Haematology Flashcards
Explain the control of erythropoiesis
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
What is polycythemia ?
Excessive erythropoiesis
Describe the maturation of RBCs
Nucleus of reticulocyte taken up by bone marrow macrophages
mRNA remains and allows Hb to still be synthesised
reticulocyte then enters blood
What is a reticulocyte
Immature RBC
Describe the degradation of RBCs
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
What does a high plasma [reticulocyte] indicate
Internal bleeding
Haemolysis
Measurement of life spans of erythrocytes can be used to detect…
Spherocytosis
Sickle cell anaemia
Structure of Hb
Tetrameric
Haem : Fe2+ at centre of protoporphyrin complex
Globin chains linked by non-covalent bonds
Describe the structure of foetal Hb
Contains 2 α2γ2 subunits
describe how iron is taken up, transported around the body and stored
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
Hb is an allosteric protein; what does this mean ?
The binding of one O2 increases the binding of another O2 and so on
Describe the oxygen dissociation curve
Sigmoidal shape ; ppO2 in active tissue foudn at the steepest part of curve ; small change in oxygen results in lots of O2 being unloaded
What is DPG ? Describe its function
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
adaptation of body to COPD
Increased 2,3 DPG
similar to Bohr effect ; ensure delivery of O2 even in poor oxygenation
What is carboxyHb
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
What is methaemoglobinaemia - causes and symptoms
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
Describe CO2 transport
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
Describe the 2 types of clotting mechanism
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
Describe the common symptoms of anaemia
What is anaemia?
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
Describe iron deficiency anaemia
Symptoms : microcytic (decreased MCV)
Occurs due to poor diet/removal of stomach/excessive menstruation/bleeding gastrointestinal ulcers/colon cancer/pregnancy
Complete this table
State whether levels decrease/increase/stay normal
Chronic bleeding will results in a different FBC to acute bleeding
Acute bleeding due to haemorrhage
Chronic bleeding due to anemia
Describe renal anaemia
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
Why is haemodilution useful in acute bleeding
Increase vol of blood to increases BP ; blood reach organs faster
Megaloblastic anaemia
What is it
Causes
Symptoms
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)
Function of folic acid
Essential for DNA synthesis
Pernicious anaemia
Caused by lack of intrinsic factor for absorption of vit B12 due to autoimmune disease
What is methotrexate
inhibitor of enzyme needed for folic acid synthesis
Haemolytic anaemias
What causes it
Symptoms
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
Sickle cell anaemia
What is it
Causes
symptoms
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
Thalassaemias
what are they
symptoms
causes
treatment
- 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
Aplastic anaemia
What is it
Symptoms
Causes
Treatment
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
Polycythaemia
what is it
causes
symptoms
treatment
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
