Physiology Review

1. Physiology Review A work in Progress

2. National Boards Part I • Physiology section • Neurophysiology (23%) • Membrane potentials, action potentials, synpatic transmission • Motor function • Sensory function • Autonomic function • Higher cortical function • Special senses

3. National Boards Part I • Physiology (cont) • Muscle physiology (14%) • Cardiac muscle • Skeletal muscle • Smooth muscle • Cardiovascular physiology (17%) • Cardiac mechanisms • Eletrophysiology of the heart • Hemodynamics • Regulation of circulation • Circulation in organs • Lymphatics • Hematology and immunity

4. National Boards Part I • Physiology (cont) • Respiratory physiology (10%) • Mechanics of breathing • Ventilation, lung volumes and capacities • Regulation of respiration • O2 and CO2 transportation • Gaseous Exchange • Body Fluids and Renal physiology (11%) • Regulation of body fluids • Glomerular filtration • Tubular exchange • Acid-base balance

5. National Boards Part I • Physiology (cont) • Gastrointestinal physiology (10%) • Ingestion • Digestion • Absorption • Regulation of GI function • Reproductive physiology (4%) • Endocrinology (8%) • Secretion of hormones • Action of hormones • Regulation • Exercise and Stress Physiology (3%)

6. Weapons in neurophysiologist’s armory • Recording • Individual neurons • Gross potentials • Brain scans • Stimulation • Lesions • Natural lesions • Experimental lesions

7. Neurophysiology • Membrane potential • Electrical potential across the membrane • Inside more negative than outside • High concentration of Na+ outside cell • High concentration of K+ inside cell • PO4= SO4= Protein Anions trapped in the cell create negative internal enviiornment

8. Membrane physiology • Passive ion movement across the cell membrane • Concentration gradient • High to low • Electrical gradient • Opposite charges attract, like repel • Membrane permeability • Action potential • Pulselike change in membrane permeability to Na+, K+, (Ca++)

9. Membrane physiology • In excitable tissue an action potential is a pulse like  in membrane permeability • In muscle permeability changes for: • Na+ •  at onset of depolarization,  during repolarization • Ca++ •  at onset of depolarization,  during repolarization • K+ •  at onset of depolarization,  during repolarization

10. Passive ion movement across cell • If ion channels are open, an ion will seek its Nerst equilibrium potential • concentration gradient favoring ion movement in one direction is offset by electrical gradient

11. Resting membrane potential (Er) • During the Er in cardiac muscle, fast Na+ and slow Ca++/Na+ are closed, K+ channels are open. • Therefore K+ ions are free to move, and when they reach their Nerst equilibrium potential, a stable Er is maintained

12. Na+/K+ ATPase (pump) • The Na+/K+ pump which is energy dependent operates to pump Na+ out & K+ into the cardiac cell at a ratio of 3:2 • therefore as pumping occurs, there is net loss of one + charge from the interior each cycle, helping the interior of the cell remain negative • the protein pump utilizes energy from ATP

13. Ca++ exchange protein • In the cardiac cell membrane is a protein that exchanges Ca++ from the interior in return for Na+ that is allowed to enter the cell. • The function of this exchange protein is tied to the Na+/K+ pump • if the Na+/K+ pump is inhibited, function of this exchange protein is reduced & more Ca++ is allowed to accumulate in the cardiac cell  contractile strength.

14. Action potential • Pulselike change in membrane permeability to Na+, K+, (Ca++) • Controlled by “gates” • Voltage dependent • Ligand dependent • Depolarization • Increased membrane permeability to Na+ (Ca++) • Na+ influx • Repolarization • Increased membrane permeability to K+ • K+ efflux

15. Refractory Period • Absolute • During the Action Potential (AP), cell is refractory to further stimulation (cannot be restimulated) • Relative • Toward the end of the AP or just after repolarization a stronger than normal stimulus (supranormal) is required to excite cell

16. All-or-None Principle • Action potentials are an all or none phenomenon • Stimulation above threshold may cause an increased number of action potentials but will not cause a greater action potential

17. Propagation • Action potentials propagate (move along) as a result of local currents produced at the point of depolarization along the membrane compared to the adjacent area that is still polarized • Current flow in biologic tissue is in the direction of positive ion movement or opposite the direction of negative ion movement

18. Conduction velocity • Proportional to the diameter of the fiber • Without myelin • 1 micron diameter = 1 meter/sec • With myelin • Accelerates rate of axonal transmission 6X and conserves energy by limiting depolarization to Nodes of Ranvier • Saltatory conduction-AP jumps internode to internode • 1micron diameter = 6 meter/sec

