Sodium metabolism


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Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.

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Sodium metabolism

  1. 1. ELECTROLYTE BALANCE : SODIUM METABOLISM Dr. Sachin Verma MD, FICM, FCCS, ICFC Fellowship in Intensive Care Medicine Infection Control Fellows Course Consultant Internal Medicine and Critical Care Web:- Mob:- +91-7508677495References :Harrison’s Principles of Internal Medicine 16th edn.API Medicine update 2006.Brenner & Rector – Diseases of Kidney.Review of Medical physiology – Ganong 21st edn.
  2. 2. DEFINITION Sodium is the most abundant ion of the extra cellular compartment. Water is the most abundant constituent of the body 50% of body weight in women & 60% of the body wt in men is water, out of which 40% is intracellular and 20% is in extracellular compartment. Total body water (60% of body wtI.C.F. (40 of E.C.F. (20% ofbody wt) body wt) Interstitial fluid 15% Intravascular 5%
  4. 4. How to measure the different body compartments TBW – Measured by deuterium oxide (D2O) ECF – Measured by Insulin, mannitol, sucrose. ICF = TBW-ECF Plasma volume – by evans blue dye, serum albumin labeled with radioactive iodine. Plasma volume Total blood volume = ----------------------- x 100 100 – HCT Sodium placed in important rule in maintaining fluid balance of the body. It is the main ion determining the osmolality of the ECF. Normal sodium concentration 135-145 meq/L. Normal plasma osmolality ranges from 275-290 mosm/L. Main ECF ions are Na+, Cl- and HCO3- main ICF ions or K+, Mg++ and organic phosphates and protein.
  5. 5. UNDERSTANDING NORMAL PHYSIOLOGICAL CONCEPTS Osmolarity – It is no of osmoles per litre of solution. It is affected by volume of various solutes & temperature of the solution. Osmolality – It is the no. of osmoles per Kg of the solvent and it is not effected by the temperature or the solutes. Osmosis – It is the movement of solvent molecules for the region low solute concentration to high solute concentration.Concept of effective and ineffective solute : Effective solute – are impermeable to cell membrane, e.g. Na +. mannitol. Ineffective solute – they are freely permeable to cell membranes e.g. urea, ethanol, methanol. Glucose at normal physiological concentration is ineffective solute but in case of insulin deficiency becomes an effective solutes. Osmolality of plasma = 2 x Na+ (meq/L) + glucose mg/dl /18+ blood urea (mg/dl)/6
  6. 6. NORMAL SODIUM METABOLISM Sodium intake - normal typical western diet consists of 150 mmol – of sodium chloride daily. Absorption of sodium from intestine is via two mechanisms first by being freely permeable across the interstitial cell and secondly by symport with glucose and aminoacids. Sodium excretion - the regulation of sodium excretion is the major determinant of sodium balance. Mainly Na+ is absorbed at 3 main regions in the nephron. 1. PCT – 2/3 of Na+ reabsorbed. 2. TALH – 25-30% is reabsorbed via apical Na+ K+ 2Cl- transporter. 3. DCT – 5% by thiazide sensitive Na+ Cl- cotransporter. Finally Na+ reabsorption also occurs in cortical and medullary collecting ducts.
  7. 7. REGULATION OF SODIUM EXCRETION Sodium excretion is regulated at 4 major steps : 1. Circulating levels of aldosterone – it primarily at on cortical collecting ducts specially T cell to increase ENACs in apical membrane. 2. Circulating number of ANP & other natriuretic hormones – ANP causes increase cGMP and this inhibits transport via ENAC. 3. Amount of AT-II, PGE2 levels in kidney – they causes increase reabsorption of Na+ and HCO3 by action on PCT. PGE2 causes natriuresis by inhibition of sodium transport via ENACs. 4. Rate of tubular secretion of K+ and H+ - Na+ reabsorption is coupled with H+ and K+ secretion in tubules and play important role in acid base metabolism.
