IOD Microcytic and Macrocytic Anaemia Flashcards
History of iron deficiency anaemia?
signs-tiredness, SOB NSAIDs, steroids, anticoagulants diet-vegan or veg periods bowel habits
Exam of iron deficiency anaemia?
bruising conjunctival pallor angular stomatitis pale mucosa tachycardic hypotensive systolic flow murmur-increased CO/turbulent flow kilonychia
Investigations?
FBC, iron and Hb, MCV, iron ,B12 and folate
FBC?
The most common blood test: used to assess number and size of cells found in blood
Often a ‘base line’ or ‘basic’ blood test
ETTA?
Stops clotting in vial so can be processed
Hb?
conc of Haemoglobin (g/L)
Hct
%of blood volume as RBC
MCV
Average size of RBC
MCH
Average haemoglobin content of RBC
MCHC
calculated measure of haemoglobin concentration in given red blood cells
RDW
_Range of deviation around RBC size
other FBC investigations?
Reticulocyte count
Blood film: microscopy
size?
big small normal
shape?
fragments-microcytic haemolytic tear drop-myelofibrosis spiculated-sickle cell ovalocyte-def, thalessaemia spherocyte-spherocytosis eliptocyte-elliptocytosis
colour?
pale normal, polychromatic (reticulocytes)
inclusions?
howell-jolly bodies (hyposplenism), nuclear remnants (thalessaemia), malarial parasites, basophilic stippling (lead poisoning)
microcytic features and causes?
reduced MCV small RBC Iron deficiency (heme deficiency) Thalassamia (globin deficiency) Anaemia of Chronic Disease
Normocytic features and causes?
normal MCV normal RBC Anaemia Chronic Disease-due to chronic condition Aplasia-less synthesis chronic renal failure
macrocytic features and causes?
B12 Deficiency
Folate Deficiency
myelodysplasia-abnormal cells
reticulocytosis-haemolysis-premature breakdown-high rbc turnover-blue centre-larger
drug induced-hydroxycarbamide-sickle and cancer-methotrexate-sodium valproate
Liver disease
hypothyroidism
what does reticulocyte count show?
failure of production or increased losses
Hb and MCV values in childhood and puberty?
13.5 g/dl to 9g/dl in 2 months and increases
as adaptation from hypoxic IU to well-oxygenated EU environment
MCV decreases from birth to 1 yr and increase in puberty
males-high hb-effects of androgens on erythropoiesis
Iron?
Essential for O2 transport
Most abundant trace element in body
Daily requirement for iron for erythropoeisis varies depending on gender and physiolgical needs
Daily iron requirements
higher when child
higher for women if pre-menopausal, preg of BF
Recommended intake assumes 75% of iron is from heme iron sources (meats, seafood). Non-heme iron absorption is lower for those consuming vegetarian diets, for whom iron requirement is approximately 2-fold greater.
Iron metabolism?
> 1 stable form of iron:
Ferric states (3+) and Ferrous states (2+)
Most iron is in body as circulating Hb
ferrous has a higher bioavailability-haem form-in meats-absorbed more
Hb: 4 haem groups, 4 globin chains able to bind 4 O2
Remainder as storage and transport proteins
ferritin and haemosiderin (high is sickle cell or thalessaemia)
Found in cells of liver, spleen and bone marrow
Absorption transprt adn storage of iron?
Iron is absorbed from duodenum via enterocytes into plasma and binds to transferrin and then transported to bone marrow to make red blood cells
Excess absorption of iron is stored as ferritin
Regulated by GI mucosal cells mechanism: max absorption in duodenum & proximal jejunum via ferroportin receptors
Amount absorbed depends on type ingested
heme, ferrous (red meat, used to contain haemoglobin)
non-heme, ferric forms which is bound to other substances.
Heme iron makes up 10-20% of dietary iron
Other foods, GI acidity, state of iron storage levels and bone marrow activity affect absorption
Distribution of iron?
duodenum enterocytes absorb iron and binds to plasma transferrin
used my muscle myoglobin and bone marrow
stored in liver Hb and Reticuloendothelial macrophages
- ingest senescent red cells, catabolise haemoglobin to scavenge iron, and load the iron onto transferrin for reuse.
Iron metabolism is unusual in that it is controlled by absorption rather than excretion. Iron is only lost through blood loss or loss of cells as they slough.
Men and nonmenstruating women lose about 1 mg of iron per day. Menstruating women lose from 0.6 to 2.5 percent more per day.
An average 60-kg woman might lose an extra 10 mg of iron per menstruation cycle, but the loss could be more than 42 mg per cycle depending on how heavily she menstruates.
hepcidin?
“ the iron-regulatory hormone hepcidin and its receptor and iron channel ferroportin control the dietary absorption, storage, and tissue distribution of iron…
Hepcidin causes ferroportin internalization and degradation, thereby decreasing iron transfer into blood plasma from the duodenum, from macrophages involved in recycling senescent erythrocytes, and from iron-storing hepatocytes.
