Metabolisme Mineral

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PertanyaanApa yang terjadi jika kita kekurangan atau kelebihan Mineral ????Apa yang terjadi jika tubuh kita kekurangan Air????

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Unsur-unsur dalam Tubuh ada 5 kelompok

1. Molekul-molekul utama dalam tubuh C, H, O, N, S-- karbohidrat, lemak, protein dan air

2. Keperluan > 100/day :Ca, P, Mg ,Na, K dan Cl

3. Trace element: Cr, Co, Cu, I, Fe, Mo, Se,F dan Zn 4. Edition element for animal : Cd, As, Ni, Si, Sn and Vanadium

5. Unsur beracun : Pb dan Hg(mercury)

MINERAL4% bobot manusia mineralAntara lain:klorida (Cl-), fosfat PO43-), bikarbonat (HCO3-), sulfat (SO42-) berada dalam darah dan cairan tubuhFe2+ pada hemoglobin; P pada asam nukleat (DNA, RNA)Fungsi : zat pembangun dan pengatur Na+ dan Cl- menjaga tekanan osmotik, keseimbangan asam basa

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Ca2+ menjaga keseimbangan asam basa, P osmotik, tulang & gigi; pembekuan darah dan aktifitas enzimFosfor: pembentukan tulang & gigi, metab energi, keseimbangan asam basaMg: aktifator enzim gugus fosfatFe2+: pembawa O2 dalam HbIod: fungsi kel. Tiroid, program iodisasi

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Garam-garam mineral (Seny. Anorganik) jumlah yang diperlukan tubuh hanya kecil tetapi diperlukan untuk semua proses dalam tubuh

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I. Metabolisme KalsiumNormal ranges

Regulated with a normal total calcium of 2.2-2.6mmol/L (9-10.5mg/dL)normal ionized calcium of 1.1-1.4mmol/L (4.5-5.6mg/dL)

Corrected calcium level

corrected calcium level when the albumin is abnormal, Corrected calcium (mg/dL) = measured total Ca (mg/dL) + 0.8 (4.0 - serum albumin [g/dL]), where 4.0 represents the average albumin level in g/dL.When there is hypoalbuminemia (a lower than normal albumin), the corrected calcium level is higher than the total calcium

Absorption

About 25 mmol of calcium enters the body in a normal diet. Of this, about 40% (10mmol) is absorbed in small intestine, and 5mmol leaves the body in feces, netting 5mmol of calcium a day

Calcium is absorbed across the intestinal brush border membranepassing through ion channels such as TRPV6. Calbindin is a vitamin D-dependent calcium-binding protein inside intestinal epithelial cells which functions together with TRPV6 and calcium pumps (PMCA1) in the basal membrane to actively transport calcium into the body

in the duodenum when calcium intake is low, in the ileum and jejunum, independent of Vitamin D, when calcium intake is high.

Excretion

The kidney excretes 250mmol a day in pro-urine, and resorbs 245mmol net loss in the urine of 5mmol/day.the kidney processes Vitamin D into calcitriol, the active form that is most effective in assisting intestinal absorption. Both processes are stimulated by parathyroid hormone.

The role of bone

Calcium flow to and from the bone is neutral, about 5mmol is turned over a day Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Calcium release from bone is regulated by parathyroid hormone. Calcitonin stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin. Low calcium intake may also be a risk factor in the development of osteoporosisCalcium regulation in the human body.Primarily calcium is regulated by the actions of 1,25-Dihydroxycholecalciferol(Vit D3), parathyroid hormone (PTH) and calcitonin and direct exchange with the bone matrix

II. PHOSPHORUS METABOLISM Phosphorus important, 1.Found in ATP high energy bonds2.Acts as a buffer in the intracellular fluid. 3.In the renal excretion of hydrogen ion. The great majority of the bodys phosphorus is stored in the bone. In the plasma, phosphorus is inorganic and most is not bound.

