Correlate: Adult Learning and Memory

Instructional Objectives: At the end of this module the student is expected to: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. Identify definitions/descriptions of teaching and learning. Identify the criteria for good teaching. Identify the criteria for good learning. Identify the definition/description of pedagogy and andragogy. Identify the factors that facilitate adult learning. Identify the principles of adult learning. Identify descriptions of the various steps involved in the inductive method of teaching. Identify descriptions of each phase of learning. Identify the learning outcomes proposed by Gagne. Identify descriptions of the different stages of memory. Identify descriptions of the two forms of memory. Identify their sites of integration. Identify the classification of memory. Identify characteristics of each. Identify the various hormones, neuropeptides and drugs that affect learning and memory. Identify descriptions of the 3 states of memory. Identify the various ways of improving memory. Identify descriptions of the 3 theories of forgetting. Identify descriptions of the different types of amnesia.

Definitions: Teaching refers to all those interactions that take place between the teacher and the students in order to bring about expected changes in behavior of the students. Such expected change in behavior, when it occurs, is called learning. Criteria for Good Teaching In order for teaching to be effective, the following criteria are suggested: 1. Teaching should be based on the psychology of learning. 2. Teaching should be well planned. 3. The teacher should have aims or goals to be accomplished. 4. Teaching should be made psychological rather than logical. 5. Teaching should provide varied experiences or situations that will ensure understanding. 6. Teaching should utilize the primary laws of learning: readiness, exercise and effect. 7. The process of teaching should utilize past experiences of students. 8. The learner should be stimulated to think and to reason. 9. Teaching should be governed by democratic principle. 10. There should be humor that evokes laughter in the classroom. 11. Evaluation should be made an integral part of learning process. Criteria for Good Learning: Learning is said to be good, if the following criteria are present: 1. It utilizes the theory of self-activity. 2. The learner has a motive for learning. 3. It utilizes the laws of learning. 4. It provides experiences or situations that will ensure understanding. 5. It utilizes the principle of transfer. 6. It has provision for individual differences. 7. It utilizes the principle of integration. 8. It utilizes group process. 9. The process involves utilization of many senses. 10. It is governed by democratic process. 11. It has provision for evaluation. 12. Both the faculty member and the students are happy. Pedagogy and Adragogy Pedagogy refers to the art and science of teaching children to learn. Androgogy in turn refers to the art and science of teaching adults to learn. Although children and adults learn continuously, adults have preferences about how they learn. Some adults rely heavily on feeling-based judgments and learn best form specific examples, from involvement and discussions. Such adult learners are called concrete experiencers. Some adults have a tentative, impartial and reflective approach to learning and are called reflective observers. Other adults have an analytical and conceptual approach, using logical thinking and rational evaluation, and are called abstract conceptualizers. Lastly, some adults approach learning pragmatically. They learn best from projects, applications and trying out some principles. These are the active experimenters. Learning in adults is facilitated in an atmosphere which:

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Encourages the learner to be active. Promotes and facilitates the learners discovery of the personal meaning of ideas. Emphasizes the uniquely personal and subjective nature of learning. Realizes the difference is good and desirable. Consistently recognizes peoples right to make mistakes. Tolerates ambiguity. Considers evaluation as a cooperative process with emphasis on self-evaluation. Encourages openness of self rather than concealment of self. Encourages people to trust in themselves as well as in external sources. Makes people feel that they are respected. Makes people feel that they are accepted. Permits confrontation.

Teachers who teach adults should therefore consider the following principles of adult learning: 1. Learning is an experience, which occurs inside the learner and is activated by the learner. 2. Learning is the discovery of the personal meaning and relevance of ideas. 3. Learning is a consequence of experience. 4. Learning is a cooperative and collaborative process. 5. Learning is an evolutionary process. 6. Learning is sometimes a painful process. 7. One of the richest resources fro learning is the learner himself. 8. The process of learning is emotional as well as intellectual. 9. The process of problem-solving and learning are highly unique and individual. As such, adult learning should consist of a cycle that involves 4 steps: Experiencing (concrete experiences), processing (reflective observation), generalizing (abstract conceptualization) and applying (active experimentation). The interrelationships between these steps are shown in the following diagram:

EXPERIENCING (concrete experiences) Using the experience participants have had already or providing them with an experience that furthers learning

APPLYING (active experimentation) Modifying old behaviors or testing new behaviors and practicing them in everyday situations

PROCESSING (reflective observation) Discussing the experiences participants have had already or sharing reactions and observations of the activity provided GENERALIZING (abstract conceptualization) Finding general trends and truths in the experience that participants have had already or forming reactions to new experiences into conclusions, new concepts, theories

THE EXPERIENTIAL LEARNING CYCLE

Step 1. Experiencing (Activity, doing)

Step 5. Applying (Planning more effective behavior)

THE ADULT LEARNING CYCLE Experiencing Applying Generalizing Processing

Step 2. Publishing (Sharing reactions and observations)

Step 4. Generalizing (Inferring principles about the real world)

Step 3. Processing (Activity, doing)

The Inductive Method There are two fundamental approaches to the learning process: the deductive method and the inductive method. The deductive method is referred to as pedagogy and will not be discussed. Focus is on the inductive method because it embodies all the principles of adult learning. There are seven steps in the inductive method: 1. Setting the climate Here, the teacher makes every effort to build an atmosphere conducive to learning. 2. Determining the learning objective This starts with life experiences, and involves issues, dilemmas, problems and concerns. 3. Doing In this step, the issues, dilemmas, problems and concerns are opened by making use of structured exercises, case studies, verbal descriptions, role plays, or personal reports. 4. Looking, Observing This focuses on what happened. IT examines what happened as closely as possible, and describes it as accurately as possible. 5. Thinking, Analyzing, Reflecting This step ask questions on What can we learn from the facts?, Why did what happened, happen?, What are underlying problems?, What are the implications?, What can we learn?. 6. Generalizing, Looking for Insights At this step, learner reach a conclusion, arrive at a principle or a generalization about what has been learned, or even relate this to an existing theory. 7. Acting In this step, the learner decides to act immediately, to delay acting, or not to act at all, as he sees fit. Both the deductive and the inductive methods of learning have their place in training and education. The inductive method offers that path of least preparation, and is thus more popular among teachers. As such, the deductive method is used too much beyond what is good for learning. Phases of Learning The process of learning involves the following phases: 1. Motivation phase In order fro learning to occur, the learner must be motivated. Motivation may either be: Incentive motivation (Achievement motivation) In this type of motivation, a reward is given whenever a learner achieves a goal.

Expectancy

2.

3.

4. 5.

6.

7. 8.

This is a process generated within the leader in which an individual strive to achieve a goal in anticipation of a reward. Such a reward may be on the near horizon. (e.g. scholarship) or on the far horizon (e.g. success as a professional). Apprehension phase Once a learner is motivated, the next step is reception of information. The learner must attend to the parts of stimulation that are relevant to his learning purpose. If he is listening to an oral communication (e.g. lecture) he must focus on its meaning a set of sentences, and not on the accent or pronunciation of the lecturer. If he is reading a textbook, he must attend to its meaning, and not on the arrangement of topics or print type. If he is observing a demonstration, he must focus on the events and objects displayed, and not on the mannerisms of the demonstrator. The process of attention involves a temporary internal state ( mental set) or readiness. The mental set adapted by the learner determines what aspects of the external stimulation are perceived. In other words, the registration of stimuli by the learner involves selective perception, and depends on previous learning, verbal cues, and direction. In order for selective perception to take place, the various features of external stimulation must be distinguished or discriminated. Acquisition phase Once the external stimulation has been attended to and perceived, learning cam proceed. The acquisition phase id that moment in time when new information enters short-term memory. During this phase, the material is transformed into a form, which is mist readily stored. This process is called coding. As a result, the material is sometimes distorted, and may either be simplified of embellished. Distortion becomes less if stimuli are grouped in certain ways, either as concepts or as principles. Retention phase This phase involves entry of learned entity into long term memory. This is the phase of learning that is least known because it is the least accessible to information. Recall phase In this phase, in order to find out whether there ha been a more or less permanent behavior modification, the learned modification is recalled so that it can be exhibited a performance. The process involved is called retrieval. Retrieval may be affected by external stimulation, and cues may be suggested to accelerate retrieval. A sophisticated learner supplies his own retrieval cues, and is thus called an independent learner. Generalization phase Retrieval of what is learned does not always occur in the same situation or within the same context that surrounded the original learning. As such, there must be generalization of the learning that has occurred. The recall of what has been learned and its application to new and different contexts is referred to as transfer of learning. Performance phase During this phase, the response generator organizes the learners response and allows him to exhibit a performance that reflects what he has learned. Feedback phase Many learning theorists consider this as the essence of reinforcement. The process of reinforcement operates in man not because a reward is actually provided, but because an anticipation of reward is confirmed.

Learning Outcomes There are five major categories of learning outcomes proposed by Gagne in 1972. All of them still apply as of the present time. They are: 1. Verbal information This includes acquisition of facts, names, principles and generalizations. For students, this serves as a necessary prerequisite for further learning. For graduates and professionals, this will be of practical importance during the learners lifetime, and will provide a vehicle for thought. 2. Intellectual skills This includes knowing how aside from knowing what. It includes discrimination, concepts, rules and higher order rules. 3. Cognitive strategies These are internally organized capabilities which the learner makes use in guiding his own attending, learning, remembering, and thinking. These govern the learners own behavior in dealing with his environment. As a result, the learner increasingly becomes a self-learner and an independent thinker. 4. Attitudes An attitude is an acquired internal state that influences the choice of personal action toward some class of things, persons or events. Many kinds of attitudes can be identified as desirable educational goals. 5. Motor skills These are learned capabilities that make possible the precise, smooth, and accurately timed execution of performance involving the use of muscles. Memory Memory is the retention and storage of learned material. From the physiologic point of view, memory can be divided into two forms: explicit memory ad implicit memory. Explicit memory (declarative memory, recognition memory) is associated with consciousness or awareness and is integrated in the hippocampus and adjacent entorhinal, perirhinal and parahippocampal portions of the medial temporal cortex. It consists of memory for events (episodic memory) and memory of words, rules and language (semantic memory). The amygdala is closely associated with the hippocampus and is concerned with encoding emotional memories.

Intrinsic memory (nondeclarative memory, reflexive memory) does not involve awareness. Its retention does not involve processing in the hippocampus but is presumed to be integrated in the striatum and certain parts of the cerebellum. It consists of nonassociative memory (habituation and sensitization), associative memory (classical and operant conditioning), skills and habits, and priming. Both explicit and implicit memory involve three stages: 1. Sensory memory Stimulation from the learners environment affects his receptors and enters the nervous system via a sensory register. This is the structure responsible for the initial perception of objects and events that the learner sees, hears or senses. The information remains here for only the smallest fraction of a second. 2. Short-term memory This lasts from second to hours, during which, processing takes place in the hippocampus, where the information is coded into a conceptual form. Material in short-term memory may last for a few seconds, but, if reviewed, may last for longer periods. During short-term memory, the memory traces are subject to disruption by trauma and various drugs. 3. Long-term memory This involves storage of information for years, and sometimes, for life. Memory can be classified into three types: 1. Semantic memory This refers to an individuals cumulative knowledge of the world such as language, concepts, and principles. 2. Episodic memory This relates to personally experienced events contextually bound to time and place. Loss can take place when the items to be recalled are not meaningful. 3. Procedural memory This refers to perceptual-motor skills or cognitive operations without intention or conscious awareness by the individual. Numerous hormones and neuropeptides have been found to affect learning and memory. Among these are: 1. ACTH neuropeptides These affect attention, concentration and motivational processes. 2. Glucocorticoids These eliminate learned behavior that is no longer relevant. Also, cortisol is believed to enhance excitability of neurons. 3. Neurohypophyseal hormones and related neuropeptides These modulate storage and retrieval of information. Neuropeptides related to vasopressin facilitate storage and retrieval of information; neuropeptides related to oxytocin inhibits storage and retrieval if information. 4. Release peptides and release-inhibiting peptides These affect learning and memory via: their influences on metabolic and endocrine processes; and their ability to elicit emotional and autonomic responses. As a rule, CNS stimulants like caffeine, physostigmine, amphetamine and nicotine, as well as CNS convulsants like picrotoxin, strychnine and pentylenetetrazol have been found to improve memory. However, the side effects or adverse effects of these drugs far outweigh their use as memory enhancers and are thus not recommended, except perhaps for caffeine (in moderation). There are three special states of memory: 1. Hypermnesia This refers to unusual memory for detail of a specific or selected situation. 2. Iconic memory This refers to the brief, detailed retention of visual stimuli. 3. Eidetic memory This refers to the unusual ability to glance at an object like a book page, look away, and recite the contents without error, as if reading the page. Forgetting Why do we forget? There are three theories of forgetting: 1. Trace decay theory According to this theory, what is learned makes some sort of change in brain cells, which gradually fade with time. 2. Interference theory According to this theory, forgetting is due to inhibition of old impressions and association by new ones. When material is organized, and learning is meaningful, the effect of interference is reduced. 3. Assimilation theory According to this theory, memory is active, and as new learning takes place, some old material is removed to make room for new material. Disorders of Memory Some of the disorders of memory include the following: 1. Alzheimers disease

2. 3. 4. 5. 6. 7.

This involves progressive loss of memory and cognitive function in middle age. Cognitive decline is correlated with loss of synapses initially involving the parietal and temporal lobes, with relative sparing of the frontal lobe. Senile dementia This is similar to Alzheimers disease, only that loss of memory and cognitive function occurs in the elderly population (60 and above). Confabulation In this disorder, the individual weaves data from the here-and-now into a recalled experience. Paramnesia This refers to a distortion of remembered data. Patchy amnesia In this disorder, the person has intact memory around a given amnesia hole. Anterograde amnesia This is characterized by loss of memory following a given significant life event, usually traumatic. Retrograde amnesia This is characterized by loss of memory for events immediately preceding a significant life event. Again, the life event is usually traumatic. DO NOT TAKE MILK when youre preparing a study available = Tryptophan

addtl notes: CAFFEINE (if youre sleepy) Coffee (5 oz cup) instant percolated Tea (5 oz cup) brew instant Soft drinks (12 oz) mountain dew tab (cans) coke shasta pepsi RC cola Red bull MEMORY TRICKS acronym acrostic link peg location system rhymes and jingles substitute words and homonyms verbatim memorizing

BEST CONDITIONS FOR MEMORIZING Get yourself some privacy. Be alert. Put aside other problems. Fill your stomach comfortably full. Avoid alcohol or drugs. Alternate between concentrating (45 min) and relaxing (15 min). Develop a positive attitude.

