Anaemia

Question 0

Why does anaemia lead to impaired collagen synthesis?

Answer 0

Fe2+ is a cofactor for proline hydroxylase/lysyl hydroxylase as well as Vit. C

Question 1

What are the signs and symptoms of anaemia?

Answer 1

Reduced O2 consumption:

• fatigue
• faintness
• intermittent claudication
• exercise intolerance
• pallor

Weakened collagen:

• koilonychia = spoon-shaped nails (flat/concave)
• glossitis = inflammation of the tongue
• angular cheilitis/stomatitis = dry, sore mouth
• flaky nails/skin
• angina
• systolic flow murmur
• palpitations
• tachycardia
• cardiac failure
• jaundice (haemolytic anaemia)
• leg ulcers (sickle-cell anaemia)
• bone deformities (thalassaemia major)

Question 2

What are some things which can cause anaemia?

Answer 2

• iron deficiency
• aplastic anaemia (bone marrow stops producing RBCs)
• Vit. B12/folate deficiency
• chronic kidney disease (reduction in erythropoietin)
• haemolytic anaemias

Question 3

What are some causes of iron deficiency?

Answer 3

• parasites e.g. tapeworms
• malnutrition
• poor Fe2+ absorption in the duodenum e.g. Coeliac’s disease
• pregnancy
• menstrual bleeding

Chronic bleeding:

• ulcers (non-steroidal inflammatory or ulcerative colitis/Crohn’s)
• gastric/oesophageal/bowel cancer
• familial adenomatous polyposis = autosomal dominant; defect in APC tumour suppressor genes -> multiple benign polyps in colon which can become cancerous (note: does not affect Fe2+ absorption)

Question 4

How is iron absorbed and stored?

Answer 4

Haem iron (meat & fish) absorbed as ferrous iron (Fe2+)

Non-haem iron (beans & green leafy vegetables) exists as ferric iron (Fe3+) and must be reduced before being absorbed

Low pH of gut keeps iron in ferrous state

10-15mg/day consumed; 1-2mg/day absorbed (80% recycled)

Iron stored in macrophages; 95% ferritin, 5% haemosiderin

Active iron: Hb, myoglobin, tissue iron (enzyme cytochromes), serum iron

Question 5

What effect does hepcidin have on iron stores?

Answer 5

Hepcidin (liver & kidneys) blocks iron transport, pushing iron into stores, inhibiting iron release from macrophages

note: erythropoietin inhibits hepcidin

Question 6

How does the body adapt to anaemia?

Answer 6

Redistribution of blood flow to vital organs:

• increased vascularisation
• vasodilatation
• increased synthesis of erythropoietin
• increased cardiac output
• increased absorption of dietary iron
• increased BPG (reduction in O2 affinity of RBCs - movement of curve to right - so O2 is more readily supplied to metabolising tissues)

Question 7

What investigations should be done when anaemia is suspected?

Answer 7

Full blood count:

• Hb
• mean corpuscular volume (low = iron deficiency, thalassaemia; normal = acute blood loss, chronic kidney disease, autoimmune rheumatic disease, marrow infiltration/fibrosis, endocrine disease, haemolytic anaemias)
• platelets
• lymphocytes, monocytes, eosinophils
• reticulocytes (immature RBCs)

Blood film:

• size of RBCs (micro/macrocytic)
• shape of RBCs (e.g. pencil-shaped)
• colour of RBCs (hypochromia = pale cells)
• serum ferritin (soluble iron in hepatocytes; level correlates with iron stores note: increased by infection/inflammation, liver disease/malignancy)
• haemosiderin (insoluble iron in macrophages in bone marrow, liver, spleen): detect using Perl stain
• kidney function test: glomerular filtration rate, creatinine, electrolytes
• % transferrin (how much iron is being transported)
• venesection: bleed and measure by how much iron they were in excess by
• bone marrow biopsy: hypercellular (attempting to produce reticulocytes but cannot)

Question 8

What is the treatment for iron deficient anaemia?

Answer 8

Iron tablets: take with vit. C to aid absorption, do not take with tea/chapattis (chelating agents reduce absorption) or antacids (increases pH which reduces iron absorption as iron is not in ferrous state)