attachment is provided by contact of a rigid element on the denture with a rigid element on the abutment tooth

4. Fixation Fixation is resistance to movement of the abutment tooth away from the prosthesis and resistance to movement of the prosthesis away from the abutment tooth. Fixation of a clasp assembly is provided by having the components of the clasp assembly encompass or encircle at least 180 degrees of the abutment tooth's circumference, the tooth or by in having three the places components of the clasp assembly contact surface approximately 120 degrees apart. Fixation of a clasp assembly is frequently call Encirclement. Fixation of an attachment is provided by the dovetail, or circular design of the component parts, or by supplemental clasp arms on the lingual of the abutment tooth 5. Passivity Direct retainers should not exert forces on the abutment teeth when the RPD is seated. They should be passive when the RPD is seated. Forces should occur only when the denture is being seated or removed. CROSS-ARCH RECIPROCATION In the design of an RPD the force exerted by a direct retainer on one side of the arch should be counterbalanced, counteracted, negated or "reciprocated" by an equal but oppositely directed force on an abutment tooth on the opposite side of the arch. This is termed Cross Arch Reciprocation. Cross-arch reciprocation probably does not occur in RPDs using attachments unless the retention is provided by retentive clasp arms. CLASP REQUIREMENTS 1. 2. 3. 4. 5. 6. Retention Stability Support Reciprocation Encirclement Passivity 2. Support Resists displacement in the v. ii. ii. i. 1. Retention 3 parts i. ii. 7. 8. 9. Location Esthetics Simple design
22
10. Minimal contact with tooth 11. Inexpensive
Terminal: engages undercut, flexible Middle: limited flexibility
iii. Proximal: rigid Retention depends upon Flexibility (MAHE-95) Depth of retentive terminal Amount of clasp below height of contour Dimensions of retentive undercut Buccolingual depth of undercut Less sharp the angle between the height distance height of contour the between and and greater the the perpendicular, needed of
contour
retentive terminal to achieve the same amount of retention Distance between survey line and the tip of retentive clasp Affects flexibility iii. Mesiodistal length of clasp arm Proportional to the flexibility Flexibility of clasp arm Depends upon (MAHE-95, AP-03) i. Material (0.010), modulus Length length iii. Diameter of clasp: flexure inversely proportional to the diameter iv. Taper: thickness at the tip Cross section: round > half round vi. Alloy: wrought > cast gingival of used: cast of the cast gold chrome (0.015), less flexure clasp length and
wrought alloy (0.020). More elasticity clasp: flexibility (AI-94) proportional to three times the
direction.

3. 4. Stability 5. 6. 7. Resistance to horizontal displacement To resist horizontal displacement Rigid Positioned on opposite side Above the height of contour Should contact before retentive component More than 180 of abutment Continuous contact Broken contact Retention function is activated only when dislodging forces act Location Close to gingival margin 8. (Akers, Circumferential) ircumferential) 7. 6. 5. Reciprocation (AIIMS-89) 4.
23
Reciprocal arm (AIIMS AIIMS-90, AIPG-93, AP-99) A rigid clasp arm placed above the height of contour on the side opposite to the retentive clasp arm. Must ust contact the tooth before retentive clasp Retentive terminal Distal third of the clasp. Flexible Should always poi point towards the occlusal surface (MAHE-2K 2K) Approach arm A minor connector that projects from the framework runs along the mucosa and turns across the gingival margin of the abutment. Minor connector Part that joins oins body of the clasp to the remainder of the RPD framework Body Part of the clasp that connects the rest and shoulders of the clasp to the minor connectors. Must ust be rigid and above the height of contour Any clasp assembly should encircle at least 1800 of the abutment tooth.
Encirclement
Passivity
TYPES OF CLASPS 1. Supra bulge approaches undercut from above the height of contour. (MAHE-98, 99, AIPG-06) AIPG 2. 3. Infra bulge (Roach or bar) approaches undercut from under the height of contour. Combination clasp circumferential and bar clasp arm or cast clasp arm and wrought wire clasp CLASP ASSEMBLY 1. Clasp assemblies are composed of (AIPG-03) Rest Part of a clasp that lies on the occlusal, occlusal incisal, or lingual surface of the tooth and resists the upward movement of the clasp by ensuring that retentive terminal of the clasp arm remain fixed at the desired desir position of the undercut. 2. Shoulder Part of the clasp that connects the body of the clasp terminals Must lie above the undercut ercut and provide stabilization 3. Retentive arm Part of the clasp comprising the shoulder which is not flexible, loca located above the height of contour

CIRCUMFERENTIAL CLASPS Clasp Akers' Clasp Indications Tooth born partial denture (removable bridge) On free-end extensions where undercut is so small that longer clasp arms will not be retentive Contraindications Ring Clasp Encircles the tooth from its point of origin Back Action Clasp Modification of ring clasp Use on isolated lower molar with undercut located mesio-lingually due to lingually tilted tooth Tipped molars Not used on molars because of length of clasp arm High muscle attachment
24
Advantages Good support and bracing Simple design Dose not distort easily Easy to adjust Contacts minimal area of the tooth Good esthetics
Disadvantages May abutments incorrectly extension on traumatize when used free-end
It covers large area of the tooth making it unaesthetic, so it used only in posterior teeth Can use small undercut areas Length of clasp produces resiliency and "stressbreaking" effect on abutments for free-end extension partial denture Easily distorted because of length Difficult to adjust Large tooth area covered Design produces "food trap" between lingual arm and major connector
Premolar and canine abutments on freeend extension On short teeth with small mesiofacial and distal undercut
Reverse Back Action Clasps (KAR-PGET-03) joining of a bar & back action clasps with all their disadvantages
Premolar denture
abutment
with
lingual
Maxillary partial denture for esthetic reasons When there is a severe soft tissue undercut inferior to marginal gingiva
Has
"stress-breaking"
action
Crosses soft tissue Excessively adjust long clasp, easily distorted, difficult to
inclination on free-end extension partial
similar to "back action clasp"
Poor esthetics Contacts large areas of tooth

Half & Half Clasp "Split Clasp" Premolar and molar abutment for freeend extension P.D. and removable bridges Isolated teeth
25
Good support and bracing Easy to adjust Contacts minimal area of the tooth Good esthetics
Food
trap
may
be
introduced connector if
between not
lingual arm and major constructed properly
Reverse Action Clasp Hairpin, Clasp hook & C Fish
When a proximal undercut must be used to a posterior teeth and high tissue undercut prevents the use of a bar clasp
On maxillary teeth where the metal is objectionable
Undercut adjacent to edentulous area may be utilized without having minor connector cross soft tissue
Poor esthetics Large area of the tooth surface is covered Possible food trap
Distofacial undercut on canines and premolars when a sharp tissue undercut prevent use of bar-type clasp
Good bracing and support May be used on free end extension P.D. or removable bridges
Embrasure Clasp Butterfly Clasp or Double Akers' Clasp
Undercut near minor connector on molars To utilize multiple abutments and Not to be used where clasp would traumatize abutment teeth Can not be used where there is insufficient space for the minor connector to cross the occlusal surface in a unilateral
Good support and bracing Distributes support, bracing and retention to several teeth
Minor connector usually too thin on occlusal in be surface resulting may
distribute occlusal support and retention to several teeth When insufficient undercuts are present on a single abutment Specially used for the purpose of a bilateral undercut bracing edentulous arch, to utilize a retentive
excessive breakage Retention excessive
Multiple (KCET-08)
Clasps
Two opposing circumferential clasps joined at the terminal end of the two reciprocal arms, used when multiple clasping is needed
Mesiodistal Clasp
On maxillary lateral incisors which are abutments for a removable bridge (tooth born partial denture) or tooth borne side of a unilateral free-end extension
Good esthetics Good support and bracing
Tooth must be prepared by dentist so that proximal surfaces of the tooth are parallel or have slight convergence incisally

BAR CLASP (AIIMS-98, 99, AP-04) Push type retention Approach from gingival direction 4. I Clasp
Used on disto buccal surface of maxillary canine
Indications Advantages Esthetics Wide varieties COMBINATION CLASP (COMEDK-04) Disadvantages Food accumulation Less bracing action Wrought round retentive arm with cast reciprocal arm Disadvantage - it is more prone to breakage and damage- (PGI-08) Rules for use Should not impinge Not desirable to provide relief near the arm Minor connector should be rigid & strong Uniform taper Approach arm crosses gingival margin at 90 Approach arm extends up to height of contour Placed as low as possible Retentive terminal engages undercut below the height of contour Types 1. T clasp Used in combination with cast reciprocal arm Retentive tip crosses under the height of contour Approach arm contacts the tooth at height of contour only Indications 1. 2. Distal extension Also in tooth supported RPD where retentive undercut is on the abutment tooth 2. Modified T Clasp Essentially a T clasp with non retentive finger of cross bar omitted Indication On canines and pre molars for esthetic reasons Disadvantage Encirclement may be sacrificed 3. Y clasp T clasp given when height of contour is high on the mesial or distal side but low at the center on the facial surface R-P-I CLASP The components of this clasp assembly are "R" - rest (always mesial) "P" - proximal plate "I" - I-bar (retentive arm) The Rest is located on the mesio-occlusal surface of a premolar or mesiolingual surface of a canine. The minor connector is located in the mesio-lingual embrasure but is not in contact with the adjacent tooth (prevents wedging). The Proximal Plate (essentially a wide minor connector) is located on a guide plane on the distal surface of the tooth. The superior edge of the proximal plate is located at the bottom of the guide plane (at approximately the junction of the occlusal and middle third of the guide plane). The proximal plate extends lingually so that the distance between the minor connector and the proximal plate is less than the mesiodistal width of the tooth. The plate is approximately l mm thick and joins the framework at a right angle. The I-bar clasp is located on the buccal surface of the premolar and on the mesio-buccal surface of the canine. The I-bar originates at the grid work and approaches the tooth from the gingival direction. The bend in the I-bar should be located at least 3 mm. from the gingival margin. This distance will prevent food entrapment and provide the length for the necessary flexibility in the clasp arm. The clasp Indications 1. 2. 3. Caries prone mouth Esthetics required Abutment tooth adjacent to distal extension More esthetic Less chance of caries

