(BQ) Part 2 book Essentials of biochemistry has contents: Water metabolism, mineral metabolism, hemoglobin metabolism, purine and pyrimidine nucleotide metabolism, replication, transcription and translation, genetic engineering, mechanism of hormone action,... and other contents.
e m e co re oo ks f eb om e c re oo ks f co m e fre ks oo eb m m m fre e co co e fre ks ks m eb oo oo m co fre oo eb m m eb oo ks ks e e co m • In a 70 kg adult the total body water is about 42 L • 28 L is of intracellular water (ICW) and 14 L of extra cellular water (ECW) • The ECW is distributed as 3.5 L plasma water (intravascular water) and 10.5 L interstitial water (extravascular) (Table 16.1) oo eb m eb e oo ks eb m Distribution of Water ks fre m co e fre fre ok s eb o Total body water can be theoretically divided into two main compartments (Fig 16.1): Extracellular water (ECW) and Intracellular water (ICW) • The ECW includes all water external to cell membranes The ECW can be further subdivided into: –– Intravascular water, i.e plasma –– Extravascular water, i.e interstitial fluid • The ICW includes all water within cell membranes and constitutes the medium in which chemical reactions of cell metabolism occur eb ks fre oo eb m e co m Total body water, includes water both inside and outside of cells and water normally present in the gastrointestinal and genitourinary systems Fig 16.1: Body water compartments m e co m co m e fre oo ks eb m fre fre ks oo m eb • It is a medium in which body solutes, both organic and inorganic, are dissolved and metabolic reactions take place • It acts as a vehicle for transport of solutes • Water itself participates as a substrate and a product in many chemical reactions, e.g in glycolysis, citric acid cycle and respiratory chain • The stability of subcellular structures and activities of numerous enzymes are dependent on adequate cell hydration • Water is involved in the regulation of body temperature because of its highest latent heat of evaporation • Water also acts as a lubricant in the body so as to prevent friction in joints, pleura, peritoneum and conjunctiva • Both a relative deficiency and an excess of water impair the function of tissues and organs TOTAL BODY WATER (TBW) AND ITS DISTRIBUTION m m co e e fre ks oo eb m co m co m m co m co m IMPORTANCE OF WATER m m m co e re ks f m m eb eb oo oo ¾¾ Electrolytes ¾¾ Regulation of Water and Electrolyte Balance ¾¾ Disorders of Water and Electrolyte Balances Water is the most abundant constituent of the human body accounting approximately 60 to 70% of the body mass in a normal adult Water content of the body changes with age It is about 75% in the newborn and decreases to less than 50% in older individuals Water content is greatest in brain tissue and least in adipose tissue co m fre eb m co m e ks fre re sf oo k ¾¾ Importance of Water ¾¾ Total Body Water (TBW) and its Distribution ¾¾ Normal Water Balance eb m ks oo oo eb m e co co m Water Metabolism Chapter outline INTRODUCTION om e ks fre fre oo ks m m eb 16 e c co e co m m m m e e e m m co CHAPTER e m e co re oo ks f om co m m co e fre ks eb m 100 m co m Gastrointestinal water loss through stool 200 2500 oo eb m m eb oo ks ks ks fre 2500 400 400 co m Sensible perspiration water loss e co e fre 1400 e Insensible water loss Through skin Through lungs mL fre Urine 1000 oo 1200 oo eb m e fre ks oo eb m m ks Source eb mL m e co m fre ok s oo Daily output of water 300 e c re oo ks f eb m co m e fre ks fre oo eb m Water from food eb m m co e re Water is lost from the body by following routes • Urinary water loss via kidney • Insensible water loss via skin and lungs • Sensible perspiration (sweating) • Gastrointestinal water loss through stool co m e co Water Output e fre ks oo eb m co m e fre oo ks eb eb o Under normal conditions: • Approximately, one-half to two-thirds of water intake is in the form of oral fluid intake, and • Approximately, one-half to one-third is in the form of oral intake of water in food • In addition, a small amount of water (150 to 350 ml/ day) is produced during metabolism of food called metabolic water • Oral water intake is regulated by a thirst center located in hypothalamus Increase in the osmolality