Microcytic anaemia Flashcards
1
Q
What is anaemia?
A
- functionally defined as an insufficient red cell mass to adequately deliver oxygen to peripheral tissues
- generally considered to be present when the Hb conc is below lower limit of 95% ref range for the population
2
Q
What are the main cells in blood?
A
- Red blood cells
- White blood cells
- Platelets
3
Q
What are the cellular components of blood derived from?
A
- bone marrow, where maturation occurs
- from multipotent haematopoetic stem cell
- these HSCs -> turn into any blood cell + self renew
- haemopoesis = formation of blood cells
- erythropoietin is an important growth factor for RBCs
4
Q
What are reticulocytes?
A
- young red cells recently released from bone marrow
- just lost their nucleus
- do however still contain some mRNA to synthesise Hb
- larger than mature red cells
- represent around 0.5-2.5% of circulating RBCs
5
Q
How do RBCs survive without mitochondria?
A
- survive via cytoplasmic enzymes
- involved in metabolism including glycolysis
6
Q
What is haemoglobin?
A
- iron containing oxygen transport metalloprotein
- within RBCs
- reduction in Hb = anaemia
- globular protein w/ quaternary structure
- 4 polypeptide subunits; 2 alpha + 2 beta chains
7
Q
Normal erythropoiesis refers to red blood cell production. What does maturation of red blood cells require?
A
- vitamin B12 + folic acid : DNA synthesis
- iron : haemoglobin synthesis
8
Q
What are possible signs and symptoms of anaemia?
A
- fatigue + loss of energy
- dyspnoea on exertion
- faintness
- palpitations
- headache
- tinnitus
- anorexia
- pallor
- koilonychia, angular stomatitis, abdo discomfort
- hyperdynamic circulation - tachycardia, flow murmurs
- angina (if pre-existing coronary artery disease)
9
Q
What is the main diagnostic test for anaemia?
A
FBC - most common blood test, assess number and size of cells found in blood, look for:
- Hb: conc of Hb
- Hct: % of blood vol as RBC
- MCV: avd size of RBC
- MHC: avg Hb content of RBC
- MCHC: calc measure of Hb conc in given RBCs
- RDW: range of deviation around RBC size
- Reticulocyte count
- Blood film: microscopy
10
Q
What do you look for in microscopy (blood film)?
A
- SIZE (big, small, normal)
- SHAPE (fragments, tear drops, spiculated, ovalocyte, spherocyte, elliptocyte)
- COLOUR (pale, normal, polychromasia)
- INCLUSIONS (howell-jolly bodies, nuclear remnants, malarial parasites, basophilic stippling)
11
Q
What Hb levels suggest anaemia in men and women?
A
-
Men
- normal: >130
- mild: 110-129
- moderate: 80-109
- severe: <80
-
Women
- normal: >120
- mild: 110-119
- moderate: 80-109
- severe: <80
12
Q
What additional tests are done to find cause of anaemia?
A
- WBC + platelet count
- Reticulocyte count
- Iron studies (ferritin, serum Fe, TIBC)
- Haematinic levels (B12/folate)
- BMAT - iron stains
13
Q
If the reticulocyte count is normal/decreased, then there is an inappropriate marrow response suggesting we look at MCV and determine the cause of anaemia. What if there is an increased reticulocyte count?
A
- suggest appropriate marrow response
- either hamolysis or blood loss
- haemolytic anaemia can be extrinsic or intrinsic to RBC
14
Q
How is anaemia classified?
A
- causes of anaemia classified according to measurement of RBC size
- using mean corpuscular volume (MCV)
- gives average volume of RBCs in blood sample
- microcytic (small cells), normocytic (normal), macrocytic (large cells)
15
Q
What are common causes for microcytic anaemia, where there is a reduce MCV suggesting small RBCs?
A
- Iron deficiency (haeme deficiency)
- Thalassaemia trait (globin deficiency)
- Anaemia of chronic disease ‘late’
- Lead
- Sideroblastic anaemia (low protoporphyrin)
16
Q
What are causes of normocytic anaemia (normal MCV)?
A
- anaemia of chronic disease ‘early’
- bone marrow hypo/aplasia
- chronic renal failure/low EPO
17
Q
What are causes of macrocytic anaemia (inc MCV)?
A
- B12 deficiency
- Folate deficiency
- Myelodysplasia
- Drug induced (eg methotrexate)
- Liver disease/alcohol
- Hypothyroidism
- Smoking
18
Q
How do Hb and MCV values change from birth to adulthood?
A
- (kind of) U shaped for both
- Hb decrement (much higher at birth) referrred to as physiologic anaemia of infancy
- occurs as part of normal physiologic adaptation from relatively hypoxic intrautarine existence -> well-oxygenated extrauterine environment
- fetal erythropoiesis is replaced -> MCV decreases from birth to 1 year of age
- after 1 year, normal childhood Hb + MCV values remain considerably lower than those occurring in adolescents + adults
- adult levels reached at puberty
- higher Hb levels in males - effects of androgens on erythropoiesis?
19
Q
Why do we need iron?
A
- essential of O2 transport
- essential component of cytochromes
- most abundant trace element in body
- daily requirement for iron for erythropoeisis
- varies depending on gender + physiological needs
20
Q
What foods are rich in iron?
