Fluid and Electrolyte Balance PDF

FLUID AND ELECTROLYTE BALANCE  OUTLINE INTRODUCTION DISTRIBUTION OF WATER IN THE BODY WATER HOMEOSTASIS DERANGEMENT OF WATER HOMEOSTASIS DISTRIBUTION OF SODIUM IN THE BODY SODIUM HOMEOSTASIS DERANGEMENT OF SODIUM HOMEOSTASIS  INTRODUCTI...

FLUID AND ELECTROLYTE BALANCE  OUTLINE INTRODUCTION DISTRIBUTION OF WATER IN THE BODY WATER HOMEOSTASIS DERANGEMENT OF WATER HOMEOSTASIS DISTRIBUTION OF SODIUM IN THE BODY SODIUM HOMEOSTASIS DERANGEMENT OF SODIUM HOMEOSTASIS  INTRODUCTION Water is an essential body constituent and homeostatic processes are important in ensuring that the total body water is maintained within narrow limits and also to maintain their distribution among the different body compartments.  INTRODUCTION Sodium is the most abundant extracellular cation and with its associated anions account for most of the osmotic activity of the ECF and also important in determining water distribution across cell membranes.  Distribution of water in the body Total body water is about 42L, 60% of body weight. ICF: 24L ECF: 18L – Interstitial: 13L – Intravascular: 5L  Total body water content according to sex and age. % body weight Infants ~70 Young males ~60 Young females ~55 Elderly males ~50 Elderly females ~45  WATER HOMEOSTASIS The daily adult water intake is between 1.5L-2L. About 200L of water is filtered by the kidney daily. About 10L enters the intestinal lumen. 1.5-2L of water is excreted in urine daily. 100mL is excreted in the faeces. 1L is lost in sweat and expired air daily-insensible loss  WATER HOMEOSTASIS Both the intake and loss of water are controlled by osmotic gradients across cell membranes in the brain’s hypothalamic osmoreceptor centers by controlling thirst and ADH secretion.  Factors affecting water homeostasis Neural factors: Thirst * Autonomic nervous system Renal factors: * Glomerular filtration rate Counter current multiplier Counter current exchange Circulating hormones: * Arginine vasopressin * Atrial natriuretic factor * Aldosterone * Cortisol * Thyroid hormones  INTAKE Daily intake of water is variable depending on body losses and psychological factors. An average intake would be around 1.5-2 litres a day. The major factor determining intake is thirst which is under the control of the thirst centre located in the hypothalamus.  Thirst Normal functioning of this centre is influenced by: ECF tonicity: hypertonicity increases thirst. Blood volume: decreased volume increases thirst. Miscellaneous factors: pain and stress, for example increase thirst.  OUTPUT A subject is in water balance when total intake and overall loss of body water are approximately equal. Variable amounts of fluid are lost from the skin (sweating) and the mucous membranes (electrolyte- free water in expired air), depending on the environmental temperature and respiratory rate. Neither of these losses can be controlled to meet water requirements A small amount of water is lost in the faeces ( ↑ECF tonicity -> – ↑Thirst (increase water intake) – ↑AVP secretion (increase renal water re- absorption) – Water shift from ICF to ECF a + b + c -> ↑ECF volume and ↓ICF volume  Water Balance ↓ECF sodium -> ↓ECF tonicity -> – ↓Thirst (decrease water intake) – ↓AVP secretion (decrease renal water excretion) – Water shift from ECF to ICF a + b + c -> ↓ECF volume and ↑ICF volume Thus total body sodium (most of which is in the ECF) can be said to control the extracellular volume (and water balance) and, as will be seen later, the extracellular volume controls the total body sodium (and sodium balance).  Water Balance An increase in the osmolarity of interstitial fluid draws water out of cells and they shrink slightly. A decrease in the osmolarity of interstitial fluid also causes cells to swell. When a person consumes water faster than the kidneys excrete it or renal function is poor-water intoxication, cells swell.  