Q 5. a. Give the effects of cortisol on protein metabolism. (2.5) b. How cortisol prevents the development of inflammation? (2.

5) KEY 5 a. Cortisol decreases amino acid transport into extrahepatic tissues. In excess cortisol, severe muscle weakness develops. (1) Increase of liver and plasma proteins: Catabolism of proteins in cells continues Amino acids release into plasma Enhanced transport of a.a in liver occurs Enhanced ezymes required for protein synthesis Increased utilization of amino acids by liver, Increased deamination of amino acids, Increased protein synthesis in liver, Increased formation of plasma proteins by liver, (1.5) Increased conversion of amino acids into glucose i.e, gluconeogenesis. KEY b. Stabilization of lysosomal membranes, thus decreasing release of proteolytic enzymes from lysosomes. Decreased capillary permeability, preventing loss of plasma into tissues Decreased WBCc migration into inflammed area, due to, Decreased formation of prostaglandins and leukotriens PGs and leukotriens cause vasodilation, capillary permeability and mobility of WBCs normally. Immune depression, with reduction of lymphocyte production. T lymphocytes specially Decreased T cells and antibodies in inflammed area decreases tissue reactions that otherwise promote inflammation. Reduces fever due to decreased release of interleukin-1 from WBCs. Decreased temp. then reduces the degree of vasodilation. Due to anti-inflammatory effects, cortisol helps combating inflammatory diseases like, RA, rheumatic fever, glomerulonephritis etc, preventing damaging effects of inflammation. (2.5) ----------------------------------------------------------------------------------------------------

Q.1a. Name 5 sensations carried by dorsal column medial lemniscal system (2.5 marks) b. Draw the dorsal column pathway (2 marks) c. Specifically mention the level of sensory decussation. (0.5 mark) Key:1a (Reference: p 588 Guyton 11th Ed.) Sensations carried by dorsal column: (ANY 5 = 0.5 Mark each = 2.5 marks) fine touch fine pressure proprioception (sense of position & movement) vibration 2 point tactile discrimination Stereognosis Graphesthesia Topognosis (Tactile localization) Extinction phenomenon Key :1c (Reference: p 588 Guyton) Level of sensory decussation : From nucleus gracilus & nucleus cuneatus in medulla, 2nd order nerve fibers (internal arcuate fibers) arise decussate in medulla Sensory decussation. ---------------------------------------------------------------------------------------------------Key :1b DORSAL COLUMN PATHWAY: (see diagram on next page) Reference: diagram provided by physiology department to book-shop. Distribution of marks: marks) 1st order neuron: Dorsal root of spinal cord mark) 2nd order neuron: From medullary nuclei (Nucleus gracilus & cuneatus) mark) 3rd order neuron: From thalamic nuclei (VPL & VPM) mark) Sensory area: S1 / Somatic sensory area 1 / Brodmanns area 3,1,2: mark)

(2 (0.25 (0.25 (0.25 (0.25

Ipsilateral ascent from dorsal white column of spinal cord: mark) Sensory decussation (crossing over) in medulla or Medial lemniscus formed after crossing over: mark) Fasiculus Gracilus & Cuneatus: (starting from T6) mark) Levels of ascent: Spinal cord, medulla, thalamus & cortex: mark)

(0.25

(0.25 (0.25 (0.25

Key :1b

Q.3 What is the nerve supply of muscle spindle? How is it stimulated? Enumerate its functions. (1.5+1.5+2 marks) th Key:3 p 675, Guyton 11 Ed. NERVE SUPPLY: Sensory nerve supply of intrafusal fibers: 2 types of sensory nerve endings: 1) Primary or annulospiral: Present around central portion of both nuclear bag & nuclear chain fibers. Endings of type IA fibers with conduction velocity: 70-120 m/sec. (0.5) 2) Secondary or flower spray: Endings of type II nerve fibers. Velocity is 30-70 m/sec. Only around nuclear chain fibers. (0.5) Motor nerve supply of intrafusal fibers: Gamma efferents supply end portion of intrafusal fibers & end portions are contractile. Conduction velocity: 15-30 m/sec. Forms 30% of nerve fibers in the ventral root of spinal nerve (motor root). Alpha motor neuron supply the extrafusal fibers. (0.5)

Muscle spindle stimulation: Muscle spindle is stimulated when its central portion is stretched by either of 2 ways: i) When muscle is stretched, along with that, muscle spindle is also stretched, so gets stimulated. (0.5) ii) Internal stretching: i-e., muscle spindle gets stretched without stretching of muscle,through gamma efferents which supply end portions of intrafusal fibers which contract so central portion is stretched, leading to stimulation. This is the mechanism of muscle tone.

