Q.1: briefly describe the causes, features and treatment of four types of hypoxia. (5) Marks. Key: 1.

Hypoxia is defined on the basis of its types: TYPES OF HYPOXIA: There are 4 types of hypoxia: 1. Hypoxic Hypoxia 2. Anemic Hypoxia 3. Stagnant / Ischemic Hypoxia 4. Histotoxic Hypoxia HYPOXIC HYPOXIA: Decreased arterial partial pressure of oxygen. In other types of hypoxia, PO2 is normal. Causes: any two (1.0 mark) Decreased PO2 in atmospheric air at high altitude. Depression of Respiratory centre (by disease / drug). Respiratory muscle paralysis. Obstructive lung disease (COPD, Asthma). Restrictive lung disease (pulmonary fibrosis, pneumothorax). Congenital heart diseases. Clinical features of Hypoxic Hypoxia: (0.5 mark) Due to decrease arterial PO2, Interstitial cells in peritubular capillaries secrete Erythropoietin resulting into polycythemia Hypoxia causes pulmonary Vasoconstriction leading to Pulmonary Hypertension & Rt. Vent. Hypertrophy resulting into Rt. Vent. Failure. Treatment of Hypoxic hypoxia: O2 treatment is most effective in this type of hypoxia. (0.5 mark) ANEMIC HYPOXIA: (0.5) mark

Arterial PO2 is normal but inadequate O2 carrying capacity of blood because of decrease in Hb conc. or due to presence of abnormal Hemoglobin like met-Hb or Hb-S or if binding site of Hb for oxygen is not available such as in carbon monoxide poisoning. CO is produced due to incomplete combustion of carbon. Hb has 250 times more affinity to bind with CO as compared to O2. Carbon monoxide Hb shifts the oxy-Hb curve to left, & as a result O2 dissociation becomes difficult. CO also inhibits cytochromes. When there is 70% carbon monoxy Hb in blood, death occurs. CO is colorless & odourless. In CO poisoning, skin is cherry red colored. There is no stimulation of resp. centre, because arterial PO2 is normal. Treatment of Anemic Hypoxia: (0.5 mark) Remove the subject from source of exposure. 100% oxygen therapy can help. Hyper-barric O2 can help (O2 with increased pressure = 2-3 atmospheric pressure)

STAGNANT / ISCHEMIC HYPOXIA: Causes: (0.5 marks)

(1)

Decreased cardiac output / sluggish blood flow due to heart failure, hemorrhage, circulatory shock and venous obstruction.

Blood remains in tissues for longer time, so tissue extracts increased oxygen from blood leading to more arteriovenous difference of oxygen concentration. So PCO2 increases, it facilitates unloading of oxygen from hemoglobin (shifts the oxy-hemoglobin association dissociation curve to right). Treatment of Stagnant / Ischemic hypoxia: (0.5 marks) Treat the underlying circulatory disease. HISTOTOXIC HYPOXIA: Definition: Inability of the tissues to utilize oxygen inspite of normal arterial PO2 and oxygen carrying capacity. Causes: (0.5 marks) Cyanide poisoning (it inhibits cytochrome oxidases, so oxidative process is inhibited). Narcotic overdosage (it inactivates the enzyme dehydrogenase leading to inhibition of tissue oxygenation). Beri-beri (it is deficiency of thymine co-enzyme which is required for many oxidative reactions). Treatment of Histotoxic hypoxia: (0.5 marks) Methylene blue or nitrites. These convert hemoglobin into met-hemoglobin. Cyanide & met-hemoglobin form cyanmet-hemoglobin (non-toxic compound).

Q.2 a). What is diffusing capacity of respiratory membrane? 1 mark b). Which factors affect exchange of gases through this membrane? (4 marks)

DIFFUSING CAPACITY OF RESPIRATORY MEMBRANE: 1 mark It is defined as a volume of the gas that will diffuse through the membrane each minute for a partial pressure difference of 1 mmHg. DIFFUSING CAPACITY OF OXYGEN (at rest): 21 ml/min/mmHg. DIFFUSING CAPACITY OF CARBONDIOXIDE (at rest): 400-450 ml/min/mmHg.

