Disturbances of fluid and electrolyte balance Csaba Hermann

Disturbances of fluid and electrolyte balance Csaba Hermann MD Dept. of Anesthesiology and Intensive Care Semmelweis University

Homeostasis • The maintenance of normal volume and normal composition of the extracellular fluid is vital to life. • Homeostasis: the various physiologic arrangements which serve to restore the normal state, once it has been disturbed • • Fluid balance Electrolyte balance Osmotic balance Acid-base balance

General principles • Diffusion: movement of the particles in a solution from the area of high concentration to the area of lower concentration • Electrolyte: inorganic substance that dissociates into ions • Osmosis: diffusion of solvent molecules (water) into region in which there is a higher concentration of a solute (electrolyte) to which the membrane is impermeable • Osmotic pressure: the pressure necessary to prevent solvent migration • Osmol: concentration of osmotic active particles

General principles • Osmolarity : number of osmoles per liter of solution • Osmolality: number of osmoles per kilogram of solvent • Measurement: depression of freezing point • Calculation (plasma): 2 x(Na+K)+glucose+BUN (mmol/l) • Tonicity: effective osmolality of a solution relative to plasma • Colloids: high molecular weight particles (> 20000 D) • Oncotic pressure (colloid osmotic pressure): the pressure necessery to prevent diffusion of solvent molecules (water) into region in which there is a higher concentration of a colloid to which the membrane is impermeable

Extracellular space Intravasal Intracellular space Interstitial space Water Electrolytes Colloids Capillary wall Cell membrane Oncotic pressure Osmotic pressure

Body Fluid Volumes

Daily Water Balance (liters) OUTPUT INPUT • FLUID INTAKE 1. 5 • INSENSIBLE 0. 8 • IN FOOD 0, 8 • SWEAT 0, 1 • METABOLIC 0. 3 • FECES 0. 2 • Total 2, 6 • URINE 1. 5 • Total 2. 6

Composition of fluids (mmol/l) Fluid ICF Plasma ISF Liquor Verejték Nyál Gastric juice H+: 40 -60 Intestinal juice Na+ 12 140 145 147 20 -40 10 20 -80 K+ 140 4 -5 4, 4 3 5 26 5 -20 HCO 312 26 27 23 15 - 120 -140 5 -15 20 -40 Cl 4 112 117 113 15 -40 10 100 -150 10

Fluid replacement • • 0 -10 kg: 100 ml/kg/d 11 -20 kg: 50 ml/kg/d > 20 kg: 20 ml/kg/d 4 -2 -1 (ml/kg/h) Patient (70 kgs) (4 -2 -1) • 1 -10 kg 4 ml/kg/h • 11 -20 kg 2 ml/kg/h • >20 kg 1 ml/kg/h Together: 40 ml/h 20 ml/h 50 ml/h 110 ml/h 2640 ml/d

Fluid Balance • The main way to regulate body water gain is by adjusting the volume of water intake, mainly by drinking more or less fluid. The thirst center in the hypothalamus governs the urge to drink. • Although increased amounts of water and solutes are lost through sweating and exhalation during exercise, loss of excess water or excess solutes depends mainly on regulating excretion in the urine. • The extent of urinary Na (and Cl) loss is the main determinant of body fluid volume, whereas the extent of urinary water loss is the main determinant of body fluid osmolarity.

Fluid Balance • Angiotensin II and aldosterone reduce urinary loss of Na+ and Cl- and thereby increase the volume of body fluids (baroreceptors: sinus caroticus, kidney) • Stimulation of ANP production: elevation of atrial wall tension (Angiotensin) • ANP promotes natriuresis, elevated excretion of Na+ (and Cl- ), which decreases blood volume. • The major hormone that regulates water loss and thus body fluid osmolarity is ADH (Hypothalamus) • The regulation of the volume of body fluids superior to the regulation of osmolarity

Water Deficit • INCREASED OSMOLARITY SENSED BY HYPOTHALAMIC RECEPTORS RELIEVES • FALL IN ECF VOLUME • FALL IN ARTERIAL BLOOD PRESSURE STIMULATION OF HYPOTHALAMIC NEURONS INCREASED THIRST RELIEVES INCREASED VASOPRESSIN OPEN PORES IN COLLECTING DUCT ARTERIOLAR VASOCONSTRICTION MORE WATER REABSORBED INCREASED WATER INTAKE FALL IN URINE OUTPUT DECREASED PLASMA OSMOLARITY

