Please enable JavaScript.

Coggle requires JavaScript to display documents.

Anaemias - Coggle Diagram

- - - - Rate limiting step of haem synthesis
    - - Sideroblastic anaemia
        
        Ring sinderoblast - nucleated RBCs
        
        Granules of toxic iron accumulation in mitochondria
      - Disordered incorporation of Fe into haem
      - Can be genetic disorder due to mutations in ALA synthase gene
  - - - 2 can be converted into active form
    - - B12 binds to intrinsic factor (IF) - for absorption in intestine
      - IF destroyed
      - Autoimmune disease
        
        Ab binds IF
      - Symptoms
        
        Decreased appetite
        
        Neurological
        
        Colour blindness
        
        Psychological disturbances
      - Diagnosis
        
        Megaloblastic anaemia
        
        Megaloblasts seen on blood smear
        
        Ab to IF
        
        Gastric analysis
      - Treatment
        
        Vit B12 injection
        
        Immunosuppressants
  - - - Poor diet
      - Cancer
      - Coeliac
      - Anti-seizure drugs
    - - Megaloblasts on blood smear
      - Low levels of folate
    - - Change diet
      - Supplements
  - - - Ferroportin
      - DMT1
      - Transferrin
    - - Free iron is toxic
      - Stored in protein complex of ferritin or haemosiderin
        
        Ferritin
        
        Intracellular protein store for iron
        
        Apoferritin binds Fe\(^{2+}\) and stores it as Fe\(^{3+}\)
        
        Buffer against overload + deficiency
    - - Excessive bleeding
        
        More RBC production
      - Inadequate iron in diet
    - - Pica
        
        Crave unusal non-food itemse.g. soil
      - Glossitis
        
        Swollen tongue
      - Cheilosis
        
        Inflammation of mouth corners
      - Nail deformity
    - - Microcytic RBCs
        
        Pale in colour
      - Hypochromic blood
      - Amount of iron in blood
        
        Transferrin, ferritin levels measured
    - - Iron supplements
      - Stop bleeding, blood transfusion
  - - - Hereditary
    - - Acquired
    - - Regulates iron absorption
      - Function
        
        Associates with TfR (transferrin receptor)
        
        Regulates hepcidin gene expression
        
        Blocks export of iron from macrophages
      - Hereditary haemochromatosis
    - - Iron chelators
      - Desferrioamine
        
        Reduces liver + plasma iron levels
      - Venesection
        
        Regular controlled bleeding
- - - - Can be lethal
    - - Clinical severity + which globin chain affected
    - - Normal to life threatening
      - Growth retardation
      - Hepatsplenomegaly
    - - Inherited genetic mutation
    - - Family history
        
        Hereditary patterns
      - Electrophoresis
        
        PCR anaysis
    - - Thalassaemia major
        
        Regular blood transfusions
      - Bone marrow/gene editing possibilites for long-term treatment
    - - Chromosome 16, 2 tandem pairs \(\alpha\)-globin genes
        
        4 \(\alpha\)-globin genes
        
        1 mission - no symptoms as 3 remain
      - Common mutations are deletions of genes
      - Malfunction in both \(\alpha\) genes
        
        No \(\alpha\)-globin produced
        
        \(\alpha^0\)-thalassaemia
        
        Common in Philippines, South East Asia + Southern China
      - Malfunction in 1 gene
        
        \(\alpha^+\)-thalassaemia
        
        Common in Indonesia, Middle East, India + Mediterranean
      - Fewer \(\alpha\)-globin causes excess in
        
        \(\beta\) chains in adults
        
        \(\gamma\) chains in newborns
      - Types + genotypes
        
        Silent carrier
        
        Deletion of single \(\alpha\) gene
        
        No effect
        
        2 gene mutations
        
        \(\alpha\)- minor/carrier
        
        Thallasaemia trait
        
        Mild hypochromic/microcytic
        
        \(\alpha\)+ homozygote - 2 same \(\alpha\) chains intact i.e. 2 x \(\alpha\)1 or 2 x \(\alpha\)2
        
        \(\alpha\)+ heterozygote (\(\alpha^0\)) - different \(\alpha\) chains intact i.e. 1 x \(\alpha\)1 + 1 x \(\alpha\)2
        
        3 gene mutations
        
        Serious disease
        
        HbH disease
        
        Jaundice
        
        Leg ulcers
        
        Folic acid deficiency
        
        Severe anaemia
        
        Hepatosplenomegaly
        
        Hypochromasia
        
        Microcytosis
        
        Fragmented red cells
        
        4 gene mutations
        
        Hb Bart's/hydrops fetalis syndrome
        
        Death in utero
    - - Chromosome 6
        
        2 \(\beta\)-globin genes
      - 200 different mutations can give rise to beta thllasaemia
      - Mutations result in reduction or abolition of \(\beta\)-globin genes
      - Point mutations
        
        Inefficient transcription
        
        Defective processing of mRNA
        
        Defective splicing
        
        Improper protein translation
        
        Post-translational stability
      - Types + genotypes
        
        \(\beta^0\) - globin chains absent
        
        \(\beta^+\) globin chains partially present
        
        Thallasaemia major
        
        \(\beta^0\beta^0\)
        
        Severe anaemia
        
        Bone marrow hypertrophy
        
        Skeletal changes
        
        Hepatosplenomegaly
        
        Thalassaemia intermedia
        
        \(\beta^0\beta^+/\beta^+\beta^+\)
        
        Normal life
        
        May require tranfusions
        
        Thalassaemia minor
        
        Mild anaemia
        
        Low MCV <80fL
        
        Raised Hb A2 and/or HbF
  - - - Glutamate to valine
        
        Valine very hydrophobic
    - - Normal RBCs
    - - Sickle cells form
    - - Prevent microcirculation
      - Shortened cell lifetime
      - Qualitative effect on globin
        
        Can't bind oxygen
      - Polymerisation of HbS
      - Numerous rounds of oxygenation and deoxygenation
        
        Irreversible sickle
      - Increased stickiness
        
        Clog circuatory system
        
        Increased thrombosis
        
        Attach to endothelial wall
    - - Inherited
    - - Bone marrow transplant
      - Alleviate symptoms of crisis
      - Prevent crisis
    - - Painful vaso-occlusive crisis
      - Tissue hypoxia
      - Blood vessel blockage
    - - Epidemiology of HbS
      - Sickle cell gives resistance to malaria