FACTORS AFFECTING EXCHANGE OF GASES THROUGH RESPIRATORY MEMBRANE: 1) Thickness of the membrane: Inversely proportional. Increased thickness in edema & fibrosis. (1) 2) Surface area of membrane: Directly proportional. Decreased on removal of an entire lung & in emphysema (1) 3) Diffusion coefficient of the gas in the substance of the membrane: It depends on solubility of the gas in the membrane & inversely on square root of molecular weight of gas. For a given pressure difference, CO2 diffuses about 20 times as rapidly as O2. O2 diffuses about twice as rapidly as N2. (1) 4) Partial pressure difference of the gas between 2 sides of the membrane: This difference is a measure of the net tendency for the gas molecules to move through the membrane. Net diffusion of gas occurs from higher partial pressure to lower between alveoli & pulmonary capillary, i-e., oxygen from alveoli to blood & carbondioxide from blood to alveoli. (1) ---------------------------------------------------------------------------------------------------

Q.3: a). enlist any six respiratory changes occurring during exercise. b). compare anatomic and physiologic dead spaces. Changes in Respiration during Exercise: (0.5*6 = 3 marks) 1) Increase in respiratory minute volume:

(3 marks) 2 marks

Normal respiratory minute volume (RMV) at rest = 500 x 12 = 6 L / min In severe exercise: RMV = up to 100 110 L / min 2) Increase in Oxygen Consumption (O.C): 250 ml / min (at rest) may increase to 4-5 L / min in exercise In exercise: C.O, B.P & Skeletal Muscle Blood Flow increases. Muscle extracts large amount of O2 from blood. 3) Utilization Co-efficient (U.C) increases: 25% (at rest) 75 85 % in severe exercise 19 ml / dl = arterial PO2 14 ml / dl = venous PO2 5 ml / dl is extracted, which is 25% It is the percentage of arterial blood which gives its O2 while passing through the tissues. 4) Diffusion Capacity for O2 increases: At rest: 20 30 ml / mm Hg / min In exercise: 65 ml / mm Hg / min 6) venous Blood gases during exercise: PO2 decreases, PCO2 & thus H+ increases. This causes Right hand shift of oxy-Hb dissociation curve leading to easy dissociation of O2 to supply skeletal muscle. 7) arterial blood gases: remain constant 8) O2 Hb dissociation curve: shifts towards right. 9) O2 consumption: increased 10: CO2 PRODUCTION: increased 11: V/Q RATIO: more evenly distributed in the lungs. 12: pulmonary blood flow: increases ------------------------------------------------------------------------------------------------------b). compare anatomic and physiologic dead spaces. 2 marks

Anatomical Dead Space= Consists of conducting airways, i-e., 150 ml. No gas exchange occurs here. Physiological dead space = Anatomical dead space + Alveolar dead space Normally there is no Alveolar dead space, so Anatomical dead space = physiological dead space / total / functional dead space. When alveolar dead space is present physiological dead space increases and is greater than anatomical dead space.

Q. 4: a). A resident of Lahore is posted to Murree hills. Enlist any six circulatory & respiratory changes you expect in his body after 2 years? (3 marks) b). what are the features of chronic mountain sickness? 2 marks Key:4 a) 3 marks (0.5 mark each, any 6 points) 1. Increase in pulmonary ventilation: Due to decreased PO2 , there ia Hypoxic stimulation of respiratory centre through peripheral chemoreceptors causing increased rate of pulmonary ventilation leading to respiratory alkalosis which does not inhibit respiratory center because the hypoxic stimulation is so strong that there is 3-7 times increase in pulmonary ventilation. 2. Decrease in affinity of Hb for O2: At high altitude increased 2, 3 DPG Formation shifts curve to right leading to increased P50 value. As a result dissociation to tissues is easier but binding of O2 to Hb in lungs is decreased respiratory alkalosis & increased pH which can shift curve to left but effect of 2, 3 DPG is predominant, so curve is shifted to right. 3. Increase in diffusing capacity of respiratory membrane for O2: [normal = 20-30 ml/mmHg]. 4. Increase in RBC formation at high altitude: At high altitude, hypoxia occurs. 5. Increase in secretion of erythropoeitin from interstitial cells of peritubular Capillaries causes increase in number of RBCs in 2-3 days, which in few weeks cause increase in RBC count and haematocrit. Normal haematocrit [4045 %] but may increase up to 60-65% 6. physiologic polycythemia: Hb may increase up to 22g/dl: normal 15g/dl 7. Increase in viscosity of blood: At high altitude initially cardiac output Increases but after some days decreases to normal or below normal due to hypoxia. 8. Pulmonary hypertention: due to hypoxic vasoconstriction in lungs. 9. Increase in vascularity. 10. Increase in number of mitochondria in cells. 11. Increase in number of myoglobin in muscle. 12. Increase in cytochrome oxidase enzyme in cells (for detoxification).

b). what are the features of chronic mountain sickness? Any four* 0.5= 2 marks (1) the red cell mass and hematocrit become exceptionally high, (2) the pulmonary arterial pressure becomes elevated even more than the normal elevation that occurs during acclimatization, (3) the right side of the heart becomes greatly enlarged, (4) the peripheral arterial pressure begins to fall, (5) congestive heart failure ensues, (6) death often follows unless the person is removed to a lower altitude.

