Body Fluids and Electrolytes

Body fluids and Electrolytes Water & Na CH2 1 Introduction This chapter is largely about the water and electrolytes ( sodium )in your plasma and how the body manages to keep you from drying up and blowing away even if you are in the hot sun and without liquid drink. Water & Na CH2 2 Composition of Body Fluids • Water is the universal solvent • Solutes are broadly classified into: • Electrolytes–inorganic salts, all acids and bases, and some proteins • Nonelectrolytes–examples include glucose, lipids, creatinine, and urea • Electrolytes have greater osmotic power than nonelectrolytes • Water moves according to osmotic gradients • The major electrolytes include: Na+, K+, Ca2+, Mg2+, Cl-, SO42-, bicarbonate and lactate, as well as few other organic anions and the trace elements • The major electrolytes occur primarily as free ions; • the trace elements occur primarily in combination with proteins Water & Na CH2 3 Electrolyte Balance • Electrolytes are important for: • Neuromuscular excitability • Secretory activity • Membrane permeability • Controlling fluid movements • Fluid and electrolytes balance is central to the management of any patient that is ill • Measurement of serum sod, pot, chloride and bicarbonate is the most commonly requested biochemical profile • The dietary requirements for electrolytes vary widely; some need to be consumed only in small amounts. Others, such as calcium, potassium and phosphorus, are excreted continuously and must be ingested regularly to prevent deficiency • Salts enter the body by ingestion and are lost via perspiration, feces, and Water & Na CH2 4 urine Body Water Content: Fluid Compartments Water occupies two main fluid compartments • Intracellular fluid (ICF)–about two thirds by volume, contained in cells (28 L) • Extracellular fluid (ECF) (14 L)– consists of two major subdivisions: 1. Plasma–the fluid portion of the blood (3.5L) 2. Interstitial fluid (IF)–fluid in spaces between cells (10.5L) Osmolality • Body compartments are separated by semipermeable membranes through which water moves freely • Osmotic pressure must be the same on both sides of a cell membrane and water moves to keep the osmolality the same even this water causes cells to shrink or expand in volume Water & Na CH2 5 Osmolality • The osmolality of ICF is normally the same as the ECF ➔ the two compartments contain isotonic solution • Plasma osmolality = 1.86 ([Na+]) + [urea]/2.8 + [glucose]/18 • Plasma osmolality = 2 ([Na+]) + [urea]/3 + [glucose]/20 • Or simply plasma osmolality = 2 ([Na+]) 6 Water & Na CH2 Extracellular and Intracellular Fluids • Each fluid compartment of the body has a distinctive pattern of electrolytes • Extracellular fluids are similar (except for the high protein content of plasma) • Sodium is the chief cation • Chloride is the major anion • Intracellular fluids have low sodium and chloride • Potassium is the chief cation • Phosphate is the chief anion • Sodium and potassium concentrations in extra- and intracellular fluids are nearly opposites • ➔This reflects the activity of cellular ATP-dependent sodiumpotassium pumps Water & Na CH2 7 Electrolyte Composition of Body Fluids Water & Na CH2 8 Figure 26.2 Water Balance and ECF Osmolality • To remain properly hydrated, water intake must equal water output • Water intake sources • Ingested fluid (60%) and solid food (30%) • Metabolic water or water of oxidation (10%) • • Water output • Urine (60%) and feces (4%) • Insensible losses (Skin and lung) (28%), sweat (8%) • Obligatory water losses include: 1. Insensible water losses from lungs and skin 2. Water that accompanies undigested food residues in feces Increases in plasma osmolality trigger ➔thirst and release of antidiuretic hormone (ADH) Water & Na CH2 9 Water & Na CH2 10 Water Intake and Output • Under normal conditions , the amounts of water taken into the body and lost from it are equal over a period of time. • Water is obtained from the diet and oxidative metabolism and is lost through the kidneys, skin, lungs and gut. • The minimum volume of urine necessary for normal excretion of waste products is about 500 ml/24 hr but, as a result of obligatory losses by other routes, the minimum daily water intake necessary for the maintenance of water balance is approximately 1100 ml. Water & Na CH2 11 Water Intake