is usually cast and is placed just below the height of contour line. Contraindications 1. Insufficient depth of the vestibule. (The inferior border of the I-bar must be located at least 4 mm. from the gingival margin) 2. 3. 4. No labial or buccal undercut on the abutment Severe soft tissue undercut Disto-buccal encirclement) RPA Clasp This clasp assembly is similar to the RPI design except a wrought wire circumferential clasp (Akers) is used instead of the I-bar. This clasp arises from the proximal plate and terminates in the mesiobuccal undercut. It is used when there is insufficient vestibule depth or when a severe tissue undercut exists. undercut (less than 180
*****
CONS & ENDO Endodontics Armamentarium
48
ENDODONTICS ARMAMENTARIUM
CLASSIFICATION INSTRUMENTS Grossman's Classification Root canal instruments are divided into 4 types according to their function. 1. Endodontic Explorers (Exploring Instruments) To locate the canal orifice. To determine or assist in obtaining patency of the root canal. Ex: Smooth broaches, Endodontic explorers 2. Debridement Instruments) To extirpate the pulp. To remove debris and other foreign material. Ex: Barbed broach. 3. Root canal shaping Instruments To shape the root canal laterally and apically. Ex: Reamers, Gates - Glidden drill, Files 4. Obturating Instruments To cement and pack guttapercha into the root canal. Ex: Pluggers (flat end-for vertical condensation), Spreaders (pointed end-lateral condensation), Lentulospirals (to deliver sealer or paste to the root canal) I.S.O. and FDI Classification 1. Group - I: Hand Use Only Hand operated instruments such as barbed and smooth broaches, reamers, K, H, and R files, plugger, spreaders etc. 2. Group - II: Engine driven Instruments Same instruments as described above. But the handles of these instruments have been replaced by latch type adapter for insertion into low speed hand pieces These instruments consist of two parts. o o 3. An operative cutting head Latch type of attachment Instruments (Extirpating OF ENDODONTIC
4.
Group - IV: Root canal points They are usually the materials used. Ex: Guttapercha points, Absorbable points.
STANDARDIZATION INSTRUMENTS Earlier, root
OF canal
ENDODONTIC instruments were
manufactured according to the manufacturer's wish with no definite specifications regarding length, diameter, shape and length of the cutting instrument. Ingle and Levine using an electrode micro comparator found variations in diameter and taper for the same sizes of instruments and later suggested some recommendations to maintain uniformity. Ingle and Levine Recommendations 1. Instruments shall be numbered from 10 to 100 150. The numbers advance by 5 units, to size 60 and then by 10 units to size 100. 2. Each number shall be representative of the diameter of the instrument in hundredths of a millimeter at the tip. Ex: No: 10 is 10/100 or 0.1 mm at the tip No: 25 is 25/100 or 0.25 mm at the tip No: 90 is 90/100 or 0.9 mm at the tip 3. The working blade (flutes) shall begin at the tip, designated site D1 and shall extend exactly 16 mm up the shaft, terminating at designated site D2. The diameter of D2 shall be 32/100 or 0.32 mm greater than of D1. Ex: No: 20 reamer shall have a diameter of 0.20 mm at D1 and a diameter of 0.20 plus 0.32 or 0.52 at D2. This sizing ensures a constant increase in taper of 0.02 mm per mm for every instrument regardless of size.
16 mm D2 D1
Group - III: Engine driven latch type - drills Similar to Group - II these instruments have latch attachment but are fabricated from a single piece of metal. So latch, shaft and cutting head are made of a single piece. Ex: Gates Glidden drill, Peeso reamer.
D2 Fig. 5.1
75
D1
D1 - diameter at the tip D2 - diameter at the tip end of the cutting blade (AIPG-94)

Other Specifications (were added later) 1. 2. The tip angle of an instrument should be 7515 (AP-02) Instrument sizes should increase by 0.05 mm at D1 between numbers 10 and 60. Ex: Numbers 10, 15 and 20. They should increase by 0.1 mm from numbers 60 to 150. Ex: Numbers 60, 70 and 80. 3. 4. 06 and 08 have been added for increased instrument selection. In addition, instrument handles have been color coded for easier recognition. Stainless steel root canal instruments are used more often today than carbon steel instruments because of their more flexibility, less likely to fracture, less susceptible to corrosion. The finer sizes of reamers and files have low resistance to torque (pressure used to rotate instrument for cutting and shaping) and break using less force than larger instruments when they bind in a root canal. As a result, small instruments are manufactured from square blanks, which are more resistant to torque, fractures, and large instruments are manufactured from triangular blanks, to improve their cutting efficiency. Instruments are available in lengths of 21, 25, 28 and 30 mm. Ordinarily, instruments of 25 mm long are used, but occasionally 21mm instruments are needed for molars especially when the patient cannot open the mouth wide and 28 and 30 mm instruments are necessary for cuspids and other teeth in which a 25 mm instrument cannot reach the apical foramen. Reamers are also available in 40 mm lengths for use in preparing root canals for endodontic treatment. Colour Coding of Handles of Instruments (AIPG-97, AP-02) EXTIRPATING INSTRUMENTS Barbed Broach (PGI-97, 98, AIPG-02) Uses To extirpate the pulp. EXPLORING INSTRUMENTS Endodontic Explorer
49
A double ended instrument with long tapered tines at either a right or an obtuse angle. This design facilitates the location of canal orifice. These instruments are very stiff and should not be inserted into canals or used for condensing guttapercha. Explorers should never be heated.
(MAHE-97,
COMEDK-04) To remove debris and other foreign material, absorbent points, cotton pellets etc. Manufacture It is manufactured from a tapered, round, soft iron wire in which angle cuts are made into the surface to produce barbs. Available as A variety of sizes from triple extra fine to extra coarse Barbs are used to engage the pulp as the broach is carefully rotated within the canal until it begins to meet resistance against the walls of the canal. Barbed broaches break easily especially if they bind in the root canal hence root canal should be enlarged before insertion of the broach. (MAHE-97) Selection By comparing the size of the broach with the size of the last instrument used in the root canal or an estimated size of the image in a radiograph One should select barbed broach that fits loosely into the apical third of the root canal. A barbed broach that is too wide does not permit removal of all the pulp tissue or it may force the pulp apically as the broach is inserted in the canal. Sterilization A barbed broach can be cleaned by scrubbing with a bur brush. To clean a broach which has tissue tags or necrotic debris, place it in a 5.2% sodium hypochlorite solution for half an hour and
6 8
Pink Grey
30 Blue 35 Green
10 Purple 40 Black 15 White 45 White 20 Yellow 50 Yellow 25 Red | |

150

then broach is rinsed in running water; air dried and is sterilized in dry heat. Rasps or R - Type Files This is similar in design to barbed broach, but has shallower and more rounded barbs. Used to enlarge the root canal but usually produce rough wall of the root canal. So it is not preferred often. INSTRUMENTS FOR CLEANING AND SHAPING REAMERS Physical Characteristics Manufactured triangular blank. Has less number of flutes.( AIPG-96, KCET-97) Do not break easily unless they have an undetected instrument (KCET-97) Flutes are loosely twisted. Uni Files (Modification of H-File) Functional Characteristics Used with a rotating - pushing motion limited to a quarter - to a half turn to engage their blades into the dentin and withdrawn - penetration, rotation and retraction. (KCET-97, PGI-02) The cut is made during retraction. S - File (Modification of H - File) FILES (AIIMS-95, KCET-98) K - File (Kerr manufacturing company) Has got the name from its manufacturing company. Manufactured from stainless steel square blank.(KCET-97) Does not break easily unless they have an undetected steel shaft or until the instrument is strained or deformed. Flutes are tightly twisted. (AIPG-95, AIIMS-06, 07) K - files can be used as `PATHFINDER' (to locate the root canal orifices) (KCET-99, AIPG90) K - Flex Files Manufactured from rhomboidal or diamond shaped blanks. Designed for more flexibility and cutting efficiency. Flexofile Manufactured by Dentsply maillefer. steel is shaft or or until the strained deformed. from stainless steel
50
Has alternating high and low flutes for more efficiency.
Hedstroem Files (H-Files) Manufactured from a round stainless steel wire machined to produce spiral flutes resembling cones or as crew or Christmas tree appearance. When placed in contact with the root canal wall the cutting edges contact the wall at angles approaching 90 degrees and when the instrument is withdrawn exert an effective honoring action. Cut in one direction only retraction. Used in wide opened canals (Blunder bluss canals). (PGI-05, COMEDK-05) Used to flare the canal from the apical region to the occlusal or incisal orifice. Fragile and fractures easily. Higher cutting efficiency than K - Instruments. Also used to engage and remove retained instruments, gutta-percha and silver points.
Manufactured from round stainless steel wire by cutting two superficial grooves to produce flutes in a double helix design. Resemble H-file in appearance. Less subject to fracture. Less efficient.
Manufactured from a solid piece of stainless steel wire that produces a sharp cutting edge. Has a double cutting edge. Similar to Unifile except that the angles of the flutes remain uniform where as pitch and depth of the flutes increases from the tip to the handle. Stiffer than H-files. Has 90 cutting tip. Can be used for straight or curved canals. Used either as a reamer or file.
Manufactured in the same way as the K - file but using a more flexible stainless steel alloy. It has more flutes than K - file. It has a non-cutting (Batt) tip and a triangular cross-section so the cutting flutes are sharper and there is more scope for debris removal.

Advantages 1. 2. More cutting efficiency Resistance to fracture NiTi Files (Nitinol Files) The name Nitinol was derived from the elements that make up the alloy, i.e. Nickel and Titanium and `nol' for the Naval ordinance Laboratory (who manufactured it for the first time). Nitinol instruments should be used with a rotational or reaming motion and are effective in the shaping of root canals. Advantages 1. 2. 3. 4. 5. 6. 7. 8. More flexible Better conformation to canal curvature Resistance to fracture Less wear Super elasticity Enhanced canal negotiation Faster instrumentation No need to pre curve Quantec Has double helical, asymmetric LightSpeed ProFile and ProFile GT Rotary nickel titanium instruments
51
These instruments are based on a constant percentage change of diameter at D, instead of the variable linear dimensional changes. These are made with a constant 29% increase in tip diameter between successive sizes.
Available in sizes with a #0.02, 0.04, 0.06 or 0.08 taper Can be distinguished by their trihelical, symmetric U-shaped flutes separated by lands Blades have slightly negative rake angles ProFile has a 16 mm working length ProFile GT has slightly more spirals at the tip portion and slightly fewer at the handle portion ProFile GT does not include #0.02 taper
Has same cross section ProFile and ProFile GT Has a unique, short flame shaped working portion and a reduced diameter shaft similar to that of a Gates-Glidden drill Available in sizes with a #020 to #140 It also includes half sizes #022.5 upto #60 Can be used in hybrid technique
GT (Greater Taper) hand files Were designed by Buchanan. Are made from Ni-Ti. The set of four hand files of varying tapers, 0.12 - 0.16, all have a tip size of ISO 20. They have pear-shaped handles and each file is designed for different areas and types of canals. For ex: 0.12 GT file is suited to canal orifices of relatively straight canals of large apical diameter, 0.06 GT file is suited to the apical third in a thin or curved canal. Used in a sequence of counter clockwise and clockwise rotations. They are intended to allow the creation of a predetermined funnel-shaped canal with fewer instruments than using the ISO series. K3
flutes
separated by lands Has positive cutting edge Available with two tip designs a cutting tip and a safety tip Available in sizes with a #0.02, 0.03, 0.04, 0.05, 0.06, 0.08, 0.010 and 0.012 taper
Similar to Quantec, has three asymmetric flutes separated by lands Has the most positive cutting angles of the instruments presently available and is considered among the most resistant to fracture because of its cross sectional geometry
Series 29 Files In accordance with ISO specifications for traditional hand instruments sizes, the percentage difference between tip diameters of sizes 10 -15 is 50%, whilst between sizes 55 and 60 is 9%. This variable percentage changes are leading for procedural errors such as ledging, difficulty in negotiating narrow and curved canals.
Available in sizes with a #0.02, 0.04, 0.06 taper
Hero 642 Has tri helical, sharp flutes resembling a Hedstroem design Available in sizes with a #020 to #45

