Cell Lines Derived from Haematopoiesis

Haematopoiesis and Blood Cells

• 7 cell lines arise from haematopoiesis:
  • Red blood cells: transport O2 from lungs to tissues
  • Neutrophils: chemotaxis, phagocytosis, killing of phagocytosed cells
  • Eosinophils: neutrophil functions + antibody-dependent damage to parasites, immediate hypersensitivity
  • Basophils: immediate hypersensitivity, modulate inflammatory response via proteases and heparin
  • Monocytes and macrophages: chemotaxis, phagocytosis, killing of micro-organisms, antigen presentation and release of IL-1 and TNF
  • Platelets: primary haemostasis (adhere to subendothelial connective tissue)
  • Lymphocytes: immune response and haemopoietic growth factors

Haemoglobin Levels

• Haemoglobin levels in adults:
  • Adult males: 130-170 g/L
  • Adult females: 120-155 g/L
  • Pregnant females: 110-140 g/L
• Children's haemoglobin levels:
  • 6 months-6 years: 110-145 g/L
  • 6 years-14 years: 120-155 g/L

Anaemia

• Anaemia arises when there is a reduction in haemoglobin levels below the reference range for age and sex of the individual
• Rate of anaemia development dictates the symptoms and signs
• Symptoms of anaemia:
  • Lassitude
  • Fatigue
  • Dyspnoea on exertion
  • Palpitations
  • Headache
  • Chest pain
• Signs of anaemia:
  • Pallor
  • Tachycardia
  • Wide pulse pressures
  • Systolic flow murmurs
  • Congestive cardiac failure

Mechanisms of Anaemia Development

• Blood loss
• Decreased red cell lifespan (haemolytic)
• Impairment of red cell formation
  • Insufficient erythropoiesis
  • Ineffective erythropoiesis
• Pooling of and destruction of RBCs in spleen
• Increased plasma volume (pregnancy)

Anaemia Morphology

• Microcytic (small) anaemia:
  • Iron deficiency
  • Thalassaemias
• Normocytic (normal) anaemia:
  • Acute blood loss
  • Anaemia of chronic disease
  • Chronic renal failure
• Macrocytic (big) anaemia:
  • Alcoholism
  • Folate deficiency
  • Vitamin B12 deficiency
  • Drugs

Iron Deficiency Anaemia

• Most common cause of microcytic anaemia worldwide: iron deficiency anaemia
• Iron is tightly managed in the body due to its potential toxicity
• Mechanisms of iron deficiency:
  • Poor dietary intake
  • Malabsorption
  • Increased loss of iron
• Manifestations of iron deficiency:
  • Koilonychia
  • Angular chelitis
  • Atrophic glossitis
  • Recurrent oral ulceration
  • Burning mouth
  • Oesophageal web (Plummer-Vinson / Patterson-Brown Kelly syndrome)
• Management of iron deficiency microcytic anaemia:
  • Investigated via blood film and iron studies
  • Treatment involves addressing underlying cause, oral supplementation, parenteral supplementation, and blood transfusion (in severe cases)

Thalassaemias

• Inherited blood disorder causing reduced haemoglobin levels
• Another cause of microcytic anaemia

Normocytic Anaemia

• Associated with:
  • Chronic inflammatory/connective tissue
  • Chronic infections
  • Chronic renal disease
  • Malignancies

Macrocytic Anaemia

• Divided into:
  • Megaloblastic erythropoiesis (abnormal red cell development due to disordered DNA synthesis)
  • Normoblastic erythropoiesis (normal red cell maturation)
• Type of anaemia: macrocytic
• Associated deficiencies:
  • Folate (vitamin B9): essential for DNA synthesis, found in green leafy vegetables
  • Vitamin B12: required for several enzymatic reactions, found in food only of animal origin
• Causes of deficiencies:
  • Folate: inadequate intake, malabsorption, increased requirement, increased loss, and drugs
  • Vitamin B12: inadequate intake, inadequate secretion of intrinsic factor, inadequate release from food, diversion of dietary B12, and malabsorption
• Clinical features of folate and vitamin B12 deficiencies:
  • Generic symptoms and signs of anaemia
  • Occasional mild jaundice
  • Glossitis
  • Oral ulceration
  • Peripheral neuropathy (loss of proprioception and vibration sense)
  • Demyelination with subacute combined degeneration of spinal cord
  • Dementia
• Management of megaloblastic anaemia:
  • Investigations: blood film and serum folate and B12
  • Treatment involves addressing underlying cause, oral supplementation, and parenteral vitamin B12 (in pernicious anaemia)

Normoblastic Macrocytosis

• Causes:
  • Alcohol excess
  • Liver dysfunction
  • Hypothyroidism
  • Drugs (methotrexate, azathioprine)

Haemolytic Normocytic Anaemia

• Divided into:
  • Congenital
  • Acquired
• Defects in congenital haemolytic anaemias:
  • Membrane defects
  • Enzyme defects (e.g. G6PD deficiency)
  • Globin defects
• Defects in acquired haemolytic anaemia:
  • Immune (autoimmune or alloimmune)
  • Non-immune (mechanical trauma, infections, or drugs)
• Clinical features of haemolytic normocytic anaemia:
  • Pallor
  • Jaundice (due to elevated bilirubin)
  • Splenomegaly (enlargement of the spleen)
  • Expansion of erythropoiesis leading to bone deformities (frontal bossing) and pathological features

Haemoglobin Function

• Role of haemoglobin: oxygen transportation
• Normal haemoglobin composition: 2 alpha and 2 beta chains
• Compositions of adult haemoglobin:
  • Hb A (normal) (alpha2beta2) 97%
  • Hb A2 (alpha2delta2) 1.8-3.6%
  • Hb F (alpha2gamma2)