basolateral membrane of the collecting duct cells. This stimulates adenyl cyclase and increases intracellular adenosine-3/-5- monophosphate(cyclic AMP) levels Cyclic AMP activates one or more cyclic AMP-dependent protein kinases, including protein kinase A, which phosphorylates proteins, alters the cytoskele ton and allows subapical vesicles containing aquaporins to fuse with the apical plasma membrane, increasing water permeability. The aquaporins are a family of water channel proteins, which are membrane bound and comprise approxi mately 260 amino acids ■ Sodiun Sodium is the principal extracellular cation. The total body sodium is around 5000-6000 mmol in a 70 kg adult. Only 2/3 of the total body sodium is exchange able, the remainder being bound in bone. Regulation of sodium content is chieved through a balance between intake, absorption and excretion (in the urine, sweat and faeces) Physiological role of sodiur Osmotic skeleton of extracellular fluid Maintains plasma and extracellular fluid osmolality by virtue of being the principal osmotically active solute. Maintains intravascular and extracellular (interstitial) fluid volumes. Increases or decreases in total body sodium tend to increase or decrease the extracellular fluid and plasma volume. Causes transmembrane potential differences that are responsible for excit ability in nerve, muscle and other cells. Permits movement of water and thereby influences cell volume Ensures potassium supply to intracellular fluid Permits dilution of urin Facilitates defence against hyperkalaemia By co-transport, facilitates both enteric uptake of solutes such as glucose and amino acids, along with their renal reabsorption. By counter-transport, influences concentration of other cations, e. g. Ca2+, in intracellular fluid and may therefore influence, e. g, response of arterioles to vasoconstrictor tone Rates of sodium transport potentially affect a variety of metabolic pathways because NaKt-ATPase is a major consumer of ATP
basolateral membrane of the collecting duct cells. This stimulates adenyl cyclase and increases intracellular adenosine-30 -50 - monophosphate (cyclic AMP) levels. Cyclic AMP activates one or more cyclic AMP-dependent protein kinases, including protein kinase A, which phosphorylates proteins, alters the cytoskeleton and allows subapical vesicles containing aquaporins to fuse with the apical plasma membrane, increasing water permeability. The aquaporins are a family of water channel proteins, which are membrane bound and comprise approximately 260 amino acids. & Sodium Sodium is the principal extracellular cation. The total body sodium is around 5000–6000 mmol in a 70 kg adult. Only 2/3 of the total body sodium is exchangeable, the remainder being bound in bone. Regulation of sodium content is achieved through a balance between intake, absorption and excretion (in the urine, sweat and faeces). Physiological role of sodium Osmotic skeleton of extracellular fluid. Maintains plasma and extracellular fluid osmolality by virtue of being the principal osmotically active solute. Maintains intravascular and extracellular (interstitial) fluid volumes. Increases or decreases in total body sodium tend to increase or decrease the extracellular fluid and plasma volume. Causes transmembrane potential differences that are responsible for excitability in nerve, muscle and other cells. Permits movement of water and thereby influences cell volume. Ensures potassium supply to intracellular fluid. Permits dilution of urine. Facilitates defence against hyperkalaemia. By co-transport, facilitates both enteric uptake of solutes such as glucose and amino acids, along with their renal reabsorption. By counter-transport, influences concentration of other cations, e.g. Ca2 þ, in intracellular fluid and may therefore influence, e.g., response of arterioles to vasoconstrictor tone. Rates of sodium transport potentially affect a variety of metabolic pathways because NaþKþ -ATPase is a major consumer of ATP. Sodium 25
Sodium homeostasis Sodium balance is maintained by a variety of mechanisms, outlined below: 26g e Afferent mechanisms Arterial baroreceptors in the carotid sinus Renal baroreceptors in the juxtaglomerular apparatus Cardiac sensors in the atria and ventricles Hepatic vascular sensors; Hypothalamic sensors. ● Efferent mechanisn Renal: glomerular filtration rate; physical forces in the proximal tubule; distal nephron. Neurohumoral: sympathetic nervous system activity; renin-angiotensin- aldosterone system; prostaglandins E2 and 12, nitric oxide, atrial natriuretic peptide, arginine vasopress normalities in sodium metabolism The serum sodium level is normally maintained between 135 and 145 mmol/l The level normally reflects total body water content. Abnormalities in serum sodium levels need