Blood Chemistry-IronBlood Chemistry-Iron
Iron containing compounds
1. Iron compounds involved in cellular
metabolism:-
• A – Haem. Iron compounds:
1-Haemoglobin : ...
Iron containing compounds
• B – non-haem members:
1- NADH Enzyme .
2- Succinic dehydrogenase enzyme.
2 – Those compounds r...
      Body iron storage
• Total iron body contents ≈ 4 gm. ¾ total
iron body is found in O2 carriers; Hb &
myoglobin ; and...
Approximate distribution of
body iron is:-
• Circulating Hb 60%
• Bodystores 25%
• Myoglobin 10%
• B.M 4%
• Enzymes 1%
• P...
RBC
2500mg
Plasma Fe Transferrin Carries
4mg
20mg Fe
Returned to
Immature
RBC in Bone
Marrow
Daily RBC in B.M Production t...
Daily iron losses and requirements
(WHO 2001(
Daily iron requirements
1. Iron is a one way element
3- daily iron requirement = amount lost + amount required
4- Increase...
Iron Absorption
• The average western diet contain 10-15 mg of iron daily.
Only 5-10% is absorbed.
• The main dietary sour...
Iron Absorption
• Inorganic compounds absorption is enhanced by
the presence of reducing substances, which
increase its so...
Control of iron absorption
mucosal block theory
Iron Transport & Storage
• Iron is transferred by specific carrier protein
called Transferrin.
• Transferrin is b-globulin...
Iron Transport & Storage
Iron Storage Forms
• ferritin : MW 45000, consist of 24 polypeptide
sub-unit cluster together to form hollow sphere
of 5 n...
Ferritin molecules store thousands
of iron atoms within their mineral
core. When excess dietary iron is
absorbed, the body...
Iron Storage Forms
• haemosiderin : it's not a single substance but a
variety of different, amorphous, iron- protein
compl...
Differential diagnosis of hypochromic
anaemia.
Serum Transferrin receptor
• It reflects both the number of erythroid
precursors & iron supply to the bone
marrow.
• Serum...
Disorders of iron metabolism
• The state of iron deficiency is defined as a
reduction below normal limits of the total
bod...
Stages of iron deficiency
anaemia
1- Negative iron balance:
when the rate of absorption of iron from
the diet is insuffici...
2- Latent iron deficiency:
A stage progress when the negative iron
balance persists and the body iron
stores become deplet...
3-Iron deficient erythropoiesis:
this progresses when the iron body stores
are exhausted as a result of persistence of
neg...
Causes of iron deficiency
anaemia
1- Decreased supply of iron.
2- Increased requirement for iron
1- Decreased supply of iron
• 1st : Inadequate diet: This is considered as a seldom
factor since the normal adult mixed di...
2-Increased requirement for
iron
There are three main causes of an
increased in daily iron requirement:
A. loss of blood
B...
1st
: blood loss
The most common causes of blood loss are:
• Menestruation.
• parasitic infection (Ancylostoma & necator
a...
2nd
: growth & pregnancy
Adolescence & pregnancy are known as periods of
accelerated growth. This makes iron deficiency ve...
3rd
: loss of iron
• chronic intravascular haemolysis can
result in the loss of considerable amounts
of iron as haemosidei...
Pathophysiology
Sever iron deficiency anaemia is accompanied by
a wide range of clinical manifestation, this can
be consid...
1st
: effects on blood & blood-
forming tissue
Decreased iron incorporation into the haemoglobin in the developing
erythro...
Laboratory Studies in Iron Deficiency
2nd
: General effects of iron deficiency
anaemia
• Koilonychia- Flattening or spoon of the nail.
• Angular stomatitis- atr...
Koilonychia
Anaemia of Chronic
Disorder
Anaemia of Chronic Disorder
• Chronic inflammatory or malignant
disorders frequently are accompanied by
a normocytic, norm...
Pathophysiology
• Chronic inflammation causes activation to macrophages and
upregulation of surface apotransferrin recepto...
Diagnosis of ACD
• Anemia (mainly normo-, event. microcytic)
• Inflammatory disease, cancer
• Low serum iron concentration...