Race Incorporates alternating non spiraled and spiraled segments along its working length to minimize torsion of engagement and torsion resulting from screwing-in forces (thus its name, Reamer with Alternating Cutting Edges) Sequence Resembling a K reamer, has a slight corkscrew configuration with variable pitch and helix angles The tip design is said to be non cutting, with the first blade positioned 1 mm from the tip EZ-Fill Safesider It is a series of non circular, uninterrupted flatsided instruments Designed on the principle that when fewer blades engage the canal walls, less stress is placed on the instrument Have D shaped cross section OBTURATING INSTRUMENTS Pluggers (Condenser) Have smooth and flat apical tips.
52
These are used for condensation of guttapercha during obturation. Used primarily for vertical condensation.
Spreaders Spreaders instruments. Available in wide variety of lengths and taper. Used to condense the filling material laterally against the canal walls creating space for insertion of additional auxiliary cones. Spreaders should always be fit into the empty canal to ensure that the force is absorbed by the gutta-percha and not the canal walls selection of spreaders. Spreaders are available that have been numbered to match the instrument size. Spreader of the same apical instrument size or one size larger is chosen so that it reaches to within 1.0 to 2.0 mm but will not penetrate the apical orifice. Lentulo Spirals Used for coating sealer on root canal walls. Used in clockwise rotary motion. are long tapered pointed
Functional Characteristics of Files Inserted into the root canal to the apex laterally pressed against one side of the canal wall and withdrawn with a pulling motion or respiring motion. The cutting action of the file can be effected in either a filing (rasping) or reaming (drilling).
MOTIONS OF INSTRUMENTATION Comparison between Reamers and Files These are also referred to as envelops of motion. They are useful for generating or controlling the cutting activity of an endodontic file.
1. Made of stainless steel. 2. Used with push motion and rotation quarter to half turn. 3. Has less number of flutes. 4. Flutes are loosely twisted. 5. Manufactured from triangular blanks.
1. Made of stainless steel. 2. Used with pull or rasping motion. 3. Has more of flutes. number
1.
Filing It indicates a push - pull action with the instrument. Filing is an effective technique with Hedstroem type instruments since they do not engage during the insertion and cut efficiently during the withdrawal motion. The disadvantage is that it can cause stripping of the canals.
4. Flutes are tightly twisted. 5. Manufactured from square blanks.
PUSH
PULL

2. Reaming It indicates clockwise or right-hand rotation of an instrument. The instrument must be restrained from insertion to generate a cutting effect. Disadvantage of this motion is increased instrument fracture. 5. Watch - Winding and Pull
PUSH TURN
PUSH
53
&
BACK & FORTH
&
It is used primarily with Hedstroem files. An inward pressure is mentioned while the file is gently rocked right and left, when that insertion stops, all rotation is ceased and the instrument is withdrawn from the canal.
3.
Turn and Pull It is a combination of reaming and filing. The file is inserted with a quarter turn clockwise and inwardly directed hand pressure (i.e., reaming) positioned into the canal. By this action the file is subsequently withdrawn (i.e. filing). It is an effective motion where the instrument is not forcefully pushed
PUSH
&
BACK & FORTH PULL
towards the apex and the preparation depths are allowed to diminish with each subsequent instrument. Disadvantages are, the process is tedious and time consuming. 6. Balanced force instrumentation It is the most efficient way to cut dentin. It is specifically designed to operate k type endodontic instruments and should not be used with Broach type or Hedstroem type instruments, since either possesses left hand cutting capacity.
&
PUSH TURN PULL
It is introduced by Roane et.al in 1985. He described the technique as "positioning and pre-loading an instrument through a clockwise rotation and then shaping the canal with a counter clockwise rotation".
4.
Watch - Winding It is the back and forth oscillation of a file (30 to 60) right and (30 to 60) left as the instrument is pushed forward into the canal. The back and forth movement of k-type files and reamers causes them to plane dentinal walls efficiently. This motion is very useful during shaping. 1. 2. 3. Less aggressive than turn and pull motion. Reduced apical ledge formation. It is effective with all k- type files.
PUSH
The technique is the file is pushed inwardly and rotated one quarter - turn clockwise. It is then rotated more than one half - turn counter clockwise. These alternate motions are repeated until the file reaches working length.
Advantages
&
CLOCKWISE COUNTER CLOCKWISE

MECHANICAL INSTRUMENTATION Engine Driven Instruments Can be used for opening root canals. They should not be used for canal preparation except as a last resort. The rapid revolution of an engine driven reamer, file or broach can create a ledge, a perforation or an obstruction especially when the instrument breaks after it binds particularly in the apical region where the root canal is narrow. Available as 1. 2. 1. Giromatic (KCET-04, AP-06) Racer 1. Gates Glidden Drill (AIPG-01) Power Driven Instruments Available as 1. 2. Gates Glidden drills Peeso Reamers
54
It has a long thin shaft ending in a flame shaped head with a safe tip to guard against perforations. The flame head cuts laterally and is used with gentle, apically directed pressure. The long shaft is designed to break at the neck, i.e. narrowest diameter that lies adjacent to the hand piece. If the drill binds during use, it will fracture at the neck of the shaft and extrude from the tooth. The fractured segment is easily removed by grasping the broken shaft with pliers and pulling it out of tooth. Uses
Giromatic Activates a stainless steel barbed broach or reamer in the root canal through a 900 reciprocating arc at a speed upto 1000 cycles/min. Disadvantages o It may pack the dentinal shavings in the canal. o Less effective for preparing root canals. o Longer time is needed for preparation. o Had a tendency to create ledges and to produce flaring at the apex.
Used to remove the lingual shoulder during access preparation for anterior teeth.
o o
To enlarge root canal orifices. To clean and shape the cervical third of root canals in the step back preparation.
It is inflexible and used in low speed. (KCET-97)
2.
Racer Uses a standard file and oscillates the file in the root canal. The instruments length can be adjusted to the working length using this contra angle. Disadvantages o Debris may be forced ahead of the instrument with resulting clogging of the canal or pushing of debris into periapical tissue.
2.
Peeso Reamer (COMEDK-06, AP-09) Has long, sharp flutes connected to a thick shaft. It cuts laterally and is primarily used for the preparation of post space when gutta percha has been removed from obturated root canal. Precaution o Both Gates Glidden and Peeso reamers are made of hardened carbon steel that corrodes easily. o These aggressive cutting instruments are inflexible and should be used with slow speed and with extreme caution to prevent over instrumentation and perforations. the
Precaution o When engine driven instruments are used, access to the apical foramen must be made first with hand instruments.

Ultrasonic and Sonic Instruments Have been developed for cleaning and shaping root canals. Ultrasonic piezoelectric instrument ceramic consists that of a unit generates MISCELLANEOUS Endodontic Irrigating Syringe
55
Used to carry and dispense irrigating solution into canal for cleansing during debridement of canal.
ultrasonic waves which activate a magneto strictive stack hand piece. The hand piece holds a k-file (AIPG-94) or a specially designed diamond file that when activated produces movements of the shaft of the file between 0.01 and 0.004 at a frequency of 20000 to 25000/ sec. The oscillating movements produce cutting action of the file and create a ultrasonic wave of sodium hypochlorite irrigant solution, which is delivered along the side of the file into the root canal. Before ultrasonic instrumentation the apical third of the root canal should be hand instrumented to at least the size of a No: 15 file. In curved root canals, a pre curved No:15, endosonic file is introduced into the canal to working length (1mm short of the apical foramen) and is activated. After activation, the file is moved in a circumferential manner with a smooth push pull stroke along the walls of the canal for a period of 1 min. The procedure is repeated with No:20 and 25 files. The ultrasonic file should be inserted into the root canal to the working length before activation to prevent ledge formation. The apical third of the canal should be filed cautiously to prevent transportation of the apical root canal and foramen. Sonic Hand Pieces Sonic hand pieces operate at 1500 to 6500 cycles / min when filing inside root canals. They are similar in shape and weight to dental hand pieces and are attached to existing air and water lines. These instruments are used in a manner similar to the ultrasonic system in instrumentation of the root canals. The only difference is that the sonic system uses water as an irrigant and does not usually require diamond files for the flare of the preparation. Type I: Bent instrument. Type II: Stretching or straightening of twist contour. Type III: Peeling-off metal at blade edges. Type IV: Partial clockwise twist. Type V: Cracking along axis. Type VI: Full fracture. He found that No. 10 file is the most frequently damaged instrument. He described the progression of breakage as first a starting point crack develops on the files edge and then metal fatigue fans out from that point, spreading towards the files axial center. SOTOKAWAS CLASSIFICATION OF INSTRUMENT DAMAGE Sotokawa classified the types of damage to instruments as, Endodontic Stoppers Used to place on file or reamer to help in determining the length of the canal. Files or reamers are measured from stopper to apex of root to determine the length of the canal. Stoppers are colour coded to correspond to a particular file or reamer or a single a colour of stopper is used for all files or reamers. Sterile Absorbent Paper Points Used to dry pulp chambers of canal. Size of the point corresponds to width of the canal Sizes are available from extra fine to extra coarse
*****
PERIODONTIA Microbiology of Periodontal Diseases
20
PLAQUE
1st introduced by BLACK (1898) to describe microbial colonies on tooth surfaces Restricted to denote only those deposits that are predominantly microbial in nature Its a lining, organized community of microorganism that usually consists of numerous species & subspecies embedded in an extracellular matrix composed of products of bacterial metabolism & substances from the serum, saliva, food (MAN-02, AIPG-06, AIIMS-07) Materia alba is a yellow or white soft sticky deposit consisting of bacteria but does not contain the regular internal pattern (AIIMS-92, AP-98) Plaque is a common causative factor for both caries and periodontal disease (PGI-05, AIIMS-95, 00, MAN-02, KCET-07) Plaque preferentially forms on the non self cleansing areas. Most of the plaque is seen on the gingival third of tooth surface (AIIMS-93, APPSC-99) PLAQUE COMPOSITION A. Water 80% (PGI-97, 98) B. Solid 20% i. Microorganisms: 70-80 % (MAN-01, AIIMS92,06) ii. >500 distinct microbial species found 1gm plaque has approx. 1011 bacteria Number of bacteria in supragingival plaque on a single tooth surface can exceed 109 1gm pure streptococcus cells packed by centrifugation contains 2.3 X 1011 bacteria One individual may contain 150 0r more different species Non-bacterial microorganisms - Mycoplasma species, Yeasts, Protozoa, Viruses Inter cellular matrix: 20-30% a. Organic matrix Polysaccharides 30%, by Bacteria dextran, levan, galactose, (MAN-95, PGI00). Dental plaque adheres to tooth because dextrans are insoluble and sticky. (AIIMS99, APPSC-99, PGI-99, 00) Protein 30%, albumin from GCF Glycoprotein from saliva Lipids 15% debris from disrupted bacteria, host cells & food debris Remaining - 25% unknown b. Inorganic matrix (KAR-04, 97, PGI-99) Predominantly - Ca & PO4 Trace elements Na, K
CLASSIFICATION Based on its position on the tooth surface toward the gingival margin 1. Supragingival plaque Found at or above the gingival margin. Marginal plaque when in direct contact with gingival margin Demonstrates a stratified organization of a multilayered morphotypes Gram Gram positive negative cocci rods, and short rods and outer predominate at the tooth surface filaments in the spirochetes predominate accumulation of bacterial
surface of mature plaque mass 2. Subgingival plaque Found below the gingival margin, between the tooth and gingival pocket epithelium Has more of anaerobic environment At the tooth-associated cervical plaque, adhering to the root cementum predominantly filamentous microorganisms; cocci and rods are also seen. Dominated by gram positive rods and cocci Deeper pockets filamentous organisms are less Apical part of the pocket filamentous organisms are virtually absent The apical border of the plaque mass is separated from the junctional epithelium by a layer of host leukocytes and the bacteria of this apical toothassociated region show an increased concentration of gram-negative rods Layers of microorganisms facing the soft tissue primarily gram negative rods and cocci along with filaments, flagellated rods and spirochetes Tissue associated plaque predominance of S. oralis, S.intermedius, Tannerella Peptostreptococcus forsythia and micros, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum Hence composition of subgingival plaque depends on pocket depth Apical part is dominated by spirochetes, cocci and rods; coronal part with more filaments Site specificity of plaque is significant with diseases of periodontium Marginal plaque initiation and development of gingivitis
BRIHASPATHI ACADEMYS S U B S C R I B E R
C O P Y
N O T
F O R
S A L E