to be interpreted in relation to the extracellular fluid volume Hyponatraemia refers to a serum sodium level under 130 mmol/l. The patho- physiological mechanisms responsible for a low level can be enumerated as follows. Pseudo-hyponatraemia, accompanied by normal osmolality and tonicity of the extracellular fluid: severe hyperproteinaemia; hypertriglyceridaemia True hyponatraemia Hypovolaemic hyponatraemia, which is due to a disproportionately greater reduction in total body sodium than in total body water, and is accompanied by features of extracellular fluid depletion. This can be due to renal losses (e. g from diuretics), gastrointestinal losses, skin losses, and intraperitoneal losses Euvolaemic hyponatraemia, which is associated with increased total body water and normal total body sodium(dilutional hyponatraemia). This can be due to arginine vasopressin excess or a reset osmostat. Hypervolaemic hyponatraemia, which is associated with a disproportion ately greater reduction in total body water than in total body sodium, and is accompanied by features of expanded extracellular fluid volume Oedematous states responsible may be due to congestive heart failure, cirrhosis of the liver, nephrotic syndrome or renal failure
Sodium homeostasis Sodium balance is maintained by a variety of mechanisms, outlined below: * Afferent mechanisms Arterial baroreceptors in the carotid sinus; Renal baroreceptors in the juxtaglomerular apparatus; Cardiac sensors in the atria and ventricles; Hepatic vascular sensors; Hypothalamic sensors. * Efferent mechanisms Renal: glomerular filtration rate; physical forces in the proximal tubule; distal nephron. Neurohumoral: sympathetic nervous system activity; renin–angiotensin– aldosterone system; prostaglandins E2 and I2, nitric oxide, atrial natriuretic peptide, arginine vasopressin. Abnormalities in sodium metabolism The serum sodium level is normally maintained between 135 and 145 mmol/l. The level normally reflects total body water content. Abnormalities in serum sodium levels need to be interpreted in relation to the extracellular fluid volume status. Hyponatraemia refers to a serum sodium level under 130 mmol/l. The pathophysiological mechanisms responsible for a low level can be enumerated as follows: * Pseudo-hyponatraemia, accompanied by normal osmolality and tonicity of the extracellular fluid: severe hyperproteinaemia; hypertriglyceridaemia. * True hyponatraemia Hypovolaemic hyponatraemia, which is due to a disproportionately greater reduction in total body sodium than in total body water, and is accompanied by features of extracellular fluid depletion. This can be due to renal losses (e.g. from diuretics), gastrointestinal losses, skin losses, and intraperitoneal losses. Euvolaemic hyponatraemia, which is associated with increased total body water and normal total body sodium (dilutional hyponatraemia). This can be due to arginine vasopressin excess or a reset osmostat. Hypervolaemic hyponatraemia, which is associated with a disproportionately greater reduction in total body water than in total body sodium, and is accompanied by features of expanded extracellular fluid volume. Oedematous states responsible may be due to congestive heart failure, cirrhosis of the liver, nephrotic syndrome or renal failure. Water and electrolyte balance 26
Redistributional hyponatraemia, which is secondary to water shifts from the ntracellular to the extracellular compartment, and associated with normal total body water and total body sodium. The extracellular fluid osmolality and tonicity are high. This can be associated with severe hyperglycaemia. Sodium deficit can be calculated by the formula:(Desired Na* minus actual Nat)x body weight(kg) x total body water(l/kg) Hypernatraemia refers to a serum sodium level greater than 150 mmol/l, and is always indicative of an absolute or relative water deficit. It is associated with he following pathophysiological mechanisms Hypovolaemic hypernatraemia, which is due to a total body water deficit that is disproportionately greater than total body sodium deficit. This is asso- ciated with renal losses (e.g, osmotic diuresis), skin losses, or gastrointesti- nal losses(e. g secretory diarrhoea). Renal water loss can be evaluated by measuring urine osmolality Hypervolaemic hypernatraemia, which is due to an increase in total bod sodium that is disproportionately greater than the increase in total body water. This is either iatrogenic and caused by hypertonic saline or sodium bicarbonate, or associated with primary hyperaldosteronism tatraemia. This is caused by eit (diabetes insipidus) or increased insensible water losses, and is associated vith a normal total body sodium content. Potassium Potassium is the major cation in the intracellular fluid. Daily dietary intake ranges