Disorders of Water Balance Dehydration Hypotonic Hydration Edema  Dehydration Water loss exceeds water intake and the body is in negative fluid balance Causes include: haemorrhage, severe burns, prolonged vomiting or diarrhoea, profuse sweating, water deprivation, and diuretic (ab)use Signs and symptoms: dry mouth/mucosal, thirst, dry flushed skin, and oliguria  Dehydration Prolonged dehydration may lead to weight loss, mental confusion Other consequences include hypovolemic shock, AKI and loss of electrolytes  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  Hypotonic fluid loss Dehydration due to loss of fluid containing significant amounts of sodium (coupled with inadequate fluid intake) may be due to: Skin losses: excessive sweating Gut losses: vomiting, diarrhoea, drainage into fistulae Renal losses: diuretic therapy, Addison’s disease, salt-losing nephritis, diabetes insipidus  Isotonic fluid loss This is less common but may occur in: Loss of blood: haemorrhage, accidents Loss of serum: burns ‘Third space’ accumulations: ileus, pancreatitis, peritonitis, crush injury  Water Excess The patient with excessive total body water may present in a variety of ways, but the common ones are peripheral oedema and hyponatraemia. Oedema may also associated with sodium excess Hyponatraemia, in the context of body water excess, is usually associated with a normal or slightly decreased total body water content (the exception being the occasional finding of hyponatraemia in oedematous conditions).  Decreased renal water excretion Antidiuresis is usually due to excessive AVP secretion but it can also be associated with a variety of drugs: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) Antidiuretic drugs Diuretic-related hyponatraemia Endocrine disorders  SIADH This condition, as the name suggests, is due to the continued secretion of AVP (or ADH) in the face of hypotonicity or increased intravascular volume or both, i.e. its secretion is inappropriate in that it occurs under conditions that normally suppress its secretion.  Aetiology Commonest cause is the ectopic production of AVP by a malignant tumour, but it can also be produced by a wide variety of conditions: Tumours Carcinoma of bronchus, prostate, pancreas Brain tumour: glioma, meningioma Brain pathology Tumours; Trauma/cerebrovascular accidents Infection: abscess, meningitis, encephalitis Pulmonary pathology Tumours: bronchial carcinoma Infection: tuberculosis, pneumonia Pneumothorax Hydrothorax  Aetiology Drugs that increase AVP secretion Hypnotics: barbiturates Narcotics: morphine, pethidine Anticonvulsants: carbamazepine Antineoplastics: vincristine, vinblastine, cyclophosophamide Miscellaneous: clofibrate, nicotine derivatives Drugs that potentiate AVP activity Hypoglycaemics: chlorpropamide, tolbutamide Paracetamol Indomethacin These drug-related conditions are best referred to as syndromes of inappropriate antidiuresis to distinguish them from SIADH. The treatment is to discontinue the drug but if this is not possible fluid restriction may be necessary.  Disorders of Renal Water Excretion An increased urinary output (polyuria) is usually always associated with an increased intake. It may be primarily due to a high fluid intake, or secondary to disorders of AVP production, AVP action at the renal level, or osmotic diuresis. Similarly, a low urine output (oliguria) may reflect a decreased fluid intake or be secondary to renal disease.  Polyuria Polyuria is a subjective symptom and difficult to define Taken as urinary volume in excess of 2.5-3 litres a day. It should not be confused with frequency (frequent passage of small amounts of urine but a normal daily output).  Aetiology A high urinary volume can be due to increased fluid intake in an otherwise normal subject or to some defect in renal concentrating ability. In order for the kidney to reabsorb water and concentrate the urine the following must be satisfied: Delivery of a dilute urine to the collecting ducts (i.e. a normal functioning ‘diluting’ segment) AVP availability. Normal response of the collecting duct to AVP High medullary to luminal osmotic gradient in the colleting duct area  Causes Osmotic diuresis: high luminal concentrations of glucose (diabetes mellitus) and sodium (diuretic therapy) produce a high urine osmolality and inhibit delivery of a dilute urine to the collecting ducts.  