RBC's & Haemostasis

Question 1

Describe the relative proportions of oxygen carried in the blood via Hb and dissolved in plasma.

Answer 1

70x oxygen bound to Hb than dissolved in plasma.

Question 2

What type of respiration occurs in Hb and how does its efficiency compare to a normal somatic cell.

How much of a RBC is Hb in terms of a) dry mass b)wet mass?

Answer 2

Anaerobic as it lacks organelles including mitochondria.

Glucose is decarboxylated to product 2xlactate and 2ATP compared to 36ATP molecules generated in aerobic respiration.

a) 95%
b) 35%

Question 3

Describe the structure of Hb and how it differs to foetal Hb.

Answer 3

Hb is a tetramer composed of 4 subunits; 2 alpha + 2 beta
Each subunit is bound to a haem group.

Foetal Hb also has 4 subunits; 2 alpha + 2 gamma
Foetal Hb has a greater affinity for oxygen

Adults have a very low percentage of foetal Hb.

Question 4

Describe the haem group in Hb.

Answer 4

The haem group is responsible for oxygen transport, it is a porphyrin ring which makes it rigid, 2D and highly coloured due to the sharing of electrons. It is also conjugated to a ferrous group (Fe2+)

Question 5

Describe the Bohr effect.

Answer 5

Takes place response to high carbon dioxide partial pressure.

High CO2, decreases the pH of the blood and this leads to a decreased affinity of Hb for O2 causing dissociation to respiring tissues.

Question 6

Outline the respiratory thresholds.

What happens in order for the body to increase respiratory drive?

Answer 6

95- normal
90-poor
88- critical. INCREASE RESP DRIVE

H+ ions detected in cerebrospinal fluid.
CO2 is a gas and can travel to CSF quickly where it reacts with blood to form carbonic acid and H+ ions. In this sense an increase respiratory drive is more dependent on CO2 concentration than H+ ions in blood as it takes longer for these to be detected as they are only detected in the carotid bodies.

Question 7

Describe the appearance, function, frequency and location of erythrocytes.

Answer 7

Appearance: Red (oxy-HB), 2umx7um, biconcave

Function: transport O2/CO2, lifespan approx. 120 days, flexible and stack themselves in vessels

Frequency: 5million/uL. PCV: 40-52% women; 36-48% men

Location: post birth- bone marrow. >20yo- membraneous bone

Question 8

Describe the cell lineage that cells follow in haematopoeisis.

Answer 8

Multipotent haematopoietic stem cell (Haemotocytoblast)

Common myeloid progenitor

Reticulocyte

Erythrocyte

Question 9

What is erythropoietin and how may it be used in the “real world”?

Answer 9

Cytokine which drives erythropoiesis. Made in kidney in response to kidney hypoxia.

Performance enhancer.

Question 10

Describe what a Reticulocyte is.

How can detection of is help us find out whats going on in the blood?

Answer 10

Erythrocyte precursor cell
Still contains nucleus and organelles.
Lifespan- 2 days

Low reticulocyte count means low levels of erythropoiesis taking place

High reticulocyte count may indicate haemolytic anaemia.

Question 11

Describe Methaemoglobinamia

Answer 11

Condition in which iron(II) in Hb is oxidised to iron(III) and thus unable to transport oxygen.

CAUSES:

1. congenital globin mutations
2. NADH hereditary diseases
3. toxic agents

Question 12

Describe Polycythaemias, both physiologically and pathologically.

Answer 12

Increases blood volume due to increased RBC’s. Also increases viscosity

Physiologically: in people that live at high altitudes.

Pathologically: clog blood vessels (risk of thrombosis), asymptomatic, no cure, all ages. JAK2 mutation.

Question 13

Describe the bodies iron requirement.

Answer 13

65% iron in body in Hb. 30% intracellularly stored in FERRITIN(very easily accessible) in liver, bone marrow and blood and HAEMOSIDERIN (less accessible). 4% IN myoglobin

Iron stored in reticuloendothelial system in spleen, liver, RBCs, WBCs, bone marrow

Usage: 1mg/day (excpetions, menstruation, pregnancy, peptic ulcers)

Question 14

What is the use of Vitamin B12 & Folic acid?