from 40-120 mmoL. The serum level ranges between 3.5 and 5 mmol/L. The total body potassium is around 3500 mmol in a 70 kg adult, representing around 50 mmol/kg Ninety-eight percent of the total body potassium is intracellular. Cellular uptake is achieved by stimulation of the cell membrane Na*/K-ATPase. Ninety per cent of the daily load is excreted by the kidneys; the remainder by the gastrointestinal tract. Renal excretion depends on renal blood flow, sodium delivery to the distal tubule, urine output, aldosterone, antidiuretic hormone, and acid-base balance. Functions of potassium Generation of transmembrane potentials, thereby affecting the electrical excitability of tissues. It is responsible for the resting membrane potentia
Redistributional hyponatraemia, which is secondary to water shifts from the intracellular to the extracellular compartment, and associated with normal total body water and total body sodium. The extracellular fluid osmolality and tonicity are high. This can be associated with severe hyperglycaemia. Sodium deficit can be calculated by the formula: (Desired Naþ minus actual Naþ) body weight (kg) total body water (l/kg) Hypernatraemia refers to a serum sodium level greater than 150 mmol/l, and is always indicative of an absolute or relative water deficit. It is associated with the following pathophysiological mechanisms: Hypovolaemic hypernatraemia, which is due to a total body water deficit that is disproportionately greater than total body sodium deficit. This is associated with renal losses (e.g., osmotic diuresis), skin losses, or gastrointestinal losses (e.g. secretory diarrhoea). Renal water loss can be evaluated by measuring urine osmolality. Hypervolaemic hypernatraemia, which is due to an increase in total body sodium that is disproportionately greater than the increase in total body water. This is either iatrogenic and caused by hypertonic saline or sodium bicarbonate, or associated with primary hyperaldosteronism. Euvolaemic hypernatraemia. This is caused by either renal water losses (diabetes insipidus) or increased insensible water losses, and is associated with a normal total body sodium content. & Potassium Potassium is the major cation in the intracellular fluid. Daily dietary intake ranges from 40–120 mmol. The serum level ranges between 3.5 and 5 mmol/l. The total body potassium is around 3500 mmol in a 70 kg adult, representing around 50 mmol/kg. Ninety-eight percent of the total body potassium is intracellular. Cellular uptake is achieved by stimulation of the cell membrane Naþ/Kþ-ATPase. Ninety per cent of the daily load is excreted by the kidneys; the remainder by the gastrointestinal tract. Renal excretion depends on renal blood flow, sodium delivery to the distal tubule, urine output, aldosterone, antidiuretic hormone, and acid–base balance. Functions of potassium Generation of transmembrane potentials, thereby affecting the electrical excitability of tissues. It is responsible for the resting membrane potential, Potassium 27
which is set by the equilibrium potential for potassium. It also prolongs the plateau of the action potential, initiates repolarisation and is responsible for 26g A cofactor in enzymatic reactions Responsible for normal cell volume by virtue of being the predominant intra- cellular solute Maintenance of cell polarity RNA synthesis and processing Protein synthesis. Hormone secretion Vascular reactivity Maintenance of acid-base balance Potassium balance Potassium homeostasis is maintained by a balance between intake, excretion ind cellular uptake and efflux. Ninety per cent of the total body potassium is available for exchange, allowing for major translocations or shifts between bod compartments. Factors stimulating Kt entry into cells Alkalosis, mainly metabolic Hormonal: insulin, beta-adrenergic agonists(catecholamines); High extracellular potassium concentration Hyperosmolarity of the extracellular fluid Factors stimulating exit from cells Low osmolarity of the extracellular fluid Hormonal: glucagon, beta-adrenergic blockade; alpha-adrenergic agonists Cell injury Renal excretion of potassium This depends on the net effect following: Reabsorption in the proximal convoluted tubule and in the ascending limb of the loop of Henle
