Pathophysiology

Lecture 2
General Concept Of Diseases
In Cell

Candra D Hamdin, M.Sc., Apt.

Department of Pharmacology and Clinical Pharmacy
1. Fundamental Mechanisms of Health and
Disease
• The cell is the smallest functional unit that an organism
• Cells are remarkably similar in their ability to exchange materials with
their immediate environment, obtaining energy from organic
nutrients, synthesizing complex molecules, and replicating
themselves
• The most disease processes are initiated at the cellular level, an
understanding of cell function is crucial to understanding the disease
process
Normal Function of The Cell (Normal Concept)
Functional Components of The Cell
• Protoplasm is composed
of :
• water (70-85%),
• proteins (10-20%),
• lipids (2-3%),
• carbohydrates, and
• electrolytes
 The Nucleus

The nucleus is the control center for the cell.

HeLa cells stained for nuclear DNA with the blue fluorescent It also contains most of the hereditary material
Hoechst dye.
The central and rightmost cell are in interphase, thus their
entire nuclei are labeled.
On the left, a cell is going through mitosis and its DNA has
condensed.
The Cytoplasm and Its Organelles
• The cytoplasm surrounds the nucleus, and it is in the cytoplasm that
the work of the cell takes place.
• Cytoplasm is essentially a colloidal solution that contains water,
electrolytes, suspended proteins, neutral fats, and glycogen
molecules.
• Although they do not contribute to the cell’s function, pigments may
also accumulate in the cytoplasm.
• Some pigments, such as melanin, which gives skin its color, are
normal constituents of the cell.
• Embedded in the cytoplasm are various organelles, which function as
the organs of the cell.
• These organelles include the ribosomes, endoplasmic reticulum,
Golgi complex, lysosomes and peroxisomes, and mitochondria.
Ribosomes
• The ribosomes serve as sites of protein synthesis in the cell.
• They are small particles of nucleoproteins (rRNA and
proteins) that can be found attached to the wall of the
endoplasmic reticulum or as free ribosomes

• Free ribosomes are scattered singly in the cytoplasm or

joined by strands of mRNA to form functional units called
polyribosomes.
• Free ribosomes are involved in the synthesis of proteins,
mainly as intracellular enzymes.
Endoplasmic Reticulum
• The rough ER segregates these proteins from other
components of the cytoplasm and modifies their structure
for a specific function.
• For example, the production of plasma protein by liver cells
take place in the rough ER.
• All cells require a rough ER for the synthesis of lysosomal
enzymes.

• The smooth ER is free of ribosomes and is continuous with

the rough ER.
• It does not participate in protein synthesis; instead, its
enzymes are involved in the synthesis of lipid molecules,
regulation of intracellular calcium, and metabolism and
detoxification of certain hormones and drugs.
• It is the site of lipid, lipoprotein, and steroid hormone
synthesis.
 Golgi Complex
• The Golgi apparatus, sometimes called the Golgi complex
• These Golgi bodies are found near the nucleus and function
in association with the ER.
• Substances produced in the ER are carried to the Golgi
complex in small, membrane-covered transfer vesicles.

• Insulin, for example, is synthesized as a large, inactive

proinsulin molecule that is cut apart to produce a smaller,
active insulin molecule within the Golgi complex of the
beta cells of the pancreas.
• The Golgi complex modifies these substances and packages
them into secretory granules or vesicles.
Lysosomes and Peroxisomes
• The lysosomes can be viewed as the digestive system of the
cell.
• They consist of small, membrane-enclosed sacs containing
hydrolytic enzymes capable of breaking down worn-out cell
parts so they can be recycled.
• They also break down foreign substances such as bacteria
taken into the cell.
• All of the lysosomal enzymes are acid hydrolases, which
means that they require an acid environment.
• The lysosomes provide this environment by maintaining a
pH of approximately 5 in their interior.
• The pH of the cytoplasm is approximately 7.2, which
protects other cellular structures from this acidity
• In some inherited diseases known as lysosomal storage
diseases, a specific lysosomal enzyme is absent or inactive,
in which case the digestion of certain cellular substances
does not occur.
Mitochondria
• The mitochondria are literally the “power cells” of the cell
because they transform organic compounds into energy that
is easily accessible to the cell.
• Energy is not made here but is extracted from organic
compounds.
• Mitochondria contain the enzymes needed for capturing
most of the energy in foodstuffs and converting it into
cellular energy.
• This multistep process requires oxygen and is often referred
to as aerobic metabolism.
• Much of this energy is stored in the high-energy phosphate
bonds of compounds such as adenosine triphosphate (ATP),
which powers the various cellular activities.