Supragingival caries Tissue-associated subgingival plaque tissue destruction i.e., different forms of periodontitis PLAQUE AS A BIOFILM Biofilm has an organized structure, contains micro colonies of bacterial cells non randomly distributed in glycocalyx Lower plaque layers are dense, microbes bound together in a polysaccharide matrix with other organic and inorganic materials Loose layer present above the lower layer is often irregular and may extend into the surrounding environment Fluid layer borders the biofilm Dental plaque biofilm has a similar structure with open fluid-filled channels throughout the plaque mass. These channels act as circulatory system Bacteria are present and proliferate in an intercellular matrix through which the channels run. It functions as a barrier too Intercellular matrix consists of organic and inorganic materials derived from saliva, gingival crevicular fluid and bacterial products Organic components of matrix polysaccharides, proteins, glycoproteins and lipids. Albumin is derived from crevicular fluid. Lipid materials contain debris from the membranes of disrupted bacterial host cells and food debris. Glycoproteins are derived from saliva that initially coats a clean tooth surface. Polysaccharides are produced by bacteria of which dextran is predominant (play a major role in maintaining biofilm integrity) Inorganic components of matrix 3. Colonization & Plaque maturation predominantly calcium and phosphorous and traces of Na, K and F. Inorganic constituents of supragingival plaque is primarily derived from saliva Inorganic constituents of subgingival plaque is derived from crevicular fluid Subgingival calculus is typically dark green or dark brown, that shows the presence of blood products hemorrhage Fluoride component of the subgingival plaque is derived from external sources such as fluoridated tooth pastes, rinses and fluoridated drinking water 3. associated with subgingival 2. 2. Initial Adhesion and Attachment of Bacteria Occur within few hours Phase 1: Transport to the surface Phase 2: initial adhesion (reversible) Phase 3: Attachment plaque and tooth-associated PLAQUE FORMATION STAGES 1. Formation of pellicle
21
subgingival plaque calculus formation and root
All surface of the oral cavity are coated with a pellicle (initial phase of plaque development Within nanoseconds after a vigorously polishing the teeth, a thin, saliva-derived layer, called the acquired pellicle covers the tooth surface (AIIMS-00, PGI-03, KCET-07) Pellicle formation is a prerequisite for plaque formation (PGI-03) Pellicle consists of glycoproteins (mucins), prolinerich proteins, phosphoproteins (Statherin), histidinerich proteins, enzymes (-amylase) and molecular receptors that act as bacterial adhesion sites Pellicle is first formed after tooth brushing (PGI-97, 99) Fully established pellicle formed in 30 min Within 24 hrs. Faintly erythrosine dye +ve & become 0.1 0.8 microns thickness
Adhere through specific molecules termed adhesins on the bacterial surface that interact with receptors in the pellicle Streptococcus sanguis binds to acidic proline-rich proteins, -amylase and sialic acid A. viscosus binds to cryptic segments of the proline-rich proteins. Such hidden receptors for bacterial adhesion are called Cryptitopes Phase 4: Colonization of the surface and biofilm formation
Microorganisms adhere to cells of bacteria already in the plaque mass The process of maturation includes, 1. Growth & coalescence of the discrete plaque colonies - Consisting mostly of streptococci evolve into more mature, highly complex structure covering a large portion of tooth surface Continued appositional growth by adherence to the tooth & plaque surface of additional organism & clumps of organism In deep older plaque streptococci and actinomyces are replaced by rod & filament like organisms (MAHE-98, KAR-PGET-01)
C O P Y
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Coaggregation Cell-to-cell recognition of genetically distinct partner cell types Occurs primarily through highly specific stereo chemical interaction of protein & carbohydrate molecule located on the bacterial cell surface (AP-99, 03) Ex: 1. 2. Fusobacteria coaggregate with all other human oral bacteria Veillonellae, Prevotellae 3. 4. 5. Fusobacterium Streptococcus sanguis Prevotella viscosus Capnocytophaga ochraceus with A. viscosus Red complex Streptococci show intrageneric coaggregation Most coaggregations are mediated by lectin like adhesins and inhibited by lactose and galactosides Primary Secondary loescheii, colonizers: colonizers: Streptococci P. intermedia, species, and P. F. Actinomycetes Capnocytophaga loescheii with Actinomyces Actinomycetes nucleatum with Green complex Capnocytophagae bind to Streptococci & & Orange complex Purple complex Microbial Complexes (COMEDK-10) Independent defined complex Yellow complex of Actinomyces naeslundii A. viscosus S. sanguis S.mitis S.oralis S.Gordonii S.intermedius V.parvula A.odontolyticus P.intermedia P.nigrescens P.micros F.nucleatum Eikenella corrodens Capnocytophga species A.A.comitans P.gingivalis Tannerella forsythus T.denticola
22
Early colonizers are either Independent of defined complexes or members of yellow and purple complexes Secondary colonizer: green, orange or red complexes Red complex species are associated with bleeding on probing
nucleatum, Porphyromonas gingivalis Coaggregation of gram negative species: F. nucleatum with P. gingivalis or Treponema denticola Special examples of coaggregation o Corncob formation seen in long standing supragingival plaque. Shows central gram negative filaments and outer coccal cells; Ex: Streptococci adhere to filaments of o Bacterionema matruchotii or Actinomyces species Test tube brush filamentous bacteria to which gram-negative rods adhere GROWTH OF PLAQUE Important changes occur within first 24 hours First 2 8 hours: streptococci cover 3 to 30% of the enamel surface Next 20 hours: steady growth After 1 day: biofilm formation Thickness of the plaque increases slowly with time increasing to 20 to 30 m after 3 days After 4 days: 30% of the total tooth crown area will be covered. Also there is a transition from the early aerobic environment characterized by gram positive facultative species to a highly oxygen deprived environment in which gram negative anaerobic microorganisms predominate During night time, plaque growth is reduced about 50% Early increase in plaque mass is largely by proliferation of bacteria already present and only a limited extent from the new adhering species Sources of nutrition for microbial organisms Early colonizers oxygen, lower redox potential of the environment Gram positive species sugars as energy source; saliva as carbon source
BRIHASPATHI ACADEMYS S U B S C R I B E R C O P Y | N O T F O R S A L E

