MCBM1Element2SLOBook2010

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Department of Physiology, Faculty of Medicine, AIMST University

MCBM 1 El 2 – General & Cellular Basis of Medical Physiology; Basics of Haematology; Nerve-Muscle Physiology

Intended Learning Outcomes (updated August 2010)

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MCBM 1 Element 2 – Physiology

Intended Learning Outcomes

This document is intended to convey what learners are expected to be able to do at the end of

this course; for convenience, learning outcomes are listed by lectures. The outcomes outlined

here will also form the basis of assessment.

CELLULAR AND GENERAL BASIS OF MEDICAL PHYSIOLOGY

Lecture 1: What is medical physiology and why and how should you learn it?

Introductory lecture

Lecture 2: Structure and function of the eukaryotic cell membrane

• With a labelled schematic diagram, briefly describe the structure of the eukaryotic cell

membrane.

• Briefly describe the salient properties of the eukaryotic cell membrane.• Classify the types of proteins present in the cell membrane (based on their orientation in the

cell membrane).

• Mention, with suitable examples, functions which proteins in the cell membrane perform.

• List the types of modifications of cell membrane and their functions.

• Briefly describe the composition and function of the cytoskeleton.

• What are tight junctions? What is their function?

• What are gap junctions? What is their function?

• What are ‘cell-adhesion molecules’? What is their function?

Lecture 3: Transport across the cell membrane

• Classify mechanisms that exist to transport molecules and ions across the cell membrane

and provide an example for each.

• Briefly describe the factors that affect conductance of ions across the cell membrane.

• Briefly describe the factors that affect diffusion of a species across all the cell membrane.

• Distinguish between simple and facilitated diffusion using an example for each

• Distinguish between active and passive transport. Give an example for each.

• Distinguish between primary and secondary active transport. Give an example for each.

• Describe the link between primary and secondary active transport.

• Describe the role of Na-K ATPase in the regulation of cell volume.

• Na-K ATPase is described as electrogenic. Why?

• Briefly explain what is meant by uniport, symport, antiport with an example for each.

• Briefly explain with a suitable example what receptor mediated endocytosis is.

• Briefly explain what is meant by: endocytosis, exocytosis, and transcytosis.

• Briefly explain what is meant by carrier-mediated transport with an example for it.






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• Briefly explain what gating of ion channels means. How are ion channels classified (based

on factors that gate the channels)?

• How do gap junctions allow transport between cells?

Lecture 4: Regulation of the cell cycle

• List the salient differences between mitosis and meiosis.

• Briefly explain the biologic significance of mitosis.

• Briefly explain the biologic significance of meiosis.

• Explain with the help of a schematic diagram, major events (or phases) in the cell cycle.

• Briefly explain why some cells divide and some do not.

• Briefly describe how the cell cycle is regulated.

• What would be the effect of a loss-of-function mutation of the p53 gene on cells? Explain.

Lecture 5: A primer in intercellular communication

• List the various types of intercellular communication.

• Describe what is meant by each of the following: neurocrine communication, endocrine

communication, paracrine communication, autocrine communication, juxtacrine

communication – with an example for each.

• Briefly describe the major differences between endocrine, neurocrine, and paracrine

communication.

• Briefly describe the cellular mechanism of action of hormones.

• Is specificity of communication an attribute common to all types of intercellular

communication? Explain.

Lecture 6: Body fluid compartments

• Classify body fluid compartments. Mention the volumes of body fluid compartments in a

healthy adult male weighing 70 kg.

• Describe the principle used in the measurement of body fluid volumes and RBC volume.

• Mention the indicator that is used to measure the volume of plasma, ECF, and total body

water. In each case, explain why these indicators are chosen for measuring them

• How you would estimate interstitial fluid volume?

• How you would estimate ICF volume?

• What is the relationship between hematocrit and blood volume? • What does the term ‘lean body mass’ refer to?

• What is the relationship between lean body mass and total body mass?

• Briefly describe the principle that is used in the estimation of body fat by the impedance

method.

• Briefly describe gender differences in body composition.






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Lecture 7: Osmosis; osmolality of body fluids; physiologic solutions

• What is meant by each of the following terms: osmosis; osmole; osmolality; effective

osmole; ineffective osmole?

• Explain the difference between osmolality and tonicity with a suitable example.

• Describe the cellular mechanism of osmosis.

• Calculate osmolality of solutions commonly administered to humans when the relevant

data are provided. Calculate osmolality of plasma when the relevant data are provided.

• Classify dehydration based on tonicity of ECF, with an example for each type. Describe the

changes in steady state volumes of ICF and ECF compartments in each type of

dehydration.

• Predict changes in ICF and ECF volumes and osmolality when solutions of known

osmolality are administered to healthy, normally hydrated individuals or individuals with

dehydration.