Mitochondrial DNA is inherited materilineally (i.e.,from the

mother) and provides a basis for familial lineage studies.
The Cytoskeleton
• In addition to its organelles, the cytoplasm contains a
network of microtubules, microfilaments, intermediate
filaments, and thick filaments.
• Because they control cell shape and movement, these
structures are a major component of the structural
elements called the cytoskeleton.
Microtubules
• Microtubules function in many ways, including the development
and maintenance of cell form; participation in intracellular
transport mechanisms, including axoplasmic transport in
neurons; and formation of the basic structure for several
complex cytoplasmic organelles, including the cilia, flagella,
centrioles, and basal bodies.
• Abnormalities of the cytoskeleton may contribute to alterations in
cell mobility and function.
• For example, proper functioning of the microtubules is essential
for various stages of leukocyte migration.
Microfilaments

Microfilaments are thin, threadlike cytoplasmic structures

Three classes of microfilaments exist:
(1) thin microfilaments, which are equivalent to the thin actin
filaments in muscle;
(2) the thick myosin filaments, which are present in muscle
cells but may also exist temporarily in other cells; and
(3) the intermediate filaments, which are a heterogeneous
group of filaments with diameter sizes between the thick
and thin filaments.
Muscle contraction depends on the interaction between the
thin actin filaments and thick myosin filaments.
 The Cell Membrane
• The cell is enclosed in a thin membrane
that separates the intracellular contents
from the extracellular environment
• It provides receptors for hormones and
other biologically active substances,
participates in the electrical events that
occur in nerve and muscle cells, and aids
in the regulation of cell growth and
proliferation.
• The cell membrane consists of an
organized arrangement of lipids
(phospholipids, glycolipids, and
cholesterol), carbohydrates, and proteins
CELL METABOLISM AND ENERGY SOURCES
• Energy metabolism refers to the processes by which fats,
proteins, and carbohydrates from the foods we eat are
converted into energy or complex energy sources in the cell.
• Catabolism and anabolism are the two phases of
metabolism.
• Catabolismbconsists of breaking down stored nutrients and
body tissues to produce energy.
• Anabolismis a constructive process in which more complex
molecules are formed from simpler ones.

Two types of energy production are present in the cell: the

anaerobic (i.e., without oxygen) glycolytic pathway, occurring
in the cytoplasm, and the aerobic (i.e.,with oxygen) pathways
occurring in the mitochondria.
The glycolytic pathway serves as the prelude to the aerobic
pathways.
Anaerobic Metabolism
Glycolysis is anaerobic process by which energy is liberated from glucose
It is an important source of energy for cells that lack mitochondria.

• Glycolysis requires the presence of nicotinamide-adenine dinucleotide

(NAD+), a hydrogen carrier.
• The end-products of glycolysis are pyruvate and NADH.
• When oxygen is present, pyruvate moves into the aerobic mitochondrial
pathway, and NADH subsequently enters into oxidative chemical
reactions that remove the hydrogen atoms.
• The transfer of hydrogen from NADH during the oxidative reactions
allows the glycolytic process to continue by facilitating the regeneration
of NAD+.
• Under anaerobic conditions, such as cardiac arrest or circulatory shock,
pyruvate is converted to lactic acid, which diffuses out of the cells into
the extracellular fluid.
CELL MEMBRANE TRANSPORT, SIGNAL
TRANSDUCTION, AND GENERATION OF
MEMBRANE POTENTIALS
Movement Across the Cell Membrane

Mechanisms of membrane transport.

(A) Diffusion, in which particles move to become equally distributed across the
membrane.
(B) The osmotically active particles regulate the flow of water.
(C) Facilitated diffusion uses a carrier system.
(D) In active transport, selected molecules are transported across the membrane
using the energy-driven (ATP) pump.
(E) The membrane forms a vesicle that engulfs the particle and transports it across
the membrane, where it is released. This is called pinocytosis.
Signal Transduction and Cell Communication

• Cells communicate with each other and with the internal and
external environments by a number of mechanisms, including
electrical and chemical signaling systems
• That control electrical potentials, the overall function of a cell,
and gene activity needed for cell division and cell replication.