Causes of Polyuria AVP deficiency: – neurogenic diabetes insipidus: – drugs that modify release of ADH – post-surgical stress, hypercapnia (temporary suppression of AVP release) Abnormalities of collecting ducts: ✓Functional: nephrogenic diabetes insipidus (inborn error of metabolism resulting in ducts being non-responsive to AVP) ✓Drugs that suppress or inhibit ADH activity at the collecting duct. ✓Structural damage: pyelonephritis, analgesic nephropathy, hypercalcaemia, hypokalaemia, nephrocalcinosis  Causes of Polyuria Loss of medullary tonicity: Defective reabsorption of sodium and chloride ions by the ascending limbs of the loop of Henle due to diuretic therapy will compromise the medullary tonicity From a laboratory diagnosis viewpoint it is convenient to classify the polyurias on the basis of the type of diuresis. Water diuresis (urine osmolality ˂200 mosmol/Kg): High intake (psychogenic polydipsia) Diabetes insipidus: – central or neurogenic – nephrogenic. Solute diuresis (urine osmolality ~300 mosmol/kg): Sodium: high intake, diuretic therapy Glucose: diabetes mellitus Urea: hypercatabolic states, renal disease.  Diabetes insipidus (DI) There are two varieties of DI, the neurogenic and nephrogenic. Neurogenic DI: The inability to produce or secrete AVP may be due to hypothalamic or pituitary disease (primary disease, trauma, tumours, infections, etc). The lack of this hormone results in the passage of very large amounts (5 to 20 L/day) of very dilute urine (osmolality 50-100 mosmol/kg). It will not result in dehydration or hypernatremia unless there is an inadequate fluid intake. The disorder responds to exogenous AVP.  Nephrogenic DI This may be due to inherited disorder whereby the collecting duct will not respond to AVP or it may be due to local mechanism (structural renal disease, metabolic disorders). It presents with a similar picture to the neurogenic variety but it will not respond to exogenous AVP.  Psychogenic overdrinking This disorder has similar features to DI—polydipsia, polyuria with a dilute urine. The difference is the patient’s response to fluid restriction. After overnight fluid restriction a normal subject will concentrate his urine to produce an osmolality greater than 750 mosmol/kg: a patient with DI, depending on the degree of defect, with rarely produce a urine osmolality above 400mosmol/kg and often it will be less than 200 mosmol/kg. In the case of psychogenic overdrinking there will usually be a normal, or near normal response (urine osmolality ˃600mosmol/kg) to fluid restriction.  Solute Diuresis In solute diuresis the polyuria is due to osmotic diuresis and hence it can be distinguished from water diuresis by urine osmolality of around 300 mosmol/kg and identification of the offending solute.  Solute Diuresis The clinical consequences, as opposed to the personal and social problems, of polyuria per se are minimal. If the oral fluid intake does not keep up with the output, as during illness, then dehydration and hypernatremia can occur. If the polyuria is longstanding, dilation of the ureters may occur.  Water deprivation Test There are many ways of performing a dehydration or water deprivation test; the following has been found useful. No water taken from 9.00pm the night before until conclusion of the test. At 7.00 am the next morning empty bladder and discard urine. Beginning at 8.00 am pass urine hourly (empty bladder complete). Estimate the osmolality and continue in this manner hourly until either the osmolality reaches 750  Water deprivation Test mosmol/L (no abnormality) or until the osmolality reaches a plateau (difference between consecutive estimations of less than 30 mosmol/kg). When a plateau is reached take a blood sample a serum osmolality and administer AVP (5 units of aqueous vasopressin intramuscularly or DDAVP nasally). Exactly one hour later collect urine and estimate the osmolality.  Water deprivation Test The interpretation of this test is as follows: A urine:plasma osmolality ratio of ˂1 and an increase in the urine osmolality (after AVP injection) of at least 50% (or to greater than 800 mosmol/kg), indicate severe neurogenic diabetes insipidus A urine:plasma osmolality ratio of ˃1 and an increase in urine osmolality after AVP by 60-70% (or to greater than 800 mosmol/kg), denote partial neurogenic diabetes insipidus  Water deprivation Test A urinary osmolality that does not reach 300 mosmol/kg at any point during the test period and shows no increase after AVP injection , is diagnostic of nephrogenic diabetes insipidus. A urinary osmolality that exceeds 300 mosmol/kg but not 800 mosmol/kg and shows no further increase after AVP, may be due either partial nephrogenic diabetes insipidus or primary polydipsia. Water deprivation Test – Some relevant points of note are: – Incomplete emptying of the bladder (residual urine interferes with the test) and surreptitious water drinking during the test will invalidate the procedure. – An otherwise normal subject who has had an excessive fluid intake for a long period may ‘wash-out’ the renal interstitial osmoles and produce a test result indicating incomplete nephrogenic DI.  