19. Synapes • Specialized junctions for transmission of impulses from one nerve to another • Electrical signal causes release of chemical substances (neurotransmitters) that diffuse across the synapse • Slows neural transmission • Amount of neurotransmitter (NT) release proportional to Ca++ influx

20. Neurotransmitters • Acetylcholine • Catacholamines • Norepinephrine • Epinephrine • Serotonin • Dopamine • Glutamate • Gamma-amino butyric acid (GABA) • Certain amino acids • Variety of peptides

21. Neurons • May release more than one substance upon stimulation • Neurotransmitter like norepinephrine • Neuromodulator like neuropeptide Y (NPY)

22. Postsynaptic Cell Response • Varies with the NT • Excitatory NT causes a excitatory postsynaptic potential (EPSP) • Increased membrane permeability to Na+ and/or Ca++ influx • Inhibitory NT causes an inhibitory postsynaptic potential (IPSP) • Increased membrane permeability to Cl- influx or K+ efflux • Response of Postsynpatic Cell reflects integration of all input

23. Response of Postsynaptic Cell • Stimulation causing an AP •  EPSP >  IPSP > threshold • Stimulation leading to facilitation •  EPSP >  IPSP < threshold • Inhibition •  EPSP <  IPSP

24. Somatic Sensory System • Nerve fiber types (Type I, II, III, IV) based on fiber diameter (Type I largest, Type IV smallest) • Ia - Annulospiral (1o) endings of muscle spindles • Ib - From golgi tendon organs • II • Flower spray (2o) endings of muscle spindles • High disrimination touch ( Meissner’s) • Pressure • III • Nociception, temperature, some touch (crude) • IV- nociception and temperature (unmyelinated) crude touch and pressure

25. Transduction • Stimulus is changed into electrical signal • Different types of stimuli • mechanical deformation • chemical • change in temperature • electromagnetic

26. Sensory systems • All sensory systems mediate 4 attributes of a stimulus no matter what type of sensation • modality • location • intensity • timing

27. Receptor Potential • Membrane potential of the receptor • A change in the receptor potential is associated with opening of ion (Na+) channels • Above threshold as the receptor potential becomes less negative the frequency of AP into the CNS increases

28. Labeled Line Principle • Different modalities of sensation depend on the termination point in the CNS • type of sensation felt when a nerve fiber is stimulated (e.g. pain, touch, sight, sound) is determined by termination point in CNS • labeled line principle refers to the specificity of nerve fibers transmitting only one modality of sensation • Capable of change, e.g. visual cortex in blind people active when they are reading Braille

29. Adaptation • Slow-provide continuous information (tonic)-relatively non adapting-respond to sustained stimulus • joint capsul • muscle spindle • Merkel’s discs • punctate receptive fields • Ruffini end organ’s (corpusles) • activated by stretching the skin

30. Adaptation • Rapid (Fast) or phasic • react strongly when a change is taking place • respond to vibration • hair receptors 30-40 Hz • Pacinian corpuscles 250 Hz • Meissner’s corpuscles- 30-40 Hz • (Hz represents optimum stimulus rate)

31. Sensory innervation of Spinal joints • Tremendous amount of innervation with cervical joints the most heavily innervated • Four types of sensory receptors • Type I, II, III, IV

32. Types of joint mechanoreceptors • Type I- outer layer of capsule- low threshold, slowly adapts, dynamic, tonic effects on LMN • Type II- deeper layer of capsule- low threshold, monitors joint movement, rapidly adapts, phasic effects on LMN • Type III- high threshold, slowly adapts, joint version of GTO • Type IV- nociceptors, very high threshold, inactive in normal joint, active with swelling, narrowing of joint.

33. Stereognosis • The ability to perceive form through touch • tests the ability of dorsal column-medial lemniscal system to transmit sensations from the hand • also tests ability of cognitive processes in the brain where integration occurs • The ability to recognize objects placed in the hand on the basis of touch alone is one of the most important complex functions of the somatosensory system.