and Output • To survive,→ multicellular organisms must maintain their ECF volume. Humans deprived of fluids die after a few days from circulatory collapse as a result of →the reduction in the total body water. • Water intake largely depends on social habits and is very variable. ➔Some people drink less than half a liter each day, and others may drink Less water More water more than 5 L in 24 hours without harm • Water losses are equally variable and are normally seen as changes in the volume of urine produced. The kidneys can respond quickly to meet the body's need to get rid of water. ➔The urine flow rate can vary widely in a very short time Water & Na CH2 12 Water and ECF osmolality Changes in body water content will alter the osmolality: • Loss of water from the ECF ➔ increase its osmolality ➔ movement of water from the ICF to the ECF. • A Slight increase in ECF osmolality ➔ stimulating the hypothalamus thirst centre, which promotes a desire to drink, and ➔the hypothalamic osmoreceptors, which causes the release of Arginine vasopressin (AVP) (antidiuretic hormone or ADH). • Vasopressin (ADH) makes the renal collecting ducts permeable to water ➔ water reLess water More water absorption and concentration of the urine • If the ECF osmolality falls, there is no sensation of thirst and vasopressin secretion is inhibited. A dilute urine is produced ➔ water loss and restoration of the ECF osmolality • Other stimuli affecting vasopressin secretion include angiotensin II,➔ arterial and venous baroreceptors and volume receptors. If there is a decrease in plasma volume of more than 10%,➔ hypovolemia becomes a 13 powerful stimulus to vasopressin release Water & Na CH2 Regulation of Water Intake: Thirst Mechanism Water & Na CH2 14 Water & Na CH2 15 Influence and Regulation of ADH • Water reabsorption in collecting ducts is →proportional to ADH release • Low ADH levels produce dilute urine and reduced volume of body fluids • High ADH levels produce concentrated urine Reabsorption of water from the filtrate under the influence of ADH • Hypothalamic osmoreceptors trigger or inhibit ADH release • Factors that specifically trigger ADH release include prolonged fever; excessive sweating, vomiting, or diarrhea; severe blood loss; and Water & Na CH2 traumatic burns 16 Disorders of Water Balance: Dehydration • It is when, water loss exceeds water intake and the body is in negative fluid balance • Causes include: hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, water deprivation, and diuretic abuse • Signs and symptoms: cottonmouth, thirst, dry flushed skin, and oliguria • Prolonged dehydration may lead to ➔weight loss, fever, and mental confusion • Other consequences include hypovolemic shock and loss of electrolytes Water & Na CH2 17 Disorders of Water Balance: Dehydration 1 Excessive loss of H2O from ECF 2 ECF osmotic pressure rises 3 Cells lose H2O to ECF by osmosis; cells shrink (a) Mechanism of dehydration Water & Na CH2 18 Disorders of Water Balance: Hypotonic Hydration • Renal insufficiency or an extraordinary amount of water ingested quickly can lead to➔ cellular overhydration, or water intoxication • ECF is diluted–sodium content is normal but excess water is present • The resulting hyponatremia ➔promotes net osmosis into tissue cells, =>causing swelling • These events must be quickly reversed to prevent severe metabolic disturbances, particularly in neurons Water & Na CH2 19 Disorders of Water Balance: Hypotonic Hydration 1 Excessive H2O enters the ECF 2 ECF osmotic pressure falls 3 H2O moves into cells by osmosis; cells swell (b) Mechanism of hypotonic hydration Water & Na CH2 20 Sodium ▪ Sodium ions are the major cations of extracellular fluid, ▪ important contributor in and plays a central role in➔ ▪ maintaining the normal distribution of water ▪ and the osmotic pressure in the between fluid compartments. ▪ The total body sodium of the average 70 kg man is approximately 3700 mmol, of which approximately 75% is exchangeable ▪ The non-exchangeable Na, which means it is incorporated into tissues such as bone and has a slow turnover rate. 21 Water & Na CH2 Sodium Water & Na CH2 ▪ Most of the exchangeable sodium is in the ECF (both the plasma and the interstitial fluid), the sodium concentration is → tightly regulated at around 140 mmol/l. ▪ Sodium intake is variable. The