Peshawar Medical College NWFP Pakistan Magnesium Peshawar Medical
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Peshawar Medical College NWFP Pakistan
Magnesium Peshawar Medical College NWFP Pakistan
Introduction • Magnesium, an abundant mineral in the body, is naturally present in many foods, added to other food products, available as a dietary supplement, and present in some medicines (such as antacids and laxatives). Peshawar Medical College NWFP Pakistan
• Magnesium is a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation. Peshawar Medical College NWFP Pakistan
• Magnesium is required for energy production, oxidative phosphorylation, and glycolysis. It contributes to the structural development of bone and is required for the synthesis of DNA, RNA, and the antioxidant glutathione Peshawar Medical College NWFP Pakistan
• Magnesium also plays a role in the active transport of calcium and potassium ions across cell membranes, a process that is important to nerve impulse conduction, muscle contraction, and normal heart rhythm Peshawar Medical College NWFP Pakistan
Magnesium Atomic No. 12 Atomic mass: 24 Peshawar Medical College NWFP Pakistan
Magnesium • Mg is one of three major minerals in human body • 4 th most abundant • Lowest in amount of the three major mineral • 20 – 35 grams is total body content Peshawar Medical College NWFP Pakistan
DISTRIBUTION • 60 – 70% is complex with calcium and phosphorous in bones • Remainder is present in the body fluids and concentrated Within cells. • Mg : calcium( within cells) is about 3 : 1 • Whole blood contains about twice as much Mg as in serum, as is concentrated in RBCs • 2% of the body’s Mg is in ECF • Serum level is 1. 5 – 2. 5 m. Eqt/L Peshawar Medical College NWFP Pakistan
DISTRIBUTION (Contd. ) • 80% is ionized and diffusible • 20% bound to proteins • Muscles contain more Mg than Ca++. (As is required as activator for many of phosphate group transfer enzymes) Peshawar Medical College NWFP Pakistan
Functions 1. Essential element because is catalyst for numerous biologic reactions 2. It helps maintain the electrical potential in: Nerves for the transmission of nerve impulses Muscle membrane for the muscle contraction 3. Involved in active transport across cell membrane 4. Inhibits ATP ase Activity Peshawar Medical College NWFP Pakistan
Functions (Contd. ) 5. Its salts are irritant to intestine, used as purgative 6. CNS depressant and lowers neuro - muscular irritability 7. In Kidney insufficiency, level in blood increases, Increased level have adverse effect on cardiac muscle Peshawar Medical College NWFP Pakistan
Dietary Sources • Widely distributed in foods Richest sources include – Nuts – Sea foods – Whole grain – Dried beans – Peas – Green leafy vegetables – Dietary deficiency is rare Peshawar Medical College NWFP Pakistan
Recommended Dietary Allowances Infants 0 – 0. 5 – 1. 0 50 mg 70 mg Children 1– 3 4– 6 7 – 10 150 mg 200 mg 250 mg Peshawar Medical College NWFP Pakistan
Recommended Dietary Allowances (Contd. ) Adults 11 – 14 15 – 18 19 – 22 23 – 50 51+ Pregnancy and Lactation Male 350 400 350 350 Female 300 300 300 + 150 mg Peshawar Medical College NWFP Pakistan
Peshawar Medical College NWFP Pakistan
Absorption and Metabolism • 40 – 45% of dietary Mg++ absorbed from an average diet • With High Mg++ diet the %age of absorption falls • Low Mg++ diet the %age of absorption increase • Absorption occurs mostly in small intestine Peshawar Medical College NWFP Pakistan
Absorption and Metabolism (Contd. ) • Ca++ and Mg++ competes for absorption sites in the intestinal mucosa, intake of one requirement for other • Mg++ and K+ are conc. inside the cells. • Any change in balance produces neuromuscular irritability Peshawar Medical College NWFP Pakistan