(0.5) When a static / slow stretch is applied to a muscle, there is increase in muscle length leading to increased discharge of impulses from both primary & secondary nerve endings & remains increased as long as muscle is stretched. Nuclear chain fibers are involved in static stretch. (0.25) When a rapid stretch is applied, there is rapid increase in length of muscle & primary nerve endings discharge increases & this discharge decreases when rapid increase in length stops. Nuclear bag fibers are involved in dynamic response (e.g., knee jerk) (0.25)

FUNCTIONS OF MUSCLE SPINDLE: marks)

(Any 4 = 0.5 mark each = 2

1) Helps to regulate length of muscle: It prevents length of muscle to go beyond limits. When a muscle is stretched, it contracts (stretch reflex). So increase in muscle length beyond limit is prevented & when muscle contracts & shortens, the discharge of impulses from muscle spindle decreases leading to muscle relaxation, so too much muscle shortening is also prevented. 2) Involved in muscle tone mechanism: 3) Are receptors in tendon jerks: which are clinically important. All tendon jerks are monosynaptic stretch reflexes & receptors are muscle spindles. 4) Stretch reflex helps in lifting of load / weight: muscle is stretched & it contracts, so helps in lifting. 5) For voluntary smooth movements: There is coactivation of alpha & gamma motor neurons. Whenever there is voluntary movement, impulses from motor cortex simultaneously go to alpha & gamma motor neurons, leading to smooth voluntary contraction

Q.2 Ahmed received a back-bone injury in a road side accident. On CT scan, he was diagnosed as a case of left hemisection of spinal cord. a. What is this syndrome called? b. What loss is expected at the level of lesion? c. What loss is expected below the level of lesion? (1+2+2 marks) Key:2 (Reference: p 606, Guyton 11th Ed.) a. Brown Sequard Syndrome (1)

b. At the level of lesion: Ipsilaterally, there is Lower Motor Neuron type of paralysis, due to damage to ventral horn motor neurons (they are lower motor neurons). (1) Ipsilaterally, there is a band of anesthesia (loss of all sensations on same side). (0.5) There is no motor or sensory loss on opposite side. (0.5) c. Below the level of lesion: Motor loss: On ipsilateral side, Upper Motor Neuron paralysis (due to damage to pyramidal & extra-pyramidal tracts) occurs. On the opposite side, there is no motor loss. (1) Sensory loss: On ipsilateral side, there is loss of fine touch, 2 point tactile discrimination, vibration & proprioception (damage to dorsal column medial lemniscal system). On opposite side, there is loss of pain & temperature, tickle, itch & crude touch. This sensory loss is 2-3 dermatomes below the level of spinal cord, because of oblique crossing over of Spinothalamic Tract to opposite side. (1)

Q.7 How is osmolarity of medullary interstitium multiplied? Illustrate with diagram. (2.5)

What is the role of urea reabsorption in it? Illustrate with diagram.

(2.5)

Key:7 (p 351-352, Guyton 11th Ed.) Basic factor is active reabsorption of sodium with secondary active transport of potassium & chloride from thick ascending segment of LOH. (0.5) Reabsorption of urea, mainly from collecting tubules & collecting ducts (following reabsorption of water under ADH effect). (0.5) Water reabsorption from distal part of renal tubules. (0.5)

(1) Role of urea reabsorption: Active reabsorption of sodium, potassium, chloride from thick ascending limb of loop, gives omolarity of 700 mOsm/L. (0.5) Urea reabsorption from collecting tubules gives osmolarity of 500 mOsm/L. This is the importance of urea reabsorption. They make total of 1200 mOsm/L at tip of LOH or tip of medullary pyramid. (0.5)

(0.5)

 Reabsorption of water from distal part of renal tubules also help to produce hyperosmolarity under the effect of ADH. Water reabsorption follows the urea reabsorption. Once medullary interstitium is hyperosmolar, urine becomes concentrated, otherwise not. (1)

Q.9 Azmat, a 65 years old known diabetic & hypertensive since last 20 years, presents with generalized edema, nausea, vomiting, mental deterioration, confusion, & sudden collapse passing on to deep coma. Lab investigations reveal: BUN (Blood Urea Nitrogen) = high, Serum Creatinine = high, pH = 7.2, Hb = 9 g/dl & high serum calcium level. a) What is the most likely diagnosis of this almost terminal condition of the patient? b) Give physiological justification for his lab investigations. (0.5+4.5) Key:9 p 406-407 Guyton 11th Ed a. Chronic Renal Failure (0.5) b. Progressive loss of function of more & more nephrons, due to diabetic & hypertensive nephropathy, both of which lead to end stage renal disease, that slowly decrease overall renal function. (0.5)