Anaerobes & asaccharolytics amino acids & small peptides P. gingivalis succinate produced by Capnocytophaga ochraceus & protoheme from Campylobacter rectus; hemin iron from host hemoglobin Prevotella hormones BACTERIAL BEHAVIOR IN BIOFILMS Organisms in a biofilm are 1000 to 1500 times more resistant to antibiotics than in their planktonic (unattached) state Resistance of bacteria to antibiotics is affected by their nutritional of status, growth agents rate, and and formaldehyde temperature, pH, prior exposure to sub effective concentration antimicrobial slower growth rate Extra cellular enzymes such as -lactamase, formaldehyde lyase dehydrogenase inactivate the antibiotics. But Macrolides are an exception super-resistant Quorum expression sensing: of bacteria bacterial genes of biofilm has multidrug resistance communication through the between each other through the regulation of specific ECOLOGICAL PLAQUE HYPOTHESIS accumulation of signaling compounds that mediate inter-cellular communication When these signaling compounds reach a threshold level (quorum cell density), gene expression can be obtained Quorum sensing plays a role in expression of genes for antibiotic resistance and encourage the growth of beneficial species Conjugation exchange of genes through direct inter bacterial connection formed by sex pilus Transformation movement of small pieces of DNA from environment into bacterial SPECIFIC PLAQUE HYPOTHESIS REVISITED chromosome Translocation intra oral transmission of bacteria from one niche to another NONSPECIFIC PLAQUE HYPOTHESIS According to this hypothesis periodontal diseases results from elaboration of noxious products by the entire plaque flora It was thought that periodontal disease was believed to result from an accumulation of plaque over time in conjunction with a decreases response & increasing host susceptibility with age SPECIFIC PLAQUE HYPOTHESIS intermedia from host steroid
23
Control of periodontal disease depends on control of plaque accumulation Treatment of periodontitis by debridement & oral hygiene measures focuses on the removal of plaque & its products
Contradicts Some individuals with considerable amount of plaque & calculus & gingivitis never developed destructive periodontitis Site specificity in the pattern of disease
This theory was put forward by Loeshe (KARPGET-98) Only certain plaque is pathogenic & its pathogenicity depends on the presence of or increases in specific microorganism Acceptance of this was confirmed by recognition of A. actinomycetemcomitans as a pathogen in localized aggressive periodontitis A. actinomycetemcomitans is a gram negative facultative anaerobe (MAHE-01) A. actinomycetemcomitans produces enzyme myeloperoxidase that prevents the adhesion of actinomyces to the tooth structure (PGI-05)
The organism associated with diseases may also be present at sound sites, but at levels too low to be clinically relevant. Disease is a result of a shift in the balance of the resident micro flora drives by a change in local environment conditions The bacterial composition of plaque remains relatively stable despite regular exposure to minor environment perturbations. This microbial homeostasis is due to a dynamic balance of both synergistic & antagonistic microbial interactions
The disease is associated with specific strains of a given species It is likely that most, if not all, recognized periodontal pathogens demonstrated difference in phenotypic properties related to ability to cause disease i.e. genetic basis for variability in virulence properties among pathogenic strains to cause periodontal disease The green stains frequently seen on children teeth are caused by chromogenic bacteria (MAHE-94, AP-98)
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CRITERIA FOR IDENTIFICATION OF Pregnancy induced Gingivitis P.gingivalis T. forsythia P. intermedia C. rectus E. corrodens Chronic Periodontitis F. Nucleatum A. actinomycetemcomitans P. micros Treponema Eubacterium species Epstein Bar Virus-1 (EBV) factors P. intermedia
24
P. intermedia, V. parvula, Haemophilus, Capnocytophaga, Campylobacter
PERIODONTAL PATHOGENS Proposed by Sigmund Socransky The following are the criteria for a periodontal pathogen 1. Must be associated with disease, as evident by increases in the number of organisms at diseased sites 2. Must be eliminated or decreased in sites that demonstrate clinical resolution of disease with treatment 3. Must demonstrate a host response, in the form of an alteration in the host cellular or humoral response 4. 5. Must be capable of causing disease in experimental animal models Must demonstrate virulence responsible for enabling the microorganism to cause destruction of the periodontal tisuues Localized MICROORGANISMS ASSOCIATED WITH SPECIFIC PERIODONTAL DISEASES Periodontal health Primary Gram positive facultative species Members of genera Streptococcus & Actinomyces (S. sanguis, S. mitis, A. viscosus, A. naeslundii) Secondarily (small portion) Gram negative species (P. intermedia, Neisseria F. & Periodontal Abscess nucleatum, Veillonella) Beneficial species S. sanguis, Veillonella parvula, C. ochraceus Found in more number at sites where no attachment loss and in low number at sites where active periodontal destruction This H2O2 is is attributed lethal to to the the mechanism cells of of A. Periimplantitis producing H2O2 by S. sanguis. It is known that actinomycetemcomitans It is also observed that high levels of C. ochraceus and S. sanguis are associated with a greater gain in attachment after therapy Capnocytophaga, Necrotizing periodontal disease Aggressive Periodontitis
Human Cytomegalo virus(HCMV) A. actinomycetemcomitans common) P.gingivalis E. corrodens C. rectus F. Nucleatum B. capillus Eubacterium brachy Capnocytophaga P. intermedia Spirochetes F. Nucleatum P. intermedia P. gingivalis P. micros T. forsythia A. actinomycetemcomitans P. gingivalis T. forsythia P. micros C. rectus Fusobacterium Capnocytophaga Microbial shift during disease From gram positive to gram negative From cocci to rods (at a later stage to spirochetes) From non motile to motile organisms From facultative anaerobes to obligate anaerobes From fermenting to proteolytic species (most
Disease
Microorganisms Facultative (59%) Anaerobic (41%) Gram positive (56%) S. sanguis, S. mitis, S. intermedius, S. oralis, A. viscosus, A. naeslundii, P. micros Gram negative (44%) F. nucleatum,
Gingivitis
C O P Y
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Morphology Forms Culture characteristics Special pathogenic characteristics
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Actinobacillus actinomycetemcomitans Virulence Grows as a white, smooth, translucent, Small, short, straight or curved Non motile Gram negative rod with Five serotypes (a to e) rounded ends on blood agar Preferably identified on a specific growth medium under 5 to 10% carbondioxide (presents star shaped internal structure) (endotoxin), (forms factors
lipopolysaccharide leukotoxin in pores
non hemolytic colony
neutrophils, monocytes, lymphocytes), collagenase tissue Leukotoxin important role in pathogenicity (connective destruction), plays the
protease (cleaves IgG)
Tannerella forsythia Grows Non shaped Highly Pleomorphic rod Gram negative obligate anaerobe --motile, spindle under conditions Require several growth factors acetylmuramic from other (F.nucleatum) Porphyromonas gingivalis Grows Non motile Pleomorphic short) Gram negative obligate anaerobe (coccal to --anaerobically An aggressive periodontal pathogen Fimbriae adhesion Capsule phagocytosis Virulence proteases, collagenase factors hemolysin, defends mediate (Nacid) species slowly only Produces enzymes proteolytic to destroy and
anaerobic
immunoglobulins complement factors
Also induces apoptotic cell death
with dark pigmentation (brown, dark green or black) on blood agar because of a metabolic end product from blood (hemin) Has a strong proteolytic activity Prevotella intermedia and Prevotella nigrescens Short, round ended, non motile Gram negative rods -- Grow anaerobically,
with dark pigmentation (brown-black colonies) on blood agar
Less virulent and less proteolytic P.gingivalis than
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Special pathogenic characteristics
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Morphology
Forms
Culture characteristics Campylobacter rectus
Rare motile organism Short rod, curved --from (Vibrio) or helical Gram negative Motility results polar flagellum
Grows
anaerobically, Produces leukotoxin C.rectus is less virulent and less proteolytic than P.gingivalis
with dark pigmentation when sulfide is added to the medium, which is transformed to FeS, giving a gray stain Fusobacterium nucleatum
Induce apoptotic cell death in mononuclear Grows anaerobically on Cigar-shaped Gram negative bacillus Several sub species blood agar Can be easily identified on specific medium (purple colonies) with pointed ends and PMN cells and trigger the release of cytokines, elastase and oxygen radicals from leukocytes Bridging organisms between primary and secondary colonizers Eubacterium species Small Pleomorphic rod Gram positive obligate anaerobe E. nodatum E. brachy E. timidum Grows anaerobically, ---
but with difficulty on standard blood agar Spirochetes Ability through
to
travel viscous
Spiral, motile Gram negative helical rods (5-15 m long) with a diameter of 0.5 m
Treponema denticola T. vincentii T. socranskii T. pallidum
Extremely difficult to grow Need strict anaerobic conditions and a specific medium
environments Can degrade collagen and dentin T. IgA, denticola IgM, destroy IgG and factors proteolytic
complement through enzymes
***** Peptostreptococcus micros Rare cocci in periodontitis Gram positive Grows obligate anaerobically
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ORAL & MAXILLOFACIAL SURGERY Exodontia & Impactions
10
EXODONTIA
The ideal tooth extraction is the painless removal of the whole tooth, or tooth-root, with minimal trauma to the investing tissues, so that the wound heals uneventfully & no postoperative prosthetic complication is created
Basic Principles for Forceps Technique Beaks should be seated as far apically as possible without compression of the soft tissues Beaks of the forceps should be as parallel as possible to the long axis of the tooth Application of excessive force should be avoided
Table: 2.1 INDICATIONS FOR EXTRACTION Common Reasons 1. 2. 3. 4. 5. 6. Carious tooth that is non restorable Periodontally involved teeth Non treatable pulpal or periapical lesion To facilitate orthodontic treatment Teeth involved in significant infection (AIIMS96) Patients inability to afford more optimal treatment because of limited finances or time Table: 2.2 CONTRAINDICATIONS FOR EXTRACTION (KAR-03) Systemic 1. Uncontrolled metabolic disease Diabetes Hyperthyroidism Osteoporosis End stage renal disease 2. Malignant disease Leukemia Lymphoma 3. 4. 5. Uncontrolled cardiac diseases Blood disorders Patients on medication should be treated with caution (corticosteroids, immune suppressive, cancer chemotherapy drugs) 6. Pregnancy is considered a relative contraindication Basic Methods 1. 2. Close / Forceps / Intra-alveolar method Open/ Trans- alveolar method Basic Components of Extraction Forceps 1. 2. 3. Mechanical Principles of Extraction 1. 2. 3. Expansion of bony socket The use of lever and fulcrum The insertion of the wedge Most important principle during extraction is that there should be least trauma to both bone and mucosa (AIPG-95 & 02) British Technique Forceps always held with palm of hand above the handle of the forceps Patient is inclined 15 20 for extraction in the lower left quadrant & 30 45 in the other 3 quadrants Dentist stands behind the patient for extraction in the lower right quadrant & in front of the patient for all other extractions
Uncommon Reasons 1. 2. 3. 4. 5. 6. 7. Malpositioned & malopposed teeth Cracked teeth Fractured tooth which is non restorable Impacted teeth Supernumerary teeth Pre prosthetic extractions Teeth associated with pathologic lesions
Local 1. 2. 3. 4. Previous radiation treatment Hemangioma (KAR-PGET-2K3) Malignant tumors Acute oral infections Acute pericoronal abscess or pericoronitis AHGS, ANUG, Acute periapical, Acute periodontal abscess
Beak Hinge Handle

North American Technique Forceps are usually held with the palm of the hand below the handles of the forceps The patient is usually inclined 30 45for all extractions Table: 2.3 Tooth 1. 2. 3. 4. 1. 2. Max. CI, LI, C & PM Max. Root tips Max. Molars Max. PM Mand. Teeth Mand. Molars 1. 2. 3. 4. 1. 2. Forceps No No. 1 No. 65 No. 10 No. 150 & 151 Ash, Mead No. 1 No. 16 & Cowhorn (AIPG-01, 02) Basic Steps in Forceps Extraction
11
Grasping the tooth engaging the beaks 1-2 mm beyond the CEJ Expansion of the bony socket Mobilization of the tooth Delivery of the tooth
Basic Forces Used to Mobilize the Tooth
1. 2. 3. 4. 5.
Apical pressure first direction of force application (KAR-PGET-97, PGI-03) Buccal force Lingual force Rotational force Traction force
Table: 2.4 APPLICATION OF FORCE RELATED TO MAXILLARY TOOTH MORPHOLOGY
Tooth