Q.5 a). What are the three forms in which carbon dioxide is transported in blood? Illustrate bicarbonate-chloride shift/Hamberger shift with the help of diagram. 1+2 marks b). What are Haldane effect and Bohrs effect? Key:5: CO2 is transported in the blood in 3 forms: 1 mark 1. As dissolved in the plasma (7%). It gives PCO2 to the blood. 2. As HCO3 in the plasma (70%). 3. As carbamino proteins or carbamino Hb (23%). Deoxy Hb can bind much more CO2 than oxy Hb. Diagram: 2 marks 1+1 mark

TISSUE LEVEL

LUNG LEVEL Bicarbonate-Chloride Shift / Hambergers Shift

Hb buffered by Hb

H+

ClOxy-Hb + H+

H+

HCO3Cl-

Carbamino Hb Peripheral tissue CO2 + H2O H2CO3 CA Reverse Bicarbonate Chloride Shift HCO3-

H+ + HCO3-

H2CO3

Carbamino proteins RBC in SYSTEMIC CAPILLARY RBC gains Chloride & Water size in venous blood > Size in arterial blood

H2O

CO2

RBC in PULMONARY CAPILLARY Water & CO2 removed, so size of RBC decreases

The Haldanes effect: 1 mark

This effect states that binding of oxygen with hemoglobin tends to displace carbon dioxide from the blood.

This effect is quantitatively far more important in promoting carbon dioxide transport than is the Bohr
effect in promoting oxygen transport.
The Bohr Effect: 1 mark

It is shift of the oxygen hemoglobin dissociation curve to the right in response to increases in blood carbon dioxide and hydrogen ions. It has a significant effect by enhancing the release of oxygen from the blood in the tissues.

Q.6 a). Define the various lung volumes & lung capacities. Also mention their values for a young adult healthy male. 4marks b) Which of these cannot be measured by direct spirometry? Key6: TIDAL VOLUME: (0.5) 1 mark

Volume of air inspired or expired with each normal breath. Value = 500 ml in adult male. INSPIRATORY RESERVE VOLUME: (0.5) Extra volume of air that can be inspired over & above normal tidal volume, when person inspires with full force. Value = 3000 ml. EXPIRATORY RESERVE VOLUME: (0.5) Maximum extra volume of air that can be expired by forceful expiration after the end of normal tidal expiration. Value = 1100 ml. RESIDUAL VOLUME: (0.5) Volume of air remaining in the lungs after most forceful expiration. Value = 1200 ml INSPIRATORY CAPACITY: (0.5) TV + IRV Amount of air a person can breathe in beginning at normal expiratory level & distending the lungs to maximum amount. = 3500 ml. FUNCTIONAL RESIDUAL CAPACITY: (0.5) ERV+ RV Amount of the air that remains in the lungs at the end of normal expiration. 2300 ml. VITAL CAPACITY: (0.5) VC = IRV + TV + ERV Maximum amount of air a person can expel from the lungs after 1st filling the lungs to their max. extent & then expiring to max. extent. = 4600 ml TOTAL LUNG CAPACITY: (0.5) Max. volume to which the lungs can be expanded with greatest possible effort. VC + RV = TLC = 5800 ml LUNG VOLUMES & CAPACITIES WHICH CANNOT BE MEASURED BY SPIROMETER: 1 mark (any two) 1) Residual volume 2) Total Lung Capacity 3) Functional Residual Capacity

Q.7 Draw oxygen-hemoglobin dissociation curve. What is its significance? Enumerate 4 features which shift the curve to right & left. (2+1+1+1) marks Key: 7:

Left Shift = Association with Hb 100 97 89 80 75

gen Oxy

saturation SHIFT to left due to:

16

Venous blood in exercise

Re

du

20

ce d

blo od f

r om

40

tiss

ue

50

normal venous blood

60

Decrease in Temp Increase in pO2 Decrease in pCO2 Increase in pH Decrease in 2,3 DPG Decrease in Metabolic rate Fetal Hb pO2 falls to 60 mmHg

12

0 0 20 40 60 80 100 120 140

P50 = 26 mm Hg Pressure of oxygen in blood / pO2 (mm Hg) Oxy-Hb dissociation curve (Sigmoid curve) for PH 7.4, PO2 40 mm Hg & Temp 37C

