Anaemia Flashcards
Define anaemia.
- a haemoglobin concentration lower than normal range.
- not a diagnosis on its own but a manifestation of an underlying disease and cause important to establish.
name a few signs and symptoms of anaemia.
- signs of insufficient O2 delivery to tissues.
- symptoms : SOB, palpitations, headache, lethargic.
- signs : Pallor, tachycardia, hypotension, systolic flow murmur, tachypnoea ( high RR).
what are some specific sign associated with anaemia, that may lead you to a diagnosis.
- Koilonychia ( spoon shaped nails) : iron deficiency.
- Angular stomatitis ( mouth corners inflamed) : iron deficiency.
- Glossitis ( inflamed, depapilation of tongue) : Vit B12 deficiency.
- Abnormal facial bones : thalassaemia.
why might anaemia develop?
break it down to RBC in BM, vessels, removal by spleen.
- BM : reduced erythropoiesis, abnormal haem, abnormal globin chains.
- Vessels : abnormal RBC, mechanical damage, abnormal metabolism.
- Spleen : increased removal by reticuloendothelial.
what might cause reduced or dysfunctional erythropoeisis?
- lack of production of EPO by kidney, in CKD.
- marrow unable to respond to EPO, after chemo/infection.
- marrow infiltrated by cancer cells or fibrous tissue.
- chronic diseases like rheumatoid arthritis where iron is not made available for marrow.
- myelodysplatic syndromes where abnormal clones of stem cells reduce capacity to make RBC + WBC.
why might defects in haemoglobin synthesis cause anaemia?
- SIDEROBLASTIC ANAEMIA : defects in haem synthesis pathway.
- insufficient iron in diet : iron deficiency anaemia.
- anaemia in chronic disease as functional iron deficient.
- mutations in globin chains in HB ( alpha/beta thalassaemia, sickle cell disease ).
how might abnormal structure and mechanical damage to RBC lead to haemolytic anaemia?
*inherited
- mutation in gene coding for plasma membrane cytoskeleton interactions.
- less flexible and more easily damaged and removed.
*acquired
- shear stress through defective heart valves.
- cell snagging on fibrin strands in small vessels with clots.
- heat burns or osmotic damage.
what defects in RBC metabolism can cause anaemia?
- G6PDH deficiency : cross-linking of HB and Heinz bodies, removed by spleen.
- Pyruvate kinase deficiency so glycolysis affected and RBC deficient in ATP and undergo haemolysis.
how might excessive bleeding cause anaemia?
- acute blood loss, like injury.
- chronic blood loss : heavy menstrual bleeding, haemorrhoids, GI bleeds, kidney or bladder tumours.
*treated with NSAID anti-inflammatory drugs.
*IRON LOST FROM BODY NOT RECYCLED!
how might the reticuloendothelial system play a part in anaemia development?
- damage in vessels, autoimmune haemolytic anaemias cause abnormal RBC so destroyed.
- by spleen leading to splenomegaly as working harder. NEVER NORMAL TO PALPATE SPLEEN below costal margin.
how might myelofibrosis cause anaemia?
- due to proliferative haemotopoietic stem cells.
- little space for haemotopoeisis.
- progenitor cells spill out of marrow into liver and spleen leading to extra-medullary haemopoeisis, so enlarged.
how might thalassemia cause anaemias?
- decreased or absent alpha or beta globin chain production.
- imbalance in composition of A2B2 so defective microcytic hypochromic RBC.
- severity depends on type.
what are reticulocytes and why are they important?
- immature RBC just released to blood, no nucleus and eliminate remaining mitochondria.
- 1% of all RBC, matures in 1 day.
- shows if marrow is capable of responding to conditions like anaemia, you’d expect high count to replenish.
what would microcytic/ macrocytic/ normocytic RBC indicate?
- microcytic : thalassaemia, chronic disease anaemia, iron deficiency, lead poisoning.
- macrocytic : vit B12, folate, liver disease.
- normocytic : BM failure.
what are the types of macrocytic anaemias?
- megaloblastic : DNA synthesis interfered and nucleus development retarded cell division delayed so large.
eg: Vit B12/ folate deficiency - macronormoblastic erythropoiesis : cytoplasm retained and erythroblasts larger than normal.
eg : liver disease, alcohol toxicity. - stress erythropoiesis : high reticulocytes and larger, high level of erythropoetin so expanded.
eg: recovery from haemorrhage, haemolytic anaemia.
why is folate important?
- abundant in green leafy veg, absorbed by duodenum and jejunum.
- converted to tetrahydrofolate and taken up by liver as stores.
*carbons for other reactions like nucleotide base synthesis for DNA and RNA.
*FOLIC ACID IN PREGNANCY to prevent neural tube defects.
what causes folate deficiency and what are the symptoms?
- causes : poor diet, increased requirement like pregnancy or anaemias, disease of absorption sites, drugs that inhibit converting to store, alcoholism, liver disease.
- symptoms : anaemia related, diarrhoea, muscle weakness.
why is vitamin B12 essential?
PRODUCED BY BACTERIA.
- essential co-factor in DNA synthesis.
- required for erythropoiesis.
- essential for normal CNS development.
*largely obtained by animal origin as produced by commensal bacteria.
how is Vit B12 absorped?
- binds to haptocorrin in saliva and is digested by pancreatic proteases.
- released B12 binds to intrinsic factor which binds to cubam receptor which is up-taken into enterocytes,
- then eventually bound to transcobalamin transported around blood stream and stored in liver.
*stores enough for 3-6 years.
what causes vitamin B12 deficiency and what are the symptoms?
name some severe complications around it?
- dietary deficiencies, lack of intrinsic factors, ileum affected, chemical inactivation of B12, parasitic infection.
- symptoms : related to anaemia, diarrhoea, parasthesia, irritability, disturbed vision.
- affects nervous system, focal demyelination, reversible peripheral neuropathy, degeneration of cord in posterior and lateral columns of spinal cord.
how does B12 and folate deficiency lead to megaloblastic anaemia?
- ultimately a thymidine deficiency, uracil instead, DNA repair enzymes detect and repair.
- results in asynchronous maturation between nuclei and cytoplasm (nucleus not fully mature and cytoplasm rate normal )
how do you treat Vit B12 and folate deficiencies?
- folate : oral folic acid.
- B12 : hydroxycobalamine intramuscular in perinicious anaemia, other causes : oral cyanocobalamine.
what could cause microcytic anaemia?
( smaller than normal, hypochromic)
TAILS
- reduced haem synthesis : Iron deficiency, Lead poisoning inhibiting enzymes involved in haem synthesis, Anaemia of chronic disease, Sideblastic anaemia inherited.
- reduced globin chain synthesis : in alpha/ beta Thalessaemia.
what is anaemia of chronic disease?
- inflammatory conditions causing release of cytokines which increases Hepcidin production, inhibits EPO.
- this decreases iron release, RBC making and iron absorption at gut.
