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Almaaqal University Biochemistry Electrolytes and Trace elements disorder Dr/ Wael Sobhy Darwish Biochemistry PhD  Introduction Electrolytes are minerals in your blood and other body fluids t...

Almaaqal University Biochemistry Electrolytes and Trace elements disorder Dr/ Wael Sobhy Darwish Biochemistry PhD  Introduction Electrolytes are minerals in your blood and other body fluids that carry an electric charge. Electrolytes affect how your body functions in many ways, including: The amount of water in your body. The acidity of your blood (pH)  Sodium (Na ) ++ Sodium is the major cation of extracellular fluids. Dietary food sources Table salt (NaCl), salty foods, animal foods, milk and some vegetables. Metabolic functions It maintains the osmotic pressure and water balance. It is a constituent of buffer and involved in the maintenance of acid-base balance. It maintains muscle and nerve irritability at the proper level. Sodium is involved in cell membrane permeability. Sodium is required for intestinal absorption of glucose, galactose and amino acids.  Sodium depletion Sodium is lost largely via the urine, with only minimal loss via the feces or skin. Excretion of sodium is regulated by aldosterone, which increases its reabsorption. Increased sodium loss in urine can occur in diseases, e.g., diabetes mellitus and Addison’s disease, following excessive doses of diuretic drugs, and in cases of renal tubular damage, as in chronic renal failure. The imbalance of sodium concentration in the blood may be Too high (hypernatremia) or Too low (hyponatremia).  Hypernatremia Hypernatremia, The sodium level in the blood becomes abnormally high when water loss exceeds sodium loss. Usually, hypernatremia results from dehydration. Dehydration occurs due to 1-Drinking too little. 2-Sweating excessively, 3- Diabetes mellitus. 7- Kidney disorders. 8- Diabetes insipidus. 9- Inadequate or ineffective vasopressin secretion or action. Hyponatremia Hyponatremia means that the sodium level in the blood is below normal. The normal blood sodium level is 135 to 145 milliequivalents/liter (mEq/L). When sodium is too low, extra water goes into your cells and makes them swell. This swelling can be dangerous, especially in the brain. Causes: Kidney failure Congestive heart failure - excess fluid builds up in the body Diuretics (water pills) Severe vomiting or diarrhea Excessive thirst (primary polydipsia) - causes too much fluid intake  Potassium(k+) Potassium is the main intracellular cation. About 98% of total body potassium is in cells only 2% in the ECF. Absorption Potassium is absorbed readily by passive diffusion from gastrointestinal tract. Excretion The major rout of K+ excretion is by the kidney and very small amount through the gastrointestinal tract, the skin Serum potassium The concentration of potassium in serum is around 3.5–5 mEq/L. Serum potassium concentration does not vary appreciably in response to water loss or retention.  Potassium homeostasis Potassium homeostasis is controlled by renal glomerular filtration and tubular secretion. Increased sodium entering the distal nephron results in an increased urinary loss of potassium. Potassium is necessary for the normal functioning of cells, nerves, and muscle contraction.  Hyperkalemia Hyperkalemia is a serious and potentially life-threatening condition Causes 1- Kidney disorders 2- Drugs that affect kidney function (Diuretic drugs) 3- Consumption of too much supplemental potassium. 4-Treatments that contain potassium 5-Addison disease can also cause hyperkalemia. (Low aldosterone) Usually, hyperkalemia must be severe before it causes symptoms, feeling weak and tired, nauseous, mainly abnormal heart rhythms , or stop beating (cardiac arrest).  