of plasma causes increased water intake by stimulating thirst center Table 16.2: Average water balance in normal adult Water derived during metabolism of food (metabolic water) m m fre m co e e fre ks oo eb m co m m Drinking water co Water Intake Daily intake of water Source m ks ks fre oo eb co m co m m m eb oo k sf • Two important factors influence the distribution of water between intracellular and extracellular compartments are: –– Osmolality or osmolarity –– Colloidal osmotic pressure • Osmolarity or osmolality is a measure of solute particles present in fluid medium • Osmolarity is the number of moles per liter of solution and osmolality is the number of moles per kg of solvent • All molecules dissolved in the body water contribute to the osmotic pressure Thus, osmolarity or osmolality determines the osmotic pressure exerted by a solution across a membrane However, for biological fluids, the osmolality is more commonly used • The osmotic pressure of a solution is directly proportional to the concentration of osmotically active particles in that solution • In a normal person, the osmotic pressure of ECF (mainly due to Na+ ions) is equal to the osmotic pressure of ICF (which is mainly due to K+ ions) Due to this osmotic equilibrium there is no net movement of water in or out of the cells • A change in the concentration of osmotically active ions in either of the water compartments creates a difference fre e co re Factors Affecting Distribution of Water • The body water is maintained within the fairly constant limits by a regulation between the intake and output of water as shown in Table 16.2 • Average daily water turnover in the adult is approximately 2500 mL However, the range of water turnover depends on intake, environment and activity ks f 28.0 L m 67% co m Intracellular water (ICW) NORMAL WATER BALANCE e 10.5 L oo eb m 3.5 L 25% m 8% b Interstitial water oo ks 14 L eb 33% eb Extracellular water (ECW) 42 L eb – m Total body water (TBW) oo Volume in normal adult m Percentage of TBW oo Compartment Total om e ks fre fre oo ks eb m co of osmotic pressure and consequently movement of water between compartments occur • Water diffuses from a compartment of low osmolality to one of high osmolality until the osmotic pressures are identical in both of them Table 16.1: Distribution of water a Plasma e c co e co m m m m e e e m m Essentials of Biochemistry m co 288 e m m e co oo ks f eb m 40 103 e c 27 10 140 m 16 155 40 202 e eb eb oo ks oo ks fre fre e • Sodium is the principal cation of the extracellular fluid and comprises over 90% of the total cations, but has a low concentration in intracellular fluid and constitutes only 8% of the total cations • Potassium by contrast, is the principal cation of intracellular fluid and has a low concentration in extracellular fluid • Similar differences exist with the anions Chloride (Cl–) and bicarbonate (HCO3–) predominate in the extracellular fluid, while phosphate is the principal anion within the cells The term electrolytes applied in medicine to the four ions in plasma, (Na+, K+, CI– and HCO3–) that exert the greatest influence on water balance and acid-base balance co m co m Total re ks f HCO3– eb Cl– oo ks f re Anions SO4– 202 e 155 HPO4– om m Total 150 co Mg ++ m m m e co co e ks ks fre fre REGULATION OF WATER AND ELECTROLYTE BALANCE m m eb eb oo oo Water and electrolyte balance are regulated together It is regulated through following hormones: • Antidiuretic hormone (ADH) or vasopressin • The renin-angiotensin-aldosterone system (RAAS) • Atrial natriuretic factor (ANF) fre oo eb m m eb oo ks ks e e • Water intake is normally controlled by the sensation of thirst and its output by the action of hormone vasopressin, also known as antidiuretic hormone co m co m Antidiuretic Hormone (ADH) oo eb m re fre ks oo eb 10 ks fre m co e fre fre ok s m m e co ks fre oo e co m m eb • The electrolytes are well distributed in body fluids and play an important role in distribution and retention of body water by regulating the osmotic equilibrium • Total concentration of cations and anions in each compartment (ECF and ICF) is equal to maintain electrical neutrality The concentration of electrolytes in extracellular