Dietary intake and excretion in urine and feces maintain homeostasis. PTH regulates renal phosphorus reabsorption with the help of calcitonin, thyroid hormone and growth hormone. There is also an internal homeostasis kept between intracellular and extracellular levels.

HYPOPHOSPHATEMIA serum phosphorus less than 2.5 mg/dl Manifestations1. Thrombocytopenia, abnormal platelet function and reduced white cell function may occur but are not usually clinically significant.2. Deficiency of cellular ATP affects the CNS and may cause reduced state of consciousness or seizures. Also seen are peripheral neuropathy and Guillain-Barre syndrome. Skeletal muscle is also affected and rhabdomyolysis or paralysis may occur. 3. Chronic hypophosphatemia may stimulate bone reabsorption and deficient mineralization.

HYPERPHOSPHATEMIA Manifestations:1. Mild hyperphosphatemia, as in chronic renal failure, causes secondary hyperparathyroidism.2 Hypocalcemia, low blood pressure and renal insufficiency accompany severe hyperphosphatemia.

Ratio Ca : P = 2 : 1

P as food aditives, if Ratio 1 : 1,2 / 1 : 1,5 osteoporotic cause

Phosphorus is absorbed more efficiently than calcium. Nearly 70 percent of phosphorus is absorbed from the intestines, although the rate depends somewhat on the levels of calcium and vitamin D and the activity of parathyroid hormone (PTH), which regulates the metabolism of phosphorus and calcium. Most phosphorus is deposited in the bones, a little goes to the teeth, and the rest is contained in the cells and other tissues. Much is found in the red blood cells. The plasma phosphorus measures about 3.5 mg. (3.5 mg. of phosphorus per 100 ml. of plasma), while the total blood phosphorus is 30-40 mg.. The body level of this mineral is regulated by the kidneys, which are also influenced by PTH. Phosphorus absorption may be decreased by antacids, iron, aluminum, or magnesium, which may all form insoluble phosphates and be eliminated in the feces.Caffeine causes increased phosphorus excretion by the kidneys.

III. Magnesium (Mg) Metabolism The normal adult human body contains approximately 1,000 mmols of magnesium (2226 g). About 60% of the magnesium is present in bone, Which 30% is exchangeable and functions as a reservoir to stabilise the serum concentration. About 20% is in skeletal muscle, 19% in other soft tissues less than 1% in the extracellular fluid. Skeletal muscle and liver contain between 79 mmol/Kg wet tissueAcid base disturbances (metabolic acidosis or alkalosis) have little effect on the distribution of serum magnesium

Magnesium balance

The recommended daily allowance (RDA) for magnesium in adults is 4.5 mg/Kg/day Magnesium is plentiful in green leafy vegetables The average magnesium intake of a normal adult is approximately 12 mmol/day. Approximately 2 mmol/day of magnesium is secreted into the intestinal tract in bile and pancreatic and intestinal juices. From this pool 6 mmol (about 30%) is absorbed giving a net absorption of 4 mmol/day.

Absorption Most of the absorption occurs in the ileum and colon. At normal intakes absorption is primarily passive. Studies suggest a role for parathyroid hormone (PTH) in regulating magnesium absorption, but the role of vitamin D and its active metabolite 1,25 dihydroxyvitamin D is more controversial. Phytates in the diet bind to magnesium and impair its absorption. However the quantities present in normal diet do not affect magnesium absorption. Other dietary factors that are thought to affect magnesium absorption are oxalate, phosphate, proteins, potassium and zinc.

maintenance of plasmaThe kidney plays a major role in magnesium homeostasis and the maintenance of plasma magnesium concentration Under normal circumstances, when 80% of the total plasma magnesium is ultrafiltrable, 84 mmol of magnesium is filtered daily and 95% of this reabsorbed leaving about 35 mmol to appear in the urine. Approximately 1520% of filtered magnesium is reabsorbed in the proximal tubular segments,6575% in TALH and the rest in the distal segments.