H E P CIDIN
(not available in clinical
practice)
Sideroblastic Anaemia
Sideroblastic Anaemia
• The sideroblastic anaemias are heterogeneous group of
disorders, which are characterized by disord...
Sideroblastic anaemia. Erythroblasts showing
perinuclear rings of iron (Perls’ stain).
Siderocytes and sideroblasts.
• Siderocyte Mature red cell containing one or more siderotic granules
(Pappenheimer bodies)...
Hereditary Sideroblastic
Anaemia
• They are X-linked inherited diseases,
which are mostly characterized by
functional defi...
Lead Poisoning
• Chronic lead poisoning was a relatively common
condition when most drinking water was supplied via
lead p...
Investigation of lead poisoning
• Blood lead levels.
• The free erythrocyte protoporphyrin.
(Lead particularly affects the...
Secondary Sideroblastic
Anaemia
1- Drug-induced Siderblastic A naemia:
• The most common cause of this condition is
the ad...
Other investigations include
• urinary coproporphyrin
• microcytic hypochromic anaemia
• The blood film shows basophilic s...
3-Idiopathic Sideroblastic
Anaemia
• It's the disease of eldery and most common one.
It's identical to the mylodyplastic s...
Iron overload
There three commonly encountered forms
of chronic overload:
1- Hereditary haemochromatosis
2- Transfusion-as...
1-Hereditary haemochromatosis
Hereditary haemochromatosis is:
• a multi-organ disease
• inherited in an autosomal recessiv...
Pathophysiology
• One of the major sign of this condition is greatly
increased % saturation with transferrin.
• Thus, when...
Laboratory Findings
• raised serum ferritin
• reduced total iron binding capacity - TIBC
• raised iron binding saturation:...
Radiograph of hand –
patient with
haemochromatosis
showing loss of joint
space and erosion of
cartilage at the
metacarpoph...
Liver biopsy for a patient with type 1 haemochromatosis,
showing staining predominantly in parenchymal cells.
Liver biopsy for a patient with type 4 haemochromatosis,
showing iron staining predominantly in Kupffer cells.
Symptoms
Treatment
• Early diagnosis and treatment with venesection permits
the avoidance of all the complications of
haemochromato...
Prognosis
• The arthropathy, hypogonadism and
hepatic cirrhosis rarely resolve with
treatment.
• Intensively treated patie...
2-Transfusion-associated Haemochromatosis
• Patients who are completely dependent on
a program of regular blood transfusio...
3- Dietary causes
• Iron overload due to dietary causes was
reported to be a serious problem among people
who are exclusiv...
The role of iron
The role of iron
The role of iron
The role of iron
The role of iron
The role of iron
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The role of iron

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  • The main dietary sources are liver, red meat, green vegetables, spinach, supplemented cereals and fish. Dietary iron falls into one of two categories
  • The role of iron

    1. 1. Blood Chemistry-IronBlood Chemistry-Iron
    2. 2. Iron containing compounds 1. Iron compounds involved in cellular metabolism:- • A – Haem. Iron compounds: 1-Haemoglobin : O2 carrying pigment in RBCs. 2-Myoglobin : O2 carrying pigment in muscles. 3-Cytochroms: electron transport enzyme for oxidation metabolism.
    3. 3. Iron containing compounds • B – non-haem members: 1- NADH Enzyme . 2- Succinic dehydrogenase enzyme. 2 – Those compounds required for iron storage:- Transferrin. Hemosidrin. Ferritin.
    4. 4.       Body iron storage • Total iron body contents ≈ 4 gm. ¾ total iron body is found in O2 carriers; Hb & myoglobin ; and ¼ body iron is in stores.