and intracellular fluid is shown in Table 16.3 There are striking differences in composition between the two fluids eb o K Ca++ m m co e fre ks oo eb m co m e fre oo ks eb m m 142 + oo oo eb m co m e fre ks oo eb m Electrolytes are the inorganic substances which are readily dissociated into positively charged (cations) and negatively charged (anions) ions Normal cellular functions and survival requires electrolytes which are maintained within narrow limits The concentration of electrolytes is expressed as milliequivalent per liter (mEq/L) rather than milligrams co m Na+ Protein Water loss from the gastrointestinal tract through stool is approximately 200 mL/day Distribution of Electrolytes Intracellular fluid mEq/L Cations eb co m e ks fre re sf oo k eb m co m Gastrointestinal Water Loss m Extracellular fluid mEq/L Organic acids Sensible perspiration via skin is negligible in cool environment but increases with surrounding temperature, body temperature or physical activity An increase in plasma osmolality causes a decrease in the rate of sensible perspiration co Ions m oo eb m Loss of water by diffusion through skin and through the lungs is known as insensible water because it is not apparent It is the only route by which water is lost without solute Normally, half of the insensible water loss occurs through the skin (about 400 mL) and half through the lungs (about 400 mL) Insensible water loss increases with increase in surrounding temperature, body temperature and physical activity e co co m m Insensible Water Loss ELECTROLYTES om e ks fre fre oo ks eb m Table 16.3: Electrolyte content of ECF and ICF In a normal individual, 1200 to 1500 mL of water is lost in urine per day Urine volume varies in response to changes in ECW volume and osmolality Sensible Perspiration e c co e co m m m m e e e m m co Urinary Water Loss 289 Water Metabolism e m e co re om e c re co m e fre ks oo eb m m m fre e co co e fre oo oo ks ks DISORDERS OF WATER AND ELECTROLYTE BALANCES eb eb Dehydration and overhydration are the disorders of water balance, which are due to an imbalance of water intake and output or sodium intake and output m co fre oo eb m m eb oo ks ks e e Dehydration may be defined as a state in which loss of water exceeds that of intake, as a result of which body’s water content gets reduced and the body is in negative water balance Dehydration may be of two types: m co m Dehydration oo eb m oo ks f eb m co m e fre oo ks eb m kidney Thus, kidney plays an important role in maintenance of electrolyte and water balance ks fre m co e fre Fig 16.3: Renin-angiotensin-aldosterone system (RAAS) in regulation of water and electrolyte balance m m e co ks fre oo eb m e co m fre ok s oo ks f eb m m co e re ks f oo eb fre ks oo eb m co m e fre oo ks eb ANF is a polypeptide hormone secreted by the right atrium of the heart It increases Na+ and water excretion by the eb o m m co e e fre ks • Renin is secreted in response to a decreased level of Na+ in the fluid of the distal tubule Renin converts angiotensinogen in plasma to angiotensin I, which in turn is converted to angiotensin II by angiotensin converting enzyme (ACE) Angiotensin II stimulates aldosterone secretion, thirsting behavior and ADH secretion Aldosterone stimulates Na+ reabsorption in the renal tubules in the exchange of H+ and K+ As a consequence of Na+ reabsorption, water is retained by the body (Fig 16.3) Atrial Natriuretic Factor (ANF) m m fre eb m co m e ks fre oo eb m co m (ADH) The major role of ADH is to increase the reabsorption of water from the kidney • An increase in plasma osmolality (due to deficiency of water) causes sensation of thirst and stimulates hypothalamic thirst center, which results in an increase in water intake An increase in plasma osmolality also stimulates hypothalamus to release ADH ADH then increases water reabsorption by the kidney All these events ultimately help to restore the plasma osmolality (Fig 16.2) • Conversely, a large intake of water causes fall in osmolality suppresses thirst and reduces ADH secretion, leading to a diuresis, producing large volume of dilute urine oo eb m m ks oo oo eb m m e co re sf oo k eb co m co m m om e ks fre fre oo ks eb m co m