Absorption and Metabolism Many of the Factors affecting Ca++ affects Mg++ Excess fat phosphates oxalic acid and phytic acid • Vit D and PTH have no effect on absorption, metabolism, excretion of Mg++ Peshawar Medical College NWFP Pakistan
Control and excretion • Body Mg++ level and pool is mainly controlled by kidney • Filtered out of the blood by glomeruli • Reabsorbed by renal tubules • Excreted in feces, is the unabsorbed dietary Peshawar Medical College NWFP Pakistan
Clinical Manifestation a. Deficiency or imbalance develops slowly due to persistent poor dietary intake or increased excretion. Mg++ slowly mobilized from bone. b. Low plasma level is associated with imbalance in ECF, leading to altered electrical potential of nerve and muscle cells. Deficiency: Leads to neuromuscular dysfunction. Peshawar Medical College NWFP Pakistan
Clinical Manifestation (Contd. ) c. Mg++ deficiency causes muscular hyper excitability , Tremors and convulsion. d. Behavioral disturbances are some time seen e. symptoms similar to Hypo calcaemic tetany are seen which can be differentiated by determining blood level of Ca++ & Mg++ Peshawar Medical College NWFP Pakistan
Mg++ deficiency can occur with – Cirrhosis liver – Malnutrition – Mal-absorption, – Diarrhea, – Laxatives – Impaired intake – Impaired absorption – Chronic alcoholism Peshawar Medical College NWFP Pakistan
Hypermagnesemia. With decrease in urinary excretion, plasma level is raised ------ Hypermagnesemia. Chronic renal disease severe dehydration Aldosterone deficiency oral intake of Mg. So 4 for constipation (specially with impaired renal functions). . Peshawar Medical College NWFP Pakistan
HYPOMAGNESEMIA Increased loss – – Diabetic ketoacidosis Diuretic therapy Hyper aldosteronism Assoc. with hypercalcaemia Renal Mg wasting Peshawar Medical College NWFP Pakistan
Reference values serum / plasma: 1. 5 – 2. 5 meqt/L 0. 65 – 1. 05 mmoles/litre CSF: up to 3. 0 meqt/L Muscles: up to 20 meqt/L RBCs: 5. 4 – 7. 8 mg /dl (5 meqt/L) Peshawar Medical College NWFP Pakistan
Sodium Natrium Na At. No. 11 Atomic mass 22. 98 Peshawar Medical College NWFP Pakistan
SODIUM • Alkali metal • Highly reactive, • Found in combined state, mostly as Salt. Peshawar Medical College NWFP Pakistan
Dietary sources Table salt “Na. Cl”, added to food Bread Cheese nuts spinach salad egg whole grain In all foods even water. 2. 5 grams of salt contain 1 gm of Na Peshawar Medical College NWFP Pakistan
REQUIREMENT Estimated safe and adequate daily dietary intake Infants 0 – 0. 5 yrs 0. 5 – 1. 0 yr 115 – 350 mg 250 – 750 mg Children 1 – 3 yrs 4 – 6 yrs 7 – 10 yrs 11+ 325 – 975 450 – 1350 600 – 1800 900 – 2700 Adults 1100 – 3300 Peshawar Medical College NWFP Pakistan
Infants requirement is low because of • Small lean body mass • Composition of feces • Cutaneous losses Minimum requirement for infants and young children is about 58 mg/day. Peshawar Medical College NWFP Pakistan
Human milk contains about 160 mg/litre Cows milk contains about 483 mg/litre Peshawar Medical College NWFP Pakistan
Absorption and Metabolism • Sodium is readily absorbed from ileum • Very little is excreted in feces except in diarrhea Peshawar Medical College NWFP Pakistan
Adults maintain sodium balance with little more than What is required by infant. • Kidneys maintain its balance in blood (Homeostasis) under the influence of a hormone “Aldosterone” on renal tubules. • When intake is decreased, aldosterone secretion Increases resulting in decrease of urinary excretion of sodium. Peshawar Medical College NWFP Pakistan
• Sweat is another major route of Sodium loss 20 -50 mg/L Peshawar Medical College NWFP Pakistan
