intro to anaemia Flashcards
define anaemia
a haemoglobin conc lower than normal range
is anaemia itself a diagnosis
no but a manifestation of an underlying disease
what are the main symptoms of anaemia
- shortness of breath
- palpitations
- headaches
- claudication (muscle pain due lack of O2)
- angina
- weakness and lethargy
- confusion
what are the main signs of anaemia
- pallor
- tachycardia
- systolic flow murmur
- tachypnoea
- hypotension
what are specific clinical signs associated with the cause of anaemia
IRON DEF:
- koilonychia (spoon nails)
- angular stomatitis (inflam corners mouth)
VIT B12 DEF:
-glossitis (imflam tongue)
THALASSAEMIA:
- abnormal facial development
what are the three causes of anaemia in bone marrow
- reduced or dysfunctional erythopoiesis
- abnormal haem synthesis
- abnormal globin chain synthesis
what are the four causes of anaemia in peripheral blood cells
abnormal structure
mechanical damage
abnormal metabolism
excessive bleeding
what are the causes for anaemia in removal or RBC
increased removal by reticuloendothelial system
how can anaemia develop from reduced erythropoiesis
- lack of response in haemostatic loop so in chronic kidney disease kidney stops making erythropoietin
- marrow does not respond to EPO
- marrow infiltrated by cancer or fibrous tissue so less haemopoietic cells
- iron not made available for RBC
- myelodysplastic syndrome abnormal stem cells in marrow
how can anaemia develop from defects in Hb synthesis
- mutations in genes for globin –> thalassemia
- defects in haem synthesis –> sideroblastic anaemia
- insufficient iron in diet to make haem
how can anaemia develop from abnormal structure (inherited)
- mutations in genes coding for proteins involved in interactions between plasma mem and cytoskeleton
- less flexible and more easily damaged
- break up in circulation and removed more quickly by RES
how can anaemia develop from mechanical damaged (acquired)
- damaged caused by mechanical valves
-cells snagging on fibrin strands in small vessels causing clots - heart damage from severe burns
osmotic damage (drowning)
what are the fragments called when RBC go under mechanical damage
schistocytes
why might anaemia develop from defects in cell metabolism
- G6PDH deficiency:
more ox stress to RBC –> Heinz bodies and cleared by RES - pyruvate kinase deficiency:
RBC no mito so deficient in ATP without pyruvate kinase so undergo haemolysis
why might anaemia develop from excessive bleeding
- acute blood loss (injury, surgery, childbirth, ruptured vessel)
- chronic bleeding (menstruation, nosebleeds, haemorrhoids, gastro bleeding in stool, kidney or bladder tumours)
- chronic NSAID usage (aspirin, ibuprofen, naproxen,)
(induce GI bleeding by inhibiting cyclooxygenase activity = toxic)
why might anaemia develop from reticuloendothelial system
- in haemolytic anaemias RBCs destroyed more quickly as abnormal or damaged
- damage can occur in blood vessels (intravascular) or in RES (extravascular)
- autoimmune anaemia causes antibodies to bind to RBC mem so recognised by spleen
what two factors can help determine cause of anaemia
RBC size
presence or absence or reticulocytes
what are reticulocytes
immature RBC
- no nucleus and eliminate remaining mitochondria
- take one day to mature
what are the causes of macrocytic anaemia
- Vit B12 def
- folate def
- myelodysplasia
- liver diease
- alcohol toxicity
what are the three types of macrocytic anaemias
- megaloblastic
- macronormoblastic
- stress
what is macrocytic anaemia
where average size of RBC is greater than normal so higher MCV
what is megaloblastic anaemia
- interfers with DNA synth during erythropoiesis during development of nucleus so nuceluar, cytoplasmic dssynchrony as cell division delayed but cell continues to grow = larger cells = megaloblasts
what are examples of causes of macrocytic anaemia
- Vit B12/ folate def
- drugs that interfer with DNA synth
- erythroid leukaemias
what is macronormoblastic anaemias
larger erythroblasts are larger than normal and give rise to larger than red cells
