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  2. 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): 2x(Na)+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
  3. Intracellular space Extracellular space Interstitial space Intravascular space Capillary wall Oncotic pressure Colloids Electrolytes Water Cell membrane Osmotic pressure
  4. Body Fluid Volumes Compartment Fluid Vol. (l) % Body Fluid % Body Wgt. Total Body Fluid 42 100 60 Intracellular Fluid (ICF) 28 67 40 Extracellular Fluid (ECF) 14 33 20 Plasma 2.8 6.6 (20% ECF) 4 Interstitial Fluid 11.2 26.4 (80% ECF) 16 Lymph & Transcellular Fluid Neg. Neg. Neg.
  5. Daily Water Balance (liters) • FLUID INTAKE 1.5 • IN FOOD 0,8 • METABOLIC 0.3 • Total 2,6 • INSENSIBLE 0.8 • SWEAT 0,1 • FECES 0.2 • URINE 1.5 • Total 2.6 INPUT OUTPUT
  6. Introduction • The maintenance of normal volume and normal composition of the extracellular fluid is vital to life. • Three types of homeostasis are involved in this maintenance:fluid balance, electrolyte balance, and acid-base balance. • The ICF contains nearly2/3rd of total body water;the ECF contains the rest. • Exchange occurs between the ICF and ECF.
  7. Distribution of Body Fluids • Water is the most abundant constituent in the body • 50% of weight in women; • 60% of weight in men • Difference due to adipose tissue composition • Total Body Water divided into 2 compartments • Extracellular : 25 – 45% • Intravascular – plasma water (25%) • Extravascular – interstitial fluid(75%) • Intracellular : 55 – 75%
  8. Distribution of Body Fluids • Movement of fluids between Extracellular and Intracellular • Determined by Osmolality (solute or particle concentration of a fluid) • Fluids cross cell membranes to achieve osmotic equilibrium (ECF osmolality = ICF osmolality). • Major ECF solutes – Sodium, Chloride, Bicarbonate • Major ICF solutes – Potassium, Organic Phosphates (ATP, creatine phosphate, phospholipids)
  9. Distribution of Body Fluids Movement of fluids between Intravascular and Interstitial Starling’s Forces • Capillary hydraulic pressure – from blood pressure • Colloid osmotic pressure – oncotic pressure (proteins)
  10. Water Balance • For steady state, water intake must equal water excretion • Water intake • Primary Stimulus is thirst • Thirst is induced either by an increase in effective osmolality or a decrease in ECF volume or blood pressure. • Osmoreceptors located in the anterolateral hypothalamus, are stimulated by a rise in tonicity.
  11. Water Balance • Water Excretion • Normal individuals have an obligate water loss consisting of urine, stool, and evaporation from the skin and respiratory tract. • principal regulation of water excretion is by arginine vasopressin (AVP) synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and secreted by the posterior pituitary gland.
  12. Water Balance • AVP binds to the V2 receptors on the basolateral membrane of principal cells in the collecting duct leads to the insertion of water channels into the luminal membrane. • The net effect is passive water reabsorption along an osmotic gradient from the lumen of the collecting duct to the hypertonic medullary interstitium.
  13. Water Balance • The major stimulus for AVP secretion is increased osmolality • Effective osmolality is primarily determined by the plasma Na concentration because major ECF solutes are Na salts • Nonosmotic factors that regulate AVP secretion include effective circulating (arterial) volume, nausea, pain, stress, hypoglycemia, pregnancy, and numerous drugs.
  14. 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%
  15. • Water output • Urine (60%) and feces (4%) • Insensible losses (28%), sweat (8%) • Increases in plasma osmolality trigger thirst and release of antidiuretic hormone (ADH)
  16. Regulation of Water - Homeostaisis • Intake - Hypothalmic Thirst Center • Thirst is quenched as soon as we begin to drink water • Feedback signals that inhibit the thirst centers include: • Moistening of the mucosa of the mouth and throat • Activation of stomach and intestinal stretch receptors
  17. Influence and Regulation ofADH • 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 • 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 traumatic burns
  18. Fluid Balance • Angiotensin II and aldosterone reduce urinary loss of Na+ and Cl- and thereby increase the volume of body fluids. • 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.