Blood pressure and renal handling of sodium FALL IN SODIUM LOAD RELIEVES FALL IN ARTERIAL PRESSURE INCREASE IN ALDOSTERONE SECRETION FALL IN GFR FALL IN FILTERED SODIUM FALL IN EXCRETION OF SODIUM, CHLORIDE, AND FLUID INCREASED CONSERVATION OF SODIUM AND FLUID INCREASE IN SODIUM ABSORPTION

Disturbances of fluid homeostasis • Disturbance of fluid balance (intake≠output) • Dehydraton, Overhydration (hyperhydration) • Disturbance of osmolarity (electrolyte intake≠water intake) • Isonatremic (isotonic) • Hyponatremic (hypotonic) • Hypernatremic (hypertonic)

Disturbances of fluid homeostasis Diagnosis: • Physical signs: skin turgor, oedema, mucous membranes, neck veins, puls, liver, level of consciousness, capillary refill, fontanel (children) • Vital sings: blood pressure; heart rate; (respiratory rate); body temperature; CVP; urine output; serum and urine Na, osmolarity; Htk; serum total protein

Dehydration • Signs: increased thirst (except: advanced age, hypotonic dehydration), weakness, decreased skin turgor, dry mucous membranes, empty neck veins, decreased urine output, elevated Htk, fever, tachycardia, hypotension, decreased CVP, lethargy, stupor, coma • Mild (loss: 4% of body weight): decresed skin turgor, sunken eyes, dry mucous membranes • Moderate (loss: 5 -8 % of body weight): + oliguria, orthostatic hypotension, tachycardia • Severe (loss: 8 -10 % of body weight): + hypotension, decreased level of consciusness, stupor

Dehydration Isotonic Se Na n Se osmolarity n Hb + Htk + Blood volume Thirst mod. increase Hypertonic Hypotonic + + increased + + no

Isotonic dehydration • Intracellular fluid volume remains constant • External loss: vomiting, diarrhoea, haemorrhage, burning • Internal loss: ileus, ascites, pleural effusion • Therapy: volume replacement wiht isotonic solution

Hypertonic dehydration • Extracellular + intracellular fluid loss; elevated osmolarity • Causes: inadequate replacement of hypotonic fluid loss, osmotic diuresis (diabetes), decreased ADH secretion, high fever, heat stroke, massive diarrhoea • Therapy: slow water replacement, hypotonic solutions are contraindicated in the first phase of replacement • Water deficit (l): 0, 6*kg*((Nameasured/Nanormal)-1)

Hypotonic dehydration • Decreased extracellular fluid volumen, elevated intracellular fluid volume • Causes: inadequate fluid replacement with hypotonic solution, elevated ADH secretion + extracellular fluid loss, Addison’s disease, diuretics, vomiting • Usually no thirst • Therapy: Isotonic fluid replacement, Na replacement in case of severe hyponatraemia

Hyperhydration • Signs: oedema, increased skin turgor, elevated CVP, distended neck veins, pulmonary oedema Se. Na Se osmolarity Hb Htk Blood volume Isotonic n n + Hypertonic + + -+ Hypotonic (-) +

Isotonic hyperhydration • Intracellular fluid volume remains constant • Causes: renal failure, heart failure; decreased oncotic pressure, increased isotonic fluid intake • Therapy: decrease intake, diuretics

Hypertonic hyperhydration • Infrequent • Causes: renal failure, excessive hypertonic fluid input • Increased thirst, fever, convulsion, coma • Therapy: diuretics, dialysis + slow replacement with hypotonic solutions

Hypotonic hyperhydration • Intracellular fluid volume is also increased • Water poisoning • Causes: heart failure, near drowning (fresh-water), increased input of hypotonic solutions (TUR syndrome) • Symptomes: weakness, nausea, vomiting, altered mental status • Therapy: diuretics + fluid replacement with isotonic solution (+ Natrium)

Hyponatraemia • Serum Na < 135 mmol/l • Causes: • Water problem (excess of water relative to sodium) • Water excretion by the kidney is impaired • Pseudohyponatraemia (hyperlipidaemia, hyperproteinaemia) • Symptoms: • Cerebral oedema • Nausea, vomiting, lethargy, confusion, seizures, coma • Therapy: • Hypertonic saline (Se Na < 125 mmol/l) • Isotonic saline (se na > 125 mmol/l) • Increase rate of se Na level should be less than 2 mmol/h (cave: Central pontin myelinolysis)