    5. 5. Approximate distribution of body iron is:- • Circulating Hb 60% • Bodystores 25% • Myoglobin 10% • B.M 4% • Enzymes 1% • Plasma iron <0.1%
    6. 6. RBC 2500mg Plasma Fe Transferrin Carries 4mg 20mg Fe Returned to Immature RBC in Bone Marrow Daily RBC in B.M Production to Replace Old Cells 1% R.E 20mg Fe Released Daily Daily RBC Turnover of Old Cells 1% ِِABSORPTION 1-2mg ONLY ِِLoss Cells From G.I Tract 1-2mg ONLY Transferri n Carrier Myoglobin  Respspiratory Enzyme 300mg Transferri n Carrier Body Stores 1000mg (male( 300-500mg (Female) Daily Fe++ Turnover
    7. 7. Daily iron losses and requirements (WHO 2001(
    8. 8. Daily iron requirements 1. Iron is a one way element 3- daily iron requirement = amount lost + amount required 4- Increased requirement is found : • A- menstruating female / 30-60 ml of blood in each cycle .This contains between 15-30 mg iron/cycle B- pregnancy (1( Foetal/placental growth requirement. (2( Expansion in maternal mother blood volume. (3( Haemorrhage in delivery involve highly significant loss of iron. 2- absorption is increased in iron deficiency and decreased when body iron stores are deleted.
    9. 9. Iron Absorption • The average western diet contain 10-15 mg of iron daily. Only 5-10% is absorbed. • The main dietary sources are liver, red meat, green vegetables, spinach, supplemented cereals and fish. Dietary iron falls into one of two categories • Inorganic iron, which mainly is present in cereals and vegetables and Haem iron, which is found in haemoglobin and myoglobin of meat products.
    10. 10. Iron Absorption • Inorganic compounds absorption is enhanced by the presence of reducing substances, which increase its solubility, such as ascorbic acid and other chelating agents such as Fructose, glucose, succinate which forms soluble complexes with iron. Conversely, inorganic iron absorption is retarted in the presence of substances, which decrease its solubility such as phosphates and phytates, which are present in cereals and also by alkaline pancreatic secretions.
    11. 11. Control of iron absorption mucosal block theory
    12. 12. Iron Transport & Storage • Iron is transferred by specific carrier protein called Transferrin. • Transferrin is b-globulin with molecular weight of 74,000, which can carry up to two ferric ions (Fe3+( per molecule. • Iron is transported to bone marrow to developing erythroblast, which carry specific receptor to transferrin. • The receptor-transferrin complex is internalized by the erythroblast, the iron is removed for utilization in haem synthesis and the receptor and apotransferrin return to the cell surface.
    13. 13. Iron Transport & Storage
    14. 14. Iron Storage Forms • ferritin : MW 45000, consist of 24 polypeptide sub-unit cluster together to form hollow sphere of 5 nm in diameter & the stored iron form the central core of the sphere. Typically, ferritin contains about 25% of iron by weight. About 2/3 of body iron stores are present as ferritin. • If the capacity for storage of iron in ferritin is exceeded, a complex of iron with phosphate and hydroxide forms. This is called hemosiderin; it is physiologically available.
    15. 15. Ferritin molecules store thousands of iron atoms within their mineral core. When excess dietary iron is absorbed, the body responds by producing more ferritin to facilitate iron storage Ferritin Storage Molecule
    16. 16. Iron Storage Forms • haemosiderin : it's not a single substance but a variety of different, amorphous, iron- protein complexes. Typically it contains about 37% of iron by weight. Haemosiderin may represent ferritin in various form of degradation. • As the body burden of iron increases beyond normal levels, excess hemosiderin is deposited in the liver and heart. This can reach the point that the function of these organs is impaired, and death
    17. 17. Differential diagnosis of hypochromic anaemia.
    18. 18. Serum Transferrin receptor • It reflects both the number of erythroid precursors & iron supply to the bone marrow. • Serum Transferin receptor only increase in ACD in the absence of storage iron; so ferritin-transferin receptor ratio is used to diagnose ACD in general hospital practice.
    19. 19. Disorders of iron metabolism • The state of iron deficiency is defined as a reduction below normal limits of the total body iron content. • Iron deficiency anaemia is the most sever manifestation of iron deficiency, develops slowly through a series of successive stages, although progression from one stage to the next is not inevitable.
    20. 20. Stages of iron deficiency anaemia 1- Negative iron balance: when the rate of absorption of iron from the diet is insufficient to meet the daily requirement, iron is mobilized from the body stores to meet the shortfall.
    21. 21. 2- Latent iron deficiency: A stage progress when the negative iron balance persists and the body iron stores become depleted. In this stage the body is deficient in iron but erythropoiesis is still normal and no adverse physiological effects are present. Many people exist for prolonged period and never develop anaemia.