Oliguria Oliguria, a low urine output, usually indicates renal dysfunction and is usually considered in sections on renal disease. However, it can occur in the absence of renal disease and will be discussed here for the sake of completeness. A definition in terms of urine volume is difficult but an excretion of less than 500-600 mL/day (often 400ml/day) is a useful figure if the average amount of solute to be cleared by the kidney is 600 mmol and the kidney can concentrate the urine up to a maximum of 1200 mosmol/kg, then 500 mL is the minimal amount of urine required  CAUSES A decrease in urine output is usually classified as prerenal, renal, and post renal depending on the site of the dysfunction. Prerenal oliguria. In this situation the kidney and urinary apparatus are normal and the decrease is due to a decreased GFR which in turn is due to hypovolaemia, e.g., dehydration, blood loss, serum loss. Renal oliguria. This indicates that the kidney is at fault (renal disease) but for the sake of completeness, we will add conditions associated with increased AVP activity.  Causes Renal disease: Both acute and chronic renal failure can present with oliguria but they can also be associated with polyuria due to uraemia-induced diuresis. Acute renal shutdown (acute tubular necrosis) may present with severe oliguria and has to be distinguished from prerenal failure.  Causes Increased AVP activity: Increased AVP activity due to SIADH or various drugs will decrease urinary output but it may not be sufficient to lower the volume to below 600 mL/day or to be noticed by the patient or clinician as a decreased urinary output.  Postrenal oliguria This occurs in an otherwise normal patient who has an obstruction to urine outflow. The obstruction can be anywhere from the kidney pelvis to the urethra. The commonest site is the prostatic area (prostatic hyperplasia or malignancy) but stones and strictures may occur at any level. Obstruction at the base of the bladder and all points onwards can produce anuria (no urine) which is uncommon in other conditions associated with a decreased urine output  Oedema Atypical 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, capillary permeability –Incompetent venous valves, localized blood vessel blockage –Congestive heart failure, hypertension, high blood volume  Oedema Hindered fluid return usually reflects an imbalance in colloid osmotic pressures Hypoproteinaemia - 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  Oedema Blocked (or surgically removed) lymph vessels: – Cause leaked proteins to accumulate in interstitial fluid – Exert increasing colloid osmotic pressure, which draws fluid from the blood Interstitial fluid accumulation results in low blood pressure and severely impaired circulation  SODIUM From a pathophysiological point of view the function of sodium is to maintain the extracellular and intravascular volumes. A decrease in the total body sodium, which is mainly extracellular, results in a decreased extracellular volume (ECV) and an increased total body sodium is associated with an increased ECV.  DISTRIBUTION The total body sodium content is around 3000 to 3500 millimoles with an excess of 90% located in the ECF compartment where it determines the volume of this compartment.  DISTRIBUTION Distribution of sodium Content Concentration (mmol) (mmol/L) Total body ~3050 Intracellular ~250 5-10 Extracellular ~2800 ~140 Plasma ~400 ~140  INTAKE OF SODIUM On a western diet the daily intake of sodium in food and drink is about 150 to 250 mmol/day, most of which is absorbed. Unlike the thirst mechanism for water there is no well defined ‘sodium centre’; however, there appears to be an ill-defined sodium appetite, e.g., subjects with the salt-depleting Addison’s disease have a salt-craving. Generally, the intake is governed by habit rather than need.  