Distribution • 1/3 rd of Na is in inorganic portion of skeleton • 2/3 rd in ECF and is osmoticaly active (water soluble and exchangeable) Peshawar Medical College NWFP Pakistan
Contd. • Total body content = 3800 – 4000 meqt (165 – 174 mg) ECF = 1750 meqt (76 mg) Soft tissues = 400 meqt (17. 4 mg) Bone = 1850 meqt (80 mg) Peshawar Medical College NWFP Pakistan
Distribution in body / tissue Whole blood = 70 meqt/L (161 mg/dl) Plasma = 143 meqt/L (330 mg/dl) Cells = 37 meqt/L (85 mg/dl) Muscle tissue = 26 – 70 meqt/L (60 – 160 mg/dl) Nerve tissue = ~ 140 meqt/L (312 mg/dl) Peshawar Medical College NWFP Pakistan
Functions • Major cation of ECF • Regulates Acid base balance, in conjunction with Cl / HCO 3 • It maintains the osmotic pressure of body fluids and protects severe fluid loss from body. • It preserves normal irritability of muscle and permeability of cells. Peshawar Medical College NWFP Pakistan
Deficiency Diseases or Symptom • When on normal diet No hyponatermia • Normal range in plasma is 135 – 145 meqt/L • Hyponatermia is mostly secondary to – Injury – Illness (G/E) – Burns – Use of diuretics Peshawar Medical College NWFP Pakistan
Deficiency Diseases or Symptom • Adrencorcortical insufficiency (Addison’s disease) • Chronic Renal disease resulting in poor re-absorption of sodium • Cirrhosis / CCF – serum sodium level, without reduction in total body content of Na. Peshawar Medical College NWFP Pakistan
Severe deficiency results in fall in tonicity as well as total volume of plasma Leading to Muscular cramps Extremities and abdomen Headache Nausea Dry skin Reduce sweating Low urine out put having high specific gravity. Peshawar Medical College NWFP Pakistan
• These are the conditions When Kidneys respond • Complete re-absorption of filtered sodium • Sodium excretion may fall to 20 meqt. / day or less. Peshawar Medical College NWFP Pakistan
Serum Sodium and adrenocortical function: Hypo-adrenalism (Addison’s disease) 113 meq/L Normal 135 – 145 meq/L Hyper-adrenalism (Cushing syndrome) 150 meq/L Peshawar Medical College NWFP Pakistan
Toxicity Diseases or Symptoms Hyper natremia may occur as a result of • Rapid administration of sodium salt • Hyper active adrenal cortex • Administration of Cortisone or deoxy cortisone • Dehydration excessive loss of water (Diabetes insipidus) May cause rise in blood pressure in susceptible individually. Peshawar Medical College NWFP Pakistan
Ions Contributing to Resting Potential • • Sodium (Na+) Chloride (Cl-) Potassium (K+) Negatively charged proteins (A-) – synthesized within the neuron – found primarily within the neuron Peshawar Medical College NWFP Pakistan
Peshawar Medical College NWFP Pakistan
POTASSIUM Kalium K At. No. 19 Atomic mass 39. 0 Peshawar Medical College NWFP Pakistan
Potassium • • • Alkali metal Highly reactive, Found in combined state, mostly as Salt. Peshawar Medical College NWFP Pakistan
Dietary sources • Chicken , Beef liver • Milk • Dried apricots, Peaches • Oranges, Banana, • All vegetables • Broccoli, Tomato Peshawar Medical College NWFP Pakistan
Requirement (mg) Infants 0 – 0. 5 yr 0. 5 – 1. 0 yr = 350 – 925 = 425 – 1275 Children 1 – 3 yr 4 – 6 yr 7 – 10 yr 11+ = 550 – 1650 = 775 – 2325 = 1000 – 3000 = 1525 – 4575 Adult = 1875 – 5600 Peshawar Medical College NWFP Pakistan
• Human milk contains about 500 mg/liter, cow’s milk contains 1365 mg/liter. Peshawar Medical College NWFP Pakistan
• In infants lean body mass and fecal losses are main determinants of potassium need. • Adults can maintain potassium balance with intake as low as infants. • Conc. of K+ is low in sweat. Less than 390 mg or 10 m. Eq/L as compared to sodium 25 – 30 m. Eq/L. Peshawar Medical College NWFP Pakistan
