MACROCYTIC ANAEMIA Flashcards
Define macrocytic anaemia.
anaemia in which hthe red cells have a LARGER than normal volume
How to measure MCV?
- modern analyser use LIGHT scatter properties of the red cells
What to compare the size of the red cell on blood film?
- compare to the nucleus of a small, mature lymphocyte
- —should be the SAME size
precursor Red cell with nucleus.
- erythroblasts/normoblasts
- DO NOT circulate in the periphery
Loss of nucleus in red cell with a small amount of RNA; circulates in the periphery.
- RETICULOCYTE (why they appear bluer)
What changes occur to result in a mature red cell.
- primitive erythroblasts - will start to accumulate Hb> cell will REDUCE in size and INCR. in nuclear maturation
- —–when Hb conc. reaches a critical stage; cell will stop dividing and nucleus is lost
Which precursor red cell goes through anucleation and why?
- Late Normoblast
- —-d.t peak accumulation of Hb
How does a megaloblastic cell appear?
an ABNORMALLY LARGE nucleated red cell precursor with an IMMATURE nucleus
- open chromatin
WHAT IS KEY about MEGALOBLASTIC ANAEMIA?
- the LACK of red cells d.t PREDOMINANT problems with DNA maturation and synthesis
- —-BUT NORMAL HB and RNA synthesis
What occurs with cell division in erythroblasts; in megaloblastic anemia?
- due to abnormal nucleus IN THE PROERYTHROBLAST
- — but in maturing erythroblasts; division is REDUCED and APOPTOSIS increases
WHy are B12 and folate important?
- essential for biochemical reactions
- —involved in DNA modification and GENE activity(NERVOUS SYSTEM impact); as well as DNA sysnthesis and nuclear maturation (blood cell defect)
Where is
- rich in meat, eggs
Cobalamin
Where is B12 absorbed?
in the DISTAL GUT
—-those who had a distal bowel resection; may face B12 deficiency
Causes of vit. B12 def. in the stomach
- atrophic gastritis
- Pernicious anemia
- gastrectomy /bypass
- PPPIs and H2-R anatagonists
WHat occurs with pernicious anemia>
- AUTOIMMUNE condition of destrc. of GASTRIC parietal cells
- —>IF deficiency with B12 malabsorption and deficiency
What may be the co-morbidites for PA?
- a.w atrophic gastritis
- personal or family hx of other autoimmune conditions (Hypothyroidism/ vitiligo/ addison’s disease
WHen may folate deficiency present itself?
- 4 months
- —-LOW stores in the body; store can easily be diminished
Where is folate absorbed?
- in the DUODENUM and JEJUNUM
What are the causes of FOLATE defi.?
- anticonvulsants drugs
- HEMOLYSIS
- EXOFOLIATING DERMATITIS
- malignancy
- pregnancy
- alcoholics and alcoholics
—–crohn’s and celiac disease
What are the clinical fts of b12/ folate def.?
Symptoms/signs of anaemia
weight loss, diarrhoea, infertility
Sore tongue, jaundice
Developmental problems
Which def. may present with neurological problems?
- Vit. B12 (may APPEAR NORMAL in labs)
posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations
How to dx with lab findings; B12-Folate def.?
- Macrocytic anemia (RED cell count is LOW)
- Pancytopenia (in some)
—-blood films show MACROOVALOCYTES and hypersegmented neutrophils
What are other LAB ivx?
- measure B12 and folate in the serum (not reliable)
- check for AUTO-ABs (anti-IF/ anti gastric-parietal cell)
- bone marrow exmam. and schilling’s test (no longer done)
How to treat megaloblastic anaemia?
- FOLIC acid oral tablets
- —-Vit. B12 (Hydroxycobalamin) INJECTIONS for life in pernicious anaemia
Causes of non-megaloblstic macrocytosis (NOT a.w with anaemia) ?
- alcohol
- liver disease and hypothyroidism
Causes of non-megaloblstic macrocytosis - a.w with anaemia) ?
- MARROW failure (MYELOMA/ aplastic anaemia/ myelodysplasia)
Why may reticulocytosis cause FALSE incr. in MCV? -
- Reticulocytosis reticulocytes are BIGGER and mistaken as a red cell
- –red cell mcv may be normal but because reticulocytes, avg MCV is thrown off - Cold AGGLUTININS
Can jaundice be seen with pernicious anaemia
- YES d.t intramedulalry hemolysis —red cells DIE premature alt in the marrow; Hb and LDH are release from dead red cells
- —Hb converts to bilirubin
How does the macrocyte come about in Megaloblastic anaemia?
What occurs as a result of the shortcomings?
- cytoplasmic developm. and Hb accumulation is NORMAL
- like in normoblasts, ince optimum Hb is reached; nucleus is extruded from the cell —-leaving behind a BIGGER-THAN-NORMAL cell
——FEWER macrocytes AND hence ANAEMIA
Why does large cell size result in MEGALOBLASTIC anaemia?
- d.t FAILURE of the cell to get SMALLER; not due to an increase in size
What causes megaloblastic anaemia?
B12 and FOLATE deficiency
—others: DRUGS/ rare inherited abnormalities
Describe the manner by which Vitamin B12 is absorbed.
- d.t acidic pH in the stomach, B12 binds to Haptocorin and empties into the gut with IF (unbound)
- IN the DUODENUM and JUJENUM, pancreatic peptidases will cleave the complex and release B12
- B12-IF complex will then bind to the CUBULIN receptors found on the brush border of the gut mucosa
What is the source of Folate?
- LIVER
- LEAFY veg
- foritfied cereba;s
How long till B12 stores deplete and where is ILEUM absorbed?
- 2-4 YEARS
- ileum
What is meant by spurious macrocytosis?
- volume of mature red cell is NORMAL
- MCV is MEASURED as high
Apart from reticulocytosis, what is the other cause of spurios macrocytosis?
- cold AGGLUTININS
(causes clumping of the red cells at room T*)
—-clumped groups are read as one red cell
——-read as having an MCV of 150 !
