Changes of electrolyte / water and acid / base homeostasis

1. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

2. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011 Erika Pétervári and Miklós Székely Molecular and Clinical Basics of Gerontology – Lecture 12 Changes of electrolyte/water and acid/basehomeostasis

3. AGING vs. … • Electrolyte/water homeostasis • pH disturbances

4. Salt and water balance in the elderly1 • In the elderly the spontaneous water intake decreases. Their regulation is insufficient e.g. their thirst sensation is impaired. Following water deprivation fluid replacement is slower and incomplete.(In old animals the angiotensin II-induced water intake is smaller than that seen in young animals. Dypsogenic effects of ADH is weakened.)

5. Salt and water balance in the elderly 2 • Upon water deprivation or salt and water loss, severe hypovolemia and hypertonicity develops (ADH refractoriness). This can also contribute to the development of orthostatic hypotension in the elderly. • Salt/water loss, diuretic therapy, inappropriate excess of ADH (e.g. operation, pain), water intake (exceeding the decreased excretion capacity) causes dangerous hypotonicity. • On the other hand, upon salt and/or water load (due to decreased excretion capacity) a fast elevation of the blood pressure can also be observed.

6. ADH effect decreases with age 120 Young Middle 110 Old 100 90 80 70 U/P inulin(urine/plasma conc. ratio) 60 50 40 30 ADH 20 10 0 0 1 2 3 4 5 6 7 8 9 10 Urine Collection Period

7. Salt and water balance in the elderly: kidney • The number of the nephrons decreases progressively with age. • GFR also decreases progressively (the glomeruli become more and more sclerotic,the basal membrane gets thicker [degeneration]), by the age of 80 GFR may decrease to 50%– this results in azotemia. • The decrease in the number of tubules (decrease in the function of the thick ascending limb of the loop of Henle where the reabsorption of Na-K-Cl without water takes place and impairment of the corticomedullary osmotic concentration gradient), – it leads to hyposthenuria. In response to ADH the increase in the specific gravity of the urine is diminished.

8. Development of hyposthenuria 1,040 Hyposthenuria Isosthenuria 1,030 1,020 Specific gravity of urine Specific gravity of plasma 1,010 1,000 2,000,000 1,500,000 1,000,000 500,000 0 Number of nephrons

9. Salt and water balance in the elderly: hormones • Responsiveness to hormones playing a role in salt and water balance impairement. • The same decrease in plasma volume elicits a smaller RAAS activation than in young individuals.The effects of aldosterone or angiotensin are diminished compared to that in young adults, too.Low EC volume induces ADH production that may lead to hypotonicity without completely normalizing the ECV.ADH production may be maintained or even increased (buttheefficacydecreases).

10. Salt and water balance in the elderly: hormones • Elderly patients cannot properly protect themselves against water overload either.Suppression of baseline RAAS activity is delayed; activation of natriuretic factors is inefficient (atriopeptin level is high, but effects are blunted), suppression of renal ADH effects is also unsatisfactory due to decreased nephron numbers and dysfunctional receptors.

11. Exsiccosis and dehydration: decrease of extracellular volume (ECV) • Exsiccosis: decreases of ECV due to salt/water, decrease of both plasma volume (hypovolemia) and interstitial volume. • Dehydration: loss of pure water (not followed by proportional loss of electrolytes), followed by proportionate decrease of volume and increase of osmotic pressure (hyperosmolarity) in both extracellular and intracellular compartments. 300 300 IC IC 200 200 EC EC Osmolarity (mOsm/liter) Osmolarity (mOsm/liter) 100 100 0 0 10 10 30 30 0 0 20 20 40 40 liter liter

12. Exsiccosis and dehydration in the elderly: causes • Decrease in thirst and kidney functions + • low fluid intake (immobilization, changed mental status), • diarrhea, • overdose of diuretics, • acutefever, • diabetes mellitus.

13. Exsiccosis and dehydration in the elderly: clinical signs • Symptoms: • lethargy, • dizziness, • fainting, • signs of volume depletion such as decreased skin turgor, • dryness of the mucous membranes, • low blood pressure, • tachycardia, • oliguria-anuria. • Lab findings: • increase in blood urea nitrogen (BUN), creatinine

14. Exsiccosis and dehydration in the elderly: management • Rehydration, either p.o. or i.v. depending on the severity. • The first half of the fluid should be administered in 12 hours, while the second half must be given at a slower rate to maintain adequate blood pressure and circulation. • Too fast fluid replacement may result in acute heart failure and pulmonary edema.

15. Hyponatremia (hypotonicity) • Common causes: • Reduced Na concentration while the water volume is normal or increased („water-intoxication”): • low-sodium diet • intravenous rehydration with hypotonic fluid • syndrome of inappropriate ADH secretion (SIADH) due to operation, stress, fear, pain, stroke, local inflammation, adenoma, tumors, increased intracranial pressure etc. • Na loss > water loss: • vomiting • diarrhea • overdose of diuretics

16. Signs and management of hyponatremia • Symptoms depend on the rate and severity of Na loss. • Characteristic signs appear at 120 mM/L or lower: • edema, • delirium, • cerebral edema, nausea, • convulsions, muscle cramps, • Cheyne-Stokes respiration • all-cause mortality (6-8×) . • Management: • 0.9 % saline solution is given to hypovolemic patients. • In SIADH: restriction of fluid intake. • Administration of hypertonic saline solution can lead to central pontinemyelinolysis and therefore, its use is not allowed.