average daily diet contains 130 to 260 mmol (8-15 g) of sodium chloride, which is nearly completely absorbed from the GIT. The body requirements is only 1 to 2 mmol/day. ▪ Sodium is initially filtered by the glomeruli, but 60 to 70% of the filtered load is reabsorbed in the proximal tubules along with HCO3and water. ▪ Another 25% to 30% is reabsorbed in the loop of Henle along with Cland more water. ▪ In the distal tubules, interaction of the adrenocortical hormone aldosterone with the coupled systems of Na+-K+ and Na+-H+ exchange ➔ directly modulates the reabsorption of Na+ from the remaining 5% to 15% of the filtered load. ▪ Sodium losses are just as variable. In practical terms, urinary sodium excretion matches sodium intake. Most sodium excretion is via the kidneys. Some sodium is lost in sweat (approximately 5 mmol/day) and in the 22 faeces (approximately 5 mmol/day). Water & Na CH2 23 Sodium and ECF volume ▪ The volume of the ECF is directly dependent upon the total body sodium content since water intake and loss are regulated to hold the concentration of sodium in the ECF constant ▪ Sodium balance is maintained by regulation of its renal excretion. ▪ Sodium excretion is dependent upon →glomerular excretion, and the glomerular filtration rate (GFR) is an ➔ important limiting factor in sodium excretion only at extremely low rates of filtration (sodium retention is a late feature of chronic renal failure). Factors that involved in Sodium Homoeostasis ▪ Aldosterone ▪ Atrial natriuretic peptide (ANP): Hormone from myocardial cells ▪ Baroreceptors ▪ Angiotensin Pathway ▪ Others Water & Na CH2 24 Regulation of Sodium Balance: Aldosterone ▪ Sodium reabsorption ▪ 65% of sodium in filtrate is reabsorbed in the proximal tubules ▪ 25% is cultivated in the loops of Henle ▪ When aldosterone levels are high, all remaining Na+ is actively reabsorbed ▪ Water follows sodium if tubule permeability has been increased with ADH ▪ The renin-angiotensin mechanism→ triggers the release of aldosterone ▪ This is mediated by the juxtaglomerular apparatus, which releases renin in response to: ▪ Sympathetic nervous system stimulation ▪ Decreased filtrate osmolality ▪ Decreased stretch (due to decreased blood pressure) ▪ Renin catalyzes the production of angiotensin II, which prompts aldosterone release ▪ Adrenal cortical cells are directly stimulated to ➔release aldosterone by elevated K+ levels in the ECF ▪ Aldosterone brings about its effects ➔ (diminished urine output increased blood volume) slowly Water & Na CH2 and 25 Regulation of Sodium Balance: Aldosterone Water & Na CH2 26 Cardiovascular System Baroreceptors ▪ Baroreceptors :alert the brain of increases in blood volume (hence increased blood pressure) ▪ Sympathetic nervous system impulses to the kidneys decline ▪ Afferent arterioles dilate ▪ Glomerular filtration rate rises ▪ Sodium and water output increase ▪ This phenomenon, called pressure diuresis,➔ decreases blood pressure ▪ Drops in systemic blood pressure ➔lead to opposite actions and systemic blood pressure increases ▪ Since sodium ion concentration determines fluid volume, baroreceptors can be viewed as “sodium receptors” Water & Na CH2 27 Atrial Natriuretic Peptide (ANP) ▪ Hormone from myocardial cells ▪ Stimulates: hypothalamus, kidney, adrenal, & medulla ▪ Is released in the heart atria as a response to stretch (elevated blood pressure) ▪ Has potent diuretic and ▪ ➔Promotes excretion of natriuretic effects sodium and water ▪ Inhibits angiotensin II production ▪ Reduces blood pressure and blood volume ➔ by inhibiting: ▪ Events that promote vasoconstriction ▪ Na+ and water retention Water & Na CH2 28 Influence of Other Hormones on Sodium Balance ▪ Estrogens: ▪ Enhance NaCl reabsorption by renal tubules ▪ May cause water retention during menstrual cycles ▪ Are responsible for edema during pregnancy ▪ Progesterone: ▪ Decreases sodium reabsorption ▪ Acts as a diuretic, promoting sodium and water loss ▪ Glucocorticoids: ▪ Enhance reabsorption of sodium and promote edema Water & Na CH2 29 Hyponatraemia Hyponatraemia: it is defined as a serum sodium concentration below the reference interval of 135-145 mmol/L and it is essentially a secondary phenomenon that reflects ➔the presence of a disease ▪ Treatment should be directed at the underlying cause and not at the hyponatraemia. ▪ Plasma sodium concentration ➔depends upon the amounts of both sodium and water in plasma, and so low sodium concentration➔ does not necessarily imply sodium depletion. ▪ Hyponatraemia, could be resulted from: • loss of sodium (rare), • excess of water (water retention) • or both. Water & Na CH2 30 Water & Na CH2 31 Depletional hyponatraemia (Sodium depletion) ▪ May be the result of: 1. excessive sweating 2- prolonged vomiting 3-persistent diarrhoea (gastrointestinal fluid loss), or 4-salt-losing enteropathies (i.e., a condition in which Na+ loss is greater than water loss). ▪ Not all patients with sodium depletion are hyponatremic. ▪ Patients with sodium loss due to osmotic diuresis may become hypernatremic if➔ more water than Sodium is lost. ▪ Sodium depletion can be present with normal sodium concentration ▪ Renal loss due to➔ diminished tubular reabsorption may be caused by: ▪ Inappropriate choice, dose or use of diuretics. Drugs that antagonize aldosterone actions such as spironolactone ▪ Primary or secondary deficiency of ➔ Water & Na CH2 other mineralocorticoids. (Addison’s disease) aldosterone and 32 Sodium depletion Causes Clinical features Excessive loss from kidneys: diuretic phase of 'acute tubular necrosis' diuretic therapy mineralocorticoid deficiency other salt-losing states From skin: massively increased sweating cystic fibrosis widespread dermatitis burns From gut vomiting, diarrhoea intestinal obstruction Inadequate intake sodium depletion will occur whenever: intake is inadequate to balance excessive losses; inadequate intake alone is rarely a cause of depletion Symptoms weakness lethargy postural dizziness syncope Signs weight loss related to decreased plasma volume tachycardia hypotension peripheral circulatory failure oliguria decreased intraocular pressure decreased skin turgor Water & Na CH2 33 Water excess: the dilutional type of hyponatraemia Water & Na CH2 34 Water excess: the dilutional type of hyponatraemia ▪ Excess of water and sodium may result from ➔ a failure of normal excretion or from excessive intake. ▪ It is related to an impairment of water excretion. ▪ Occasionally, excessive intake is alone sufficient to cause water intoxication. The increased water load is shared by the ICF and ECF. ▪ The clinical features of water overload are related to➔ cerebral overhydration, the incidence and severity depending➔ upon the extent of the water excess and its time course. ▪ Gradually water retention (over several days), ➔may be asymptomatic ▪ Acute water retention may ➔show sign of severe water Water & Na CH2 35 intoxication Water & Na CH2 36 The dilutional type of hyponatraemia Is secondary to ➔the excessive retention of water; Na+ may be normal or increased. ▪ ▪ It occurs in oedema, uncontrolled diabetes, nephrotic syndrome total body ascites from: chronic cardiac failure, hepatic cirrhosis, and malnutrition. ▪ Water retention results from➔ impaired water excretion rarely from increased intake and ▪ Water retention hyponatraemia is called also ➔ syndrome of inappropriate antidiuresis (SIAD) appear in : infection, malignancy, trauma, chest disease, drug induced and inappropriate high ADH secretion. Water & Na CH2 37 The dilutional type of hyponatraemia Water & Na CH2 38 Hyponatraemia: Assessment and Management In assessment of hyponatraemic patients the following points should be taken ➢ How dangerous is the case ➢ Is it water retention or sodium loss ➢ What is the proper treatment Severity In assessing the risk of the case the following points should be known ➢The serum sodium concentration: 120 mmol/l is considered as threshold after which the risk will decline by increasing the sodium conc. ➢ How quickly the sodium concentration has fallen from normal concentration. ➢ History; is it loss of fluid from the gut or/and kidney (indicator for sodium loss). The patient should be asked about sodium loss symptoms, like dizziness, weakness and light headedness ➢ The presence of signs and symptoms related to hyponatraemia: symptoms reflect: neurological dysfunction resulting from ➔cerebral over-hydration induced by hypo osmolality, nausea, malaise, headache, lethargy and reduced level of consciousness, seizures and coma 39 Water & Na CH2 Water & Na CH2 Clinical Examination The clinical features of ECF compartment 40 Disorders of Water Balance: Edema ▪ Accumulation of fluid in the interstitial space, leading to ➔tissue swelling ▪ Caused by anything that increases flow of fluids out of the bloodstream or hinders their return ▪ Factors that accelerate fluid loss include: ▪ Increased blood pressure or capillary permeability ▪ Incompetent venous valves, localized blood vessel blockage ▪ Congestive heart failure, hypertension, high blood volume ▪ Hypoproteinemia – low levels of plasma proteins ▪ Forces fluids out of capillary beds at the arterial ends ▪ Fluids fail to return at the venous ends ▪ Results from protein malnutrition, liver disease, or glomerulonephritis 41 Water & Na CH2 Water & Na CH2 ➢The response to edema is secondary hyperaldosteronism. ➢Aldosterone causes➔ sodium (and water) retention, thus expanding the ECF volume Patients with oedema become hyponatraemic despite sodium retention because ➔the effective hypovolaemia also stimulates AVP secretion, ➔resulting in additional water retention 42 Treatment of Hyponatremia ➢ Hypovolaemic patients are sodium depleted and should be given sodium. ➢ Normovolaemic patients are likely to be retaining water and should be fluid restricted. ➢ Oedematous patients have an excess of both total body sodium and water; they should be given a diuretic to induce natriuresis, and be fluid restricted. ➢ More aggressive treatment (usually requiring hypertonic saline) may be indicated if➔ symptoms attributable to hyponatraemia are present, or the sodium concentration is less 110 mmol/l. Waterthan & Na CH2 43 Hypernatraemia Hypernatraemia is an increase in the serum sodium concentration above the reference interval of 135-145 mmol/L. Develops either because of : water loss or sodium gain. Water depletion ▪ Pure water loss may arise from: decreased intake or ▪ Pure water depletion is seen much less frequently than sodium. excessive loss. depletion of both water and ▪ Sodium can not be excreted alone but is➔ always accompanied by some loss of water. The lost fluid may be isotonic or hypotonic with respect to plasma. ▪ Water and sodium loss can result in➔ hypernatraemia if the => water loss exceeds the sodium loss. This can happen in osmotic diuresis like in ➔poorly controlled diabetes mellitus, or due to excessive sweating or diarrhoea, especially in children. ▪ Usually, loss of body fluids because of vomiting or diarrhoea usually results in hyponatraemia ▪ Less commonly, ➔ excessive loss of water without sodium loss is unusual, except in diabetes insipidus (lack of ADH). Water & Na CH2 44 The mechanisms of hypernatraemia Water & Na CH2 45 Water & Na CH2 ➢Hypernatraemia ➔may be associated with : a decreased, normal or expanded ECF ➢Severe water depletion induces➔ cerebral dehydration leading to ➔cerebral haemorrhage. ➢Prolonged dehydration➔ the brain cells produce ➔osmotically active compounds and cerebral oedema may then follow rapid fluid replacement ➢Hypernatraemia may develops in response to ➔insulin treatment of uncontrolled diabetes because of falling plasma concentration of glucose causes➔ decrease in plasma osmolality and contraction of extracellular fluid volume. 46 Water & Na CH2 47 Water depletion Water & Na CH2 ▪ The management of water depletion involves: 1. treatment of the underlying cause 2. replacement of fluid shortage. ▪ Water should preferably be given orally or through a nasogastric tube. ▪ If this is not possible, either 5% dextrose or, if there is also some sodium depletion, hypotonic saline, should be given intravenously. Causes Clinical features Increased loss from kidneys: renal tubular disorders diabetes insipidus increased osmotic load due to diabetes mellitus, osmotic diuretics or high protein intake from skin: sweating from lungs: hyperventilation from gut: diarrhoea (in infants) Decreased intake Infancy and old age (dysphagia) Unconsciousness restriction of oral intake Symptoms thirst dryness of mouth difficulty in swallowing weakness confusion Signs weight loss dryness of mucus membranes decreased saliva secretion decreased urine volume (early) 48 Water & Na CH2 Hypernatraemia Sodium gain: Can be due to increased intake decreased excretion “salt poisoning” ➢ Hypernatraemia due to sodium gain ➢ It is much less common than water loss. ➢ It can occur in several clinical situations ➢ or like: ▪ In the life-threatening acidosis in which ▪ Infants are susceptible to hypernatraemia if given high-sodium feeds either accidentally or on purpose. sodium bicarbonate is given Hypernatraemia is often associated with hypercalcaemia and hypokalaemia, as seen in ➔liver disease, cardiac failure, pregnancy, burns, and osmotic diuresis. The pathophysiological Sodium gain is ➢ Hyperaldosteronism (Conn's syndrome), where there is excessive aldosterone secretion and ➔subsequent sodium retention by the renal tubules. ➢ Patients with Cushing's syndrome, where there is excess cortisol production. Cortisol has➔ weak mineralocorticoid activity. 