Module 1: Chipped Away

Instructional Objectives: At the end of this module the student is expected to: 1. 2. Identify the toxic chemical component of cassava. Discuss the structure and functions of the cell. 2.1. Identify/Recall the cell if given description or microscopic slide. 2.2. Identify the various organelles, inclusions and cytoskeleton if given descriptions. 2.3. Identify the differences between organelles and inclusions. 2.4. Identify the roles of organelles and cytoskeleton. 2.5. Identify the following when given descriptions. 2.5.1. cell cycle and its phases 2.5.2. mitosis and its stages 2.5.3. meiosis and its stages Identify/describe the 3 major sources of high-energy phosphates that take part in energy conservation or energy capture. Identify definition of respiratory chain, electron transfer, redox pair & oxidative phosphorylation. Identify the importance of standard reduction potential. Identify the standard reduction potential fro the common redox pairs. Identify the descriptions of the respiratory chain & oxidative phosphorylation. State the 4 major groups of inhibitors of mitochondrial ATP synthesis and their examples. State/identify the mechanism of action of cyanides. Recall the MLDL of cyanides. Enumerate/recall the diagnostic signs and symptoms of cyanide poisoning. State/identify the treatment of cyanide poisoning.

3. 4.

5. 6. 7. 8. 9.

1.

Identify the toxic chemical component of cassava. Cassava contains cyanogenic glycosides (linamarin) w/c is converted to toxic hydrocyanic acid or prussic acid when it comes in contract with linamarase.

2.

Discuss the structure and functions of the cell. 2.1. Identify/Recall the cell if given description or microscopic slide. The cell is the smallest unit of the living structure capable of independent existence. It is composed of two basic parts: cytoplasm and nucleus. The size varies from 8 to 200 m. Size: mycoplasmas (smallest) Shape: lining of blood vessels & body cavities flattened line ducts of glands cuboidal line most of the digestive tract rectangular & columnar RBC biconcave disks skeletal muscle elongated & fusiform nerve cells irregular in shape & possess elongated processes Nucleus contains blueprint for all cell structures & activities encoded in the DNA of the chromosomes largest organelle in cell 3 major components: o chromatin, genetic material o nucleolus, site of rRNA synthesis o nucleoplasm, macromolecules & nuclear particles (maintenance of cell) nuclear envelope: 2 parallel unit membranes that fuse to form nuclear pores fibrous lamina: lamins A, B, C; stabilize nuclear envelope nuclear pores: controlled pathways between nucleus & cytoplasm chromatin: 2 types o heterochromatin electron dense o euchromatin less coiled; nucleosome, basic structural unit nucleolus: spherical, 2 distinct component: o nuclear organizer o pars fibrosa o pars granulosa nuclear matrix: fits space between the chromatin & nucleoli o nucleoskeleton formation of a protein base to w/c DNA loops are bound Cytoplasm surrounds the nucleus and is bounded by the plasma membrane region of the cell responsible for the formation & release of energy, fro the synthesis of proteins, for growth and motility and for the many other functions area for the cell where most of the work is accomplished components are organelles, inclusions, & matrix 2.2. Identify the various organelles, inclusions and cytoskeleton if given descriptions. Organelles include: MITOCHONDRIA double membrane, powerhouse of the cell (ATP production), affected by toxic subs. a. outer membrane porin b. inner membrane cristae c. intermembrane space/outer chamber d. matris space/mitochondrial matrix/inner chamber RIBOSOMES protein synthesis w/c composed of tRNA and protein ENDOPLASMIC RETICULUM functions as mechanical support, synthesis of proteins and transport Rough ER maker of secretory proteins such as glycoproteins, protein secretion, consist of cisternae, presence of polyribosomes, synthesis of phospholipids, and initial glycosylation of glycolipids Smooth ER lacks polyribosomes, lipid synthesis, metabolism of CHO, & detoxification of drugs & poisons GOLGI APPARATUS glycosylation of lipids and proteins, cell secretion, it finishes, sorts, and ships cell products, has cisternae LYSOSOMES contains hydrolytic enzymes, diegestive compartments, suicide bag PEROXISOMES oval bodies enclosed by single membrane that transfer hydrogen from various substances to oxygen producing and then degrading hydrogen peroxide PROTEOSOMES are multiple-protease complexes that digest targeted fro destruction by attachment to ubiquinone Inclusions include: FOOD SUBSTANCES carbohydrate, fats GLYCOGEN PIGMENTS

a. b. c. d. e. f.

carbon phagocytosed by macrophages in the RS carotene carrots and tomatoes silver and lead hemosiderin & bilirubin melanin lipofuschin golden brown pigment found in the liver, nerve, & heart cells

2.3. Identify the differences between organelles and inclusions. Organelles are living substances performing definite functions. Inclusions are inert or non-living substances that do not perform definite functions. 2.4. Identify the roles of organelles and cytoskeleton. Cytoskeleton/Cytomusculature a network of fibers extending throughout the cytoplasm it provides structural support to the cell, cell motility, and regulation 3 main types of fibers; 1. microtubules (thickest) tubulin, provide framework that maintains the processes cylindrical shaped for movement; centriole and centrosome (9+2) 2. microfilaments/actin filaments 3. intermediate fibers myosin; producing forces associated with cell movements 2.5. Identify the following when given descriptions. 2.5.1. cell cycle and its phases The Cell Cycle is the alternation between mitosis and interphase. Phases: G1, S, and G2 Following Mitosis (M), cells initiate a new cycle (G1) in w/c RNA and protein synthesis takes place, and cell volume, previously reduced by in mitosis is restored to normal size cells may become nondividing (G o) or continue through G1 where they become committed to begin DNA synthesis (S) and complete the cell cycle (G2), the site of accumulation of energy to be used for mitosis and the synthesis for tubulin to be assembled in microtubules during mitosis and then proceed to mitosis (M) again. Following mitosis, two daughter cells are produced. 2.5.2. mitosis and its stages MITOSIS is a form of cell division resulting in the production of two cells, each with the same chromosome number and genetic complement as the parent cell. Phases: Prophase: condensation of chromosomes Prometaphase: chromosomes take on the appearance of double structures, each represented by a pair of sister chromatids Metaphase: chromosomes line up on the equatorial plane of the cell Anaphase: sister chromatids of each chromosomes are pulled apart and directed toward the opposite poles Telophase: completes daughter cell formation and is characterized by cytokinesis (division of cytoplasm) 2.5.3. meiosis and its stages MEIOSIS is the process in gametogenesis during w/c one replication of the chromosomes is followed by two divisions to produce four haploids. Stages: Meiosis is a continuum composed of two phases. Meiosis I: homologous chromosomes replicate substages: Leptotene, Zygotene, Pachytene, Diplotene, Diakinesis chromosomes duplicate so that there would be 23 pairs of duplicated chromosomes in all (22 pairs of autosomal and a pair of sex chromosomes) genetic exchange occurs due to crossing over at the completion of this stage, the daughter cell has 23 haploid number of duplicated and crossed over chromosomes Meiosis II: sister chromatids separate no additional duplication of DNA occurs chromatids separate so each daughter cells has the haploid no. of duplicated chromosomes **when two haploid gametes fuse, a mature oocyte is formed in females and a mature spermatozoon formed from one male and thus a new individual is formed, a diploid zygote Table 1: Comparison between Meiosis I and Meiosis II

Stages Prophase Metaphase Anaphase Telophase 3.

Meiosis I each homologues is composed of two sister chromatids that synapse and formed bivalents bivalents are at the equator homologues separate and move to opposite poles at each pole, there is one homologue from each pair of homologous chromosomes

Meiosis II duplicated chromosomes are present; one from each pair of homologous chromosomes duplicated chromosomes are at the equator centromeres divide and daughter chromosomes move to the opposite poles at each pole, there is the haploid no. and one of each kind

Identify/describe the 3 major sources of high-energy phosphates that take part in energy conservation or energy capture. GLYCOLYSIS breaking down of sugar, the major pathway found in the cytosol of all mammalian cells for the metabolism of glucose to pyruvate and lactate; it is also a main pathway for the metabolism of fructose and galactose derived from the diet and also provides ATP in the absence of oxygen; has a net formation of 2 high energy phosphates. CITRIC ACID CYCLE/KREBS CYCLE/TCA is a series of reaction in the matrix of the mitochondria that bring about catabolism of acetyl residues, liberating equivalents w/c leads to the release and capture of ATP; generates little amount of energy, by the conversion of succinyl CoA to succinate, one ~P is produced in the cycle thus, in a molecule of glucose the two turns of the TCA produces 2~P. OXIDATIVE PHOSPHORYLATION is a system in the mitochondria that couples respiration to the generation of ATP. It has the greatest quantitative source of ~P in aerobic organisms.

4.

Identify definition of respiratory chain, electron transfer, redox pair & oxidative phosphorylation. Respiratory chain or ETC series of catalyst that collect and transport reducing equivalents and direct them to their final reaction with oxygen to form water Electron transfer reaction occurs when electrons are transferred between an electron donor (reducing agent) and an electron acceptor (oxidizing agent) Redox pairs in a reaction w/c one losses electron (oxidation) and the other gains electron (reduction) e.g. NADH/NAD+ Oxidative Phosphorylation a system in the mitochondria that couples respiration to the generation of the high energy intermediate, ATP Identify the importance of standard reduction potential. 1) 2) 3) 4) It is a measure (in volts) of the relative affinity of the electron acceptor of each pairs of electrons. It allows prediction of the direction of the flow of electrons from one redox couple to another. It also indicated that the more negative the value, the greater is its capacity to yield electrons and the more effective it is as a reducing agent. It makes possible to calculate the overall change in free energy across the entire transport chain beginning with NADH.

Identify the standard reduction potential fro the common redox pairs. System Eo volts H+/H2 - 0.42 NAD+/NADH - 0.32 Lipoate;ox/red - 0.29 Acetoacetate/3-hydroxybutyrate - 0.27 Pyruvate/lactae - 0.19 Oxaloacetae/malte - 0.17 Ubiquinone;ox/red + 0.10 Cytochrome c1; Fe+/Fe+ + 0.22 Cytochrome a; Fe+/Fe+ + 0.29 Oxygen/water + 0.82 Identify the descriptions of the respiratory chain & oxidative phosphorylation. Respiratory Chain This involves transfer of electron from one substrate to another, w/c would release H+ as well as energy. This H+ and energy will be used in oxidative phosphorylation.

5.

Oxidative Phosphorylation During the RC in the mitochondrial membrane, the transfer of electrons from 1 substrate to another releases H+ as well as energy. The energy released during the oxidation pumps the H+ ions to the outer surface of the inner membrane. Because of this, substrates that are integrated into the complexes also act as proton pumps. Proton pumps push H+ into the outer surface of the membrane creating a proton circuit. The accumulation of protons (H+) of the outside membrane creates electrochemical potential deferences across the membranes. This is characterized by a change of pH and an electron gradient. The generated gradient, in turn, activates ATP synthase located at the several protein subunits known as F1-F0 complex. H+ in the protein circuit moves inward the mitochondrial matrix via F1-F0 subunits. The gradient produced by the passing protons are utilized by the activated ATP synthase to phosphorylate ADP and Pi forming ATP to result in oxidative phosphorylation produces 11 ~P in the form of ATP. 6. State the 4 major groups of inhibitors of mitochondrial ATP synthesis and their examples. 1) Proton pump inhibitors or Respiratory chain inhibitors block respiration in the presence of either ADP uncouplers arrest respiration by blocking the RC act at 3 sites and can therefore totally arrest respiration block both electron transport and proton pump e.g. cyanide and carbon monoxide: inhibits cytochrome oxidase antimycin A: block electron transfer from cyt b to cyt c rotenone and piericidin A: block by combining stoichiometrically w/ NADH-dehydrogenase amobarbital myxothiazol DCMU-3-1,1 dimethyl urea 2) Phosphorylation inhibitors or Inhibitors of ATP synthase or Oxidative phosphorylation abolish the burst of O2 consumption after adding ADP but have no effect on uncouplers stimulated respiration inhibitors w/c block oxidation and phosphorylation e.g. oligomycin: completely block oxidation & phosphorylation in intact mitochondria. However, by the presence of the uncoupler dinitrophenol, oxidation proceeds w/o phosphorylation indicating that oligomycin does not act directly on the RC but subsequently on a step in phosphorylation aurovertin: inhibit F1 venturicidin: inhibit Fo and CFo DCCD (Dicyclohexyl carbodiimide): block proton flow through Co and CFo Transport inhibitors or Inhibitors of ADP/ATP translocase either prevent the export ATP or the uniport of raw materials across the mitochondrial inner membrane inhibits adenine dinucleotide translocase inhibits the transporter of ADP into the mitochondria e.g. atractyloside: w/c inhibits OP that is dependent on the transport of adenine nucleotide across the inner mitochondrial membrane boukrekic acid NEM Krebs cycle inhibitors or Uncouplers w/c block one or more of TCA cycle enzyme, or an axillary rxns. action of the uncouplers is to dissociate oxidation in the respiration chain from phosphorylation e.g. 2,4 dinitrophenol valinomycin thermoyenin arsenite aminooxyacetate FCCP

3)

4)

7.

State/identify the mechanism of action of cyanides. Cynide inhibits mitochondrial cytochrome oxidase and blocks electron transport resulting in decreased oxidative metabolism and oxygen utilization. Results in lactic acidosis. Recall the MLD (minimum lethal dose) of cyanides. at average fatal adult dose of hydrogen cyanide is 50-60 mg cyanide poisoning in women can lead to teratogenic effects on the fetus adult men most predominant lethal dose: NaCN (sodium cyanide salts) = 150 mg KCN (potassium cyanide salts) = 200 mg HCN (hydrogen cyanide gas) = 50 mg

8.

Enumerate/recall the diagnostic signs and symptoms of cyanide poisoning. A. Initial effects headache faintness vertigo excitement anxiety burning sensation (mouth and throat) increase heart rate hypertension *nausea and vomiting are common; a bitter almond odor may be detected on the breath B. Later effects coma convulsions paralysis respiratory depression pulmonary edema arythmias

bradycardia C. Exposed to small moderate amounts rapid breathing dizziness headache nausea rapid heart beat Exposed to large amounts convulsions loss of consciousness

hypotension restlessness weakness eye irritation vomiting

D.

very slow heart beat breathing stops

9.

