Clinical Biochemistry 2nd stage college of medicine Dr. Suhayr Aesa
MINERALS METABOLISM
PhosphorusPhosphorus: Dietary sources are cheese, milk, nuts. Eggs and organ meats.
Absorption and regulation is similar to that of Calcium.
Functions:
Constituent of bone and teeth
Needed for the synthesis of energy rich molecules like ATP and Creatin phosphate.
It forms Phosphate buffer in blood.
Constituent of phospholipids, biomolecules and coenzymes (TPP).
Sodium and Potassium
Sodium and Potassium: They are important in cell, muscle physiology, transmission of messages and other biological processes.Sodium is the principal cation of extra cellular fluid. It is commonly found in all types of foods. Recommended daily allowance (RDA) is 5-10 gm. It is excreted in the urine. The concentrations are maintained by Aldosterone.
Potassium is intracellular cation; daily requirement is 1 gm/day. Its excretion is through kidney, linked to sodium excretion. Since both are widely distributed, deficiency of the two elements is rarely found.
Functions:
Sodium maintains osmotic pressure of extra cellular fluid and ECF balance.
It has a role , along with others, in the neuromuscular excitability
Sodium is exchanged with Hydrogen in renal tubules to acidify urine.
Sodium pump keeps sodium in far higher concentration outside the cell .This results high polarization, create resting membrane potential.
Sodium and Potassium maintain the degree of hydration of plasma proteins, and there by viscosity of blood.
Potassium is critically important for the functioning of cardiac muscle.
Hypernatremia: It occurs nearly always due to water deficiencies rather than Na2+ excess. Increased sodium is found in ECF. It may be due to increased sodium in the body, decreased body water. It is usually seen in patients with dehydration, on steroid therapy or excess sodium intake.
Hyponatremia: It is common in patients who are in diuretics or excessive sweating, kidney disease, diarrhea and congestive heart failure.
Hyperkalemia is found in patients who are on excess intake orally or given intravenous drip. Other causes are decreased excretion by the kidney, diseases like Anuria, tissue damage or Diabetes Mellitus.
Hypokalemia: Low potassium is not due to dietary deficiency but due to conditions like vomiting, diarrhea. Habitual users of laxatives are prone to the condition.
Trace elements
Daily requirements of some elements is very less .Such elements are included in trace elements.
Iron
In body it is found in Haemoglobin, Myoglobin, ferritin, hemosiderin, transferrine and enzymes like cytochromes etc. RDA is 10-20mgs. Sources are meat, fish, eggs, cereals, green leafy vegetables. Milk is deficient in Iron.
Absorption:
is through intestinal mucosa.
Requires acidic pH of stomach. Ascorbic acid and Ceruloplasmin promotes absorption. It combines with intracellular binding protein Apoferritin to ferritin. Almost 300 ferric ions can bind to one molecule of apoferritin..
For transport, free iron binds to Apotransferrin, in blood to form transferrin. It is the major transport form of iron. It also prevents toxicity of free iron. Excessive binding of iron causes denaturation of ferritin molecule. It undergoes aggregation, to form hemosiderin. Mobilization of iron from hemosiderin is very slow. Thus there is
accumulation of hemosiderin, the condition is called hemosiderosis. Massive deposits of hemosiderin in tissues lead to hemachromatosis. If this takes place in liver, it causes cirrhosis. In pancreas, it damages β cells, result in Bronze diabetes. The skin of the patient has bronze coloration. Oxidative damage to cardiac muscle is a biggest concern. Iron is stored in liver, spleen and bone marrow.
Fig (1): Homeostasis of Iron in blood
Causes of iron deficiency:Storage depletion
Reduced dietary intake.
Malnutrition
Hemolysis
Children who are on milk diet only are prone to iron deficiency.
Chronic bleeding, irregular menstrual cycles
Peptic ulcer, piles
Hook worm infection
Repeated malarial infections.
Iron deficiency cause anemia or hypochromic microcytic anemia.
It is associated with low hemoglobin and ferritin.
Copper (Cu)
Humans contain around 100 mgs of copper. Liver, brain, kidney and heart are rich in copper. Free copper is 4%, 96 % is bound to Ceruloplasmin in body.
Sources: cereals, legumes, raisins, nuts etc
Functions:
Cofactor of enzymes like cytochrome oxidase, dopamine decarboxylase, tyrosinase, Cytochrome C oxidase and superoxide dismutase and monoamine oxidases are dependent on copper. Tyrosyl oxidase is important for collagen metabolism
Ceruloplasmin (serum ferroxidase) catalyses Fe++ to Fe+++, a pre requisite for the incorporation of iron into transferrin.
Ceruloplasmin promotes iron absorption.
Copper deficiency:Causes anemia.(Microcytic,normochromic anemia)
Failure of melanin formation because tyrosine oxidase becomes inactive.
Menkes disease or Kinky hair syndrome: It is fatal sex linked recessive disorder in which there is cerebral and cerebellar degeneration, connective tissue abnormalities and kinky hair.
Both serum [Copper] and [Ceruloplasmin] is low.
Absorption of copper from the intestine is grossly impaired, but treatment with parentral copper has not proved successful.
It is X- linked disorder. Patient has normal absorption of iron but transport across the serosa aspect of mucosal membrane is defective. Patient suffers from mental retardation.
Wilsons disease: It is an Autosomal, recessive disorder.
There is a decrease in the biliary excretion of copper.
Blood and tissue copper is high in these patients. It leads to retention of copper, followed by hepato-lenticular degeneration. However, Ceruloplasmin synthesis is incomplete in the liver.
Patient suffers from progressive hepatic cirrhosis and finally liver failure.