• Classify overhydration based on tonicity of ECF with an example for each type.

• Appreciate the physiologic basis for use of various solutions in the management of

dehydration.

Lectures 8 and 9: An introduction to the concept of homeostasis and analysis of physiologic

control systems

• Explain what is meant by the term ‘homeostasis’ with suitable examples.

• Briefly describe Claude Bernard’s contribution to the concept of homeostasis?

• Describe (using a schematic diagram) the components and working of a ‘negative feedback

control system’.

• Describe the meaning of the following terms (with examples): set point, sensor, integrator,controller, effector, variable, gain of a system.

• Distinguish ‘feedback control’ from ‘feedforward control’ using examples.

• Distinguish negative feedback control from positive feedback control with an example for

each.

• Homeostatic mechanisms have finite capacity. Illustrate.

• Also, students will appreciate that homeostatic mechanisms have survival value and that

disease may be viewed as a deviation from homeostasis.

BASICS OF HAEMATOLOGY:

Lecture 10: Bone marrow and haematopoiesis; classification of formed elements of blood:

• Enumerate the important sites of haematopoiesis at various stages in life.

• Distinguish yellow marrow from red bone marrow.

• Classify formed elements of blood.






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• Describe the organisation of the bone marrow and provide a general theoretical description

of the process of haematopoiesis and its regulation.

• Predict the general consequences of disease processes affecting the bone marrow.

Lecture 11: Structure and function of red blood cells (RBC):

• Describe the morphologic characteristics of mature RBC.

• Describe the functions of the cytoskeleton with special reference to RBC.

• Describe the structure of haemoglobin and enumerate its properties (including its reactions

with oxygen).

• List the factors that affect the oxygen carrying capacity of haemoglobin.

• What is the oxygen carrying capacity of adult haemoglobin?

• Hb F has greater affinity for oxygen compared to Hb A. What is the underlying

mechanism?

Lecture 12: Erythropoiesis:

• Describe how red blood cells are formed from precursor cells in the bone marrow. How is

this process regulated?

• Describe the role of vitamins and minerals in erythropoiesis.

• Describe the functions of erythropoietin and the effects of other hormones on

erythropoiesis.

• Describe the metabolism of iron with special reference to its utilization for haematopoiesis.

• Briefly describe how absorption of iron from the gastrointestinal tract is regulated.

• Briefly describe how iron is transported to sites of hematopoiesis.

• Briefly describe how iron is stored in the bone marrow.• What is a reticulocyte? How does it appear under the compound microscope? What is the

normal reticulocyte count? What is the significance of the reticulocyte count?

• Explain the mechanisms responsible for anemia when there is a deficiency of each one of

the following: iron, vitamin B12, folic acid, and pyridoxine.

Lecture 13: Anaemia

• What is the normal concentration of hemoglobin in blood – in adult males, adult females,

newborns, and infants?

• How is anaemia defined in clinical practice?• Explain the physiologic basis of exercise intolerance and breathlessness in an individual

with anaemia.

• How is blood hemoglobin concentration estimated? Outline the principle of the Sahli’s

method for estimating blood hemoglobin.






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• Define the following RBC indices – mean corpuscular volume, mean corpuscular

hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width

Mention the normal ranges for each and the significance of deviations from normal.

• Describe how anaemias are classified on the basis of RBC indices.

• Briefly describe the peripheral blood picture observed in each one of the following

anaemias: iron deficiency anaemia; vitamin B12 deficiency anaemia; and folate deficiency

anaemia.

• What is the basic defect in thalassaemia?

• What is the basic defect in sickle cell anaemia?

• What is the basic defect in hereditary spherocytosis?

• Define polycythemia. How is polycythemia classified? Give an example of each. Briefly

describe the mechanism of each type of polycythemia.

Lecture 14: Blood groups:

• What is the basis of classification of blood groups?

• Describe the ABO and Rhesus system of blood groups.

• Describe the pattern of inheritance of the A, B and Rhesus antigens.

• State ‘Landsteiner’s law’.

• Explain why O, Rh-blood group is a universal donor , and AB, Rh

+blood group is a

universal recipient.

• How is cross-matching done? What is its importance?

• Explain the consequences of ABO incompatibility.

• Explain the consequences of Rh incompatibility.

• Describe the pathogenesis of hemolytic disease of the newborn (erythroblastosis foetalis).• What is the physiologic basis of the strategy used to prevent hemolytic disease of the

newborn?

Across this Block

• Describe the source, metabolism and excretion of bilirubin.

• Define jaundice. What are the three major types of jaundice?

• On the basis of laboratory tests, how would you identify each type of jaundice?

Lecture 15: Leukocytes • Describe the morphology of each of the following types of white blood cells as seen in a

stained blood smear, using a schematic diagram: neutrophil, eosinophil, basophil,

monocyte, lymphocyte.

