Anaemia Flashcards
Main causes of anaemia
Decreased production
Increased destruction
Causes of decreased production of RBCs
Dx = Low reticulocytes
BM problem
Haematinics - Iron, Vitamin 12 and folate
Anaemia of chronic disease
Kidney disease
Causes of increased RBC destruction
Haemolysis
Thalassaemia
Blood loss
Causes of microcytic anaemia
Iron deficiency
Thalassaemia
Anaemia of chronic disease Myelodysplasia Sideroblastic anaemia Hyperthyroidism Heavy metal poisoning
Iron homeostasis
Normal body = 3-4gms of iron
2gms in red cells
Rest is bound in proteins or stored
Need 20mg/day for erythropoiesis
1-3mg/day absorbed and rest is recycled
No regulated system of excretion - soughing of enterocytes and menstrual loss
Iron cycle
ABSORPTION:
Non-Haem Fe
- Duodenal entercytes abserob Fe2 through apical membrane DMT1
- Excreted by ferroportin from enterocyte into the plasma
Haem Fe
- Unknown pathway but more bioavailable
STORAGE:
Stored in hepatocytes, spleen and BM
TRANSPORT:
Transferred in plasma bound to transferrin
Regulation of iron absorption
HEPCIDIN:
- Binds ferroportin and induces its degradation
- –> decreases iron absorption
- Acute phase reactant
- Regulated by HFE, TfR2, HJV, hypoxia and EPO
Transcriptional control of DMT-1 and ferroportin
- Induced by hypoxia
Causes of iron deficiency anaemia
GIT Bleeding:
- Gastric ulcers
- Malignancy
- Diverticulitis
Menstruation Diet Other: - Coeliac - Gastric bypass - Pregnancy - PCRV - GIT parasites
Diagnosis of cause of iron deficiency anaemia
Film - microcytic hypochromic red cells
Iron studies - high transferrin, low transferrin saturation and ferritin
Investigate for source of blood loss
Management of iron deficiency anaemia
Iron replacement therapy:
- Oral, IM or IV
Monitor Hb and reticulocyte count for response
Treatment failure:
- Non compliance
- Ongoing losses
- Malabsorption
- B12/folate deficiency
- ACD
- THALASSAEMIA
Anaemia of chronic disease
Multifactorial disease
Common causes - infection, neoplasia, inflammation
Inflammation –> IL-1, IL-6, TNF-alpha –> increased hepcidin
Reduced reticulocytosis, reduced RBC lifespan, and abnormal Fe homeostasis
Treat underlying disease
Fe replace
EPO
Causes of macrocytic anaemia
Megaloblastic erythropoiesis:
- B12 deficiency
- Folate deficiency
- Antifolate drugs - MTX, trimethoprim
- Anti-DNA synthesis drugs - AZA, hydroxyurea, zidovudine, chemotherapy
Reticulocytosis
- Haemolysis
- Bleeding
Others:
- BM pathology - Aplastic anaemia, MM, MDS
- Liver disease
- Copper deficiency
- Downs
Vitamin B12 absorption and metabolism
From animal products
Ingested as cobalamin - released from food by pepsin and acid
Bound by transcobalamin
Pancreatic enzymes release cobalamin –> binding by intrinsic factor
B12-IF complex absorbed in terminal ileum
Transcobalamin transports in the body
Stored in the liver
Role of Vitamin B12 in the body
- Reduces homocystiene to methionine in the cytoplasm –> various metabolic pathways including nucleic acid synthesis
- Used in the TCA cycle in mitochondria - MM-CoA –> Succinyl-CoA
Causes of Vitamin B12 deficiency
Pernicious Anaemia
- AID –> loss of parietal cells –> loss of intrinsic factor
- Test IF antibodies and Parietal cell antibodies
Diet Intestinal pathology: - Coeliac - Ilieal resection - Sprue
Gastrectomy