Answer 14

Important in fast dividing tissues (growth)

1. DNA formation
2. Nuclear maturation
3. RBC’s, skin, gametogenesis,

Question 15

Describe a type of anaemia caused by Folic acid & Vit-B12 defence?

Answer 15

Megaloblastic anaemia
Other causes - lymphoma, old age, diet, malnutrition, veganism

Treatment-
Oral folic acid
Intramuscular hydroxocobalamin

Question 16

Name an anaemic condition caused by iron deficiency.

Answer 16

Hypochromic microcytic anaemia

Question 17

Describe 5 functions of the endothelial cells

Answer 17

1. Inner lining surface
2. Normally secretes inhibitory factors of haemostasis, injury results in secretion of von Willebraud factor
3. Control blood fluidity (size and contribute to clotting)
4. signal inflammatory cells to areas needing repair
5. Gate keeper between blood &brain/ tissues. It controls extravasion

Question 18

Outline the three steps involved in platelet based pathway to repair blood vessels

Answer 18

1. Vasoconstriction
   Platelets release vasoconstrictors and prothrombotic agents (serotonin, ADP thromboxane A2)
2. Platelets form haemostatic plug
   By adhesion, activation and aggregation
3. Coagulation makes meshwork on clot
   Activates cascade enzymes
   Part of coagulation requires nearby platelet membrane

Question 19

Outline the lineage that a thrombocyte (platelet) is derived from.

Answer 19

Multipotent haematopoietic stem cell

Common myeloid progenitor

Megakaryocyte

Thrombocyte (platelet)

Question 20

Describe the term thrombocytopenia.

Describe the normal platelet count and size.

Answer 20

Low platelet count in blood

Normal platelet count 50x less than RBCs

Size: 0.5um

Question 21

Explain the role of activation in platelet based pathway to repair blood vessels.

Answer 21

Requires exocytosis, change of shape and increased respiratory rate.

The change of shape involves expression of pseudopodia

Question 22

Explain the role of the haemostatic plug in platelet based pathway to repair blood vessels.

Answer 22

Adhesion to exposed collagen

Activation by exocytosis of dense granules
The mechanism of this involves extracellular ADP activating P2Y receptor which leads to cation flow. The platelets release TXA2 and the ADP stimulate a positive feedback response on the platelets.

Aggregation is stimulated by ADP & blocked by prasugrel

Question 23

Describe coagulation factors.

Define a tissue factor.

Answer 23

Coagulation factors circulate in the blood as inactive precursors. Most (exc. V VIII) are enzymes that cleave to other factors thus switching them on.

A tissue factor is a factor held behind the endothelial lining, thus only exposed when there is damage to the endothelium where they are able to interact with precursors.

Question 24

How does low BP and/or atrial fibrillation lead to thrombosis?

How is this combated?

Answer 24

Low bp increases chance of spontaneous thrombus formation.

Afib means increased risk for stroke because blood may not be properly pumped out of the heart, which may cause it to pool and form a clot.

Blood thinner adminstrated to patients. In lab, citrate and heparin stop blood clotting

Question 25

Whats the difference between plasma and serum?

Answer 25

Plasma is fluid portion of blood. | Serum is leftover fluid after clotting. It is lacking in fibrinogen, clotting factors II, V and VIII

Question 26

Outline the steps involved in producing cross linked fibrin

Answer 26

Fibrinogen (glycoprotein) is converted to fibrin by thrombin (enzyme). Factor XIII and calcium ions are involved in cross linking the fibres.

Question 27

Explain how thrombin is activated.

Answer 27

By Factor Xa (poorly) in the presence of its cofactor, Factor Va (efficient). Together= thrombinase

Question 28

Describe the three pathways in which Factor Xa is activated?