  19. • 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 fn. is poor-water intoxication,cells swell
  20. Disorders of Water Balance • Dehydration • Hypotonic Hydration • Edema
  21. Sodium Balance • 85 to 90% of all Sodium is extracellular, actively pumped out of the cell by the Na–K ATPase pump • ECF volume is a reflection of total body Sodium content • Regulatory mechanisms ensure that Sodium loss balances Sodium gain. • Excess Na in diet  ECF expansion  increased renal excretion
  22. Sodium Balance • Filtered Sodium • About 60% is reabsorbed in PCT • 25 to 30% in the thick ascending limb of the loop of Henle (Loop diuretics) • 5% in the DCT (thiazide-sensitive) • Final Na reabsorption in the cortical and medullary collecting duct (Aldosterone)
  23. Disorders of Water and Sodium Balance HYPOVOLEMIA – combined salt and water loss exceeding intake leading to ECF volume contraction Causes Extrarenal – •Gastrointestinal (vomiting, nasogastric suction, drainage, fistula, diarrhea). • About 9L of fluids enter GIT/24hrs (2L ingestion, 7L secretion). Almost 98% is reabsorbed, faecal loss is 100 – 200ml/day. •Enhanced secretion or impaired reabsorption
  24. Disorders of Water and Sodium Balance Causes •Skin/respiratory (insensible losses, sweat, burns) •Insensible water loss typically about 1500ml/24hr •Increased during febrile illness, prolonged heat exposure, •Increased water /salt loss through sweat •Hyperventilation, mechanically ventilated persons, neonates
  25. Disorders of Water and Sodium Balance • Third space loss (burns, peritonitis, pancreatitis) “ECF”, not in equilibrium with ECF or ICF, effectively lost burns – subcutaneous tissue retroperitoneal space in acute pancreatitis peritoneal cavity in acute peritonitis •Severe Hemorrhage
  26. DISORDER OF NA BALANCE • Disorders of Na+ homeostasis can occur because of excessive loss, gain, or retention of Na+, or as the result of excessive loss, gain, or retention of H2O. It is difficult to separate disorders of Na+ and H2O balance because of their close relationship in establishing normal osmolality in all body water compartments. • In the proximal tubules, 70 to 80% of filtered Na+ is actively reabsorbed, with H2O and Cl− following passively to maintain electrical neutrality and osmotic equivalence. • In the descending loop of Henle, H2O, but not electrolytes, is passively reabsorbed because of the high osmotic strength of interstitial fluid in the renal medulla. In the ascending loop of Henle, Cl− is reabsorbed actively, with Na+ following. • At the level of the distal tubule, the first of the two primary Na+/H2O regulating processes occurs. Here, aldosterone stimulates the cortical collecting ducts to reabsorb Na+ (with water following passively) and secrete K+ (and to a lesser extent, H+) to maintain electrical neutrality.
  27. • Hyponatremia • Hyponatremia is defined as a decreased plasma Na+ concentration • (<130 to 135 mmol/L). • Hyponatremia typically manifests clinically as nausea, generalized weakness, and mental confusion at values <120 mmol/L, ocular palsy at <110 mmol/L, and severe mental impairment at between 90 and 105 mmol/L • The rapidity of development of hyponatremia influences the Na+ concentrations at which symptoms develop [i.e., clinically apparent symptoms may manifest at higher Na+ concentrations (≈125 mmol/L) when hyponatremia develops rapidly]
  28. • Hyponatremia can be hypo-osmotic, hyperosmotic, or • isosmotic. Thus, measurement of plasma osmolality is an • important initial step in the assessment of hyponatremia. Of • these, the most common form is hypo-osmotic hyponatremia.
  29. Hypernatremia • Hypernatremia (plasma Na+ >150 mmol/L) is always hyperosmolar. • Symptoms of hypernatremia are primarily neurologic (because of neuronal cell loss of H2O to the ECF) and include tremors, irritability, ataxia, confusion, and coma. • As with hyponatremia, the rapidity of development of hypernatremia will determine the plasma Na+ concentration at which symptoms occur. • Acute development may cause symptoms at 160 mmol/L, although in chronic hypernatremia, symptoms may not occur until Na+ exceeds 175 mmol/L
  30. • In many cases, the symptoms of hypernatremia may be masked by underlying conditions. Indeed, most cases of hypernatremia occur in patients with altered mental status or in infants, both of whom may have difficulty in rehydrating themselves despite a normal thirst reflex. • Thus, hypernatremia rarely occurs in an alert patient with a normal thirst response and access to water. • Hypernatremia arises in the setting of • (1) hypovolemia (excessive water loss or failure to replace normal water losses), • (2) hypervolemia (a net Na+ gain in excess of water gain), • (3) normovolemia. • Again, assessment of TBW status by physical examination and measurement of urine Na+ and osmolality are important steps in establishing a diagnosis
  31. POTASSIUM DISORDERS • The total body potassium of a 70 kg subject is ≈3.5 mol (40 to 59 mmol/kg), of which only 1.5 to 2% is present in the ECF. • Nevertheless, plasma K+ is often a good indicator of total K+ stores, unless abnormal K+ is due to abnormal cellular shifts. • Disturbance of K+ homeostasis has serious consequences. For example, a decrease in extracellular K+ (hypokalemia) is characterized by muscle weakness, irritability, and paralysis. • Plasma K+ concentrations less than 3.0 mmol/L are often associated with marked neuromuscular symptoms and indicate a critical degree of intracellular depletion. • At lower concentrations, tachycardia and cardiac conduction defects are apparent by electrocardiogram (flattened T waves) and can lead to cardiac arrest
  32. POTASSIUM DISORDERS • High extracellular K+ (hyperkalemia) concentrations may produce symptoms of mental confusion, weakness, tingling, flaccid paralysis of the extremities, and weakness of therespiratory muscles. • Cardiac effects of hyperkalemia include bradycardia and conduction defects evident on the electrocardiogram as prolonged PR and QRS intervals and “peaked” T waves. • Prolonged severe hyperkalemia >7.0 mmol/L can lead to peripheral vascular collapse and cardiac arrest. • Symptoms are almost always present at K+ concentrations >6.5 mmol/L. Concentrations >10.0 mmol/L in most cases are fatal, but as with Na+, symptoms vary with the rapidity of onset.
