Mineral Metabolism PDF

Mineral metabolism Definition of Minerals They are inorganic elemental atoms that are nutritionally essential. They are not changed by digestion or metabolism. Functions of Minerals Some participate with enzymes in metabolic processes (cofactors) Some have structural fun...

Mineral metabolism Definition of Minerals They are inorganic elemental atoms that are nutritionally essential. They are not changed by digestion or metabolism. Functions of Minerals Some participate with enzymes in metabolic processes (cofactors) Some have structural functions (Ca, P in bone; S in keratin) Acid-base and water balance (Na, K, Cl) Nerve & muscle function (Ca, Na, K). Other functions: Iron → help in building the vital oxygen carrier hemoglobin. Iodine → builds thyroid hormone, regulates the rate of all body metabolism. Cobalt → the central core of vitamin B12. Chlorine→ in hydrochloric acid in the stomach. Minerals in Foods -Found in all food groups. -More reliably found in animal products. -Often other substances in foods decrease absorption (bioavailability) of minerals *Oxalate, found in spinach, prevents absorption of most calcium in spinach. *Phytate, form of phosphorous in most plants makes it poorly available. Classification 1-Macro or Major Minerals 1. They are required in amounts greater than 100 mg/day. 2. They include 7 elements: Sodium, potassium, magnesium, calcium, phosphorus, sulfur, chloride. 2-Micro or Trace minerals (body needs relatively less) 1. They are required in amounts less than 100 mg/day. 2. They include 12 elements: chromium, cobalt, copper, fluoride, iodine, iron, manganese, molybdenum, selenium, zinc, silicon and nickel Macrominerals I. Calcium Sources: 128 1. Milk and milk products (the richest sources). 2. Beans, leafy vegetables and egg yolk. Absorption: 1. Site: upper small intestine. 2. Absorption of calcium is active process and requires calcium binding protein present in the intestinal mucosal cells. 3. Absorption is regulated by: a) Vitamin D: [1,25 dihydroxy cholecalciferol]: through the formation of calcium binding protein (calbindin). b) Parathyroid hormone: Increase calcium absorption through the conversion of vitamin D to 1,25 dihydroxy cholecalciferol in the kidney. 4. Factors affecting calcium absorption: a) Factors promoting calcium absorption: 1) High protein diet: Amino acids form with calcium a soluble calcium salts which are easily absorbed. 2) pH: an acidic pH in the upper small intestine is essential for calcium absorption. 3) High dietary lactate or citrate: that form soluble salts with calcium. b) Factors inhibiting calcium absorption: 1) High dietary phosphate, oxalate and phytate: which form insoluble salts with calcium. 2) Alkalinity: excessive alkali intake (as during treatment of peptic ulcer) decreases calcium absorption. 3) Impaired fat absorption: fatty acids form insoluble calcium soaps with calcium. Body calcium: Calcium is the most abundant mineral in the body (about 1200 grams). 1) 99% present in bones and teeth: in the form of hydroxyapatite: 3 Ca3 (PO4)2Ca(OH)2 a) Calcium salts in bones are not inert. They are in a constant state of turnover in skeleton being deposited in sites of bone formation and released at sites of bone resorption. In adult male about 700 mg calcium enter and leave bones each day. b) Calcium in bones acts as a reservoir, which helps to stabilize calcium ions in plasma and extracellular fluid. 129 c) Parathyroid hormone and active vitamin D stimulate osteoblasts while estrogen hormone inhibits osteoclasts. Thus after menopause= ↓estrogens -↓ bone mass (osteoporosis). 2) 1 %: of calcium is present in body fluids and other tissues. Plasma calcium: Level: 8.5 - 10.5 mg I dl. 1. Blood calcium lies entirely in the plasma (No calcium in RBCs). 2. Forms: Plasma. calcium is present in 2 forms; ionized and non ionized. a) Ionized: (50 %) It is the active fraction. Its deficiency causes tetany. b) Non ionized: (50 %) (Diffusible) Complexes with organic ions e.g. citrate: (5 %). (non diffusible) It is bound to protein mainly albumin (45%). Its deficiency occurs with conditions of hypoproteinemia and causes no tetany. 