Fig 16.2: Regulation of water balance Renin-Angiotensin-Aldosterone System (RAAS) co e c co e co m m m m e e e m m Essentials of Biochemistry m co 290 e m om e c re oo ks f eb m fre e co m co m e ks oo eb m m m co co e e fre fre ks ks oo eb eb m co e fre ks m eb oo oo eb m m co m e co e m eb oo ks ok s fre fre Regulation of water and electrolyte balance ks fre m e co m Overhydration e co re oo ks f eb m m co e re ks f oo eb oo Factors affecting distribution of water Distribution of electrolytes Case History A 40-year-old female was brought to the hospital with complaints of persistent vomiting, loose motions, cramps and extreme weakness, sunken eyes and dry tongue Questions a Name the condition arising due to the above symp toms b What are the causes for the condition? c Which are the different types of the condition? d Suggest the treatment m m Body water compartments and their composition Dehydration m om ks oo eb m m e co ks fre oo eb Water distribution and its balance in the body eb o fre fre ks oo eb m co m e fre oo ks eb Composition of extracellular fluid m Symptoms of overhydration Nausea, vomiting, headache, muscular weakness confusion and in severe cases convulsions, coma and even death occurs Solve the Following Water balance and its regulation in the body m oo ks m co e e fre ks oo eb co m Overhydration is a state of pure water excess or water intoxication More often, water intoxication results due to the retention of excess water in the body, which can occur due to: • Renal failure • Excessive administration of fluids parenteral • Hypersecretion of ADH (syndrome of inappropriate ADH secretion, SIADH) This results in reduced plasma electrolytes with decreased osmolality EXAM QUESTIONS Short Notes m Overhydration or Water Intoxication eb ks fre oo eb m co m co m m Symptoms of dehydration • Symptoms of simple dehydration are intense thirst, mental confusion, fever and oliguria (decreased urine output) Treatment • Treatment of simple dehydration: The patient is asked to drink plenty of water If oral administration is not possible, an isotonic solution of 5% dextrose is given intravenously • Treatment of dehydration due to combined deficiency of water and electrolyte: An isotonic solution of sodium chloride (normal saline) is given intravenously m co m e e co re sf eb m Causes of dehydration • Simple dehydration results from deprivation of water either due to no or inadequate intake of water or due to excessive loss of water from body, e.g in diabetes insipidus • Dehydration due to combined deficiency of water and electrolyte occur as a result of vomiting, diarrhea, excessive sweating, salt wasting renal disease, and adrenocortical insufficiency (Addison’s disease) • Symptoms of dehydration due to combined deficiency of water and electrolytes are wrinkled skin, dry mucous membranes, muscle cramps, sunken eyeballs and increased blood urea nitrogen With increasing severity, weakness, hypotension and shock may occur m oo eb m m m co oo k • Dehydration due to combined water and electrolyte sodium deficiency is more common than simple dehydration fre e ks fre fre oo ks eb m • Simple dehydration or pure water deficiency is due to deprivation of water without corresponding loss of electrolytes Simple dehydration is associated with hypernatremia, i.e increased level of sodium and increase in ECW osmolality due to loss of water from the body Dehydration due to Combined Deficiency of Water and Electrolyte, Sodium co e c co e co m m m m e e e m m co Dehydration due to Pure Water Deficiency, without Loss of Electrolytes, Called Simple Dehydration 291 Water Metabolism e m e co re om e c re co m e fre ks oo eb eb m co e fre fre e co 19 The water produced during metabolic reactions in an adult is about: a 100 mL/day b 300 mL/day c 500 mL/day d 700 mL/day m m 18 Osmotically active substances in plasma are: a Sodium b Chloride c Proteins d All of these ks ks 20 The daily water loss through gastrointestinal tract in an adult is about: a 500 mL/day b 200 mL/day c 300 mL/day d 400 mL/day oo eb 21 Body water is regulated by the hormone: a Oxytocin b ACTH c FSH d Epinephrine m m eb oo oo eb m e fre d 16 d ks c 15 d co m co m e d 14 a ks fre d 13 a 21 a