Sp r training 2012 salt and water

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Sp r training 2012 salt and water

  1. 1. Salt and Water SpR training July 2012 Roderick Warren
  2. 2. Salt and water physiology Aldosterone Vasopressin Where they act What they do What happens with the crisps and beer
  3. 3. Collecting ductprincipal cell –aldosterone andADH receptors
  4. 4. ADH release:• Osmolality (responds to 1% change)• Effective blood volume (responds to 5-10% change)
  5. 5. Aldosterone release:• Potassium• Effective blood volume (detected at JGA) ENaC – epithelial sodium channel NCCT – sodium-chloride cotransporter NKCC2 – sodium-chloride-potassium cotransporter
  6. 6. Other natriuresis pathwaysANP Release: atrial distension (and other triggers) Effects: increases GFR (affects renal blood flow); decreases Na resorption by NCCTBNP Similar to ANPPressure natriuresis
  7. 7. In the pub1. Eat crisps and nuts Salt intake Increased osmolality ADH release5. Feel thirsty, drink beer Fluid intake Increased volume Aldosterone suppressed9. Go to loo Excrete salt and water
  8. 8. Sodium balance Recommended intake <100 mmol per day – 6g sodium chloride per day – 2.4g sodium per day Average intake 150-200 mmol per day
  9. 9. Sodium balance IN OUT 2 litres water Water 2 litres water 150 mmol salt Salt 150 mmol salt
  10. 10. Causes of hyponatraemia
  11. 11. Pseudohyponatraemia? Incorrect measurement due to presence of lots of lipid or protein e.g. hypertriglyceridaemia Often wrongly used to mean hyponatraemia due to another osmotic substance
  12. 12. Non-hypotonic hyponatraemia Glucose  All draw water into blood Urea  Reduce serum osmolality Mannitol Ethylene glycol  Detect by discrepancy between calculated and actual osmolality(PS basically, serum osmo = plasma osmo)Bunting et al, Crit Care Med 1986; 14: 650
  13. 13. Calculated versus actual osmolality Na 122  Measured osmo 320 K 4.0 Urea 3.4  Gap 370-240=60 Gluc 4.5 Osmo = (122+4) x 2  Ethylene glycol + 3.4 + 4.5 intoxication = 260
  14. 14. When to measure osmolality Reasonable practice in all cases But remember what it’s for: – to diagnose a non-measured solute – ethanol – methanol – ethylene glycol
  15. 15. Hyperglycaemia Osmotic effect of high glucose draws water into blood, and dilutes sodium (and everything else) Correction factor – 1 mmol/L Na = 3.5 mmol/L glucose Possibly more pronounced at glucose > 25 mmol/L – 1 mmol/L Na = 1.4 mmol/L glucoseRef Hiller et al, Am J Med, 1999; 106: 399. Penne et al Diabetes Care 2010; 33: e91.
  16. 16. Hyperglycaemia Admission – simple Admission – HONK hyperglycaemiaNa 124 Na 146Glucose 45 Glucose 45Urea 8.2 Urea 28.2 After IV insulin After IV insulinNa 139 Na 160
  17. 17. Hypotonic hyponatraemia: causesShout them out
  18. 18. SIADHDiuretics Glucocorticoid Heart failurePrimary adrenal failure deficiency CirrhosisPrimary renal disease Pregnancy NephroticPseudohypoaldosteronism Reset osmostat syndrome Excess water intakeGI loss (vomiting, diarrhoea)Skin loss (burns, sweating)Third space (pancreatitis)Dietary deficiency (anorexia)
  19. 19. Hypovolaemic Euvolaemic Hypervolaemic SIADH Diuretics Glucocorticoid Heart failureRenal deficiency Primary adrenal failure Cirrhosissodium Pregnancyloss Primary renal disease Nephrotic Reset osmostat Pseudohypoaldosteronism syndrome Excess water intake GI (vomiting, diarrhoea)Other Skin (burns, sweating)sodium Third space (pancreatitis)loss Dietary deficiency (anorexia)
  20. 20. Assessing volume statusEither: Actual obvious Dry Normal or euvolaemic Dry 7 22 ClinicalThink you can do better? Normal 8 21 Two expert nephrologists carefully reviewed 58 patients For detecting volume depletion: with hyponatraemia • sensitivity 47% Clinical judgement compared • specificity 49% with response to IV salineChung et al Am J Med 1987; 83: 905
  21. 21. Hypovolaemic hyponatraemiaCause ClueDiuretic ObviousPrimary adrenal Symptoms, signs, cortisolPrimary renal Renal failure, urine dipstickD&V Usually obvious from historyAnorexia Usually obviousSkin loss Usually obvious from context“Third space” Uncommon
