clinical MANAGEMENT OF HYPONATRAEMIA.pptx

management of hyponatremia

1. MANAGEMENT OF HYPONATRAEMIA BY DR UBA-MGBEMENA OKEZIE INTERNAL MEDICINE RESIDENT AS PARTIAL FULFILMENT OF CHEMICAL PATHOLOGY POSTING UCTH

2. SALT AND WATER

3. OUTLINE INTRODUCTION PATHOPHYSIOLOGY CLASSIFICATION CLINICAL FEATURES DIAGNOSIS TREATMENT CONCLUSION

4. Introduction. Hyponatremia is one of the commonest biochemical abnormalities in clinical practice. Reference interval for serum sodium – 135-145mmol/L (may differ btw Labs) Hyponatremia is defined as a plasma concentration less than 135mmol/L. Occurs in up to 22% of hospitalized patients ( over 1 in 5 patients). Important to detect; if left untreated ,may be associated with poor outcomes.

5. INTRODUCTION Disorders of serum Na+ concentration are caused by abnormalities in water homeostasis leading to changes in the relative ratio of Na+ to water body Water intake and circulating AVP, key effectors in the defence against serum osmolarity ; and defects in one or both of these defence mechanisms cause most cases of hyponatraemia and hypernatraemia .

6. INTRODUCTION CTD May be classified into Mild hyponatremia : 130-134mmol/L Moderate hyponatremia : 125-129mmol/L Severe hyponatremia :<125mmol/L Clinically significant hyponatremia <130mmol/L

7. E pidemiology In the US, among hospitalized patient, hyponatremia had a prevalence of 15-20%. In Calabar , a study on hyponatremia in patients on antipsychotics by Olose et al revealed a prevalence of 19.6%. P attern of electrolyte profile among admitted children (1-18 years) at UCTH by Lawson Ekpe et al.- 39.6% had hyponatremia .

8. Epidemiology. No racial or sexual predilection exists for hyponatremia . However , symptoms are more likely to occur in young women than in men . Hyponatremia is more common in elderly persons, because they have a higher rate of comorbid conditions ( eg , cardiac, hepatic, or renal failure) that can lead to hyponatremia .

9. Epidemiology ctd . Severe hyponatremia (< 125 mEq /L) has a high mortality rate. In patients whose serum sodium level falls below 105 mEq /L, and especially in alcoholics, the mortality is over 50%. Also, hyponatremia is an important predictor of mortality in several conditions viz liver cirrhosis, chronic kidney disease and acute STEMI.

10. Pathophysiology. Sodium is the most abundant extracellular cation . Alongside its anions determines up to 80-90% of plasma osmolality. Plasma osmolality is key in influencing movement of fluid from the intravascular to interstitial compartment and between the interstitial and intracellular compartment.

11. Sodium homeostasis For a 70 kg adult daily Na + intake is 100-150 mmols in addition to 1.5-2.5 L of oral daily in­take of fluids. Approximately 8 L more are pro­duced and secreted by various parts of GIT. These secretions contain 1200-1400 mmol of Na + 6 to 6.5 L is reabsorbed in the small intes­tine and the remainder is reabsorbed in the large intestine Only 100 ­-200 mL of fluid and 4-5 mmol of Na + are ex­creted in the stool.

12. Sodium homeostasis – excretion. The kidney has two important functions for Na + and water balance: filtration and reabsorp­tion . Normally filtration is autoregulated , so it is the reabsorptive mechanisms that adjust to variable input and output. Every minute 125 mL (180 L/day) of filtrate containing 17 mmoL of Na + (daily 25,000 mmoLs ) enters the proximal tubule (PT); 99% is reabsorbed and 1% excreted. Daily, it can excrete 0.5 to 25 L of urine with osmolality varying from 40-1400 mosm /L. Thus, depending on the demands, urine volume can vary 50-fold and urine osmolality 35-fold.

13. Reabsorption of filtered Na + load varies in the different parts of the nephron ; 65% of filtered Na + is reabsorbed the Prox. Tubule via Na cotransporters , paracellular pathway and Na-H+ exchanger (stimulated by Ang II) 20 %, and thick ascending part of loop of Henle ( aLOH ), via Na + K + 2Cl cotransporters (loop diuretics) 10% at the distal tubule (DT ),via NaCL co transporter 4% at the collecting duct (CD) via epithelial Na channels .