oo eb m oo ks f eb m co m e fre oo ks 17 Vasopressin (ADH): a Enhance reabsorption of water from kidney b Decreases reabsorption of water c Increases excretion of calcium d Decreases excretion of calcium m co e d 12 d 20 b fre b 11 c 19 b ks b 10 a 18 d oo ks f m co e re ks f oo eb 16 Insensible loss of body water of normal adult is about: a 50–100 mL b 100–200 mL c 300–500 mL d 600–1000 mL oo m e co ks fre oo eb m e co m fre ok s eb o 15 The daily water allowance for normal adult (60 kg) is about: a 200–600 mL b 500–800 mL c 800–1500 mL d 1800–2500 mL eb fre ks oo eb m co m e fre oo ks eb m Answers for MCQs m m m m co e e fre ks m eb oo Source of daily output of water is: a Urine b Insensible water (skin and lungs) c Sensible water (sweats and stool) d All of the above Metabolic water is: a Water from food b Drinking water c Water derived from metabolism d Total body water Water and electrolyte balance is regulated by, except: a ADH b Renin-angiotensin-aldosterone system (RAAS) c Atrial natriuretic factor (ANF) d Insulin Main anions of ICF is: a Cl– b HPO4– – c HCO3 d SO4–– 14 The largest portion of total body water is found in which of the tissue? a Intracellular fluid b Extracellular fluid c Interstitial fluid d Plasma m oo eb m co m co m Distribution of water between intracellular and extracellular compartments depends on all of the following, except: a Osmolality b Osmolarity c Colloidal osmotic pressure d Surface tension 13 In a 70 kg adult, the total body water content is: a 42 L b 28 L c 14 L d 3.5 L m e ks fre re sf oo k eb m Which of the following hormones affects fluid and electrolyte balance? a Epinephrine b Glucagon c Thyroxine d Aldosterone 12 Which of the following has least water content? a Pancreas b Brain c Liver d Adipose tissue m co m m e co co Which of the following is correct about intracellular water (ICW)? a Amount less than ECW b Amount more than ECW c Amount equal to ECW d None of the above co m eb eb eb m 11 Which of the following has greatest water content? a Liver b Adipose tissue c Brain d Kidney In ICF, main cation is: a Na+ b K+ ++ c Ca d Mg++ m m fre oo oo ks 10 Main cation of ECF is: a Na+ b K+ ++ c Ca d Mg++ Chief anion of ECF is: a Cl– b HCO3– c HPO4– d Protein co om e ks fre fre m eb oo ks Multiple Choice Questions (MCQs) a b 17 a e c co e co m m m m e e e m m Essentials of Biochemistry m co 292 e m e co re oo ks f m om e c re oo ks f eb co m e fre ks oo eb Sodium readily absorbed from the gut and is excreted from the body via urine There is normally little loss of sodium occur through skin (sweat) and in the feces Urinary excretion of sodium is regulated by aldosterone, which increases sodium reabsorption in kidney m co eb eb oo oo ks ks fre e • 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 m e fre oo eb m eb oo ks ks ks fre e The plasma concentration of sodium is 135-145 mEq/L, whereas blood cells (intracellular) contain 35 mEq/L co m co m Plasma Sodium m m m co Metabolic functions oo eb m m co m e fre oo ks eb Absorption and excretion m m co fre fre ok s eb o m • 1–5 gm • gm NaCl per day is recommended for adults without history of hypertension and gm NaCl per day with history of hypertension fre ks fre oo eb Chromium Cobalt Copper Fluoride Iodine Iron Manganese Molybdenum Selenium Zinc e e co m Microminerals or Trace elements m eb m m Recommended dietary allowance per day e m e co e oo ks fre Table 17.1: Minerals required in human nutrition co m eb m e fre ks oo eb m co m co m Sodium is the major cation of extracellular fluids Table salt (NaCl), salty foods, animal foods, milk and some vegetables m co m co m e fre METABOLISM OF SODIUM, POTASSIUM AND CHLORIDE Sodium Potassium Chlorine Calcium Phosphorus Magnesium Sulfur co e re ks f oo oo eb m Dietary food sources ks oo eb m ¾¾ Metabolism of Sulfur ¾¾ Metabolism of Trace Elements (Microminerals) Minerals are inorganic elements, required for a variety of functions The minerals required in human nutrition can be grouped into macrominerals and microminerals (trace elements) (Table 17.1) • The macrominerals are required in excess of 100 mg/day • The microminerals or trace elements are required in amounts less than 100 mg/day • The principal functions