Absorption and Metabolism • K is readily absorbed from gut. • Very little K is lost in feces • Kidneys regulate its secretion under the influence of change in acid-base balance and activity of adrenal cortex. • Hyper kalemia not likely to develop even after ingestion or injection of large amount of K, if kidney function is intact. Peshawar Medical College NWFP Pakistan
DIETARY INTAKE AND EXCRETION • Daily intake recommended 1. 5 … 4. 5 grams • Average Diet contains 4 … 8. 0 grams EXCRETION • Excreted mostly in Urine • K ions filtered freely in the glomerular filterate • 93 % is reabsorbed mostly in the proximal convoluted tubules Peshawar Medical College NWFP Pakistan
Postassium • Major cation in ICF, maintains intracellular osmotic pressure. • ECF K+ is also an important factor in the skeletal and cardiac muscle activity • Contraction and depolarization of heart require potassium Peshawar Medical College NWFP Pakistan
Functions Proper plasma potassium level is essential for : 1. Normal heart function 2. Normal function of skeletal muscle fibers 3. Many enzyme reactions 4. Neuron and muscle activity Peshawar Medical College NWFP Pakistan
Functions 5. Resting membrane potential 6. An important role in the renal tubule, where K+ compete with H+ for exchange with Na+ 7. K + are required for the activity of Na / K- ATPase 98% body potassium is found within cells Peshawar Medical College NWFP Pakistan
Hypokalemia 1. Decrease K+ intake Starvation Malnutrition Old age K free fluid I. V Peshawar Medical College NWFP Pakistan
Hypokalemia 2. Excessive renal loss a. Diuresis with Frusemide and Thiazide b. Metabolic Alkalosis _ Deficiency of H+ ion – Tubular cells – More K+ ions undergo change with Na+ – Accelerate hypokalemia Peshawar Medical College NWFP Pakistan
Hypokalemia c. Renal Diseases – Excessive loss of K+ ion due to any cause/diuretic – Recovery phase of Acute Renal Failure – Chronic Pyelonephritis – Renal tubular Disorders Peshawar Medical College NWFP Pakistan
Loss from GIT • Vomiting • Diarrhea • GI. Fistulas • Excessive use of purgatives Peshawar Medical College NWFP Pakistan
Hypokalemia 4. Excessive Transfer to Cells a. Glycogenesis b. Paralysis Peshawar Medical College NWFP Pakistan
Causes of Hypokalemia • When Glucose is converted to glycogen for storage, some K is also stored. • Treatment with insulin results in glucose metabolism and storage along with K with-drawl from blood and results in Hypokalemia • K replacement should be considered. Peshawar Medical College NWFP Pakistan
Causes of Hypokalemia • Chronic wasting disease K lowering / deficit associated with malnutrition prolonged –ive Nitrogen balance and GE losses. • K is stored with nitrogen as muscle protein. Therefore, when breakdown occurs, K also transferred from ICF to ECF and removed by kidney. Peshawar Medical College NWFP Pakistan
Symptoms • Anorexia • Nausea • Muscle weakness • Mental depression • Respiratory weakness Peshawar Medical College NWFP Pakistan
Symptoms • Dyspnea • Rapid and irregular pulse • Low BP • ECG Changes: T-wave inversion • Reduce insulin secretion Peshawar Medical College NWFP Pakistan
Hyperkalemia • In health, generally not seen • K+ ion excretion is efficient • However certain clinical conditions lead to hyperkalemia Peshawar Medical College NWFP Pakistan
1. Release from tissues a. Crushed or infected tissues b. Intra vascular hemolysis c. Hematomas d. Burnt tissues e. Extensive surgical operations f. Sudden lysis of tumors Peshawar Medical College NWFP Pakistan
2. Renal Insufficiency • Excretion by the distil convoluted Tubules if lower, leads to retention of K+ • It is normally the case , when oligouria is associated Peshawar Medical College NWFP Pakistan
