Iron deficiency

Question 1

Major food sources of iron (and why)

Answer 1

Foods of animal origin

Have high bioavailability (iron from plants = low solubility and have chelators that prevent absorption)

Question 2

Where is iron absorbed?

Answer 2

Duodenum by enterocytes

Question 3

Most of the iron in the body is in the form of…?

Answer 3

Circulating haemoglobin

Question 4

How can iron be absorbed by enterocytes?

Answer 4

As an ion (Fe2+)
As part of a protein e.g. haem
Their brush border has a ferric reductase enzyme that can reduce Fe3+ to Fe2+.

Question 5

What enhances iron absorption?

Answer 5

Acid pH, iron deficiency, pregnancy, and hypoxia

Question 6

What are transferrins?

Answer 6

Iron-binding plasma glycoproteins that control the level of free iron in plasma
Each molecule has the ability to carry two Fe3+ atoms.

Question 7

How is iron transported from enterocytes to inside the cell?

Answer 7

Iron is taken up from enterocytes by transferrin and transported in the blood to the bone marrow and other cells. This then binds to a transferrin receptor on the surface of the cell and is transported into the cell by endocytosis.

Question 8

Inside the cell, how is iron released and stored?

Answer 8

Inside the cell, transferrin releases the ions and they are taken up by ferritin (a large hollow globular protein) and stored inside. The receptor/transferrin complex is transported back to the cell surface/release ready for another round.

Question 9

What is ferritin and what is it’s role?

Answer 9

Ferritin releases iron in a controlled fashion when needed, acting as a buffer. It is a cytosolic protein but small amounts are secreted into the serum where it functions as an iron carrier.

Question 10

Define iron deficiency anaemia

Answer 10

Diminished red blood cell production due to low iron stores in the body

Question 11

What does iron deficiency anaemia show on blood film?

Answer 11

Microcytic, hypochromic cells

Question 12

Define anaemia using Hb level for men over 15 years old

Answer 12

Below 130 g/L

Question 13

Define anaemia using Hb level for women over 15 years old AND children age 12-14

Answer 13

Below 120 g/L

Question 14

Define anaemia using Hb level for pregnant women

Answer 14

Below 110 g/L

Question 15

Define anaemia using Hb level for postpartum women

Answer 15

Below 100 g/L

Question 16

A serum ferritin level of less than (blank) confirms iron deficiency

Answer 16

15 micrograms/L

Question 17

Causes of iron deficiency anaemia

Answer 17

Dietary deficiency (rarely a cause on its own)
Malabsorption (e.g. coeliac disease, gastrectomy, or H pylori, IBD, hookworm)
Increased loss e.g. menstruation, gastric ulcers, varices, GI cancers, NSAIDs, blood donation, self-harm, haematuria, nosebleeds
Increased requirement e.g. pregnancy, growth

Question 18

Most common cause of iron deficiency anaemia in pre-menopausal women

Answer 18

Menstruation

Question 19

Most common cause of iron deficiency anaemia in men and pre-menopausal women

Answer 19

GI blood loss

Question 20

Complications of iron deficiency anaemia

Answer 20

Cognitive and behavioural impairment in children
Impaired muscular performance
Heart failure
Adverse effects on immunity

Question 21

What to ask in history?

Answer 21

PC/HPC - symptoms of anaemia (including angina, palpitations, ankle swelling)
ROS - GI bleeding, weight loss, fever, fatigue, change in bowel habit
PMH - overt bleeding, heavy bruising, blood donation, recent illness/surgery
Obs history - menstrual, pregnancy, breastfeeding
DH - NSAIDs, aspirin, SSRIs, clopidogrel, corticosteroids
FH - iron def anaemia, bleeding disorders and telangiectasia, colorectal carcinoma, haematological disorders
SH - diet, travel

Question 22

Symptoms of iron def anaemia

Answer 22

Dyspnoea
Fatigue
Headache 
Cognitive dysfunction
Restless leg syndrome
Vertigo

Rare symptoms - dysphagia (from post-cricoid webs), haemodynamic instability, syncope