14. Pathophysiology ctd . Sodium and water balance is maintained by a system of ‘sensors’ and ‘effectors’ Sensors include chemoreceptors ( osmoreceptors ) found in the brain - circumventricular organs –lamina terminalis and subfornical organ and in the kidneys. Sense changes in circulating osmolality, leading to release of ADH and thirst. Baroreceptors located in the carotid sinus and aortic arch sense changes in MAP and stimulate ADH release and thirst also.

15. Pathophysiology ctd Intact sodium and water balance revolves around an intact thirst mechanism, ADH release and renal handling of sodium and water. ADH (AVP) is a peptide hormone synthesized in the supraoptic and paraventricular nucei of the hypothalamus. Secretion is stimulated when systemic osmolality increases above 285mosm/kg. Acts on renal V2 type receptors in the THICK asc loop of henle and principal cells of collecting duct Stimulating insertion of aquaporin 2 water channels.

16. Classification According to osmolality Hypotonic hyponatremia Isotonic hyponatremia Hypertonic hyponatremia According to volume status Hypovolemic hyponatremia Euvolemic hyponatremia Hypervolemic hyponatremia

17. HYPOVOLAEMIC HYPONATRAEMIA Hyponatraemia causes marked neurohumoral activation, increasing levels of circulating AVP. The increase in AVP preserves BP via vascular and baroreceptor V 1A receptors and increases water reabsorption via renal V 2 receptors. Activation of renal V 2 receptors can lead to hyponatraemia in the setting of increased free water intake.

18. Salt- losing nephropathies Hyponatraemia with reduced Na+ intake. Due to impaired renal tubular function Reflux nephropathy Interstitial nephropathy Post obstructive uropathy Medullary cystic disease Recovery phase of acute tubular necrosis

19. Thiazides donot inhibit renal concentration mechanisms,AVP retains full effect Loop diuretics less frequently assoc wth hyponatraemia , blunt countercurrent mechanisms

20. Increased excretion of osmotically active nonreabsorbable or poorly reabsorbable solutes Volume depletion and hyponatraemia Glycosuria Ketonuria (starvation, diabetic or alcoholic acidosis) Bicarbonaturia ( RTA or metabolic alkalosis)

21. Mineralocorticoid ( aldosterone ) deficiency syndrome Characterized by hyponatraemia with ECF volume contraction ( provides a nonosmotic stimulus for vasopressin release) Urine[Na+] above 20mmol/l, and high K+.

22. Cerebral salt wasting syndrome Follows SAH, head injury, neurological procedures etc Primary defect is salt wasting from kidneys(? Role of BNP) with subsequent volume contraction, which stimulates vasopressin release Uncommon Hyponatraemia + hypovolaemia + intracranial diseases Responds to aggressive Nacl repletion

23. EUVOLAEMIC HYPONATRAEMIA SIADH Glucocorticoid def Hypothyroidism Drugs Stress

24. SIADH A defect in osmoregulation causes vasopressin to be inappropriately stimulated, leading to high urinary concentration Excess vasopressin: CNS disturbances such as haemorrhage , tumours , infections, and trauma Ectopic vasopressin: small cell lung cancers, cancer of the duodenum and pancreas and olfactory neuroblastoma Idiopathic: seen in the elderly(10%)

25. HYPERVOLAEMIC HYPONATRAEMIA Increase in total body NaCl accompanied by a proportionately greater increase in body water leading to reduced serum Na+ ARF or CRF( U Na >20) Nephrotic syndrome, cirrhosis, CCF( U Na <20) (arterial underfilling ) The degree of hyponatraemia provides an indirect index of associated neurohumoral activation and is an important prognostic indicator in hypervolaemic hyponatraemia

26. LOW SALT INTAKE AND HYPONATRAEMIA- BEER POTOMANIA Classically occurs in alcoholics whose sole nutrient is beer. Beer is very low in protein and salt content( only 1-2mM of Na + ) Also in vegetarians Typically presents with low urine osmolarity (100-200mOsm/kg) and Na + concentration of <10-20mM Low dietary intake of solutes, reduced urinary solute excretion limits water excretion such that hyponatraemia ensues after relatively modest polydipsia

27. Hyponatraemic encephalopathy Headache Confusion and restlessness leading to: Drowsiness Myoclonic jerks Generalised convulsions eventually, death Risk factors- children <16yrs,premenopausal women,hypoxaemia