  35. SIADH • The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is defined by the hyponatremia and hypo-osmolality resulting from inappropriate, continued secretion or action of the antidiuretic hormone arginine vasopressin (AVP) despite normal or increased plasma volume, which results in impaired water excretion. • Etiology • SIADH is most often caused by either inappropriate hypersecretion of ADH from its normal hypothalamic source or by ectopic production. The causes of SIADH can be divided into four broad categories: • nervous system disorders, neoplasia, pulmonary diseases, and drug induced (which include those that [1] stimulate AVP release, [2] potentiate effects of AVP action, or [3] have an uncertain mechanism).
  36. SIADH Causes • SIADH may be due to: • 1. Intracranial pathology (head injury, haemorrhage, meningitis, encephalitis, or brain tumor), where there is direct stimulation of hypothalamic ADH release. • 2. Pulmonary pathology (pneumonia, TB, assisted ventilation), where volume receptors in the pulmonary vascular bed falsely report a message of vascular depletion to the hypothalamus. • 3. Ectopic production of ADH by tumors, particularly bronchial carcinomas. • 4. Cortisol deficiency – since these hormones antagonize ADH, a deficiency of either will result in unopposed ADH action. • 5. Pain, from trauma or surgery, stimulates ADH release. • 6. Drugs, including psychoactive drugs (antidepressants, narcotics, carbamazepine), sulphonylureas, oxytocin for labour induction, vincristine for chemotherapy
  37. • In the absence of a single laboratory test to confirm the diagnosis, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is best defined by the classic criteria introduced by Bartter and Schwartz in 1967, which remain valid today. The criteria can be summarized as follows [2] : • Hyponatremia with corresponding hypoosmolality • Continued renal excretion of Na+ • Urine less than maximally dilute • Absence of clinical evidence of volume depletion - Normal skin turgor, blood pressure within the reference range • Absence of other causes of hyponatremia - Adrenal insufficiency (mineralocorticoid deficiency, glucocorticoid deficiency), hypothyroidism, cardiac failure, pituitary insufficiency, renal disease with salt wastage, hepatic disease, drugs that impair renal water excretion • Correction of hyponatremia by fluid restriction
  38. • Serum Na+, potassium, chloride, and bicarbonate • Plasma osmolality • Serum creatinine • Blood urea nitrogen • Blood glucose • Urine osmolality • Serum uric acid • Serum cortisol • Thyroid-stimulating hormone • Plasma AVP
  39. DIABETES INSIPIDUS • Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg). It has the following 2 major forms: • Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized by decreased secretion of antidiuretic hormone (ADH; also referred to as arginine vasopressin [AVP]) • Nephrogenic DI, characterized by decreased ability to concentrate urine because of resistance to ADH action in the kidney
  40. • Decreased secretion or action of AVP usually manifests as DI, a syndrome characterized by the production of abnormally large volumes of dilute urine. • The 24-h urine volume is >50 mL/kg body weight and the osmolarity is <300 mosmol/L. The polyuria produces symptoms of urinary frequency, enuresis, and/or nocturia, which may disturb sleep and cause mild daytime fatigue or somnolence. • It is also associated with thirst and a commensurate increase in fluid intake (polydipsia). Clinical signs of dehydration are uncommon unless fluid intake is impaired
  41. • Pituitary diabetes insipidus • Acquired • Head trauma (closed and penetrating) • Neoplasms • Primary • Craniopharyngioma • Pituitary adenoma (suprasellar • Nephrogenic diabetes insipidus • Acquired • Drugs • Lithium • Demeclocycline • Methoxyflurane • Amphotericin B • Aminoglycosides
  42. • In a patient whose clinical presentation suggests diabetes insipidus (DI), laboratory tests must be performed to confirm the diagnosis. A 24-hour urine collection for determination of urine volume is required. In addition, the clinician should measure the following: • Serum electrolytes and glucose • Urinary specific gravity • Simultaneous plasma and urinary osmolality • Plasma antidiuretic hormone (ADH) level
  43. • A urinary specific gravity of 1.005 or less and a urinary osmolality of less than 200 mOsm/kg are the hallmark of DI. Random plasma osmolality generally is greater than 287 mOsm/kg. • Suspect primary polydipsia when large volumes of very dilute urine occur with plasma osmolality in the low-normal range. Polyuria and elevated plasma osmolality despite a relatively high basal level of ADH