A
- meats: liver, beef, lamb, ham, turkey, chicken, veal, pork
- seafood: shrimp, dried cod, mackerel, tuna, sardines, haddock
- vegetables: spinach, beet greens, sweet pot, peas, broc, kale
- breads + cereals: white bread, macaroni, bran, oat, corn, rye
- fruits: prunes, watermelon, dried apricots/peaches, strawberries, raisins, dates, figs
- others: eggs, dried peas, corn syrup, maple syrup, lentils
21
Q
Where is dietary iron predominantly absorbed?
A
Duodenum
22
Q
How is iron distributed in the adult body?
A
- Fe3+ ions circulate bound to plasma transferrin
- accumulate within cells in form of ferritin
- stored iron can be mobilised for reuse
- more than 2/3rds of body’s iron content is incorporated into Hb in developing erythroid precursors + mature red cells
- most of remaining body iron found in hepatocytes + reticuloendothelial macrophages, which serve as storage deposits
- reticuloendothelial macrophages ingest senescent RBCs, carabolise Hb to scavenge iron + load iron onto transferrin for reuse
- iron metabolism is controlled by absorption rather than excretion, iron is only lost through blood loss or loss of cells
23
Q
What is the stable form of iron and where is most of it found?
A
- > 1 stable form of iron: Fe2+ and Fe3+
- Most iron in body as circulating Hb
- Remainder as storage + transport proteins
- ferritin + haemosiderin
- found in cells of liver, spleen + bone marrow
24
Q
Describe iron absorption
A
- regulated by GI mucosal cells mechanism
- max absorption in duodenum + prox jejunum
- via ferroportin receptors
- amount absorbed depends on type ingested
- heme, ferrous (meat) > than non-heme, ferric forms (cereals)
- heme iron makes up 10-20% of dietary iron
- other foods, GI acidity, state of iron storage levels + bone marrow activity affect absorption
25
Q
Discuss the role of hepcidin in iron regulation
A
- iron regulatory hormone hepcidin + its receptor and iron channel ferroportin control dietary absorption, storage + tissue distribution of iron
- hepcidin causes ferroportin internalisation 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 + the liver and by erythropoietic demand for iron
26
Q
Describe iron transport and storage
A
- iron transported from enterocytes
- then either into plasma or stored as ferritin
- once attached to transferrin, binds to transferrin receptors on RBC precursors
- a state of iron deficiency will see reduced ferritin stores + then increased transferrin
27
Q
Is ferritin water soluble?
A
Yes, it is the primary storage protein and providing reserve.
28
Q
What does transferrin saturation tell us?
A
- ratio of serum iron and total iron binding capacity
- revealing % of transferrin binding sites that have been occupied by iron
29
Q
Where is transferrin made and why is it important?
A
- made by liver
- production inversely proportional to iron stores
- vital for iron transport
- uptake of iron from protein needs transferrin to be attached to the cell via the transferrin receptor
30
Q
What is TIBC and when is it high/low?
A
- total iron binding capacity
- measurement of capacity of transferrin to bind iron
- an indirect measurement of transferrin (the iron transport protein)
- TIBC is technically easier to measure in lab than transferrin levels directly
- in IDA: TIBC is high - more transferrin produced aiming to transport more iron to tissues in need
- in ACD: TIBC is low - less transferrin produced (but more ferritin), aim to reduce availability of iron for pathogens - mainly regulated by increased hepcidin production
31
Q
What are causes of iron deficiency?
A
1) Not enough in:
- poor diet
- malabsorption eg. coeliac
- inc physiological needs eg. pregnancy
2) Losing too much:
- blood loss
- menstruation, GI tract loss, parasites - infestation of gut by hookworm
32
Q
What are lab investigations for iron deficiency?
A
- FBC: Hb, MCV, MCH, reticulocyte count
- Iron studies: ferritin, transferrin sats, TIBC
- blood film
- ?BMAT + iron stores
33
Q
As iron deficiency anaemia develops, how do the lab findings change?
A
- occurs in several stages
- initially IDA is normocytic + normochromic
- serum ferritin is most sensitive lab indicator of mild iron def
- serum ferritin decreases as IDA progresses
- 60 -> 20 -> <12
- transferrin sats + free erythryocyte protoporhyrin values do not become abnormal until tissue stores are depleted of iron
- a decrease in Hb conc occurs when iron is unavailable for haem synthesis
- MCV and MCH do not become abnormal for several months after tissue stores depleted of iron
34
Q
What are the lab results in iron deficiency anaemia for:
- ferritin
- transferrin saturation
- TIBC
- serum iron
A
- ferritin - LOW
- TF sat - LOW
- TIBC - HIGH
- serum iron - LOW / NORMAL
35
Q
What is angular stomatitis?
A
Inflammation of corners of mouth
36
Q
What is atrophic glossitis?
A
- sore inflammed tongue
- where papillae on dorsal surface are lost
- leaving smooth erythematous surface
37
Q
What are the BSG guidelines for management of IDA?
A
- upper + lower GI investigations in all postmenopausal female and all male patients
- all pts should be screened for coeliac disease
- colonoscopy is preferred to CT colography + barium enema
- h. pylori should be eradicated if present
- faecal occult blood testing is of no benefit
- rectal exam is seldom contributory + may be postponed until colonoscopy
- urine testing for blood is important