and deficiency manifestations of each of the macro- and microminerals are summarized in Table 17.2 Macrominerals eb eb m co m e ks fre re sf co m m eb oo k ¾¾ Metabolism of Sodium, Potassium and Chloride ¾¾ Metabolism of Calcium, Phosphorus and Magnesium Sodium m fre ks oo oo eb m e co co m Mineral Metabolism Chapter outline INTRODUCTION om e ks fre fre oo ks m m eb 17 e c co e co m m m m e e e m m co CHAPTER Cofactor for phosphate transferring enzymes, constituent of bones and teeth, muscle contraction, nerve transmission Sulfur Constituent of proteins, bile acid, glycosoaminoglycans, vitamins like thiamine, lipoic acid, involved in detoxication reactions om m e c co m co m co m m Impaired glucose metabolism Microcytic hyporchromic anemia, depigmentation of skin, hair Excessive deposition in liver in Wilson’s disease Constituent of bone and teeth, strengthens bone and teeth Dental caries e ks fre fre oo ks Iodine Constituent of thyroid hormones (T3 and T4) Iron Constituent of heme and non-heme compounds and transport, storage of O2 Manganese Cofactor for number of enzymes, e.g arginase, carboxylase, kinases, etc Not well-defined Molybdenum Constituent of xanthine oxidase, sulfite oxidase and aldehyde oxidase Xanthinuria Selenium Antioxidant, cofactor for glutathione peroxidiase, protects cell against membrane lipid peroxidation Cardiomyopathy Cofactor for enzymes in DNA, RNA and protein synthesis, constituent of insulin, carbonic anhydrase, carboxypeptidase, LDH, alcohol dehydrogenase, alkaline phosphatase, etc Growth failure, impaired wound healing, defects in taste and smell, loss of apetite oo eb m m co fre ks oo eb m m co m co e fre oo eb m m eb oo ks ks oo eb m eb m It is due to loss of water and the symptom is therefore those of dehydration and if it is due to excess salt gain, leads to hypertension and edema e fre Symptoms of hypernatremia ks fre e co • Water depletion, may arise from a decreased intake or excessive loss with normal sodium content, e.g diabetes insipidus m co ks • Water and sodium depletion, if more water than sodium is lost, e.g diabetes mellitus (osmotic diuresis), excessive sweating or diarrhea in children • Excessive sodium intake or retention in the ECF due to excessive aldosterone secretion, e.g Cohn’s syndrome and in Cushing’s syndrome oo m Causes of hypernatremia fre e m e co ks fre oo eb e co m m Hypernatremia Hypernatremia is an increase in serum sodium concentration above the normal range of 135–145 mEq/L ok s fre eb Microcytic anemia m m oo ks fre e co m eb oo Cretinism in children and goiter in adults e fre ks e Constituent of oxidase enzymes, e.g tyrosinase, cytochrome oxidase, ferroxidase and ceruloplasmin, involved in iron absorption and mobilization Clinical Conditions Related to Plasma Sodium Level Alterations re e re m eb eb Unknown Macrocytic anemia co Constituent of vitamin B12 e e fre Muscle spasms, tetany, confusions, seizures oo oo eb m co m Potentiate the effect of insulin ks oo ks f Magnesium Growth retardation, skeletal deformities, muscle weakness, cardiac arrhythmia ks f m co m ks fre e m re sf Constituent of bone and teeth, nucleic acids, and NAD, FAD, ATP, etc Required for energy metabolism oo eb m Tetany, muscle cramps, convulsions, osteoporosis, rickets Zinc eb e co Constituent of bone and teeth, blood clotting, regulation of nerve, muscle and hormone function Fluoride eb o re Deficiency secondary to vomiting and diarrhea Copper m oo ks f Principal extracellular anion, electrolyte balance, osmotic balance, and acid base balance, gastric HCI formation Cobalt m e Chloride Chromium co m eb Muscle weakness, paralysis and mental confusion, acidosis m Principal intracellular cation, buffer constituent, water and acid base balance, neuromuscular irritability Microminerals or trace elements co m m fre ks Potassium oo k eb m oo Dehydration, acidosis, excess leads to edema and hypertension Phosphorus m eb eb Principal extracellular cation, buffer constituent, water and acid base balance, cell membrane permeability m Sodium e co eb m co Deficiency manifestation oo Metabolic function Macrominerals Calcium m om e ks fre fre oo ks Table 17.2: Principal functions and deficiency manifestations of