Morphology Have conical roots Lateral incisors being slightly longer & slender Canine usually the longest Alveolar bone thin on the labial side Bifurcated usually in the apical 1/3 to 1/2 Roots extremely thin & subject to fracture Single root Have 3 large roots Buccal roots are relatively close together vigorous
Direction of Force Initial movement in labial direction, a less palatal force is then used, followed by rotational force (MAHE-94)
1.
Anteriors
2.
First Premolar Second Premolar 1st & 2nd Molars
Buccal pressures should be greater than palatal pressures Rotational force should be avoided Buccal pressure, lingual pressure and removal in buccal or lingual direction
3. 4.
Strong buccal force is used with minimal palatal forces
Table: 2.5 APPLICATION OF FORCE RELATED TO MANDIBULAR TOOTH MORPHOLOGY Tooth 1. Anteriors Morphology Have fine roots with flattened sides 3. Molars Have 2 roots flattened mesio distally Direction of Force Labial/buccal direction Extracted with lateral movements Only in the case of the 2nd premolar can initial movements be rotatory Figure of 8 with strong buccal and lingual motion is used to expand the socket & the tooth is delivered in the bucco occlusal direction
2. Premolars
Have tapered roots and their apices may be distally inclined
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Stobies technique Is used when two adjacent teeth have to be removed B. Dislocation of adjacent - tooth, TMJ
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Displacement of root - in the soft tissue, maxillary antrum Excessive hemorrhage Soft tissue injuries Syncope Respiratory arrest Cardiac arrest
Other Complications
Complications during the Post Operative Period Post operative pain due to Damage to hard and soft tissues Dry socket (alveolar Osteitis) Acute osteomyelitis of the mandible Traumatic arthritis of the tempero mandibular joint Post Operative Swelling due to Edema Hematoma formation Infection Delayed wound healing Trismus Creation of an oro antral communication Bleeding Temporomandibular injuries Facial nerve paralysis
Policy for Leaving Root Fragments 3 conditions must exist for a tooth to be left in the alveolar process Root fragment must be small Root deeply embedded in bone Root must not be infected
Risks is considered greater when Removal of root will cause excessive destruction of surrounding tissue Removal of root endangers vital structures Attempts of recovering the root can displace it into the maxillary sinus or tissue spaces MULTIPLE EXTRACTIONS Order of Extraction Maxillary teeth should be removed first because Infiltration anesthesia has more rapid onset Debris may fall into empty sockets of lower teeth Disadvantage hemorrhage may interfere with visualization Extract the most posterior teeth first 2 teeth most difficult to remove are the first molar and canine (MAHE-95 & 97) DRY
SOCKET
(ALVEOLAR
OSTEITIS)
FIBRINOLYTIC ALVEOLITIS (AIPG-99, 07, PGI-95, KAR-98, 04, AP-04) Is a Localized Osteitis involving either the whole or a part of the condensed bone lining a tooth socket (the lamina dura) Characterized by an acutely painful tooth socket containing bare bone and broken down blood clot (APPG-99, KAR-PGET-04) The pain of dry socket is usually experienced on the 3rd day of extraction (range is 2 4 days after extraction) Etiology Trauma and Infection Predisposing Factors Infection of socket occurring either before during or after the extraction Trauma: extractions Bacteriological origin: a number of bacteria are known to possess fibrinolytic activity. It has been recently postulated that Treponema Use of excessive force during
After multiple extractions, suture is placed at the inter dental septum (AP-05)
COMPLICATIONS OF EXTRACTION Failure to secure anesthesia Fracture of tooth root, mandible/ maxilla A. Complications occurring during Extraction Procedure
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denticolum may have an etiological role in the genesis of dry socket Pregnant than others Prevention Scaling of the teeth, any gingival inflammation should be treated prior to extraction Minimum amount of local anesthetic solution necessary for administered Teeth should be removed in the least trauma Prophylactic days reduces use the of antibiotics of especially Management Rest to the Temporomandibular joint Analgesics and anti inflammatory agents dry socket metronidazole from the day of extraction for 3-4 incidence significantly Wound debridement Nerve blocks preferred to LA infiltrations DELAYED HEALING Causes Management (KAR-99, AIPG-07) The aim of treatment should be the relief of pain and the speeding of resolution The socket should be irrigated with warm normal saline and degenerating blood clot should be removed Sharp bony spurs should be either excised with longer forceps or removed with a wheel stone A loose dressing composed of zinc oxide and oil of clove Analgesic tablets and hot saline mouth bath are prescribed A pack composed of Whiteheads Varnish contains benzoin, styrax, balsam of tolu, iodoform and solvent ether ACUTE OSTEOMYELITIS OF THE MANDIBLE Sometimes it may be difficult to differentiate between a patient affected with a severe dry socket and one suffering from Acute osteomyelitis of the mandible There is marked pyrexia and pain is very severe Often the mandible is exquisitely tender on extra oral palpation The onset of impairment of labial sensation some hours or even days after the extraction is characterized of acute osteomyelitis of the mandible Predisposing Factor Traumatic extraction of lower molar under LA, in the presence of acute gingivitis, periodontitis or pericoronitis Prevention
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To do prophylactic scaling of teeth whenever indicated To treat acute condition first and control the infection A patient suffering from this condition should be admitted as an emergency to a hospital where facilities for its effective treatment exist
women
and
those
taking
oral
contraceptives appear to be more susceptible
TRAUMATIC ARTHRITIS OF THE TMJ May happen if the lower jaw is not supported The risk can be minimized by supporting the mandible during surgery Difficult extractions should be done surgically should be
producing
analgesia
The most common cause of delayed wound healing is infection. Area of bone removal under the flap must be irrigated copiously with saline and all foreign debris must be removed with a curette
Wound dehiscence - If a soft tissue flap is replaced and sutured without an adequate bony support the unsupported soft tissue flap often sags and separates along the line of incision
Suturing the wound under tension Dry socket or alveolar osteitis causes delayed healing
TRISMUS (AIPG-01) Defined as inability to open the mouth due to muscle spasm Causes Post operative edema Haematoma formation Inflammation of the soft tissue, trauma to a muscle during the insertion of the needle, irritating solutions Low grade infection within the muscle
Treatment & Prevention Diazepam (valium) 2.5 to 5.0 mg four times per day doses coupled the application of warm moist compressions for 15 to 20 minutes per hour will usually relieve the symptoms in several days Mild analgesics may also be used for discomfort Physiotherapy consisting of opening and closing the mouth as well as movement from side to side

for 5 - 10 minutes every 3 - 4 hours will also assist recovery Hemorrhage or low grade infection may require hot mouth washes and the use of the antibiotic depends on the individual situation and the amount of infection present Use of sharp sterile needles The area of insertion can be cleaned and painted with a suitable antiseptic solution Needle is inserted less traumatically and no muscles are penetrated unnecessarily Avoid repeated insertions by carefully observing land marks and constantly improving technique OROANTRAL COMMUNICATION The apices of the maxillary cheek teeth are often closely related to the antrum. Sometimes the roots are separated from the antral cavity only by the soft tissue lining of the air sinus. If this is destroyed by periapical infection or perforated during removal of a tooth or root, an oro antral communication will be created Displacement of a root into the maxillary sinus is most likely to happen during extraction of the maxillary 1st molar (MAHE-95) Closure of oro antral communication Mucoperiosteal flaps should be raised and the height of the bony socket reduced without increasing the size of the bony defect 2. BLEEDING Causes The extraction of a tooth leaves an open wound with tooth soft tissues and bone open which allows additional oozing and bleeding The tongue is an inquisitive organ that tends to play with the area of surgery and occasionally dislodges blood clots which initiates secondary bleeding The tongue may also cause secondary bleeding by creating small negative pressure that suctions the blood clot form the socket One of the prime factors in preventing bleeding is to take a thorough history from the patient regarding this specific potential problem (MAHE-98) Primary control of bleeding during surgery depends on gaining control of all factors that may prolong bleeding Surgery should be as less traumatic as possible with clean incisions and gently management of the soft tissues Care should be taken not to crush the soft tissue since crushed tissue tends to ooze for long periods Secondary Bleeding (MAN-99, AIPG-00) 4. 3.
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Sharp bony spicules should be smoothened and removed All granulation tissue should be curetted from the periapical region of the socket, flaps and from around the neck of adjacent teeth The wound should be inspected carefully for the presence of any specific bleeding arteries. If such arteries exist in the soft tissue, they should be controlled with direct pressure or if pressure fails by clamping the artery with a hemostat and ligating it with a resorbable suture The bleeding socket is covered with damp 2 by 2 inch sponge that has been folded to fit directly into the area from which the tooth was extracted The patient bites down firmly on this gauge for at least 30 minutes Do not dismiss the patient from the office until hemostasis has been achieved If bleeding persists and careful inspection of the socket reveals that no arterial bleeding exists the surgeon should take additional measures to achieve haemostasis 1. Gelatin foam: this material is applied in the extraction socket and held in place with a figure eight suture placed over the socket. The absorbable gelatin sponge forms a scaffold for the formation of blood clot and the suture helps to maintain the sponge in position during the coagulation process Cellulose: (surgical) this material promotes coagulation more than the absorbable gelatin sponge when the cellulose is packed with the socket it almost always causes delayed healing of the socket. Therefore packing the socket with cellulose is reserved for more persistent bleeding Thrombin: Prepared from bovine thrombin. It bypasses all steps in the coagulation cascade and helps to convert fibrinogen to fibrin enzymatically which forms a clot .The sponge with the topical thrombin is secured in place with a figure 8 suture Collagen: promotes platelet aggregates and thereby helps accelerate blood coagulation Collaplug as a plug These materials are readily packed into a socket and are easier to use Collatape as a tape
Is caused due to some secondary trauma that is potentiated by the patients continuing to suck on
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the area or to spit blood from the mouth instead of continuing to apply pressure with a gauze sponge Management A local anesthetic should be administered so that the socket can be inspected All blood saliva is removed using suction The soft tissue is checked for diffuse oozing versus specific artery bleeding If hemostatis is not achieved by any of the local measures a laboratory screening test to determine hemostatic defect of the patient should be done If the patient has diagnosed coagulopathy then blood transformation with enough factor replacement is done to active initial hemostasis The patient is then given antifibrolytic agent such as amino caproic acid for 10 days following extraction Ecchymosis A final haemostatic complication relates to intra operative and operative bleeding into the adjacent soft tissues. Blood that escapes into tissue spaces especially subcutaneous tissue spaces appears as bruising of the overlying soft tissue 2-5 days after surgery. This is termed as Ecchymosis (AIIMS-92) Patients who undergo extraction and who are older than 50 years should be warned that they may have some ecchymosis of the submandibular region & may extend to neck and chest. There is probably no way to prevent it but can be minimized by atraumatic surgery. The patient should be told that the application of moist heat may hasten the resolution of ecchymosis TEMPEROMANDIBULAR JOINT INJURIES A. Trauma to the capsule The main cause is due to the stretching of the capsule of TMJ during extraction procedure when excessive force is applied This can be prevented by providing adequate stability to TMJ during extraction It is usually associated with post operative pain and limitation of movement Conservative management- rest to the joint. Soft diet, analgesics and restriction of opening B. Dislocation of condyle Application of excessive force mouth COMPONENTS 1. INDICATIONS 1. 2. 3. To luxate the teeth prior to forcep application To remove root remnants / inter radicular bone
15
Failure to support the mandible while extracting a difficult tooth More likely to occur under general anesthesia when masticatory muscles are relaxed
Management Reduction is done with the thumb wrapped with gauze or bandage to avoid injury by teeth and placed on the occlusal surfaces of mandibular posterior teeth and finger under the lower border of the mandible. Mandible is then pushed downward backward rotating the chin upwards Patient should be warned not to open his mouth too widely or to yawn. Patient is instructed to support the jaw during yawning Extra oral bandage support for the joint is applied and worn until tenderness in the affected joint subsides FACIAL NERVE PARALYSIS It is a postoperative complication caused due to injection of local anesthetic solution in the capsule or the deeper lobe of parotid gland or injection of local anesthetic solution superficial into the muscle of facial expression Postoperative patients may experience transient facial nerve weakness primarily involves the marginal mandibular branch but also occur in the zygomatic branch
DENTAL ELEVATOR
An instrument having blade that engages tooth / root and elevates them from the socket, also expands the alveolar bone
To remove teeth which cannot be engaged by forcep beaks (impacted / malposed / badly carious teeth)
4.
Can be useful during the extraction of multiple adjacent teeth (MAN-98, KAR-01, AIPG-02)
Handle usually large in size to facilitate a good grip, may be at a line or at right angle to shank (cross bar / T bar)
Causes
2. 3.
Shank should be strong enough to withstand and transmit forces Blade its working tip transmits forces to tooth / root / bone, can vary in size and shape
C O P Y | N O T F O R S A L E