17. Hypernatremia (hypertonicity) • Na concentration >150 mM/L • It means usually either relative or absolute water loss and hypovolemia. • Hypertonicity is significant. • Common causes: • restricted fluid intake • exsiccosis (e.g. diabetic osmotic diuresis, sweating)

18. Signs and management of hypernatremia • Symptoms: • coma, • seizures, • intracellular dehydration, • hypovolemia, • renal failure, • decreased capacity of kidneys to concentrate urine. • Management: • normal saline solution (0.9%) • slow infusion! (fast infusion may cause hypertensive crisis)

19. Potassium disorders: hypokalemia • Hypokalemia: K<3.5 mM/L • Common causes: • insufficient intake, • increased loss due to diuresis, • vomiting, • primary or secondary hyperaldosteronism. • Signs: • muscle weakness,musclecramps • paralytic ileus, • metabolicalkalosis • sleepiness, changesinthemental status, • extrasystole, tachycardia,ventricular fibrillation, • ECG: ST depression, T wave flattening, U waves, prolonged QT. • Treatment: potassium repletion (oral).

20. Potassium disorders: hyperkalemia • Hyperkalemia: K>5.5 mM/L • Common causes: • overdose on drugs containing potassium, • renal failure, • cell lysis, • use of potassium sparing diuretics in renal failure, • side-effect of NSAIDs • hypoaldosteronism. • Signs: • fatigue, muscle weakness, • paresthesias in the lower limbs, • metabolicacidosis, • changesinthemental status, • bradycardia, sinoatrial, atrioventricular, ventricular blocks, • ECG: flattened P waves, ST depression, wide QRS, tall, peaked T waves, short QT

21. Management of hyperkalemia • forced diuresis with 40-60 mg of furosemide, • 0.9% NaCl solution, • treat the underlying acidosis, • cation-exchange resin p.o., • in case of abnormal ECG findings 10-20 ml of CaCl2 should be given in about 10 minutes, • Na-bicarbonate and/or 40% glucose + short-acting insulin can be administered, • dialysis is appropriate for severe, refractory cases.

22. AGING vs. … • Electrolyte/water homeostasis  • pH disturbances: • The normal pH value does not change with age, but aging-associated alterations in its regulation may contribute to development of disturbances in acid-base homeostasis.

23. Metabolic alkalosis in the elderly • Common causes: • vomiting • repeated removal of gastric fluid • secondary hyperaldosteronism (e.g. chronic congestive heart failure with edemas) • diuretics-induced hypokalemia and secondary hyperaldosteronism (aggravating already existing secondary hyperaldosteronism of patients with heart failure) • hypokalemia promotes: • cellular H+ / K+ exchange (internal K+-balance) • bicarbonate reabsorption in the proximal tubules • Na+ /H+ exchange in the distal tubules (external K+-balance) •  Hypokalemia and alkalosis are involved in a vicious circle.

24. Metabolic acidosis in the elderly • Common causes: • diabetic ketoacidosis • lactic acidosis • decreased erythropoietin production - anaemia • salicylate-toxicosis(NSAID) • diarrhea • renal failure • renal tubular acidosis (e.g. diabetic nephropathy) • Compensation: generally weak in the elderly • Compensation by hyperventilation is weaker, while: • sensitivity of the central and peripheral respiratory regulation (for CO2, H+and hypoxia) is decreased. • The aging kidney shows an impaired reaction to acidosis, therefore, it takes longer to normalize pH.

25. Respiratory alkalosis in the elderly • Common causes: • hypoxia • sepsis • pulmonary embolism • heart failure (enhanced sympathetic tone) • liver failure (NH3 accumulation) • mild salicylate-toxicosis (regular use of NSAIDs for pain) • frequent situations with anxiety

26. Respiratory acidosis in the elderly • Common causes: • the central and peripheral respiratory regulation is less sensitive to hypercapniaand hypoxia (by the age of 70 sensitivity to hypoxia decreases by 50%, to hypercapniaby 40-50%; arterial pO2 decreases 0.3% per year) • medications decreasing the sensitivity of the respiratory center (e.g. opiates) • decreased vital capacity (VC) and FEV1 • decreased chest wall compliance (kyphoscoliosis, obesity) • neuromuscular diseases can worsen the function of the respiratory muscles • decreased respiratory surface (severe emphysema) • chronic bronchitis is more frequent (mucociliary clearance , longer exposition time to environmental pollutants, smoking)

27. Compensation of the respiratory pH-disorders in the elderly • Compensatory capacity of both the kidneys and the lungs is narrowed. • In respiratory acidosis, oxygen therapy may be needed. • Its danger: due to decreased CO2-sensitivity hypoxia regulates ventilation – oxygen therapy may result in hypoventilation and CO2 coma! • Assisted ventilation may be necessary.

28. Mixed acid-base disturbances • In the elderly mixed acid-base disturbances are very common. • In acute respiratory insufficiency (pneumonia) combined with heart failure respiratory acidosis is mixed with metabolic acidosis. • In serious heart failure: decreased tissue perfusion leads to lactate (metabolic) acidosis, but diuretic therapy influences the balance towards metabolic alkalosis.