Hypernatraemia • Se Na > 145 mmol/l • Causes: inadequate water intake and increased free water loss; intake of hypertonic sodium solution • Symptoms: • Increased thirst • Central nervous system abnormalities (confusion, weakness, lethargy, seizures, coma) • Therapy: water repletion, correction rate of Na level should be no greater than 2 mmol/h (cave: cerebral oedema)

ADH • SIADH (syndrome of inappropriate ADH secretion) • Ectopic production • Brain diseases • Lung diseases • Therapy: decrease of water intake • Diabetes insipidus • Decreased ADH secretion (central), decreased ADH effect in the kidneys (renal) • Therapy: ADH (central), hydrochlorothiazide, indomethacine (renal)

Potassium • Most abundant cation of ICF, helps maintain ICF volume • Key role in the resting membrane potential and action potential of neurons and muscle fibers • K+ level is controlled by aldosterone • Hydrogen-potassium exchange in cell membrane • Minimal potassium intake: 1 mmol/kg

Hyperkalaemia • Se K > 5 mmmol/l • Causes • Impaired excretion • Renal failure, mineralocorticoid deficiency, pseudohypoaldosteronism, drugs (potassium sparing diuretics, ACE-inhibitors NSAID, cyclosporin) • Shifts of K out of cells • Tissue breakdown, acidosis, insulin deficiency

Hyperkalaemia • Symptoms: • Cardiac (peaked T waves, loss of P waves, heart blocks, ventricular arrhytmias, widening of QRS complexes, asystole) • Paresthesias, weakness, paralysis • Acidosis • Therapy • Direct antagonism of hyperkalemic effect on cell membrane polarization • Calcium gluconate • Movement of extracellular K into intracellular compartment • Insulin (+glucose) • Sodium bicarbonate • β 2 -adrenergic agonists

Hyperkalaemia • Therapy • Removal K from the body • Loop diuretics • Sodium polystyrene sulfonate • Dialysis

Hypokalaemia • Se K < 3, 5 mmmol/l • Causes: • Increased excretion: diarrhoea, renal losses, mineralocorticoid excess, magnesium depletion • Shifts of K into cells: drugs (insulin, β 2 -adrenergic agonists, theophylline, caffeine), alkalosis, hyperthyreoidism • Symptoms: • Cardiac: flat t waves, ST depression, U wave, QT interval prolongation, arrhytmias • Muscle paralysis, rhabdomyolysis • Coma • Metabolic alkalosis

Hypokalaemia • Therapy • Supplementation of K • (Knormal-Kmeasured) * ttkg * 0. 2 + daily need • Infusion rate: no more, than 20 (30) mmol/h • Oral supplementation • 1 gr potassium-chloride containes 13, 4 potassium, 1 gr potassium-citrate containes 9, 2 mmol/l potassium

Acid-base disorders

Acid-base balance • H 2 O H+ + OH- (steady state: p. H 7 (6, 8)) • A Henderson-Hasselbach Equation p. H = - log [H+]= p. K+log [anion/undissociated acid] • Extracellular space: 7. 38 p. H 7. 42 • Intracellular space: p. H ~ 6. 8 • Source of H+: intake, metabolism (50 mmol/d), CO 2: 12500 , mmol/d) • Elimination of H+: kidney, lung (CO 2), gastrointestinal tract, liver

Analysis of acid-base balance • Respiratory • Metabolic • Buffer system (HCO 3 -, BE) • Strong ion difference (Na+, K+, Cl-, lactate-) – Stewart method

Buffers • A buffer is a substance, that has the ability to bind or release H+ in solution, thus keeping the p. H of the solution relatevily constant despite of considerable quantities of acid or base • The important buffer systems in blood include proteins, carbonic acid-bicarbonate buffers and phosphates. Buffer p. K Concentration Buffer capacity Bicarbonate 6, 1 24 mmol/l 75 % Hgb 8, 25 oxy. Hgb 6, 95 24 mmol/l 25 % Proteins - Phosphates 6, 8

Buffers • Carbonic acid – bicarbonate system: • H 2 CO 3 H+ + HCO 3 - H 2 O + CO 2 • A Henderson-Hasselbach Equation p. H = - log [H+]= p. K+log [anion/undissociated acid] • p. H= 6. 1 + log[HCO 3/0. 03 x. Pa. CO 2 (amount of carbonic acid)] • Plasma proteins • Dissociation of their carboxyl or free amino groups • Hemoglobin • Dissociation of imidazole groups • Phosphates : low plasma concentration

