201 HI - Physiology

Question 1

Hematocrit

Answer 1

Packed cell volume (PCV)
Volume occupied by RBCs after centrifugation of blood

Normal: ~45%

Question 2

What is in the buffy coat of hematocrit?

Answer 2

Platelets & WBCs

Question 3

Mean corpuscular (cell) volume (MCV)

Answer 3

Average volume of each RBC

MCV = PCV/RBC count × 10

Normal: 80-100 fL

Question 4

Mean corpuscular (cell) haemoglobin (MCH)

Answer 4

Average amount of haemoglobin in each RBC

MCH = (haemoglobin conc)/(RBC count) × 10

Normal range: 28-32 pg

Question 5

Mean corpuscular (cell) haemoglobin concentration (MCHC)

Answer 5

% of the RBC volume occupied by Hb

MCHC = (haemoglobin conc)/PCV × 100

Normal: 33-34%

Question 6

Normal red cell distribution width (RDW)

Answer 6

11 - 15%

Question 7

Anisocytosis

Answer 7

Increased RDW - high variation size

Seen in iron deficiency & B12 deficiency

Question 8

Anaemia

Answer 8

Decrease in RBC count or Hb conc below lower limit of normal for a particular age or sex
- Decreases oxygen carrying capacity of blood

Question 9

Etiological classification of anaemia

Answer 9

Nutritional - Iron deficiency, B12 or folic acid deficiency
Aplastic - Decreased production of bone marrow
Haemorrhagic - acute (trauma) & chronic (ulcers)
Haemolytic - sickle cell anaemia

Question 10

Morphological classification of anaemia

Answer 10

Microcytic hypochromic

• iron-deficiency anaemia
• thalassemia
• chronic blood loss
• anemia of chronic disease

Normocytic normochromic

• aplastic anemia
• acute hemorrhage
• chronic renal failure - lack erythropoietin

Macrocytic

• B12 & folic acid deficiency
• Alcoholism
• Liver disease

Question 11

What happens to blood flow during anemia?

Answer 11

Circulation becomes quicker - due to decrease viscosity in blood

Question 12

Polycythemia

Answer 12

High RBC, high Hb conc

Primary - polycythemia vera
Secondary - hypoxia
Relative - dehydration

Question 13

4 mechanisms of hemostasis

Answer 13

1. Vasoconstriction
2. Platelet plug formation
3. Formation of blood clot
4. Fibrosis – growth of fibrous tissue to seal the defect

Question 14

Platelet plug formation (5)

Answer 14

1. Platelets attach to exposed collagen – von Willebrand factor (vWF) on injured endothelium
2. Platelet activation – swell up and throw multiple pseudopodia
3. Release ADP & thromboxane A2
4. More platelets aggregate → temporary plug
5. Clotting → more permanent plug

Question 15

Platelet adhesion

Answer 15

GP1b proteins on platelets attach to von Willebrand factor (vWF) in subendothelial collagen

Question 16

Bernard Soulier syndrome

Answer 16

Absence of GP1b → platelets cannot stick to subendothelial collagen

Question 17

Platelet activation

Answer 17

Platelet activated after binding to vWF → release ADP & thromboxane A2

Question 18

Platelet aggregation

Answer 18

ADP & thromboxane A2 cause platelet to aggregate

Question 19

Clopidogrel

platelet plug formation

Answer 19

blocks ADP receptor – prevents platelet aggregation

Question 20

Aspirin

platelet plug formation

Answer 20

Inhibits cyclooxygenase enzyme that forms thromboxane A2 – prevents platelet aggregation

Question 21

Abciximab

platelet plug formation

Answer 21

Antagonist of GPIIb/IIIa - absence of platelet aggregation – Glanzmann’s thrombasthenia 血小板無力症

Question 22

GP1b

Answer 22

Binding between platelet & vWF

Question 23

GPIIb/IIIa

Answer 23

Binding between fibrinogen & platelet

Question 24

The final common pathway of clotting

Answer 24

1. Prothrombin (II) → (by prothrombin activator) Thrombin (IIa)
2. FIbrinogen (I) → (by thrombin) Fibrin (Ia)

II → I

Question 25

The extrinsic pathway of clotting

Answer 25

1. TF released from injured tissue → activates VII 2. VII activates X – along w calcium & tissue factor 3. Xa + calcium, phospholids & Va → prothrombin activator 4. → common pathway VII → X