    22. 22. 3-Iron deficient erythropoiesis: this progresses when the iron body stores are exhausted as a result of persistence of negative iron balance. 4-Iron deficiency anaemia: this is the final stage of this sequence of events, which develop after the BM is affected.
    23. 23. Causes of iron deficiency anaemia 1- Decreased supply of iron. 2- Increased requirement for iron
    24. 24. 1- Decreased supply of iron • 1st : Inadequate diet: This is considered as a seldom factor since the normal adult mixed diet contain 18 mg of iron/day, although it’s considered as a contributing factor to the more rapid onset of iron deficiency due to another primary cause. • 2nd : Malabsorption of dietary iron: This relatively a common complication of diseases of the upper alimentary tract such as coelic disease. Partial gastrectomy or chronic anti-acid ingestion are major causes for the absence of stomach acid and subsequently impairs the absorption of dietary iron.
    25. 25. 2-Increased requirement for iron There are three main causes of an increased in daily iron requirement: A. loss of blood B. growth & pregnancy C. loss of iron
    26. 26. 1st : blood loss The most common causes of blood loss are: • Menestruation. • parasitic infection (Ancylostoma & necator americanus). • Carcinoma, • duodenal ulcer. • hiatus hernia. • haemoroids and menorrhgia.
    27. 27. 2nd : growth & pregnancy Adolescence & pregnancy are known as periods of accelerated growth. This makes iron deficiency very common. For example: • In normal, uncomplicated pregnancy, maternal total red cell volume increases 20%-40%. This imposes an extra requirement for iron of up to 500mg. • The developing feotus, requires about 300mg. • Blood loss at delivery is compounded the iron balance. • The excess requirement for iron in pregnancy is offset partially by amenorrhea which saves about 200mg of iron.
    28. 28. 3rd : loss of iron • chronic intravascular haemolysis can result in the loss of considerable amounts of iron as haemosidein in the urine.
    29. 29. Pathophysiology Sever iron deficiency anaemia is accompanied by a wide range of clinical manifestation, this can be considered under two main headings: • Effects on the blood & blood-forming tissue • Effects on other tissue
    30. 30. 1st : effects on blood & blood- forming tissue Decreased iron incorporation into the haemoglobin in the developing erythroblast leads to: • Decreased Hb concentration denoted by decreased MCHC • Increased free protoporphyrin concentration within the cell • Mature microcytic red blood cell due to extra mitotic division before the nucleus die. • Thus, the anaemia which accompain iron deficiency anaemia typically is hypochromic and microcytic. • Reticulocytopenia is present. • The bone marrow represents erythroid hypoplasia, decreased macrophage iron and normoblast have ragged cytoplasm. • One of the whole mark in the iron deficiency anaemia is the combination of raised TIBC with reduced % saturation of transferrin and decreased iron concentration. Ferritin levels are also reduced.
    31. 31. Laboratory Studies in Iron Deficiency
    32. 32. 2nd : General effects of iron deficiency anaemia • Koilonychia- Flattening or spoon of the nail. • Angular stomatitis- atrophic lessions at the corner of the mouth. • Glossitis- smoothed, inflamed tongue. • Atrophic gastritis- inflammation of the lining of the stomach • Achlorhydria- decrease in gastric secretion • Pica: Soil-geophagia & Ice- pagophagia
    33. 33. Koilonychia
    34. 34. Anaemia of Chronic Disorder
    35. 35. Anaemia of Chronic Disorder • Chronic inflammatory or malignant disorders frequently are accompanied by a normocytic, normochromic anaemia, which is refractory to all treatment except that which causes regression of the primary condition. This form of anaemia is known as anaemia of chronic disorders (ACD).
    36. 36. Pathophysiology • Chronic inflammation causes activation to macrophages and upregulation of surface apotransferrin receptors. Binding of significant quantities of apotransferrin to macrophage reduces TIBC. • Inflammation also stimulates neutrophils to synthesis and release large quantities of apolactoferrin, which acts as iron binding protein. The apolactoferrin is bound to specific receptors on the activated macrophages and acts like a magnet for the circulating iron. Any iron that is bound to the apolactoferrin:receptor complex is internalized by the macrophage and stored as ferritin. Thus increasing tissue iron stores. • Erythropoietic activity of the BM is suppressed in ACD. This most likely to be caused by the release of growth inhibitors such as IL-1, γ-interferon and tumor necrosis factor in response to the primary condition. RBC life span is also reduced.