3. Factors affecting plasma calcium (calcium homeostasis): a) Hormonal regulation: Three hormones are concerned with regulation of blood calcium. These are parathyroid hormone, active vitamin D (calcitriol) and calcitonin. 1) Parathyroid hormone (PTH): It increases plasma calcium level through: i- Mobilization of calcium from bones (bone resorption). ii- Absorption of calcium from intestine (through conversion of vitamin D into calcitriol "active vitamin D" in the kidney). iii- Reabsorption of calcium by renal tubules i.e. ↓Ca2 excretion in urine and ↑ phosphate excretion. 130 2) Calcitriol: 1,25 dihydroxycholecalciferol: It increases blood calcium level through: i- Absorption of calcium from the intestine. ii- Reabsorption of calcium by renal tubules. iii- Mobilization of calcium from bones. 3) Calcitonin: It is a hormone that is secreted by the parafollicular. or "C" cells of the thyroid gland. It is released in response to hypercalcaemia and causes decrease of blood calcium level through inhibition of calcium mobilization from bones, or increasing calcium deposition in bones. b) Other factors: 131 1) Solubility product: Normally Ca/P ratio must be constant. Ca x P in children is 50 and in adults are 40. If plasma phosphate increases {as in renal failure) the plasma, calcium decreases to keep the ratio constant. 2) Blood pH: Ionization of calcium occurs at normal blood pH, 7.4. The more the acidosis of the blood pH, the more formation of ionized calcium. 3) Plasma proteins: In cases of hypoproteinemia, the non-diffusible calcium decreases. Functions of calcium: 1. Calcification of bones and teeth. 2. Regulation of transmission of nerve impulses. 3. Regulation of contraction of muscles. 4. Decrease of neuromuscular excitability. Deficiency of ionized calcium leads to tetany. 5. Cardiac conduction. 6. Calcium acts as a second messenger for hormonal action by acting together with calmodulin and cAMP. 7. Blood and milk clotting. 8. Maintenance of cell membrane permeability. 9. Activation of certain enzymes e.g. pyruvate kinase. Excretion: 1. Most of calcium excretion is eliminated with feces. 2. Small amount of calcium is excreted in urine (about 200 mg/day). Requirements: Adult man and women: 800 mg / day Pregnant, lactating and postmenopausal women: 1500 mg / day Infants (less than 1 year): 300 - 500 mg / day 132  Children (1 – 18 years) : 800 - 1200 mg / day Abnormal plasma calcium: 1. Hypercalcemia: Causes: 1) Primary hyperparathyroidism: usually due to adenoma (benign tumor). Serum calcium usually ranges 12-20 mg/dl. 2) Ectopic cells as in some malignancy -+ t PTH 3) Excess intake of vitamin D: or calcium or both. Usually it is due to over dosage or self-medication with vitamin D. 4) Milk-alkali syndrome: This is hypercalcemia present in patients who received, for long periods, excessive absorbable alkalies and milk (source of calcium), for the treatment of peptic ulcer. 5) Bone diseases: (bone resorption) As in malignancy, leukemia, multiple myeloma. 6) Drugs: As thiazide diuretics. 7) Other causes: As thyrotoxicosis, Cushing's syndrome. Effects: Stone formation: e.g renal stones. Calcification in different tissues. Treatment diuretics, Corticosteroids. 2. Hypocalcemia: Causes: 1) Hypoparathyroidism. 2) Alkalosis. 3) Kidney diseases where activation of vitamin D is inhibited. Effects: 1) Acute deficiency: if ionized calcium is much decreased, tetany results. 2) Chronic deficiency: In children, Rickets and in adults, Osteomalcia (osteoporosis). Rickets: Is a disorder of defective calcification of bone. This may be due to a low levels of vitamin D in the body or due to a dietary deficiency of Ca and P or both. Osteoporosis: Is characterized by demineralization of bone resulting in the progressive loss of bone mass. 133 Occurrence: The elderly people (over 60 years) of both sexes are at risk for osteoporosis. However, it more predominantly occurs in post-menopausal women which are the major cause of disability among the elderly. Etiology: The ability to produce calcitriol from vitamin D is decreased with age, particularly in the postmenopausal women. Deficiency of sex hormones in women has been implicated in the development of osteoporosis. Treatment: Estrogen administration along with Calcium supplementation in