  22. 22. If in doubt DiureticsRenal sodium Primary adrenal failure Urine Na not lowloss Primary renal disease Pseudohypoaldosteronism GI (vomiting, diarrhoea)Other sodium Skin (burns, sweating) Urine Na lowloss Third space (pancreatitis) (<20 mmol/L) Dietary deficiency (anorexia)
  23. 23. Diuretic-induced hyponatraemiaGitelman syndrome (likethiazide treatment) –hypokalaemia, alkalosis,hypocalciuria,hypomagnesaemiaBartter syndrome (likeloop diuretic) – alkalosis,hypokalaemia,hypovolaemia,hypercalciuria
  24. 24. Diuretic-induced hyponatraemia 94% of reported cases are with thiazides Rapid onset (hours-days) – longer with loops Why? Possible causes: – patients on thiazides are in water balance or slight water excess (perhaps due to ADH release) – short half-life of loop diuretics (brief electrolyte excretion, then avid retention)
  25. 25. Adrenal failure Aldosterone deficiency – normally protects sodium (at expense of potassium) Cortisol deficiency – tonic inhibition of ADH – profound cortisol deficiency causes SIADH-like picture
  26. 26. Hypervolaemic hyponatraemia Usually clinically obvious Said to be dilutional (though I think poorly understood) ADH stimulated by reduced stretch receptor stimulus due to... – poor cardiac output – reduced intravascular volume
  27. 27. Hypothyroidism is not a cause Serum sodium distribution in 1000 hypothyroid patients and 5000 controls 95% ranges:  132-144 (hypothyroid)  134-144 (control) Hypothyroidism lowers serum Na by 0.48 mmol/L Warner et al, Clin Endo 2006; 64: 596.
  28. 28. Syndrome of inappropriateantiduretic hormone
  29. 29. Causes of SIADH Drug causes Non-drug causesTricyclic antidepressants; Malignancy:Selective serotonin reuptake  most, but especially lung. inhibitors; Infections:Opioids;  pulmonary (pneumonia,Antipsychotics (e.g. haloperidol, TB, empyema); chlorpromazine, flupentixol,  cerebral (e.g. meningitis, trifluoperazine); abscesses).Dopamine agonists; Nervous system disease:Nicotine;  haemorrhage;MDMA (Ecstasy).  infarction;Anti-epileptics (carbamazepine,  demyelination (e.g. MS, valproate); Guillain-Barré).
  30. 30. Normal ADH release
  31. 31. Patterns of SIADH a – Random b – Non-suppressible basal ADH levels, but normal response to raised plasma osmolality c – Reset osmostat. ADH rises in response to plasma osmolality, but is always higher than it should be.
  32. 32. What happens in SIADH?Syndrome of inappropriateantidiuretic hormoneWhy doesn’t the patient swellup?
  33. 33. What happens in SIADH? Compensatory Inappropriate mechanisms – ADH aldosterone etc Salt and Water Water water Water retention excretion Water Salt Salt SaltNormal state Hyponatraemia Hyponatraemia Tendency to Euvolaemia hypervolaemia
  34. 34. Experimental SIADH Leaf et al 1953 J Clin Invest 1953; 32: 868
  35. 35. Experimental SIADH Leaf et al 1953 J Clin Invest 1953; 32: 868
  36. 36. SIADH in theory Onset Maintenance Recovery Serum sodium concentration 24-hour urine sodiumexcretion
  37. 37. SIADH in theory1. Fluid intake is required to become hyponatraemic2. During onset, urine sodium excretion is high3. SIADH = euvolaemia with total sodium deficit4. In steady state, urine sodium = sodium intake5. Sodium intake is required to correct hyponatraemia6. In recovery, urine sodium is low  (as for recovery from hyponatraemia of any cause)
  38. 38. Limitations: urinary sodium Range of sodium intake 60-250 mmol Range of water intake 1200-4000 mL Urinary sodium concentration – from 15 mmol/L to 208 mmol/L
  39. 39. Limitations: urinary osmolality “Urine osmolality < serum osmolality excludes SIADH” Average protein intake 70g/d = 350 mmol urea Average sodium + chloride = 300 mmol Average potassium = 60 mmol Total about 700 mmol Average urine osmo = about 3-400 mOsm/kghttp://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/19710023044_1971023044.pdf
  40. 40. SIADH may be steady state Onset Maintenance Recovery Average urine osmo about Serum sodium 3-400 concentration 24-hour urine sodiumexcretion
