Iron in HEALTH and DISEASE

Question 1

Where is iron present?

Answer 1

• Hb
• Myoglobin
• enzymes (cytochromes)

Question 2

Why is iron dangerous?

Answer 2

chemical reactivity
(may cause Oxidative stress and free radical prdn)

—-should be transported, stored SAFELY

Question 3

Can the body excrete iron?

Answer 3

NO

Question 4

Where is MAJORITY of the body’s iron found?

Answer 4

In the haem

- Fe2+ ion sits in PROPHYRIN ring

Question 5

How much iron is lost every day?

Answer 5

1 mg

loss d.t loss of cells –bleeding, mucosal cells

Question 6

How much serum iron at any given time?

Answer 6

4 mg

Question 7

Where is iron absorbed?

Answer 7

• in DUODENUM

- —by duodenal mucosa

Question 8

Which iron is readily absorbed?

Answer 8

• HAEM-IRON

Question 9

What enhances iron absorption?

Answer 9

• ascorbic acid (reduces IRON to FE2+)

- alcohol

Question 10

what inhibits iron absorption?

Answer 10

• Tannins (TEA)
• pHYTATES (CEREALS/ BRAN, NUTS AND SEEDS)
• calcium (dairy products

Question 11

WHat is involved in IRON absorption?

Answer 11

• duodenal cytochrome B in the luminal surface (converts FERRIC 3+ iron to FERROUS iron)
• DMT-1 transports ferrous iron INTO the duodenal enterocyte
• Ferroportin (exports iron FROM the enterocyte—to transferin for transport)

Question 12

What regulates iron absorption?

Answer 12

HEPCIDIN (produced in the liver)

—-incr. in response to INCR. IRON load and inflammation (malignancy)

Question 13

What is MOA of hepcidin>

Answer 13

• BINDS to ferroportin and CAUSES its DEGEN.

- –so iron is TRAPPED in duodenal cells and macrophages

Question 14

What occurs to hepcidin levels when iron is deficient?

Answer 14

• DECREASES

Question 15

How to assess iron status? (3 compartments)

Answer 15

1. Functional Iron (Hb conc.)
2. Transport iron/ IRON supply to tissues (% saturation of TRANSFERRIN)
3. Storage iron (serum FERRITIN/ tissue biopsy- rare)

Question 16

What is transferrin?

Answer 16

• transports iron from DONOR tissues (macrophages/ intestinal and liver cells) to the tissues EXPRESSING transferrin receptors
• —-ALLOWS the SAFE transport of iron

Question 17

What tissue is rich in transferrin receptors?

Answer 17

• erythroid marrow (cells )

Question 18

What is transferrin saturation?

Answer 18

• measures IRON SUPPLY

- —serum iron/ total iron binding capacity (to transferrin) x 100%

Question 19

What occurs in iron overload?

Answer 19

• transport system is compromised

- –transferrin saturation is 100%

Question 20

What does transferrin saturation reflect?

Answer 20

• the proportion of diferric transferrin

HIGH affinity for cellular transferrin receptors

Question 21

What does a small level of serum ferritin indicate?

Answer 21

• indirect measure of STORAGE iron

- –reflects intracellular ferritin synthesis

Question 22

When may ferritin serum levels go up?

Answer 22

• with INFECTION and malignancy

it’s an ACUTE phase protein

Question 23

When is it best to look at ferritin levels?

Answer 23

• for IRON deficiency.

Question 24

What does it mean by negative iron balance?

Answer 24

losing iron more than you are absorbing

Question 25

What are the consequences of NEGATIVE iron balance?

Answer 25

1. exhaustion of iron stores 2. iron deficient erythropoiesis * FALLING MCV) 3. Microcytic anaemia 4. Epithelial changes (Skin/ koilonychia/ angular stomatitis)

Question 26

What does hypochromic and microcytic anaemia indicte?

Answer 26

DEFICIENT Hb synthesis

Question 27

What 2 parameters to CONFIRM dx of iron deficiency>

Answer 27

- Decr. Hb iron | - Reduced STORAGE iron (FERRITIN)

Question 28

What causes iron def.?