combination with vitamin D to postmenopausal women reduces the risk of fracture. Milk fever (Parturient paresis): Milk fever, postparturient hypocalcemia, or parturient paresis is a disease, primarily in levels dairy cattle, beef cattle, ewes Characterized by reduced blood calcium Occurs within 72 hours following parturition during late stage of gestation. Symptoms: loss of appetite, nervousness, turning head back to flanks Grass tetany: A metabolic disease due to low Mg level in blood and in many cases low blood calcium. In ruminant (beef cattle, dairy cattle and sheep) Usually after grazing on pastures of rapidly growing grass, especially in early spring. Symptoms: nervousness, staggering, convulsion, coma and death. II. Phosphorus Sources: Milk and milk products, chicken, beans, salmon, fish, bread, egg yolk, whole wheat Absorption: 1. Phosphorus (in the form of phosphate) is absorbed by an active transport mechanism in the mid jejunum and enters blood stream via portal circulation. 2. Absorption is regulated by active vitamin D (calcitriol). 3. Factors affecting absorption of calcium will affect-in the same manner-the absorption of phosphorus. Body phosphorus: Metabolism of phosphorus follows calcium inversely. 1. Total body phosphorus is about 800 g. 134 2. Most of phosphorus (80%) is present in the skeleton (bones and teeth) in the form of hydroxyapatite: 3 Ca3 (P04)2 Ca(OH)2 3. The other 20 % is present in other tissues (mostly intracellular) and body fluids. Blood phosphorus: 1. Normal plasma inorganic phosphorus: 3-5 mg/dl. 2. Other forms are present: In plasma: phospholipids. In RBCs: organic phosphate e.g. ATP, glucose-6-phosphate. 3. Factors affecting blood phosphorus: a) Parathyroid hormone (PHT): It inhibits renal tubular reabsorption of phosphate → ↑ phosphate excretion in urine → ↓ plasma phosphate. b) Active vitamin D "Calcitriol": Calcitriol increases blood phosphorus through stimulation of: *Absorption of phosphorus from the intestine. * Bone resorption i.e. mobilization of phosphorus from bones. * Renal reabsorption by renal tubules. c)Renal function: Renal failure → failure of excretion in urine → ↑ plasma inorganic phosphate. Functions of phosphorus: (is the main intracellular anion). It enters in the structure of the following compounds: 1. Bones and teeth (in the form of hydroxyapatite). 2. Plasma buffers (phosphate buffers). 3. Cellular components: Nucleic acids: DNA, RNAs. Phospholipids: e.g. lecithin, cephalin. Phosphoproteins. Coenzymes: e.g. NAD, NADP High energy phosphate compounds e.g. ATP, GTP, creatine and phosphate. Cyclic AMP and cyclic GMP. Carbohydrate intermediates e.g. glucose-6-phosphate, fructose-1- phosphate. Excretion: Mostly (90%) is excreted in urine. Alterations of serum phosphate: 135  1. Causes of Hyperphosphatemia Hypoparathyroidism. Acidosis. Hypervitaminosis D. RBCs Hemolysis. Toxicity Signs: - Diarrhea, nausea, and vomiting. -Mineralization of soft tissues. Treatment: Low-phosphorus diet IV saline. 2. Causes of Hypophosphatemia: Hyperparathyroidism. Vitamin D deficiency. Renal tubular disease. Chronic alcoholism. Excessive use of antacids. Malabsorption. Treatment: Mild/ moderate: Dietary interventions, Oral supplements. Severe: IV replacement using potassium phosphate or sodium phosphate. Requirements: Recommended Daily Allowance (RDA): 1000 mg / day III. Magnesium Sources: Leafy green vegetables (containing chlorophyll). Absorption: Occurs in the upper small intestine. Body magnesium: 1. Mostly (70%) in the skeleton (bones and teeth). 2. The remaining 30% is present in the other tissues and body fluids mostly intracellular. Blood magnesium: 1. Plasma magnesium: 2-3 mg/dl. 136 2. RBCs content of magnesium is 3 times greater than plasma content. Functions: 1. It enters in the structure of skeleton (bones and teeth). 2. It activates many enzymes e.g. kinase enzymes. 3. It is required for the active transport of other cations (Ca , Na , K ) across the cell membrane. 