No single hormone has been shown to be specifically related to magnesium homeostasis. Several hormones including PTH, antidiuretic hormone (ADH), calcitonin, glucagon and insulin have been shown to affect magnesium reabsorption. Of these,PTH is the most important. PTH increases reabsorption in the distal tubules by a cyclic AMP mediated process

IV.SODIUM METABOLISM Extracellular fluid contains about 3000 mEq of sodium, which is the main osmotic component An increase or decrease as small as 1% of the total extracellular fluid volume can have serious effects

About 30,000 mEq of sodium undergo filtration at the glomeruli each day.

regulation of sodium in the body 1. Renin is the enzyme responsible for the conversion of antiotensinogen to angiotensin I. An angiotensin converting enzyme converts angiotensin I to angiotensin II. Angiotensin causes vasoconstriction as well as the secretion of aldosterone from the adrenal gland. Renal hypoperfusion, adrenaline and other catecholamines stimulate renin secretion from the juxtaglomerular apparatus of the glomeruli.

2. Aldosterone is a hormone that is controlled by the renin-angiotensin system and acts to increase reabsorption of sodium in the cortical collecting duct.3. Dopamine from the kidney inhibits reabsorption in the proximal tubules.

4. Prostaglandins block reabsorption in the tubules and stimulate renal vasodilatation. 5. Atrial natriuretic peptide blocks reabsorption of sodium in the collecting duct.

HYPONATREMIA 1 Hyponatremia is sodium level under 135 mEq/L but is actually an excess of waterwith no effect from the amount of total body sodium 2 Hypotonicity is always associated with hyponatremia, whereas hyponatremia can be hyper-, iso- or hypotonic.

3 Hypertonic hyponatremia is caused by osmotically active particles in the extracellular fluid (such as glucose) and a shift of water from intracellular to extracellular fluid as a result. Thus, low serum sodium is accompanied by normal or high osmolality.

4 Isotonic hyponatremia is also called pseudohyponatremia since it is an artifact caused by high lipid or protein in the serum. 5 True hyponatremia is hypotonic with sodium is under 125 mEq/L and serum osmolality under 0.250 Osm/kg.

6 Hyponatremia can further be divided into hypovolemic states (GI, renal or third-space losses), isovolemic states and hypervolemic states (CHF, nephrotic syndrome, cirrhosis).

SIADH (syndrome of inappropriate ADH secretion) is non-osmotically induced and connected with various disorders of the CNS (tumors, trauma, psychiatric disturbances) and of the lungs (oat cell carcinoma, infection, bronchospastic disease).One type of SIADH, called reset osmostat is seen in patients with chronic illness or malnutrition. The set point for sodium concentration is lowered and the body maintains that value. SIADH is isovolemic.

HYPERNATREMIA 1. Hypernatremia is clinically significant above 155 mEq/L.2. Hypernatremia is always hypertonic. Asal usul gangguan

Renal causesa. Decreased effect of ADH (1) central diabetes insipidus failure of secretion or synthesis of ADH due to tumor, trauma, sarcoidosis or histiocytosis (2) nephrogenic diabetes insipidus high levels of ADH with no effect, due to renal disease, sickle cell anemia, urinary tract obstruction, hypercalcemia, hypokalemia, lithium or demeclocycline use.

b. Osmotic diuresis as in hyperglycemia both water and sodium reabsorption are affected, but water losses are more than sodium losses.

2. Extrarenal causesa. Reduced fluid intake the body loses water through urine and feces, as well as insensible losses via the skin and mucus membranes. A minimum of about 700 ml/day is necessary in cool climates, more in warmer areas. b. Vomiting and diarrhea increase gastrointestinal losses.c. Sweating and burns increase losses via the skin.