Answer 28

- more likely women and children - vegetarian - too much bleeding - not absorbing enough (CELIAC disease)

Question 29

What are chronic causes of blood loss?

Answer 29

1. menorrhagia 2. GI (tumors/ ulcer/ NSAIDs/ parasitic infection) 3. Hematuria

Question 30

What is meant by OCCULT blood loss?

Answer 30

- GI blood loss of 8-10 ml per day (tsp)--4-5 mg of iRON | - -----MAX iron absorption is 4-5mg; negative iron balance may occur

Question 31

What is iron malutilisation?

Answer 31

- anaemia of chronic disease

Question 32

Where is iron malutilisation commonly seen?

Answer 32

in hospitalized pts

Question 33

Why is iron def. seen in chronic disease pts?

Answer 33

d.t INFLAMMATORY macrophage IRON block ---- Body's reaction in making iron LESS available to the pathogen

Question 34

How does the inflammatory rxn result in IRON block?

Answer 34

Increased transcription of ferritin mRNA stimulated by inflammatory cytokines so ferritin synthesis increased Increased plasma hepcidin blocks ferroportin-mediated release of iron Results in impaired iron supply to marrow erythroblasts and eventually hypochromic red cells

Question 35

What occurs in Hereditary hemochromatosis?

Answer 35

- mutation in HFE gene - -----decr. SYNTHESIS of HEPCIDIN - ----incr. iron absorption ----eventual iron accumulation and RISK of END-ORGAN damage.

Question 36

How does hereditary hemochromatosis present as?

Answer 36

- fatigue - JOINT pain - IMPOTENCE - arthritis - CIRRHOSIS - DIABETES - cardiomyopathy

Question 37

How to dx Hereditary hemochromatosis?

Answer 37

- transferin sat. >50% | - ---incr. iron stores (serum ferritin >300in men and >200microgrma/l in pre-menopausal women)

Question 38

How to confirm dx of HHC?

Answer 38

0 LIVER biopsy | ----FIBROSCAN available to assess cirrhosis

Question 39

How to TREAT Hereditary hemochromatosis?

Answer 39

``` WEEKLY VENESECTION (450-500ml) ----intial aim to EXHAUST iron stores (<20 mcg/L ferritin) ---maintain at 50 mcg/L after ```

Question 40

chance of a first degree relative having hereditary hemochromatosis?

Answer 40

First degree relative of cases (esp. in SIBLINGS) - 1 in 4 chance ! ----kids WAIT until they are adults; for informed consent

Question 41

Is haemochromatosis asymptomatic?

Answer 41

YES until irreversible organ damage OCCURS

Question 42

What are the sources of iron-loading anaemias?

Answer 42

- repeated red cell transfusions | - excessive IRON absorption related over erythropoiesis

Question 43

What disorders cause iron loading anemias?

Answer 43

(anaemia in the presence of HIGH serum ferritin/ transferrin) - massive ineffective erythropoiesis (Thalassaemia and Sideroblastic anaemias) - refractory hypoplastic anaemias (red cell APLASIA and MYELODYSPLASIA)

Question 44

What refractory hypoplastic anaemias cause iron-loading anaemias?

Answer 44

red cell aplasia | myelodysplasia

Question 45

Explain the consequence of iron loading.

Answer 45

red cell transfusion and incr. iron absorption--> IRON OVERLOAD--> DAMAGE TO LIVER, HEART AND ENDOCRINE glands

Question 46

How to treat IIary iron overload?

Answer 46

----IRON chelating agents (DESFERROIOXAMINE--S/c or Iv) - --desferipone - -deferasirox

Question 47

Why is venesection not ideal in IIaryiron overload?

Answer 47

--- not ideal to perform on an already ANEMIC pt

Question 48

What is seen in Sideroblastic anaemia?

Answer 48

- EXCESS iron build up in MITOCHONDRIA (failure to incorp/ iron in to haem)

Question 49

Why is iron essential?

Answer 49

- oxygen transport | - electron transport (mitochondrial prodn of ATP)