State/identify the treatment of cyanide poisoning. Amyl nitrite (ampule), Sodium nitrite (IV), Sodium thiosulfate (IV) The rationale for nitrite therapy is that the nitrites cause formation of methemoglobin by combining with hemoglobin. Methemoglobin has a higher affinity for cyanide than cytochrome oxidase and thus promotes its dissociation from this enzyme. Thiosulfate reacts with cyanide so the latter is slowly released from cyanomethemoglobin, forming the non-toxic thiocyanate, w/c is excreted in the urine. Pathway Glycolysis Rxn. catalyzed by Glyceraldehyde-3-phosphate dehydrogenase Phosphoglycerate kinase Pyruvate kinase Method of ~P prodn. Respiratory chain oxidation of 2NADH Phosphorylation at substrate level No. of ~P formed per mole of Glucose 6* 2 2 6 6 6 2 4 6 38 2

Citric Acid Cycle

Phosphorylation at substrate level Respiratory chain oxidation of Pyruvate dehydrogenase 2NADH Respiratory chain oxidation of Isocitrate dehydrogenase 2NADH Respiratory chain oxidation of ketoglutarate dehydrogenase 2NADH Succinate thiokinase Phosphorylation at substrate level Respiratory chain oxidation of Succinate dehydrogenase 2NADH Respiratory chain oxidation of Malate dehydrogenase 2NADH Total per mole of glucose under aerobic respiration Total per mole of glucose under unaerobic respiration

Module 2: A Fish Named Wanda

Instructional Objectives: At the end of this module the student is expected to: 1. 2. 3. 4. 5. Identify the physico-chemical properties of the cell membrane. Identify the descriptions of each briefly. Identify the different types of ion channels of the cell membrane. Identify descriptions of each. Identify the types of membrane junctions formed by adjacent cell membranes. Identify descriptions of the different processes involved in the transport of solutes and solvent across the cell membrane. Identify the differences between: 5.1. Simple diffusion and facilitated transport 5.2. Facilitated transport and active transport 5.3. Primary and secondary active transport 5.4. Endocytosis, exocytosis and transcytosis Predict whether a substance would be transported across the cell membrane or not, given the concentration of the substance intracellularly and extracellularly, as well as its relative permeability. Assuming the substance is transported, predict the direction of transport. Predict the possible effect on cells subjected to varying concentrations of solutions (hypotonic, isotonic, hypertonic). Identify the membrane potentials as to the following: 8.1. Types and their descriptions 8.2. Mechanisms involved 8.3. Ionic bases Identify the series of events, in sequence that takes place in the cell membrane of an excitable cell, from the time an adequate stimulus is applied up to the time an action potential develops.

6.

7. 8.

9.

10. Identify/Describe the mechanism of conduction of: 10.1. graded potential 10.2. action potential in myelinated and unmyelinated axons

1.

Identify the physico-chemical properties of the cell membrane. Identify the descriptions of each briefly. CELL MEMBRANES Functions: a) b) c) d) Structure: FLUID MOSAIC MODEL proposed by singer and Nicholson in 1972 cell membrane is composed of lipid bilayer in w/c globular proteins insert into and float within the bilayer membrane has a very elastic strx., only 7.5 to 10 nanometers thick it is composed of proteins (55%), phospholipids (25%), cholesterol (13%), other lipids (4%), and carbohydrates (3%) Characteristics: a) b) its a lipoprotein complex possesses the property of semipermeability allows substances of small molecular size to pass through largely attributed aqueous channels formed by integral proteins possesses the property of selective permeability allows movement of large molecules across it provided that molecules are needed by the cell; attributed to integral proteins, w/c provide mechanisms for movt. of certain subs. behaves as a core conductor ability of the cell membrane to allow the spread of excitation from one part to the rest of the membrane acts as a condenser ability of the cell membrane to store large amounts of energy (ATP) w/in it acts as a rectifier ability of the cell membrane to go back to its original state after excitation acts as a resistor limits movement of ions across the cell membrane as a result of friction offered the membrane to the flow of substances across it serve as receptor sites include receptors for the following substances: peptide hormones, neurotransmitters, microbial products, viruses, lectin, and antigens membranes receptors can be proteins, glycoproteins, lipids, or glycolipids

separates cellular contents from extracellular fluid serves as a physical barrier that regulate the transport of substance into/out of the cell maintains the composition of the intracellular membrane contains sites of reception of external stimuli or humoral messengers, w/c regulate cell activity

c)

d)

e) f) g)

h)

PROTEINS 2 types: 1) Intrinsic or Integral Proteins 70% of the membrane proteins they penetrate the membrane are amphipathic (the uncharges hydrophobic portions are located in the anterior of the membrane, charged hydrophilic portions lies in the surface) most span the entire membrane (transmembrane proteins): have 2 polar regions, one on each side of the membrane and are connected by a nonpolar segment in the nonpolar interior of the membrane 2) Peripheral or Extrinsic Proteins do NOT penetrate the membrane, are attached to the regions of one of the integral proteins or polar heads of the lipids; are NOT amphipathic; usually located on the cytoplasmic aspect of the cell membrane **Membrane proteins can serve as (1) channels, (2) carriers, (3) pumps, (4) receptors, and (5) enzymes **Protein kinase C is an impt. signal transduction protein **Fibronectin help cells to attach via all surface glycoproteins called integrins LIPIDS are amphipathic (hydrophilic/polar at one end and hydrophobic/nonpolar at the other end)

major lipid are phospholipids (phosphate radical is hydrophilic & polar while the fatty acid radical is hydrophobic & nonpolar) hydroxyl radical of cholesterol is hydrophilic while its steroid nucleus is hydrophobic glycolipids may function as receptors for antigens cholesterol/phospholipids ratio is inversely proportionate to the fluidity of the membrane 4 major phospholipids: o phospahtidylcholine addtl grp: choline outer o sphingomyelin addtl grp: choline outer o phosphatidylethanolamine 1 amino inner

CARBOHYDRATES are found projecting from the external surface of the membrane bound to lipids (glycolipids), form a fuzzy coat on cell surface referred to as glycolcalyx functions: o protection of the cell from interaction with inappropriate proteins, from both physical & chemical injuries o for cell-to-cell recognition o for cell adhesion 2. Identify the different types of ion channels of the cell membrane. Identify descriptions of each. Ungated Channels or Leak Channels always open; e.g. K+ leak channels Gated Channels 3 types: 1) voltage- gated channels: opening & closing of gates depend on the membrane potential : e.g. some Na+ & K+ channels 2) ligand-gated channels: require initial binding w/ substance (ligand) before channels open : extracellular mediator e.g. neurotransmitter-gated channels : intracellular mediator e.g. nucleotides & ions such Ca++ 3) mechanically-gated channels or stretch activated channels: respond to mechanical distortion : e.g. hair cells of inner ear 3. Identify the types of membrane junctions formed by adjacent cell membranes. TIGHT JUNCTIONS or ZONULA OCCLUDENS Most apical principal fxn is to form tight seal that prevent the flow of material between epithelial cells (paracellular) in either direction; seal adjacent epithelial cells in a narrow band just beneath their apical surface. ZONULA ADHERENS or FASCIA ADHERENS or ADHERING JUNCTIONS This junction encircles the cell; a noteworthy feature is the insertion of numerous actin microfilaments. hold epithelial cells and cardiac muscles tightly cadherins: transmemebrane proteins whose extracellular segments bind to each other catehin: connected to actin filaments GAP JUNCTIONS or NEXUS intracellular channels 1.5 to 2 nm in diameter that allows to free passage ions & molecular bet. them; permits membrane potential to pass from cell to cell occur almost anywhere along the lateral membrane; found in nearly all mammalian tissues-skeletal muscle is a major exception constructed 4 copies of transmembrane protein called connexins gap jxn protein unit called connexins from hexamins with a hydrophilic pore, individual unit of the gap jxn is called a connexon: connexon in adjacent cell membranes are aligned to from a hydrophilic channel bet. two cells metabolic inhibitors esp. that block OP can inhibit the formation of jxns DESMOSOMES or MACULA ADHERENS a complex disk-shaped structure at the surface of one cell that is matched with an identical strx. at the surface of the cell only fxn appears to be that of providing as esp. firm adhesion of one cell to the next hemidesmosomes: half of a desmosome; in the contact zone between certain epithelial cells & basal lamina Functional point of view on classification: 1) Adhering junctions: zonula adherens, hemidesmosomes, & desmosomes

2) Impermeable or tight junctions: zonula occludens 3) Communicating junctions: gap jxns

4. Identify descriptions of the different processes involved in the transport of solutes and solvent across the cell membrane. Transport across, but not through membranes all require metabolic energy Endocytosis a region of plasma membrane is pinched off to form an endocytic vesicle inside the cell. During vesicle formation, some fluid, dissolved solutes & particulate mat7eri7al from t7he7 ext7racellular medium are trapped inside the vesicle & internalized by cell. Types of endocytosis: a) Phagocytosis (cell eating) ingestion of large particles or microorganisms & usually occur only in specialized cells such as macrophages b) Pinocytosis (cell drinking) produce smaller endocytic vesicles (0.1 0.2 m in diameter) than phagocytosis. It is also known as a constitutive process because it occurs continually & specific stimuli are not requires. Types of Pinocytosis: fluid-phase endocytosis a nonspecific uptake of the extracellular medium & all its dissolved solutes receptor-mediated endocytosis a more efficient process that uses receptors on the cell surface to bind specific molecules Exocytosis a process of excreting impt. macromolecules out of the cell. These molecules are synthesized in the ER, modified in the Golgi complex, and packed inside the transport vesicles. These transport vesicles move to the cell surface, fuse to the cell membrane, and release the components outside the cell. Transcytosis (cytopemsis) refers to the transport of material when it is first endocytosed, then the vesicle is transported to the outer side of the cell where it fuses with the opposite plasma membrane and the content are released by endocytosis. This requires energy. Transport across and through membranes: Driving forces in the system: a. concentration gradient/force or chemical gradient force b. electrical gradient across the membrane c. pressure gradient: hydrostatic & osmotic pressure gradient d. metabolic energy in the form of ATP Simple Diffusion free movement of molecules by random molecular motion (Brownian movt.). There will be net movt. of solute from an area of greater concentration to an area of lesser concentration of solutes; net movt. stops when the concentration of solutes is uniform throughout the soln., diffusion is proportional to the area of the membrane and to the concentration gradient. The rate of net diffusion through a membrane follows Ficks law: J = - PA (Ci Co) * if (-) J = efflux where: J = net rate of diffusion * if (+) J = influx P = membrane permeability coefficient A = area of membrane Ci = conc. of subs. inside membrane Co = conc. of subs. outside membrane (Ci Co) = concentration gradient 2 types of Simple Diffusion: Diffusion through lipid matrix - permeability to a substance increase with the lipid solubility of substance - e.g. oxygen, CO2, alcohol, FA

Diffusion through membrane channels or pores diffusion of water-solute substance through the aqueous channels or pores formed by transmembrane proteins e.g. water, urea, ions

Osmosis net movt. of water (solvent) molecules from a region of high to low water conc. across a semi-permeable membrane; can be prevented by applying pressure to the more concentrated soln., the amount of pressure required is a measure of the osmotic pressure gradient bet. the 2 chambers. Osmotic pressure: pressure that would have to be applied to the soln. to prevent water movt. into the soln. from a compartment of pure water. The total solute concentration of a solution is known as its osmolarity or osmolality.

Bulk flow and Solvent Drag large numbers of water molecules tend to stream through the pores in unison ( bulk) rather than to move randomly as occurs in pure diffusion. When theres bulk flow, water tend to drag along some molecules of solutes: this is called a solvent drag. Protein-mediated/carrier-mediated transport require carrier transmembrane proteins characteristics: saturation there is a maximum rate at w/c the system can operate specificity specific to a substance 2 general types: 1) Active transport Primary Active Transport Processes - carrier-mediated & directly use energy in the form of ATP, include: a. Na-K pump or Na-ATPase exclude 3 Na+ from the cell & take 2 K+ into the cell for each mole of ATP hydrolyzed b. Ca++ pump in SR of muscle cells c. K+/H+ pump of gastric mucosal cells Secondary Active Transport Processes - make use of energy stored in an ion-concentration gradient that is established across the cell membrane by one of the primary pumps; includes: a. Na-glucose symport or Na-glucose co-transport of Na+ and glucose form outside to inside of cell by the same carrier molecule b. Na-Ca antiport or Na-Ca exchanger: 3 Na+ ions are transported into the cell for each Ca++ ion transported into the cell for each Ca++ ion transported out of the cell also called Na-Ca counterpart Facilitated transport/Facilitated diffusion do NOT require energy; net transport is along a concentration gradient Identify the differences between: 5.1. Simple diffusion and facilitated transport Simple Diffusion Net movt. from higher to lower concentration Do NOT require the presence of carrier proteins Does NOT require energy Fluxes do NOT saturate 5.2. Facilitated transport and active transport Facilitated Transport Requires the presence of carrier proteins Net movt. from higher to lower concentration Does NOT require energy 5.3. Primary and secondary active transport Primary Active Transport Carrier-mediated Directly uses energy in the form of ATP Secondary Active Transport Carrier-mediated Makes use of energy stored in an ion concentration gradient that is established across the membrane by one of the primary pumps Active Transport Requires the presence of carrier proteins Move substances uphill (from region of lower to higher concentration) Uses energy Facilitated Transport Net movt. from higher to lower concentration Require presence of carrier proteins Does NOT require energy Reaches a maximal flux since carrier proteins becomes saturated 2)

5.

5.4. Endocytosis, exocytosis and transcytosis Endocytosis Exocytosis Transcytosis

Engulf or ingestion of extracellular materials

Extrusion of materials from the cell

Material is first endocytosed, transported to the other side of the cell, fuse with opposite plasma membrane, then exocytosed Requires energy

Requires energy

Requires Ca++ and energy

6.

Predict whether a substance would be transported across the cell membrane or not, given the concentration of the substance intracellularly and extracellularly, as well as its relative permeability. Assuming the substance is transported, predict the direction of transport. Predict the possible effect on cells subjected to varying concentrations of solutions (hypotonic, isotonic, hypertonic). Isotonic solution if the total osmotic pressure of two solutions are equal, the solutions are said to be isoosmotic/isotonic if the extracellular and intracellular osmotic pressures are equal, there is no net movement of water at NaCl concentration of 154 mM, the volume of the cells is the same as their volume in plasma; this concentration of NaCl is said to be isotonic to the red cell Hypotonic solution if solution A has less total osmotic pressure than solution B, A is said to be hypoosmotic/hypotonic to B if the osmotic pressure of the ECF is lower than that of the cytoplasm, water enters the cell, the cell will continue to swell until the intracellular and extracellular osmotic pressure are equal this also refers to a solution with a concentration less than 14mM Hypertonic solution if solution A has a grater osmotic pressure than solution B, A is said to be hyperosmotic/hypertonic with respect to B in a hypertonic solution, water leaves the cell ( cell shrinking) and the cellular solutes become more concentrated until the effective osmotic pressure of the cytoplasm is again equal to that of the ECF this refers to a solution with concentration greater than 154 mM

7.

8.