Transport ion di dalam kolon ditandai oleh adanya pompa Na+/H+ ; Cl- /HCO3- di sisi luminalDi sisi basolateral Na+ , K+ ATP ase dan transport Cl- yang dipermudahPerbedaan potensial listrik transmukosa dalam colon 30 mv mempermudah masuknya Na+ luminal ke sel epitel Masuknya Cl- ke dalam ruang-ruang interselular lateral dari lumen melalui tight junction (sel-sel epitel bersebelahan melalui transpor yang difasilitasi)

V. POTASSIUM METABOLISM Intracellular fluid has about 3000 mEq of potassium; extracellular fluid only 65 mEq. This ratio must be maintained in order to enable the proper functioning of cell membranes. Potassium is influenced by factors such as insulin and epinephrine, which increase cellular uptake, and high total body potassium levels, which reduce cellular uptake. Within the kidney, aldosterone stimulates the secretion of potassium and the reabsorption of sodium. Diuretics cause increased potassium secretion due to increased sodium and fluid in the collecting tubules.

HYPOKALEMIA 1. Serum potassium under 3.5 mEq/L 2. Most potassium is intracellular and so it takes severe depletion of intracellular potassium before any changes in serum potassium are felt.

1. Renal causesa. Primary hyperaldosteronism as in adrenal tumors, adrenal hyperplasia or ectopic ACTH can cause hypokalemia. Excess ingestion of European licorice or some tobacco products also causes hypokalemia via primary hyperaldosteronism.b. Tumors, renal artery stenosis or malignant hypertension may cause secondary hyperaldosteronism. It is also the mechanism for the hypokalemia seen in congestive heart failure and cirrhosis.c. Potassium wasting is seen in renal tubular acidosis types I (distal) and II (proximal). High levels of renin and aldosterone, renal potassium wasting, metabolic acidosis and polyuria characterize Bartters syndrome. Chronic magnesium depletion causes potassium wasting which is refractory to potassium supplements and needs magnesium supplementation first.d. Drugs such as diuretics, penicillins, gentamicin, and amphotericin B increase potassium excretion.

2. Extrarenal causesa. Low intake or gastrointestinal losses from diarrhea and/or vomiting, chronic laxative useb. Redistribution of potassium from plasma to intracellular fluid as with insulin, adrenaline, bicarbonate. b. Therapies for megaloblastic anemia (and neoplasms) deplete potassium stores due to cell proliferation.c. Hypokalemic periodic paralysis is a rare syndrome with rapid drops in potassium levels and resultant paralysis.

Manifestations: Muscle weakness and paralysis etc.

HYPERKALEMIA Serum potassium levels more than 5.5 mEq/L 1. Renal causesa. Aldosterone deficiency may be due to decreased renin production in renal disease, primary adrenal disease or congenital enzyme defects. Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce renin secretion.b. Severe renal failure with GFR less than 10 ml/min causes disturbances in potassium transport in the tubules.c. Aldosterone resistance is seen in renal disease due to sickle cell anemia, SLE, amyloidosis, interstitial renal disease, and obstructive nephropathy and in the use of potassium-sparing diuretics or spironolactone.

2. Extrarenal causes lack of insulin, succinylcholine use, acute cell necrosis, crush injury, hemolysis, acidosis, hyperosmolarity and hyperkalemic periodic paralysis (rarer than the hypokalemic form) all cause hyperkalemia.3. Pseudohyperkalemia may occur after blood is drawn due to hemolysis. The actual potassium level may be normal, but hemolysis causes it to be artificially high. In this case, blood should be drawn again and processed quickly.

Manifestations: Weakness or paralysis due to changes in transmembrane potential. Arrythmias usually appear at levels above 6 mEq/L.

