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Iron
Metabolism
John Santangelo
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Extravascular Pathway for RBC Destruction
Hemoglobin
Haem
Fe2+
Recycled
Globin
Phagocytosis & Lysis
Amino Acids
ferrous (Fe+2) is
more readily
absorbed in the
small intestine
than the ferric (Fe
+3) form, which is
not very soluble.
Bilirubin
Excreted
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The History of Iron
The importance of dietary iron has been recognizedfor centuries.
In 4000 BC the Persian physician, Melampus, gave
iron supplements to sailors to make up for the ironlost from bleeding wounds.
In the 17th century, chlorosis was treated with iron.
It wasnt until 1932 that the value of iron therapy
was proven.
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Iron Exists in several oxidation
states.
There are 2 forms of iron:
Heme; animal
Non-heme; plants
In the human body and food, iron exists inFerric (Fe+3) andferrous (Fe+2) forms.
Heme contains the iron bound to the porphyrin
ring, called a metalloporphyrin.
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ferrous (Fe+2) is more readily
absorbed in the small intestinethan the ferric (Fe +3) form, which
is not very soluble.
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Iron in human body
Total iron in human body ~3.8 g (men),~2.3 g (women);
Iron is localized mostly in cells;
1-2 mg are taken up from food (10 % absorption);
1-2 mg are released with skin and gut tissues.
Fe metabolism is conservative;
Transferrin is the major Fe binder in blood plasma.
Most ferritin is found in hypatocytes (liver), spleen,
bone marrow;
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Storage and Excretion
StorageIron is delivered by transferrin to the liver, bone marrow and spleen.
Primary storage form of iron is Ferritin in cells and tissues.
Secondary storage form of iron is Hemosiderin (protein).
Stored more in the liver, then bone marrow and spleen.
ExcretionNot needed iron as ferritin it is excreted with the mucosal cells that are
shed off into the lumen of GI tract every 2-3 days.Most iron is lost from the GI Tract,, then skin, kidney.
Small amount lost in urine.
During menstrual cycle lost iron accounts for 17.5mg per cycle.
Every mL ofBlood contains 0.5 mg iron.
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Functions of Iron
Cofactor for enzymesHeme dependent enzymes used in:-
-Oxygen transport and storage
-Electron transport, energy metabolism and detoxification of
drugs
-Antioxidant-Defense mechanism by binding free iron to ensure bacteria
does not use it to grow fight infection.
-DNA synthesis and cell replication -as amino acid metabolism.
-Thyroid hormone production
Non heme dependent enzymes used in:-
-Neurotransmitters, and pro-oxidant functions
-Regulation of intracellular iron by levels of transferrin receptors
present
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Interactions
Vitamin C- Improves iron absorption. Ascorbic acid forms a
chelate with nonheme iron, which remains soluble in the smallintestine therefore increasing intestinal absorption of non heme
iron.
Vit. C rich foods should be eaten at the same meal as iron source.
Vitamin A- Deficiency in vitamin A may intensify iron deficiencyanemia.
Low plasma retinol concentrations are associated with decreased
iron.
Combination of Vit. A and iron, together, seems to improve anemia
Copper- Required for iron transport to the bone marrow for RBC
production.Zinc- Iron and zinc supplements taken together withoutfood can
inhibit the absorption of Zinc.
Solution: Dont take supplemental iron on a empty stomach.
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Interactions
Calcium- Decreases the absorption of iron when consumed
together.
Solution: Avoid consuming calcium rich foods at the same time
of a meal containing iron.
Coffee and Tea- Decreases iron absorption by 60% ! Tannins
(polyphenols) bind to iron affecting iron availability.
Solution: Do not consume coffee/tea at the time of meal
containing iron or just after.
Phytates- Interferes with iron absorption. Phytates bind
minerals such as iron, forming a complex that is insoluble and
therefore poorly absorbed,
(Found in maize, whole grains, legumes, spinich).
Solution: Avoid consumption of phytates with the iron
containing meal.