Identify the membrane potentials as to the following: 8.1. Types and their descriptions 8.2. Mechanisms involved 8.3. Ionic bases MEMBRANE POTENTIALS or transmembrane potential (Vm) refers to the voltage difference between the inside and outside of the cell. Diffusion Potential is the voltage difference (electric gradient) created by net diffusion of ions. The concentration gradient which causes net diffusion of particles from a region of higher to a region of lower concentration is called the CONCENTRATION FORCE. 1. Equilibrium potential (Veq) The equilibrium potential of a given ion species is the voltage difference of Vm which is equal in force but opposite in direction to the concentration force affecting the ion. At the Veq there is no net movement of the ion because the forces acting upon it are exactly balanced. The Veq of the different ions has been determined. In most neurons in the body, the Veq for K+ is about (-) 90 mV, inside negative; the Veq of Na+ is about (+) 60 mV, inside positive. Thus, the Veq for each ion is different in magnitude and possibly, even in direction from those for other ions since the concentration gradients are different. The Veq for an ion can be determined by the NERNST EQUATION: Veq = - 61 log [C]i at 37 C [C]o where: Veq = equilibrium potential for a given ion [C]i = intracellular concentration of the ion [C]o = extracellular concentration of the ion

2.

e.g. Veq K+ = - 61 log [K+]i [K+]o The Resting Membrane Potential (RMP) or resting potential, or steady potential or polarized state

Resting membrane potential is the electrical potential difference (transmembrane potential) between the inside and outside of the cell that is not stimulated (a cell at rest). All cells under resting condition have an electrical potential difference across the plasma membrane oriented so that the inside of the cell is negatively charged with respect to the outside. This is due to the fact that there is slightly greater number of (-) charges than (+) charges inside the cell and a slightly greater number of (+) charges than (-) charges outside the cell. How is the RMP established? According to Bernstein, it is due to the relative difference in the membrane permeability to the different ions present inside and outside of the cell as well as to the concentration gradient for each ion. It is estimated that the cell membrane in the resting state is 50-70 times more permeable to K+ than Na+. The intracellular concentration of K+ is about 145 mmol (meq/L), and the ECF concentration is about 4 meq/L, resulting in a 30:1 conc. gradient. An opposite gradient exists for Na+ ions: intracellular Na+ is about 15 meq/L ECF concentration is about 150 meq/L. Normally at rest K+ tends to move out of the cell along its conc. gradient (from inside to outside of cell). Likewise Na+ tends to diffuse along conc. gradient (opposite direction). Since membrane is much more permeable to K+ than Na+, then passive K+ efflux (exit) will be much grater than passive Na+ influx (entry). Thus, more positive ions are going out than (+) ions entering until the inside of the cell is negative relative to the outside. The point at w/c the outer membrane becomes positive and the inner negative is known as the steady state of the cell, and the potential at w/c it occurs is known as the RMP. Thus, the RMP is largely due to K+ efflux (K+ exit). The RMP can be measured directly by the use of microelectrodes, on electrode inserted into the cell, and another one placed outside the cell. The RMP range from (-) 50 to (-) 100 mV depending upon the cell. In nerve cells, RMP varies from (-) 70 to (-) 90 mV. The RMP in nerves is usually at (-) 70 mV. At a resting potential of (-) 70 mV neither K+ nor Na+ is at its equilibrium potential. Thus, there is net movement of Na+ into the cell and K+ out. If such net ion movement occurs, you would expect the concentration of intracellular Na+ to increase and intracellular K+ to decrease. However, this does not occur; instead, conc. gradient of K+ and Na+ are maintained. This is because of the activity of the Na-K pump. Thus, the Na-K pump also maintains the RMP. As long as the conc. gradients of Na+ and K+ remain fixed and the ion permeabilities of the plasma membrane do not change, the electrical potential across the RMP will remain constant. 3. Graded Potentials (GPs) GPs are local changes in the membrane potential in either a depolarizing or hyperpolarizing direction. They are usually produced by some specific change in the cells environment (stimulus) acting on a specialized region of the membrane. They are called graded potentials because the amplitude of the potential change is variable (graded) and related to the magnitude of the external event w/c produces the change in membrane potential. Whenever a local change in membrane potential occurs a current will flow between this region and the adjacent regions of the plasma membrane that are at the resting potential. Thus, GPs cause to flow in the intracellular and extracellular fluids in the region around them. The greater the potential change, the greater the current flow. By convection, the direction in w/c positive ions move is designated the direction of current flow. Negatively charged particles simultaneously move in the opposite direction. Local current flow is decremental; i.e. its amplitude decreases with increasing distance; thus, the resulting change in membrane potential also decreases with distance form the site of origin of the potential. *Characteristics of graded potentials: 1) Response is graded and related to the magnitude of the external event 2) Can be summated 3) Has no threshold and has no refractory period 4) Is conducted decrementally (amplitude decreases with distance) 5) Duration varies with the initiating condition 6) Can be a depolarization or hyperpolarization 7) May be initiated by a stimulus, a neurotransmitter, or may be spontaneous *Examples of graded potentials include: a) Synaptic potential EPSP (excitatory postsynaptic potential) IPSP (inhibitory postsynaptic potential) b) Motor end plate potential EPP (end plate potential) MEPP (miniature end plate potential) c) Receptor potential (generator potential) d) Potential that occurs spontaneously; pacemaker potential 4. Action Potentials (APs)

APs are rapid alterations in the membrane potential resulting in a reversal of membrane potential polarity from the normal resting negative potential to a positive membrane potential and then ends with an almost equally rapid change back again to the negative resting potential. (ex. from -70 mV to +30 mV then back to -70 mV) Thus, we have the ff. phases of the AP: 1) Upstroke or depolarization phase this is the rapid depolarization of the membrane after threshold potential (TP) is reached. An AP occurs only when the membrane is depolarized from its resting potential to its TP by a stimulus. Overshoot this is the portion of the AP during w/c the membrane is positive. The peak of the AP is the overshoot potential. Down stroke or repolarization phase this is the rapid return of the membrane towards its resting potential. When repolarization is about 70% completed, the rate of repolarization decreases; this slower fall is called after-depolarization. Undershoot phase (hyperpolarization, after-hyperpolarization, positive afterpotential) the membrane potential becomes more negative than its resting value.

2) 3)

4)

The major factor in the production of these phases is the voltage-gated or voltage-sensitive K+ and Na+ channels. The voltage-gated Na+ channel has two gates: 1) activation gate or m gate w/c covers the extracellular side of the Na+ channel, and the 2) inactivation gate or h gate w/c covers the intracellular side of the channel. Both gates must be open for Na+ to flow through the channel. When the m gate is open, the channel is said to be activated; when the h gate is closed, the channel is said to be inactivated. The voltage-gated K+ channel is regulated by a single gate, the n gate, w/c covers the extracellular side of the channel. When the n gate is open, the K+ channel is activated. It does not have an inactivation gate. The m and n gates close during the resting state, and open when the Vm is depolarized (less negative). The h gates open when the Vm is polarized (at rest) and closed during the resting state, these are not inactivated because the n gates are open. The flow of ions during the AP is passive and depends upon the conc. gradient and on interactions among ions and with the channel. The gating mechanism produces the phases of the AP. How? 1) Upstroke this is due to a positive feedback cycle (Hodgkin cycle) or regenerative process. This is the positive feedback relation between depolarization and increased Na+ permeability, w/c leads to the rapid depolarizing phase of the AP. Recall that at rest, the m and n gates are closed and h gates are opened. When stimulus depolarizes the membrane, m gates on some of the Na+ channels open Na+ permeability increases more Na+ enters the cell membrane depolarizes further causes more m gates to open allows more Na+ to enter further depolarize the membrane and so on The process continues until all the voltage-gated Na+ channels have become totally activated (opened) cause reversal of polarity (overshoot) peak. 2) Downstroke this is due: a) inactivation of the Na+ channels, and b) activation of the K+ channels. The same voltage change that opens the ma gates also closes the gate. However, closure of h gates occur a few milliseconds after the gates open. Closure of h gates stops the flow of Na+ into the cell repolarization. K+ channels are activated by the opening of the n gates K+ efflux repolarization. K+ channels open slowly; they mainly open just at the same time that Na+ channels are beginning to become inactivated (are closing). The two events together (decreased Na+ entry and increased K+ efflux) greatly speeds the repolarization process. The h gates will reopen when the Vm returns to or nearly to the original RMP removing the inactivation of the Na+ channels. 3) Undershoot or positive afterpotential this is due to the slow losing of the K+ channels. The n gates close slowly when the membrane is repolarizing during the downstroke. Many K+ channels remain open for several milliseconds after the repolarization process of the membrane is complete. This allows excess K+ ions to diffuse out of the nerve fiber membrane becomes more negative hyperpolarization (positive afterpotential). Eventually the n gates close and the Vm returns to its resting level.

*Characteristics of after potentials: 1) Response is all-or-none and amplitude is independent of initiating event. All-or-none means that the nerve fiber under a given set of conditions gives a maximal response or no response at all.

2) 3) 4) 5) 6) 7) 8) 5.

Cannot be summated Has a threshold that is usually 10-15 mV depolarized, relative to the resting potential Has a refractory period Is conducted without decrement; the amplitude is constant Duration is constant Is a depolarization (with an overshoot) Is initiated by membrane depolarization

Threshold Potentials (TP) Threshold potential is the critical level of cell membrane depolarization at w/c an AP is initiated by a threshold stimulus; this is also known as the firing level. The TP of most excitable membranes is a level about 15 mV more depolarized than the RMP. Stimuli that are just strong enough to depolarize the membrane to this level are called threshold stimuli. If depolarization is less than threshold, the positive feedback cycle is not triggered and no AP occurs; the membrane will just return to its resting level as soon as the stimulus is removed. These weak depolarization are subthreshold potentials, and the stimuli that cause them are subthreshold or subliminal stimuli. Stimuli of more than threshold magnitude (suprathreshold stimuli) also elicit APs, but the APs have exactly the same amplitude as those caused by threshold stimuli. This is because once threshold is reached; membranes events are no longer dependent upon stimulus strength: APs either occur maximally or they do not occur at all (all or none law).

9.

Identify the series of events, in sequence that takes place in the cell membrane of an excitable cell, from the time an adequate stimulus is applied up to the time an action potential develops.

10. Identify/Describe the mechanism of conduction of: 10.1. graded potential 10.2. action potential in myelinated and unmyelinated axons Propagation of action potential in unmyelinated axon Once generated, AP must be conducted along the axon. Each AP triggers by local current flow, a new AP at an adjacent area of the membrane. The new AP is identical to the old AP & the new AP produces local currents of its own when depolarizes the next region adjacent to it produce another AP, & so on along the length of the membrane. The AP reaching the end is identical to the initial one. Unmyelinated membrane, conduction is slower because it needs to be stimulated to the entire membrane. Once depolarized, no point of stopping. Propagation of action potential in myelinated axon Myelin makes it more difficult for current to flow bet. intracellular and extracellular fluid compartments. Thus, APs do not occur along the sessions of the membrane protected by myelin (internode), but occurs at the node of Ranvier (point of discontinuity bet. successive internodes). Thus, AP jumps from one node to the next as it propagates along a myelinated fiber. This method of propagation of AP from one to node is called saltatory conduction w/c causes more rapid propagation of AP. Fibers with myelin have faster rate of conduction that needs excitation because depolarization takes place only at the nodes of Ranvier. Addtl notes: 1) If measured transmembrane potential (Vm) = Equilibrium potential (Veq) of a particular ion [Vm=Veq] that ion is in electrochemical equilibrium across the membrane NO NET FLOW of that ion across the membrane If Vm is of the same sign (+/-) but larger in magnitude then Veq of a particular ion [Vm>Veq; same sign] electrical force is larger than conc. force net movt. in the direction determined by the electrical force If Vm is of the same sign but less in magnitude than Veq of a particular ion [Vm<Veq; same sign] conc. force is larger than electrical force net movt. in the direction determined by the conc. force If Vm is of opposite sign to that of the Veq of a particular ion electrical and conc. forces are in the same direction net movt. determined by both electrical & conc. forces

2) 3) 4)

Module 3: Some Like It Hot

Instructional Objectives: At the end of this module the student is expected to: 1. Discuss the tissue. 1.1. Identify tissue and its types if given descriptions. 1.2. Identify epithelium and its types if given description or microscopic slide. 1.2.1. Identify the differences in characteristics & roles of each epithelium 1.2.2. Recall occurrences of each type in the body 1.2.3. Identify the descriptions of the various epithelial specialization Discuss membranes. 2.1. Identify the descriptions of serous, mucous and cutaneous/skin membranes. 2.2. Identify the differences in structure, occurrences, and roles between serous and mucous membranes.

2.

Discuss a gland. 3.1. Identify a gland if given description or microscopic slide. 3.2. Identify the differences between: 3.2.1. exocrine & endocrine glands 3.2.2. merocrine, apocrine, and holocrine glands 3.2.3. serous, mucous and mixed glands 3.2.4. simple and compound glands Identify the parts of a gland as an organ of secretion. 4. Describe the skin. 4.1 Identify the skin if given description or microscopic slide. 4.1.1. Identify the layers & sublayers 4.1.1.1. tissue content 4.1.1.2. structural content 4.1.1.3. vascular & nervous supply 4.1.2. Identify the roles of the skin

3.

5. Identify the degrees and severity of burns. 6. Identify the kinds and the harmful effects of ultraviolet radiation (UVR). 7. Identify the various skin types and their sunburn sensitivity. 8. Identify the ways of preventing sunburn. 9. Recommend treatment of sunburn. 10. Given problems of the same nature relate problem to the epithelium and the integumentary system.

