Anaemias

Question 1

Vitamin B6

Answer 1

• Pyridoxal Phosphate (PLP)- metabolically active form
• co-factor for ALA synthase
• binds to haemaglobin and enhances O2 binding
• co-factor for synthesis of several neural transmitters and involved in glucose metabolism

Question 2

Sideroblastic anaemia

Answer 2

• vitamin B6 deficiency

- Sideroblasts: disordered incorporation of Fe into Haem, Toxic accumulation of Fe in mitochondria

Question 3

Vitamin B12 (cobalamin)

Answer 3

• Water soluble
• Blood, brain, NS
• Largest vitamin, 1355Da
• DNA synthesis, fatty acid and amino acid metabolism
• Animals, fungi and plants can’t synthesise it, Bacteria has enzymes for synthesis
• Form a corin ring and basic structure but human body can convert to different forms
• parietal cells of stomach secrete INTRINSIC FACTOR (IF) required for absorption

Question 4

Causes of Pernicious Anaemia (Vit B12 deficiency)

Answer 4

• Failure to secrete intrinsic factor

- Prevention of B12 absorption

Question 5

Symptoms of Pernicious Anaemia

Answer 5

• Decreased appetite and weight loss, abdominal pain
• Neurological involvement
• Colour blindness
• Psychological disturbances

Question 6

Diagnosis of Pernicious Anaemia

Answer 6

• Megaloblasts
• Abnormal precursors in bone marrow
• Antibodies to intrinsic factor
• Gastric analysis

Question 7

Treatment of Pernicious Anaemia

Answer 7

• vit B12 injection

- immunosupressants

Question 8

Folic Acid Deficiency

Answer 8

• Causes
  
  • Usually poor diet
  • Cancer patients, celiac disease
  • Anti-seizure drugs
• Diagnosis
  
  • Megaloblasts and other abnormalities
  • Low levels of folate
• Treatments
  
  • Food, supplements (oral or injection)

Question 9

Iron storage

Answer 9

• Free iron is toxic

- Iron is stored in a protein complex as ferritin or hemosiderin

Question 10

Ferretin

Answer 10

• Intracellular protein store for iron
• Apoferretin binds free ferrous iron (Fe2+) and stores it in ferric state (Fe3+)
• Iron stored in a non-toxic form
• release and transport Fe where it is required
• Buffer against iron overload and deficiency
• As it accumulates it aggregates as hemosiderin
• Iron in hemosiderin is difficult to provide where needed

Question 11

Iron deficiency

Answer 11

• Causes: Bleeding, Inadequate iron in diet
• Symptoms: Pica, glossitis, cheilosis, nail deformity
• Diagnosis: Microcytic red blood cells, Hypochromic blood, Amount of iron in body (transferrin, ferritin)
• Treatment: Iron supplements

Question 12

Iron overload

Answer 12

• Primary (hereditary), Secondary (acquired)
• HFE protein regulates iron absorption
• HFE can associate with TfR, regulates hepcidin gene expression, blocks export of iron from macrophages
• Treatment: normally requires iron chelators
• Desferrioamine; reduces liver and plasma iron levels
• Venesection

Question 13

Haemoglobinopathies

Answer 13

• Thalassaemias - rate of globin synthesis
• Structural Haemoglobinopathies- abnormal globin structure
• Affect oxygen transport

Question 14

Ontogeny of globin chains

Answer 14

• Throughout the existence of an individual globin chains in Hb vary.
• Yolk sac is site of embryonic RC production with three embryonic Hbs described
• Hb Portland and 2x Gower Hbs

Question 15

Thalassaemia

Answer 15

• Defect in amount of globin; reduced alpha and/or beta chains
• poor O2 transport
• cause: inherited
• Clinical Spectrum; Normal to life threatening, Growth retardation, Hepatosplenomegaly, Bone overgrowth, bone pain
• Diagnosis: hereditary patterns, electrophoresis
• Treatment: Thalassaemia major, regular blood transfusions

