IC2 Flashcards
Describe the composition of blood.
Blood is split into 2 major components: plasma (50-60%) and formed components (40-50%).
Plasma contains water (92%), proteins (7%) and other solutes (1%)
Proteins comprise of albumins (60%), globulins, fibrinogen (35%) and regulatory proteins (<1%).
Other solutes comprise of electrolytes, organic nutrients, and organic wastes.
Formed elements comprise largely of RBCs (99.9%), and the rest are WBCs and platelets (~0.1%)
State and describe the different types of WBCs (leukocytes).
1) Neutrophils (50-70%)
- 3-5 lobed nucleus, with pale, neutral-colored granules (bactericidal compounds)
- Early responders to inflammation/injury, involved in phagocytosis of pathogens
2) Lymphocytes (20-30%)
- Relatively large, spherical nucleus with thin cytoplasmic layer surrounding it
- Major functions in both innate (NK cells) and adaptive (B and T lymphocytes) immune responses
3) Monocytes (2-8%)
- Large nucleus, usually oval/kidney-shaped
- Generate tissue macrophages and phagocytose pathogens not effectively dealt with by neutrophils
4) Eosinophils (2-4%)
- Bilobed, with reddish-orange granules
- Phagocytose Ab-coated pathogens, through release of granules containing toxic compounds. Important against multicellular parasites.
5) Basophils (<1%)
- Bilobed nucleus, with deep purple/blue granules
- Migrate to injury sites and release granules containing histamine/heparin enhancing local inflammation.
Define Hematocrit and state the average Hematocrit for both men and women
Hematocrit = the relative volume of RBC out of total blood volume.
42% (for women), 46% (for men)
How many O2 molecules can 1 Hb molecule carry?
4
Describe the general trend in erythropoiesis sites as a person becomes older
- Sites change from long bones to short bones from fetus to adulthood (possibly because long bones tend to break more easily)
o Fetus: Yolk sac. Then liver, spleen, lymph node.
o < 5 years: all bone marrow (mostly in big bones)
o 5-20 years: bone marrow in ribs, sternum, vertebrae, proximal ends of long bones.
o > 20 years: bone marrow in ribs, sternum, vertebrae
Not in long bones anymore
State how erythropoietin levels are regulated and state some conditions which trigger erythropoietin release
Regulated by tissue oxygenation.
Conditions:
Hypoxia due to decreased RBC number or function
Decreased oxygen availability
Increased tissue demand for oxygen
Anemia
Reduced blood flow to kidney
Blood donation
Why do male have higher RBC count than females?
Male hormone stimulates increased RBC production (erythropoiesis) via increasing level of erythropoietin, estrogen does not + menses (for women)
What is reticulocyte count indicative of?
Indicative of erythropoiesis
Higher count indicates erythropoiesis is occuring -> may indicate acute bleed
Lower count may indicate anemia
Describe the process of RBC breakdown and how the components of Hb (heme, iron, globin) is reutilised
Lack of protein synthesis by RBC makes membranes fragile -> they are engulfed by macrophages in the spleen and rupture.
Hemoglobin released from ruptured RBC is degraded into its components (Heme and Globin)
* Heme group is degraded to a yellow pigment called bilirubin which is excreted via liver and bile into urine and feces.
o Too much bilirubin build-up may result in jaundice
* Iron in heme is recycled. It is bound to ferritin reused in bone marrow or stored in liver.
* Globin is metabolized into amino acids and is released into the circulation.
State the name and colours of the various hemoglobins:
a) Hb after O2 diffuses into tissue = ______
b) Hb after binding to CO2 = ______
c) Hb bound to O2 = ______
a) Hb after O2 diffuses into tissue = deoxyhemoglobin; colour dark red
b) Hb after binding to CO2 = Carbaminohemoglobin; blue hue
c) Hb bound to O2 = Oxyhemoglobin; bright red
Explain the process of blood clotting
1) Vasoconstriction
Occurs immediately
Damage to vessel wall causes constriction of smooth muscle (Vascular spasm) initiated by sympathetic nervous system.