• Briefly describe the functions of each type of leukocyte.

• Name the various tissue macrophages.

• Describe how a monocyte/macrophage functions.






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• Briefly describe how leukopoiesis is regulated.

• What is the normal total leukocyte count? What is the normal differential leucokyte count?

• List two common causes of leukocytosis and leukopenia.

• Distinguish leukocytosis from leukemia.

Lecture 16: Composition of Plasma; Functions of Plasma Proteins

• What is the normal plasma volume?

• What is meant by packed cell volume (or haematocrit)?

• Briefly describe the composition of plasma.

• Classify plasma proteins on the basis of their electrophoretic mobility.

• Outline the functions of plasma proteins.

• Describe the pathophysiologic consequences of hypoproteinemia.

• Describe the factors that affect movement of fluid across capillaries.

• What is lymph? How is it formed? How does it compare to blood in its composition?

• How does hypoalbuminemia result in oedema?

Lectures 17 and 18: Haemostasis

• What is haemostasis? What is primary (temporary haemostasis)? What is definitive

hemostasis?

• Describe the structure and functions of platelets.

• What is the normal platelet count?

• Briefly describe how platelet production is regulated.

• List two common causes of thrombocytopenia, and two causes of thrombocytosis.

• Where are platelets sequestered? Explain.• Briefly describe the role of platelets in haemostasis.

• List the clotting factors with their roman numerals and common names.

• Where are clotting factors synthesized?

• Describe the cascade of physiologic responses that ensues when a blood vessel wall is

damaged and bleeding results.

• Distinguish stimuli that activate the intrinsic and the extrinsic clotting cascades.

• Describe the role of vitamin K in haemostasis.

• Describe the mechanisms that exist to lyse clots. What is the functional significance of this

system?• What is meant by clot retraction? What is the underlying mechanism?

• Give examples of in vitro and in vivo anticoagulants. What is the mechanism of

anticoagulant action of the following: heparin, warfarin, potassium oxalate, and ammonium

oxalate.






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• What is bleeding time? How is it estimated? What is the normal value? What does bleeding

time signify? Name two conditions in which bleeding time is prolonged and describe the

mechanism that prolongs bleeding in each case.

• What is the basic defect in von Willebrand’s disease?

• What is the basic defect in hemophilia A?

• Why does vitamin C deficiency predispose to vascular fragility?

• What is clotting time? How is it estimated? What is the normal value? What does clotting

time signify? Name two conditions in which clotting time is prolonged.

• What is prothrombin time? What is activated partial thromboplastin time? What is the

normal value of each? What is the purpose of these tests?

PHYSIOLOGY OF NERVE AND MUSCLE:

Lecture 19: Functional organization of neurons; introduction to glia; and neurotrophins.• Describe the structural and functional organization of neurons.

• What is meant by axoplasmic transport? How does it take place?

• What is anterograde transport and what is retrograde transport ?

• What are glial cells? How are they different from neurons? List the types of glial cells.

• Briefly describe the functions of each type of glial cell.

• What are neurotrophins? Give examples. Describe the known functions of neurotrophins.

Lecture 20: Membrane potentials 1: genesis of the resting membrane potential (RMP)

• What is meant by resting membrane potential? How is it recorded?

• Describe the mechanism of the resting membrane potential.

• Explain why the magnitude of the resting membrane potential differs between tissues.

• Explain what is meant by ‘equilibrium potential’ of an ion? What is the Nernst equation?

• In nerve and muscle, the resting membrane potential is close to the equilibrium potential of

potassium. What is the underlying mechanism?

• Explain the effect of a rise in plasma concentration of [K] from 5 mM to 10 mM on the

RMP in cardiac muscle cells.

Lecture 21: Membrane potentials 2: electrotonic potentials, action potentials

• What are electrotonic potentials? What are the two basic types of electrotonic potentials?

• In nerve-muscle physiology, what is the term excitability used to refer to?

• What is an action potential? What is a ‘nerve impulse’? What triggers an action potential?

• Draw a labelled schematic diagram of the action potential in a nerve fibre.

• Describe the ionic basis of the action potential in a nerve fibre.






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• Describe what happens to excitability of the nerve fibre during and immediately after the

action potential.

• How is an action potential propagated?

• Describe what is meant by: absolute refractory period, relative refractory period.

• Describe the “all-or-none” law in reference to nerve and muscle excitability.

• What is meant by orthodromic and antidromic conduction?

• Describe how conduction of nerve impulses occurs in myelinated neurons, and the

physiological advantages of myelination. What would be the functional consequence of a

disease process causing extensive demyelination of neurons?

Lecture 22: Classification of nerve fibres; properties of mixed nerves

• What is a mixed nerve?

• What is the Erlanger-Gasser classification of nerve fibres in a mammalian peripheral

nerve?

