Anaemia Flashcards
what is anaemia?
reduction in amount Hb in given volume of bood
what are the mechanisms of anaemia?
- Reduced production or red cells/ haemoglobin in bone marrow
- Reduced survival of red cells in the circulation- haemolysis
- Loss of blood from the body (haemorrhage)
- Pooling of red cells in a very large spleen
how is iron controlled?
- iron controlled by absorption from diet
- there is no mechanism by which iron is excreted
- excess iron is toxic to heart and liver
how is iron absorbed?
regulated by hepcidin according to body cells
how is iron stored?
stored as ferritin in liver
ferritin= protein shell forms around Fe to store
how is iron transported?
transported as Transferrin
in blood forms stable complex to transport
required as Fe is toxic and unstable
what are the causes of reduced production and reduced survival of RBCs?
- Hereditary spherocytosis
- Autoimmune haemolytic anaemia
- G6PD deficiency
- Iron deficiency anaemia
- Anaemia of chronic disease
- Megaloblastic anaemia (due to Vit B12 deficiency)
what are the classifications of red cell based on size?
microcyte
normocyte
macrocyte
what is the haemoglobin status of each cell size?
microcyte- hypochromic
normocyte & macrocyte- normochromic
what are the common causes of microcyte?
- defect in haem synthesis
- Iron deficiency anaemic
- Anaemia of chronic disease
- Defect in globin synthesis (thalassaemia)
- Defect in alpha chain synthesis (alpha thalassaemia)
- Defect in beta chain synthesis (beta thalassaemia)
what are the mechanisms and examples of a normocyte?
- recent blood loss (increase blood plasma-> negative feedback -> reduced Hb conc)
- GI haemorrhage, trauma
- failure of production of RBC
- Early stages iron deficiency
- Bone marrow failure or suppression (chemo)
- Bone marrow infiltration (leukaemia)
- pooling of RBC in spleen
- Hypersplenism (liver cirrhosis)
- Splenic sequestration in sickle cell anaemia
what are the causes of macrocyte?
- Liver disease and ethanol toxicity
- Reticulocytes released due to loss of RBCs
- Major blood loss with adequate iron stores
- Haemoloytic anaemia
- Megaloblastic anaemia due to:
- Drug interference with DNA synthesis
- Lack vit B12/ folic acid
what does erythrocyte function depend on?
- Integrity of membrane
- Hereditary spherocytosis, autoimmune haemolytic anaemia
- Haemoglobin structure and function
- Sickle cell anaemia
- Cellular metabolism
- G6PD deficiency
- Any defect in these results in shortened erythrocyte survival (haemolysis)
what is the cause of hereditary spherocytosis?
- Inherited RBC membrane defect causing destabilisation of cellular membrane resulting in chronic, premature extravascular haemolysis
- Genetic component
what is the presentation of hereditary spherocytosis?
- jaundice- high bilirubin
- anaemic signs and symptoms (pallor, fatigue, activity intolerance)
- splenomegaly
- abnormal blood film, count and LFTs
what is the blood film of hereditary spherocytosis?
- Bilirubin mainly unconjugated and raised
- Decreased haemoglobin
- Poikilocytosis (variation in shape)- Spherocytosis
- Round cells without central pallor
- Polychromatic macrocytes and increased reticulocytes
- Reticulocytes= naïve red blood cells (larger than mature RBCs)
- Increased to try and compensate for destruction in red blood cells
- Reticulocytes= naïve red blood cells (larger than mature RBCs)
where is bilirubin conjugated?
liver
what are the causes of increased unconjugated bilirubin?
- Increased production
- Produced by breakdown of RBCs
- Impaired conjugation
- Impaired hepatic uptake of bilirubin
what are the complications of hereditary spherocytosis?
- Transient aplastic crisis caused by infections
- Megaloblastic anaemia replated to folate deficiency
- Gallstones - Due to increased breakdown of haemoglobin to bilirubin
what is the presentation of gallstones?
- Upper right abdominal pain
- Jaundice
- Raised conjugated bilirubin
- Caused by stone obstructing common bile duct (obstructive jaundice)
- Liver able to conjugate bilirubin but it is not passing from bile ducts and gall bladder into duodenum
what is the treatment for hereditary spherocytosis?
- Folic acid (because of increased need)
- Splenectomy (if severe) to increase the red cell life span
what is haemolytic anaemia?
- anaemia caused by immune destruction of RBCs by autoantibodies against antigens on RBCs surface
what is haemolysis?
destruction of RBCs
what is the lab evidence of haemolysis?
- LDH raised
- Unconjugated hyperbilirubinemia
- Reduce haptoglobins
what are the acquired causes of haemolytic anaemia?
(environmental factors which can damage RBCs)
- Non- immune
- Drugs
- Snake venom
- Malaria
- Haemolytic uraemic syndrome
- Microangiopathic
- Immune mediated
- Auto-immune
- Test by measuring DAT (direct antiglobulin test)
- Antibodies bind to antigen on erythrocyte membrane in a patient with autoantibodies
- Test by measuring DAT (direct antiglobulin test)
- Allo immune (post blood transfusion)
- Auto-immune
what are the inherited causes of haemolytic anaemia?