■ Chemical messengers exert their effects by binding to cell

membrane proteins or receptors that convert the chemical signal
into signals within the cell, in a process called signal transduction.
■ Cells regulate their responses to chemical messengers by
increasing or decreasing the number of active receptors on their
surface.
Membrane Potentials
• Time course of the action potential recorded at one point of
an axon with one electrode inside and one on the outside of
the plasma membrane.
• The rising part of the action potential is called the spike. The
rising phase plus approximately the first half of the
repolarization phase is equal to the absolute refractory
period

(A). The portion of the repolarization phase that extends

from the threshold to the resting membrane potential
represents the relative refractory period
(B). The remaining portion of the repolarization phase to
the resting membrane potential is equal to the negative
after potential
(C). Hyperpolarization is equal to the positive relative
refractory period.
BODY TISSUES
• Groups of cells that are closely associated in structure and
have common or similar functions are called tissues. Embryonic Origin of Tissue Types
• Four categories of tissue exist: epithelium, connective All of the approximately 200 different types
(supportive) tissue, muscle, and nerve. of body cells can be classified into four basic
• These tissues do not exist in isolated units, but in or primary tissue types: epithelial,
association with each other and in variable proportions, connective, muscle, and nervous
forming different structures and organs.
Epithelial Tissue
Cell Differentiation
Epithelial cells have strong intracellular
• The formation of different types of cells and the disposition protein filaments (i.e.,cytoskeleton) that
of these cells into tissue types is called cell differentiation, a are important in transmitting mechanical
process controlled by a system that switches genes on and stresses from one cell to another
off.
• Embryonic cells must become different to develop into all
of the various organ systems, and they must remain
different after the signal that initiated cell diversification has
disappeared
Stratified and Pseudostratified Epithelium
• Stratified epithelium contains more than one layer of cells,
with only the deepest layer resting on the basement
membrane.
• It is designed to protect the body surface.
• Stratified squamous keratinized epithelium makes up the
epidermis of the skin.
• Keratin is a tough, fibrous protein existing as filaments in
the outer cells of skin.
• A stratified squamous keratinized epithelium is made up of
many layers.
• The layers closest to the underlying tissues are cuboidal or
columnar

• Pseudostratified epitheliumis a type of epithelium in which

all of the cells are in contact with the underlying
intercellular matrix, but some do not extend to the surface.
• A pseudostratified ciliated columnar epithelium with goblet
cells forms the lining of most of the upper respiratory tract.
 Representation of the various epithelial tissue types.
Glandular Epithelium
• Glandular epithelial tissue is formed by cells specialized to
produce a fluid secretion.
• The macromolecules typically are stored in the cells in small,
membrane bound vesicles called secretory granules.
• For example, glandular epithelia can synthesize, store, and secrete
proteins (e.g., insulin), lipids (e.g., adrenocortical hormones,
secretions of the sebaceous glands), and complexes of
carbohydrates and proteins (e.g., saliva)

• Epithelial glands can be divided into two groups: exocrine and endocrine glands.
• Exocrine glands,such as the sweat glands and lactating mammary glands, retain
their connection with the surface epithelium from which they originated.
 Connective or Supportive Tissue
• Connective tissue is unique in that its cells produce the
extracellular matrix that supports and holds tissues
together.
• Connective tissue has a role in tissue nutrition.
• The close proximity of the extracellular matrix to blood
vessels allows it to function as an exchange medium through
which nutrients and metabolic wastes pass.
• Adult connective tissue proper can be divided into two main
types: loose or areolar and dense connective tissue.
• Diagrammatic representation of cells that may be
seen in loose connective tissue.
• The cells lie in an intercellular matrix that is bathed
in tissue fluid that originates in capillaries.
• Loose con known as areolar tissue, is soft and pliable.