macrominerals and microminerals Element co e c co e co m m m m e e e m m Essentials of Biochemistry m co 294 e m e co re oo ks f eb m oo ks f re e c om m co e re ks f oo eb m fre e co m co m e fre ks oo eb m m m m fre e co co e fre ks ks oo oo Symptoms of hypokalemia Muscular weakness, tachycardia, electrocardiographic (ECG) changes (flattering of ECG waves), lethargy, and confusion eb m m co m Chloride e e Dietary food sources Table salt, leafy vegetables, eggs and milk fre oo eb m m eb oo ks ks co Chloride is the major anion in the extracellular fluid space ks fre m co e fre Hypokalemia (low plasma concentration) Causes of hypokalemia • Gastrointestinal losses: Potassium may be lost from the intestine due to vomiting, diarrhea • Renal losses: Due to renal disease, administration of diuretics oo eb m m om m First manifestation is cardiac arrest, changes in electro cardiogram, cardiac arrhythmia, muscle weakness which may be preceded by paraesthesia (abnormal tingling sensation) eb ks fre oo eb m e co m fre ok s eb o Symptoms of hyperkalemia eb e co e fre oo ks eb m • Renal failure: The kidney may not be able to excrete a potassium load when GFR is very low • Mineralocorticoid deficiency: For example, in Addison’s disease • Cell damage: For example, in trauma and malignancy m m co m Excretion • Potassium excretion occurs through three primary routes, the gastrointestinal tract, the skin and the urine Under normal conditions, loss of potassium through gastrointestinal tract and skin is very small The major means of K+ excretion is by the kidney • When sodium is reabsorbed by distal tubule cations (e.g K+ or H+) in the cell move into the lumen to balance the charge Thus during the sodium reabsorption there is an obligatory loss of potassium 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 m Causes of hyperkalemia oo ks oo eb m Absorption Potassium is absorbed readily by passive diffusion from gastrointestinal tract co m ks eb m co e fre ks ks oo eb m Recommended dietary allowance per day 2–5 gm Hyperkalemia Hyperkalemia is a clinical condition associated with elevated plasma potassium above the normal range (3.5–5 mEq/L) eb oo eb m co m e fre Dietary food sources Vegetables, fruits, whole grain, meat, milk, legumes and tender coconut water Clinical Conditions Related to Plasma Potassium Level Alterations m co m e ks fre re sf oo k eb m co m Potassium is the main intracellular cation About 98% of total body potassium is in cells (150–160 mEq/L), only 2% in the ECF (3.5–5 mEq/L) m Metabolic functions • Potassium maintains the intracellular osmotic pressure, water balance and acid-base balance • It influences activity of cardiac and skeletal muscle • Several glycolytic enzymes need potassium for their formation • Potassium is required for transmission of nerve impulses • Nuclear activity and protein synthesis are dependent on potassium oo oo eb m e co co m m • Retention of water: Retention of water dilutes the constituents of the extracellular space causing hypo natremia, e.g in heart failure, liver disease, nephrotic syndrome, renal failure, syndrome of inappropriate ADH secretion (SIADH) • Loss of sodium: Such losses may be from gastrointestinal tract, e.g vomiting, diarrhea, or in urine Urinary loss may be due to aldosterone deficiency (Addison’s disease) Symptoms of hyponatremia are constant thirst, muscle cramps, nausea, vomiting, abdominal cramps, weakness and lethargy Potassium co fre e ks fre fre oo ks eb m Causes of hyponatremia e c co e co m m m m e e e m m co Hyponatremia It is a significant fall in serum sodium concentration below the normal range 135 to 145 mEq/L 295 Mineral Metabolism e m m e co oo ks f eb m re e c om m co e re oo ks f eb m fre e co m co m e fre oo ks oo ks eb eb m m m fre e co co e fre ks ks oo oo eb m co e fre ks m eb oo oo eb m m co m e ks oo eb m re fre eb m m Dietary sources The main dietary sources of calcium are milk and dairy products, (half a liter of milk contains approximately 1,000 mg of calcium) cheese, cereal grains, legumes, nuts and vegetables ks fre m co e fre fre ok s eb o eb oo eb m e co m Functions Formation of bone and teeth: 99% of the body’s calcium is located in bone in the form of