Acid-base disorders • Acidosis: p. H<7. 35 • Alkalosis: p. H>7. 45 • Metabolic disturbance: addition of acid or alkali (stronger, than the buffers) or removal of acid or alkali • Respiratory disturbance: rise or decline in arterial p. CO 2 • Compensation: • Kidneys • Lung

BGA p. H arterial 7. 37 -7. 45 mixed venous 7. 35 -7, 43 p. CO 2 Hgmm(k. Pa) 35 -46(4, 6 -6, 1) 37 -50 (4, 9 -6, 6) actual/standard 21 -26/21 -26 bicarbonate (mmol/l) 21 -26/21 -26 BE (mmol/l) -2, 5 - +2, 5 Anion gap (mmol/l) 10 -14 (Siggaard-Andersen Curve Nomogram) 10 -14

Metabolic acid-base disorders • Dysfunction of the primary regulating organs • Renal failure • Exogenous administration of drugs or fluids that alter the body’s ability to maintain normal acid-base balance • Methanol, ethylene glycol, salicylates • Abnormal metabolism that overwhelms the normal defense mechanisms • Ketoacidosis (diabetic, alcoholic, starvation, metabolic error) • Lactic acidosis

Practical classification of metabolic acid-base disorders • Iatrogenic • Fixed • Symptom of an ongoing acute illness • Only metabolic acidosis has real clinical importance

Metabolic acidosis p. H<7. 35, HCO 3<20 mmol/l, BE<-3 mmol/l Anion gap (Na++K+) - (Cl-+HCO 3 -) normal range: 10 -15 mmol/l • Elevated anion gap: lactic acidosis, ketoacidosis, renal failure, exogenous administration of acids • Non-anion gap acidosis: renal tubular acidosis, gastrointestinal acidosis, Iatrogenic acidosis (administration of Cl, dilutional acidosis)

Metabolic acidosis • Symptoms: • Increased sympathetic activity • Decreased inotropy, arterial vasodilatation – critical p. H (7, 2) • Decreased oxy-Hgb binding • Hyperkalaemia • Insulin resistance • Free radical formation • Bone demineralization • Emesis • Decreased sensorium • Hyperventilation

Metabolic acidosis • Therapy of underlying disease • Maximizing respiratory compensation • Na. HCO 3 mmol = -BE* 0, 3 * kg • Maximal rate of infusion: 1. 5 mmol/kg/h • Adverse effects: hypernatraemia, increased CO 2 production, intracellular acidosis • Tromethamin (Tris-buffer, Tham) • Penetrates cells • Maximal daily dose: 5 mmol/kg • Adverse effect: hypoglycaemia, respiratory depression, fatal hepatic necrosis

Metabolic alkalosis p. H>7. 45, HCO 3>26 mmol/l, BE>3 mmol/l Causes: • Chloride responsive • Vomiting, gastric drainage • Chloride wasting diarrhea (villous adenoma) • Diuretics • Post-hyperpnoe • Chloride-unresponsive • Mineralocorticoid excess • Cushing’s syndrome • Bartter’s syndrome • Hypokalaemia • Sodium salt administration (acetate, citrate) • Massive blood transfusion • Sodium-lactate (Ringer’s solution) • Parenteral nutrition

Metabolic alkalosis • Symptoms • • Hypoventilation, repiratory depression Neuromuscular excitability Hypokalaemia Seizures Increased oxy-Hgb affinity Altered coronary blood flow, vasoconstriction Decreased cerebral blood flow

Metabolic alkalosis Therapy • Therapy of underlying disease • Chloride responsive alkalosis: Na. Cl • Chloride-unresponsive alkalosis: HCl, KCl • Mineralocorticoid excess: Spironolactone

Respiratory alkalosis p. H>7. 45, p. CO 2<35 Hgmm • Causes: • Hypoxic respiratory failure • Salicylate intoxication • Early sepsis • Hepatic failure • Arteficial hyperventilation • Symptomes • Decreased cerebral or coronary blood flow • Neuromuscular excitability • Therapy: • Therapy of underlying disease • Increasing the dead space

Respiratory acidosis p. H<7. 35, p. CO 2>45 Hgmm • Cause: • Respiratory failure • Symptoms: • Symptoms of metabolic acidosis + coma • Therapy: • Therapy of underlying disease • Mechanical ventilation