RULES WHILE USING ELEVATORS Never use an adjacent tooth as a fulcrum unless that tooth has to be extracted Never use a buccal plate at the gingival line as a fulcrum except when odontectomy is performed or in the 3rd molar area Never use the lingual plate at the gingival line as fulcrum Always use finger guards to protect the patient in case the elevator slips Be certain that forces applied by the elevator are under control and exerting pressure in the correct direction When cutting through h the inter septal bone, take care not to engage the root of the adjacent tooth thus inadvertently forcing it from its alveolus WORK PRINCIPLES OF ELEVATORS 1. Lever Principle Lever is the simplest machine to change the direction or magnitude of a force 3. Wheel & Axle Principle Mechanical Advantage = l/h l = 10 mm h = 4 mm l/h = 10/4 = 2.5 Therefore, Mechanical advantage = 2.5 Where, E Effort l Length R Resistance h Height Formula for Wedge: E x l = R x h, or R/E = l/h
16
Mechanical Advantage Long arm is 3/4 of total length Short arm is 1/4 of total length Downward force of 10 lbs acting at end of long arm causes an output force of 30 lbs at end of short arm Therefore, the Mechanical Advantage is 3

Formula for Wheel & Axle: R/E or RW/ra Where, R Resistance E Effort RW Radius of Wheel Ra Radius of Axle
Mechanical Advantage =
= = 3
Mechanical Advantage = Rw/ra RW = 42 mm ra = 9 mm RW/ra = 42/9 = 4.6 Therefore, Mechanical advantage = 4.6 Each pound of pressure applied to the Crossbar is multiplied 4.6 times (MAHE (MAHE-2K) CLASSIFICATION I. According to their Working orking principle 1. 2. 3. Lever principle Straight elevator, Crane pick elevator Wheel & Axle Potts elevator, Winter elevator, Cryers, Winter cryers Wedge principle Apex elevators (AIPG-96), Apical elevators
Formula of Levers: R x SA = LA x E Where, R Resistance E Effort SA Short Arm LA Long Arm 2. Wedge Principle

II. According to their Form 1. 2. 3. Straight Straight elevator, Coupland elevator Angular Hockey stick, Warwick james, Miller elevator Cross bar Potts elevator, Winter elevators, Cryer, Winter cryers III. According to their Function 1. 2. 3. Tooth elevators Straight, Coupland, Miller, Potts, Warwick James, Winter elevator Root elevators Cryers, Winter cryers, Crane pick, Apex elevator Apical elevators Root tip pick 6 Fundamental steps 1. 2. 3. 4. Straight elevator (London hospital pattern / Coleman) Having a straight blade with one convex surface and another flat serrated working surface Handle may be serrated Most commonly used elevator to luxate teeth Definition Coupland retractor (Gouge) Having a straight blade with one convex surface and another concave working surface Used to elevate teeth (smaller one for unerupted tooth whereas larger one for widely spaced teeth) Cryer elevator An elevator with a triangular blade Working tip is angulated Have two working surfaces one convex and another flat Used for extraction of root stumps of mandibular molars (when one root is moved out and another left behind) Winter cryers A Cryer elevator with cross bar Principle and uses are same as that of Cryer IMPACTIONS 5. 6. Raising a flap Removal of bone Tooth division Removal of tooth Wound toilet Primary closure 8. 9. 7. Teeth shown radiographically to have i. Complicated root patterns or ii. Roots with conflicting lines of withdrawal When inserting immediate dentures Heavy buccal plate extraction
17
suggests difficult forceps
10. Teeth exhibiting bruxism may have denser bone & stronger PDL attachment
An impacted tooth is a tooth that is completely / partially unerupted at its chronological age and is positioned against a physical barrier, such as another tooth, bone / soft tissue, so that its further eruption is unlikely described according to its anatomic position
CLASSIFICATION OF IMPACTED TEETH Classification helps to Describe the general position of the impacted 3rd molar Aids in estimating the difficulty in removing the tooth Maxillary and Mandibular 3rd molars are classified radiographically by angulation, depth, and length or relationship to the anterior aspect of the ascending mandibular ramus ASSESSMENT OF MANDIBULAR THIRD MOLAR IMPACTION Classification I. WINTERS (1926) 1. 2. Based on ANGULATION of long axis of 3rd molar to long axis of 2nd molar Based on relationship to occlusal plane of 2nd molar (DEPTH) II. PELL & GREGORY (1942) 1. Based on relationship to anterior border of ramus and distal aspect of 2nd molar
Root tip pick A delicate instrument with sharp, pointed angulated working tip Used to tease small root tips from their sockets
TRANSALVEOLAR/OPEN/SURGICAL EXTRACTION Indications 1. 2. 3. 4. 5. 6. Attempts at forceps extraction have failed Retained roots, especially those in close proximity to the maxillary sinus History of difficult or attempted extractions Heavily restored tooth Hypercementosed & ankylosed teeth Geminated & dilacerated teeth
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Table: 2.6 CAUSES OF IMPACTION Local 1. Obstruction to the normal path of eruption caused by Irregularity in position Density of overlying and surrounding bone Supernumerary tooth Pathological lesions like odontomes, cysts Thick scar band Lack of space in dental arch due to Crowding, and dental arch 2. 3. 4. 5. 6. Non absorbing, over retained deciduous teeth Non absorbing alveolar bone Ectopic position of tooth bud Associated soft tissue or bony lesions Habits involving tongue, finger, thumb sucking Table: 2.7 REMOVAL of IMPACTED TEETH Indications 1. 2. 3. 4. 5. 6. 7. 8. 9. Pericoronitis or its prevention Dental caries or its prevention Periodontal disease or its prevention Prevention of root resorption Odontogenic cysts & tumors Pain of unexplained origin Fracture of the jaw/tooth in the line of fracture Prosthetic problems e.g. under prosthesis Orthodontic relapse/facilitation with of orthodontic and/or tooth movement 10. Tooth interfering orthognathic reconstructive surgery 5. 1. 2. 3. 4. Contraindications Extremes of age Compromised medical status Excessive risk of damage to adjacent structures supernumerary tooth, discrepancy between dimensions of tooth 3. 1. 2. Systemic
18
Prenatal heredity Post natal conditions which interfere with its development like congenital syphilis Endocrine disorders of Thyroid Parathyroid Pituitary glands Downs Syndrome Osteopetrosis Cleidocranial dysostosis rickets, anemia, tuberculosis
Hereditary linked disorders
When there is a question about the future status of the second molar Uncontrolled active pericoronal infection
A. Classification Based on Angulation Employs a description of the angulation of the long axis of the impacted third molar with respect to that of the second molar Teeth with certain inclinations have a readymade pathway for withdrawal whereas pathways of teeth of other inclinations require substantial amounts of bone removal
Winters Classification According to the position of the impacted 3rd molar to the long axis of the second molar 1. 2. 3. 4. 5. 6. 1. Mesioangular Horizontal /transverse/inverted Vertical Distoangular Buccoangular Linguoangular Mesioangular Impaction The long axis of the impacted tooth is tilted towards the long axis of the second molar Most commonly seen - 43% of all impactions
| N O T F O R S A L E
C O P Y

2. Horizontal Impaction 3. 4. Long axis of the impacted tooth is almost perpendicular to that of the second molar 3% of all impaction least common Long axis of the impacted tooth runs in the same direction as that of the second molar 38% of all impactions Long axis of the third molar is angled away from that of the second molar 6% of all impactions It is the most difficult angulation for removal (MAHE- 95, AIIMS-96, APPG- 07) May cause fracture of ramus of mandible MAXILLARY THIRD MOLARS Relationship to the Occlusal Plane - Winters The depth of the impacted tooth is compared with the height of the adjacent second molar The degree of difficulty is measured by the thickness of the overlying bone Divided into POSITION A, B & C The highest position of the tooth is a level with or above the occlusal line Occlusal surface of the impacted tooth is level or nearly level with the occlusal plane of the second molar Position B Highest position is below the occlusal plane but above the cervical level of the 2nd molar Occlusal surface of the impacted tooth is between the occlusal plane and cervical line of the second molar Position C Highest position of the tooth is below the cervical level of 2nd molar Occlusal surface of the impacted tooth is below the cervical line of the second molar Classification 3 Position A Classification 2 (Pell & Gregory) Classification 1 Distoangular Impaction Vertical Impaction Class II
19
The space available between the anterior border of the ramus and distal side of the 2nd molar is less than the mesiodistal width of the crown of the 3rd molar It denotes that the distal portion of the 3rd molar crown is covered by the bone from the ascending ramus
Class III The 3rd molar is totally embedded in the bone from the ascending ramus because of absolute lack of space The tooth is located completely within the ramus of the mandible
Based on the position of the long axis of the impacted maxillary third molar in relation to the long axis of the second molar 1. 2. 3. Vertical Distoangular Mesioangular
Based on Relative depth of the impacted third molar in the maxillary bone Class A The lowest portion of the crown of the impacted maxillary third molar is on a line with the occlusal plane of the second molar Class B The lowest portion of the crown of the impacted maxillary third molar is between the occlusal plane of the second molar and the cervical line Class C The lowest portion of the crown of the impacted maxillary third molar is at or above the cervical line of the second molar
Based on Relationship of the impacted maxillary third molar to B. Relationship to the Anterior Border of Ramus PELL & GREGORY Based on the amount of impacted tooth that is covered with bone of the mandibular ramus Divided into Classes I, II & III according to the space available between the second molar and the ascending ramus of the mandible Class I Sufficient space is available between the anterior border of the ascending ramus and the distal side of the second molar for eruption of 3rd molar
the maxillary sinus 1. Sinus Approximation (SA) - no bone or a thin partition of bone between the impacted maxillary third molar and the maxillary sinus is known as the Maxillary Sinus Approximation 2. No Sinus Approximation (NSA) - 2 mm or more of bone between the impacted maxillary third molar and the maxillary sinus is known as No Maxillary Sinus Approximation