Question 26

The intrinsic pathway of clotting

Answer 26

1. XII activated on contact with collagen 2. XIIa activates XI 3. XIa activates IX 4. IXa + VIIIa + calcium & phospholipids → activate X 5. → common pathway XII → XI → IX → X

Question 27

Anticoagulant mechanisms of endothelial surface

Answer 27

1. Smoothness of the endothelial cell surface - prevents contact activation of the intrinsic clotting system 2. A layer of glycocalyx on the endothelium - repels clotting factors and platelets - preventing activation of clotting 3. Normal endothelium produced NO & prostacyclin (PGI2) – prevents platelet adhesion & aggregation 4. Thrombomodulin - binds thrombin 5. Antithrombin III inactivates thrombin

Question 28

Clinically used plasminogen activators

Answer 28

Alteplase - tissue plasminogen activator – stroke | Streptokinase - MI

Question 29

Tranexemic acid

Answer 29

Prevent bleeding by inhibiting the fibrinolytic pathway - Inhibits plasminogen activation and thus prevents fibrinolysis

Question 30

What may cause bleeding disorders? (2)

Answer 30

Liver disease – cirrhosis, hepatitis etc can lead to decreased production of clotting factors Vitamin K deficiency – vitamin K is needed for the addition of carboxyl group to glutamic acid of factors II, VII, IX and X in liver

Question 31

Haemophilia A

Answer 31

Factor VIII deficiency | - X linked recessive disease

Question 32

Haemophilia B

Answer 32

Factor IX deficiency | - X linked recessive disease

Question 33

Haemophilia C

Answer 33

Factor XI deficiency | - Autosomal recessive inheritance

Question 34

Features of Haemophilia

Answer 34

Bleeding w minor trauma – tooth extraction Bleeding following surgery Haemarthrosis 關節炎 – bleeding into joints

Question 35

Clot retraction

Answer 35

Compacts the clot and bring the torn edges together | - Due to actin, myosin, thrombosthenin of platelets

Question 36

Left side emboli vs right side emboli

Answer 36

Left side can block anywhere in blood | Right side only lung

Question 37

Which test tests for extrinsic + common pathway?

Answer 37

Prothrombin test (PT)

Question 38

Which test tests for intrinsic + common pathway?

Answer 38

Activated partial thromboplastin time (aPTT)

Question 39

Test of haemostasis - bleeding time

Answer 39

Time taken for standardized wound to stop bleeding Normal: 1-6 min Prolonged in platelet & vWF deficiency

Question 40

Test of haemostasis - clotting time

Answer 40

1. Blood collected in capillary tube 2. Time taken for clot formation assessed Normal: 1-6 min Prolonged in clotting factor deficiency

Question 41

Test of haemostasis - Activated partial thromboplastin time (aPTT)

Answer 41

1. Anticoagulated blood 2. Excess calcium & phospholipid added → stimulate clotting 3. Kaolin or silica then added to activate intrinsic pathway Tests intrinsic & common pathway

Question 42

Test of haemostasis - Prothrombin time (PT)

Answer 42

Prothrombin time (PT) 1. Blood collected with anticoagulant 2. Excess calcium & TF added to activate extrinsic pathway 3. Time for clotting noted Normal value: 0.9 – 1.3 - High – increased risk of bleeding - Low – increased risk for clot formation Test extrinsic & common pathway

Question 43

Test of haemostasis - thrombin time

Answer 43

Used to estimate fibrinogen levels 1. Anticoagulated blood 2. Excess calcium & thrombin added 3. Time taken to clot noted Prolonged in afibrinogenemia

Question 44

Which condition has high MCHC?

Answer 44

Hereditary spherocytosis 遺傳性球囊病

Question 45

Bleeding time & clotting time are both prolonged in which disease?

Answer 45

vonWillebrand disease

Question 46

Why does hemolytic anemia cause splenomegaly?

Answer 46

Spleen is over-functioned, as it cannot remove the abnormal RBCs as quick as they are generated

Question 47

β thalassemias

Answer 47

β chain defect Minor - ↑ HbA2 (α2δ2) - 1 β chain problem Major - ↑ HbF (α2γ2) - 2 β chain problem

Question 48

α thalassemia

Answer 48

α chain defect HbH disease - ↑ HbH (β4)

Question 49

3 things that cause vasoconstriction

Answer 49

1. Myogenic – injury to sm of blood vessel 2. Neurogenic – stimulation of pain fibres 3. Chemicals – released from platelets (thromboxane A2 & serotonin) & endothelium (endothelin)