VI. iron metabolism

Have 4 to 5 grams of iron in their bodies About 2.5 g is contained in the hemoglobin needed to carry oxygen through the blood Approximately 2 grams in adult men, and somewhat less in women of childbearing age, is contained in ferritin complexes that are present in all cells, but most common in bone marrow, liver, and spleen

Women who must use their stores to compensate for iron lost through menstruation, pregnancy or lactation, have lower non-hemoglobin body stores, which may consist of 500 mg, or even less. About 400 mg is devoted to cellular proteins that use iron for important cellular processes like storing oxygen (myoglobin), or performing energy-producing redox reactions (cytochromes)

A relatively small amount (3-4 mg) circulates through the plasma, bound to transferrin Because of its toxicity, free soluble iron (soluble ferrous ions Fe(II)) is kept in low concentration in the body.

iron deficiency anemia is the primary clinical manifestation of iron deficiency. Oxygen transport is so important to human life that severe anemia harms or kills people by depriving their organs of enough oxygen loss for healthy people in the developed world amounts to an estimated average of 1 mg a day for men, and 1.52 mg a day for women with regular menstrual periods. People with gastrointestinal parasitic infections, more commonly found in developing countries, often lose more.

Absorbing iron from the diet

Dietary iron is a variable and dynamic process The absorption is in the form of heme iron and in its ferrous Fe2+ form. A ferric reductase enzyme on the enterocytes' brush border reduces ferric Fe3+ to Fe2+

Intestinal lining cells by Fe3+, A protein called divalent metal transporter 1 DMT1, which transports all kinds of divalent metals into the body, then transports the iron across the enterocyte's cell membrane and into the cell. These intestinal lining cells can then either store the iron as ferritin, which is accomplished by Fe3+ binding to apoferritin or apotransferrin

Ferritin that is not combined with iron is called apoferritin.Apoferritin is a protein of 450 kDa consisting of 24 subunits, apparent molecular weight of 19 kDA or 21 kDAEach ferritin complex can store in mitochondrial or reticuloendothelial system about 4500 iron (Fe3+) ions

Ferritin serves to store iron in a non-toxic form Free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen speciesSerum ferritin FR5Rl is the most convenient laboratory test to estimate iron stores. Ferritin concentrations increase drastically in the presence of an infection or cancerthe protein component of the egg yolk is primarily ferritin

Mitochondrial ferritin has many roles pertaining to molecular function. It participates in ferroxidase activity, binding, iron ion binding, oxidoreductase activity, ferric iron binding, metal ion binding as well as transition metal binding. Within the realm of biological processes it participates in oxidation-reduction, iron ion transport across membranes and cellular iron ion homeostasis

TransferrinTransferrin Iron Delivery and the Role of Iron Regulatory ProteinsApotransferrin is a protein of MW 90.000 kda consisting of globulin, binding 2 atom iron in the formation transferrin in plasmaIron binding capacity normal 20-23% saturatedIron overload capacity carier transferrin decreaseEritropoeitin hormon can regulation transport iron with mechanism unknow.

Transport iron at ferritin (ferritin storage)form to plasma Fe3+ Fe2+ reduction.And than Fe2+ Fe3+ iron can binding at transferrin

Ferritin as storage iron in reticuloendithelial, but ferritin can denaturation with subunit apoferritin loss, agregate misel form hemosiderinHemosiderin ready for sinthesis hemoglobin but very poorly

Like transferrin, ferritin can also become unstable, and ineffective. Think of ferritin like a big sink; when this sink gets full, ferritin and its iron can be changed into something called hemosiderin

For those with normal iron metabolism, unabsorbed iron, about 90% of iron ingested through diet and supplements, is taken up by specific cells in the intestinal tract, called enterocytes. These cells become engorged with iron, die, drop off, and are excreted in feces.

Hemosiderin or haemosiderin is an iron-storage complex. It is always found within cells (as opposed to circulating in blood) and appears to be a complex of ferritin, denatured ferritin and other material. The iron within deposits of hemosiderin is very poorly available to supply iron when needed.

Hemosiderosis :Hemosiderin may deposit in diseases associated with iron overload These diseases are typically diseases in which chronic blood loss requires frequent blood transfusions, such as sickle cell anemia and thalassemia.

Hemokromatosis : if hemosiderin deposit lack sell and organ function

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