CR Physiology

Question 1

RBC formation before birth

Answer 1

Mesoblastic Stage (~3 weeks) = blood cells with nucleus form in yolk sac and mesothelial layers of placenta

Hepatic Stage (~6 weeks) = erythropoiesis mainly in liver and in the spleen

Myeloid Stage (~3 months) = bone marrow gradually becomes prime source of RBCs.

Question 2

RBC formation After Birth

Answer 2

Up to 5 years = Bone marrow in all bones
5 to 20/25 years = Marrow of the long bones
25+ years = mainly produced in marrow of membranous bones (vertebrae, sternum, ribs etc…).

Question 3

Process of Erthyropeoiesis

Answer 3

Haematopoietic stem cell –> proerthroblast (common myeloid progenitor cell) –> erythroblast –> reticulocyte

Question 4

What controls erythropeoiesis

Answer 4

Erythropoietin (EPO) produced in fibroblast interstitial cells in the kidney (PT)

EPO cells Sensitive to Hypoxia

Question 5

Process of senescent RBC removal

Answer 5

After 120 days, RBCS are removed by macrophages (pass through spleen)
• Surface antigens in old RBCs are different to those in young ones.
• Also, have a raised methaemoglobin in the cell.
• Also, lack of deformability. Olds cells = more rigid.

RBCs = broken by osmotic lysis.
• Haem prosthetic groups = broken down into amino acids
• Haem is broken down by haemoxygenase  biliverdin.

Question 6

Biliverdin pathway

Answer 6

Biliverdin –> bilirubin (biliverdin reductase) –> Unconjugated bilirubin (bound to albumin in splenic macrophages) –> Conjugated bilirubin (attached to glucuronic acid in the liver)

Question 7

Extrinsic clotting pathway

Answer 7

Tissue factor present on subendothelial cells (not normally exposed to flowing blood). Injury exposes

Tissue factor interacts with factor VII –> VIIa
VIIa catalyses X –> Xa

Question 8

Common clotting pathway

Answer 8

Xa forms Xa complex as it mixes with factor V and collagen
Catalyses prothrombin –> thrombin
Thrombin catalyses fibrinogen –> fibrin

Question 9

Intrinsic clotting pathway (AMPLIFICATON PHASE)

Answer 9

Extrinsic pathway produces insufficient thrombin for clot

Thrombin activates factors V, VIII, XI
V catalyses thrombin to prothrombin
VIII catalyses X to Xa
XI within pathway so upregulated

Question 10

What can cause intrinsic clotting pathway

Answer 10

Endothelial damage without outside exposure

Can be caused by hydrophilic material, bacterial toxin
Also, requires serine proteases

Question 11

Intrinsic clotting pathway (regular)

Answer 11

1) Factor XII –> factor XIIa.
2) Causes factor XI –> Xia
3) Causes Factor IX –> IXa.
4) Factor IXa activates X to Xa with the help of factor VIII

Question 12

Role of Plasmin

Answer 12

Main enzyme responsible for removal of clots (fibrinolysis) when damaged tissue is healed.
• Plasmin circulates as inactive precursor plasminogen
• Plasminogen = binds to plugs as they form, get incorporated into the final clot
• Held inactive by alpha-2-antiplasmin

Question 13

D-dimer

Answer 13

product of fibrin breakdown = protein fragment that circulates in the blood

D-dimer test for suspected thrombotic disorders

Question 14

Antithrombin

Answer 14

Inhibits thrombin, Xa, VII, IX, XI.

Member of SERPIN (Serine Protease Inhibitor) family.

Inhibitor activity increases 5-10 000-fold in presence of heparin.

Question 15

Protein C and Protein S

Answer 15

Vitamin K dependent glycoprotein synthesised in liver

• Protein C = serine protease that activates Va and VIIIa.
• Protein S = cofactor for activated protein C

Question 16

Haemophilia types

Answer 16

• A = caused by a deficiency factor of VIII (8)
DDAVP can be given (mild cases)
• B = caused by deficiency of factor IX (9)

Question 17

Inherited Platelet Disorders

Answer 17

SERIOUS
• Lack GpIb = Bernard Soulier Syndrome –> VWF cannot bind.
• Lack of GpIIb = Glanzmann’s –> no ability to bind fibrinogen into the clot

LESS SERIOUS
• Von Willebrand Disease
Autosomal inheritance where VWF is deficient or defect. Three types:
o TYPE 1 = mild to moderate deficiency (protein works but there is a lack of it)
o TYPE 2 = protein is present but might be reduced as well as being defective.
o TYPE 3 = total absent protein.

Question 18

Synthesis of Nitric Oxide (NO)

Answer 18

• Flowing blood is the main regulatory factor in endothelial NO synthesis.
o Friction of moving blood opens calcium channels
o Allows calcium to enter the endothelium.
o Activates calmodulin –> activates eNOS.

• Acetylcholine present in plasma can also activate NO synthesis by binding to ACh receptors on endothelium and allowing Ca to enter.

Question 19

Mechanism of NO dilation

Answer 19

NO diffuses from endothelium into nearby smooth muscle cell

• Activates guanylate cyclase. This converts guanosine triphosphate (GTP) to cGMP.
o Removes calcium from cytoplasm of the muscle = makes it relax.
o Open potassium channels which hyperpolarise the cell (stop it contracting).

Question 20

Functions of NO

Answer 20

• NO relaxes and dilates arterial smooth muscles
o Opposes the effects of noradrenaline and angiotensin.