Question 16

Alpha thalassaemias

Answer 16

• Chromosome 16, 2 tandem pairs a-globin genes
• 4 a-globin genes
• Majority of mutations are deletions of the a-globin genes
• Both a genes malfunction, no a globin produced a0-thalassemia
• aberrant a+-thalassemia, fewer a-globin chains, excess b-chains in adults and g chains in newborns

Question 17

Alpha thalassemias - types and genotypes

Answer 17

• Silent carriers; deletion of single gene has no effect
• 2 gene mutation-50%
  
  • a-thalassaemia minor/carrier
  • a-thalassaemia trait
  • a+ homozygote (a-/a-) or a0 heterozygote (–/aa)
  • mild microcytic, hypochromic anaemia
• 3 gene mutation-25%-HbH disease, jaundice, leg ulcers, folic acid deficiency, severe anaemia, hepatosplenomegaly, microcytosis, hypochromasia, fragmented red cells
• 4 gene mutation-0%- Hb Bart’s or hydrops fetalis syndrome, death in utero

Question 18

Beta thalassemias and mutations

Answer 18

• Chromosome 6, 2 b-globin genes
• 200 different mutations
• Mutations can result in reduction or abolition of b-globin function
• Point mutations classified according to stage of globin stage expression in which defect appears;
  
  • Inefficient transcription
  • Defective processing of mRNA transcript
  • Defective splicing of mRNA
  • Improper protein translation
  • Post-translational instability
• b0-globin chains are absent, b+-globin chains partially present

Question 19

Thalassemia major (BoBo)

Answer 19

• severe anaemia
• BM hypertrophy-skeletal changes
• hepatosplenomegaly

Question 20

Thalassemia intermedia (B+Bo/B+B+)

Answer 20

• normal life but can require transfusions

Question 21

Thalassemia minor (trait)

Answer 21

• Mild microcytic, hypochromic anaemia, lower than normal MCV <80fL
• Have raised Hbs A2 – normal variant of HbA that consists of 2 alpha and 2 delta and found in normal human blood and/or raised HbF 2 alpha and 2 gamma

Question 22

Sickle cell anaemia

Answer 22

• Tetramers aggregate; prevent microcirculation
• Shortened cell lifetime
• Qualitative affect on globin
• HbS fully oxygenated, Hb remains soluble
• Under low oxygen conditions, HbS loses solubility
• Polymerisation of HbS
• Numerous rounds of oxygenation and deoxygenation irreversible sickle
• Increase stickness, attach to endothelial walls, increased risk of thrombosis
• Anaemia develops as RBC eliminated by reticuloendothelial system

Question 23

Sickling disorders (HbS)

Answer 23

• Causes: inherited
• Symptoms: painful vaso-occlusive crisis; blood vessel blockage, tissue hypoxia, Elevated haemolysis
• Diagnosis: electrophoresis/PCR, enlarged spleen, heart, liver, Biochemical findings; Hyperuricemia, Reduced zinc levels
• Treatment: Alleviate symptoms of crisis, Prevent crisis, Bone marrow transplant

Question 24

Malaria

Answer 24

• ~10% world population infected
• 2 million deaths per year (mainly pregnant women/young children)
• 4 different species infect humans: vivax, malariae, ovale, falciparum
• falciparum; most serious and causes the majority of deaths
• Pulmonary edema: fluid accumulation in the lungs

Question 25

Transmission of malaria

Answer 25

• infection with sporozoite from infected mosquito
• invade hepatocytes and mature into merozoites which invade RBCs undergo several stages of development eventually rupturing the erythrocyte
• Pathology is mainly mediated by immune reactions to parasite + pRBCs obstructing the flow of blood in vital organs
• Immune complexes involving parasites or parasite products damaging the endothelial cells which line the blood vessels.
• Hi levels of pyrogens/ proinflammatory mediators causing systemic organ damage