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Dietary iron1-2 mg/day
Liver1000 mg
Spleen600 mg
Plasma transferrin3 mg
Slough mucosal cell1-2 mg/day
Myoglobin300 mg
utilization
Bone marrow300 mg
Erythrocyte1800 mg
utilization
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Iron absorptionIron absorption
Fe+++
Fe++
Fe++
Fe++
ferritin
Fe+++ - transferrin
Promote absorption
-Fructose
-Vitamin C
-Heme iron
-Amino acidInhibit absorption
-Phosphate
-Phytate
-Tannin-Soil clay
HCl
Ferrous Fe++
More readily
absorbed
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Common diseases
Iron deficiency
Iron overload
Anaemia of chronic disease
Vegetarian groups
Iron Functions
Oxygen carriers
Haemoglobin
Oxygen storage
Myoglobin
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Iron Toxicity
Iron can damage tissues (Haemachromatosis)
Catalyzes the conversion of hydrogen peroxide to free-radical
ions
Free-radicals can attack:cellular membranes
Proteins
DNA
Iron excess possibly related to cancers, cardiac toxicity and
other factors
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Iron distribution
35 45 mg / kg iron in adult male body
Total approx 4 g
Red cell mass as haemoglobin - 50%
Muscles as myoglobin 7%
Storage as ferritin - 30%
Bone marrow (7%)
Reticulo-endothelial cells (7%)
Liver (25%)
Other Haem proteins - 5%
Cytochromes, myoglobin, others
In Serum - 0.1%
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Iron Transport in Blood
Red cells
As haemoglobin
PlasmaBound to Transferrin
Carries iron between body locations
eg between gut, liver, bone marrow, macrophages
Iron taken up into cells by transferrin receptors
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The serum contains about 0.1% of body iron
Over 95% of iron in serum bound to transferrin
Serum iron is a routine blood testMeasures all serum iron (not in red cells)
Low levels:
Iron deficiency
Other: Random variation; acute or chronic inflammation;
pre-menstrual.
High levels:
Iron OverloadOther: Random variation, OCP, pregnancy, recent iron
ingestion.
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Ferritin
A routine blood test reflects iron stores
Low serum levels
Indicate Iron deficiency (high specificity)
High serum levels
Iron overload
Other- Ferritin may be increased in serum by:
Tissue release (hepatitis, leukaemia, lymphoma)
Acute phase response (tissue damage, infection, cancer)Interpretation
Low levels always indicate Fe deficiency.
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Iron Loss
Physiological
Cell loss: gut, desquamation
Menstruation (1mg/day)
Pregnancy, lactation
Pathological
Bleeding
Gut, menorrhagia, surgery, gross haematuria
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Iron Deficiency
Laboratory changes:
Low iron (poor specificity)Low ferritin (excellent specificity)
Elevated Transferrin (TIBC)
Low transferrin saturationHypochromic, microcytic Anaemia
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Causes of Iron deficiency
Increased demand for iron
Infancy and adolescence
Pregnancy and lactation
Iron loss
Bleeding
Decreased iron intake or absorption
Hepciden
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In physiologic conditions
Menstruation
In pathologic conditions
Surgery,
Haemoglobinuria,
haemoptysisGastrointestinal tract pathology
In therapeutic procedures
Phlebotomy
In blood donation
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Iron DeficiencyDecreased Iron Intake or Absorption
Vegetarians or malnutrition (low-cost diet)
Malabsorption syndromes
Sprue, Ulcrative colitis, and Crohns disease
After gastric and intestinal surgery
Intestinal parasitosis
Helicobacter pyloriinfection
Autoimmune atrophic gastritis
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Iron Deficiency
Clinical Manifestations
Fatigue
Decreased exercise tolerance
Tachycardia
Dermatologic manifestations
Decreased intellectual performance
Dysphagia
Depression, increased incidence of infectionsRestless legs syndrome
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Symptoms of anemia
Fatigue
Dizziness
Headache
Palpitation
Dyspnoea
Lethargy Disturbances in menstruation
Impaired growth in infancy
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Symptoms of iron deficiency
Irritability
Poor attention span
Lack interest in surroundings
Poor work performance
Behavioural disturbances
Pica