  9. 9. Hypertonicity HypovolemiaOsmorecptors Barorecptors angiotensin -II Hypothalamus Thirst
  10. 10. DEFENSE OF ECF VOLUME AND IONIC COMPOSITION OF THE BODY Angiotensin Renin Angiotensin -I HypovolemiaAdrenal cortex ACE Angiotensin -II Hyperosmalarity Aldosterone Hypothalamus Vasoconstriction Kidney Thirst ADH Na+, water retention
  11. 11. HYPONATREMIAETIOLOGYI. Pseudohyponatremia A. Normal plasma osmolality 1. Hyperlipidemia 2. Hyperproteinemia 3. Posttransurethral resection of prostate/bladder tumor. B. Increased plasma osmolality 1. Hyperglycemia 2. MannitolII. Hypoosmolal hyponatremia A. Primary Na+ loss (secondary water gain) (Hypovolemia) 1. Integumentary loss: sweating, burns. 2. Gastrointestinal loss : tube drainage, fistula, obstruction, diarrhoea. 3. Renal loss : Diuretics, osmotic diuresis, hypoaldosteronism, salt-wasting nephropathy, postobstructive diuretics, nonoliguric ATN.
  12. 12. HYPONATREMIAETIOLOGY B. Primary water gain (secondary Na+ loss) (Euvolemic) 1. Primary polydipsia. 2. Decreased solute intake (e.g. beer potomania) 3. AVP release due to pain, nausea, drugs. 4. SIADH 5. Glucocorticoid deficiency 6. Hypothyroidism C. Primary Na+ gain (exceeded by secondary water gain) (Hypervolemic) 1. Heart failure 2. Hepatic cirrhosis 3. Nephrotic syndromeHyponatremia is the most common electrolyte imbalance in clinicalpractice. Its incidence is 0.97% and prevalence of 2.42% in hospitalizedadult patients when 130 meq/L is the diagnostic criteria.
  14. 14. ETIOGENESIS OF SOME IMPORTANT CAUSES OF HYPONATREMIA Factitious pseudohyponatremia – depends upon the methods use for S. Na+ estimation. 1. Flamephotometry (older method) 2. Ion selective electrode method – newer, more accurate Pseudohyponatremia - Every 100 mg/dl of increase in S. glucose causes S Na+ top decrease by 1.6 meq/L but this correction factor should be 2.4 meq/L. Plasma TG (g/dl) x 0.002 = meq/L decrease in S. Na+. Plasma protein level -8 (g/dl) x 0.025 = meq/L decrease in S. Na+. Hyponatremia in hypothyroidism – Due to decrease C.O, GFR and increase AVP secretion in response to hemodynamic stimuli. Hyponatremia in cortisol occurs due to hyper secretion of ADH. Premenopausal women are susceptible to develop severe cerebal edema in association with acute hyponatremia due to inhibition of Na+ K+ ATPase by estrogen and progesterone it may also cause hypothalamic and pituitary infarction. Beer potomania – low protein diet and large consumption of beer may cause renal excretory capacity to be overwhelmed and result in hyponatremia.