Diagram: 2 marks Significance of oxy-Hb curve: (Any 1 = 1 mark) 1. This curve demonstrates a progressive increase in percentage of Hb bound with oxygen as blood partial pressure of oxygen increases, i-e, per cent saturation of hemoglobin. 2. Lower / left part of curve: deoxegenated blood returning from tissues Upper / right part of curve: Oxygenated blood leaving the lungs At pO2 below 40 mmHg, there occurs rapid decrease in affinity of Hb with O2. So dissociation is useful to overcome tissue needs. Shift of curve to left: (Any 4 = 1 mark)

Decrease in temp. Decrease in pCO2 Increase in pO2 Increase in pH Decrease in 2, 3 DPG Fetal Hb (2, 3 DPG has poor affinity to bind with gamma chains of fetal Hb). Decrease in metabolic rate.

volume (%) / O2 content ml / 100 ml

a te d

bloo

Right shift = Dissociation from Hb Total O2 ngs 20 m lu o r f d

still 90%

Hb saturation (%)

normal arterial blood

Shift of curve to right:

(Any 4 = 1 mark)

Increase in temp. Increase in pCO2 Decrease in pO2 Decrease in pH Increase in 2,3 DPG (from glycolysis), in RBCs normally. It binds easily with beta chains of adult Hb. (2, 3 DPG increases at high altitude, in anemia, chronic heart / lung disease & in chronic hypoxic conditions)

Increase in metabolic rate (exercise, thyroxin, androgens, Growth hormone)

Q.8: a deep sea diver was working for 1 hour at a depth of 200 feet under the sea. Suddenly he saw a shark and rushed to the sea surface. What problem can develop due to this sudden environmental change? Briefly mention the features and treatment of this condition (1+2+2) Key: De-Compression Sickness / Dysbarism / Bends / Divers paralysis / Bends: 1mark

Normally deep sea divers ascend to sea-level gradually so that Nitrogen from the body fluids and tissues is removed gradually, so no harmful effect on the body is produced. (1) If deep sea divers ascend to sea level rapidly, Decompression sickness results because on rapid ascent to sea level there is bubble formation in body fluids either intracellularly or extracellularly as the dissolved nitrogen tries to come out.

features:

(2) marks

Bubble formation in blood vessels of brain may cause Paralysis. Bubble formation around nerves may cause Paresthesia, itching and severe pain. There may be severe pain around joints (bends) when bubbles form around joints. In pulmonary vessels bubbles may cause Dyspnea or choaks. In coronary arteries, bubbles may cause Cardiac damage.

Treatment:

(2)

Recompression of diver in pressurized chambers. Then pressure is decreased gradually. Pressurized tents for treating people who develop this sickness after returning to surface. Slow and gradual decompression: A diver who has been on the sea bottom for 60 min at a depth of 190 feet is decompressed according to following schedule: 10 min at 50 feet depth 17 min at 40 feet depth 19 min at 30 feet depth 50 min at 20 feet depth 84 min at 10 feet depth Thus if diver has worked at sea bottom for 1 hr, needs a decompression time of about 3 hrs.

b). Nitrogen narcosis: 1 mark a) . At ordinary atmospheric pressures i.e. at sea level N2 dissolved in body tissues and fluid has no harmful effect but breathing compressed air under high pressures like in this case especially under 100ft will result in mental effects resembling alcohol intoxication or similar to a gas anesthetic. (1mark) It exerts its effects because at high pressures it is more soluble in lipids i.e myelin of the nerves and alters the ionic conduction through membrane resulting in decreased neuronal excitability leading to confusion, decreased mental activity, and euphoria

Q.9: draw and label the respiratory centre. What is the role of 4 important areas/centres of the respiratory centre? 1+4 KEY 9: DRAWING with labelling: 1 MARK

Role of 4 important areas/centres of the respiratory centre?

Dorsal Respiratory Group (DRG): 1 mark Function: Discharges rhythmic respiratory signals (inspiratory ramp signals)

Ventral Respiratory Group (VRG): 1 mark LOCATION: Ventral part of medulla Function: a. b. Center remain inactive during quite breathing Active only in increased pulmonary ventilation (e.g. exercise), during which signal from DRG spill over to VRG

Pneumotaxic Center: 1 mark Location: Upper part of Pons Function: a. b. c. Switches off Ramp Signal Controls rate and duration of Inspiratory ramp signals Strong stimulation may reduce Inspiratory phase to 0.5 sec respiratory rate to 30 40/min

Apneustic Center: 1 mark Located in lower part of pons Function: a. b. c. Prevent inspiratory neurons from being switched off prolonged inspiration Shortens expiration Such Respiration called apneusis