49 Sodium excess The clinical features are related to the expansion of ECF volume. Causes Clinical features Increased intake excessive parenteral administration absorption from saline emetics peripheral oedema dyspnoea pulmonary oedema venous congestion hypertension effusions weight gain Decreased excretion decreased glomerular filtration: acute and chronic renal failure increased tubular reabsorption: primary mineralocorticoid excess: Cushing's syndrome Conn's syndrome secondary mineralocorticoid excess: congestive cardiac failure nephrotic syndrome hepatic cirrhosis with ascites renal artery stenosis Water & Na CH2 50 Clinical features of Hypernatraemia All important. ➢ With mild hypernatraemia (sodium <150 mmol/l), if the patient has ➔obvious clinical features of dehydration, it is likely that the ➔ECF volume is reduced and that one is dealing with ➔loss of both water and sodium. ➢ With more severe hypernatraemia (sodium 150 to 170 mmol/l), pure water loss is likely if ➔ the clinical signs of dehydration are mild in relation to the severity of the hypernatraemia. ➔ This is because pure water loss is distributed evenly throughout all body compartments (ECF and ICF). (The sodium content of the ECF is unchanged in pure water loss.) ➢ With gross hypernatraemia (sodium >180 mmol/l), one should suspect ➔salt poisoning if there is little or no clinical evidence of dehydration; the amount of water that ➔would need to be lost to➔ elevate the sodium to this degree should be clinically obvious Water & Na CH2 51 Treatment ➢ Patients with hypernatraemia due to pure water loss need free water; this may be given orally, or intravenously as 5% dextrose. ➢ If there is clinical evidence of dehydration indicating➔ probable loss of sodium as well, ➔ sodium should also be administered. ➢ Salt poisoning is ➔a difficult clinical problem to manage. The sodium overload can be ➔treated with diuretics and the natriuresis replaced with water ➢ Caution must be exercised with the use of intravenous dextrose in salt poisoned patients-they are ➔volume expanded already and susceptible to pulmonary oedema. Water & Na CH2 52 Water & Na CH2 Other osmolality disorders ▪ A high plasma osmolality may sometimes be encountered for reasons other than hypernatraemia. Causes include: 1. Increased urea in renal disease 2. Hyperglycemia in diabetes mellitus 3. ▪ The presence of ethanol or some other ingested substances If the osmolal gap (➔the difference between the measured and calculated osmolality) is large, this suggests ➔the presence of significant contributor to the osmolality unaccounted for in the calculation. In practice, this is almost always due to the presence of ethanol in the blood ▪ The consequences of disordered osmolality are due to the changes in volume which arise as water moves in or out of cells to maintain osmotic balance. 53 ▪ From the three examples mentioned, only glucose causes significant fluid movement. ▪ Glucose cannot freely enter cells, and an increase in ECF concentration causes ➔ water to move out of cells and leads to intracellular dehydration. ▪ This can lead to➔ contraction of brain volume and the rupture of small blood vessels with haemorrhage as tissues pull away from its surroundings ▪ Urea and ethanol permeates cells and do not cause such fluid shifts, as long as concentration changes occur slowly Water & Na CH2 54 Laboratory assessment of water and sodium status The plasma sodium concentration is ➔dependent upon the relative amounts of sodium and water in the plasma. It may be raised, normal or, the amount of water in the ECF. low in states of sodium excess or depletion,➔ according to Sodium should be measured in the following: ▪ Patients with dehydration or excessive fluid loss for the