TISSUE group of associated similarity structured cells that perform specialized functions 1) Connective provide structural support; medium for exchange; reservoir of hormones controlling cell growth; aid in defense & protection of body; storage of fat 2) Muscle contract & relax; comprise striated, cardiac & skeletal. 3) Nervous transmission of information; receive stimuli & conduct impulse 4) Epithelial line internal surface of body; protects underlying tissues; transcellular transport of molecules; secretion of mucous, hormones, enzymes; absorption of material from lumen; control movement of materials via selective permeability; detection of sensations. Epithelial tightly bound contiguous cells forming sheets covering/lining the body display little intracellular space & little extracellular matrix coz cells are close together separated from underlying connective tissues by extracellular connective tissue (basal lamina); basal surface rest on basement membrane avascular thus they tend to bound to a connective tissue, nourishment is thru diffusion apical surface of membrane are specialized high mitotic activity & turnover of cells Table 1. Types of Epithelia Type SIMPLE Lining: alveoli, loop of Henle, parietal layer of Brownian capsule, blood & lymph vessels, inner & middle ear, parietal & pleural cavities Ducts of glands, ovary covering, kidney tubules Lining: oviducts, ductuli efferentes, uterus, small bronchi, digestive tract Lining: trachea, primary bronchi, epididymis, ductus deferens, auditory tube, tympanic cavity, nasal cavity, lacrimal sac, male urethra, large excretory ducts Limiting membrane, fluid transport, gaseous exchange, lubrication/reducing friction, lining membrane Shape Locations Functions

Squamous

Flattened

Cuboidal

Cuboidal

Secretion, absorption, protection Transportation, absorption, protection, secretion

Columnar

Columnar Cells rest on basal lamina, not all reach epithelial surface

Pseudostratified

Transportation, absorption, protection, secretion, & lubrication

STRATIFIED Squamous (nonkeratinized) Squamous (keratinized) Cuboidal Flattened (w/ nuclei) Flattened (w/o nuclei) Cuboidal Lining: mouth, epiglottis, esophagus, vocal folds, vagina Epidermis of skin Secretion, protection

Protection

Lining: ducts of sweat glands

Absorption, secretion

Columnar

Columnar Dome-shaped (relaxed) Flattened (distended)

Conjunctiva of eye, large excretory ducts, portions of male urethra

Secretion, absorption, protection

Transitional

Lining: urinary tract, urethra

Protection, distensible

Epithelial Specializations: 1) Apical Domain microvilli w/c are small fingerlike cytoplasmic protections emanating from the free surface of the cell into the lumen; major function is transport & absorption stereocilia w/c are long microvilli found only in the epididymis & in long sensory hairs of cochlea; usually rigid because of their core of actin filaments; increase surface area; function in signal generation cilia w/c are long motile hair like structures emanating from the apical surface; core is composed of complex arrangement of microtubules known as axoneme; propels mucus & other substance over the surface of epithelium 2) Basolateral domain (in lateral membrane) occluding junctions w/c functions in joining cells to form an impermeable barrier, preventing material from taking an intracellular route in passing across epithelial sheath, anchoring junctions w/c maintains cell-to-cell or cell-to-basal lamina adherens; communicating junctions w/c permits movement of ions or signaling molecules between cells, thus coupling adjacent cells both electrically & metabolically (in basal surface) plasma enfoldings w/c are enfoldings of the plasma membrane that increase surface area available for transport; hemidesmosomes w/c attach the basal cell membrane to the underlying basal lamina

MEMBRANES epithelial layer and underlying connective tissue 4 types: 1) Mucous membrane (mucosa) lines cavities open to the exterior (e.g. digestive, respiratory, excretory, reproductive tracts) 2) Serous membrane (serosa) lines cavities not open to the exterior. There are two parts the visceral & parietal membranes w/c lines the pleural cavity (as pleural membranes), pericardial cavity (pericardium), and abdominopelvic cavity (peritoneum). Each coelomic cavity is lines with a serous membrane, parietal (somatic) on the outer side & visceral on the inner side. a) parietal (-pleura, pericardium, peritoneum) derived from somatic mesoderm. The parietal or somatic serous membrane is on the outer side of the coelomic cavity, the side with embryonic parietal or somatic mesoderm and ectoderm overlying. b) Visceral (-pleura, pericardium, peritoneum) derived from splanchnic mesoderm. This is on the inner side of the coelomic cavity, the side with embryonic splanchnic mesoderm and endoderm beneath. Cutaneous membrane (skin) Synovial membrane however, this is not really an epithelial membrane (therefore not a true membrane).

3) 4)

GLANDS originate from epithelial cells that leave the surface where they develop & penetrate into the underlying connective tissue, manufacturing a basal lamina around themselves; parenchyma or the secretory units & stroma represents the elements of the connective tissue that invade & support the parenchyma; manufacture their product intracellularly by synthesis of macromolecules that are usually packaged & stored in vesicles called secretory granules; secretory product maybe polypeptide hormones, mucigen, milk, combination of lipid, protein & carbohydrates. 2 types of glands based on method of distribution of their secretory products: 1) Exocrine secrete product via ducts 2) Endocrine lost connections to the originating epithelium, thus secrete their product into blood or lymphatic vessels for distribution *cytokines are signaling molecules; perform the function of cell-to-cell communication released by signaling molecules; act on target cells w/c possess receptors for a signaling molecules *glands that exhibit regulated secretory pathway concentrate & store their secretory products until the proper signaling molecule for its release is received *exocrine glands are classified accdng. to their secretions:

a) b) c) d)

mucous secrete mucinogens, large glycosylated proteins that upon hydration swell to become a thick viscous gel like protective lubricant known as mucin; e.g. salivary of tongue & palate serous membrane secrete an enzyme rich in watery fluid; e.g. pancreas mixed contain acini that produce mucous secretions as well as acini that produce serous secretions; e.g. submandibular cytogenic produce living cells; e.g. testis & ovary

*exocrine exhibit 3 mechanisms for releasing their secretory products: a) merocrine release via exocytosis, as a result neither cell membrane cytoplasm becomes a part of the secretion b) apocrine small portion of the apical cytoplasm is released along w/ the secretory gland c) holocrine secretory cell matures & becomes the secretory product *based on number of cells, histology: a) unicellular cup shaped columnar cells with flat basal nucleus & pale cytoplasm b) multicellular simple or compound; secretory portion may have tubular invaginations of lining epithelium or alveolar/acinar w/c are glandular invaginations of the epidermis w/c terminate in flask shaped structures *based on morphology: a) simple tubular b) simple branched tubular c) simple coiled tubular d) simple acinar e) simple branched acinar f) compound tubular g) compound acinar h) compound tubuloacinar SKIN largest organ of the body; composed of an epidermis & underlying dermis Functions: protection against injury, bacterial invasion & desiccation regulation of body temperature reception of continual sensations from the envt. excretion from sweat glands absorption of UV radiation Layers of the skin: epidermis outermost layer; stratified squamous; no blood vessels & few nerve endings; nourished by diffusion; deeper layers bathed with interstitial fluid from the dermis cells of epidermis: keratinocytes produce keratin melanocyets produce melanin langerhans cells participate in immune response merkel cells function for touch sensations layers of epidermis: statum basale deepest layer stratum spinosum stratum granulosum contain keratohyalin stratum lucidum layer of dead cells stratum corneum dead dry squamous cell, shed off

dermis tough, elastic, composed of collagen

Layers of dermis: papillary superficial region, contains papilla, capillaries, nerve ending reticular main deeper fibrous layer, consist of collagen & elastic fibers, provide skin strength, extensibility & elasticity, contains sebaceous gland, sweat gland, fat cells & blood vessels

ULTRAVIOLET RADIATION (UVR) often called black light is one of many kinds of waves that are placed on the electronic spectrum. UVR is between visible light and x-rays on the spectrum. It consists of high-frequency wavelengths, invincible to the human eye, ranging from 200 to 400 nanometers. While the most common source of UVR is the sun. Certain benefits include blood pressure gradually falling for twenty-four hours, and lowered pressure (persisting) for several days (WHO, 1979). The harmful effects of UV light outweigh the positive outcomes, though. Health risks arise from chronic and excessive exposure to UVR. It damages the skin w/c can be seen in a sunburn or a tan. The effect of UV rays depends on the season, time of the day, latitude, and cloud cover (WHO, 1979). Accumulated exposure to the sun can cause skin cancer. UV light also increases the risks of cataracts and other eye problems, and can subdue the immune system (Strange, 1995). Not all UVR behaves the same way. There is a great difference between long-wavelength UVR and short-wavelength UVR. While

longer wavelength rays causes tanning, shorter wavelength UVR causes sunburn and skin cancer (Hazen, 1996). As a result of these considerable differences among UV light, UVR is divided into the ff. three bands: UVA (320 400 nm), UVB (290 320 nm), and UVC (200 290 nm). Ultraviolet A Radiation stretching from 320 to 400 nm, is placed beyond the violet portion of the visible spectrum. Short wavelength UVA is more damaging than long wavelength UVA. Although not much is known about the effects of UVA radiation, it is known that, in general, UVA rays cause the skin to tan. Most researchers believe that UVA rays multiply to harmful effects of UVB radiation or accelerate the growth of existing cancer cells. UVA prematurely wrinides and withers skin, giving it an aged look (Brink, 1996). Although the other two types of ultraviolet radiation cannot, UVA radiation can penetrate window glasses. The link between UVA and skin cancer is currently being explored. Ultraviolet B Radiation existing from 290 to 320 nm, is more damaging than UVA, alone causing more than ninety percent of skin cancers including melanomas, most deadly of skin cancers (Trichopoulu, 1996). UBV is located on the lower of the zones ultraviolet radiation absorption band, also known as Huggins bands, and is responsible for most sunburn. Scattering plays an important role in the damaging effects of UVB radiation, increasing the intensity of sunlight. Scattering is greatest in the shorter wavelengths; therefore, UVB is subject to the most atmospheric scattering (Giese, 1976). UVB radiation is strongest at low altitudes and high altitudes. At higher altitudes, the sun is low in the sky, therefore, it takes a longer path through the atmosphere and more of the UVB is absorbed (Parson, 1996). Although UVB rays are of very low intensity compared to UVA radiation. UVB is the most dangerous and detrimental to living things, and more specifically to human beings . While most living things are protected from UVB radiation by feathers & fur human beings don not have this natural form of defense. The best form of defense against UVB radiation is sunscreen, measured in terms of sun protection factor (SPF). For instance, a sunscreen of fifteen confers fifteen times more protection against UVB radiation, studies have not yet proven that they block UVA rays well (Wentzell) major concern of researchers is the depletion of the ozone layer, resulting in increased UVB radiation reaching the Earth. Currently, many UVB rays are prevented fro reaching the Earth, but depletion of the ozone layer would only make human more susceptible too burning and cancer. In fact, the ozone layer has thinned by six to seven percent in the mid latitudes of the Northern Hemisphere, which include the United States, since 1979 (Brink, 1996). This increase allows six to fourteen percent more UVB rays through the Earths surface. UVB is the one type of ultraviolet radiation with which we, humans, must be most concerned. Ultraviolet C Radiation reaching from 200 to 290 nm, does not reach us; it is absorbed by the ozone layer (Marwick, 1995). It is a misconception that ozone is found at the Earths surface, though. Only nitrogen, oxygen, carbon dioxide, argon, neon, helium, krypton, xenon, hydrogen, methane, and nitrous oxide exist there. Despite this statement, research has shown that at higher levels f the atmosphere between fifteen and thirty-five kilometers, above the Earths surface, ozone is found (Giese, 1976). The existence of oxygen on the Earths surface is the reason an ozone layer exists. Without the ozone layer and its absorption of UVC light, life on Earth would not be possible. Preventing Sunburn: natural protection clothing sunscreens Sunscreening agents: UV absorbing agents para-amino benzoic acid (PABA) in ethanol lotions UV scattering & blocking systemic/oral DEGREES OF BURNS: First Degree Burns minor burn involving only the top of layer of skin. A sunburn is an example of a first degree burn. This type of burn is red and hot, but there is no swelling or blistering. Treatment: For first and second degree burns you must begin to minimize the damage quickly. Put the affected area in cool running water until the burning feelings leave. This can take longer than 10 minutes. Do not stop this cooling off step too early. If the victim is burnt through the clothing, as in a spill of hot liquid, do not remove the clothing immediately immerse the burnt area in the cool water. Butter, oil, lotions, or creams should not be applied to burns. They will worsen it. Covering the burn with adhesive dressing bandages is also not advisable, burns need to breath. Second Degree Burns involves the top layer of the skin as well as part of the underneath. The skin is a light red and blistery, somewhat swollen and moist and oozing. The pain is very severe. Treatment: -doThird Degree Burns involves all layers of the skin. The burn will destroy the nerves and blood vessels in the skin. There is very little pain at first. The burn area is white, yellow, black, or cherry red. The skin will be dry and leathery. As the burns heal there will be dense scarring and possible skin grafting. Treatment: For third and fourth degree burns call for emergency medical assistance or take them immediately to the emergency room. Do not remove any clothing stuck to the burnt area, cover with a clean cloth. Fourth Degree Burns goes through all the layers of the skin and down into the muscle and the bone. It looks like a third degree burn and does great harm to the body structure. The nerves that are burnt have little pain.

Treatment: -do-

Table 2. Skin Types Skin types SKIN TYPE I SKIN TYPE II SKIN TYPE III SKIN TYPE IV SKIN TYPE V SKIN TYPE VI Skin categories always burn, never tan always burn, sometimes tan sometimes burn, sometimes tan sometimes burn, always tan never burn, always tan Skin sensitivity very sensitive to sunlight sensitive to sunlight normal sensitivity to sunlight skin is tolerant to sunlight skin is brown, very tolerant skin is black, extreme tolerance

Table 3. Skin Characteristics Skin categories never tans, always burns sometimes tans, usually burns usually tans, sometimes burns always tans, rarely burns Skin color in unexposed area pale or milky, white alabaster very little brown, sometimes freckles light tan, brown, or olive distinctly pigmented brown, dark brown, or black Tanning history develops red sunburn, painful swelling, skin peels usually burns, pink or red coloring appears, can gradually develop light brown tan rarely burns, moderately rapid tanning response rarely burns, very rapid tanning response Skin sensitivity value 4 - 10

10 12

11 14

12 16

Module 4: The Prince and the Pea

Instructional Objectives: At the end of this module the student is expected to: 1. Describe the connective tissue. 1.1 Identify the components of connective tissue 1.1.1 cells and their characteristics 1.1.2 fibers & types & their descriptions 1.1.3 ground substance & its composition 1.2 Identify the CT and its types if given description or microscopic slide 1.3 Identify the characteristics, occurrences & roles of each CT 1.4 Identify the differences between CT & other types of tissue Describe the Mononuclear Phagocyte System (MPS). 2.1. Identify the cells belonging to the MPS 2.2. Recall their distribution and functional significance Describe the tendon. 3.1. Identify the description of tendon and 3.1.1. tissue component & role 3.1.2. preponderant cell and fibers 3.1.3. differences between tendon and ligament Describe a tendon cyst. 4.1. Identify the description of a tendon cyst and 4.1.1. its manifestations 4.1.2. your recommendation for management

2.

3.

4.

1.