Dense connective tissue exists in two forms: dense irregular

and dense regular.
 Muscle Tissue
• Muscle Tissue Three types of muscle tissues exist: skeletal,
cardiac,and smooth.
• Skeletal and cardiac muscles are striated muscles.
• The actin and myosin filaments are arranged in large parallel
arrays in bundles, giving the muscle fibers a striped or
striated appearance when they are viewed through a
microscope.
• Molecular structure of the thin actin filament and the
thicker myosin filament of striated muscle.
• The thin filament is a double-stranded helix of actin
molecules with tropomyosin and troponin molecules lying
along the grooves of the actin strands.
• During muscle contraction, the ATP-activated heads of the
thick myosin filament swivel into position, much like the
oars on a boat, form a cross-bridge with a reactive site on
tropomyosin, and then pull the actin filament forward.
• During muscle relaxation, the troponin molecules cover the
reactive sites on tropomyosin.
Cell Junctions and Cell-to-Cell Adhesion

Three basic types of intercellular junctions are observed: tight

junctions, adhering junctions, and gap junctions

The chief types of intercellular junctions found in epithelial

tissue
Pathophysiology
Lecture 3
General Concept Of Diseases
In Clinical View

Candra D Hamdin, M.Sc., Apt.

Department of Pharmacology and Clinical Pharmacy
I. Fundamentals of Disease

A. Homeostasis
1. The human body strives to maintain internal stability.
2. The process of maintaining normal balance within the body is called
homeostasis.
I. Fundamentals of Disease (Continued)
B. Disease
1. When homeostasis is not
maintained, disease
ensues.
2. Medical professionals who
study diseases are called
pathologists.
II. Pathologists are practitioners who frequently specialize in the
field.
A. Two common specialties are:
1. Anatomic pathology – pathologists who perform autopsies to
determine cause of death
2. Clinical pathology – pathologists who review lab specimens to
determine evidence of abnormal tissue, presence of chemicals
II. Pathologists are practitioners who frequently specialize in the
field.
B. Pathophysiology – the study of abnormal
functions in the body and how disease
processes work.
III. Pathogenesis

A. The development of a disease is

referred to as pathogenesis (-genesis =
origin or development).
B. The sequence of events that leads from
cause of disease to structural and
functional abnormalities, to how the
disease manifests itself and finally to the
resolution or recovery of the disease.
III. Pathogenesis
C. Example: common cold
1. Cause = exposure and inoculation of cold virus
2. Incubation time = virus multiplies
3. Manifestation = host begins to have signs and
symptoms (sore throat, itchy eyes, runny nose,
etc.)
4. Recovery = return to previous state of health
III. Pathogenesis
D. pathogenesis of a diseases may be
explained in terms of time:
1. acute disease – disease of sudden onset
which runs a severe but short course
2. chronic – long-term (sometimes reoccurring)
illness
IV. Predisposing Factors (risk factors)
Factors that increase probability of a person’s becoming ill
1. Age
Newborn babies
1. immature immune system
2. liver enzymes necessary for detoxification of
some substances are often lacking
3. fewer nutritional reserves
4. less body fat to insulate against cold
IV. Predisposing Factors (risk factors)

1. Elderly
1) decrease in immune function
2) decline in homeostatic mechanisms
3) depression; isolation; malnutrition

2. Sex - some diseases are more prone to one gender than the other
1. men more likely to develop gout
2. women more likely to develop osteoporosis
IV. Predisposing Factors (risk factors)

3. Genetic makeup (familial tendencies for: diabetes, asthma,

migraines, etc.)
4. Stress - increases body’s production of corticosteroids, which
decreases immune system function.
IV. Predisposing Factors (risk factors)

5. Lifestyle - personal habits in regard to diet, exercise, weight control,

smoking, alcohol consumption, sexual practice
6. Occupation - exposure to loud noises, pollutants, repetitive
movements, heavy equipment, high places, etc.
IV. Predisposing Factors (risk factors)

7. Preexisting illness
1. illnesses can lower body’s resistance and make individuals more susceptible
to other diseases
2. chronic illness interferes with proper function of some body systems,
therefore complicating disease
IV. Predisposing Factors (risk factors)

8. Environmental exposure
1. prolonged exposure to cold or heat can lower the body’s resistance
2. exposure to allergens
3. long-term exposure to sunlight
4. long-term exposure to occupational chemicals
V. Two Main Disease Categories
* Disease processes can be categorized into one of two groups: structural
or functional
1. Structural Disease (sometime called Organic Disease)
a. involves physical and biochemical changes within the cells
b. structural changes in cells are initiated by two types of agents:
i. Exogenous - those that are external, i.e. trauma, chemical injury, and
microbial infections.
ii. Endogenous - those that are internal, i.e. vascular insufficiency,
immunological/ autoimmune reactions, and diseases that are a result of
abnormal metabolism.
V. Two Main Disease Categories
B. The hallmark characteristic of structural disease is the lesion.
The word lesion comes from Latin language and means “to hurt.”