  15. 15.  Hyponatremia in AIDS -May occur due to multiple cuases such as administration of I/V fluids, CMV adrenalitis, mycobacterial infections and SIADH caused by CNS and pulmonary infection. Diuretics specially thiazide diuretic lead to Na+, K+ depletion and ADH related water retention. Loop diuretics decrease medullary interstitial tonicity and impair maximal urinary concentrating ability and risk limits the ability of ADH to promote water retention. SIADH - Most common cause of evolemic hypoosmolality. 20-40% of prevalence among all cases of hypoosmolal patients
  16. 16.  Diagnostic criteria for SIADH. 1. Decreased effective osmolality of ECF (plasma osmolality of <275 mosmol/kg. 2. Inappropriate urinary concentration (urine osmolality >100 mosm/kg with hyponatremia. 3. Clinical euvolemia (hypouricemia <4 mg%, low BUN <10mg% 4. Increased urinary Na+ but <40 mEq/L despite normal salt intake. 5. Absence of other causes of euvolemic hypoosmolality. 6. Normal renal, pituitary, acid basedand K+ balance.ETIOLOGY Neoplasm – carcinomas – lungs, duodenum, ovary bladder Infection – abscess, cavitation, pneumonias, TB, AIDS, meningitis. Vascular – CVA, cavernous sinus thrombosis. Neurological – GBS, MS, ALS, Hydrocephalus. Respiratory–PPV, pneumothorax, asthma. Drugs – Chlorpropamide, SSRI, MAOi, oxytocin, desmopressin, carbamazepine.
  17. 17. CLINICAL FEATURES The clinical manifestation of hyponatremia are related to osmotic water shift leading to increased ICF volume, brain cell swelling and cerebral edema. Symptoms progressively occurs as Na+ conc. Decreases less than 130 meq/L. Symptoms Signs Lethargy, apathy, Altered sensorium, decrease disoreintation, nausea, DTR, cheyne stokes anorexia, agitation respiration, hypothermia, pseudobulbar palsy, seizures.
  18. 18. DIAGNOSIS AND MANAGEMENT Hyponatremia is not a disease but a manifestation of a variety of disorders and requires accurate history physical examination and lab investigations for diagnosis. Important investigation for the diagnosis of hyponatremia are – 1. Plasma osmoalality 2. Urinary osmolalaity 3. Urine sodium concentration Therapeutic strategy in hyponatremia is dictated by the underlined disorder as well as 1. presence or absence of symptoms. 2. Duration of the disorder 3. The risk of neurological complications.
  19. 19. Plasma osmolality High Normal LowHyperglycemia Hyperproteinemia hyperlipidemia Maximal volume of maximally mannitol bladder irrigation dilute urine (<100 mosmol/kg ECF volume Primary polydipsia reset osmostat Increased Normal Decreased Heart failure hepatic SIADH Urine Na+ cirrhosis nephrotic Hypothyroidism concentration syndrome renal adrenal insufficiency insufficiency < 10 mmol/L > 20 mmol/L Extrarenal Na+ loss remote Na+ wasting nephropathy diuretic use remote vomiting hypoaldosteronism diuretic vomiting
  20. 20. TREATMENT OF HYPONATREMIA The underlying treatment of hyponatremia depends upon presence or absence of symptoms. Goals of treatment - 1. To increase plasma sodium concentration. Restricting water (if <120 mEq/L) to <500-1000 ml/day intake and promoting water loss. 2. Correction of underlying disorder. ECF volume should be restored in hypovoleumic patients which can be calculated according to the following equation Water excess =Total body water x (125/plasma Na+) - 1 The rate of plasma Na+ concentration should not be >0.5 to 1 mmol/L/hr in asymptomatic patients. In severe symptomatic patients plasma Na+ concentration should be raised by 1 to 2 mmol/L/hr for first 3 for hours or until seizures subside In both conditions plasma Na+ concentration should not be raised > than 12 mmol/L in 24 hrs.
  21. 21. Treatment of underlying disorders Adrenal insufficiency – I/V glucocorticoid administration (100-200 gm) hydrocortisone 1 L of 5% DNS over 4 hours – for acute conditions. ACE inhibitor and loop diuretic are given in volume expanded states with increase RAAS activity such as CHF & nephrotic syndrome. In correctable conditions like metastatic lung cancer (SIADH) treated with demeclocycline (900-1200 mg/day). Stop I/V hypotonic solutions, offending drugs. Treatment of SIADH - severe water restriction, upto 25-50% of maintenance of water intake is required and correction if possible of underlying disorder.