4. It is important for muscle contraction, nerve impulse transmission and it decreases neuromuscular excitability. Hypomagnesemia: Mg deficiency causes neuromuscular irritation, weakness and convulsions. These symptoms are similar that observed in Ca deficiency, which are relieved only by Mg. Malnutrition, alcoholism and cirrhosis of liver may lead to Mg deficiency. Low level of Mg may be observed in uremia, rickets and abnormal pregnancy. Hypermagnesemia is usual due to renal insufficiency. It causes muscle weakness, hypotension, sedation and confusion. Excretion: Mostly (75 %} in feces. Reguirements::For adults: 400 mg/day. IV. Sodium Sources: The main source is table salt. Absorption: It occurs in small intestine (ileum}. It is nearly completely absorbed. Body sodium: It is regulated by aldosterone. 1. 2/3 of sodium is present in tissues and body fluids (sodium is the main extracellular cation). 2. About 1/3 of sodium is present in skeleton. Plasma sodium: 137-143 mmol/L. Factors affecting plasma sodium: 1. Aldosterone and the rennin angiotensin system (Plasma sodium). 2. Changes in glomerular filtrate and renal blood flow. 3. Atrial natriuretic peptide. Functions: 1. Maintenance of osmotic pressure and volume of plasma and extracellular fluid. 137 2. Transmission of nerve impulses. 3. Contraction of muscles. 4. Regulation of acid base balance. 5. Sodium acts as substrate for Na+/K+ ATPase enzyme (sodium potassium pump). Excretion: Mainly (95%) in urine and sweat. Reguirements: For adults: 5 g/day. Abnormal plasma sodium: 1. Hypernatremia (excess plasma sodium): It is caused by: Cushing syndrome: due to excessive glucocorticoids. Conn's disease: due to excessive aldosterone secretion. Diabetes insipidus (low ADH): due to rapid loss of water. Drugs: as ACTH or cortisone. 2. Hyponatremia (decrease plasma sodium) : It is caused by: Addison's disease: due to deficiency of aldosterone. Renal failure: where renal reabsorption of sodium is inhibited. Hypotonic dehydration: where loss of water and sodium (electrolytes) is treated by administration of water only. Edema which occurs in cirrhosis or congestive heart failure Diuretics: e.g. thiazides, which block tubular reabsorption of sodium. Toxicity: Hypertension in susceptible individuals. V. Potassium Sources: Vegetables, fruits and nuts. Absorption: Rapidly occurs in the small intestine. Body potassium: It is regulated by aldosterone. 1. 2/3 of potassium is present in tissues and body fluids (potassium is the main intracellular cation). 2. About 1/3 is present in skeleton. Plasma potassium: 3.5-5 mmol/L. Functions: 1. Maintenance of osmotic pressure and volume of intracellular fluid. 2. Transmission of nerve impulses. 3. Contraction of muscles. 4. Regulation of acid base balance. 138 5. Substrate for Na+ /K+ ATPase. Excretion: Mainly in urine. Requirements: 4 g/day. Alterations of plasma potassium: 1. Hyperkalemia (excess plasma potassium): it is caused by: Addison's disease: due to deficiency of aldosterone. Acidosis: (respiratory or metabolic): due to shift of K from intra to extracellular in exchange with H +. Tissue necrosis: e.g. major trauma and burns due to leakage of tissue contents of potassium. Acute renal failure and advanced chronic renal failure, associated with oliguria. Uncontrolled diabetes mellitus: the lack of insulin and associated acidosis prevents K from entering cells. Acute hyperkalemia: if plasma K gets more than 6.5 mmol/L, cardiac arrhythmias and even cardiac arrest may result. 2. Hypokalemia: (decreased plasma potassium): it is caused by: Alkalosis: (respiratory or metabolic). Treatment of hyperglycemia: by insulin without giving potassium because insulin helps K+ to enter cells. Excessive vomiting and diarrhea. Cushing syndrome: due to excessive glucocorticoids. Primary and secondary hyper-aldosteronism. Diuretic therapy. VI. Chloride Sources: Table salt. Absorption: Occurs in small intestine. Plasma chloride: 96-106 mmol/L. Functions: 1. Chloride is the main extracellular anion. Together with sodium, it maintains the osmotic pressure and volume of plasma and extracellular fluid. 2. Chloride ions are essential for formation of HCl in the stomach. 3. Activation of enzymes: Cl· activates salivary and pancreatic amylase enzymes. Excretion: Mainly in urine. Requirements: For adults: 5 g/day. 139 Alterations of plasma chloride: 1. Hyperchloremia: Hyperchloremic acidosis: Occurs when HC03 is lost in exchange with chloride as in renal tubular acidosis and hyperventilation. Glomerulonephritis. Eclampsia (toxicity of pregnancy). 