Lesion is a widely used term to describe many types of cellular changes that result in tissue
abnormalities. (cuts, fractures, masses, etc.)

Lesions are primarily detected by observation with the naked eye or with a microscope.
V. Two Main Disease Categories
II. Functional Disease (sometimes called physiological disease)
1. Diseases in which the onset begins without the presence of any
lesion.
2. The basic change is physiologic and is referred to as a
pathophysiologic change.
3. Examples of functional disease are tension headaches and
functional bowel syndrome.
4. Although mental illnesses have been considered functional
disorders, present research now indicates that many have a
genetic or organic basis (on a biochemical level).
VI. Examples Of Varying Effects Of Structural And
Functional Diseases

Disease Type of Disease Nature of

Manifestations
Common cold Structural (viral infection) Structural (runny nose, sneezing)

Tension headaches Functional (muscle spasm)

Functional (pain)

Benign tumor that produces mass Structural (tumor)

Structural (mass)

Exogenous obesity caused by Functional (hunger)

craving food Structural (obesity)

Cancer of esophagus Structural (cancer) Functional (inability to eat)

VII. Closer Look at Causes of Disease
A. To better understand and identify different structural diseases
and their cause, they are commonly sub-classified:
1. Infectious Diseases
a. those diseases that are caused by invasion and colonization of pathogenic
microorganisms