  41. 41. Limitations: urinary osmolality Average urine osmo = about 3-400 mOsm/kg Maybe 6-800 on waking Maybe 200 after drinking
  42. 42. So how can we diagnose SIADH? By ruling out other diagnoses. But you can exclude if:  random urine osmolality <100 mOsm/kg  random urine sodium <20 mmol/L  except in the recovery phase
  43. 43. Low urine Na (and osmo) during recovery phase Onset Maintenance Recovery Serum sodium concentration 24-hour urine sodiumexcretion
  44. 44. Example 1 76-year old admitted with chest infection. Clinically euvolaemic.Day 1 2 3 4 5 6 7S Na 130 125 118 117 119S Osmo 260 250S Urea 5.6 4.3 4.0 4.8S Creat 65 68 58 63S Cort 680U Na 76U Osmo 420
  45. 45. Example 1 Hyponatraemia Clinically euvolaemic No renal failure Normal cortisol Non-low urine sodium and osmolality Could well be SIADH
  46. 46. Example 2 45-year old admitted with D&V. Looks dry.Day 1 2 3 4 5 6 7S Na 130 125 118 117 119S Osmo 260 250S Urea 5.6 6.3 8.0 9.8S Creat 65 68 98 123S Cort 680U Na <20U Osmo 180
  47. 47. Example 2 Hyponatraemia Clinically hypovolaemic Degree of renal failure Normal cortisol Low urine sodium and osmolality History of GI loss
  48. 48. Example 3 76-year old admitted with chest infection. Clinically euvolaemic.Day 1 2 3 4 5 6 7S Na 130 125 118 117 119 124 130S Osmo 260 250S Urea 5.6 4.3 4.0 5.8 6.9 5.8 5.7S Creat 65 68 58 73 76 68 65S Cort 680U Na <20U Osmo
  49. 49. Example 3 Hyponatraemia Clinically euvolaemic No renal failure Normal cortisol Low urine sodium DURING RECOVERY Uninterpretable
  50. 50. Example 4 66-year old with heart failure. Oedematous.Day 1 2 3 4 5 6 7S Na 126 127 125S Osmo 260 260S Urea 9.6 11.3 12.0S Creat 124 136 140S Cort 680U Na 40U Osmo
  51. 51. Example 4 Clinical picture is heart failure So that’s the diagnosis Non-low urine sodium excludes GI loss In steady-state, urine sodium = sodium intake, including if hypervolaemic Fluid restriction is appropriate even if SIADH superimposed
  52. 52. Treatment of hyponatraemia
  53. 53. Treatment of hypotonic, hypovolaemichyponatraemia Hypovolaemic Diuretics Treatment:Renal Primary adrenal failuresodium • Salt and waterloss Primary renal disease Pseudohypoaldosteronism • +/- Glucocorticoids GI (vomiting, diarrhoea)Other Skin (burns, sweating)sodium Third space (pancreatitis)loss Dietary deficiency (anorexia)
  54. 54. Treatment of hypotonic,hypervolaemic hyponatraemia Hypervolaemic Treat underlying cause: Heart failure • e.g. rate control, digoxin Renal • e.g. sepsis Cirrhosis sodium loss Nephrotic Remove fluid: syndrome • paracentesis • diuretics? Other sodium Fluid restrict loss
  55. 55. Treatment of hypotonic, euvolaemichyponatraemia Euvolaemic Treat cause of SIADH: SIADH • e.g. stop drug GlucocorticoidRenal deficiency • e.g. antibiotics orsodium chemotherapy Pregnancyloss Reset osmostat Fluid restrict: Excess water intake Give drugs:Other • demeclocyclinesodiumloss • vaptan
  56. 56. When is acute treatment needed? Sodium Effect 130-135 Usually asymptomatic 120-130 Non-specific malaise <120 Confusion, ataxia, headache Lower Depressed consciousness, seizures, death
  57. 57. When is acute treatment needed?Acute vs chronic (> or < 48 hr) Acute: increased risk of cerebral oedema Chronic: increased risk of CPMCondition Confusion, seizures, other neurologySodium concentration 120 mmol/L is a common thresholdPragmatism Availability of HDU/ICU, and of hypertonic saline
  58. 58. What is acute treatment?Boluses of hypertonic saline If neurologically obtunded 100mL bolus of 3% saline, up to three times Will raise serum Na by 5-6 mmol/LInfusion of hypertonic saline 0.5 ml/kg/hr Will raise serum Na by 7-10 mmol/L/24 hrMohmand et al Clin J Am Soc Nephrol 2007; 2: 1110
  59. 59. What about normal saline? Exacerbates hyponatraemia…? Infusion of 2 litres normal saline Mean pre-treatment Na 126; n=17 Saline seems to help if urine osmolality <500Musch et al Q J Med 1998; 91: 749
  60. 60. What do you do in a normal UKhospital?Serum sodium = 117 mmol/L If significant neurological symptoms, definitely admit to ICU Otherwise: – send serum osmo, cortisol, urine osmo early – zero oral fluid – give 1 litre 0.9% saline initially – monitor Na frequently