OUTPUT To maintain sodium balance the intake must equal the output. Almost all of the intake has to be excreted in the urine and the kidney is the main controller of homeostasis A small amount of sodium (10-20 mmol/day) is excreted in the sweat and faeces,  Regulation of sodium balance – Aldosterone The renin-angiotensin mechanism triggers the release of aldosterone This is mediated by juxtaglomerular apparatus, which releases renin in response to: – Sympathetic nervous system stimulation – Decreased filtrate osmolality – Decreased stretch due to decreased blood pressure Regulation of sodium balance Adrenal cortical cells are directly stimulated to release aldosterone by elevated K+ levels in the ECF Aldosterone brings about its effects (diminished urine output and increased blood volume) slowly Renin catalyzes the production of angiotensin II, which prompts aldosterone release  CVS 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 Regulation of sodium balance 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"  ANP Reduces blood pressure and blood volume by inhibiting: – Events that promote vasoconstriction – Na+ and water retention Is released in the heart atria as a response to stretch (elevated blood pressure) Has potent diuretic and natriuretic effects Promotes excretion of sodium and water Inhibits angiotensin II production  Atrial natriuretic peptide (ANP) ANP is released from the atrium in response to stretching (e.g. increased blood volume, hypervolaemia); it causes: Increased GFR Increased glomerular filtration fraction Natriuresis Kaliureis Diuresis Decreased renin and aldosterone secretion It is unclear how ANP induces natriuresis but the most likely mechanism is variation of the intrarenal blood flow causing increased GFR and increased filtration fraction (constriction of the efferent glomerular arterioles). Its action in inhibiting renin and aldosterone secretion may also be a factor. 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  GFR The amount of sodium presented to the tubules depends, in the first instance, on the amount filtered (determined by the renal blood flow and its sodium content) and there is some evidence that the GFR influences the tubular re- absorption rate, e.g. a decreased GFR is associated with sodium retention. Under normal circumstances there is a balance between the amount filtered and the amount reabsorbed (glomerulotubular balance), i.e. increased filtered sodium is balanced by increased tubular re-absorption and vice versa, and the FENa is normally maintained at less than 1%.  Aldosterone A decrease in the renal blood flow (hypovolaemia, low EABV) causes renin release and subsequently an increased production of angiotensin II which causes vasoconstriction and secretion of aldosterone. Aldosterone increases the distal renal tubular re-absorption of sodium ions and increases the excretion of potassium and hydrogen ions. The sodium ions enter the tubular cells through specific sodium channels (this mechanism is blocked by amiloride) leaving a negatively charged luminal aspect (due to the retained Cl-) which ‘encourages’ the secretion of the positively charged cellular hydrogen and potassium ions.  Summary From the above it will be appreciated that: Increased intravascular volume (or effective arterial blood volume) results in increased renal sodium excretion (decreased aldosterone plus increased ANP). Decreased blood volume produces renal sodium retention (increased aldosterone, decreased ANP)  HYPERNATREMIA Hypernatremia is generally defined as a serum sodium concentration in excess of 145 mmol/L but for practical and clinical purposes a value in excess of 148 mmol/L is more realistic. As a working proposition it is reasonable to assume that hypernatremia equals a negative water balance which is due to decreased water intake.  