b. examples of pathogenic infection: fungal infection, bacterial infection,

and viral infection
VII. Closer Look at Causes of Disease
2. Neoplasms (“new growth”)
a. the uncontrolled growth of abnormal cells
b. growth may be benign or malignant (cancerous)
VII. Closer Look at Causes of Disease
3. Immunologic Diseases
Three immunologic categories:
1. overreaction by immune system (hypersensitivity)
2. underreaction by immune system (immune deficiency disease such as AIDS).
3. autoimmune disease – destruction of one’s own tissues by antibodies produced by
one’s own immune system
VII. Closer Look at Causes of Disease
4. Nutritional Diseases- diseases created by
insufficient resources for the body
1. protein deficiency – difficulty in healing or
formation of new body tissue; decrease in
antibody production
2. vitamin or mineral deficiencies – may lead to
interference in biochemical reactions of
metabolism
3. Obesity
VII. Closer Look at Causes of Disease
5. Metabolic Diseases
a. an upset in the biochemical reactions that govern body processes or
metabolism
b. Sub-classified as nutritional because the upset is often connected to
carbohydrate, fat, or protein metabolism
VII. Closer Look at Causes of Disease
6. Genetic Diseases
a. inherited or hereditary diseases due to transmission of
defective gene(s) or chromosome(s) from one or both parents
b. examples of genetic diseases might be: diabetes, Down
Syndrome, hemophilia, cleft lip
VII. Closer Look at Causes of Disease
7. Congenital Disease (also referred to an anomaly or defect)
a. defect in fetal development that may create a functional (physiologic) or
structural (physical) abnormality which presents itself at birth
b. these defects may be genetic; they may be exposure to chemicals, drugs, or
viruses during the pregnancy; they may be a spontaneous event
VII. Closer Look at Causes of Disease
8. Trauma
a. physical force that mechanically disrupts the structure of the body (therefore,
disrupts body function)
b. result of trauma is generally referred to as an injury
c. results of trauma include bruises, abrasions, cuts, fractures, burns, etc.
VII. Closer Look at Causes of Disease
9. Physical Agents - diseases that result from physical agents such as
temperature extremes, electrical shock, radiation, and poisons
VII. Closer Look at Causes of Disease
10. Inflammatory Diseases - diseases that are usually secondary to
primary disease such as infection or autoimmune disease.
VIII. The Disease Process
A. Manifestations of Disease
a. To treat a patient, a physician must first know the manifestations of a
disease.
b. Manifestation refers to how a disease “presents or shows itself”.
VIII. The Disease Process
c. Manifestation is also called clinical presentation and includes both signs and
symptoms.
1. Signs
i. objective physical observations as noted by the person who examines the patient
ii. this examination is called a physical or the physical examination
VIII. The Disease Process
iii. During the physical, the health professional may use techniques such as:
• ausculation (use of stethoscope to listen to body cavities)
• palpation (feeling lightly or pressing firmly on internal organs or structures)
• percussion (tapping over various body areas to produce vibrating sound that is
indicative of air, fluid, size of organ)
iv. Examples of signs are: temperature, blood pressure, respiratory rate, abnormal heart
sounds, mass, enlarged organs, edema
VIII. The Disease Process
2. Symptoms refer to the patient’s awareness of abnormalities or
discomfort. Symptoms are not measurable and are based on the
patient’s subjective perception, i.e. pain, nausea, weakness, fatigue,
dizziness
VIII. The Disease Process
3. laboratory tests, radiologic, and clinical procedures to detect
chemical and physiologic abnormalities to aid in establishing the
diagnosis
VIII. The Disease Process
C. Etiology and Related Terms
a. The etiology of disease is its cause (term literally means the study of causes).
1. If the cause of a disease has never been discovered (disease is unknown),
the cause is referred to as idiopathic.
2. One may also refer to an idiopathic disease as “unknown etiology”.
VIII. The Disease Process
b. Iatrogenic disease (-iatro = medicine, physician) means that the
disease arose as a result of a prescribed treatment
*examples:
i. Cushing-like Syndrome as a result of steroid therapy
ii. immunosupression and/or anemia as a result of chemotherapy
VIII. The Disease Process
C. A nosocomial disease is one that was acquired from a clinical setting (e.g.
hospital; physician’s office; clinic).
1. postoperative patient develops staph infection from surgical instrument that wasn’t
properly sterilized
2. child develops cold after being exposed to other sick children at the pediatrician’s office
VIII. The Disease Process
D. Diagnosis
a. Process of assigning a name to a patient’s condition.
b. When clusters of findings with more than one disease are found, they are
called syndromes.
c. Diagnosis is needed to determine the treatment and potential outcome of a
disease.
VIII. The Disease Process
E. Treatment (therapy)
a. Treatment of a disease should be as precise as possible in order to attempt a
cure.
b. Treatment interventions may include: exercise, nutritional modifications,
physical therapy, medications, surgery, and education
VIII. The Disease Process
c. Three common therapies are:
1. Supportive therapy –
conservative therapy that includes
rest, optimal nutrition, fluids,
possible antibiotics to prevent a
secondary infection while the
immune system is recovering
VIII. The Disease Process
2. Palliative therapy – not a curative therapy; provides relief from signs and
symptoms of their disease
a. Examples of this therapy might include: steroids, pain relievers, possible surgery
(removal of tumor, etc.)
b. This treatment used for terminal illnesses and other serious chronic conditions for
which there is no cure
VIII. The Disease Process
3. Preventive therapy – care that is
given to prevent disease, i.e.
*Examples of preventive therapy might
include: mammograms, blood pressure
screenings, routine dental care, colon
cancer tests
VIII. The Disease Process
F. Prognosis
a. The prognosis is the predicted or expected outcome of the disease
b. Prognosis is often listed as:
1. Good (full recovery)
2. Guarded (full recovery may or may not occur)
3. Poor (not expected to recover)
IX. Additional Terminology
Communicable disease – a disease that can be transmitted from one
person to another
Epidemic – a disease that affects many people in a given region at the
same time
IX. Additional Terminology
Endemic – a disease that appears to be indigenous to a particular area
or region (not of epidemic proportions)
Localized disease – disease is confined to one area of body.
Systemic (generalized) disease – disease that spreads throughout the
body or to many systems
IX. Additional Terminology
Asymptomatic (Sub-clinical) disease– a disease in which symptoms are
not noticeable to the patient; presence of disease (signs) is detected by
routine physical or tests
Self-limiting disease – a disease that does not require treatment to be
cured; it will resolve on its own.
THE END OF 3rd COURSE
Any Questions?