what are examples of causes of macronormoblastic anaemia
- liver disease
- alcohol toxicity
- myelodysplastic
what is stress erythropoiesis
conditions associated with a high reticulocyte count (reticulocytes are larger than RBCs)
- high level of erythropoeitin leads to expanded and accelerated erthyropoeisis
what are examples of causes of stress erythropoiesis
- recovery from blood loss due to haemorrhage
- recovery from haemolytic anaemia
what is folate
synthetic form of folic acid
where is folate synthesised
bacteria and plants
where is folate present
variety if animal and vegetable food sources mainly leafy greens
where is folate absorbed
mainly duodenum and jejunum
what is folate converted to by intestinal cells
tetrahydrofolate
where is folate stored
liver
what is folate important for
recipient reactions include synth of nucleotides for DNA and RNA synthesis
what are the causes of folate deficiency
- poor diet
- increased requirement (preg, increased erythropoiesis, skin disease)
- diseases of duodenum and jejunum (coeliac, crohns)
- alcoholism
- liver disease and heart failure
what symptoms of folate def
- related to anemia
- reduced tase
- diarrhoea
- numb feet and hands
- muscle weakness
- depression
when is folate especially important to take
before contraception and during first 12 weeks of pregnancy
why is folate important for pregnancy
prevents majority of neural tube defects
what is vitamin B12 required for
- cofactor for DNA synthesis (due to role in folate metabolism
- required for normal erythropoiesis
- normal function and development of CNS
what is vit B12 produced by
bacteria but largerly obtained from animal origin from commensal bacteria in animal stuff
how is B12 released from food
proteolysis in stoach
what does B12 bind to after it is released from food in stomach
haptocorrin
what is the haptocorrin B12 complex digested by
pancreatic proteases in small intestine
what does B12 bind to after the haptocorrin complex is digested
intrinsic factor produced by gastric parietal
what does the intrinsic factor B12 complex bind to
cubam receptor which mediates uptake of complex by receptor mediated endocytosis into enterocytes
after lysosomal release in enterocytes ho does B12 exit the basolateral mem
through MDR1
what does B12 bind to after exiting through MDR1
transcobalamin in blood
how long can the store of B12 last for
3-6 years
what are the causes of B12 def
- diet (mainly vegans)
- lack of intrinsic factor (pernicious anaemia)
- diseases of ileum
- lack of transcobalamin
- chemical inactivation
- parasite
- some drugs can chelate intrinsic factor
what is pernicious anaemia
decreased or absent intrinsic factor causes progressive exhaustion of B12
- autoimmune disease
what are the sympoms of vit B12 def
- anaemia symptoms
- glossitis and mouth ulcers
- diarrhoea
- paraesthesia
- disturbed vision
- irritable
what is subacute combined degeneration of the cord
degeneration of posterior and lateral columns of spinal cord
what is subacute combined degeneration of the cord caused by
B12/ folate def
- 12 can cause demyelination
- folate de can cause neural defects in preg
what are the symptoms of subacute combined degeneration of the cord
onset weakness , numb, arms, legs and trunk
changes in mental state
how are B12 and folate linked
Vit B 12 is required to convert methyltetrahydrofolate (stable) tetrahydrofolate
how does a def in B12 affect folate cycle
lack of B12 will trap folate in stable methyltetrahydrofolate form preventing conversion to tetrahydrofolate to be used in other reactions such as synthesis of thymidine for DNA synthesis
why do B12 and folate def cause megaloblastic anaemia
- lead to thymidine def
- absence of thymidine uracil is added to DNA
- DNA repair enzyes detect and repair by excision
- asynchronous maturation between nucleus and cytoplasm (nuc does not mature with ope chromatin)
how to treat folate def
oral folic acid
how to treat vit B12 def
- pernicious anaemia : hydroxycobalamine intramuscularly NOT ORALLY as will not absorb
- other causes : oral cyanocobalamine