- Abnormal red cell membrane (hereditary spherocytosis)
- Abnormal Hb (sickle cell anaemia)
- Defect in glycolytic pathway (pyruvate kinase deficiency)
- Defect in enzymes of pentose shunt (G6PD deficiency)
what are the causes of autoimmune haemolytic anaemia?
- Idiopathic
- Associated with disorders of immune system
- Systemic autoimmune disease (SLE)
- Underlying lymphoid cancers (lymphoma)
what is G6PD?
- G6PD is an enzyme in pentose shunt
- Pentose shunt= protects from oxidant damage
- Glycolytic pathway provides energy for the cell
what does G6PD deficiency cause?
premature haemolysis
- Oxidative stress as inadequate G6PD, GSH (reduced glutathione)
- Build up free radicals and peroxides causing oxidative damage to trigger haemolysis
- Accelerated removal of damaged RBCs
what is in the blood film of G6PD deficiency?
- Irregularly contracted cells in blood film and Heinz bodies showing oxidant damage
- Heinz bodies= precipitated oxidised haemoglobin
- Ghost cell= intravascular haemolysis
how do you confirm G6PD deficiency?
blood assay
what needs to be avoided in G6PD deficiency?
oxidant drugs
broad beans
naphthalene
what can cause haemolysis?
infection
what are the causes of iron deficiency anaemia?
- Decreased intake iron
- Eating disorders
- Dietary restrictions
- Decreased absorption
- Celiac disease
- Surgery
- Excessive dietary calcium
- Increased need
- Pregnancy
- Growth
- Increase loss (most common)
- Blood loss
- Trauma/ haemorrhage
- Menstrual
- Bleeds/lesions
- GI (often occult)
- Blood loss
what are the signs and symptoms of IDA?
- Fatigue
- Pallor
- Compensatory mechanisms
- Palpitations
- Increased pulse
- Increase CO, tachypnea
- Selective shunting of blood to vital organs
what are the lab results of IDA?
- Low RBC
- Low/normal reticulocytes
- Low haemoglobin, hematocrit
- Hypochromic-microcytic erythrocytes
- Decreased serum iron
- Decreased transferring saturation (major iron transport protein)
- Increased total iron binding capacity
- eliptocytes
what are the different types of poikilocytosis?
what is the management of iron deficiency anaemia?
- PO iron supplements (ferrous sulfate)
- Parenteral iron
- Severe, persistent anaemia
- Intolerance of PO iron
- Nonadherence to PO supplement/ dietary changes
- Increase dietary iron
- Heme iron (meat) absorbed better than non-heme iron (Nuts, legumes, eggs)
- Vit C increased absorption, calcium decreases absorption
- Blood transfusion
what is anaemia of chronic disease?
- Anaemia in patients wo are un well
- No bleeding, no reduced survival, no marrow infiltration, no iron/B12/ folate deficiency
what are the common causes of ACD?
- Infections such as TB and HIV
- Rheumatoid arthritis and other autoimmune diseases
- Malignancy
- Treating the anaemia requires treating the underlying cause
what is the pathophysiology of ACD?
- Pro-inflammatory cytokines (IL-T, TNF-alpha, IL-6) released due to systemic inflammation
- Cause increased hepcidin secretion by liver
- Decreases iron absorption by GI tract
- Decreases iron sequestration in reticuloendothelial system (transport)
- Decreases iron available for erythropoiesis
- Causes decreased secretion of erythropoietin
- Causes direct inhibition of erythropoiesis
- Decreases erythrocyte lifespan
what is megaloblastic anaemia?
- Anaemia associated with megaloblastic morphological changes in the bone marrow due to asynchronous nucleocytoplasmic maturation
- Delay in maturation of nucleus while cytoplasm matures/cell grows
what is seen in the bone marrow of megaloblastic anaemia?
megaloblastic features
- Megaloblasts= large with nucleocytoplasmic dissociation
- Impaired DNA synthesis, nuclear maturation and cell division
- Adequate cytoplasmic maturation and cell growth
how is megaloblastic anaemia diagnosed?
bone marrow examination
what change in RBC is megaloblastic anaemia associated with?
macrocytic RBC
very high MCV
what are the causes of megaloblastic anaemia?
- Vitamin B12 and folate (most common)
- Required for DNA synthesis
- Absence leads to severe anaemia which can be fatal
- Secondary to agents or mutations that impair DNA synthesis
- Drugs (azathioprine cytotoxic chemotherapy)
- Folate antagonists (methotrexate)
- BM cancers (myelodysplastic syndrome)
what are the causes of vit B12 deficiency and treatment?
what is B12 required for?
- Vit B12 is required for DNA synthesis and integrity of the nervous system
- Converts methyl-THF to THF using homocysteine to methionine
what is folic acid required for?
- folic acid is required for DNA synthesis and homocysteine metabolism
- methyl THF convered by Vit B12 is produced from dietary folate
what are the causes of folic acid deficiency and treatments?
what neurological disorder does vit B12 deficiency cause?
- dementia and SACD (sub-acute combined degeneration) or spinal cord
what neurological disorder does lack folic acid cause?
developmental neural tube defects
what are the blood parameters for iron deficiency, ACD, thalassaemia trait and ACD + ID combined?
- Hb
- MCV
- RBC
- Serrum Fe
- Ferritin
- Transferritin
- Transferritin saturation
what is the ESR for ID and ACD?
what is the Hb electrophoresis for ID and Thalassaemia?
