Aneamia Flashcards
what is the normal range for bilirubin?
below 17 umol/L
what does high unconjugated bilirubin suggest?
prehepatic jaundice e.g. haemolysis
cause of spherocytes?
hereditary spherocytosis
Disruption of vertical linkages in membrane of erythrocyte usually ankyrin and spectrin
What is reticulocytisis a sign of
haemolysis → underdeveloped cells in circulation means RBC turnover is happening too quickly
what is the difference between haemolysis and haemolytic anaemia?
haemolysis is RBC breakdown, haemolytic anaemia = lifespan reduced to the extent that Hb is low
treatment options for haemolytic anaemia?
folic acid → supports increased requirement for erythropoiesis
splenectomy if severe → increase RBC life span
one consequence of haemolysis?
Gallstone formation due to increased breakdown of haemoglobin to bilirubin causing obstructive jaundice
Liver can still conjugate bilirubin but it’s not passing from the bile ducts and gallbladder into the duodenum
what does it mean for bilirubin to be conjugated vs unconjugated
water soluble, not as attached to albumin
Unconjugated is insoluble in blood and attached to albumin
How does conjugated vs unconjugated bilirubin affect the body and how are they excreted
unconjugated toxic to tissues and organs, can’t be excreted in urine,accumulates in prehepatic jaundice
conjugated pretty non-toxic, excreted in urine (dark),accumulates in post hepatic jaundice
what is autoimmune haemolytic anaemia?
haemolysis mediated by autoantibodies against own RBCs
How is autoimmune haemolytic anaemia diagnosed
DAT (direct antiglobulin test) checking for autoantibodies
AIHA aetiology
idiopathic, related to other immune disorders e.g. SLE, underlying lymphoid cancers
Signs of Haemolysis
raised LDH, unconjugated hyperbilirubinaemia, low haptoglobins
Bone marrow responds via reticulocytosis
Defect in rbc means inherited and defect in rbc environment means acquired
- what are irregularly contracted cells and Heinz bodies a sign of?
Oxidant damage to rbc which indicates G6PD deficiency
What does G6PD do
important in HMP shunt → coupled to glutathione metabolism → protects from oxidant damage
sources of oxidants?
generated in the blood stream e.g. during infection
exogenous e.g. fava beans, drugs like naphthalene
what is intravascular vs extravascular haemolysis?
intravascular = acute damage
extravascular = removal by spleen
what does ferritin do?
Iron stores in liver
Transferrin
Allows iron to be transported in blood
what does low transferrin indicate?
Iron overload (as becomes saturated with iron)
signs of iron deficiency anaemia?
fatigue, koilonychia, angular stomatitis, glossitis, microcytic anaemia
Causes of iron deficiency anaemia
bleeding e.g. GI (would see dysphagia, dyspepsia,abd pain)or menstrual, diet, hookworm, malabsorption e.g. coeliac disease or h. pylori gastritis,change in bowel habit (haematemesis,rectal bleeding,melaena),NSAIDS
when might increased iron be required?
Pregnancy
Infancy
what measurement abnormality does RBC hypochromia indicate?
Low MCHC
treatment of iron deficiency?
iron replacement e.g. ferrous sulphate tablets
what causes increased iron absorption from the gut and increased release from storage?
low hepcidin
Normal Hb range
133-167
does a normal ferritin always exclude iron deficiency?
no → can be normal if both iron deficiency and anaemia of chronic disease
what is the difference between macrocytic and megaloblastic anaemia?
megaloblastic is a type of macrocytic anaemia
Megaloblasts are large with nucleocytoplasmic dissociation
what is megaloblastic anaemia commonly caused by?
Folate or B12 deficiency
Can occur secondary to agents or mutations that impair dna synthesis eg
Drugs azathioprine cytotoxic chemo
Folate antagonist eg methotrexate
BM cancers eg myelodysplatic syndrome
What does b12 and folate do
B12: DNA synth, integrity of nervous system
folate: DNA synth, homocysteine metabolism
colour status of normocytic, macrocytic and microcytic anaemia RBCs?
normocytic and macrocytic = normochromic
microcytic = hypochromic
what does microcytosis result from?
Reduced synthesis of HB
haem and globin issue examples respectively?
haem: iron deficiency, anaemia of chronic disease
globin: thalassaemia
causes of normocytic anaemia?
recent blood loss
bone marrow failure e.g. chemo, leukaemia → RBC production failure
pooling of RBCs in spleen
Environmental factors which can damage rbc
Environmental factors affected rbc
Non immune-microangiopathic,haemolytic uraemic syndrome,malaria,snake venom,drugs
Immune mediated-autoimmune,allo immune (post blood transfusion)
Ghost cells
Are cells that are pale due to loss of haemoglobin content
Can be due to Intravascular haemolysis which include conditions such as G6PD deficiency,autoimmune haemolytic anaemia and toxins such as snake venom
Haemolytic anaemia inherited vs acquired causes
Inherited
Abrnkmak rbc membrane eg Heridetary spherociytosis
Abnormal Hb eg sickle cell anaemia
Defect in glycolytic pathways eg Pyruvate kinase deficiency
Deficiency in G6PD
Acquired
Damage to rbc membrane via AIHA or snake bite
Damage to whole rbc eg MAHA (microangiopathic haemolytic anaemia)
Oxidant exposure damage to rbc and Hb eg dapsone or primaquine
Anaemia of chronic disease
Hb low,MCV low or normal,ferritin high,,serum iron low,transferrin normal/low
Hepcidin made by liver when iron stores high and also made when inflammation has occurred eg in infection such as TB/HIV,rheumatoid arthritis,malignancy,autoimmune disease
Treatment needs to target underlying cause
Why does b12/folate deficiency occur
B12:due to diet eg veganism,gastric eg gastrectomy or autoimmune (pernicious anaemia -anti gastric parietal cell and intrinsic factor antibodies),terminal ileum eg chrons disease or ileal resection. Can treat via supplements for diet but other two require hydroxocobalamin injections
Folic acid-diet (poverty/alcholism),malabsorption due to coeliac disease or jejunal resection,increased demand due to pregnancy,lactation or increased cell turnover (Haemolysis). For all give supplements
