Anaemias Flashcards
1
Q
Vitamin B6
A
- 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
2
Q
Sideroblastic anaemia
A
- vitamin B6 deficiency
- Sideroblasts: disordered incorporation of Fe into Haem, Toxic accumulation of Fe in mitochondria
3
Q
Vitamin B12 (cobalamin)
A
- 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
4
Q
Causes of Pernicious Anaemia (Vit B12 deficiency)
A
- Failure to secrete intrinsic factor
- Prevention of B12 absorption
5
Q
Symptoms of Pernicious Anaemia
A
- Decreased appetite and weight loss, abdominal pain
- Neurological involvement
- Colour blindness
- Psychological disturbances
6
Q
Diagnosis of Pernicious Anaemia
A
- Megaloblasts
- Abnormal precursors in bone marrow
- Antibodies to intrinsic factor
- Gastric analysis
7
Q
Treatment of Pernicious Anaemia
A
- vit B12 injection
- immunosupressants
8
Q
Folic Acid Deficiency
A
- 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)
9
Q
Iron storage
A
- Free iron is toxic
- Iron is stored in a protein complex as ferritin or hemosiderin
10
Q
Ferretin
A
- 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
11
Q
Iron deficiency
A
- 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
12
Q
Iron overload
A
- 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
13
Q
Haemoglobinopathies
A
- Thalassaemias - rate of globin synthesis
- Structural Haemoglobinopathies- abnormal globin structure
- Affect oxygen transport
14
Q
Ontogeny of globin chains
A
- 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
15
Q
Thalassaemia
A
- 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
16
Q
Alpha thalassaemias
A
- 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
17
Q
Alpha thalassemias - types and genotypes
A
- 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
18
Q
Beta thalassemias and mutations
A
- 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
19
Q
Thalassemia major (BoBo)
A
- severe anaemia
- BM hypertrophy-skeletal changes
- hepatosplenomegaly
20
Q
Thalassemia intermedia (B+Bo/B+B+)
A
- normal life but can require transfusions
21
Q
Thalassemia minor (trait)
A
- 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
22
Q
Sickle cell anaemia
A
- 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
23
Q
Sickling disorders (HbS)
A
- 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
24
Q
Malaria
A
- ~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
25
Q
Transmission of malaria
A
- 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