hydroxyapatite crystal [3Ca3 (PO4)2 Ca (OH)2] The hardness and rigidity of bone and teeth are due to hydroxyapatite Blood coagulations: Calcium present in platelets involved in blood coagulation, the conversion of an The significance of this reaction is to convert milk into a more solid form to increase its retention in the stomach for a longer period of time and facilitate its gastric digestion in infants m m e co ks fre fre Calcium is the most abundant mineral in the body The adult human body contains about kg of calcium About 99% the body’s calcium is present in bone together with phosphate as the mineral hydroxyapatite [Ca10 (PO4)6 (OH)2], with small amounts in soft tissue and extracellular fluid oo ks eb m m oo ks m co e fre ks oo eb m e co m co m ks f oo eb m co m e fre ks oo eb m Hypochloremia • A decreased chloride concentration is seen in severe vomiting, metabolic alkalosis, excessive sweating and Addison’s disease Calcium oo e ks fre re oo k eb m co m Hyperchloremia • An increased chloride concentration occurs in dehydration, metabolic acidosis and Cushing’s syndrome METABOLISM OF CALCIUM, PHOSPHORUS AND MAGNESIUM eb co m m e co co sf Plasma chloride The concentration of chloride in plasma is 95–105 mEq/L Functions • As a part of sodium chloride, chloride is essential for water balance, regulation of osmotic pressure, and acid-base balance • Chloride is necessary for the formation of HCl by the gastric mucosa and for activation of enzyme amylase • It is involved in chloride shift Clinical Conditions Related to Plasma Chloride Level Alterations inactive protein prothrombin into an active thrombin requires calcium ions Muscle contraction: Muscle contraction is initiated by the binding of calcium to troponin Release of hormones: The release of certain hormones like parathyroid hormone, calcitonin, etc requires calcium ions Release of neurotransmitter: Influx of Ca2+ from extracellular space into neurons causes release of neurotransmitter Regulation of enzyme activity: Activation of number of enzymes requires Ca2+ as a specific cofactor For example: – Activation of enzyme glycogen phosphorylase kinase which then triggers glycogenolysis – Activation of salivary and pancreatic α-amylase Second messenger: Calcium acts as a second messenger for hormone action For example, it acts as a second messenger for epinephrine or glucagon Ca also functions as a third messenger for some hormones such as antidiuretic hormone (ADH) Membrane excitability: Calcium ions activate the sodium channels Deficiency of calcium ions lead to decreased activity of Na-channels, which ultimately leads to decrease in membrane potential so that the nerve fiber becomes highly excitable causing muscle tetany Cardiac activity: Cardiac muscle depends on extra cellular Ca2+ for contraction Myocardial contractility increases with increased Ca2+ concen tration and decreases with decreased calcium concentration 10 Membrane integrity and permeability: Calcium is required for maintenance of integrity and permeability of the membrane 11 Hydrolysis of casein of milk: Calcium is required for the formation of Ca-paracaseinate (insoluble curd) m oo m eb Absorption Rapidly and almost totally absorbed in the gastrointestinal tract Excretion Under normal conditions chloride excretion occurs by way of three routes; the gastrointestinal tract, the skin and urinary tract Chloride is excreted, mostly as sodium chloride and chiefly by way of the kidney m om e ks fre fre m eb oo ks Recommended dietary allowance (RDA) per day 2–5 gm co e c co e co m m m m e e e m m Essentials of Biochemistry m co 296 ... in both of them Table 16.1: Distribution of water a Plasma e c co e co m m m m e e e m m Essentials of Biochemistry m co 28 8 e m m e co oo ks f eb m 40 103 e c 27 10 140 m 16 155 40 20 2 e eb eb... m c 13 b 21 a 29 b 37 d 45 b oo co m ks fre e d 12 a 20 d 28 c 36 b 44 a oo sf oo k m eb d 11 d 19 b 27 c 35 d 43 d 49 A hemolytic sample will cause falsely increased levels of each of the following,... Regulation of plasma calcium (25 -HCC: 25 -Hydroxycholecalciferol) Clinical Conditions Related to Plasma Calcium Level Alterations co e c co e co m m m m e e e m m Essentials of Biochemistry m co 29 8