Haematology

Question 1

Explain the control of erythropoiesis

Answer 1

Controlled by erythropoietin (EPO) a polypeptide hormone
EPO released by peritubular kidney cells in response to low [O2] during anemia, high altitude or COPD
Increases number of stem cell to become RBC
Recombinant EPO used to treat renal failure due to anaemia

Question 2

What is polycythemia ?

Answer 2

Excessive erythropoiesis

Question 3

Describe the maturation of RBCs

Answer 3

Nucleus of reticulocyte taken up by bone marrow macrophages

mRNA remains and allows Hb to still be synthesised

reticulocyte then enters blood

Question 4

What is a reticulocyte

Answer 4

Immature RBC

Question 5

Describe the degradation of RBCs

Answer 5

Occurs in reticuloendothelial system if spleen, liver and bone marrow

Components of erythrocyte are recycled ;

proteins degraded, iron retained in stores , porphyria from haem converted to bilirubin in liver

Question 6

What does a high plasma [reticulocyte] indicate

Answer 6

Internal bleeding
Haemolysis

Question 7

Measurement of life spans of erythrocytes can be used to detect…

Answer 7

Spherocytosis
Sickle cell anaemia

Question 8

Structure of Hb

Answer 8

Tetrameric
Haem : Fe2+ at centre of protoporphyrin complex
Globin chains linked by non-covalent bonds

Question 9

Describe the structure of foetal Hb

Answer 9

Contains 2 α₂γ₂ subunits

Question 10

describe how iron is taken up, transported around the body and stored

Answer 10

Fe³⁺ → Fe²⁺ by stomach acid

Fe²⁺→ Fe³⁺ in duodenum

Fe³⁺ + apoferritin → ferritin (store of iron)

when iron is required, transported in blood with transferrin protein

transferrin delivers iron to bone marrow

iron binds to Hb

Question 11

Hb is an allosteric protein; what does this mean ?

Answer 11

The binding of one O2 increases the binding of another O2 and so on

Question 12

Describe the oxygen dissociation curve

Answer 12

Sigmoidal shape ; ppO2 in active tissue foudn at the steepest part of curve ; small change in oxygen results in lots of O2 being unloaded

Question 13

What is DPG ? Describe its function

Answer 13

2,3-diphosphoglycerate

present in RBCs at same molar conc as Hb

allosteric effector of Hb; binds to deoxyHb and makes it harder for oxygen to bind Hb and instead be released to adjacent tissues

reduces affinity of Hb for O₂ ; in its absence Hb would unload very little O₂ to tissues

Question 14

adaptation of body to COPD

Answer 14

Increased 2,3 DPG

similar to Bohr effect ; ensure delivery of O2 even in poor oxygenation

Question 15

What is carboxyHb

Answer 15

Hb has a much greater affinity for CO ; does not dissociate

tissue becomes deprived of O2

smokers have higher level of COHb ; contributes to vascular diseases

Question 16

What is methaemoglobinaemia - causes and symptoms

Answer 16

What is it? Occurs when Fe²⁺ converted to Fe³⁺ = elevated methaemoglobin (Hb containing Fe³⁺). Fe³⁺ cannot carry O₂

Causes :

genetic lack of glucose-6-phosphate dehydrogenase = Hb remains in reduced state

anti malarial, sulphonamides may cause this in susceptible patients

Symptoms : cyanosis, dizziness, respiratory distress, tachycardia

Question 17

Describe CO₂ transport

Answer 17

some dissolved in blood ; some bound to Hb ; the rest carries as HCO₃^-

this is catalysed by carbonic a hydrate in RBC

Hb buffers the H+ produced

if HCO₃^- may leave cell, Cl^- enters to maintain charge

Question 18

Describe the 2 types of clotting mechanism

Answer 18

Intrinsic - when blood is exposed to foreign surfaces (such as collagen from injured blood vessel wall)

extrinsic - damaged tissue releases thromboplastin

mechanism is the same for both once activated:

Factor X is activated via action of serine proteases

active factor X cleave prothrombin to form thrombin + factor XIII

thrombin converts fibrinogen to fibrin

fibrin stabilised by factor XIII = clot

Question 19

Describe the common symptoms of anaemia
What is anaemia?