(0.5) Nephron function in chronic renal failure 1) loss of functional nephrons requires the surviving nephrons to excrete more water & solutes. (0.5) 2) ISOSTHENURIA: Inability of kidney to concentrate or dilute urine (0.5) Effects of renal failure on body fluids: 1) Water retention due to renal failure lead to development of edema. (0.5)

2) UREMIA: Increase in urea & other non-protein nitrogens (Azotemia), which include: Urea, Uric acid & Creatinine. (0.5) 3) Acidosis in renal failure: Normally body produces more metabolic acid than metabolic alkali In renal failure, acid accumulates in body fluids. So PH dropped to 7.2 from 7.4. (0.5) 4) Anemia occured in chronic renal failure due to decreased erythropoietin Secretion (0.5) 5) Osteomalacia (partial absorption of bones) in chronic renal failure due to reduced production of active Vit. D & by phosphate retention by kidneys. Another cause of skeletal demineralization in chronic renal failure is rise in serum phospate conc. due to reduced GFR. It causes increased binding of phosphate with calcium, leading to low serum ionized calcium conc. causing stimulation of PTH (Secondary hyperparathyroidism) & resulting release of calcium from bones. (0.5)

----------------------------------------Q12. Enlist the physiological action of estrogen in female body. Key: 12 (p1017, 1018 Guyton 11th Ed) (Each point carries 0.5 marks so 10 points= 5 mark)

(5)

The physiological functions are: 1. At puberty, cause marked growth and enlargement of female sex organs 2. Change of vaginal epithelium from cuboidal type to stratified type 3. Cause proliferation of the uterine endometrium and epithelium of fallopian tubes 4. Cause development of breast stroma, duct system and deposition of fat in the breasts 5. Stimulate bone growth and inhibit osteoclastic activity. Early union of epiphysis with the shafts in the long bones

6. Protein deposition in the sexual organs, bones, fat deposition on buttocks and thighs, increase metabolic rate 7. Cause the skin to become soft, smooth, vascular with increase warmth 8. Cause the cervical mucosa to become thin, alkaline and watery 9. Sodium and water retention by the renal tubules 10.Behavioral changes at the puberty

Q4. Enumerate the factors which control Insulin secretion. Give reasons for polydipsia and polyphagia in DM? (03+ 02) Key 4: (pp 968,974 Guyton 11th Ed.) Factors which increase insulin secretion: (0.25 mark for each factor = 1.5 marks for any 6 factors) most potent stimulant or control factor is plasma glucose level. When it increases insulin is secreted. Increased free fatty acids level stimulate insulin. Increased plasma level of certain amino-acids (arginine and leucine). GIT hormones like gastrin, CCK, Secretin, GIP. General hormones which are hyperglycemic: GH, Glucagon, cortisol, may be estrogens and progesterones. Parasympathetic stimulation and Acetylcholine. Beta adrenergic stimulators. Sulfonylureas (drugs used in DM) Factors which inhibit insulin secretion:

(0.25 mark for each factor = 1.5 marks for any 6 factors) Hypoglycemia. Starvation. Somatostatin. Insulin itself. Thiazide diuretics Beta adrenergic blockers Alpha adrenergic stimulators. Polydipsia (increased thirst) in DM: (01) In DM Insulin deficiency less uptake of glucose hyperglycemia osmotic diuresis intracellular dehydration increased thirst. In DM due to glucosuria (osmotic diuresis ) dehydration polydipsia. In DM due to osmotic diuresis polyuria dehydration polydipsia. Polyphagia (increased appetite) in DM: (01) Activity of Glucostat cells in satiety centre in ventro-medial nucleus of hypothalamus depends on their glucose utilization. If insulin is deficient as in DM no cellular uptake of glucose depressed activity of glucostat cells in satiety centre Hunger centre becomes un-inhibited polyphagia. Q.8 Name various buffers in the blood. How do these help to regulate acid-base balance of the body? (5 marks) Key:8 BLOOD BUFFERS (Plasma & RBCs): HCO3 buffer, PO4 buffer, Protein buffer, Hb buffer in RBCs Blood buffers tend to minimize the change in pH. Normal blood pH = 7.4 BUFFERING ACTION OF BICARBONATE BUFFER IN BLOOD: It consist of HCO3 (salt) & acid (H2CO3 which is dissolved CO2). HCO3 means NaHCO3 because Na+ is main cation in plasma. Ratio = salt/acid = NaHCO3/H2CO3 = 20/1 pka of this buffer system (HCO3) = 6.1 6.1 + log20 = 6.1 + 1.3 = 7.4 pka = -log of dissociation constant of acid (1.5 mark)