    37. 37. Diagnosis of ACD • Anemia (mainly normo-, event. microcytic) • Inflammatory disease, cancer • Low serum iron concentration • This could be true also for iron deficiency anemia • FERRITIN – increased • TRANSFERRIN – decreases • IRON STORES – sufficient
    38. 38. H E P CIDIN (not available in clinical practice)
    39. 39. Sideroblastic Anaemia
    40. 40. Sideroblastic Anaemia • The sideroblastic anaemias are heterogeneous group of disorders, which are characterized by disordered incorporation of iron within the haem in developing erythroblasts. • The resulting toxic accumulation of iron in the mitochondria of erythroblast leads to the formation of iron encircling the nuclei (ringed sideroblast) and ineffective erythropoiesis ensues. However, ringed sideroblasts are not specific indicators of sideroblastic anaemia: they are frequently found in leukaemia, megaloblastic anaemia and alcoholism. • The sideroblastic anaemias are classified according to their aetiology as: • Hereditary • Secondary or idiopathic
    41. 41. Sideroblastic anaemia. Erythroblasts showing perinuclear rings of iron (Perls’ stain).
    42. 42. Siderocytes and sideroblasts. • Siderocyte Mature red cell containing one or more siderotic granules (Pappenheimer bodies) • Normal sideroblast Nucleated red cell containing one or more siderotic granules, granules few, difficult to see, randomly distributed in the cytoplasm, reduced proportion of sideroblasts in iron deficiency and anaemia of chronic disorders • Abnormal sideroblasts Cytoplasmic iron deposits (ferritin aggregates): increased granulation, granules larger and more numerous than normal, easily visible and randomly distributed, proportion of sideroblasts usually parallels the percentage saturation of transferrin (e.g. haemolytic anaemia, megaloblastic anaemia, iron overload, thalassaemia disorders) Mitochondrial iron deposits (non-ferritin iron): ring sideroblasts in inherited and acquired sideroblastic anaemias
    43. 43. Hereditary Sideroblastic Anaemia • They are X-linked inherited diseases, which are mostly characterized by functional deficiencies of enzymes of the haem synthetic pathway, most commonly δ-aminolaevulinic acid (δ-ALA) synthetase or ferrochelatase. • Affected male have hypochromic, dimorphic anaemia with mild ineffective erythropoiesis and erythroid hyperplasia.
    44. 44. Lead Poisoning • Chronic lead poisoning was a relatively common condition when most drinking water was supplied via lead pipes. • Lead is absorbed by inhalation or ingestion. • Most absorbed lead accumulates in bone & bone marrow. • In bone marrow, lead is associated with red cell precursors and more specifically with mitochondrial membranes and disrupts haem synthesis. • This leads to sever sideroblastic changes. • Lead also cause damages to red cell membrane and inhibits glycolytic activity. • These two activities result in mild haemolysis which contributes to anaemia of chronic lead poisoning.
    45. 45. Investigation of lead poisoning • Blood lead levels. • The free erythrocyte protoporphyrin. (Lead particularly affects the enzymes involved in haem synthesis; thus a screening test for early lead poisoning is the measurement of haem precursors). • An abdominal radiograph may show radio-opaque lead fragments in the gastrointestinal tract. • Also lead lines may be seen on examination of a radiograph of bony structures because lead interferes with the growing ends of bones.
    46. 46. Secondary Sideroblastic Anaemia 1- Drug-induced Siderblastic A naemia: • The most common cause of this condition is the administration of drugs such as Chloramphenicol and alcohol. These drugs inhibit the synthesis of δ A L A synthetase and ferrochelatase. • The blood picture is the same as in hereditary sideroblastic anaemia.
    47. 47. Other investigations include • urinary coproporphyrin • microcytic hypochromic anaemia • The blood film shows basophilic stippling in the red cells and reticulocytosis. The basophilic stippling result of the acculmulation of pyrimidine nucleotides in the cytoplasm and is only present in the youngest red cells.
