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- Rama Nada

-Ensherah Mokheemer

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Don’t forget to refer to page index wherever you see *

Quick revision:

In the previous lecture we said that:

- your body contains 4-5g of iron (4g in females & 5g in males)

- in the environment iron is found in two forms; ferric (Fe+3) &

ferrous (Fe+3), but the body can benefit only from the ferrous iron

(it’s the form that being absorbed in the intestine).

- In the body there are two types of iron; non-heme iron & heme

iron.

Heme iron Non-heme iron Absorbed as a whole structure Must be dissolved before uptake

Absorbed more efficiently from the whole small intestine

Absorbed poorly and only from the duodenum

From animal food sources only From plant sources

- The absorption of heme iron occurs in the whole small intestine

and very little amount is absorbed in the colon.

The doctor revised the length of each part of the small intestine:

Duodenum: 26 cm, jejunum: 2.5 meter, ileum: 3.5 meter.

- The absorption of non-heme iron is restricted to the duodenum.

- The majority of the body’s iron supply comes from the jejunum.

- The amount of iron that is absorbed from the lumen of the

intestine is equal to the amount of iron that is lost from the body.

- The daily intake of iron is 15-20 mg, only 3-6% of this amount is

being absorbed.

- Iron is bound to transferrin to be transported in the plasma, while

it’s bound to a protein called ferritin to be stored in the cells

Now we’ll start the new lecture…

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Look to the different five groups in the previous table:

- The loss is different therefor the need is different.

- The estimated unit is mg/day.

- The first group (Adult male & post-menopausal female): the total

daily requirement ranges from 0.5 to 1 mg and the total daily loss

is 0.5 to 1 mg.

- The doctor continued to read the rest of the groups from the

table…

- Note that the total daily need is equal to the total daily loss

- The stared groups (menstruating females, pregnant female and

female (age 12-15)) are more likely to develop iron deficiency.

- Iron daily requirement ranges from 0.5 to 3 mg.

The distribution of iron in the body:

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- The total amount of iron in the body ranges from 4g in females

and 5g in males, the majority of this iron is in haemoglobin (65%).

- 30% of iron is bound to ferritin & hemosiderin to be stored in

hepatocytes (in the liver).

- 3.5% is found in myoglobin*.

- Note the difference in the amount of iron between males and

females in all aspects.

Factors favouring and factors reducing

we said in the previous lecture that there is enzyme in the small

intestine reduces ferrous from ferric in addition to other factors such as

acidity*, the following table shows the factors which favour iron

absorption and the factors which reduce iron absorption:

Note that:

- The first six favouring factors are opposite to the first six reducing

factors.

- In poor groups of people where there is high consumption of tea

and phytates** there are higher likelihood to develop iron

deficiency anaemia.

Causes of iron deficiency

*it is an iron- and oxygen-binding protein found in the muscle tissue *the acidity of stomach is stronger than the acidity of lemon juice **it is the storage form of phosphorous in many plant tissues, such as: bran, seeds, cereals and grains. So, it presents in large amount in bread.

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Causes of iron deficiency

The doctor read the table but for the gastrointestinal blood loss he only

mentioned: peptic ulcers, aspirin ingestion, piles (haemorrhoids).

Factors affecting erythropoiesis

1- Oxygen supply; tissue oxygenation is the most essential regulator

of RBCs production.

2- Vitamins; B12 & Folic acid mainly.

3- Iron

4- Proteins; haemoglobin is mainly protein.

5- Trace elements; copper & cobalt*.

6- Healthy bone marrow; where erythropoiesis occurs

7- Liver functions: storage, protein synthesis and hormone synthesis

8- Hormones; erythropoietin, androgen, thyroid hormone, growth

hormone, and corticosteroids.

* The most critical determinants of hemoglobin concentration are availability of iron and the presence of

heme. Thus, anything affecting the availability of iron might also affect the synthesis of heme and

hemoglobin. Copper, zinc, cobalt, manganese, and cadmium, because of their similarity in physiochemical

characteristics to iron, are able to interfere with normal iron metabolism and, consequently, heme and

hemoglobin synthesis.

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Haemoglobin

1- The structure of hemoglobin; it’s mainly protein

• Hemoglobin concentration in males is 16 g/100mL blood, while its

concentration in females is 14g/100mL blood. To consider one figure we say

15g/100mL.

• Each hemoglobin molecule is composed of four subunits; 2 α and 2 β,

in the case of adult hemoglobin.

• Each α subunit contains 141 amino acids, while each β subunit

contains 146 amino acids.