Answer 19

Reduced levels of Hb
Symptoms : SoB , lethargy, tachycardia
Nail bed and conjuctiva may be pale
In elderly patients may cause angina
Glossitis (painful red tongue) and angular cheilitis (fissures at corner of mouth)
Elevated DPG

Question 20

Describe iron deficiency anaemia

Answer 20

Symptoms : microcytic (decreased MCV)
Occurs due to poor diet/removal of stomach/excessive menstruation/bleeding gastrointestinal ulcers/colon cancer/pregnancy

Question 21

Complete this table
State whether levels decrease/increase/stay normal

Answer 21

Chronic bleeding will results in a different FBC to acute bleeding
Acute bleeding due to haemorrhage
Chronic bleeding due to anemia

Question 22

Describe renal anaemia

Answer 22

Chronic kidney disease complication - lack of stimulation to produce RBCs due to less EPO (kidneys make EPO)
Normal sized RBCs but less of them
Treated with Fe and EPO

Question 23

Why is haemodilution useful in acute bleeding

Answer 23

Increase vol of blood to increases BP ; blood reach organs faster

Question 24

Megaloblastic anaemia
What is it
Causes
Symptoms

Answer 24

Abnormal RBC maturation due to defective DNA synthesis ; megaloblasts(large RBC with excessive cytoplasm) will be formed instead of healthy RBC
Due to vitamin B12 or folate deficiency
Symptoms : jaundice (due to excessive breakdown of Hb due to increased in effective erythropoiesis)

Question 25

Function of folic acid

Answer 25

Essential for DNA synthesis

Question 26

Pernicious anaemia

Answer 26

Caused by lack of intrinsic factor for absorption of vit B₁₂ due to autoimmune disease

Question 27

What is methotrexate

Answer 27

inhibitor of enzyme needed for folic acid synthesis

Question 28

Haemolytic anaemias

What causes it

Symptoms

Answer 28

Increased rate of RBC destruction

spherocytosis - is genetic - abnormal reduction in RBC membrane protein

acquired - haemolytic transfusion reaction (rejection of transfused blood) ; malaria ; drug-induced

symptoms ; jaundice ; enlarged spleen ; folate deficiency

Question 29

Sickle cell anaemia

What is it

Causes

symptoms

Answer 29

Abnormal Hb that is insoluble at low pO2 ; RBC become sickle shaped and can block microcirculation

Genetic : single nucleotide polymorphism OR valine replacues glutamic acid

symptoms ; haemolytic anaemia, pain

complications : risk of stroke ; reduced life expectancy

treatment : blood transfusions

Question 30

Thalassaemias

what are they

symptoms

causes

treatment

Answer 30

• Alpha thalassemia: Missing or mutated genes related to the alpha globin protein.
• Beta thalassemia (also called Cooley anemia): Gene defects that affect production of beta globin protein.
• Symptoms :
• reduced RBC vol and Haematocrit
• Paleness.
• fatigue
• shortness of breath.
• Lack of appetite.
• Dark urine.
• Jaundice
• In children, slow growth and delayed puberty.
• Bone deformities in the face.
• Abdominal swelling.
• Treatment : transfusions and folate supplements ; iron tablets contra indicated

Question 31

Aplastic anaemia

What is it

Symptoms

Causes

Treatment

Answer 31

Insufficient production of RBCs, WBCs and platelets (pancytopenia) ; although may just be RBCs (pure red cell aplasia)

causes: mostly acquired - virus/radiation/drugs

Symptoms :

• Decreased resistance to infections,
• increased bleeding,
• increased tiredness

treatment :

bone marrow transplant

immunosuppressants

colony stimulating factors to increase WBC

Question 32

Polycythaemia

what is it

causes

symptoms

treatment

Answer 32

Increased Hb content and hamatocrit ; increased blood viscosity and poor tissue perfusion

symptoms ; red skinn ; cyanosis ; headaches ; blurred vision; hypertension, dizziness, unusual bleeding

causes :

primary - bone marrow stem cell defect , bone marrow cancer

secondary - increased EPO due to altitude, smoking, renal or liver carcinoma/COPD/sleep apnea

treatment :

Primary— bleeding; myeolosuppression