Intro to anaemia & Vit B12 and folate metabolism

Question 1

Define anaemia

Answer 1

A haemoglobin concentration lower than the normal range

Question 2

What are the signs and symptoms of anaemia? (non-specific signs)

Answer 2

Symptoms:
- shortness of breath
- palpitations
- headaches
- claudication
- angina
- weakness and lethargy
- confusion

Signs:
- pallor
- tachycardia
- systolic flow murmur
- tachypnoea
- hypotension

Question 3

What are the specific signs associated with the cause of anaemia?

Answer 3

• Kilonychia - spoon shaped nails - iron deficiency
• Angular stomatitis - inflammation of corners of mouth - iron deficiency
  *Glossitis - inflammation and depapillation of tongue - Vit B12 deficiency
• Abnormal facial bone development - thalassaemia

Question 4

What are the causes of anaemia that occur in the bone marrow?

Answer 4

1. Reduced erythropoiesis
   - Chronic kidney disease stops kidney from making EPO
   - Chemo/ toxic insult/ parvovirus infections can cause bone marrow to stop responding to EPO
   - Cancer (myelofibrosis) reduces number of HPSC
   - Anaemia of chronic disease (RA) → low iron (iron is not made available to marrow for RBC production)
   - Blood cancers known as myelodysplastic syndromes → abnormal marrow stem cells
2. Abnormal Haem/globin synthesis
   - Mutations in genes encoding the globin chain (sickle cell + alpha and beta thalassaemia)
   - Sideroblastic anaemia→ affects haem
   - Lack fo iron in diet/ anaemia of chronic disease (iron deficiency)
   - Anaemia of chronic disease → sufficient iron is in the body but not made available for erythropoiesis

Question 5

What are the causes of anaemia that occur in peripheral RBCs?

Answer 5

• Abnormal structure
• Mechanical damage
• Abnormal metabolism
  
  • G6PDh deficiency→ oxidative stress in RBC→ heinz bodies→ removed
  • Pyruvate kinase deficiency→ RBC lack ATP→ removed
• Excessive bleeding
• Increased removal by the reticuloendothelial system

Question 5

What is haemolytic anaemia and what are its cause?

Answer 5

Abnormal RBCs are removed faster than they can be replaced

1. Inherited
   
   • Mutations in genes coding for plasma membrane and cytoskeleton → cells become less flexible and damaged → hereditary spherocytosis
2. Acquired mechanical damage
   
   • Shear stress when RBC passes through a defective heart valve
   • RBC snagging on fibrin strands in small blood vessels
   • Heat damage in burns → water loss from RBCs
   • Osmotic damage (freshwater→ cells burst)

Question 6

How can G6PDH deficiency and pyruvate kinase deficiency lead to haemolysis and anaemia?

Answer 6

G6PDH deficiency
- low G6PDH = low regeneration on NADPH = less reduction of GSSH to GSH = low GSH
- GSH is a scavenger of ROS → H2O2 causes protein damage and aggregates of crosslinked haemoglobin form (HEINZ BODIES)

Pyruvate kinase deficiency
- final enzyme in glycolysis
- RBCs depend on glycolysis for ATP
- pyruvate deficiency = low ATP = RBC undergoes haemolysis

Question 7

What is chronic bleeding and how can it cause anaemia

Answer 7

A small amount of bleeding over a long time

• heavy menstrual bleeding
• repeated nosebleeds
• haemorrhoids
• occult GI bleeding (blood lost in stool) - ulcers in stomach, diverticulitis, polyps in large intestine, intestinal cancer
• kidney or bladder tumour (blood lost in urine)

Question 8

Give 3 examples of NSAIDs and how can chronic NSAID usage cause anaemia?

Answer 8

E.g. aspirin, ibuprofen, naproxen
NSAIDs induce GI bleeding via:
- inhibition of cyclooxygenase (COX) activity