• What is meant by a compound nerve action potential (CNAP)?

• Draw a schematic diagram of a CNAP.

• Describe the classification used for sensory neurons.

Lecture 23: Functional organization of skeletal, cardiac and smooth muscle:

• Describe the functional organization of skeletal, cardiac and smooth muscle types under the

following headings: microanatomy, electrical properties, and mechanical properties.

• What are the types of fibres in skeletal muscle?

• What are the types of smooth muscle? Give an example of each.

Lecture 24: Mechanism of neuromuscular transmission

• Describe the mechanism of neuromuscular transmission with special reference to

transmission in skeletal muscle.

• What is meant by miniature end-plate potential? What is the underlying mechanism?

• Explain the pathogenesis of the muscle weakness that occurs in myasthenia gravis and

mention therapeutic strategies for overcoming this defect

• What is the basic defect in Lambert-Eaton syndrome and what is the effect of this on

neuromuscular transmission?

• What would be the effect of an acetylcholinesterase inhibitor on muscle strength in anindividual with autoantibodies to nicotinic acetylcholine receptors in skeletal muscle motor

end plate?

Lecture 25: Mechanism of contraction and relaxation of skeletal muscle

• Describe the molecular mechanism of contraction of skeletal muscle.

• Describe the sliding filament theory of muscle contraction.






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• Describe the role of regulatory proteins and calcium in muscle contraction.

• Briefly describe the relationship between length and tension in skeletal muscle.

• Briefly describe how forces generated by contraction of sarcomeres are transmitted to

result in muscle shortening.

• What is isometric contraction? What is isotonic contraction? Give an example for each.

What is the fundamental difference between these two types of muscle contractions?

• What is the physiologic mechanism of rigor mortis?

Lecture 26: Properties of skeletal muscles in the intact organism

• Describe the differences between type I and type II muscle fibres.

• What is a motor unit?

• What is meant by muscle tone?

• Tone in skeletal muscles is neurogenic. What is the evidence supporting this statement?.

• Describe the size principle.

• Describe how force of skeletal muscle contractions is graded.

• Describe the acute and chronic effects of denervation of skeletal muscle.

• Describe how electromyography can be used to assess properties of skeletal muscle.

• Explain what is meant by denervation hypersensitivity (or supersensitivity) and the

mechanisms involved.

Lecture 27: Comparison of properties of skeletal, smooth and cardiac muscle

• Compare and contrast the electrical and mechanical properties of the three muscle types.

• How does the RMP in smooth muscle compare to that in skeletal muscle?

• How is activity of smooth muscle and cardiac muscle regulated, and how does this comparewith regulation of skeletal muscle?

• Outline the molecular basis of smooth muscle contraction. How does it differ from that in

skeletal muscle?

• How is grading of muscular force achieved in cardiac and smooth muscle?

• Cardiac muscle cannot be tetanized. Explain the underlying physiologic basis.

• What is the relationship between length and tension in cardiac muscle and smooth muscle?

• What is the relationship between cytosolic [Ca] and the force of cardiac muscle

contraction, smooth muscle contraction?

• Briefly describe the role of gap junctions in the heart and in visceral smooth muscle.

Lecture 28: Synapses: basic mechanism of transmission; synaptic integration

• What is a neuronal synapse? Describe the basic mechanism of transmission of impulses

across a neuronal synapse.

• Describe possible responses (to synaptic transmission) in postsynaptic neurons and the

mechanism of each.






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• Describe what is meant by the term synaptic integration.

• What is the ionic basis of an excitatory post-synaptic potential (EPSP)?

• What is the ionic basis of an inhibitory post-synaptic potential (IPSP)?

• How do EPSPs and IPSPs affect excitability of postsynaptic neurons?

• What is the difference between post-synaptic potentials and action potentials?

• How are neurotransmitters classified based on responses they elicit in postsynaptic

neurons?

• What is meant by synaptic delay?

Lecture 29: Structural and functional organization of the autonomic nervous system (ANS)

• Briefly describe the functional organisation of the autonomic nervous system.

• Why has the parasympathetic limb of the ANS been called the “anabolic nervous system”?

• Explain how the organization of the sympathetic nervous system enables it to contribute to

the fight or flight reaction.

Lecture 30: Neurotransmitters and neurotransmitter receptors in the ANS

• Name the major neurotransmitter released by each of the following types of autonomic

neurons: sympathetic preganglionic neurons; sympathetic postganglionic neurons;

parasympathetic preganglionic neurons; and parasympathetic postganglionic neurons.

• Enumerate the adrenergic and cholinergic receptors located in the autonomic nervous

system and effector sites. List examples of physiologic effects mediated by each one of

these receptors.

• Briefly describe the various types of disposition of neurotransmitters released into the

synaptic cleft with suitable examples.

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