3. Chronic Dehydration & Shock • Decreased formation of urine • K+ retention Peshawar Medical College NWFP Pakistan
4. Acidosis : H+ ion displaces K+ ion 5. Fever : temp excessive break down of tissues body proteins 6. Addisons Disease Less K+ secreted by distal tubules into urine 7. I. V. administration Peshawar Medical College NWFP Pakistan
Symptoms 1. Heart – ECG changes when plasma K+ reaches 7 mmoles/L – T-waves becomes high peaked – P-waves disappears – QRS-complex broad – Wide spread cardiac blocks appear – Bradycardia and arrhythmias appear – Sudden death may take place Peshawar Medical College NWFP Pakistan
Symptoms 2. Nervous Symptoms – Mental confusion – Weakness of muscles – Tingling of the extremities Treatment: – Removal of the primary cause Peshawar Medical College NWFP Pakistan
Chloride Cl At. No. 17 Atomic mass 35. 5 Peshawar Medical College NWFP Pakistan
CHLORIDE Halogen – highly reactive, high electro negativity special affinity to electropositive alkali metal to form ionic compound. Peshawar Medical College NWFP Pakistan
Dietary sources: Exist almost exclusively as Na. Cl Intake of Cl- is adequate as long as Na. Cl Human milk contains 11 m. Eq/L chloride Peshawar Medical College NWFP Pakistan
REQUIREMENT (in mg) Infants 0 – 0. 5 – 1. 0 275 – 700 400 – 1200 Children 1– 3 4– 6 7 – 10 11+ 500 – 1500 700 – 2100 925 – 2775 1400 – 4200 Adult 1700 – 5100 Peshawar Medical College NWFP Pakistan
Distribution in body • Whole Blood – 250 mg/dl • Plasma – 375 mg/dl • CSF – 440 mg/dl • Cells – 190 mg/100 grams • Muscles – 40 mg/100 grams Peshawar Medical College NWFP Pakistan
Absorption and excretion • Chloride is absorbed from small intestine and • Excreted through kidney. • Mechanism of Chloride uptake is unclear, but it appears to • depend on an exchange process with HCO 3 • Skin is another route of Loss---5 mmole/day depends on weather • Feces------5 mmoles/day • Urine----100 -200 mmoles/day Peshawar Medical College NWFP Pakistan
REGULATION • Control of absorption and excretion is similar to that of Sodium • Increase in blood volume decreases reabsorption of Chloride and vice versa • Plasma level of Chloride varies with Na and to a great extent depends on the plasma concentration of Na and HCO 3 Peshawar Medical College NWFP Pakistan
METABOLISM • Any abnormality in Na metabolism will also result in derangements of chloride metabolism. • When Na losses are excessive as in profuse sweating, diarrhea or endocrine disorders. • There is an accompanying loss of chloride with loss of gastric juice. Peshawar Medical College NWFP Pakistan
FUNCTIONS • Major Anion of ECF • Essential in fluid balance • Regulation of osmotic pressure • Acid base equilibrium and formation of HCl Peshawar Medical College NWFP Pakistan
FUNCTIONS • Highest concentration being in CSF and secretion of GIT, helps in digestion and provision of acidic environment Peshawar Medical College NWFP Pakistan
Chloride being present in cell (RBC) as a component crosses cell membrane to establish equilibrium between cell contents and extra cellular fluid and minimize fluid shift. Chloride also enhances the ability of blood to carry large amounts of CO 2 to the lungs and aids in potassium conservation. Peshawar Medical College NWFP Pakistan
Hypo-chloremic Alkalosis • Loss of chloride exceeds that of Na causing an increase in bicarbonate and results in hypo-chloremic alkalosis. Peshawar Medical College NWFP Pakistan
Sulfur S At. No. 16 Atomic Mass: 32 Peshawar Medical College NWFP Pakistan
Sulfur • Sulfur an important non metal of cell protein. • All cells of body Peshawar Medical College NWFP Pakistan
