Hemachromatosis

Question 1

Definition and classification of haemochromatosis

Answer 1

Definition: excessive accumulation of body iron

Classification
1. Hereditary (primary ): mutations of genes encoding HFE, Tf2, hepcidin, HJV
2. Haemosiderosis (secondary)
~ parenteral iron overload: transfusions, SCD, haemolyses, aplastic anaemia
~ increased oral intake of iron
~ infective Erythropoiesis: beta thalassaemia
~ chronic liver disease: ALD

Pathogenesis
~ absence of hepcidin - absorption of iron even after elevation of body iron stores
~ symptoms appear after Iron > 20g

Question 2

Tissue damage mechanism

Answer 2

1. Free radical formation. - lipid peroxidation
2. Activation of hepatic stellate cells - collagen deposition
3. ROS interaction with DNA.- little cell injury - HCC

~ haemosiderin gets deposited in
Liver > pancreas> myocardium> pituitary> adrenal > thyroid > Para thyroid> joint> skin

Question 3

Morphology of liver

Answer 3

Gross: early :normal or slightly dark
Later : chocolate brown
~ cirrhosis : initial micronodular then macro

Micro: granular, golden yellow pigment in cytoplasm, Prussian blue stains blue
~ fibrosis develops slowly and progressively

Question 4

Clinical features

Answer 4

~ during fifth and sixth decade
~ males affected
~ triad: micronodular cirrhosis + diabetes mellitus (bronze diabetes) + skin pigmentation
~ death: Cirrhosis + cardiac disease + HCC

Question 5

Laboratory findings

Answer 5

~ increased serum iron
~ increased percentage saturation
~ increased serum ferritin
~ reduced TIBC