2. Hypochloremia: a) Hypochloremic alkalosis: decreased plasma chloride due to: 1) Intestinal obstruction ~ excessive vomiting. 2) This leads to decrease plasma chloride and increase plasma bicarbonate as compensatory mechanism, causing alkalosis. b) Addison's disease. c) Diabetes insipidus. VII. Sulfur Sources: Sulfur containing amino acids: Methionine, cysteine and cystine. Sulfur containing vitamins: Thiamin (B1), Biotin, lipoic acid. Neutral S in diet (-SH). Functions : Structural conformation and biological functions of proteins, vitamins, keratin (hair, nail, skin). Formation of other important sulfur containing compounds: Heparin, glutathione , taurocholic acid. Transmethylation reactions by S- adenosyl methionine. Dietary requirements: Adequate intake of S- containing essential amino acid methionine will meet the body needs. Fate of Sulfur 1-Amino acids (80%): *Oxidation= (S2O3 (Thio-sulphate) SO3 (Sulphite) SO4 (Sulphate) *Excretion: in urine *Neutral sulphate in : GSH (cysteine-glutamic-glycine) 2- Vitamin: utilization 140  3- Carbohydrate: Mucopolysaccharides (GAGs) 4- Lipids: sulpholipids (glycolipids) 5-Proteins: ergothionine (antioxidant): in (RBCs-liver-semen). 6- Ethereal sulfate (10%): products of phenol detoxification (indican)= in urine in constipation, intestinal putrifaction. 7- Organic sulphats: PAPS (Sulphate+ nucleotides)= Sulpher donner. ATP+ S ======= Adenosine-5-phosphosulfate ========= PAPS Ppi ATP--ADP Micro minerals (Trace elements) I. Iron Sources: 1. Liver, heart, kidney, spleen and fish. 2. Sugar cane syrup (molasses). 3. Dates and egg yolk. 4. Contrary to popular belief, spinach is a poor source of iron because it is bound to phytate, which is difficult to absorb. Absorption: Absorption of iron occurs in the duodenum and the proximal part of the jejunum. 1. Diet contains about 10-20 mg iron/day. Usually only 10-20% of this amount is absorbed. 2. Mechanism: Mucosal block theory: According to this theory, iron is absorbed in the ferrous state (Fe++). Inside mucosal cells, it is oxidized to ferric state (Fe+++) and combines with apoferritin to form ferritin. Ferritin liberates ferrous ions into the capillaries (plasma) and apoferritin is regenerated again. The rate of this liberation depends on body needs. The intestinal content of apoferritin is limited and when all apoferritin molecules become saturated with iron, absorption is blocked. 141 3. Factors affecting iron absorption: most of dietary iron is present in the ferric state (Fe+++) as ferric organic compounds. a) Factors increasing iron absorption: 1) Cooking of food and gastric HCI facilitates the liberation of ferric ions (Fe+++) from organic compounds. 2) Reducing substances: vitamin C and cysteine (-SH) of dietary protein help the reduction of ferric ions (Fe+++) into the absorbable ferrous (Fe++) state. 3) Body needs: absorption occurs only if the body is in need to iron. More iron is absorbed when there is iron deficiency or when erythropoiesis is increased. b) Factors decreasing iron absorption: 1) High dietary phosphate and phytate: They form insoluble, non-absorbable organic iron complexes. 2) Steatorrhea: Where fatty acids form non-absorbable iron soaps. 3) Alkalies and tea. Body iron: 1. The total body iron of an adult male is 3-5 grams. 142 2. It is distributed as follows: RBCs iron (Hemoglobin): 6696, tissue iron (3396) and plasma iron 1%. 3. RBCs iron: (hemoglobin): see hemoglobin metabolism. 4. Tissue iron: it includes: a) Available iron forms (29 %): can be used by tissues when there is body need. 1) Ferritin: It is the main storage form of iron. It is present in iron stores: liver, spleen, bone marrow and intestine. 2) Hemosedrin: When body contains very high content of iron more than the capacity of apoferritin, some of iron is found in granules called hemosedrin that deposited in tissues. These granules are composed of iron, protein, and polysaccharides. Hemosedrin may be a degraded ferritin. b) Non-available iron forms (4%): cannot be used even if there is body needs. All these forms arc hemoproteins i.e. contain heme ring. 1) Myoglobin: It is hemoprotein formed of a single heme ring attac!ted to one long polypeptide chain. It is present in muscles and heart. It acts as oxygen reservoir for quick utilization by contracting muscles. 