Sulfur is an essential component of amino acids COOH NH 2 – C CH 2 – S – H Cysteine COOH NH 2 – C – H CH 2 – S – CH 3 Methionine Peshawar Medical College NWFP Pakistan
Functions • Sulfur is essential for all animal species as they all require S – containing AA. • Important constituent of body protein. • Important component of Muco-polysaccharides Chondriotin sulphate found in Tendons, Cartilage, skin & bones • Also present in Heparin, Insulin and many coenzymes Thiamin, biotin, coenzyme A and Glutathione. Peshawar Medical College NWFP Pakistan
Important functions • - S - bridge gives stability to polypeptide units in insulin and immunoglobulin • Important component in intermediary metabolism and detoxification mechanism • Keratin proteins of hair and nails are rich in Sulphur • Active sites of many coenzymes • Bile salts contain Sulphur Peshawar Medical College NWFP Pakistan
DIETARY SOURCES • Sulfur mainly is obtained from organic sources. • Proteins containing amino acid cysteine and methionine. • Proteins contains about 1% Sulfur by weight. • Foods such as milk, meat, legumes and eggs are good sources Peshawar Medical College NWFP Pakistan
Inorganic sulphates of Na, K, Mg are although available in food but not considered as good sources. Peshawar Medical College NWFP Pakistan
Daily requirements Not yet established precisely. Diet adequate in the AA (Cys and Meth) considered adequate to meet requirement. Peshawar Medical College NWFP Pakistan
Absorption of Sulphur in diet is in two forms. 1. Inorganic Sulphur: Na K Mg Suphates And is absorbed as such from the intestine. Peshawar Medical College NWFP Pakistan
ABSORPTION 2. • Sulphur is ingested as organic sulphates, as in proteins • Sulphur containing amino acid are absorbed by active transport. • Catabolism of S containing amino acids yields inorganic sulphates, which are converted in liver to conjugated sulphates by conjugation Peshawar Medical College NWFP Pakistan
Absorption of Sulphur Organic Sulphur from Sulpholipids and Glycoprotein is first digested to form amino acid and SO 3 / SO 4 If SO 4 is formed then it is absorbed but if SO 3 is formed then it is excreted in feces Peshawar Medical College NWFP Pakistan
Absorption of Sulphur Bacteria converts SO 3 to SO 4 and is absorbed. All S after absorption is ultimately oxidized in liver to sulphates and later excreted in urine. Peshawar Medical College NWFP Pakistan
Distribution • It accounts for about 175 gram in adult man(150 -200 grams of TBW) Peshawar Medical College NWFP Pakistan
Distribution • Mainly found a organic compounds: – Methionine Many proteins – Cystein Hormones – Heparin Keratin – Glutathione Tissue and body fluids – Thiamine Biotin , Co. A – Lipoic acid Taurocholic Acid Peshawar Medical College NWFP Pakistan
Excretion 1. A normal healthy individual excretes about 1 gram/day Sulfur via Urine a. Inorganic sulfates : 80% (Detectable with Bacl 2 directly) b. Organic sulfates : 10% (Detectable with Bacl 2 after hydrolyzing with HCl) ( conjugated) c. Neutral Sulfur : 10%. This fraction is un-oxidized Sulfur containing organic compounds like AA, thiosulfate Peshawar Medical College NWFP Pakistan
Excretion 2. Sulphur is lost from body by excretion in bile. 3. Increased in excessive tissue protein catabolism like in fever or with chemotherapy/ raditherapy 4. Decreased Sulphur excretion in Renal impairment Peshawar Medical College NWFP Pakistan
Reference values Blood contains 0. 1 -1. 0 mg/dl Sulfur as organic compound Total : 2. 2 – 4 -5 mq/dl Inorganic : 0. 5 – 1. 1 Organic : 0. 1 – 1. 0 Neutral : 1. 7 – 3. 5 Peshawar Medical College NWFP Pakistan
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