    48. 48. 3-Idiopathic Sideroblastic Anaemia • It's the disease of eldery and most common one. It's identical to the mylodyplastic syndrome refractory anaemia with sideroblast (RAS). • Characteristic dyserythropoietic changes include macrocytosis, poikilocytosis, basophilic stippling and ringed sideroblast affecting all stages of erythroblast development. • In the early stages of the disease platelets and leucocytes appear normal.
    49. 49. Iron overload There three commonly encountered forms of chronic overload: 1- Hereditary haemochromatosis 2- Transfusion-associated haemochromatosis 3- Dietary causes
    50. 50. 1-Hereditary haemochromatosis Hereditary haemochromatosis is: • a multi-organ disease • inherited in an autosomal recessive manner • the most common genetic disease in Northern Europe • The disease results from the excessive absorption of iron which is subsequently deposited in tissues such as the pancreas, heart and liver. • The normal body content of iron is 2-6 g; patients with haemochromatosis may have 50-60 g.
    51. 51. Pathophysiology • One of the major sign of this condition is greatly increased % saturation with transferrin. • Thus, when iron is absorbed inappropriately and released in circulation some may be unable to bind to transferrin because it's already fully saturated. • About 30% of the circulating iron exists as ferric or ferrous and waiting for binding sites to be available. • These ionic iron acts as a catalyst for formation of toxic oxygen radicals in the presence of NADPH. • Oxygen radical compound are short-lived and extremely reactive causing extensive localized tissue damage. • The most common one is hydroxyl radical (OH.). • Accumulated organ damage can result in hepatic cirrhosis, skin pigmentation, diabetes and congestive heart failure.
    52. 52. Laboratory Findings • raised serum ferritin • reduced total iron binding capacity - TIBC • raised iron binding saturation: – >60% transferrin saturation in males – >50% transferrin saturation in females • liver biopsy for parenchymal iron deposition • exclusion of secondary causes by examination of a blood film, and if necessary, the bone marrow. (The patient's siblings should be screened by measurement of iron, TIBC and genetic Screening tests.)
    53. 53. Radiograph of hand – patient with haemochromatosis showing loss of joint space and erosion of cartilage at the metacarpophalangeal joints.
    54. 54. Liver biopsy for a patient with type 1 haemochromatosis, showing staining predominantly in parenchymal cells.
    55. 55. Liver biopsy for a patient with type 4 haemochromatosis, showing iron staining predominantly in Kupffer cells.
    56. 56. Symptoms
    57. 57. Treatment • Early diagnosis and treatment with venesection permits the avoidance of all the complications of haemochromatosis. • At first venesection should be performed weekly, and each time the patient attends a full blood count should be done, as well as checking the liver function. Iron, TIBC and ferritin should be checked monthly. • Venesection stops when haemoglobin reaches 10 g per dl, and follow up is by checking bloods and venesection every three months. • Chelation with desferrioxamine may be tried in rare patients who cannot tolerate venesection because of cardiac failure or anaemia.
    58. 58. Prognosis • The arthropathy, hypogonadism and hepatic cirrhosis rarely resolve with treatment. • Intensively treated patients show an 11% five year mortality rare compared to 67% in those not treated. • Hepatocellular carcinoma, cardiac disease and liver failure are the main causes of death.
    59. 59. 2-Transfusion-associated Haemochromatosis • Patients who are completely dependent on a program of regular blood transfusion as in thalassemia are exposed to extensive iron intake, which can't be excreted. • Each transfusion of 400ml carries with it 200ml of iron. • Steady accumulation of iron can lead to haemochromatosis. This can be removed by administration of chelating agent.
    60. 60. 3- Dietary causes • Iron overload due to dietary causes was reported to be a serious problem among people who are exclusively cooking in iron pots. • Acute iron poisoning due to ingestion of large number of iron tablets for therapeutic use is one of the most common causes of fatal poisoning in young children. • Chronic use of iron supplements in the absence of iron deficiency can lead to iron overload, because iron is absorbed by passive diffusion across the gut in this condition regardless of the state of the body iron stores.
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