Describe the connective tissue. 1.1 Identify the components of connective tissue 1.1.1 cells and their characteristics 1.1.2 fibers & types & their descriptions 1.1.3 ground substance & its composition

CONNECTIVE TISSUE originate form the mesenchyme (mesoderm) composed of: 1) cells 2) extracellular matrix consisting of ground substance and fibers maybe fluid, gel-like, or firm chief cells type: Connective Tissue Proper fibroblast Cartilage chondroblast Bone osteoblast Blood-forming tissue hemocytoblast or hematopoietic stem cell The major differences of CTs reflect cell type, fiber type, and proportion of the matrix contributed by fibers. functions: 1) Providing structural support/framework. 2) Serving as a medium of exchange through w/c nutrients and metabolic wastes are exchanged between cells and their blood supply. 3) Aiding in defense and protection. 4) Forming a site for storage of fat. 5) Provide a matrix that connects and binds the cells and organs that ultimately supports the body. Extracellular Matrix Ground substance amorphous materials filling the space between cells and fibers of the CT function: because its viscous, it serves as a lubricant and a barrier to the penetration of invaders composed of the ff: a) Glycosaminoglycan linear polysaccharides formed by repeating disaccharide units usually composed of uronic (glucoronic or iduronic) and hexosamine (glucosamine or galactosamine) b) Proteoglycans composed of a core of protein bound covalently with 4 main glycosaminoglycans: dermatan sulfate, heparin sulfate, chondroitin sulfate & keratin sulfate aggrecan is an impt. ECM proteoglycan dominant in cartilage examples of cell-surface proteoglycans are syndecans and fibroglycan c) Multiadhesive proteins compounds that contain a protein moiety to w/c carbohydrates are attached function in cell-to-cell interaction and adhesion of cells to substrate examples are fibronectin (synthesized by fibroblast & epithelial cells that serves as binding sites for cells, collagen, glycosaminoglycan and mediates normal cell adhesion and migration) and laminin (functions in adhesion of epithelial cell to basal lamina) Fibers consist of 2 systems: 1. Collagen Fiber System consist of collagen and reticular fiber Collagen inelastic, great tensile strength; constitute a family of proteins most abundant protein in the body according to strx. & func., they can be classified in the following groups: i. Collagen that forms long fibrils (collagen types I, II, III, V, XI) w/c aggregate to form long fibrils ii. Fibril-associated collagen (collagen types IX, XII, XIV) short strx. that bind collagen to one another to other components of ECM iii. Collagen that form networks (type IV collagen) molecules assemble in a meshwork that constitute structural component of basal lamina

iv. Collagens that form an anchoring fibrils (type VII collagen) Reticular Fibers consist mainly of collagen type III on association with other types of collagen, glycoproteins, and proteoglycans has high content of sugar chains agyrophilic due to affinity to silver salts abundant in smooth muscle, endoneurium, & framework of hematopoietic organs (lymph nodes, spleen, bone marrow) its smaller diameter & loose disposition create flexible network in organs subjected to change in volume (spleen, uterus, liver, etc.) REPRESENTATIVE TISSUES MAJOR FUNCTIONS Resistance to tension Resistance to pressure Structural maintenance in expansible organs Support of delicate structures, filtration Participates in type I collagen function Anchors skin epidermal basal lamina to underlying stroma

MAJOR TYPES OF COLLAGEN FIBERS I II III IV V VI/VII

Skin, tissues, bone , dentin Cartilage, vitreous body Skin, muscle, blood vessels, frequently together w/ type I All basement membranes Fetal tissues, skin, bone, placenta, most interstitial tissues Epithelia

2.

Elastic Fiber System composed of 3 types of fibers: oxytalan (not elastic and are highly resistant to pulling force), elaunin, elastin develop in 3 successive stages: 1. oxytalan containing fibrillin (a protein necessary to deposition of elastin) 2. irregular deposition of elastin between oxytalan microfibrils forming elaunin 3. elastin gradually accumulates until occupies center of the fibril w/c are then surrounded by a thin sheath of microfibrils forming the elastic fibers composed of elastin (elasticity) and microfibrils (stability) amorphous materials are glycine & proline

Cellular Components 2 categories: Fixed cells resident population of cells that have developed & remain in place w/in the CT, where they perform their functions a stable and long lived popn. that includes: a) Fibroblast most abundant cell type in the CT function: responsible for the synthesis of almost all the ECM/ extracellular components like collagen, elastin, proteoglycan, glycosaminoglycan & multiadhesive protein; production of growth factors that influence cell growth and differentiation 2 stages of activity: active (fibroblast) and quiescent/inactive (fibrocyte) b) Myofibroblast are modified fibroblast that demonstrate characteristics similar to those both fibroblast & smooth muscle cells differs in smooth muscle due to the absence of external lamina/basal lamina Pericytes surround endothelial cells of capillaries & small venules and technically reside outside the CT compartment because they possess their own basal lamina Adipose cells/ Adipocytes/ Fat cells are fully differentiated cells that function in the synthesis, storage, release of fat and production of heat unilocular fatcells from white adipose tissue multilocular fat cells form brown adipose tissue Mast cells

c)

d)

e)

f)

arise from bone marrow stem cells cytoplasm filled with basophilic secretory granules that contains preformed mediators: histamine (increases vascular permeability, impt. in inflammation) and proteoglycan also contains neutral proteases, eosinophil chemotactic factors of anaphylaxis (ECFA), leukotriene 2 popns. of mast cells in CT: (1) connective tissue mast cell found in skin and peritoneal cavity (2) mucosal mast cell found in intestinal mucosa and lungs mast cell surface contain specific receptors for IgE (immunoglobin type produced in plasma cell) function: storage of chemical mediators of inflammatory response & immediate hypersensitivity reactions contain heparin & chondroitin sulfate

Macrophage derived from bone marrow precursor cells that divide producing monocyte monocyte cross walls of venules and capillaries to penetrate CT monocytes mature and become macrophages (monocyte and macrophages are the same cells at different stages of maturation) function: act as defense elements by phagocytosing cell debris, abnormal extracellular matrix elements, neoplasmic cells, bacteria; antigen-presenting cells participating in processes of partial digestion and presentation of antigen to other cells belong to the MPS

Transient cells Originate in the bone marrow & circulate in the bloodstream Short-lived, they must be replaced continually from a large popn. of stem cells, these includes: a) Plasma cells are derived from B lymphocytes and manufacture antibodies nucleus described as having a clock-like appearance only few in CT; average life span: 10 20 days

b) Leukocytes or White blood cells

function: exit bloodstream during inflammation, invasion by foreign elements, and immune responses to perform various functions migrate from the blood vessels by diapedesis e.g. Lymphocytes Neutrophil pus Eosinophil cytotoxins, allergic inflammation Basophils similar to mast cells Monocytes macrophage

1.2 Identify the CT and its types if given description or microscopic slide 1.3 Identify the characteristics, occurrences & roles of each CT 1.4 Identify the differences between CT & other types of tissue Classification of Connective Tissue A. Embryonic Connective Tissue 1. Mesenchymal Connective Tissue 2. Mucous Connective Tissue B. Connective Tissue Proper 1. Loose (Areolar) Connective Tissue 2. Dense Connective Tissue Dense Irregular Connective Tissue Dense Regular Connective Tissue i. Dense Regular Collagenous CT ii. Dense Regular Elastic CT 3. Reticular Tissue 4. Adipose Tissue C. Specialized Connective Tissue 1. Cartilage 2. Bone 3. Blood NOTE: see attached paper (Figure 4-5)

TYPE OF CONNECTIVE TISSUE

DESCRIPTION The first definitive tissue formed from the mesoderm germ layer; gel-like ground substance containing fine fibers; star-shaped mesenchymal cells.

FUNCTION/SIGNIFICANCE

LOCATION OR OCCURRENCE IN THE BODY

Embryonic CT (mesenchyme tissue)

gives rise to all other CT types

primarily in embryo

Connective Tissue Proper wraps & cushions organs; its macrophages phagocytize bacteria; plays an impt. role in inflammation; holds & conveys tissue fluid widely distributed under epithelia of the body, e.g. forms in lamina propria of mucous membranes; packages organs; surrounds capillaries

Loose/Areolar CT

gel-like matrix w/all 3 fiber types; cells; fibroblasts, macrophages, mast cells, & some WBC

Dense Connective Tissue primarily parallel collagen fibers; a few elastin fibers; major cell type is the fibroblast attaches muscles to bones or to muscles; attaches bones to bones; withstands great tensile stress when pulling force is applied in one direction

Dense Regular Collagenous CT

tendons, most ligaments, aponeuroses

Dense Regular Elastic CT

same as for other dense CT, but predominant fiber is elastin

provides durability with stretch

walls of the aorta, some parts of trachea and bronchi; forms the vocal cords and the ligamenta flava connecting the vertebrae dermis of the skin; submucosa of digestive tract; fibrous capsules of organs and of joints

Dense Irregular CT

primarily irregularly arranged collagen fibers; some elastic fibers; major cell type is the fibroblast network of reticular fibers in atypical loose ground substance; reticular cell predominate matrix as in areolar, but very sparse; closely packed adipocytes, or fat cells, have nucleus pushed to the side by large fat droplet

able to withstand tension exerted by many directions; provides structural strength

Reticular CT

fibers form a soft internal skeleton that supports other cell types

lymphoid organs (lymph nodes, bone marrow, & spleen)

Adipose CT

provides reserve food fuel; insulates against heat loss; supports and protects organs

under skin; around kidneys and eyeballs; in bones and w/in abdomen; in breast

Specialized Connective Tissue Cartilage

Hyaline cartilage

amorphous but firm matrix; collagen fibers form an imperceptible network; chondroblasts produce the matrix and when mature (chondrocytes) lie in lacunae similar to hyaline cartilage, but more elastic fibers in matrix matrix similar but less firm than in hyaline cartilage; thick collagen fibers predominate hard, calcified matrix containing many collagen fibers; osteocytes lie in lacunae ; very well vascularized red and white blood cells in a fluid matrix

supports and reinforces; has resilient cushioning properties; resists compressive stress

forms most of the embryonic skeleton; covers the ends of long bones in joint cavities; forms costal cartilages of the ribs; cartilages of the nose. Trachea, and larynx supports the external ear (pinna); epiglottis intervertebral disc; pubic symphysis; disc of knee joint

Elastic cartilage

maintains the shape of a strx. While allowing great flexibility tensile strength with the ability to absorb compressive shock bone supports and protects (by enclosing); provides levers for the muscles to act on; stores calcium and other materials and fat; marrow inside bones is the site for blood cell formation transport of respiratory gases, nutrients, wastes, and other substances

Fibrocartilage

Bone

bones

Blood

contained w/in blood vessels

2.

Describe the Mononuclear Phagocyte System (MPS). 2.1. Identify the cells belonging to the MPS 2.2. Recall their distribution and functional significance

MONONUCLEAR PHAGOCYTE SYSTEM A widely distributed family of both free and fixed macrophage derived from bone marrow precursor cells by way of monocytes; their substantial phagocytic activity is mediated by immunoglobulin and the serum complement system. In both connective and lymphoid tissues, they may occur as free and fixed macrophages; in the sinusoids of the liver, as Kupffer cells; in the lung, as alveolar macrophages; and in the nervous system, as microglia. The term proposed by Van Furth (1969) to include all highly phagocytic cells and their precursors. This includes a number of cell types previously assigned to the reticuloendothelial system and several additional ones. It excludes fibroblasts, endothelial cells, dendritic cells, and other that ingest vital dyes at very low rates. The great appeal of the unifying concept of a MPS is that all of its members belong to the same cell lineage, originating in the bone marrow and being transported in the blood to their functional sites in the tissues. All members of MPS arise from a common stem cell in the bone marrow, possess lysosomes, and are capable of phagocytosis. Macrophages constitute the MPS: is the largest normal blood cell (14 20m) they have a single indented nucleus they correspond to 8-10% of circulating leukocytes and are part of the MPS they are widely distributed throughout the body and are known as scavenger cells of the body they are very impt. in inflammation particularly in phagocytosis and immunity they are adaptable, long-lived phagocytic cells with a variety of plasma membrane receptors and tremendous secretory activity potential their name often varies accdng. to their location, their immune bone marrow forms are called monoblasts and promonocytes in peripheral blood they are called monocytes, in tissues they are called often referred as macrophages or histiocytes CELL TYPES Monocyte Macrophage Kupffer cells blood CT, lymphoid tissue, lings, bone marrow liver LOCATION MAIN FUNCTION precursor of macrophages production of cytokines, chemotactic factors, & several other molecules that participate in inflammation (defense), antigenprocessing and presentation same as macrophage

Microglia cells Langerhans cells Dendritic cells Osteoclasts Multinuclear Giant cell 3.

nerve tissue of the CNS skin lymph nodes bone (fusion of several macrophages) CT (fusion of several macrophages)

same as macrophage antigen processing and presentation antigen processing and presentation digestion of bone segregation and digestion of foreign bodies

Describe the tendon. 3.1. Identify the description of tendon and 3.1.1. tissue component & role 3.1.2. preponderant cell and fibers 3.1.3. differences between tendon and ligament

TENDON Tendons are dense regular CT that attached muscles to bone by virtue of their richness in collagen fibers. They are white and inextensible. Consist of parallel, closely packed bundles of collagen separated by small quantity of intercellular ground substance. Fibrocytes have elongated nuclei parallel to the fibers Collagen bundles of the tendons (primarily bundles) aggregate into larger bundles (secondary bundles) enveloped by LCT with blood vessels and nerves. Presence of fluid that function as lubricant permitting easy sliding movement of the tendon with its sheath. LIGAMENT A ligament is a band or sheet of fibrous tissue connecting two or more bones, cartilages, or other strxs., or serving as support for fasciae or muscles. Ligaments are similar to tendons, except that the elements are somewhat less regularly arranged; it is also a little stretchable than tendon. Tendons vs. Ligaments Tendons attach muscles to bones, and ligaments attach bones to bones. Tendons and ligaments are dense, regular CT, consisting almost entirely of thick bundles of densely packed parallel collagen fibers. The cells of developing tendons & ligaments are spindle-shaped fibroblasts fibrocyte. The orientation of the collagen fibers in one direction makes the tendons and ligaments very strong in that direction. Because collagen is a white protein, most tendons and ligaments appear white; some ligaments, however, also contain elastin, w/c gives them a slightly yellow appearance. Major Histological Differences between Tendons and Ligaments include the ff: collagen fibrils of ligaments are often less compact some fibrils of many ligaments are not parallel some fibrils are more flattened than tendons and form sheets or bands of tissue Tendons & ligaments grow by 2 different processes: Appositional growth surface fibroblasts divide to produce addtl. fibroblast w/c secrete matrix to the outside of existing fibers Interstitial growth fibrocyte proliferate and secrete matrix inside the tissue 4. Describe a tendon cyst. 4.1. Identify the description of a tendon cyst and 4.1.1. its manifestations 4.1.2. your recommendation for management