2) Respiratory cytochromes (b, c., c, a, a 3): These are components of respiratory chain in mitochondria. They act as electron carriers. 3) Catalase and peroxidase: -These are two enzymes that act on the toxic hydrogen peroxide (H2O2 converting it into H2O. 4) Tryptophan oxygenase (pyrrolase): -This enzyme is important for tryptophan metabolism. 5) Cytochrome P 45o: i- These are a specific group of enzymes that present in liver, lung, kidney, gut, adrenal cortex, heart, and brain. They are used in xenohiotics metabolism. Plasma iron: a) Plasma iron: Ranges from 6o- 160 ug/dl. b) Plasma transferrin: 1) This is a plasma glycoprotein that acts as carrier for iron. It is synthesized in the liver. 143 2) Each molecule can carry 2 atoms of iron in ferric state (Fe+++). 3) Transferrin may carry up to 180-450 ug iron/dl. This is known as total iron binding capacity of transferrin (TIBC). As the plasma iron is 6o-t6o ug/dl, thus only 30% of the TIBC of transferrin is saturated. 4) TIBC is therefore defined as maximum amount of iron that can be carried by transferrin per deciliter. 5) Abnormalities of plasma TIBC concentration: In iron deficiency anemia: Plasma iron is decreased. Liver synthesizes more transferrin with subsequent increase of TIBC. In liver diseases: Both plasma iron and transferrin synthesis tend to decrease (↓plasma iron and ↓TIBC). In iron overload: transferrin synthesis is inhibited. This leads to increased plasma iron and decreased Total iron binding capacity. c) Plasma ferritin: 1) Ferritin is present mainly in iron stores: liver, spleen, bone marrow and intestine. 2) Very low concentration of ferritin is present in plasma. 3) Measurement of plasma ferritin gives a good idea about body iron stores. A low plasma ferritin indicates the presence of depleted iron stores e.g. in iron deficiency anemia. A raised plasma ferritin is found in iron overload and also in many patients with liver disease and cancer. Functions of iron: Iron enters in the structure of the following compounds: Hemoglobin: which carries oxygen. Myoglobin: which stores oxygen. Respiratory enzymes: which use oxygen. Cytochrome P 45o: which detoxicates drugs and oxygen. Other enzymes: catalase, peroxidase and tryptophan oxygenase. Transport and storage of plasma iron : 1. Absorbed iron enters in the portal blood in ferrous state (Fe++). 2. In the plasma, it is rapidly oxidized to ferric state (Fe+++). A protein containing copper called ceruloplasmin catalyzes this oxidation. 3. Then ferric ions are carried by a transferrin, which is taken mostly by bone marrow to synthesize hemoglobin. 144 4. Iron, from iron stores (ferritin) can be released into plasma and carried by transferrin to be utilized by bone marrow and other tissues. Excretion: 1. Iron excreted in the feces is mainly exogenous i.e. dietary iron that has not been absorbed. 2. In males there is an average loss of endogenous iron of about 1 mg/day. It is derived from desquamated cells from skin and the intestinal mucosa. 3. In females, there are additional sources of loss, due to menstruation and pregnancy. 4. Urine contains negligible amount of iron. Reguirements: 1. Adults: 10 mg/day. 2. Pregnant and lactating women: 30 mg/day. Alterations of plasma iron: 1. Iron deficiency anemia: Causes: 1) Deficient intake. 2) Impaired absorption: e.g. steatorrhea, abdominal surgery. 3) Excessive loss e.g. menstrual loss, gastrointestinal bleeding due to some parasites (anchylostoma). Biochemical changes: 1) Plasma iron is decreased. 2) Plasma TIBC is increased. 2. Iron overload: Causes: 1) Repeated blood transfusion. 2) Intravenous administration of iron. 3) Hemochromatosis (hemosiderosis, bronze diabetes): a- This is a rare hereditary disease characterized by abnormal increase of iron absorption. b- Iron is deposited in the form of hemosedrin in: Liver: causing liver cirrhosis. Pancreas: causing fibrosis and diabetes mellitus. Skin: causing bronze discoloration of skin. Biochemical changes: 1) Plasma iron is increased. 145 2) Plasma TIBC is decreased. 