  61. 61. Rate of correctionUrgent correction needed e.g. seizures 5-8 mmol/L in the first hourFirst day 8-12 mmol/LFirst 48 hours 12-18 mmol/L
  62. 62. Fluid restrictionIn milder cases, begin at one litre More liberal restriction may be OK if previous fluid intake was highVery tight restriction may be needed E.g. 500ml or zero
  63. 63. Fluid restrictionNeeds to be strict and tight Must be thirsty, or ineffective Will cause rise in urea/creatinine
  64. 64. What happens in SIADH? Compensatory Inappropriate mechanisms – ADH aldosterone etc Salt and Water Water water Water retention excretion Water Salt Salt SaltNormal state Hyponatraemia Hyponatraemia Tendency to Euvolaemia hypervolaemia
  65. 65. What happens in fluid restriction? Aldosterone ↑ Fluid restriction ANP, BNP ↓ Dehydration Salt and water Water retention Water Water Salt Salt Salt Hyponatraemia Hyponatraemia Normal state (but Euvolaemia Hypovolaemia a bit dry)
  66. 66. Demeclocycline Dose 600-1200mg daily Induces nephrogenic DI in 70% of cases Usually 2-3 days to take effect – but can be dramatic onsetProblems Avoid if eGFR<30 Can cause irreversible nephrotoxicity Nausea Photosensitivity Hypersensitivity to tetracyclines (anaphylaxis, urticaria)
  67. 67. Vaptans V2-receptor antagonists Directly inhibit ADH
  68. 68. Vaptans
  69. 69. TolvaptanSALT-1 and SALT-2 trials 448 patients with hyponatraemia Euvolaemic or hypervolaemic CCF, cirrhosis, SIADH Randomized to: – placebo – tolvaptan 15mg od, increased as neededSchrier et al N Eng J Med 2006; 355: 2099.
  70. 70. VaptansSchrier et al N Eng J Med 2006; 355: 2099.
  71. 71. VaptansProblems Few side effects – thirst, dry mouth Cost: – £75-£150 per day – £27,000 to £54,000 per year – to raise serum Na by about 5 mmol/L Restricted use – recurrent profound hyponatraemia
  72. 72. UreaOsmotic diuretic Rapid entry into cells – avoids sudden plasma volume explansion Barely penetrates brain – avoids cerebral oedema 0.5 – 1 g/kg/dayUnavailable in UK 10 cans of baked beans 1kg meat
  73. 73. Why treat chronic hyponatraemia?No decent long-term therapy Why bother? Long-term adaptation to hyponatraemia?But possibly: Gait disturbance Falls Osteoporosis
  74. 74. Gait and hyponatraemia Centre of pressure path, while walking right to left •Before correction (Na 124) •After correction (Na 135) Renneboog et al Am J Med 2006 119 e1-8
  75. 75. Profound cortisol deficiencyCauses SIADH-like picture (or just SIADH?) Cortisol is tonic inhibitor of ADH secretionAcute reversal with glucocorticoid Rapid excretion of free water Rapid rise in serum sodium Risk of myelinolysis
  76. 76. Profound hyponatraemia needsintensive monitoring Frequent checks of serum sodium Meticulous fluid balance If rising too rapidly consider: – stop saline – give dextrose – desmopressin
  77. 77. Cerebral salt wastingDescribed in neurosurgical patients Thought to be mediated by BNP (SIBNP?) Hyponatraemia post SAH Cue scratching of heads Is it SIADH? Is it CSW?
  78. 78. SIADH CSW1. ADH ↑ 1. BNP ↑ causing water retention causing salt and water loss2. Renin, aldo ↓ 2a. ADH ↑ causing salt and water loss causing water retention 2b. Renin, aldo ↑ salt and water retention What’s the difference? Fluid replete Potentially fluid deplete Urine sodium ↑ or normal Urine sodium ↑ or normal Maybe renin, aldo ↓ Maybe renin, aldo ↓ Treatment: fluid restrict or Treatment: saline saline
  79. 79. SIADH and lung cancerPrevalence? 3/23 in a study from KuwaitCXR In allFurther investigation e.g. CT If persistent If other symptoms/signs
  80. 80. Serum osmolality Low (<270) High -treat cause -urea, glucose, toxins Fluid volume statusDeplete Replete Overloaded-history of D&V? - treat cause-diuretics? - CCF, liver-cortisol? Check cortisol, urine osmo, urine NaLow urine osmo RepleteLow urine Na Non-low urine osmoLook for GI loss Non-low urine Na Normal cortisol Probable SIADH – fluid restrict

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