Hepcidin is feedback regulated by iron concentrations in plasma and the liver and by erythropoietic demand for iron.”
serum Fe?
variable during the day-low if iron def
ferritin?
primary storage protein and providing reserve-water soluble-low in iron def
transferrin stas?
ratio of serum iron and total iron binding capacity-% occupancy
low in iron def
total iron binding capacity?
capacity of transferrin to bind to iron-indirectly measures transferrin
high in iron def
stages in development of IDA?
Before anaemia develops, iron deficiency occurs in several stages.
Serum ferritin is the most sensitive laboratory indicators of mild iron deficiency. Stainable iron in tissue stores is equally sensitive, but is not performed in clinical practice.-gold standard-bone marrow biopsy-staining-invasive and time consuming
The percentage saturation of transferrin with iron and free erythrocyte protoporphyrin values do not become abnormal until tissue stores are depleted of iron.
A decrease in the haemoglobin concentration occurs when iron is unavailable for haem synthesis.
MCV and MCH do not become abnormal for several months after tissue stores are depleted of iron.
Causes of iron def?
NOT ENOUGH IN Poor Diet Malabsorption Increased physiological needs LOSING TOO MUCH Blood loss menstruation, GI tract loss, parasites
results of IDA?
Anaemic Microcytic Low reticulocyte Low production Low iron low Ferritin High transferrin Low iron sats
IDA blood film?
Ansiocytosis-abnormal cell size Poikilocytosis-abnormal shape Elliptocytes Hypochromia-less pigment Microcytosis Size-compare to lymphocyte
IDA management?
Refer to gynae, iron supplements (constipation) oral or iv, dietary, Iv acts quicker, transfusion if severe
is iron def a diagnosis?
No-always try to find cause of this!
Thalessaemia?
low MCV, high ferritin low Hb
shows globin def not haem def
iron therapy doesn’t work
macrocytosis low reticulocyte count?
Vitamin B12/Folic acid deficiency
Drug-related
(interference with B12/FA metabolism-methotrexate and folate)
macrocytosis nonmegaloblastic?
Alcoholism ++ Hypothyroidism Liver disease Myelodysplastic syndromes Reticulocytosis (haemolysis)
megaloblastic?
Megaloblastic changes of blood cells are seen in B12 and Folic Acid deficiency. They are characterized on the peripheral smear by macroovalocytes and hypersegmented neutrophils.
folate uses?
DNA synthesis-AGT
causes of folate def?
increased demand?
decreased intake?
decreased absorption?
increased demand?
preg/bf infancy ad growth spurts heamolysis and rapid cell turnover disseminated cancer urinary losses-HF
decreased intake?
poor diet
elderly
chronic alcohol intake
decreased absorption?
medication
coeliac
jejunal resection
tropical sprue
vit B12?
Essential co-factor for methylation in DNA and cell metabolism
Intracellular conversion to 2 active coenzymes necessary for the homeostasis of methylmalonic acid (MMA) and homocysteine and methionine
mma checked as b12 not sensitive
foods with B12?
Foods containing vit B12:
Animal sources: Fish, meat, dairy
UK intake recommendations are 1.5mcg/day
EU: 1mcg/day and USA: 2.4mcg/day
average western intake 5-30mcg/day
Body (liver) storage: 1-5mg so many years for deficiency
What is needed for Vit B12 absorption?
Requires the presence of Intrinsic Factor for absoprtion in terminal ileum
IF made in Parietal Cells in stomach
Transcobalamin II and Transcobalamin I transport vitB12 to tissues
causes of VitB12 deficiency?
impaired absorption-pernicious anaemia
gastrectomy or ileal resection
ZE syndrome
parasites
Decreased intake-malnutrition and vegan diet
congenital causes-
IFR def or cobalamin mutation CG1 gene
increased needs-haemolysis, HIV,PREG growth spurts
meds alcohol-folate def more and poor diet NO PPI/H2A metformin
haematological effects of VitB12 def?
MCV normal or high-Megaloblastic anaemia
Ineffective erythropoeisis
Hb-normal or low
reticulocyte count-low
LDH(lactate dehydrogenase)-raised-IM haemolysis or malignancy
blood film-macrocytes, ovalocytes, hypersegmented neuts
BMAT-Hypercellular, megaloblastic, giant metamyelocytes-unusual
MMA-highly sensitive-increased-not standard lab test-highly sensitive
effects of VitB12 def?
Brain: cognition, depression, psychosis Neurology: myelopathy, sensory changes, ataxia, spasticity (SC columns degeneration) (SACDC) Infertility Cardiac cardiomyopathy Tongue: glossitis, taste impairment Blood: Pancytopenia
Pernicious Anaemia?
Autoimmune disorder
Lack of IF
Lack of
B12 absorption
Gastric Parietal cell antibodies
IF antibodies
test for ABs and give B12 injections-twice for 2 weeks and once every 3 months