BUFFERING ACTION OF PHOSPHATE BUFFER IN BLOOD: It consist of salt (NaH3PO) & acid (H2CO3). PO4 means NaH3PO4 because Na+ is main cation in plasma. Ratio = salt/acid = NaH3PO4/H2CO3 = 20/1 pka of this buffer system (PO4) = 6.1 6.8 + log 20 = 6.8 + 1.3 = 7.4 pka = -log of dissociation constant of acid (1.5 mark) PROTEIN BUFFER IN BLOOD: SALT=Na-Proteinate Ratio (Salt/Acid) =? ACID=Acid Protein or H-Protein pka of protein buffer =? (0.5 mark)

BUFFERING ACTION OF HEMOGLOBIN BUFFER IN BLOOD: Cation in RBCs = K+ For Hb buffer, salt = K-Hemoglobinate Acid = Acid Hemoglobin = HHb Ratio =? & pka =? Hb is very important buffer in blood CO2 is transported as HCO3 & in free form. From tissues CO2 is carried by RBCs. In RBCs, CO2 + H2O form H2CO3 H2CO3 (unstable) & dissociates into H+ & HCO3H ion combines with Hb to form HHb (buffered by Hb to form acid-Hb). There is involvement of Hb & plasma proteins in buffering of CO2. (1 mark)

(0.5 mark)

Q.10 a. Give the mechanism of decomposition and reformation of Rhodopsin / visual purple in human eye. b. What is night blindness & how it is treated? (3+2 marks) Key.10(Fig.50.5, p 629 Guyton 11th Ed.) Decomposition of Rhodopsin: Light energy is absorbed by Rhodopsin

(0.25)

Rhodopsin begins to decompose within a very small fraction of a sec because there is photoactivation of electrons in the retinal portion of the Rhodopsin (0.25) Photoactivation changes the cis form of retinal into an all-trans form. (0.25) The all-trans retinal begins to pull away from the scotopsin (0.25) Formation of Bathorhodopsin occurs. (0.25)

Bathorhodopsin is a partial split combination of all-trans retinal and scotopsin. (0.25) Bathorhodopsin is extremely unstable and decays in nanoseconds to Lumirhodopsin. (0.25) Lumirhodopsin decays in microsec to Metarhodopsin I, then in about a millisec to Metarhodopsin II, slowly (in sec), into the completely split products Scotopsin & All-trans retinal. (0.25) Metarhodopsin II Also called Activated Rhodopsin (0.25)

 Excites electrical changes in the rods, and the rods then transmit the visual image into the CNS in the form of optic nerve action potential. (0.25) Re-formation of Rhodopsin 1st stage is reconversion of All-trans retinal to 11-cis retinal Process requires metabolic energy & Enzyme: Retinal isomerase. 11-cis retinal recombines with scotopsin to from Rhodopsin. Rhodopsin remains stable until next decomposition by light energy.

(0.5) (0.5) (0.5) (0.5)

Rhodopsin retinal visual cycle

Fig. 50.5 Guyton 11th Ed. b) NIGHT BLINDNESS / NYCTALOPIA It occurs in severe vit. A deficiency.

(0.5 Marks)

(0.5)

Retinal & rhodopsin formed in the absence of Vit A are severely depressed and insufficient. (0.5) Amount of light at night is too little to permit adequate vision in vit A deficient person. (0.25) Dietary deficiency of Vit. A occurs in months. (0.25)

 Recovery in Night Blindness takes place in Less than one hour by I/V Vit A (0.5) Q.11Draw & briefly discuss the pathway of light reflex. Define consensual light reflex. What is its basis? Key:4 (1 mark for diagram + 2.5 marks for discussion) (1+2.5) (0.5+1)

Light impinges on retina, Impulses pass from optic nerve to Pretectal nuclei. (1) Then to ipsilateral Edinger-Westphal nucleus. 0.5 Then to Parasympathetic nerves. 0.5 Finally Constrict the sphincter of iris. 0.5 Definition of Consensual light reflex: When light is directed towards one eye, pupil of the other eye also constricts.

Mechanism of consensual light reflex:1mark light into right pupil retina optic nerve Pretectal nucleus & Opposite Edinger-Westphal nucleus oculomotor N Ciliary ganglion pupillary muscles constriction of left pupil.