  22. 22. TREATMENT OF SEVERE HYPONATREMIA Symptomatic Asymptomatic Acute Duration < Chronic Duration >48 hr or Chronic Rarely < 48 hr unknown 48 hr Emergency correction Some immediate correction needed No immediate correction needed • Hypertonic saline 1-2 mL/kg/hr needed• Hypertonic saline (3%) at • Coadministration of forosemide1-2mL/kg/hr • Change to water restriction upon 10%• Coadministration of increase of [Na], or if symptoms resoivefurosemide Perform frequent measurement of serum and urine electrolytes Do not exceed 12 mEq/L/day Long-Term management • Identification and treatment of reversible etiologies • Water restriction • Demoeclocycline 300 to 600 mg bid- Allow 2 weeks for full effect, or • Urea 15 g to 60 g gd - Immediate effect • V2 receptor antagonist – Under investigation, conivaptan, VPA-925.
  23. 23. SODIUM REPLACEMENTSodium Replacement : When corrective therapy requires the infusion the isotonic saline or hypertonic saline, the replacement therapy can be guided by the calculated sodium deficit. This is determined as follow (using a plasma Na+ of 130 mEq/L as the desired end – point of replacement therapy). Sodium derficit (mEq.)= Normal T.B.W x (130-current Plasma Na +) Example : For a 60 Kg. Male with plasma Na+ 120 meq/L. Sodium deficit=0.60X60X(130-120)meq., =360 meq. Because 3% N.S. contain 513 meq of Na+/L, the vol. Of hypertonic saline needed to correct Na+ deficit of 360 meq will be 360/513=700 ml. Using a max. rate of rise of 0.5 meq/L/hour. For plasma Na + the Na+ concentration deficit of 10 meq/liter in the example – should be corrected over at least 20 hours.
  24. 24. (ODS) OSMOTIC DEMYELINATION SYNDROME This is a neurological disorder characterized by flaccid paralysis, dysarthria & dysphagia. It occurs due to rapid correction of hyponatremia. Other features of that may occur in this disorder are quadriparesis weakness of lower face and tongue overfew days to weeks. The lesion may extend dorsally to involve sensory tract and leave patients in locked in syndrome. Risk factors for ODS –Malnutrition due to chronic alcoholic liver disease, hypokalemia, cerebral anoxic injury. Water restriction in primary polydipsia and intravenous saline therapy in ECF volume contracted patients may also lead to rapid correction of hyponatremia as a result of ADH suppression and brisk water diuresis.
  25. 25. HYPERNATREMIA It is defined as plasma Na+ concentration >145mmol/L. Hypernatremia is generally mild unless thirst mechanism is abnormal or access to water is limited e.g. infants, physically challanged, impaired mental status, postop patient, intubated patients in ICU. May be due to - Primary Na+ gain - Primary water deficit1. Free water loss – may be renal or extra renal Extra renal – 1. Skin & respiratory tract (Insensible water loss) due to evaporation 2. GI loss : Diarrhoeas 1. Osmotic – Lactulose, sorbitol, malabsorption, viral gastroenteritis, - in all these conditions water loss > Na+ loss – Hypernatremia 2. Secretory – Cholera, carcinoid syndromes, ViPomas- in these conditions fecal osmolality is similar to plasma osmolality so plasma Na+ concentration remain same or decreases with ECV contraction.
  26. 26. RENAL LOSS Most common cause of hypernatremias. 1. Drug induced - Loop diuretics – interfere with counter current mechanism and produces isoosmotic, solute diuresis, 2. Osmotic diuresis - Due to presence of non reabsorbed organic solutes in the tubular lumen osmotic diuresis in which water loss > Na+ K+ loss e.g. hyperglycemia, I/V mannitol increased urea in body.DIABETES INSIPIDUS It is a syndrome characterized by production abnormally large volume of dilute urine. The 24 hours urine volume is >50 ml /kg body weight and the osmolarity is <300 mosmol/L. Causes non osmotic water loss. It is of two types : 1. Central diabetes insipidus – due to impaired ADH secretion. 2. NDI nephrogenic diabetes insipidus – due to end organ resistance to the action of ADH.