Defective structure and function of epithelial tissue especially affected are the hair, the skin, the nails, the
tongue, the mouth, the hypopharynx and the stomach
Increased frequency of infection
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Pica
The habitual ingestion of unusual
substances
earth, clay (geophagia)
laundry starch (amylophagia)
ice (pagophagia)
Usually is a manifestation of iron deficiencyand is relieved when the deficiency is
treated
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Iron Deficiency
Clinical Manifestations
Skin and conjuctival pallor
Koilonychia
Angular cheilosis
Burning tongue
Glossitis
Hair loss (alopecia areata)
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Iron Deficiency Anemia (IDA)
Most common cause of anemia
Microcytic hypochromic anemia
MCV, MCH, MCHC are reduced blood film : small red cells (microcytic)
: pale red cells (hypochromic)
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Microcytic Hypochromic
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Megaloblastic Anaemia
(Pernicious Anaemia)
Hypersegmented Neutrophilsand
Oval Macrocytes
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Koilonychia
Spoon shaped fingernail that occurs in
Iron deficiency anaemia
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Oral iron - GI irritation
- Diarrhoea
- Constipation
IV iron - anaphylactoid
- hypotension
- muscle cramp
Side effects of Iron Therapy
Black Stools
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Iron DeficiencyDiagnosis
Microphotograph
of bone marrow
staining for iron.
Iron is stained
blue and it is
mainly in themacrophages
(lower left)
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Females 11 14 15
15 18 15
19 24 15
25 50 15
51 + 10
Pregnant 30
Lactating 1st
6
months
15
2nd
6
months
15
C ategory Age (years) R DA Iron(mg)
Infants 0 0.5 6
0.5 1 10
Children 1 3 10
4 6 10
7 10 10
M ales 11 14 12
15 18 12
19 24 10
25 50 10
51 + 10
Iron requirements (RDA)
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Laboratory findings (2)
Iron metabolism tests
serum iron concentration q
total iron-binding capacity (TIBC)o
saturation of transferrin q
serum ferritin levels q
sideroblasts q
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Response to treatment
Less irritable & increased appetite within
24 hrs
Bone marrow response by 48 hrs Increased reticulocyte count by 3rd day
Increased Hb level by 2 months
Body iron store repletion
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Hemochromatosis
Also known as accumulating disease.
This is a genetic disorder in which the
intestine is not able regulate iron absorption.
Result: iron absorption increases = build up
of excess iron = organ damage.
Most often seen in Caucasian males around
age 20
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Accumulation
Iron accumulation in tissues
causes damage/ failure to:
Liver
Heart
Pancreas
Skin
May generate free radicals which
can damage normal cells.
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Too much Iron
Haemochromotosis
Uncontrolled Iron absorption leads to Iron overload
1. Liver2. Heart
3. Pancreas
4. Skin5. Joints
Iron accumulates in: And causes:
1. Cirrhosis
2. Cardiomyopathy
3. Diabetes
4. Bronzing
5. Arthritis
It is Autosomal recessive
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Autosomal recessive
An abnormal gene on one of the autosomal chromosomes (one
of the first 22 "non-sex" chromosomes) from each parent isrequired to cause the disease.
People with only one abnormal gene in the gene pair are called
carriers, but since the gene is recessive they do not exhibit the
disease.
In other words, the normal gene of the pair can supply the
function of the gene so that the abnormal gene is described as
acting in a recessive manner.
BOTH parents must be carriers in order for a child to havesymptoms of the disease. A child who inherits the gene from
one parent will be a carrier.
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Iron studyIron study
1. Serum iron
2.Total iron binding capacity (TIBC)
3. %Transferrin saturation (% sat)
4. Ferritin
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Normal
Iron Overload
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Iron
Overload
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Haemochromatosis
Rust In Peace
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Guess who?
PrincessDiana
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Cowasaki