iron

Question 1

Mention the sources, recommended daily intake (RDA) and functions of Iron

Answer 1

Iron is one of the micronutrients which occur in ferrous (fe2+) and ferric (fe3+) forms.

It is poorly absorbed and poorly excreted. Deficiency + excess can occur

Haem-containing proteins (75%). Non-haem containing proteins (25%). Free iron is toxic.

Sources:
1. Endogenous sources (breakdown of haem of Hb in RBC
2. Exogenous sources (Dietary sources)
- Plants → Leafy greens, beans, nuts, dates
- Animal → Organ meat (heart, liver, kidney), muscle meat, egg yolk, fish.

Functions:
1. Part of haemoglobin
2. Part of metalloenzymes

RDA ⇒ 10mg/day

Question 2

Describe the factors favoring and hindering the absorption of Iron

Answer 2

Iron is primarly absorbed in the proximal small bowel (duodenum). It is readily absorbed in Fe2+ form, but dietary is mainly Fe3+

Factors Favouring:
1. Gastric secretion convert Fe3+ to Fe2+ (HCL)
2. Ascorbic acid and reducing substances favored absorption (Vit C)

Factors Hindering:
1. Phytate → found in plant based diets
2. Polyphenols → Black and herbal tea, coffee, wine, legumes, cereals, fruit
3. Calcium → Inhibits both heme and non-heme iron at point of initial uptake into enterocytes
4. Animal proteins → Casein, whey, egg white and soy protein
5. Oxalic acid → Found in spinach, chard, beans
6. Proton pump inhibtors → Omeprazol

Question 3

Describe the Transport of Iron

Answer 3

For Non-Haem Iron:
1. It is absorbed as such into intestinal mucosal cells
2. Then it is transported into enterocytes by protein Divalent Metal transporter (DMT1). Vitamin C enhances absorption of nonheme Fe because it is the coenzyme for duodenal cytochrome b
3. Duodenal cytochrome b, a ferrireductase, reduces Fe3+ → Fe2+

For Haem Iron:
1. Intestinal uptake of heme by a heme carrier protein HCP)
2. Within the enterocytes, Heme oxygenase releases Fe2+ from the heme inside the entereocyte.

-when iron demand is low, Fe2+ is oxidized to Fe3+ and stored by ferritin
-when iron demand is high,Fe2+ is transported across basolat membrane into blood by ferroportin
hephaestin and ceriloplasmin oxidized Fe2+ to Fe3+

Question 4

Describe the Storage of Iron

Answer 4

Iron is stored mostly in the liver, spleen, as ferritin or haemosiderin

Ferritin is a protein with a capacity of about 4500 iron ions per protein molecule

Ferritin is the major form of iron storage but at higher concentrations, iron is also stored as haemosiderin.

Question 5

Interpret the laborotary investigations to assess iron status (plasma iron ,TIBC, ferritin, and transferrin)

Answer 5

Total Iron Binding Capacity (ug/dL) (TIBC) ⇒ Maximum amount of iron that can be bound by transferring if this were 100% saturated
→ Transferrin saturation is the amount of iron that is bound to transferrin, expressed as a % of the TIBC.

Fe panel ranges:
1. Serum Ferritin ⇒ 40 - 15 ug/ml
2. Total Iron ⇒ 60-170mcg/dL
3. TIBC ⇒ 240 - 450 mcg/dL
4. Transferrin saturation ⇒ 20% to 50%

Question 6

Describe the Iron deficiencies when there is excess

Answer 6

Fe (Excess)
1. Acquired (Haemosiderosis)
→ Accidental ingestion (common in children <6y/o) results in excessive iron accumulation in tissues due to high dietary intake
→ Repeated blood transfusion
→ Liver disease
→ Presents as visible hemosiderin staining or pigmentation.

2. Genetic (Hereditary Haemochromatosis)
   → Prevalent in Northern european ancestry (AR)
   → Mutation in the HFE gene
   → Chronic hyperabsorption of dietary iron.
   → Presents as hyperpigmentation with hyperglycaemia (bronze diabetes) and damage to the liver.

In excess, the lab investigation has:
1. Elevated plasma iron
2. Transferring becomes 75%-90% saturated
3. Plasma Ferritin is elevated

Question 7

Describe the iron disorders of deficiency

Answer 7

Due to:
1. Low intake (most inaemia in developed countries)
2. Lack of adequate iron absorption due to exposure to oxygen → Iron then forms a highly insoluble oxide.
3. Fe deficiency resulting microcytic or hypochromic anemia

Iron Deficiency Anemia (IDA)
Caused by:
1. Deficient iron intake (poor diet)
2. Increased requirements of iron (pregnancy / menstruation)
3. Impaired absorption of iron (intestinal causes)
4. Excessive loss of iron (in case of bleeding)
→ Results in decreased hemoglobin synthesis and, consequently decreased RBC size.

Lab investigation:
1. Low plasma ferritin
2. Low plasma iron
3. Microcytic hypochromic anemia
4. High red cell distribution width

Diagnosis of IDA is challenging when there is coexisting inflammation, as the ferritin can be up to 100ug/L. Ferritin levels rise during the acute phase inflammation.
→ Still, Ferritin is the best indicator of iron deficincy and a low ferritin alone is diagnostic of IDA.