• Each subunit binds one heme molecule and each heme molecule binds

one oxygen molecule (two atoms), thus one hemoglobin molecule

carries 4 oxygen molecules (8 atoms)

How many oxygens each RBC can carry?

Each hemoglobin can carry 4 O2's. One RBC contains 250 million Hb

molecules (1 RBC can carry as many as 1 billion molecules of O2)

Hemoglobin structure

Heme (Metalloporphyrin); 4% Globin (protein part); 96%

Iron protoporphyrin

Function: it carries oxygen

(reversible binding)

Function: it carries CO2, H+ and

2,3-BPG (reversible binding)

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2- Hemoglobin synthesis

• 65% of hemoglobin synthesis occurs in the Erythroblasts, those cells

have nuclei and the remaining (35%) occurs in the reticulocyte, those

cells have fragmented nuclei.

The synthesis of hemoglobin take place in two distinct areas:

Globin synthesis:

- The synthesis of globin part (protein) occurs in the ribosomes in

the cytosol.

Heme synthesis:

1- Heme synthesis that takes place in the mitochondria begins by the

condensation (binding) of glycine with succinyl CoA, under the

effect of delta-amino levulinic acid (delta-ALA), vitamin B6 is a

coenzyme here. This step is stimulated by erythropoietin and

inhibited by the heme.

2- The resulted substance from step 1 is undergo further reactions to

form protoporphyrin.

3- 4 Protoporphyrin will bind to 4 iron to form 4 heme molecules

4- 4 heme molecules will bind 4 globin subunits (2 α and 2 β) to form

one hemoglobin molecule

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.

The causes of hypochromic microcytic anaemia

In this type of anaemia, the cells are small (microcytic), MCV is less than

70 fL or 70 μm3, and contain low hemoglobin (hypochromia).

1- Lack of iron (iron deficiency)

2- Problem in iron release from macrophages to serum (anaemia of

chronic inflammation or malignancy)

3- Failure of protoporphyrin synthesis (this causes sideroblastic

anaemia)

4- Failure of globin synthesis (this causes α or β thalassaemia)

5- Lead also inhibits haem and globin synthesis

Note that the problems are either in Iron or Protoporphyrin or

Globin

1 2

3

4

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The doctor read these notes from slides:

• Iron deficiency anemia is estimated to affect about 30% of the world

population.

• Iron deficiency anemia is still the most important deficiency related to

malnutrition.

• Iron deficiency anemia (IDA) and thalassaemia (TT) are the most

common forms of hypochromic microcytic anemia.

• IDA is a common clinical problem throughout the world and an

enormous public health risk in developing and even in industrialized

countries.

• Traditionally, several methods other than serum ferritin were used to

assess IDA (to be discriminated from thalassemia).

- 1gram hemoglobin carries 1.34mL Oxygen (almost constant).

- 100mL plasma carry 0.3 mL of Oxygen.

- You can calculate how many mL of oxygen is present in your body

(the whole blood) by the following method:

In 100 mL blood there is 15gram Hb (remember 15% in average), so:

1gram Hb 1.34 mL Oxygen

15gram Hb X

X= 15gram x 1.34mL= 20g/mL (20gram oxygen in 100 mL of blood)

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When heme binds oxygen we say oxidation or oxygenation? And

what is the difference?

It’s called oxygenation, because the binding here is reversible, this

means that heme will eventually release the oxygen.

If it was irreversible then it will be oxidation (not the case here).

Types of hemoglobin

We discussed previously two types of hemoglobin; fetal hemoglobin

(HbF) & adults hemoglobin (HbA), there are still other types

mentioned in the following table:

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- There are 6 types of Hb, the lower three are found only in the

embryo (in the first trimester), while the first three are found in

the embryo, newborn as well as adults.

- The proportion of fetal Hb in adults is usually less than two

(around 1-1.5%), but there are some people have higher than that

almost up to 2% , we still considered it normal, but if the fetal

haemoglobin is higher than 2% in this case we consider it

abnormal.

- In new-borns 80% of Hb is fetal Hb, its replaced gradually by adult

Hb and eventually totally (90%) by the sixth month after birth, this

is the usual case sometimes it extends to the ninth month, but its

important to become normal (around 2%) at the end of the first

year.

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Besides hemoglobin, heme is part of the structure of other proteins like:

Myoglobin an oxygen binding pigment found in red (slow) muscle.

Neuroglobin an oxygen binding globulin in the brain

(it carries oxygen in the nervous system).

Sorry for any mistake

Best of luck

97%

1% 2.50%

In newborns

HbA HbF HbA2

97%

1% 2.50%

In adults

HbA HbF HbA2