appropriate replacement ▪ To monitor the parental fluid replacement ▪ Patients with unexplained confusion, abnormal behaviour or signs of CNS irritability. Specimens • Serum, heparinised plasma, whole blood, sweat, urine, faeces, or gastrointestinal fluids may be assayed. Erythrocytes contain only one tenth of the Na+ present in plasma; thus, ➔haemolysis does not cause a significant decrease in observed Na+ values for serum or plasma unless it is severe, in which case a dilutional effect occurs. • Sodium is currently most often determined electrochemically with an ion-selective electrode (ISE) or by flame emission spectrophotometry (FES). Reference intervals The interval for serum Na+ is 136 to 145 mmol/L from infancy throughout life. 55 Water & Na CH2 Water & Na CH2 56 Case Study Clinical presentation ▪ A 56 year old man diagnosed with oat cell carcinoma of the lung develops progressive lethargy and confusion. ▪ Laboratory findings ▪ Laboratory investigation produced the following results. Water & Na CH2 57 Cont. Case study. Comment on laboratory findings Plasma sodium levels are low and urine osmolality is close to upper limit. This is suggestive of hyponatremia. Possible causes of the abnormality In health sodium concentration in the body is controlled by Antideuretic Hormone secreted by the pituitary gland in the hypothalamus. Increase in plasma osmolality which is mainly due to sodium concentration in the blood is sensed by osmoreceptors in the hypothalamus. This induces secretion of Antideuretic hormone (ADH) by the pituitary gland. The hormone act on the distal convoluted tubule of the kidney. This makes the kidney to retain water in the blood thus diluting the ECF and bringing plasma osmolality to normal. In oat cell carcinoma the cancer cells contain neurosecretory bodies which secrete Antideuretic Hormone and other hormones like Adenocorticotrophic Hormone (ACTH)and calcitonin. This abnormal (ectopic) secretion of ADH causes unnecessary water retention by the kidney leading to dilution of Extra Cellular Fluid. Retention of water by the kidneys explains the excretion of urine of high osmolality by the patient. According to the evidence found the patient has dilutional hyponatremia due to inappropriate ADH secretion. Water & Na CH2 58 Cont. Case study. Clinical and laboratory evidence Lethargy and confusion are typical symptoms of hypomatremia. Low concentration of sodium in the brain ECF result in lethargy. Confusion is due to water intoxication. Additional laboratory investigation Sodium is the main determinant of plasma osmolality, in dilutional hyponatremia plasmaosmolality should be low.Plasma osmolality= 2[Na+]+[urea]+[glucose] 2[119] +5+6.2=249mOsmo/kg From the calculations plasma osmolality of the patient is lower than the minimum normallevel. This is 282 mOsmo/kg. This evidence support the fact that water is being retainedthus diluting the ECF.To be certain that this is dilutional hyponatrenia, the patient should have. 1.Normal renal createnine clearance rate. 2.To confirm the dilution of plasma, albumin concentration should be measured andshould be low Water & Na CH2 59 Example questions ▪ Q1. What are the clinical and biochemical features of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)? Q2. A 50 year old man with a psychiatric condition presents in an acute confusional ▪ state and is found to have a plasma sodium of 108 mmol/L, osmolality of 228 mmol/kg and a plasma urea of 2.1 mmol/L. The urine sodium is 10 mmol/L with a urine osmolality of 70 mmol/kg. What is the likely diagnosis and what further tests would be helpful? Q3. A doctor enquires about the differential diagnosis and further investigation of a 60 year old female with a plasma sodium of 125 mmol/L two days post-op. Outline your approach and what further biochemical tests may assist with the diagnosis. Q5. Discuss the regulation of fluid and water balance in man. ▪ ▪ Q6. You are contacted by a junior doctor for assistance in investigating a plasma ▪ sodium of 155 mmol/L in a 35 year old man. What questions would you ask, what further investigations might be helpful and what are the possible causes? Q7. Describe how a water deprivation test is performed and comment on the results you would expect in central diabetes insipidus, nephrogenic DI and primary polydipsia. Water & Na CH2 61 ▪