Hypokalemia Hypokalemia, the level of potassium in blood is too low. A low potassium level can make muscles feel weak, cramp, twitch, or even become paralyzed, and abnormal heart rhythms may develop. Causes Vomiting, diarrhea, or excessive laxative use. Too much potassium is excreted in urine. In many adrenal disorders, such as Cushing syndrome, the adrenal glands produce too much aldosterone  Calcium ++ (Ca ) Calcium is the most abundant mineral in the body and carry an electric charge when dissolved in body fluids. About 99% of the body’s calcium is stored in the bones. But muscle cells and blood also contain calcium. About 40% of the calcium in the blood is bounded to albumin protein in the blood. Protein-bound calcium acts as a reserve source of calcium for the cells but has no active function in the body. Only unbound calcium (Ionized( affects the body’s functions. Function of Calcium -Formation of bone and teeth -Muscle contraction -Normal functioning of many enzymes -Blood clotting -Normal heart rhythm  Hypercalcemia: Symptoms Digestive problems such as nausea or vomiting, poor appetite, or constipation. Feeling thirsty, and may urinate a lot. If severe, hypercalcemia leads to confusion and eventually coma. Causes: -Hyperparathyroidism: One or more of the four parathyroid glands secrete high parathyroid hormone. High calcium intake: People with peptic ulcers if they drink a lot of milk and take calcium-containing antacids for relief. The resulting disorder is called the milk-alkali syndrome. -Too much vitamin D intake:  Cancer: Cancer cells increases the calcium level in blood. Calcium released into the blood when cancer spreads (metastasizes) to bone and destroys bone cells. Multiple myeloma (a cancer involving bone marrow) can also lead to the destruction of bone and result in hypercalcemia. Bone disorders: If bone is broken down (resorbed) or destroyed, calcium is released into the blood, sometimes causing hypercalcemia. In Paget disease, bone is broken down, due to hyperparathyroidism. Severe hyperthyroidism: lead to increasing resorption of bone tissue.  Hypocalcemia Hypocalcemia, the calcium level in blood is too low. A low calcium level may result from a problem with the parathyroid glands, diet, kidney disorders, or certain drugs. Hypocalcemia lead to, muscle cramps, and people may become confused, depressed, and forgetful and have tingling in their lips, fingers, and feet as well as stiff, achy muscles. Calcium and vitamin D supplements may be used to treat hypocalcemia. Hypocalcemia causes problems only when the level of unbound calcium (ionized calcium) is low.  Magnesium (Mg++ ): Magnesium carries an electric charge when dissolved in body fluids such as blood. The majority of magnesium in the body is uncharged and bound to proteins or stored in bone. Bone contains about half of the body’s magnesium and it is very little in the blood. The level of magnesium in the blood depends on obtaining and exertion of magnesium. Function of magnesium 1. Formation of bone and teeth and for normal nerve and muscle function. 2. Act as a co-enzyme. 3. Metabolism of calcium and potassium.  Hypermagnesemia Hypermagnesemia, the level of magnesium in the blood is too high. It is uncommon. Causes. It usually develops only when people with kidney failure are given magnesium salts or take drugs that contain magnesium (such as some antiacids or laxatives). Hypermagnesemia may cause -Muscle weakness -Low blood pressure – Impaired breathing. When hypermagnesemia is severe, the heart can stop beating. Hypomagnesemia Hypomagnesemia, the level of magnesium in blood is too low. Causes: 1. People consume less Mg in their diet or because the intestine cannot absorb nutrients normally 2. The kidneys or intestine excrete too much magnesium and in diarrhea. 3. Consuming large amounts of alcohol reduces the consumption of food and increases the excretion of magnesium 4. High levels of aldosterone, vasopressin, or thyroid hormones, 5. Drugs that increase magnesium excretion, including diuretics, the antifungal drug amphotericin B, and the chemotherapy drug cisplatin 6. Breastfeeding, which increases requirements for magnesium  Iron (Fe): Iron is an essential constituent of haemoglobin and enzymes such as cytochrome oxidase, catalase and peroxidase. Function: 1- Transport oxygen to tissues (through Hb) 2- In oxidation-reduction reactions (cytochrome system). Sources: meat, liver, eggs, spinach and fruits. Absorption: Iron is present in food in ferric (Fe+++) form which must be reduced to ferrous (Fe++) form to be easily absorbed in duodenum and stomach. Gastric HCl and some organic acids reduced it by reducing substances such as cysteine or ascorbic acid.  Transport and storage Iron is transported in plasma in ferric form, which remains firmly bound to transferrin. The normal concentration of protein bound iron in plasma is 50 - 180μ gm/ 100 ml. Iron is stored as ferritin in mucosal cells of intestine, liver, spleen and bone marrow. Iron overload Hemosiderosis and hemochromatosis are the conditions associated with iron overload. Hemosiderosis: Hemosiderosis is a term that has been used to imply an increase in iron stores as hemosiderin without associated tissue injury. Hemosiderosis is an initial stage of iron overload.  