1. DR.KHIN MAR AYE BIOCHEMISTRY UNIT HOD FOM

2. Objective To discuss the regulation of water and sodium. Internal and external balance of potassium Renal excretion of potassium. Hypo and Hyperkalemia

3. Body Water Content Total water content declines throughout life Healthy males are about 60% water; healthy females are around 50% This difference reflects females’: Higher body fat Smaller amount of skeletal muscle In old age, only about 45% of body weight is water Infants have low body fat, low bone mass, and are 73% or more water

4. Fluid Compartments Water occupies two main fluid compartments Intracellular fluid (ICF) – about two thirds by volume, contained in cells Extracellular fluid (ECF) – about one third, consists of two major subdivisions Plasma (IVF) Interstitial fluid (ISF) Other ECF – lymph, cerebrospinal fluid, eye humors, synovial fluid, serous fluid, and gastrointestinal secretions

6. Composition of Body Fluid Water is the universal solvent Solutes are broadly classified into: Electrolytes – Cations -sodium, potassium, hydrogen, magnesium, and calcium Anions: chloride, bicarbonate, phosphate, and sulfate Nonelectrolytes – glucose, lipids, creatinine, and urea Electrolytes have greater osmotic power than nonelectrolytes Water moves according to osmotic gradients

7. ECF & ICF 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

8. Water Balance

9. 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 (28%), sweat (8%) Increases in plasma osmolality trigger thirst and release of antidiuretic hormone (ADH)

10. Regulation of Water Intake The hypothalamic thirst center is stimulated by: Decreases in plasma volume of 10% Increases in plasma osmolality of 1-2% Thirst is quenched as soon as we begin to drink water Feedback signals that inhibit the thirst centers include: Damping of mucosa of the mouth Moistening of the throat Activation of stomach and intestinal stretch receptors

12. Regulation of Water output Obligatory water losses include: Insensible water losses from lungs and skin Water that accompanies undigested food residues in feces Obligatory water loss reflects the facts that: Kidneys excrete 900-1200 mOsm of solutes to maintain blood homeostasis Urine solutes must be flushed out of the body in water

13. Disorders of Water Balance: 1. Dehydration Water loss exceeds water intake and the body is in negative fluid balance Causes : 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

15. 2. Hypotonic hydration (Water intoxication) Causes: Renal insufficiency or an extraordinary amount of water ingested quickly can lead to cellular overhydration, or water intoxication, excessive Intravenous fluid 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

17. Regulation of Sodium Normal blood sodium level = 135 – 147 mEq/L Sodium reabsorption 65% of sodium in filtrate is reabsorbed in the proximal tubules 25% is reclaimed 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

18. 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

19. Regulation of Sodium by Aldosterone 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

20. Disorders of Sodium Balance Hyponatremia Hyponatremia represents a decrease in plasma sodium concentration below 135 mmol/L. Hypernatremia Hypernatremia implies a plasma sodium level above 145 mmol/L.

21. Hyponatremia Causes Excessive sodium losses and replacement with sodium-free water Excessive water intake in relation to output

22. Excessive sodium losses and replacement with sodium-free water Exercise- or heat-induced sweating Gastrointestinal losses Renal losses (some chronic renal diseases)

23. Excessive Water Intake in Relation to Output Excessive administration of sodium-free solutions Repeated irrigation of body cavities with sodium- free solutions Irrigation of gastrointestinal tube with distilled water Kidney disorders that impair water elimination Increased ADH level

24. Clinical Features of Hyponatremia Muscle cramps, Weakness, Headache, Depression, Personality changes, Lethargy and coma (due to Hypoosmolarity and movement of water into brain cells) GI symptoms : Anorexia, nausea, vomiting, Abdominal cramps, diarrhea

25. Hypernatremia Causes Excessive Water Losses – watery Diarrhoea, excessive sweating, hyperventilation, excess ADH Decreased Water Intake- inability to swallow, Unconsciousness, impaired thirst sensation Excessive Sodium Intake

26. Clinical features of Hypernatremia Oliguria or anuria Dry skin and mucous membranes Tongue rough and fissured Decreased salivation Headache, agitation and restlessness, Seizure and coma

27. Potassium  Potassium is the chief intracellular cation  Relative intracellular-extracellular potassium concentrations directly affects a cell's resting membrane potential, therefore a slight change on either side of the membrane has profound effects (ie. on neurons and muscle fibers)  Potassium is part of the body's buffer system, which resists changes in pH of body fluids; ECF potassium levels rise with acidosis as potassium leave cells and fall with alkalosis as potassium moves into cells

28. Regulation of K + Normal serum K + level = 3.5 – 5.2 mEq/L External K + balance is mainly controlled by kidney and to less extent by GIT 99% of filtered potassium is reabsorbed in the proximal tubules Obligatory losses is 10-20mmol/day

29. Factors effecting K + excretion Amount of Na + available for absorption The relative availability of H + and K + ions in the distal tubules Aldosterone directly or indirectly stimulates K + excretion

30. Internal Distribution Factors effecting K + shifting from ICF to ECF - Insulin deficiency - acidosis - Hyperosmolality - Cell death Factors effecting K + movement into cells: - After insulin therapy - Alkalosis

31. Hypokalemia Serum K + < 3.5 mmol/L Causes Decreased K + intake (rare) Tran-cellular K + shift - Alkalosis - Insulin therapy

32. Renal Osmotic diuresis Diuretics (Thiazide) Mineralocorticoid excess GIT - Diarrhoea - Vomiting (K + loss, alkalosis)

33. Hyperkalemia Serum K + ≥ 6.5 mmol/L Need urgent treatment. Causes: 1. Hemolysis 2. Trans- cellular K + movement - Tissue damage - systemic acidosis - insulin deficiency

34. 3. Decreased K + excretion - Acute renal failure - Chronic renal failure (late) - Potassium sparing diuretics 4. Addison’s disease

35. Clinical features of Hyperkalemia The symptoms of hypokalemia and hyperkalemia are similar Muscle weakness Paralysis Change in ECG pattern

36. Complications Since potassium controls electrical conduction in the heart, hypokalemia or hyperkalemia can result in arrhythmias, or skipped heart beats. In severe cases, the heart may become unable to adequately pump blood or go into cardiac arrest.

37. Learning outcome Explain regulation of water and sodium. List the disorders of water balance. Explain imbalances of sodium. Compare internal and external balance of potassium Discuss the renal excretion of potassium Discuss the clinical manifestation and complications of hypokalemia and hyperkalemia.

38. References Lippincott’s Illustrated Review Color Atlas of Biochemistry Basic Medical Biochemistry Acid- Base Balance from -Internet Body Fluid & Electrolytes - Internet