3) Plasma ferritin is increased. II. Copper Sources: The richest sources are: liver, kidney, dried legumes and nuts. Absorption: Mainly occurs in the upper small intestine. Body copper: 1. The adult human body contains about 100-150 mg of copper. 2. 64 mg (50%) are found in muscles and the remaining present in other tissues including liver and bones. Blood copper: 1. In the plasma: 90 ug/dl. It is present in association with 2 proteins: a) Ceruloplasmin: (90%) A copper binding protein. Each molecule can bind 6 atoms of copper. It acts as ferroxidase enzyme during iron metabolism (Fe++ Fe+++), b) Albumin: (10%) It is loosely bound form of copper. It acts as a carrier for transport of copper in plasma. 2. In RBCs: 100 ug/dl. It is present in association with the enzyme superoxide dismutase (erythrocuprein}, which deals with the toxic free radical superoxide ion (O-2) generated during aerobic metabolism. Functions: 1. Copper is essential for: Hemoglobin synthesis. Bone formation. Maintenance of myelin of the nerves. 2. Copper is essential constituent of several metaloenzymes: 146  Ceruloplasmin: which oxidizes Fe++into Fe+++ in the plasma. Superoxide dismutase: which eliminates the toxic effect of superoxide ions (O-2). * Superoxide dismutase is present in RBCs (erythrocuprein), liver (hepatocuprein) and brain (cerebrocuprein). c) Cytochrome oxidase. 3. Copper activates many enzymes: e.g. tyrosinase, uricase and dopamine hydroxylase. Excretion: 1. Mainly with bile. 2. Urinary excretion is minimal due to large molecular weight of ceruloplasmin. Requirements: Adults: 2- 3 mg/day. Alterations of plasma copper: 1. Hypercupermia: (excess plasma copper and ceruloplasmin): Ceruloplasmin is considered as acute phase protein i.e. its plasma level is increased in infections and malignancy. 2. Hypocupermia: (decreased plasma copper and ceruloplasmin): a) Anemia: Hypochromic and microcytic anemia. b) Impaired bone mineralization. c) Wilson's disease (hepatolenticular degeneration): characterized by accumulation of large amounts of copper in: Liver causing hepatic cirrhosis. Lenticular nucleus of the brain causing lenticular degeneration with abnormal movement. Cornea: Causing greenish-brown discoloration of the corneal margin, which is called: Kayser - Fleisher rings. Kidney causing renal tubular damage which leads to: Increased excretion of copper and ceruloplasmin. This results in low serum copper (hypocupremia) and ceruloplasmin. Increased excretion of amino acids. This results in aminoaciduria. The cause of Wilson's disease is most probably due to either: Excessive copper absorption from intestine. Inadequate excretion of copper in bile. III. Zinc Sources: Meat, liver, eggs, seafood, milk, and whole grain cereals. 147 Absorption: Zinc absorption occurs mainly in small intestine, especially from the duodenum. Body zine: 1. The adult male body contain about 2 g of zinc. 2. About 20 % of total body zinc is present in the skin. 3. The remaining is present in skeleton (bones and teeth), spermatozoa, prostate, epididymis and pancreas. Plasma zine: Adults: 70-150 ug/dl. Functions of zinc: 1. Zinc is essential for growth and reproduction. 2. It plays a role in tissue repair and wound healing. 3. Zinc forms a complex with insulin in p islet cells of the pancreas. This helps crystallization, storage and release of insulin. 4. Zinc is required for mobilization of vitamin A from the liver and subsequently maintains the normal concentration of vitamin A in plasma. 5. Zinc is essential component of a number of enzymes e.g.: Alkaline phosphatase. Carbonic anhydrase. Superoxide dismutase Carboxyp-eptidase. RNA polymerase. Reguirements: An adult male: 10-20 mg/day. Excretion: Mainly in feces (mostly unabsorbed dietary zinc). Zinc deficiency: It causes: 1. Hypogonadism. 2. Poor healing of wounds. 3. Poor appetite and retard growth in children. 4. Liver cirrhosis. 5. Diarrhea and dermatitis. 6. Confusion, apathy and depression. IV.Iodine Sources: 1. Iodinized table salt will provide daily body needs. 2. Fish, seafoods, weeds, and vegetables grown near seaboard. Absorption: Occurs mainly from small intestine. Body iodine: 1. The adult male body contains about 2s-so mg iodine. 