Metabolisme Mineral

Blok 8
 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)

 MINERAL

4% bobot manusia mineral

Antara lain:klorida (Cl-), fosfat PO43-), bikarbonat
(HCO3-), sulfat (SO42-) berada dalam darah dan
cairan tubuh
Fe2+ pada hemoglobin; P pada asam nukleat (DNA,
RNA)
Fungsi : zat pembangun dan pengatur
Na+ dan Cl- menjaga tekanan osmotik,
keseimbangan asam basa
 Ca2+ menjaga keseimbangan asam basa, P
osmotik, tulang & gigi; pembekuan darah dan
aktifitas enzim
Fosfor: pembentukan tulang & gigi, metab energi,
keseimbangan asam basa
Mg: aktifator enzim gugus fosfat
Fe2+: pembawa O2 dalam Hb
Iod: fungsi kel. Tiroid, program iodisasi

Garam-garam mineral (Seny. Anorganik)

jumlah yang diperlukan tubuh hanya kecil
tetapi diperlukan untuk semua proses
dalam tubuh
 Metabolisme Kalsium
Normal ranges
Regulated with a normal total calcium of 2.2-
2.6 mmol/L (9-10.5 mg/dL)
normal ionized calcium of 1.1-1.4 mmol/L (4.5-
5.6 mg/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% (10 mmol) is
absorbed in small intestine, and 5 mmol
leaves the body in feces, netting 5 mmol 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 250 mmol a day in pro-urine, and

resorbs 245 mmol net loss in the urine of
5 mmol/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 5 mmol 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
osteoporosis
Calcium 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
 PHOSPHORUS METABOLISM
Phosphorus,
1.Found in ATP high energy bonds
2.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

Manifestations
1. 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.
 Magnesium 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 tissue
Acid 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 plasma

The 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
 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 water
with 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 causes
a. 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 causes
a. 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.
 brush border
lumen side
Na+ 1o 3 Na +
o active

varius
substrates
Na+
o 2
2
active uphill symport ATPase 1o blood side

2 K+

H+ O 3
H+
Na+ / H +
anti porter HCO
-
3
o
9
Cl
-

o 4
ATP
ADP
low Na+
hi K +
H+

o 5
varius organic become ionized o
8 amines
organic bases
cations+
-
organic varius organic HCO
anions o 6 anions
/
3
o
7 Na+
-
organic acids
OH - / HCO3- -
OH / HCO3-
This mekanism is
blocked by low
concentration of organic acids
 Transport ion di dalam kolon ditandai oleh adanya pompa
Na+/H+ ; Cl- /HCO3- di sisi luminal
Di sisi basolateral Na+ , K+ ATP ase dan transport Cl- yang
dipermudah
Perbedaan 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)
 POTASSIUM METABOLISM
1. 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.
2. Potassium is influenced by factors such as insulin and epinephrine, which
increase cellular uptake, and high total body potassium levels, which
reduce cellular uptake.
3. 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 causes
a. 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 causes
a. Low intake or gastrointestinal losses from diarrhea and/or vomiting, chronic
laxative use
b. 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 causes
a. 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.
 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
kDA
Each 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 species
Serum ferritin FR5Rl is the most convenient laboratory test to
estimate iron stores.
Ferritin concentrations increase drastically in the presence of
an infection or cancer
the 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
 Transferrin
Transferrin Iron Delivery and the Role of Iron Regulatory
Proteins
Apotransferrin is a protein of MW 90.000 kda consisting of
globulin, binding 2 atom iron in the formation transferrin in
plasma
Iron binding capacity normal 20-23% saturated
Iron overload capacity carier transferrin decrease
Eritropoeitin 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
hemosiderin
Hemosiderin 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