Answer 28

1. Extrinsic Xase (Tissue factor + Factor VIIa) 2. Intrinsic Xase (Factor VIII + Factor IX) 3. Thrombin itself in positive feedback mechanism

Question 29

Coagulation factors can be subdivided into two categories. Prothrombins and Thrombins Describe the differences and give examples.

Answer 29

``` Prothrombins Examples: factor 2,7,9,10 They are enzymes They require Vitamin K for their synthesis. This is taken endogenously and is important for gamma-carboxylation of enzymes. Require Ca2+ for activation ``` ``` Thrombins Examples: 1,5,8 Thrombin ACTIVATES them 5 and 8 are cofactors Increased concentration in inflammation, pregnancy and oral contraceptives ```

Question 30

Describe the function of plasmin and how it is activated.

Answer 30

Lyses fibrin therefore breaks down clots Circulates in blood from liver as Plasminogen Tissue Plasminogen activator (TPA) found on surface of endothelium, causes plasminogen maturation

Question 31

Describe the function of Protein C

Answer 31

Inhibits coagulation by inactivating clotting factor Va and Xa. It works alongside co-factor protein S to inactivate Va. Protein C itself is activate don endothelium and made in liver

Question 32

Describe the function of Antithrombin III

Answer 32

Works well with heparin, heparin increases response Peptide made in liver Blocks activity of thrombin, Factor 9 and 10

Question 33

Describe Vitamin K deficiency inc. prevalence, cause and the effect of warfarin.

Answer 33

Results in clotting deficiency as Vitamin-K essential to synthesis prothrombins such as clotting factor 2,7,9,10 Rare because vitamin k is made by bacteria in body and rich in green veg Causes: GI disease/inability to absorb fat Warfarin prevents Vit-k recycling so stores deplete after a few days

Question 34

Describe haemophilia A and detail how it is different to haemophilia B

Answer 34

Congenital lack of factor VIII X linked Affects longer blood vessels Causes wounds to bleed for days, blood enters joints and muscles Treatment- injected purified F-VIII(very expensive and rare) Haemophilia B "Christmas disease"- same symptoms as H-A Lack in factor IX

Question 35

Describe atherogenesis as a disease of inflammation, lipids and endothelium.

Answer 35

Formation of abnormal fatty or lipid masses in arterial walls It causes inflammation as monocytes enter lesion, become foam cells, die and release contents which further attracts monocytes, cytokines and chemo-attractants LDL deposits in lesion, cholesterol esters solidify and are oxidised forming toxic oxygen radicals which are immunogenic. These are consumed by macrophages, become foam cells, rupture and attract monocytes. Endothelium express chemoattractants which leads to the attraction of monocytes which breakdown inner lining exposing collagen which stimulates coagulation. Lost endothelium decreases the vessels ability to dilate.

Question 36

Consider pharmacological control of blood clotting. Describe the function of anti-platelet drugs with examples.

Answer 36

Good in arterial clots Used to treat acute coronary symptoms Aspirin blocks formation of thromboxane A2 Increase bleeding time without increasing clotting time Propylaxis for MI ADP inhibitors e.g. Prasugrel, Clopidogrel

Question 37

Consider pharmacological control of blood clotting. Describe the function of anti-coagulants drugs with examples.

Answer 37

Prevent clotting in veins and low pressure pulmonary circulation Prophylaxis in patients with risk of DVT and PE Heparin - inhibit coagulation by working alongside antithrombin III to inhibit Factor Xa Novel Oral anticoagulants 1. Dabigatran (thrombin inhibitor) 2. Rivaroxaban (Factor Xa inhibitor) Warfarin Vitamin K antagonist, slow onset, requires constant monitoring

Question 38

Consider pharmacological control of blood clotting. Describe the function of fibrinolytics with examples.

Answer 38

clotting in arteries and vessels with high BP. Treatment for MI, PE, DVT, Thromboembolytic stroke Block tissue plasminogen activator 1. Streptokinase - produced by some species of strept Effective and cheap 2. Urokinase