148 2. It is present in: Thyroid gland: (50%): as thyroglobulin. Other tissues and body fluids (50%): as T3 and T4 Plasma iodine: 1. Organic iodine: 4-8 ug/dl. 2. Inorganic iodine: 1-2 ug/dl. Functions: The only known function of iodine is the formation of thyroid hormones (T3 - T4). Excretion: Mainly (70%) in urine. Reguirements: For adult: 100- 1'so ug/day. Deficiency: Hypothyroidism (myxodema in adults and cretinism in children). *Goitrogens: occurring naturally in foods can cause goiter by blocking absorption or utilization of iodine (cabbage, turnips, peanuts, soybeans) V. Selenium - Selenium is an antioxidant. It is an essential component of the enzyme glutathione peroxidase (GSH-Px) which. Catalyzes the reaction: 2 GSH + H2O2 GSSG + 2 H2O - This reaction acts as protective mechanism against the oxidative damage of hydrogen peroxide (H202) and fatty acid hydroperoxide by destroying them: 1. In RBCs, it protects hemoglobin and red cell membranes. 2. In liver, it is important for detoxifying lipid hydroperoxides. 3. In lens of the eye, it prevents its oxidative damage. Deficiency of selenium (GSH-Px): It causes: 1. Hemolytic anemia. 2. Liver cirrhosis. 3. Cataract. Metabolism Selenium is stored in the body as selenocysteine in selenoproteins 149  Excreted in urine and in breath as dimethyl selenide with a garlic-like odor Relationship of glutathione peroxidase, selenium, and vitamin E. VI. Manganese - Manganese is essential for: 1. Normal bone structure. 2. Reproduction (spermatogenesis and ovulation). 3. Normal function of the central nervous system. - Manganese is a component of: 1. Pyruvate carboxylase enzyme. 2. Superoxide dismutase enzyme. -Manganese activates: the arginase enzyme. VII. Cobalt Functions: 1. Cobalt is a component of vitamin Ba:a, which is necessary for normal blood cell formation. Cobalt gives vitamin Bu its red color. 2. Enzymes requiring vitamin Ba:a for their activities are: Methylmalonyl CoA mutase. Methyltetrahydrofolate oxidoreductase. Homocysteine methyltransferase. Ribonucleotide reductase. Deficiency of cobalt ↓vitamin B12 causes pernicious anemia. VIII. Chromium It acts only together with insulin to promote glucose utilization. Its deficiency leads to impairment of glucose utilization by tissues. IX. Molybedenum 150  It is a component of oxidase enzymes e.g. xanthine oxidase. X. Flouride It increases the hardness of bones and teeth. Its deficiency causes dental carries and osteoporosis. It is supplied in drinking water to support bones and teeth. Excess flouride leads to flourosis: mottling and discoloration of the enamel of teeth and changes in bones. Nutrient and Adult Signs of Sources Functions RDA Deficiency Calcium (Ca) 1.Milk and -bone and teeth -Tetany, 1000- 1200mg/day milk products formation, - Rickets, (the richest -blood clotting, -Osteoporosis sources). - nerve transmission, 2. Beans, leafy - muscle contraction vegetables and -heart action egg yolk Phosphorus (p) -bone and tooth - bone loss 700 mg/day High- protein formation, - poor growth Tetany, foods -acid-base balance, - Rickets, Milk ,milk - energy metabolism -Osteoporosis products, grains Magnesium (Mg) -aids thyroid hormone -tremor, 310-420 mg /day secretion spasm, Grains, nuts, -activator and - muscle beans, coenzyme in protein weakness and Green and carbohydrate cramp, vegetables, metabolism -blood vessel construction in the heart and brain -hypertension Sodium (Na) 151  ( 500 mg/day) - water balance -Muscle table salt - acid-base balance cramps natural food -muscle action -Cold skin (milk, meat , - glucose absorption egg, celery) -Weakness of processed respiratory foods muscle with Potassium (K) difficult (2000-3500 mg /day) -water balance breathing - metabolic reaction -poor Whole grains, -muscle action intestinal meat legumes, -Insulin release muscle fruits, - cardiac arrest Chlorine (Cl) vegetables, 750 mg/day -Component of HCl in stomach, fluid balance and acid-base Hypochloremi Table salt balance. a: Sulfur(S) Diet adequate in -essential constituent protein contains of cell protein adequate sulfur - hair, skin, nails General Meat , egg, - vitamin structure protein , cheese - collagen structure malnutrition Milk, nuts, -high- energy sulfur legumes bonds in energy metabolism 152