Rama Nada. -Ensherah Mokheemer. 1 P a g e

Transcription

1 - 3 - Rama Nada -Ensherah Mokheemer - 1 P a g e

2 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 Absorbed as a whole structure Absorbed more efficiently from the whole small intestine From animal food sources only Non-heme iron Must be dissolved before uptake Absorbed poorly and only from the duodenum 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 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 2 P a g e

3 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: 3 P a g e

4 - 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) % 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. *it is an iron- and oxygen-binding protein found in the muscle tissue *the acidity Causes of stomach of iron is stronger deficiency 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 4 P ain g e large amount in bread.

5 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. 5 P a g e

6 Haemoglobin 1- The structure of hemoglobin; it s mainly protein 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) 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 O 2 's. One RBC contains 250 million Hb molecules (1 RBC can carry as many as 1 billion molecules of O 2 ) 6 P a g e

7 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 7 P a g e

8 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 8 P a g e

9 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) mL 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 15gram Hb 1.34 ml Oxygen X X= 15gram x 1.34mL= 20g/mL (20gram oxygen in 100 ml of blood) 9 P a g e

10 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: 10 P a g e

11 - 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. 11 P a g e

12 In newborns 1% 2.50% 97% HbA HbF HbA2 In adults 1% 2.50% 97% HbA HbF HbA2 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 12 P a g e