* Endothelial cells contract, exposing basal lamina
* Endothelial cells of opposite sides may stick together
Purpose: Limit amount of blood lost from damage while waiting for platelet and coagulation phase to occur
2) Platelet plug formation
Occurs within seconds
Collagen fibres that are exposed from vessel damage are recognised by platelets.
Platelets adhere to collagen fibre (mediated by Von Willebrand factor or VWF) and secrete chemicals that causes more platelets to be recruited to the site and stick, eventually forming a platelet plug (positive feedback)
* VMF is a plasma protein produced by platelets
* VMF binds platelets to exposed collagen fibre via glycoprotein receptors
* Platelet adhesion activates platelets leading to morphological change (become more extended)
* Adhesion also trigger release of granules containing platelet agonists (e.g ADP, Thromboxane A2) -> more aggregation
o ADP attract and activate more platelets
o Thromboxane A2 promote aggregation and further vasoconstriction
Functions:
* Closure of leak by formation of temporary patch
* Release of chemical mediators, to regulate blood clotting
* Contraction of blood clot
3) Fibrin clot formation
Occurs within minutes
Platelets release prothrombin activator which activates prothrombin (produced by liver and Vit K dependent) to form thrombin which cuts fibrinogen to produce fibrin
* Prothrombin activator = complex of Factor Xa, Va and Ca2+.
Fibrin links platelets through glycoprotein receptors (Coagulation phase). However fibrin links are weak and are reinforced by factor XIIIa that form crosslinks between fibrin strands to form fibrin mesh
Remodelling process occurs to fix the damaged vessel walls
Explain the characteristics/ processes of the coagulation cascade in terms of extrinsic, intrinsic and common pathways
Extrinsic:
o Damaged tissue wall releases tissue factor/thromboplastin, forms a complex with factor VII and activating it (VIIa) and together with Ca2+, leads to activation of factor X (form Xa)
o Factor Xa (10a) is the point which extrinsic and intrinsic pathways meet
o Occurs within seconds
Intrinsic:
o Exposure to collagen fibres OR exposure to foreign surface (e.g glass) cause conformational change to platelets, leading to activation of factor XII (to XIIa)
o Chain reaction occurs where coagulation factors activate one another (XIIa activate XI, XIa activate IX)
o At the end of the chain reaction, a complex with additional cofactor is formed (IXa and VIIIa) which activates factor X
o Occurs within minutes
Common pathway:
o Factor Xa in combination with 5a (Va) activate thrombin and induces thrombin birth (from prothrombin). Thrombin causes further activation of platelets and enhanced formation of fibrin. Fibrin forms strands, making up the mesh that stabilises the platelet plug in arterial clot and holds the RBCs in a venous clot
State the functions of Thrombin in the Coagulation Cascade (4)
- Enhances its own generation (positive feedback loop)
- Factor XIII activation (stabilization of fibrin mesh)
- Platelet activation
- Release of PF 3 (platelet factor 3) from platelets (activation of intrinsic pathway)
Describe the process of fibrinolysis
o During clot formation plasminogen is trapped inside the clot. Plasminogen is a plasma protein and protease precursor made by the liver.
o The surrounding tissue and vascular endothelial cells slowly release tissue plasminogen activator (tPA) which cleaves the inactive plasminogen to form the protease plasmin.
o Plasmin digests fibrin, thereby dissolving the clot.
o Macrophages remove the remains of the clot.
Explain what Partial thromboplastin time (PTT)/ activated PTT (aPTT) and Prothrombin time (PT) measures and what factors are unique to each.
aPTT: Measures the efficacy of the intrinsic and the common coagulation pathways. Factors specific to this test are Factor XII, XI, IX, VIII
PT: Measures the efficacy of the extrinsic and common pathways. Factors specific to this test is Factor VII
