201 HI - Physiology Flashcards
Hematocrit
Packed cell volume (PCV)
Volume occupied by RBCs after centrifugation of blood
Normal: ~45%
What is in the buffy coat of hematocrit?
Platelets & WBCs
Mean corpuscular (cell) volume (MCV)
Average volume of each RBC
MCV = PCV/RBC count × 10
Normal: 80-100 fL
Mean corpuscular (cell) haemoglobin (MCH)
Average amount of haemoglobin in each RBC
MCH = (haemoglobin conc)/(RBC count) × 10
Normal range: 28-32 pg
Mean corpuscular (cell) haemoglobin concentration (MCHC)
% of the RBC volume occupied by Hb
MCHC = (haemoglobin conc)/PCV × 100
Normal: 33-34%
Normal red cell distribution width (RDW)
11 - 15%
Anisocytosis
Increased RDW - high variation size
Seen in iron deficiency & B12 deficiency
Anaemia
Decrease in RBC count or Hb conc below lower limit of normal for a particular age or sex
- Decreases oxygen carrying capacity of blood
Etiological classification of anaemia
Nutritional - Iron deficiency, B12 or folic acid deficiency
Aplastic - Decreased production of bone marrow
Haemorrhagic - acute (trauma) & chronic (ulcers)
Haemolytic - sickle cell anaemia
Morphological classification of anaemia
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
What happens to blood flow during anemia?
Circulation becomes quicker - due to decrease viscosity in blood
Polycythemia
High RBC, high Hb conc
Primary - polycythemia vera
Secondary - hypoxia
Relative - dehydration
4 mechanisms of hemostasis
- Vasoconstriction
- Platelet plug formation
- Formation of blood clot
- Fibrosis – growth of fibrous tissue to seal the defect
Platelet plug formation (5)
- Platelets attach to exposed collagen – von Willebrand factor (vWF) on injured endothelium
- Platelet activation – swell up and throw multiple pseudopodia
- Release ADP & thromboxane A2
- More platelets aggregate → temporary plug
- Clotting → more permanent plug
Platelet adhesion
GP1b proteins on platelets attach to von Willebrand factor (vWF) in subendothelial collagen
Bernard Soulier syndrome
Absence of GP1b → platelets cannot stick to subendothelial collagen
Platelet activation
Platelet activated after binding to vWF → release ADP & thromboxane A2
Platelet aggregation
ADP & thromboxane A2 cause platelet to aggregate
Clopidogrel
platelet plug formation
blocks ADP receptor – prevents platelet aggregation
Aspirin
platelet plug formation
Inhibits cyclooxygenase enzyme that forms thromboxane A2 – prevents platelet aggregation
Abciximab
platelet plug formation
Antagonist of GPIIb/IIIa - absence of platelet aggregation – Glanzmann’s thrombasthenia 血小板無力症
GP1b
Binding between platelet & vWF
GPIIb/IIIa
Binding between fibrinogen & platelet
The final common pathway of clotting
- Prothrombin (II) → (by prothrombin activator) Thrombin (IIa)
- FIbrinogen (I) → (by thrombin) Fibrin (Ia)
II → I
The extrinsic pathway of clotting
- TF released from injured tissue → activates VII
- VII activates X – along w calcium & tissue factor
- Xa + calcium, phospholids & Va → prothrombin activator
- → common pathway
VII → X
The intrinsic pathway of clotting
- XII activated on contact with collagen
- XIIa activates XI
- XIa activates IX
- IXa + VIIIa + calcium & phospholipids → activate X
- → common pathway
XII → XI → IX → X
Anticoagulant mechanisms of endothelial surface
- Smoothness of the endothelial cell surface - prevents contact activation of the intrinsic clotting system
- A layer of glycocalyx on the endothelium - repels clotting factors and platelets - preventing activation of clotting
- Normal endothelium produced NO & prostacyclin (PGI2) – prevents platelet adhesion & aggregation
- Thrombomodulin - binds thrombin
- Antithrombin III inactivates thrombin
Clinically used plasminogen activators
Alteplase - tissue plasminogen activator – stroke
Streptokinase - MI
Tranexemic acid
Prevent bleeding by inhibiting the fibrinolytic pathway
- Inhibits plasminogen activation and thus prevents fibrinolysis
What may cause bleeding disorders? (2)
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
Haemophilia A
Factor VIII deficiency
- X linked recessive disease
Haemophilia B
Factor IX deficiency
- X linked recessive disease
Haemophilia C
Factor XI deficiency
- Autosomal recessive inheritance
Features of Haemophilia
Bleeding w minor trauma – tooth extraction
Bleeding following surgery
Haemarthrosis 關節炎 – bleeding into joints
Clot retraction
Compacts the clot and bring the torn edges together
- Due to actin, myosin, thrombosthenin of platelets
Left side emboli vs right side emboli
Left side can block anywhere in blood
Right side only lung
Which test tests for extrinsic + common pathway?
Prothrombin test (PT)
Which test tests for intrinsic + common pathway?
Activated partial thromboplastin time (aPTT)
Test of haemostasis - bleeding time
Time taken for standardized wound to stop bleeding
Normal: 1-6 min
Prolonged in platelet & vWF deficiency
Test of haemostasis - clotting time
- Blood collected in capillary tube
- Time taken for clot formation assessed
Normal: 1-6 min
Prolonged in clotting factor deficiency
Test of haemostasis - Activated partial thromboplastin time (aPTT)
- Anticoagulated blood
- Excess calcium & phospholipid added → stimulate clotting
- Kaolin or silica then added to activate intrinsic pathway
Tests intrinsic & common pathway
Test of haemostasis - Prothrombin time (PT)
Prothrombin time (PT)
- Blood collected with anticoagulant
- Excess calcium & TF added to activate extrinsic pathway
- 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
Test of haemostasis - thrombin time
Used to estimate fibrinogen levels
- Anticoagulated blood
- Excess calcium & thrombin added
- Time taken to clot noted
Prolonged in afibrinogenemia
Which condition has high MCHC?
Hereditary spherocytosis
遺傳性球囊病
Bleeding time & clotting time are both prolonged in which disease?
vonWillebrand disease
Why does hemolytic anemia cause splenomegaly?
Spleen is over-functioned, as it cannot remove the abnormal RBCs as quick as they are generated
β thalassemias
β chain defect
Minor - ↑ HbA2 (α2δ2) - 1 β chain problem
Major - ↑ HbF (α2γ2) - 2 β chain problem
α thalassemia
α chain defect
HbH disease - ↑ HbH (β4)
3 things that cause vasoconstriction
- Myogenic – injury to sm of blood vessel
- Neurogenic – stimulation of pain fibres
- Chemicals – released from platelets (thromboxane A2 & serotonin) & endothelium (endothelin)