28. CHRONIC HYPONATRAEMIA Persistent chronic hyponatraemia results in an efflux of organic osmolytes ( creatine,betaine , glutamate, myoinositol , and taurine ) from brain cells; this response reduces intracellular osmolality and the osmotic gradient favouring water entry. This usually happens after 48hrs Symptoms include..nausea, vomiting, confusion and seizures at [Na+] <125mmol/l Asymptomatic.. Subtle gait and cognitive defects and hyponatraemia -associated reduction in bone density

29. OSMOTIC DEMYELINATION SYNDROME Asymmetric cellular response to correction of chronic hyponatraemia . Reaccumulation of organic osmolytes by brain cells is attenuated and delayed resulting in degenerative loss of oligodendrocytes . Overly correction of hyponatraemia (> 8-10 mmol /l in 24hrs or 18mmol/l in 48hrs) resulting in disruption of the BBB allowing entry of immune mediators leading to demyelination . Lesion classically in pons causing central pontine myelinolysis usually 1 or 2 days after over correction of hyponatraemia Presents with paraparesis or quadriparesis,dysphagia,dysarthria , diplopia , a locked-in syndrome and loss of consciousness

30. ODS Extra pontine myelinolysis can occur in the cerebellum, lateral geniculate body,thalamus , putamen , and cerebral cortex or subcortex . Depending on extent and localization of extra pontine lesions : ataxia, mutism , parkinsonism, dystonia , catatonia. Lowering [Na+] after overly correction of hyponatraemia can attenuate ODS

31. DIAGNOSTIC EVALUATION OF HYPONATRAEMIA Underlying cause Detailed drug history/ smoking history Clinical assessment of volume status Clinical symptoms and physical examination for signs Radiological imaging(CXR, CT) for pulmonary or CNS causes of hyponatraemia Laboratory investigations

32. Laboratory investigations Serum osmolarity Fasting lipid profile Serum proteins Serum E/U/Cr Plasma/serum glucose level Serum uric acid Thyroid function test Plasma aldosterone and renin levels.

33. LAB INVESTIGATIONS Urine electrolytes Urine osmolarity Urine- plasma electrolytes ratio Plasma copeptin , apelin and MR- proANP

34. TREATMENT The European and American guidelines have been developed The treatment for hyponatraemia is chosen on the basis of duration and symptoms. For acute or severely symptomatic hyponatremia , both guidelines adopted the approach of giving a bolus of hypertonic saline Fluid restriction as first line treatment for chronic hyponatraemia The professional organizations involved in the United States guideline were Tufts University Office of Continuing Education and In 2 MedEd ; the initiative was also supported by an unrestricted educational grant from Otsuka America Pharmaceutical The professional organizationsinvolved in the European guideline were the European Renal Association– European Dialysis and TransplantationAssociation , the European Society of Endocrinology, and the EuropeanSociety of Intensive Care Medicine

35. Hyponatremia correction Alternatively, another equation for correction Sodium deficit = (Desired serum sodium- actual serum sodium) x Total body water. Alternatively, Using 3% Hypertonic saline : 1ml/kg of 3% saline is estimated to raise serum Na by 1mmol/L.

36. CONCLUSION Hyponatraemia is a common sodium disorder. Complications of hyponatraemia can result in profound coma There is need for urgent intervention when complications arise.

37. THANK YOU

38. References. PATTERN OF ELECTROLYTE PROFILE AMONG ADMITTED CHILDREN (1-18 YEARS) AT THE UNIVERSITY OF CALABAR TEACHING HOSPITAL, NIGERIA. Ekpe E. L et al - https:// medrech.com/index.php/medrech/article/view/410 accessed November 30th, 2020. Patel S. Sodium balance-an integrated physiological model and novel approach. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2020 Dec 9];20:560-9. Available from:  https://www.sjkdt.org/text.asp?2009/20/4/560/53242

39. References Hyponatremia : A practical approach https ://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192979 / accessed on November 28 th , 2020. https:// emedicine.medscape.com/article/242166-overview#a2 Accessed on Novenber 26 th , 2020. Hyponatremia – fishing in troubled waters by K. Sampathkumar . FRCP, India slideshare presentation. https:// www.aafp.org/afp/2015/0301/p299.html Accessed on November 29 th , 2020.