Hemochromatosis: Hemochromatosis is a clinical condition in which excessive deposits of iron in the form of hemosiderin are present in the tissues, with injury to involved organs as follows: – Liver: Leading to cirrhosis – Pancreas: Leading to fibrotic damage to pancreas with diabetes mellitus – Skin: Skin pigmentation. – Endocrine organ: leading to hypothyroidism, testicular atrophy – Joints: Leading to arthritis. – Heart: Leading to arrhythmia and heart failure.  Copper (Cu) Copper plays an important role in iron absorption. Ceruloplasmin, the major copper containing protein in plasma oxidizes ferrous ion to ferric state before its binding to transferrin. Copper is required for the synthesis of hemoglobin. Being a constituent of enzyme tyrosinase, copper is required for synthesis of melanin pigment. Copper is required for the synthesis of collagen and elastin. Normal plasma copper concentrations are usually between 100 to 200 mg/dl of which 90% is bound to ceruloplasmin.  Signs of copper deficiency include: 1. Neutropenia (decreased number of neutrophils) and hypochromic anemia. 2. Osteoporosis 3. Decreased pigmentation of skin due to depressed copper dependent tyrosinase activity. 4. In the later stages neurological abnormalities probably caused by depressed cytochrome oxidase activity. Inborn errors of copper metabolism There are two inborn errors of copper metabolism: 1. Menkes syndrome 2. Wilson’s disease.  Wilson’s disease It is an autosomal recessive disorder in which excessive accumulation of copper occurs in tissues. The possible causes are: An impairment in binding capacity of copper to ceruloplasmin or inability of liver to synthesize ceruloplasmin or both. An impairment in excretion of copper in bile. Symptoms Accumulation of copper in liver, brain, kidney and eyes leading to copper toxicosis. Excessive deposition of copper in brain and liver leads to neurological symptoms and liver damage leading to cirrhosis. Copper deposition in kidney leads to renal tubular damage and those in cornea form yellow or brown ring around the cornea, known as Kayser-Fleisher (KF) rings. The disease is also characterized by low levels of copper and ceruloplasmin in plasma with increased excretion of copper in urine.  Fluorine (F) The body receives fluorine mainly from drinking water. Some sea fish and tea also contain small amount of fluoride. Inorganic fluoride is absorbed readily in the stomach and small intestine and distributed almost entirely to bone and teeth. About 50% of the daily intake is excreted through urine. Functions Fluoride is required for the formation of bone and teeth. Fluoride becomes incorporated into hydroxyapatite, the crystalline mineral of bones and teeth to form fluoroapatite. Fluoroapatite increases hardness of bone and teeth and provides protection against dental caries and attack by acids.  Deficiency symptoms Deficiency of fluoride leads to dental caries and osteoporosis. Toxicity Excessive amounts of fluoride can result in dental fluorosis. This condition results in teeth with a patch, dull white. A brown mottled appearance can also occur. It is known to inhibit several enzymes especially enolase of glycolysis.  Functions Zinc (Zn) Zinc is a constituent of a number of enzymes. For example, A – Carbonic anhydrase B– Alkaline phosphatase C– DNA and RNA-polymerases Zinc is necessary for the growth and division of cells. Zinc is an important element in wound healing as it is a necessary factor in the biosynthesis and integrity of connective tissue. Zinc is required for the secretion and storage of insulin from the β-cells of pancreas. Gustin, a Zn containing protein present in saliva is required for taste function. Therefore, zinc deficiency leads to loss of taste acuity.  Deficiency manifestation Zinc deficiency has many causes, but malnutrition and malabsorption are the most common. Clinical symptoms of zinc deficiency include: 1. Growth failure 2- Hair loss 3- Anemia 4- Loss of taste sensation 5- Impaired spermatogenesis 6- Neuropsychiatric symptoms. Acrodermatitis enteropathica: A rare inherited disorder of zinc metabolism is due to an inherited defect in zinc absorption that causes low plasma zinc concentration and reduced total body content of zinc, it is manifested in infancy as skin rash