  27. 27.  In complete CDI – after water deprivation test maximal urinary osmalality <300 mosmol.L which increases substantially with ADH. In partial CDI maximal urinary osmolality is between 300 –800 mosmol/L which increases >10% after ADH administration. In NDI maximal urinary osmolality is between 300 –500 mosmol/L and does not rises with ADH administration.CDI - Etiology Congenital – genetic causes AVP – neurophysin gene mutation. – Malformation e.g. holoprosencephaly, craniofacial defects. Acquired – head trauma Neoplasm e.g. craniopharyngioma, pituitary adenoma. Granulomas e.g. neurosarcoid, histiocytosis. Infections e.g chronic meningitis, viral encephalitis. Inflammatory e.g.SLE, Scleroderma, Wegener’s granulomatosis. Vascular e.g. aneurysm, HIE.
  28. 28. NDI - etiology Genetic – X-linked recessive, AR, AD, AVP receptor, aquaporin gene defects. Acquired – drugs – Li, Cisplatin, Rifampin, demeclocycline. Metabolic – hypercalcemia, hypokalemia Vascular – sickle cell disease, ATN. Granulomas and Neoplasm pregnancy
  29. 29. Clinical features Clinical features of hypernatremia are primarily neurological. Major neurological –symptoms include : - Nausea, Muscular weakness, altered mental status, neuromuscular irritability, focal neurological deficit and occasionally coma or seizures and they depend upon the rapidly of outset, its duration and its magnitude. In severe acute hypernatremia brain shrinkage may be substantial, exerting traction on the venous causing intra cerebral and SAH. The patients may also complain of polyuria or excessive thirst. The signs and symptoms of volume depletion are often present in patient with history of excessive sweating, diarrhea or osmotc diuresis. In chronic hypernatremia brain cell initially take up Na+ and K+ later accumulates organic osmolytes such as inositol to restore the brain ICF volume.
  30. 30. DIAGNOSIS AND MANAGEMENT OF HYPERNATREMIA Complete history and physical examination often provide clues to the underlying cause of hypernatremia. Measurement of urine volume and osmolality. Calculating : Plasma Na+ Concentration - 140 Water deficit = ----------------------------------- x total body water 140 Rapid correction of hypernatremia is dangerous because sudden decrease in osmolality can cause rapid shift of water into the cells resulting in swelling of brain cells. Treatment of hypovolemic hypernatremia – is by restoring volume by I/V NS. Treatment of hypervolemic hypernatremia is by removing sodium excess by diuresis. Sodium excess (mEq) = 0.6xwt in Kg x (patient’s serum sodium – 140)
  31. 31.  In cases of volume disturbances D-5%, DNS are given as preferred solutions. In hypovolemic patients Ist colloid & 0.9% NS is given before hypotonic solutions or free water is administrated.TREATMENT OF DIABETES INSIPIDUS In the treatment of CDI desmopression intranasally plays important role. It can be given 1-2 µg qd or bid injection or 10- 20 µg by bid or tid by nasal spray. Besides chlorpropamide, clofibrate carbamazepine can also be given for treatment of CDI. Thiazide diuretic and low Na+ diet is given for management of NDI. Besides in the management of NDI - NSAIDs amiloride and lithium can also be given in selected patients.
  32. 32. CLINICAL APPROACH TO HYPERNATREMIA ECF volume Increased Not increased Administration of Minimum volume of maximal hypertonic NaCl or NAHCO3 concentrated urine No YesUrine osmole excretion rate >750 Insensible water less gastrointestinal mosm/day water less remote renal water loss. No YesRenal response to desmopressin Diuretic osmotic diuresis Urine osmolality increase Urine osmolality unchanged CDI NDI