Causes of hypernatremia *Pure water depletion (inadequate intake in face of normal losses) Subject too old, too young, or too sick to drink Access to water denied Oesophageal obstructions Thirst centre lesions *Sodium and water depletion (hypotonic fluid loss) Extrarenal GIT: vomiting, diarrhoea Skin: excessive sweating  Causes of hypernatremia Renal Osmotic diuresis: glucose Diuretic therapy Diabetes insipidus: neurogenic, nephrogenic →Salt gain (without proportional gain in water) Iatrogenic: IV hypertonic saline/sodium bicarbonate Salt ingestion: intentional, accidental Primary mineralocorticoid excess  Euvolemic hypernatraemia These are the patients who are predominantly water depleted because, in the face of normal fluid losses from the body, they are unable to take fluid in, i.e. it could be one who is: – Too young, too old, or too sick to drink; – With no access to water; – With lesions of the thirst centre; – With an obstructed oesophagus; or – Receiving inappropriate iv therapy.  Hypovolaemic hypernatraemia This describes patients who, in addition to not taking in adequate fluid, are losing hypotonic fluid from the body, i.e. they are both water and salt depleted but the water depletion is relatively greater than the salt depletion. They are hypovolaemic and present with overt clinical evidence of this condition (high pulse rate, hypotension, etc).  Hypovolaemic hypernatraemia If they lose fluid from an extrarenal site they will be passing a small amount of highly concentrated urine with a low sodium content (renal retention of water and sodium stimulated by hypovolaemia). If the origin of the fluid loss is the kidney the urine volume is variable and the urine osmolality is often similar to that of the plasma (urine:plasma osmolality ratio ~1) except in diabetes insipidus in which large volumes of dilute urine are excreted (urine:plasma osmolality 30 mmol/L).  Causes of hyponatraemia Euvolaemic (TBNa, normal) Pseudohyponatraemia (eutonic) Hyperlipidaemia Excess intracellular solute (hypertonic) Hyperglycaemia Acute water overload ((hypotonic) Rapid water intake PLUS Hypovolaemia Drugs Stress: post-surgery, psychogenic Endocrine: hypothyroidism, cortisol deficiency  Causes of hyponatraemia Chronic water overload(hypotonic) SIADH Drugs Renal failure Endocrine: hypothyroidism, cortisol deficiency Hypovolaemic (TBNa, decreased) Extrarenal causes (hypotonic) GIT: vomiting, diarrhoea Skin: burns Renal causes (hypotonic) Diuretic therapy Addison’s disease Salt-losing nephritis Hypervolaemic (TBNa, increased/Oedematous; hypotonic) Cardiac failure Nephrotic syndrome Liver cirrhosis  Hypertonic hyponatraemia A low serum sodium concentration associated with a high serum osmolality usually indicates hyperglycaemia. Severe hyperglycaemia, e.g., ˃40 mmol/L, can cause hyponatraemia by virtue of its osmotic effect. The high extracellular osmolality (tonicity) draws water out of cells into the extracellular compartment, causing dilutional hyponatraemia.  Hypertonic hyponatraemia In such cases, when the glucose is taken up by the cells (e.g., following insulin therapy) the excess extracellular water will pass back to the cells. A useful rule-of-thumb for calculating the true serum sodium concentration after the removal of glucose is to divide the serum glucose concentration (in mmol/L) by 4 and add this figure to the measured serum sodium concentration.  Hypotonic hyponatraemia Patients with hyponatraemia and a low serum osmolality may be Hypervolaemic, Euvolaemic, or hypovolaemic. Hypervolaemic. This describes the oedematous patients with hyponatraemia. The commonest cause of hyponatraemia associated with oedema is diuretic therapy. However, a number of untreated oedematous subjects present with hyponatraemia which is presumably due to retention of more water relative to sodium.  Hypovolaemic They are the subjects who have lost hypotonic fluids by renal or extrarenal route and thereafter replaced their salt and water loss by drinking pure water, but still remain dehydrated. This is a depletional hyponatraemia (not to be confused with dilutional hyponatraemia which is associated with euvolaemia).  Euvolaemic This describes subjects who are hyponatraemic but who are neither oedematous nor dehydrated. The pathophysiology is water excess due to decreased renal water excretion (dilutional hyponatraemia). This may occur as an acute or chronic process:  Acute water overload This occurs when there is rapid water intake (oral or more usually iv) in a patient who has a problem excreting water due to: Hypovolaemia (inducing AVP secretion): haemorrhage, burns. Stress: post-surgery, psychogenic (AVP) Drugs Endocrinopathies  Chronic water overload Chronic water overload: SIADH, drug effects, hypothyroidism, cortisol deficiency. THANK YOU