Other symptoms - dizziness, weakness, irritability, palpitations, pica, pruritus, sore tongue, tinnitus, impairment of body temperature regulation

Angina, ankle oedema, dyspnoea at rest unlikely unless Hb <70

Question 23

Signs of iron def anaemia

Answer 23

Pallor
Atrophic glossitis
Dry and rough skin, dry and damaged hair
Diffuse and moderate alopecia
Angular cheilosis
Nail changes e.g. longitudinal ridging and koilonychia

Tachycardia, murmurs, cardiac enlargement, and heart failure may occur if severe

Question 24

Signs and symptoms of hookworm infection

Answer 24

Cutaneous larva migrans, itchy rash, cough and wheeze a few weeks after exposure, abdominal pain, diarrhoea, anorexia, weight loss, fatigue.

Question 25

Signs and symptoms of coeliac disease

Answer 25

Diarrhoea, abdominal pain, bloating and flatulence, indigestion, constipation, fatigue, weight loss, dermatitis herpetiformis, infertility, peripheral neuropathy, ataxia, delayed puberty.

Question 26

Signs and symptoms of inflammatory bowel disease

Answer 26

Abdominal pain/cramps, diarrhoea, weight loss, fatigue. Remission and flare-ups.

Question 27

Signs and symptoms of GI cancer

Answer 27

Change in bowel habit, abdominal pain, blood in the stools, bloating, weight loss

Question 28

Signs and symptoms of ulcer

Answer 28

Indigestion, abdo pain

Question 29

Bloods to confirm suspected iron def anaemia

Answer 29

FBC - Hb, MCV
Ferritin
Consider testing vitamin B12 and folate

Question 30

Define microcytosis

Answer 30

Mean cell volume (MCV) less than 80 femtolitres

Question 31

Red blood cell changes associated with iron def

Answer 31

Hypochromia
Anisocytosis (variation in size of RBCs)
Poikilocytosis (irregular shaped RBCs)
May have pencil cells

Question 32

Investigations for all people with confirmed iron deficiency anaemia

Answer 32

Screen for coeliac disease (anti-tissue transglutaminase antibodies)
Test the urine for blood.
Consider stool examination to detect parasites (if appropriate)
Consider others where appropriate

Question 33

Differentials for iron def anaemia

Answer 33

Thalassaemia - MCV and MCH reduced, very low for degree of anaemia, increase in serum iron and ferritin, low total iron-binding capacity, target cells, DNA analysis/Hb electrophoresis for definitive diagnosis

Sideroblastic anaemias (very rare) - can be due to alcoholism, hepatosplenomegaly, increase in serum iron and ferritin, low total iron-binding capacity, sideroblasts in marrow

Anaemia of chronic disease - usually normocytic and normochromic

Lead poisoning (rare in adults) - history of risk factors

Question 34

Management

Answer 34

Address underlying causes and refer where appropriate
Advise the person to maintain an adequate balanced intake of iron-rich foods
Oral ferrous sulfate 200 mg tablets two or three times a day — treatment should continue for 3 months after iron deficiency is corrected
Monitor 2-4 weeks, check again after 2-4 months, then every 3 months for 1 year, recheck again after another year

Question 35

What if ferrous sulfate is not tolerated?

Answer 35

Consider oral ferrous fumarate tablets or ferrous gluconate tablets.

Question 36

Side effects of ferrous sulphate

Answer 36

Constipation; diarrhoea; gastrointestinal discomfort; nausea

Question 37

How to reduce side effects of ferrous sulphate

Answer 37

Take with food
Can take lower doses e.g. twice a day instead of TDS
Swap to ferrous gluconate or fumarate
S/Es usually settle down with time

Question 38

When should ongoing prophylactic dose of iron be considered?

Answer 38

Recurring anaemia and further investigations are not indicated or appropriate.
An iron-poor diet 
Malabsorption
Menorrhagia
Had a gastrectomy
Women who are pregnant.
People undergoing haemodialysis