Disorders of Sodium Balance

1. Disorders of Sodium Balance

2. Functional anatomy and physiologyof renal sodium handling • Majority of the body’s sodium content is located in the ECF, where it is the most abundant cation • Total body sodium is a principal determinant of ECF volume • Regulation of sodium excretion by the kidney is crucially important in maintaining normal ECF volume, and hence plasma volume

3. Sodium intake is in the range 50–250 mol/day • The functional unit for renal excretion is the nephron • The glomerular filtration rate (GFR) is approximately 125 mL/min (equivalent to 180 L/day)

4. Over 99% of this filtered fluid is reabsorbed into the blood in the peritubular capillaries during its passage through successive segments of the nephron,largely as a result of tubular reabsorption of sodium

5. Nephron segments Proximal tubule • This is responsible for the reabsorption of 65% of the filtered sodium load • Fluid and electrolyte reabsorption is almost isotonic in this segment, as water reabsorption is matched very closely to sodium fluxes

6. The loop of Henle • The thick ascending limb of the loop of Henle reabsorbs a further 25% of the filtered sodium but is impermeable to water, resulting in dilution of the luminal fluid

7. Early distal tubule • 6% of filtered sodium is reabsorbed • This segment is also impermeable to water, resulting in further dilution of the luminal fluid

8. Late distal tubule and collecting ducts • 3% of filtered sodium is reabsorbed here • This part of the nephron has a variable permeability to water, depending on the availability of antidiuretic hormone (ADH, or vasopressin) in the circulation

9. Regulation of sodium transport • A large number of interrelated mechanisms serve to maintain whole body sodium balance and hence ECF volume by matching urinary sodium excretion to sodium intake

10. Important sensing mechanisms include volume receptors in the atria and the intrathoracic veins, pressure receptors located in the central arterial tree (aortic arch and carotid sinus) and the afferent arterioles within the kidney

11. Renin release from kidney is stimulated by: • reduced perfusion pressure in the afferent arteriole • increased sympathetic nerve activity • decreased sodium chloride concentration in the distal tubular fluid

12. Disorders of Water Balance • Daily water intake can vary over a wide range, from 500 mL to several litres a day • 800 mL/day water is lost (insensible losses) through the stool, sweat and the respiratory tract

13. 400 mL/day water is generated by oxidative metabolism (metabolic water) • Kidneys are chiefly responsible for adjusting water excretion to maintain constancy of body water content and body fluid osmolality (normal range 280–295 mmol/kg)

14. There are mechanisms to allow for the excretion of a ‘pure’ water load when free water intake is high, and for the avid retention of water by the kidneys when water is restricted • These functions are largely achieved by the properties of the loop of Henle and the collecting ducts

15. Further changes in the urine osmolality on passage through the collecting ducts depend on the level in the plasma of the peptide ADH, which is released by the posterior pituitary gland under conditions of increased plasma osmolality or other stimuli such as hypovolaemia

16. Parallel to these changes in ADH release are changes in water-seeking behaviour triggered by the sensation of thirst, which becomes activated as plasma osmolality rises

17. For adequate dilution of the urine there must be: • Adequate solute delivery to the loop of Henle and early distal tubule • Normal function of the loop of Henle and early distal tubule • No ADH in the circulation. • If any of these processes is faulty, water retention and hyponatraemia may result

18. Disturbances in body water balance, in the absence of changes in sodium balance, alter plasma sodium concentration and hence plasma osmolality • When extracellular osmolality changes abruptly, water flows rapidly across cell membranes with resultant cell swelling or shrinkage

19. Cerebral cell function is very sensitive to such volume changes, when an increase in intracerebral pressure occurs due to the constraints imposed by the bony skull, thereby reducing cerebral perfusion

20. Hyponatraemia • Aetiology and clinical assessment • Hyponatraemia (plasma Na < 135 mmol/L) is a common electrolyte abnormality • Often detected asymptomatically

21. It may also present with profound disturbances of cerebral function, manifesting as • Anorexia • Nausea & vomiting • Confusion • Lethargy • Seizures • Coma

22. The degree of cerebral symptomatology depends more on the rate of development of the electrolyte abnormality than on its severity • When plasma osmolality falls rapidly, water flows into cerebral cells which become swollen and ischaemic

23. when hyponatraemia develops gradually, cerebral neurons have time to respond by reducing intracellular osmolality, through excreting potassium and reducing synthesis of intracellular organic osmolytes • The osmotic gradient favouring water movement into the cells is thus reduced and cerebral symptomatology avoided

24. The causes of hyponatraemia are best categorised according to any associated change in ECF volume status, i.e. the total body sodium

25. Hypovolaemic (sodium deficit with a relatively smaller water deficit) • Diuretic therapy (especially thiazides) • Renal Na losses • Adrenocortical failure

26. Gastrointestinal Na losses Vomiting Diarrhoea • Skin Na losses • Burns

27. Euvolaemic (waterretention alone) • SIADH* • Primary polydipsia • Excessive electrolyte-free water infusion • Hypothyroidism

28. Hypervolaemic(sodium retention with relatively greater water retention) • Congestive cardiac failure • Cirrhosis • Nephrotic syndrome • Chronic renal failure (during free water intake)

29. Investigations • Plasma and urine electrolytes and osmolality

31. Management • The treatment for hyponatraemia is critically dependent on the rate of development, severity and underlying cause

32. If hyponatraemia has developed rapidly (over hours to days), morbidity due to cerebral oedema is more likely, and it is safe to correct the plasma sodium rapidly by using hypertonic (3%) sodium chloride solutions

33. On the other hand, rapid correction of hyponatraemia which has developed slowly (over weeks to months) can itself be hazardous to the brain • This is because cerebral cells adapt to slowly developing hypo-osmolality by reducing the intracellular osmolality, thus maintaining normal cell volume

34. An abrupt increase in extracellular osmolality can lead to water shifting out of the cerebral neurons, abruptly reducing their volume and risking detachment from their myelin sheaths • The resulting ‘myelinolysis’ can produce permanent structural and functional damage to mid-brain structures, and is generally fatal

35. Na correction of the plasma concentration in chronic asymptomatic hyponatraemia should not exceed 10 mmol/L/day, and an even slower rate is generally safer • Underlying cause should be treated

36. Patients with Euvolaemichyponatraemia generally respond to fluid restriction in the range 600–1000 mL/day, accompanied where possible by withdrawal of the precipitating stimulus • Oral vasopressin receptor antagonists (vaptans) may be used to block the ADH mediated component of water retention

37. In hypervolaemic patients diuretics in conjunction with strict fluid restrictioncan be used