In the hand, a ganglion cyst is a particular type of benign lump w/c shows up next to a joint or a tendon. Inside, it is like a balloon filled with a thick liquid. It may be soft or hard, may or may not be painful, and may get bigger or smaller ion its own. It may also be referred to as a mucous cyst, a mucinous cyst or a synovial cyst. What caused it? Normally, joints and tendons are lubricated by a special fluid w/c sealed in a small compartment. Sometimes because of arthritis, an injury, or just for no good reason, a leak occurs from the compartment. Now, the fluid is thick, like honey, and if the hole is small, it can be like having a pinhole in a tube of toothpaste when you squeeze the tube, even though the hole is small and the toothpaste is thick, it will leak out and once it is out, there is no way it can go back in on its own. It works almost like a

one way valve, and fills up a little balloon next to the area of the leak. When we use our hands for normal activities, our joints squeeze and create a tremendous pressure in the lubricating compartment this can pump up a balloon leak with so much pressure that it feels as hard as a bone. The lubricating fluid has special proteins dissolved in it w/c make it thick and also make it hard for the body to absorb it when it has leaked out. The body tries to absorb the liquid, but many joints only be able to draw out the water, making it even more thick. Usually, by the time the lump is big enough to see, the liquid has gotten to be as thick as jelly. Common sites for ganglions are: The wrist on the back dorsal wrist ganglion, on the front volar wrist ganglion, or sometimes on the thumb side. These come from one of the wrist joints, sometimes aggravated by wrist sprain. The palm at the base of the finger flexor tendon sheath. These come from the tube w/c holds the finger tendons in place, and are often due to tendon irritation tendonitis. The back of the end joint of the finger mucous cyst, next to the base of the fingernail. These can cause a groove in the fingernail, or rarely can become infected and lead to a joint infection. These are usually due to some arthritis or bone spurs in the joint. Ganglion cysts used to be treated by slamming them with a heavy book such as a Bible w/c explains the term Bible therapy. This isnt a good idea, as you could cause further injury. Medical treatment options include: a) Close monitoring confirm that this actually is the problem. If the ganglion cyst isnt causing pain or interfering with movement; some doctors prefer to wait and see. The cyst may simply disappear on its own. Needle aspiration one of the test to diagnose ganglion cysts involves drawing off the fluid with a fine needle, possibly inject the area with cortisone. This works much better for cysts coming from the tendon than those coming from joint. In many cases (around 75%), this treatment empties the cyst and no further action is needed. Surgery the cysts are surgically removed, usually by a specialist such as an orthopedic surgeon. Ganglion cysts of the feet will usually require surgery.

b)

c)

Module 5: Dizzy Delia

Instructional Objectives: At the end of this module the student is expected to: 1. Discuss the characteristics and function of blood. 1.1. Identify the characteristics and function of blood 1.2. Identify blood if given description or microscopic slide 1.3. Identify the differences of various blood cells as to structure and functions Identify the hematopoietic organs: 2.1. during embryonic life 2.2. at birth 2.3. in adults Discuss the bone marrow. 3.1. Identify the bone marrow if given description or microscopic slide 3.2. Identify the developing blood cells if given description 3.3. Identify the structural changes as developing blood cells matures Identify the various factors involved in the control of hemopoiesis. Identify descriptions of the steps involved in: 5.1. RBC synthesis 5.2. Heme synthesis 5.3. Globin synthesis Define anemia. Identify the mechanism involved in the development of nutritional anemia. Identify the signs and symptoms of nutritional anemia. Identify the basic laboratory tests needed for the diagnosis of anemia. Identify the normal value for each tests. Given similar problems/situations: 9.1. Identify the possible problem 9.2. recommend possible situations

2.

3.

4. 5.

6. 7. 8. 9.

1.

Discuss the characteristics and function of blood. 1.1. Identify the characteristics and function of blood 1.2. Identify blood if given description or microscopic slide 1.3. Identify the differences of various blood cells as to structure and functions PHYSICAL CHARACTERISTICS FUNCTIONS FORMED ELEMENTS erythrocytes: transport oxygen, mainly bound to its hemoglobin transports carbon dioxide, bound to its hemoglobin and carried in plasma as CO2 or HCO3 leukocytes: bodys chief defense against infection circulates body via vascular system (round & inactive) recirculates blood system after diapedesis as its defensive capabilities (immune response) platelets: responsible for blood clotting, control hemorrhage FLUID plasma:

consist of cells (formed elements) and fluid (plasma) erythrocytes (RBC) leukocytes (WBC) thrombocytes (platelets) heterogeneity separates in layers when centrifuged RBC (bottom): 42 47% WBC (middle): 1% (buffy coat) Plasma (top): 52 57% (somewhat supernatant) unidirectional movt. in a closed circulatory system propelled by rhythmic contractions of the heart serum clear yellow liquid in a blood clot that separates from the coagulum anticoagulants avoids blood clotting when added to the blood hematocrit volumetric estimation of RBC

transports nutrients, metabolic residues, hormones (chemical messages bet. distant organs) regulates body temp., acid-base and osmotic balance

ERYTHROCYTES (RBC) STRUCTURAL APPEARANCES stays in the circulatory system (no diapedesis) anucleate and biconcave surrounded by plasmalemma FUNCTIONS circulates the blood system carrying oxygen to tissues shape provides large surface-tovolume ratio (facilitates gas exchange) as membrane skeleton for cell shape links several membrane component w/ other cytoskeletal elements; flexibility (low viscosity) w/c reinforces membrane oxygen carrying protein increase indicates demand of O2

50% integral proteins peripheral protein: associated w/ inner surface of membrane cytoskeletal spectrin: forms meshwork 40% lipids 10% carbohydrates hemoglobin: 33% (acidophilic) of RBC

reversible combinations: *forms oxyhemoglobin (RBC + O2) *forms carbaminohemoglobin (RBC + CO2) irreversible combinations: *forms carboxyhemoglobin (RBC + CO) reticulocytes *young RBCs recently released by bone marrow into blood stream (often w/ residual rRNA) *1% of total no. of RBCs *low RBCs (w/ high O2 tension @ lower altitude) *high RBCs (w/ low O2 tension @ higher altitude) mature RBCs lose their nucleus, mitochindria, ribosomes and cytoplasmic enzymes glucose source of energy enzymes for glucose metabolism (glycolytic & hexose-monophosphate shunt pat.) life span: 120 days normal concentration count: male: 4.1 6 million/microliter female: 3.9 5.5 million/microliter

carrying capacity do not synthesize hemoglobin anaerobically degraded to lactate (in O2 poor inflamed areas) dead RBC removed by macrophages (spleen & bone marrow) due to defective complex oligosaccharide attached to integral proteins

LEUKOCYTES (WBC) STRUCTURAL APPEARANCES does not stay in the circulatory system (w/ diapedesis) nucleate w/ granules 2 groups accrdng. to nuclear shape and granule types FUNCTIONS

migrates from bone marrow to connective tissues w/ multiple functions and mostly die by apoptosis (programmed cell death)

I. GRANULOCYTES cell shape: polymorphonuclear (w/ 2 or more lobes) specific granules (bind w/ neutral, basic, acidic) azurophilic granules (are lysosomes w/ enzymes) poorly developed golgi complex & RER few mitochondria short life span

synthesize less proteins (not much) *depend more on glycolysis (low energy) *can func. in an O2 poor inflamed areas due to glycogen all are non-dividing terminal cell (apoptosis in CT)

Neutrophil 60 70% of leukocytes (1st) nuclear shape: drumstick like appendages on one of the lobes specific granules (more abundant) azurophilic granules cytoplasm: w/ glycogen life) represents the inactive X chromosome (drumstick like) in females actively phagocytic, kills bacteria in inflamed areas, poorly oxygenates region or in necrotic tissue life span: 1 4 days (6 7 hrs. half

Eosinophil 2 4% of leukocytes (2nd) nuclear shape: bilobed increase in no. associated w/ allergic refractile specific granules (large & elongated; eosin stain) *w/ internum (crystalline core) surrounded by

reactions accounts for eosinophilia of granules that kills parasitic worms (schistomes)

externum/matrix *contains major basic protein w/ large no. of arginine residues *50% of total granule protein

Basophil liberates granules against antigens metachromasia changes color supplements func. of mast cells in immediate hypersensitivity reactions similar to granules of mast cell but diff. strx. & stem cells in bone marrow

0.5% (3rd) nuclear shape: irregular lobe specific granules *fewer and more irregular *w/ heparin (metachromatic)

II. AGRANULOCYTE 6,000 10, 000/ microliter of blood nuclear shape: mononuclear (round & indented) nonmotile & spherical (suspended in cir. blood) motile & flattened (on solid substrate) only azurophilic granules undergoes diapedesis *cellular and humoral defense against foreign materials *cells & microorganisms (release chemicals by chemotaxis) during inflammatory response increased (no. varies according to age, sex & physiologic condition)

Monocyte nuclear shape: oval, horse-shoe, kidney-shaped; gen. eccentrically placed w/ less condensed chromatin lightly stained fine azurophilic granules (as lysosomes) complex cytoplasm: slightly basophilic small mitochondria, few RER, golgi complex, polyribosomes undergo diapedesis lysosomal granules formed by golgi

Lymphocytes nuclear shape: spherical (sometimes indented) & appears as coarse clumps w/ more condensed chromatin highly stained few azurophilic granules cytoplasm: slightly basophilic few mitochondria, small golgi complex, w/ free ribosomes classified accdng. to surface molecules small & medium-sized lymphocytes

the only type w/c recirculates the blood after diapedesis believed to be activated by specific antigens all func. related to immune reactions defense against: 1. invading microorganisms 2. foreign molecules 3. cancer cells

THROMBOCYTES (platelets) 200,000 400,000/ microliter anucleated disk-like cell cell coat (glycosaminoglycans & glycoproteins) appears as clumps granules: hyalomere (peripheral zone blue) undergoes diapedesis promotes blood clotting *repair gaps in blood vessels (prevent blood loss) *platelet adhesion assemble to form a contractile system for movt. & aggregation take up and store serotonin from

 platelet)

*dense tubular system (actin & myosin) granulomere (central zone purple) *abundant membrane-bound granules *dense bodies (delta granules) * alpha granules (lambda granules) w/ open canalicular system marginal bundle (periphery of the life span: 10 days 3. Blood coagulation 4. Clot retraction

plasma contains lysosomal enzymes maintains cells ovoid shape *liberates active molecules stored *connects to invaginations of the platelet plasma membrane origin: fragmentation of giant polyploid megakaryocytes (bone marrow)

1. Primary aggregation 2. Secondary aggregation

5. Clot removal

Erythropoiesis

Granulopoiesis

Platelet formation

Proerythroblasts *large cell w/ loose, lacy chromatin *clearly visible nucleoli *cytoplasm: basophilic

Myeloblast *no cytoplasmic granules

Basophilic erythroblasts *w/ strongly basophilic cytoplasm *condensed nucleus that has no visible nucleolus *basophilia of these 2 cell types is caused by the large no. of polyribosomes involved in the synthesis of Hb Polychromatophilic erythroblasts *Polyribosomes decreases and areas of the cytoplasm begin to be filled w/ Hb *staining causes several colors to appear in the cell

Promyelocyte *first azurophilic granules being secreted in golgi zone, develop golgi complex

Megakaryoblasts *15-50m in diameter and has a large ovoid or kidney-shaped w/ numerous nucleoli *these nucleus becomes highly polyploid before platelets begin to form Megakaryocytes *giant cell w/ an irregularly lobulated nucleus *coarse chromatin *no visible nucleoli *cytoplasm contains numerous mitochondria Platelets *have conspicuous granules, originating from the golgi complex *contains biologically active substances

Myelocyte *moderate no. of azurophilic granules and initial secretion of specific granules in golgi complex Metamyelocyte *abundant specific granules and few azurophilic granules, atrophic golgi complex

Orthochromatophilic/Normoblast *nucleus continues to condense *no cytoplasmic basophilia is evident, resulting in a uniformly acidophilic cytoplasm Reticulocyte *series of cytoplasmic protrusions and expels nucleus, encased in a thin layer of cytoplasm *has small no. of polyribosomes

Band forms *slightly smaller *nucleus U-shaped *coarse clumps of chromatin *specific granules fills cytoplasm Mature granulocyte *functioning adult cell *negative feedback mechanism regulates release from marrow, may involve hormone leukopoietin ---------------------------------------Lymphoblast *large cell capable of incorporating H - thymidine

Mature erythrocyte *loses its polyribosomes

NOTE: Monoblast is part of granulopoiesis ------------------------------------------Monoblast *committed progenitor cell that is virtually identical to the myeloblast in its morphologic characteristics

Prolymphocytes *smaller and have more condensed chromatin but more of the cell-surface antigens that mark prolymphocytes as T or B lymphocytes *B-lymphocytes (bone marrow) *T-lymphocytes (spleen, lymph nodes, tonsils)

Promonocyte *large cell w/ basophilic cytoplasm and a large, slightly indented nucleus *the chromatin is lacy and nucleoli are evident Monocyte *large amount of RER is present w/ an extensive golgi complex in w/c granule condensation can be seen to be taking place *these granules are primarily lysosomes w/c are observed as fine azurophilic granules in blood monocytes

2.

Identify the hematopoietic organs: 2.1. during embryonic life 2.2. at birth

2.3. in adults During embryonic life a) Primitive blood islands of yolk sac appear on the 19th day to 20th day of gestation cells produced are largely erythrocytes and some granulocyte & megakaryocyte precursor b) Liver occurs at the 5th to 6th week off gestation remains the primary site until the 6th month of gestation Spleen occurs at the 4th to 8th month of embryonic life Bone marrow Occurs at the 4th month of embryonic life and is the main hematopoietic organ after the 6 th month

c) d)

At birth, during infancy, and in children a) Bone marrow marrows of bones in the axial and extremities In adult a) Bone marrow marrows of bones of the axial skeleton and proximal ends of femur and humerus 3. Discuss the bone marrow. 3.1. Identify the bone marrow if given description or microscopic slide 3.2. Identify the developing blood cells if given description 3.3. Identify the structural changes as developing blood cells matures

BONE MARROW blood forming tissue located between the trabeculae of spongy bone major hematopoietic organ is a rich, cellular, highly vascularized LCT that has a volume at 30 to 50 ml/kg of BW composed of 2 major compartments: a. Hematopoietic compartment known as hematopoietic cords site of inflammation and maturation of blood cells this compartment includes both hematopoietic cells (functional element) & stromal cell (supporting tissue) hematopoietic cells are only transient residents of marrow and when they mature they move toward a sinus these mature cells traverse the endothelial cell lining of the sinus and eventually gain access to the peripheral blood through the vascular compartment b. Vascular compartment composed of the nutrient artery, central longitudinal vein, arterioles, and sinuses theres no pattern to the arrangement of hematopoietic cell within the marrow cavity occurrences: for the first 4 years of life all marrow cavities are composed of red hematopoietic marrow after 4 years the red marrow in long bones is gradually replaced by yellow fatty tissue after 25 years hematopoiesis is limited to the marrow at the skull, ribs, sternum and proximal ends of long bones Erythroblast constitute between 25 to 30% of the marrow cells and are produced near the sinuses Granulocytes produced in nests close to the trabeculae and arterioles Lymphocytes *produced in lymph nodes w/c are randomly dispersed throughout the marrow *they may leave the bone marrow and travel to the thymus where they mature to T-lymphocytes *some remain in the bone marrow where they mature into B-lymphocytes Megakaryocytes lie adjacent to the endothelium of sinusoidal wall and discharge platelets directly into the lumen of the sinus 2 other types of cells normally assoc. w/ bone osteoblast and osteoclast based on appearance in x-s bone marrow is classified: hematopoietic active red marrow (hematogenous bone marrow) *lies adjacent to the endosteum *color produced due to the presence of blood and blood0forming cells fatty yellow marrow *occupies the central cavity

4.

*composed of adipocytes whose color is produced due to numerous number of adipose cell Identify the various factors involved in the control of hemopoiesis.