MAXILLARY CANINE (MAN-98) Class I Palatally placed maxillary canine 1. 2. 3. 1. 2. 3. Horizontal Vertical Semi vertical Horizontal Vertical Semi vertical Crown is placed on palatal aspect and root towards the buccal alveolar process Class IV impacted canine in the alveolar process between the roots of the incisors and 1 premolar
st
20
2.
Amber Line Drawn from the surface of bone lying distal to 3rd molar to the crest of the inter dental septum between the 1st and 2nd molars Significance: The amount of alveolar bone enclosing the tooth the margin of the tooth lying in front of the amber line will be visible after raising the flap (UPSC-01, AIPG-04)
Class II Labially or buccally placed maxillary canine
3.
Red Line Perpendicular line dropped from amber line to an imaginary point of application for an elevator Mesioangular - CEJ on mesial surface of tooth Distoangular - CEJ on distal surface of tooth Significance: Used to measure the depth at which the impacted tooth lies in the mandible (KAR-PGET-01)
Class III involving both buccal and palatal bone
CLASS V impacted in edentulous maxilla ADA code on Procedures & Nomenclature Describes the amount of soft and hard tissue over the coronal surface of an impacted tooth Soft tissue impactions Complete bony impactions Partial bony impactions Combined ADA & AAOMS Classification of
Root Pattern of an Impacted Third Molar Determines Line of withdrawal of tooth Point of application of elevator Presence of curved roots may indicate tooth division RADIOLOGICAL PREDICTION OF INJURY TO THE INFERIOR ALVEOLAR NERVE Depends on the Relationship of the Tooth to the Canal 1. Related but not involving the canal Close proximity of the root to the canal but intervening bone separates the tooth 1. 2. 3. Separated Adjacent Superimposed
Procedural Terminology 07220: removal of impacted tooth - overlying soft tissue 07230: removal of impacted tooth - partially bony impacted 07240: removal of impacted tooth - completely bony 07241: removal impacted tooth - completely bony, with unusual surgical complications Winter WAR lines The position and depth of the tooth can be assessed by taken intra oral X-ray or even lateral extra oral xray and tracing can be done Originally advocated by George Winter 3 imaginary lines are drawn which are known as Winters lines Position and Depth: George & Winter WAR lines 1. White Line Drawn along the occlusal surfaces of erupted mandibular molars and extended posteriorly over the 3rd molar region Significance: Axial inclination of the impacted tooth gives an indication of the depth of the tooth 2. Related to changes in the canal Darkening of the root Dark and bifid root Narrowing of the root Deflected root Density of the root is altered, when the root impinges on the canal When the canal crosses the root apex, it can be identified by the double periodontal membrane shadow of the bifid root apex If sudden narrowing of the root is noted where the canal crosses, it indicates the deep grooving or perforation of the root or involvement of the root with the canal
Trace the outline of the root as well as the canal, which will show no disturbances
C O P Y
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The root may be seen deflected buccally, buccall lingually or mesially, distally when it reaches the canal 3. Related with changes in canal Interruption (loss of lines) of the dense roof and floor of the canal is seen as two white radio opaque lines (Tram lines) Either of those two lines or both may be disrupted to indicate deep grooving of the roots. Converging (narrowing) canal when canal crosses root apex, there is reduction in its diameter; hour our glass appearance indicates partial encirclement of the canal Diverted canal: The canal appears diverted, when it changes its direction. This is due to an upward displacement of the canal passing through the root Relationship with Inferior Alveolar Canal 4. 3. 2. Various Flap Designs 1.
21
Second molar sulcus incision flap ( (Envelope flap) Adequate for most mesially inclined and superficial impactions Second and first molar sulcus incision flap (Envelope flap) Allows better visibility Variant can be used d where third molar shelf is well developed Adequate molar for mesially inclined flap and with superficial impactions Second sulcus incision vestibular extension (Bayonet ayonet flap) Excellent buccal visibility Good access for bone removal and tooth sectioning Second molar paramarginal marginal flap with vestibular extension ( L- shaped flap, Wards flap) Optimizes marginal attachment healing next to second molar Requires that the main surgical to the third molar is at a distance from the second molar
BONE REMOVAL
Aims To expose the crown by removing the bone overlying it To remove the bone obstructing bstructing the pathways for removal of a tooth Adequate amount of bone should be removed to enable for elevation. But the extensive bone removal can be minimized by sectioning the tooth 2 ways of bone removal Hand piece and bur technique Chisel and mallet technique Atraumatic tooth removal Optimal socket healing By a consecutive sweeping action of the bur By an osteotomy cut - section of bone is removed Contra angle
Objectives
FLAP DESIGN (AIPG-93)

Allows optimal visibility Access to the impacted tooth Position of third molar Wide base Good blood supply Important for subsequent healing of the surgically created defect Critical anatomic structures Distal periodontium of the second molar Lingual nerve Buccinator muscle
Bone removal with burs
Factors to be considered
Bone removal with airotor
The complication of using an airotor at 30 30,000 rpm is the danger of developing emphysema (KAR-PGET-98)
Bone removal with chisels Disadvantage: patient discomfort while tapping Experience is needed
ORAL & MAXILLOFACIAL SURGERY Exodontia & Impactions The direction of the bevel of the chisel during bone cutting is towards the bone to be sacrificed (PGI-97, 98)
Bur technique Either 7/8 round bur or a straight number 703 fissure bur is used. Either of these burs can be used for bone removal or for sectioning of a tooth. Burs should be always used along with copious saline irrigation to avoid thermal trauma to the bone 1st step: The bur is used in a sweeping motion around the occlusal, buccal and distal aspect of the mandibular 3rd molar crown to expose it as to have its orientation 2nd step: Once the crown has been located the buccal surface of the tooth is exposed with the bur to the cervical level of the crown contour and a buccal trough or gutter is created The buccal trough should be made in the cancellous bone It is important that the adequate amount of trough is created to remove any bony obstruction for exposure and the delivery of the tooth, especially around the distal aspect of the crown. The distolingual portion of the tooth should be exposed without cutting through the lingual bony plate to prevent damage to the lingual nerve TOOTH REMOVAL Tooth belongs to the oral surgeon, but the bone belongs to the patient Primary goal is to remove all components of the tooth in an atraumatic way Tooth sectioning With burs With chisels Advantages Less postoperative pain and swelling Less damage to the adjacent tooth Danger of injury to the neurovascular bundle is less Risk of fracture of jaw is reduced WHARFE assessment - Macgregor 1985 (KAR-02) Path of Exit Space available Distal cusps covered Mesial cusp covered Both covered 0 1 2 3 Enlarged Impaction relieved 2 3 Normal Possibly enlarged 1/3 to 2/3 complete > 2/3 complete Follicles 0 1 1 3 Root shape and development Favorable curvature Unfavorable curvature Complex < 1/3 complete 1 2 3 2 80-89 90 + 3 4 35-39 mm 2 1-30 mm 31-34 mm 0 1 Height of the mandible
22
Angulation of 2nd molar 1-59 degrees 60-69 70-79 0 1 2
Difficulty Index for removal of impacted mandibular Winters classification Horizontal Distoangular Mesioangular Vertical 2 2 1 0 Classification Angulation Mesioangular Horizontal / transverse
third molars - Pedersen 1988 Difficulty Index Value 1 2

Vertical Distoangular Depth Level A Level B Level C Ramus Relationship / Space Available Class I Class II Class III Difficulty index Very difficult Moderately difficult Minimally difficult 7 to 10 5 to 7 3 to 4 1 2 3 1 2 3 Factors making impaction surgery more difficult According to A. Garcia & co workers, Pell-Gregory Pell classification is not a reliable predictor of surgical difficulty in vertical impacted lower 3 molars and
rd
23
3 4
Separated from 2nd molar Separated from inferior alveolar nerve* Soft tissue impaction * Present in young patient
Distoangular position Class III ramus Class C depth Long, thin roots* Divergent curved roots Narrow periodontal ligament* Thin follicle* Dense, inelastic bone* Contact with 2nd molar Close to inferior alveolar nerve Complete bone impaction * Present in older patients
classification of non-vertical vertical molars on Pell-Gregory Pell scales is difficult. Br J Oral Maxillofacial Surg 2000; 83:585-587 MISCELLANEOUS During extraction procedure, best time to administer analgesics is before the anesthesia wears off (AIIMS92) The sucker used to control excess hemorrhage should have a pressure of 0.14 kg per sq. cm (20 lb/sq.inch) During extraction, in case the maxillary tuberosity fractures but remains attached to the mucoperiosteum with intact blood supply, then the treatment is to reposition the flap and stabilize with sutures (MAHE-99, AIPG-01 01) Reactionary hemorrhage is that occurs after surgery within 24 hours (KAR-99) because of high blood pressure (MAHE-98) Warwick James elevator fits well in the operators hand and can be rotated between the thumb and finger (AIPG-01) Winters WAR lines Factors making impaction surgery less difficult Mesioangular position Class I ramus Class A depth Fused conical roots Roots 1/3rd to 2/3rd formed* Wide periodontal ligament* Large follicle* Elastic bone* ***** Medical history in extraction pts is to determine bleeding disorders (MAN-99 99) In an asthmatic pt treatment is usually done in afternoon (AIIMS-06) Best time for extraction in pregnancy is 2nd trimester
(TNPSC-99)
Rubber Band extraction is method of extraction done in pts with bleeding disorders like hemophilia & Hemangioma (COMEDK-03 03)

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NEET

HUMAN ANATOMY Scalp

severe bleeding, inflammation

Periosteum of the skull bones (continuous with endocranium at sutural lines)

Cephalohaematoma / traumatic cephalohydrocele takes shape of related bone

Arteries Supratrochlear Artery

Branches of INTERNAL CAROTID

Posterior to auricle Occipital Artery

BRIHASPATHI ACADEMY SUBSCRIBERS COPY NOT FOR SALE

Joins Sub-occipital venous plexus

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PHYSIOLOGY General Physiology

Peripheral Nervous system

Cerebrospinal Nerves Supplies Body wall and Limbs

Autonomic Nervous System

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Plasma Vol Pl. V x

BRIHASPATHI ACADEMY SUBSCRIBERS COPY NOT FOR SALE

along concentration and electrical gradient

BRIHASPATHI ACADEMY SUBSCRIBERS COPY NOT FOR SALE

BRIHASPATHI ACADEMY SUBSCRIBERS COPY NOT FOR SALE

PHYSIOLOGY General Physiology

lipid bilayer enriched in

BRIHASPATHI ACADEMY SUBSCRIBERS COPY NOT FOR SALE

cholesterol. It is positively charged and quite

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May have role in synthesizing membrane bound proteins

It transports proteins made by the ribosomes through the cisternae

Ribosomes 4 Spherical particles with 80 to 85 % of cells RNA

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They are responsible in movement of chromosomes during cell division

BRIHASPATHI ACADEMY SUBSCRIBERS COPY NOT FOR SALE

PHYSIOLOGY General Physiology

3. shape and move

through this membrane

BRIHASPATHI ACADEMY SUBSCRIBERS COPY NOT FOR SALE

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compounds (ATP) potassium calcium pump, potassium- hydrogen

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Equilibrium potential (in MV) + 60 - 90 - 70

iv. Other transport process o across epithelial Na+ K

CARBON NUMBERING SYSTEM

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BIOCHEMISTRY Carbohydrates HAWORTH (OPEN CHAIN) STRUCTURE OF CARBOHYDRATES

PYRANOSE RING STRUCTURES

Asymmetric carbon atom- C atom with 4 different groups attached to it.

No of isomers = 2n (n = no of asymmetric carbon atoms).

KEY POINTS ABOUT MANNOSE Occurs in glycoproteins Epimer of glucose at C2

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Rate Limiting Step Substrate Level Phosphorylation Steps

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Occurs in mitochondria Only aerobic pathway Amphibolic

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BIOCHEMISTRY Carbohydrates HEXOSE MONO-PHOSPHATE SHUNT

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BIOCHEMISTRY Carbohydrates GALACTOSE METABOLISM

DADH Oral Mucous Membrane

ORAL MUCOUS MEMBRANE

Functions 1. 2. 3. 4. 5. 6. 7. Protection Sensation Thermal regulation Secretion Absorption Excretion Aesthetics

proliferation and sequential differentiation

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DADH Oral Mucous Membrane

DADH Oral Mucous Membrane