VIVA: Pathology - Haemopoietic system Flashcards
How are the causes of anaemia classified?
- Blood loss*: acute or chronic
- Increased RBC destruction (haemolysis)*:
- Inherited genetic, e.g. spherocytosis, G6PD deficiency, thalassaemia, sickle cell
- Acquired genetic, e.g. paroxysmal nocturnal haemoglobinuria
- Antibody-mediated, e.g. transfusion reaction, drug-related, Rh disease
- Mechanical trauma, e.g. HUS, DIC, TTP, cardiac valves, runners - Decreased RBC production*:
- Inherited genetic, e.g. Fanconi’s anaemia, thalassaemia
- Nutritional, e.g. vitamin B12/folate deficiency, iron deficiency
- EPO deficiency, e.g. in renal failure or other chronic disease
- Immune-mediated, e.g. aplastic anaemia
*needed to pass + one example of each
Describe the pathogenesis of iron deficiency anaemia
Causes:
- Chronic blood loss, poor diet, impaired absorption, increased requirements
Pathogenesis:
1. Iron stores used up first leading to decreased ferritin * and haemosiderin
2. Once reserves depleted, serum iron and transferrin saturation decrease *
3. Erythroid activity increases but without iron in bone marrow the RBCs become hypochromic and microcytic *
*needed to pass
Give examples of anaemias that are more common in specific ethnic groups
One needed to pass with one example:
- Hereditary spherocytosis: northern European
- G6PD deficiency: 10% African American, African, Middle Eastern, Mediterranean
- Sickle cell: African (up to 30%)
- Thalassaemia trait: African, Asian, Mediterranean, Indian
- Pernicious: Scandinavian, Caucasian
Classify haemolytic anaemias
1 needed to pass:
- Intravascular vs extravascular
- Extrinsic vs intrinsic to RBC
- Hereditary vs acquired
Describe the common features of haemolytic anaemias
- Decreased RBC life span (<120 days) due to premature destruction*
- Increased erythropoietin and erythropoiesis
- Accumulation of products of haemoglobin catabolism
- Reticulocytosis
*needed to pass + one other
Give some important causes of intravascular haemolysis
2/4 to pass:
- Mechanical injury: cardiac valves, microangiopathic, repetitive physical trauma
- Complement fixation: ABO incompatible blood transfusion
- Intracellular parasites: malaria
- Exogenous toxins: Clostridia
Apart from anaemia, what are the results/manifestations of intravascular haemolysis?
3/7 to pass (including *):
- Haemoglobinaemia *
- Haemoglobinuria
- Unconjugated hyperbilirubinaemia (jaundice) * from catabolism of haem groups in mononuclear phagocyte system
- Haemosiderinuria and renal haemosiderosis
- Decreased serum haptoglobin due to binding with free Hb and then clearance by mononuclear phagocyte system
- Free Hb oxidised to metHb
- Reticulocytosis
What are the causes of iron deficiency anaemia?
Chronic blood loss (e.g. GIT*, menorrhagia)
Increased requirements (e.g. children, pregnancy)
Dietary lack (e.g. in developing world, infants with prolonged breastfeeding, elderly, extreme diet)
Impaired absorption (e.g. coeliac, gastrectomy)
*needed to pass + three other examples from any categories
What are the symptoms of iron deficiency anaemia?
4 to pass:
- General: pallor, fatigue, lethargy, weakness, dyspnoea, angina
- Features of underlying cause: melaena, menorrhagia
Are there any specific clinical features of iron deficiency anaemia?
1 needed to pass:
- Koilonychia
- Alopecia
- Glossitis
- Pica
- Pharyngeal web
What are the laboratory findings in iron deficiency anaemia?
- Microcytic hypochromic anaemia* (low Hb)
- Low serum iron levels
- Low serum ferritin levels (correlates well with body iron stores)
- High total iron-binding capacity, high transferrin levels
- Low transferrin saturation levels
*needed to pass + three others
What is the pathogenesis of pernicious anaemia?
- Chronic atrophic gastritis caused by immunologically mediated* (possibly autoimmune) destruction of gastric mucosa:
- Likely an autoreactive T-cell response which produces gastric mucosal injury and production of autoantibodies which may exacerbate epithelial injury - Loss of parietal cells leads to reduced intrinsic factor production which in turn leads to reduced vitamin B12 (cobalamin) absorption from the gut, resulting in macrocytic anaemia
- 3 types of antibodies present in many patients with pernicious anaemia, however their role in pathogenesis is unclear:
- Type 1 antibody blocks B12-IF binding
- Type 2 antibody blocks B12-IF complex binding to ileal receptors
- Type 3 antibody recognises alpha and beta subunits of gastric proton pump (most likely a response to gastric injury rather than causative)
- needed to pass
What are the clinical manifestations of pernicious anaemia?
- Insidious onset (due to large existing B12 stores) and progressive unless treated
- Moderate to severe megaloblastic anaemia causing weakness, fatigue, lethargy, pallor*
- Leucopaenia and thrombocytopaenia
- Mild jaundice (due to ineffective erythropoiesis and enhanced peripheral haemolysis)
- Atrophic glossitis (shiny glazed appearance)
- Neurologic manifestations may include spastic paraparesis, sensory ataxia and severe paraesthesias (more commonly in lower limbs)
*needed to pass
What is haemophilia A?
A reduction in the amount or activity of factor VIII, which is a co-factor for factor IX in the activation of factor X
X-linked recessive trait affecting males and homozygous females (however 30% have no family history so probably due to a new mutation)
Why do patients with haemophilia A bleed?
Lack of factor VIII affects the intrinsic pathway leading to inappropriate fibrinolysis and inadequate coagulation
Normally the extrinsic pathway produces an initial burst of thrombin activation that activates the intrinsic pathway via factors XI and XII: this is unable to occur in haemophilia A
Thrombin also normally activates TAFI (thrombin activatable fibrinolysis inhibitor) which inhibits fibrinolysis