which is set by the equilibrium potential for potassium. It also prolongs the plateau of the action potential, initiates repolarisation and is responsible for diastolic depolarisation in cardiac pacemaker cells. A cofactor in enzymatic reactions. Responsible for normal cell volume by virtue of being the predominant intracellular solute Maintenance of cell polarity. Receptor-mediated endocytosis. RNA synthesis and processing. Protein synthesis. Hormone secretion. Vascular reactivity. Maintenance of acid–base balance. Apoptosis. Potassium balance Potassium homeostasis is maintained by a balance between intake, excretion, and cellular uptake and efflux. Ninety per cent of the total body potassium is available for exchange, allowing for major translocations or shifts between body compartments. Factors stimulating Kþ entry into cells Alkalosis, mainly metabolic; Hormonal: insulin, beta-adrenergic agonists (catecholamines); High extracellular potassium concentration; Hyperosmolarity of the extracellular fluid. Factors stimulating exit from cells Acidosis, mainly respiratory; Low osmolarity of the extracellular fluid; Hormonal: glucagon, beta-adrenergic blockade; alpha-adrenergic agonists (catecholamines); Cell injury. Renal excretion of potassium This depends on the net effect following: Reabsorption in the proximal convoluted tubule and in the ascending limb of the loop of Henle. Water and electrolyte balance 28
Secretion, which depends on the basolateral NatKt-ATPase, and the luminal voltage-gated potassium channels. Abnormalities in potassium homeostasis Serum potassium is normally maintained between 3.5 and 5.0 mmol/l A reduc tion of l mmol/l reflects a deficit of 150-400 mmol in total body potassium. Hypokalaemia can be related to the following pathophysiological mechanisms Redistribution due to transcellular shifts: alkalosis, beta 2-adrenergic stimu- lation, insulin, rapid cell growth in acute anabolic states · True hy Renal losses, associated with urine potassium greater than 20 mmol in 24 hours. This can be produced by diuretics, mineralocorticoids, high dose glucocorticoids, or in states of osmotic diuresis Gastrointestinal losses: malabsorption; secretory diarrhoea; laxative abuse Hyperkalaemia can be related to Pseudohyperkalaemia: improper blood collection with haemolysis; marked leukocytosis; marked thrombocytosis True hyper Reduced excretion: acute renal failure; potassium-sparing diuretics Increased intake or release: potassium supplements; rhabdomyolysis Transcellular shifts of potassium: acidosis; beta blockers; cell destruction (tumour lysis) ■ Magnesium Magnesium is the second most abundant intracellular cation. The total body ontent in an adult is around 2000 mmol (24 g). Sixty per cent is contained in bone, and 20% in muscle. The normal calcium: magnesium ratio in bone is 50: 1 the ratio being higher in trabecular than in cortical bone. Only 1% is contained in the extracellular fluid Daily intake is around 10-12 mmol. Requirements are increased in childhood, pregnancy, critical illness and in magnesium-losing states (renal, gastrointest inal or cutaneous). The serum concentration ranges from 0.8-1.2 mmol/l 25%-30% is protein bound, 10%0-15% is complexed and 50%-60%(the phy- siologically active fraction) is ionised. The intracellular concentration is around 40 mmol/l
Secretion, which depends on the basolateral NaþKþ -ATPase, and the luminal voltage-gated potassium channels. Abnormalities in potassium homeostasis Serum potassium is normally maintained between 3.5 and 5.0 mmol/l. A reduction of 1 mmol/l reflects a deficit of 150–400 mmol in total body potassium. Hypokalaemia can be related to the following pathophysiological mechanisms: * Redistribution due to transcellular shifts: alkalosis, beta 2-adrenergic stimulation, insulin, rapid cell growth in acute anabolic states. * True hypokalaemia: Renal losses, associated with urine potassium greater than 20 mmol in 24 hours. This can be produced by diuretics, mineralocorticoids, high dose glucocorticoids, or in states of osmotic diuresis. Gastrointestinal losses: malabsorption; secretory diarrhoea; laxative abuse; cation-binding resins; villous adenoma. Hyperkalaemia can be related to: * Pseudohyperkalaemia: improper blood collection with haemolysis; marked leukocytosis; marked thrombocytosis. * True hyperkalaemia: Reduced excretion: acute renal failure; potassium-sparing diuretics. Increased intake or release: potassium supplements; rhabdomyolysis; haemolytic states. Transcellular shifts of potassium: acidosis; beta blockers; cell destruction (tumour lysis). & Magnesium Magnesium is the second most abundant intracellular cation. The total body content in an adult is around 2000 mmol (24 g). Sixty per cent is contained in bone, and 20% in muscle. The normal calcium: magnesium ratio in bone is 50:1, the ratio being higher in trabecular than in cortical bone. Only 1% is contained in the extracellular fluid. Daily intake is around 10–12 mmol. Requirements are increased in childhood, pregnancy, critical illness and in magnesium-losing states (renal, gastrointestinal or cutaneous). The serum concentration ranges from 0.8–1.2 mmol/l. 25%–30% is protein bound, 10%–15% is complexed and 50%–60% (the physiologically active fraction) is ionised. The intracellular concentration is around 40 mmol/l. Magnesium 29