34. Receptors in skin • Most objects that we handle are larger than the receptive field of any receptor in the hand • These objects stimulate a large population of sensory nerve fibers • each of which scans a small portion of the object • Deconstruction occurs at the periphery • By analyzing which fibers have been stimulated the brain reconstructs the pattern

35. Mechanoreceptors in the Skin • Rapidly adapting cutaneous • Meissner’s corpuscles in glabrous (non hairy) skin- (more superficial) • signals edges • Hair follicle receptors in hairy skin • Pacinian corpuscles in subcutaneous tissue (deeper)

36. Mechanoreceptors in the Skin • Slowly adapting cutaneous • Merkel’s discs have punctate receptive fields (superficial) • senses curvature of an object’s surface • Ruffini end organs activated by stretching the skin (deep) • even at some distance away from receptor

37. Mechanoreceptors in Glabrous (non hairy) Skin

38. Somatic Sensory Cortex • Receives projections from the thalamus • Somatotopic organization (homunculus) • Each central neuron has a receptive field • size of cortical representation varies in different areas of skin • based on density of receptors • lateral inhibition improves two point discrimination

39. Somatosensory Cortex • Two major pathways • Dorsal column-medial lemniscal system • Most aspects of touch, proprioception • Anterolateral system • Sensations of pain (nociception) and temperature • Sexual sensations, tickle and itch • Crude touch and pressure • Conduction velocity 1/3 – ½ that of dorsal columns

40. Somatosensory Cortex (SSC) • Inputs to SSC are organized into columns by submodality • cortical neurons defined by receptive field & modality • most nerve cells are responsive to only one modality e.g. superficial tactile, deep pressure, temperature, nociception • some columns activated by rapidly adapting Messiner’s, others by slowly adapting Merkel’s, still others by Paccinian corp.

41. Somatosensory cortex • Brodman area 3, 1, 2 (dominate input) • 3a-from muscle stretch receptors (spindles) • 3b-from cutaneous receptors • 2-from deep pressure receptors • 1-rapidly adapting cutaneous receptors • These 4 areas are extensively interconnected (serial & parallel processing) • Each of the 4 regions contains a complete map of the body surface “homonculus”

42. Somatosensory Cortex • 3 different types of neurons in BM area 1,2 have complex feature detection capabilities • Motion sensitive neurons • respond well to movement in all directions but not selectively to movement in any one direction • Direction-sensitive neurons • respond much better to movement in one direction than in another • Orientation-sensitive neurons • respond best to movement along a specific axis

43. Other Somatosensory Cortical Areas • Posterior parietal cortex (BM 5 & 7) • BM 5 integrates tactile information from mechanoreceptors in skin with proprioceptive inputs from underlying muscles & joints • BM 7 receives visual, tactile, proprioceptive inputs • intergrates stereognostic and visual information • Projects to motor areas of frontal lobe • sensory initiation & guidance of movement

44. Secondary SSC (S-II) • Secondary somatic sensory cortex (S-II) • located in superior bank of the lateral fissure • projections from S-1 are required for function of S-II • projects to the insular cortex, which innervates regions of temporal lobe believed to be important in tactile memory

45. Pain vs. Nociception • Nociception-reception of signals in CNS evoked by stimulation of specialized sensory receptors (nociceptors) that provide information about tissue damage from external or internal sources • Activated by mechanical, thermal, chemical • Pain-perception of adversive or unpleasant sensation that originates from a specific region of the body • Sensations of pain • Pricking, burning, aching stinging soreness

46. Nociceptors • Least differentiated of all sensory receptors • Can be sensitized by tissue damage • hyperalgesia • repeated heating • axon reflex may cause spread of hyperalgesia in periphery • sensitization of central nociceptor neurons as a result of sustained activation

47. Sensitization of Nociceptors • Potassium from damaged cells-activation • Serotonin from platelets- activation • Bradykinin from plasma kininogen-activate • Histamine from mast cells-activation • Prostaglandins & leukotriens from arachidonic acid-damaged cells-sensitize • Substance P from the 1o afferent-sensitize

48. Fast A delta fibers glutamate neospinothalamic mechanical, thermal good localization sharp, pricking terminate in VB complex of thalamus Slow C fibers substance P paleospinothalamic polymodal/chemical poor localization dull, burning, aching terminate; RF tectal area of mesen. Periaqueductal gray Nociceptive pathways

49. Nociceptive pathways • Spinothalamic-major • neo- fast (A delta) • paleo- slow (C fibers) • Spinoreticular • Spinomesencephalic • Spinocervical (mostly tactile) • Dorsal columns- (mostly tactile)

50. Peripheral Gating theory involves inhibitory interneruon in cord impacting nocicep. projection neurons inhibited by C fibers stimulated by A alpha & beta fibers TENS Central Direct electrical + to brain -> analgesia Nociceptive control pathways descend to cord Endogenous opiods Pain Control Mechanisms