There is dysfunction of lenticular region of brain Defective tubular reabsorption in kidney leads to amino aciduria.
Copper deposition in the eye, as golden brown or green ring around the cornea. Patients are treated with Pencillamine, which binds to tissue copper and mobilizes it.
Magnesium:
It is an intracellular ion, essential for life.
Sources: Widely distributed in vegetables, chlorophyll, cereals, beans, potatoes, cheese and animal tissues.
Maximum concentration is found in bones, little in Extra-cellular fluid (ECF) and soft tissues.
2/3 in blood is in ionic form, rest is bound to protein.
It is absorbed from the small bowel.
It is excreted through feces, urine and sweat.
Functions:
Role in enzyme action. It is a cofactor for peptidases, ribonucleases, glycolytic enzymes etc.
Its action is similar to that of calcium in neuromuscular irritability.
High levels depress nerve conduction, low levels may cause Tetany.
Major part is found in bones. In teeth, it is present as dentin and enamel.
Magnesium deficiency occurs rarely in man.
Fluorine
It is solely derived from water, tea, and fish Daily intake should not be more than 3mg.
Excess is toxic, lethal dose is 2.5 gm. It is absorbed by diffusion from intestine. Mostly it is found in the bones and teeth. It is eliminated in the urine.
Functions:
Fluorine is important for tooth development and prevention of Dental Caries.
High consumption, leads to high concentration of Fluorine in enamel and dentine.
It decreases calcium deposition.
Teeth acquires mottling of enamel, teeth develop pits and discoloration.
Bones contain traces of fluorine. Small quantities of it promotes bone development,
increases retention of calcium and phosphate, prevent osteoporosis
High level of fluoride in bone causes abnormal rise in calcium deposition, increases bone
density
Flurosis is due to toxicity of fluoride. Excess can be due to high dietary intake, contaminated water or inhalation of fluorine.
It damages mitochondria
Inhibit enzymes which depend on Mg, like Succinic dehydrogenase.
Protein synthesis decreases in muscle, heart, kidney, lungs, pancreas and spleen.
Collagen synthesis is adversely affected.
Iodine
Sources: Vegetables, fruits obtained from sea shore, sea fish are rich in iodine. People who live on hills do not get iodine from diet. They are prone to suffer from deficiency. It is absorbed from small intestines and transported as protein complex in plasma. See the details of iodine metabolism, thyroid hormone synthesis from the chapter on hormones.
Zinc
Sources are liver, milk, fish, dairy products, cereals, legumes, pulses, oil seeds, yeast and spinach etc.It is absorbed in duodenum and ileum. Absorption of Zinc from the intestine appear to be controlled in a manner similar to Iron. It is transported bound to a protein (α2-macroglobulin andtransferrin)
It is excreted in urine and feces.
Diets rich in calcium, phosphates interfere with Zn absorption. RDA is 15-20mgs for adult, 3-15mgs for infants and children It is bound as complex of protein Metallothionein. The sulfur groups of the protein chelate zinc. The body does not store Zinc to any appreciable extent in any organ, urinary excretion is fairly constant at 10 μmol/day.
Functions:
Zinc is important for the activity of a number of enzymes like
Carbonic anhydrase
Alkaline phosphatase
Alchol dehydrogenase
Porphobilinogn synthase
Leucine aminopeptidase
Carboxy peptidase
Aldolase in glycolysis
DNA, RNA polymerases as zinc has crucial role in DNA.
Release of vitamin A from liver requires Zinc. Retenene reductase (zinc enzyme) participates in the regeneration of rhodopsin (visual cycle).
Insulin is secreted, stored as a complex of Zinc
It is important for wound healing.
Deficiency of Zinc:
Patients requiring total parentral nutration, pregnancy, lactation, old age and alcoholics have been reported as being associated with increased incidence of Zinc deficiency. It is usually associated with protein energy malnutrition (PEM) It is caused by diuretics, chelating agents and anti-cancer drug treatment
results in dwarfism and hypogonadism
Delayed sexual development
It decreases spermatogenesis in males and irregular menstrual cycles in females.
It stimulates ribonuclease activity; thereby it affects the synthesis of mononucleotides and nucleic acids.
Hepatosplenomegaly
Severe Zinc deficiency can lead to a postular skin rash, loss of body hair, diarrhea and mood change.
Selenium
Selenium is rich in liver, kidney, finger nails. Usually plant products are good sources than animal based diet. It is absorbed from duodenum, transported as selenomethionine. It forms a complex with plasma proteins for transport. In tissues, free selenium is released. It is excreted in urine. RDA 50-100 μg Adult 20-120μg Children
Functions:
• Glutathione peroxidase is a selenium dependent enzyme. The enzyme has a role in oxidative damage by free radicals. The enzyme is critically important for the membrane stability of Red blood cells. Selenium has sparing action on vitamin E, by three ways. It promotes digestion, absorption of lipids and vitamin E. It is a part of glutathione peroxidase, prevents peroxidation of PUFA in the membranes. This in turn reduces the requirement of vitamin E. It helps in the retention of vitamin E in the blood. It is a cofactor for an enzyme involved in the synthesis of thyroid hormone.
Deficiency of selenium:
Liver cirrhosis
Pancreatic degeneration
Myopathy, infertility
Failure of growth
Toxicity:
- Selenium toxicity is called Selenosis
- Toxic dose is 900micro gram/day
- It is present in metal polishes and anti-rust compounds
The Toxicity symptoms are Hair loss,failing of nails, diarrhea,weight loss and gaslicky odour in breath(due to the presence of dimethyl selenide in expired air). Halogenated aromatic hydrocarbons are useful in the treatment of Selenosis.