IOD Microcytic and Macrocytic Anaemia

Question 1

History of iron deficiency anaemia?

Answer 1

signs-tiredness, SOB
NSAIDs, steroids, anticoagulants
diet-vegan or veg
periods
bowel habits

Question 2

Exam of iron deficiency anaemia?

Answer 2

bruising
conjunctival pallor
angular stomatitis
pale mucosa
tachycardic
hypotensive
systolic flow murmur-increased CO/turbulent flow
kilonychia

Question 3

Investigations?

Answer 3

FBC, iron and Hb, MCV, iron ,B12 and folate

Question 4

FBC?

Answer 4

The most common blood test: used to assess number and size of cells found in blood

Often a ‘base line’ or ‘basic’ blood test

Question 5

ETTA?

Answer 5

Stops clotting in vial so can be processed

Question 6

Hb?

Answer 6

conc of Haemoglobin (g/L)

Question 7

Hct

Answer 7

%of blood volume as RBC

Question 8

MCV

Answer 8

Average size of RBC

Question 9

MCH

Answer 9

Average haemoglobin content of RBC

Question 10

MCHC

Answer 10

calculated measure of haemoglobin concentration in given red blood cells

Question 11

RDW

Answer 11

_Range of deviation around RBC size

Question 12

other FBC investigations?

Answer 12

Reticulocyte count

Blood film: microscopy

Question 13

size?

Answer 13

big small normal

Question 14

shape?

Answer 14

fragments-microcytic haemolytic
tear drop-myelofibrosis
spiculated-sickle cell
ovalocyte-def, thalessaemia
spherocyte-spherocytosis
eliptocyte-elliptocytosis

Question 15

colour?

Answer 15

pale normal, polychromatic (reticulocytes)

Question 16

inclusions?

Answer 16

howell-jolly bodies (hyposplenism), nuclear remnants (thalessaemia), malarial parasites, basophilic stippling (lead poisoning)

Question 17

microcytic features and causes?

Answer 17

reduced MCV
small RBC
Iron deficiency 
(heme deficiency)
Thalassamia 
(globin deficiency)
Anaemia of Chronic Disease

Question 18

Normocytic features and causes?

Answer 18

normal MCV
normal RBC
Anaemia Chronic Disease-due to chronic condition
Aplasia-less synthesis
chronic renal failure

Question 19

macrocytic features and causes?

Answer 19

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

Question 20

what does reticulocyte count show?

Answer 20

failure of production or increased losses

Question 21

Hb and MCV values in childhood and puberty?

Answer 21

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

Question 22

Iron?

Answer 22

Essential for O2 transport
Most abundant trace element in body

Daily requirement for iron for erythropoeisis varies depending on gender and physiolgical needs

Question 23

Daily iron requirements

Answer 23

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.

Question 24

Iron metabolism?

Answer 24

> 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

Question 25

Absorption transprt adn storage of iron?

Answer 25

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

Question 26

Distribution of iron?

Answer 26

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.

Question 27

hepcidin?

Answer 27

“ 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.”

Question 28

serum Fe?

Answer 28

variable during the day-low if iron def

Question 29

ferritin?

Answer 29

primary storage protein and providing reserve-water soluble-low in iron def

Question 30

transferrin stas?

Answer 30

ratio of serum iron and total iron binding capacity-% occupancy low in iron def

Question 31

total iron binding capacity?

Answer 31

capacity of transferrin to bind to iron-indirectly measures transferrin high in iron def

Question 32

stages in development of IDA?

Answer 32

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.

Question 33

Causes of iron def?

Answer 33

``` NOT ENOUGH IN Poor Diet Malabsorption Increased physiological needs LOSING TOO MUCH Blood loss menstruation, GI tract loss, parasites ```

Question 34

results of IDA?

Answer 34

``` Anaemic Microcytic Low reticulocyte Low production Low iron low Ferritin High transferrin Low iron sats ```

Question 35

IDA blood film?

Answer 35

``` Ansiocytosis-abnormal cell size Poikilocytosis-abnormal shape Elliptocytes Hypochromia-less pigment Microcytosis Size-compare to lymphocyte ```

Question 36

IDA management?

Answer 36

Refer to gynae, iron supplements (constipation) oral or iv, dietary, Iv acts quicker, transfusion if severe

Question 37

is iron def a diagnosis?

Answer 37

No-always try to find cause of this!

Question 38

Thalessaemia?

Answer 38

low MCV, high ferritin low Hb shows globin def not haem def iron therapy doesn't work

Question 39

macrocytosis low reticulocyte count?

Answer 39

Vitamin B12/Folic acid deficiency Drug-related (interference with B12/FA metabolism-methotrexate and folate)

Question 40

macrocytosis nonmegaloblastic?

Answer 40

``` Alcoholism ++ Hypothyroidism Liver disease Myelodysplastic syndromes Reticulocytosis (haemolysis) ```

Question 41

megaloblastic?

Answer 41

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.

Question 42

folate uses?

Answer 42

DNA synthesis-AGT

Question 43

causes of folate def?

Answer 43

increased demand? decreased intake? decreased absorption?

Question 44

increased demand?

Answer 44

``` preg/bf infancy ad growth spurts heamolysis and rapid cell turnover disseminated cancer urinary losses-HF ```

Question 45

decreased intake?

Answer 45

poor diet elderly chronic alcohol intake

Question 46

decreased absorption?

Answer 46

medication coeliac jejunal resection tropical sprue

Question 47

vit B12?

Answer 47

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

Question 48

foods with B12?

Answer 48

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

Question 49

What is needed for Vit B12 absorption?

Answer 49

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

Question 50

causes of VitB12 deficiency?

Answer 50

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 ```

Question 51

haematological effects of VitB12 def?

Answer 51

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

Question 52

effects of VitB12 def?

Answer 52

``` Brain: cognition, depression, psychosis Neurology: myelopathy, sensory changes, ataxia, spasticity (SC columns degeneration) (SACDC) Infertility Cardiac cardiomyopathy Tongue: glossitis, taste impairment Blood: Pancytopenia ```

Question 53

Pernicious Anaemia?

Answer 53

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