Factors act mainly by stimulating proliferation of immature cells supporting the differentiation of maturing cells enhancing the functions of mature cells Multilineage GFs - Interleukin (1,3,6,11) - CSF (SCF, GM-CSF) Lineage Specific GFs - Interleukin (2,4,5,7,8,9) - CSF (G-CSF, M-CSF) 5 best-known hematopoietic GFs:

1.

2.

3.

4.

5.

Granulocyte Colony Stimulating Factor (G-CSF) Chromosome 17 macrophages, endothelium, fibroblast producing cells *stimulate formation granulocytes *enhance metabolism of granulocytes *stimulate malignant (leukemic) cells Granulocyte + Macrophage CSF Chromosome 5 T-lymphocytes, endothelium, fibroblast stimulate in vitro and in vivo production of granulocytes and macrophages Macrophage CSF Chromosome 5 macrophages, endothelium, fibroblast *stimulate formation of macrophages in vitro *increases anti-tumor activity of macrophages Interleukin 3 (Il 3) Chromosome 5 T-lymphocytes stimulate in vivo and in vivo production of all myeloid cells influences the activities of cells from the pluripotential stem cells to the mature progeny of the myeloid cell line Erythropoietin (EPO) Chromosome 7 renal interstitial cell (outer cortex) *stimulate RBC production *produced by the kidney

5.

Identify descriptions of the steps involved in: 5.1. RBC synthesis Erythropoiesis (Gr. erythros, red + poiesis, a making) Changes that take place during maturation of RBC 1. cell volume decreases 2. nucleoli diminish in size until they become invincible in the light microscope *nuclear diameter decreases *chromatin becomes increasingly more dense *pyknotic appearance 3. gradual decrease in the no. of polyribosomes (basophilic cells), with a simultaneous increase in the amount of hemoglobin ( an acidophilic protein) w/in the cytoplasm 4. mitochondria and other organelles gradually disappear

Erythrocyte maturation: cell division: 3 5 days (pro-erythroblast mature erythrocyte) duration: 7 days hormone: erythropoietin (gene in Chromosome 7 codes for a heavily glycosulated polypeptide of 165 amino acid, has a molecular weight of 30, 400 and is produced in the peritubular cells in the kidney (90%) and in the liver (10%) and substances such as iron, folic acid, cyanocobalamin (Vit. B12) **about 10% of the erythroblast die in the bone marrow even during normal erythropoiesis **ineffective erythropoiesis is substantially increased in some anemias such as thalassemia major and megaloblastic anemia

ERYTHROCYTE DIFFERENTIATION Proerythroblast Basophilic erythroblast Polychromatophilic erythroblast Orthochromatophili c erythroblast Large cell with loose, lacy chromatin and clearly visible nucleoli, its cytoplasm is basophilic. A strong basophilic cytoplasm and a condensed nucleus that has no visible nucleolus; basophilia of these two cells types is caused by large no. of polyribosomes involved in the synthesis of hemoglobin. Polyribosomes decrease and the areas of the cytoplasm begin to be filled with hemoglobin; staining causes several colors to appear in the cell. Nucleus continues to condense and no cytoplasmic basophilia is evident, resulting in a uniformly acidophilic cytoplasm. Cells put forth a series of cytoplasmic protrusions and expels its nucleus, encased in a thin layer of cytoplasm; still has a small no. of polyribosomes that when treated with the dye brilliant cresyl blue aggregate to formed a stained network; contain residual RNA and are still able to synthesize Hb; remain the marrow for about 1-2 days and are released into the circulation, where they lose their RNA and become mature RBCs after another 1-2 days. Mature RBC are non-nucleated biconcave disk.

Reticulocyte

Erythrocyte

5.2. Heme synthesis HEME SYNTHESIS 1) Condensation of glycine & succinyl Co-A to form Delta-aminolevulenic acid. - this rxn. occurs in the mitochondria in the presence of pyridoxal phosphate, Co-A, ferrous iron, & deltaALA synthetase - also an important control site in the heme synthesis 2) The delta-aminolevulenic acid ALA leaves the mitochondria; and in the cytoplasm, 2 linear delta-ALA condense & catalyze to form the pyrole, porphobilinogen. - this dehydration rxn. is catalyzed by the cytoplasmic enzyme, ALA dehydratase - an important intermediate - porphobilinogen is the primary building block for the formation of all natural tertrapyroles (including not only heme but also cobalamin) Four porphobilinogen molecules condense to form linear tetrapyrole (hydroxymethylbilane), w/c subsequently cyclize to form uroporphyrinogen-III. - the cyclization rxn. requires both URO-I synthetase (porphobilinogen deaminase) & URO-III synthetase Decarboxylation of the side chain of uroporphyrinogen, catalyzed by the cytoplasmic enzyme uroporphyrinogen decarboxylase results in the formation of coproporphyrinogen III. Inside the mitochondria, the enzyme coproporphyrinogen oxidative decarboxylase catalyzes the unsaturation of the porphyrin rings & conversion of propionate side chains to vinyl group, forming protoporphyrinogen IX. Protoporphyrinogen is oxidized to protoporphyrin IX by protoporphyrinogen oxidase. The final step in the mitochondria is the chelation of iron w/ the protoporphyrin ring catalyzed by ferrochelatase.

3)

4) 5) 6) 7)

5.3. Globin synthesis

Chromosome 16

Chromosome 11

---------------------

G A --------------------------------

Globin chain

Globin tetrad Hemoglobin

22

22

22

Hb Portland Hb Gower I Hb Gower II Embryonic Hemoglobins

Hb Barts Hb H Abnormal Hemoglobins found in thalassemia

22 22

22

Hb F HbA2 HbA Adult Hemoglobins TYPES OF HEMOGLOBIN Intrauterine erythropoiesis is associated with the production of embryonic hemoglobins, Gower I, Gower II, and Portland, in the first trimester of gestation. These embryonic hemoglobins are made from the combination of embryonic globin chains, () and () in pairs, or embryonic chains in combinations with () and () chains. These primitive hemoglobins are usually detectable after 8 weeks gestation because the production of embryonic chains ceases at this time. Hemoglobins F (HbF) (22) is the predominate hemoglobin formed during liver and bone marrow erythropoiessis in the fetus. HbF composes 90% to 95% of the total hemoglobin production in the fetus until 34 to 36 weeks of gestation. In adults, hemoglobin A (HbA), w/c consists of two chains and two chains (22), is the major hemoglobin. Although HbA is found as early as 9 weeeks gestation, -chain synthesis does not exceed that of -chain synthesis until after birth. Thus, the normal full-term infant has from 50% to 85% HbF. After birth, the percentage of HbA increases with the age of the infant until the normal adult levels are reached by the end of the first year of life. HbF production constitutes less than 2% of the total hemoglobins of adults. Most, if not all HbF in adults are restricted to a few erythrocytes sometimes referred to as F cells (less than 8% erythrocytes). From 13% to 25% of the hemoglobin in these F cells is HbF. The switch from HbF to HbA after birth is incomplete and, in parr, reversible. For example, patients with hemoglobinopathies or anemia may have increased levels of HbF, often proportionate to the decrease in HbA. In bone marrow, recovering from suppression, HbF levels often rise. This is due to small increases in HbF production within F cells in addition to an increase in the number of erythroblasts producing HbF. HbA2 appears late in fetal life, composes less than 1% of the total hemoglobin at birth, and reaches normal adult values after 1 year 91.7% to 3.5%). 6. Define anemia. Identify the mechanism involved in the development of nutritional anemia. ANEMIA a pathological condition characterized by blood concentrations of hemoglobin below normal values although anemias are usually associated with a decreased number of erythrocytes, it is also possible for the number of cells to be normal but for each cell to contain a reduced number of hemoglobin (hypochromic anemia) may be caused by: a. loss of blood (hemorrhage) b. insufficient production of erythrocytes by bone marrow c. production of erythrocytes with insufficient hemoglobin, usually related to iron deficiency in the diet d. accelerated destruction of blood When youre anemic, your body either produces to a few RBCs, or destroys them faster than they can be replaced or losses too many of them. If your diet lacks certain vitamins and minerals, the production of hemoglobin an slow down. If something in the body destroys or attacks RBC, the bone marrow tries to produce more blood. If destruction of RBCs is rapid, the marrow cant catch up. This problem is often inherited. The resulting anemia is called hemolytic anemia. A sever bleeding episode can result in temporary anemia until the body has had time to make up the blood that was lost; even small, persistent losses of blood may cause anemia if you have a poor diet; a healthy person whose diet contains plenty of iron and vitamins can produce large amounts of new blood, reducing the risk of anemia.

Types of anemia caused by decreases in red cell production include nutritional deficiency such as: a. iron deficiency anemia b. vitamin B12 anemia (cobalamin anemia) c. folate deficiency anemia d. starvation and generalized malnutrition Other types of anemia are caused by genetic disorders (thalassemias and sickle-cell), hemorrhage, immunologicantibody mediated abnormalities, physical effects (trauma, burns), drugs and chemicals (aplastic anemia, megablastic anemia), chromic diseases and malignancies 9renal diseases, hepatic diseases, neoplasia), infections (viral, bacterial, protozoa).

How iron deficiency anemia develops? Iron deficiency anemia develops gradually, in stages. The symptoms develop in later stages. Stage 1: Iron losses exceeds intake, depleting iron reserves, primarily in bone marrow. Blood levels of ferritin (a protein that stores iron) progressively decrease. Stage 2: Because of depleted iron reserves cant meet the needs of developing red blood cells, fewer RBCs are produced. Stage 3: Anemia begins to develop. Early in this stage, the RBCs appear normal, but there are fewer of them. Hemoglobin levels and hematocrit are reduced. Stage 4: The bone marrow tries to compensate for the lack of iron by speeding up cell division and producing very ] small (microcytic) RBCs, w/c are typical of iron deficiency anemia. Stage 5: As iron deficiency and anemia progresses, the symptoms of iron deficiency anemia may develop and symptoms of anemia worsen. Folic acid

folic acid or folacin, is a coenzyme needed for body protein and hemoglobin factors that cause are inadequate intake such as in the case of alcoholics from w/c their main source of caloric intake are alcoholic beverages w/c do not contain enough of the vitamin to satisfy the daily requirement, alcohol may also interfere folate metabolism narcotic addicts are prone to folate deficiency because of malnutrition; indigent and elderly individuals who subsists of junk food develop folate deficiency as well other factors of folate deficiency are increased demand (pregnant women high demand fro developing fetus) and malabsorption

Vitamin B12 anemia cobalamin or Vit. B12 is necessary in minute amounts for the formation of nucleoproteins, proteins, and red blood cells, and for the functioning of the nervous system often due to inability of the stomach to produce glycoprotein, w/c aids in the absorption of this vitamin pernicious anemia results w/ characteristics symptoms of ineffective production of RBCs also caused by effective release of cobalamin from food; common in people in older than 70 years old wherein they are unable to split cobalamin bound tightly to enzymes of meat (hydrochloric acid and pepsin in stomach) Treatment: iron deficiency anemia can be corrected with improved diet, iron pills or injections of iron from the doctor Folate and Vit. B12 can be corrected by eating foods high in vitamin B12 and folic acid and cessation of drinking alcohol

7.

Identify the signs and symptoms of nutritional anemia. The most common sign of iron deficiency anemia and other types of nutritional anemia: mild paleness of the skin, along with decreased pinkness of the lips, the lining of the eyelids, and the nail beds. A person w/ anemia will feel tired and weak because the bodys tissues are being starved of oxygen. In fact, fatigue is the main symptom of most types of anemia. The severity of symptoms is in part related to the severity of anemia. Mild anemia can occur w/out symptoms and may be detected only during a medical exam that includes a blood test. Other common signs of anemia may include: irritability fatigue lightheadedness weakness fainting breathlessness tachycardia dizziness headache tinnitus (ringing in the ears) difficulty sleeping difficulty concentrating Depending on the condition causing the anemia, other signs and symptoms may occur, such as jaundice 9yellowtinged skin), dark tea-colored urine, easy bruising or bleeding, and enlargement of the spleen and liver. In infants and preschool children, iron deficiency anemia can result in developmental delays and behavioral disturbances, such as decreased motor activity and problems with social interaction and attention to tasks. Recent research studies indicate that behavioral problems may persist into and beyond school age if the iron deficiency is not properly managed.

8.

Identify the basic laboratory tests needed for the diagnosis of anemia. Identify the normal value for each test. Complete blood count (CBC) counts your RBCs, WBCs, & platelets and measures your hemoglobin Blood smear blood is taken from your finger and smeared on a microscope slide to examine RBCs directly, RBCs have different appearances depending on the type of anemia; may be deformed, too big, too small, too variable in size or shape, or filled with visible abnormalities Reticulocyte count counts young RBCs to determine how fast they are made Serum iron, iron binding capacity, and ferritin tests to determine enough iron in blood Folic acid and cobalamin levels blood these of these nutrients Red cell fragility identifies RBCs that can be destroyed too easily Bone marrow biopsy and Coombs test Given similar problems/situations: 9.1. Identify the possible problem 9.2. recommend possible situations hypoxia stimulates erythropoietin erythropoietin stimulate bone marrow production of RBC LABORATORY TESTS IN ANEMIA DIAGNOSIS I. Complete blood count (CBC) Red Cell Count Red blood cell count normal value for male: 4.6 6.2 x 106/mm normal value for female: 4.2 5.4 x 10/mm 1. Hemoglobin *normal value for male: 13 18 g/dL *normal value for female: 12 16 g/dL 2. Hematocrit (packed RBC pr unit volume of blood) *percentage of the volume of a blood sample occupied by the cell *normal value for male: 42 52% or 0.42 0.52 (SI unit) *normal value for female: 37 48% or 0.37 0.48 (SI unit) B. Red blood cell indices 1. Mean cell volume (MCV) *average volume of RBCs calculated from hematocrit and red cell count *normal value: 82 98 fL 2. Mean cell hemoglobin (MCH) *the hemoglobin content of the average red cell *normal value: 27 32 pg 3. Mean cell hemoglobin concentration (MCHC) *average hemoglobin concentration in a given volume of packed RBCs *normal value: 32 38% 4. Red cell distribution width (RDW) C. White blood cell count *normal value: 5,000 10,000/mm 1. Cell differential 2. Nuclear segmentation of neutrophils D. Platelet count *normal value: 130,000 400,000/mm E. Cell morphology 1. Cell size 2. Hemoglobin content 3. Anisocytosis 4. Poikilocytosis 5. Polychromasia II. Reticulocyte count III. Iron supply studies A. Serum iron B. Total iron binding capacity C. Serum ferritin, marrow iron stain IV. Marrow examination A. Aspirate 1. E/G ratio 2. Cell morphology 3. Iron stain B. Biopsy 1. Cellularity 2. Morphology A.

9.

NOTE: