Microcytic anaemia

Question 1

What is anaemia?

Answer 1

• 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

Question 2

What are the main cells in blood?

Answer 2

• Red blood cells
• White blood cells
• Platelets

Question 3

What are the cellular components of blood derived from?

Answer 3

• 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

Question 4

What are reticulocytes?

Answer 4

• 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

Question 5

How do RBCs survive without mitochondria?

Answer 5

• survive via cytoplasmic enzymes
• involved in metabolism including glycolysis

Question 6

What is haemoglobin?

Answer 6

• iron containing oxygen transport metalloprotein
• within RBCs
• reduction in Hb = anaemia
• globular protein w/ quaternary structure
• 4 polypeptide subunits; 2 alpha + 2 beta chains

Question 7

Normal erythropoiesis refers to red blood cell production. What does maturation of red blood cells require?

Answer 7

• vitamin B12 + folic acid : DNA synthesis
• iron : haemoglobin synthesis

Question 8

What are possible signs and symptoms of anaemia?

Answer 8

• 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)

Question 9

What is the main diagnostic test for anaemia?

Answer 9

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

Question 10

What do you look for in microscopy (blood film)?

Answer 10

• 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)

Question 11

What Hb levels suggest anaemia in men and women?

Answer 11

• Men
  
  • normal: >130
  • mild: 110-129
  • moderate: 80-109
  • severe: <80
    ​
• Women
  
  • normal: >120
  • mild: 110-119
  • moderate: 80-109
  • severe: <80

Question 12

What additional tests are done to find cause of anaemia?

Answer 12

• WBC + platelet count
• Reticulocyte count
• Iron studies (ferritin, serum Fe, TIBC)
• Haematinic levels (B12/folate)
• BMAT - iron stains

Question 13

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?

Answer 13

• suggest appropriate marrow response
• either hamolysis or blood loss
• haemolytic anaemia can be extrinsic or intrinsic to RBC

Question 14

How is anaemia classified?

Answer 14

• 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)

Question 15

What are common causes for microcytic anaemia, where there is a reduce MCV suggesting small RBCs?

Answer 15

• Iron deficiency (haeme deficiency)
• Thalassaemia trait (globin deficiency)
• Anaemia of chronic disease ‘late’
• Lead
• Sideroblastic anaemia (low protoporphyrin)

Question 16

What are causes of normocytic anaemia (normal MCV)?

Answer 16

• anaemia of chronic disease ‘early’
• bone marrow hypo/aplasia
• chronic renal failure/low EPO

Question 17

What are causes of macrocytic anaemia (inc MCV)?

Answer 17

• B12 deficiency
• Folate deficiency
• Myelodysplasia
• Drug induced (eg methotrexate)
• Liver disease/alcohol
• Hypothyroidism
• Smoking

Question 18

How do Hb and MCV values change from birth to adulthood?

Answer 18

• (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?

Question 19

Why do we need iron?

Answer 19

• 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

Question 20

What foods are rich in iron?

Answer 20

• 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

Question 21

Where is dietary iron predominantly absorbed?

Answer 21

Duodenum

Question 22

How is iron distributed in the adult body?

Answer 22

• Fe³⁺ ions circulate bound to plasma transferrin
• accumulate within cells in form of ferritin
• stored iron can be mobilised for reuse
• more than 2/3^rds 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

Question 23

What is the stable form of iron and where is most of it found?

Answer 23

• > 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

Question 24

Describe iron absorption

Answer 24

• 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

Question 25

Discuss the role of **hepcidin** in iron regulation

Answer 25

* 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

Question 26

Describe iron transport and storage

Answer 26

* 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

Question 27

Is ferritin water soluble?

Answer 27

Yes, it is the primary storage protein and providing reserve.

Question 28

What does transferrin saturation tell us?

Answer 28

* ratio of serum iron and total iron binding capacity​ * revealing % of transferrin binding sites that have been occupied by iron

Question 29

Where is transferrin made and why is it important?

Answer 29

* 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**

Question 30

What is TIBC and when is it high/low?

Answer 30

* 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

Question 31

What are causes of iron deficiency?

Answer 31

**_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

Question 32

What are lab investigations for iron deficiency?

Answer 32

* FBC: Hb, MCV, MCH, reticulocyte count * Iron studies: ferritin, transferrin sats, TIBC * blood film * ?BMAT + iron stores

Question 33

As iron deficiency anaemia develops, how do the lab findings change?

Answer 33

* 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

Question 34

What are the lab results in iron deficiency anaemia for: * ferritin * transferrin saturation * TIBC * serum iron

Answer 34

* ferritin - LOW * TF sat - LOW * TIBC - HIGH * serum iron - LOW / NORMAL

Question 35

What is angular stomatitis?

Answer 35

Inflammation of corners of mouth

Question 36

What is atrophic glossitis?

Answer 36

* sore inflammed tongue * where papillae on dorsal surface are lost * leaving smooth erythematous surface

Question 37

What are the BSG guidelines for management of IDA?

Answer 37

* **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