• Prevents unwanted intravascular coagulation.
o Always a small basal release of NO (friction of blood passing over endothelium causes mechanical sheer stress.
- Prevents leukocytes and platelets from adhering to surface.

• Improves oxygen delivery. During hypoxia released from epithelium.
o Reacts with haemoglobin to form nitroxyhaemoglobin.
o Displaces O2 from Hb.

Question 21

NO Storage

Answer 21

Stored as nitrate

1. NO constantly synthesized by pulmonary arterioles. Diffuses into venous blood
2. Converted to nitrous acid and then to nitrite by the high PO2 and high pH in pulmonary venous blood
3. Nitrite can be converted back to NO in hypoxic and acid conditions.

Question 22

Adrenergic receptors

Answer 22

o Beta 1: increase heart contractility and rate

o Beta 2: act to relax the muscle and increase ventilation + O2 uptake
- Cause vasodilation of blood vessels around skeletal muscle.

Question 23

what happens in excess post-exercise oxygen consumption (EPOC) ‘oxygen debt’

Answer 23

• ATP and creatine phosphate are resynthesized.

- Excess lactate is resynthesized into glucose and glycogen.

Question 24

Ventilation regulation

Answer 24

Mainly regulated by paCO2

• Also, weakly regulated by hypoxia detectors in carotid bodies (only significant if below 60 mmHg)

• Initially results in temporary increased ventilation which leads to excess CO2 blow off
o Leads to respiratory alkalosis

• Picked up by the chemoreceptors, which inhibit increased ventilation (as CO2 is main drive and low)

Therefore = ventilation system is inadequate to cope with the low PO2 (in altitude sickness)

Question 25

High altitude acclimatisation

Answer 25

• Metabolic acidosis (retention of acid, increased excretion of bicarbonate).
o Respond to hypoxaemia/respiratory alkalosis by decreasing activity of proton secreting ATP-ase in the kidney, decreasing renal excretion of acid.
-Increases bicarbonate secretion

• An increase in erythrocyte number.
o Done by interstitial cells in the kidney.
o NOTE = if too high  clogs up capillaries

• Reduced pulmonary vascular resistance.
o Due to reduced hypoxic vasoconstriction
o Collateral circulation open between pulmonary arteries and veins.
-Mediated by increased NO synthesis in the pulmonary endothelium.

Question 26

Acute mountain sickness (AMS) signs and symptoms

Answer 26

Scored 0-3 for severity of 
•	Headache
•	Poor Sleep
•	Tiredness
•	Loss of appetite
•	Nausea, Vomiting

Question 27

Treatment of AMS

Answer 27

• If mild = rest

• If more severe:
o Descent
o Oxygen

o Dexamethasone = four times daily.
o Acetazolamide = three times daily
- Carbonic anhydrase inhibitor.
- CA is important for renal absorption of bicarbonate.
- Inhibition –> increased bicarbonate secretion = metabolic acidosis.

Question 28

Main bicarbonate filtration and reabsorption in the Kidney

Answer 28

Filtered in the glomerulus, mainly reabsorbed in the proximal tubule

Question 29

High altitude cerebral oedema signs and symptoms

Answer 29

• Ataxia
• Nausea/vomiting
• Hallucination or disorientation
• Confusion
• Reduced conscious level
• Coma.

Question 30

High altitude cerebral oedema Mechanism of Action

Answer 30

• Brain neurones and glia have a very high metabolic rate.
o Majority of the ATP they produce –> used to pump sodium out of the cells.
 Maintains osmotic equilibrium

• Hypoxemia = low oxygen, low ATP. Sodium leaks into the nerve cell. It pulls water with it and the brain cell swells. This raises ICP and blocks cerebral veins.

Question 31

High altitude cerebral oedema treatment

Answer 31

• Descend immediately
• Acetazolamide (reduces formation of CSF)
• Oxygen
• Dexamethasone = prevents brain swelling.
• Hyperbaric chamber

Question 32

High Altitude Pulmonary Oedema (HAPE)

signs and symptoms

Answer 32

• Dyspnoea
• Reduced exercise tolerance
• Dry cough
• Blood stained sputum
• Crackles on auscultation

Question 33

High Altitude Pulmonary Oedema (HAPE) Mechanism of Action

Answer 33

• PAH develops if there is no acclimatisation.
• Raised pressure leads to fluid leaving the blood and entering the alveoli.
o Worsens gas exchange (which is already compromised).
o Increases hypoxia which further raises PAH etc…
 osmotic equilibrium

Question 34

High Altitude Pulmonary Oedema (HAPE) Treatment

Answer 34

• Descend immediately
• Sit patient upright, give oxygen
• Nifedipine (CC blocker).
o Blocks constriction of pulmonary arteries.
• Hyperbaric chamber
o Increases paO2 of oxygen.
• Viagra (stimulates NO synthesis as it slows the breakdown of cyclic GMP): sildenafil

Question 35

Rhesus Blood Groups

Answer 35

• Three pairs inherited as triplet:
o C or c
o D or no D (d)
o E or e

Question 36

How is rhesus determined

Answer 36

Determined by D = either D positive or D negative
• D-positive = not anti-D antibodies
• D-negative = anti-D antibodies (these are only produced if in contact with D positive)

Rhesus factor is dominant so you could be either homozygous positive (++), heterozygous positive (+-) or heterozygous negative (–)