1. Case discussion
and topic review
Presenter Dr. Pradip Katwal
Moderator Dr. Thomas John
Dept of internal medicine
BPKIHS DHARAN,NEPAL

2. • 67 yrs female
• Presenting complains-
fever- 4 days
vomiting-4 days
loose stool-4 days ( for 2 days)
Past h/o- no significant illness

3. Case summary
• Elderly lady without significant pass illness
presented to emergency with h/o low grade
fever without chills and rigors, multiple
episodes of non-projectile vomiting
associated with nausea and watery stool not
containing blood or mucus for initial two day
and has not passed stool since then. She also
complains of weakness and was unable to sit
from the supine position.
• No headache, no seizures, no abdominal pain
• H/o of treatment in local hospital for two days
before presentation.

4. At Presentation CHEST- b/l symmetrical and
equal air entry
B/l normal vesicular
breath sounds
• Gcs-14/15 no crepts
• Pulse-113 beats/min CVS - apical impulse 5th ics
• B.P-80/40 mmhg medial to MCL
(supine) S1 S2 M(-)
P/A- Soft non tender
• Afebrile
no organomegaly
• Rr-18 breath/min Bowel sound-sluggish
• JVP-not visible CNS-GCS 14/15
higher mental function
cranial nerve- normal
• Pallor(+)
motor-
dehydration(+) Power 3/5
skin turgor decreased proximal musle of b/l limbs
Rest-WNL
sensory-intact
no nuchal rigidity

5. PROVISIONAL DIAGNOSIS
• ACUTE INFECTIVE GASTROENTERITIS
IN PRESENTED IN HYPOVOLUMIC
SHOCK

6. Initial management
Inj. Normal saline 1 liter iv bolus
Then Inj.NS 5OO ml iv 6 hourly
Inj.5%dextrose 500 ml 8 hourly
Inj. Ciprofloxacin 200 mg iv BD
Inj. Metronidazole 500 mg iv TDS
Inj Pantoprazole 40mg iv OD

7. INVESTIGATIONS
• HB-12.2 • SUGAR-84
• UREA-41
• TLC-14600/MM3 • CREATININE-0.8
• DLC-N70,L30 • NA-118
• PT-179000/mm3 • K-2.5
• ABG-
• URINE RE/ME-WNL • PH-7.288
• STOOL RE/ME- • HCO3-14.6
SENT TO CENTRAL • PCO2-28.4
• LACTATE-1.0
LAB

8. DIAGNOSIS
• ACUTE INFECTIVE GASTROENTERITIS IN
HYPOVOLUMIC SHOCK WITH
DYSELECTROLYTEMIA
-HYPOKALEMIA
-HYPOOSMOLAR HYPOVOLUMIC
HYPONATREMIA
-METABOLIC ACIDOSIS
-PARALYTIC ILEUS

9. Management
Inj. Normal saline 1 liter iv bolus
Then Inj.NS 5OO ml iv 6 hourly with 30meq KCl in
each pint
Inj.5%dextrose 500 ml 8 hourly
Inj. Ciprofloxacin 200 mg iv BD
Inj. Metronidazole 500 mg iv TDS
Inj Pantoprazole 40mg iv OD
 Inj 3%NS 100 ml TDS

10. DAY 3 OF ADMISSION
• Subjective- Multiple • Sugar-108
episodes of vomiting
• Urea-13
• Bowel sounds-sluggish
• Creatinine-1.0
• Proximal muscle weakness • Na-121
• K-2.5
• PULSE-98 • Stool re/me-WNL
• B.P.-90/60 mmhg
• Afebrile
• 16 breath/min
• Urine output-400ml

11. DISORDERS OF
SODIUM BALANCE

12. HYPONATREMIA
• Hyponatremia is defined as a plasma
[Na+] < 135 mEq/L

13. Hyponatremia
• Physiology of Serum sodium concentration
regulation:
1. Renin-angiotensin-aldosterone system
2.Stimulation of thirst
3.Renal handling of filtered sodium
4.Secretion of ADH

14. Hyponatremia
• Epidemiology: ocw.jhsph.edu
▫ Frequency
 Hyponatremia is the most common
electrolyte disorder
 Occurring in 22% of hospitalized
patients.

15. Clinical features
• Symptoms primarily neurological
▫ Nausea
▫ Vomiting
▫ Headache
▫ Seizure
▫ Coma

16. Hyponatremia
• Types
▫ Hypovolemic hyponatremia
▫ Euvolemic hyponatremia
▫ Hypervolemic hyponatremia
▫ Low solute intake and hyponatremia
▫ Pseudohyponatremia

17. Osmolality
• Calculated Plasma Osmolality:
P osm = 2 (Na) + glucose/18 + BUN/2.8
Normal = 290 (275-290 mM)
• Measured osmolality (MO)
▫ Osmolality measured by osmometer.
▫ works on the method of depression
of freezing point.
• Urine Osmolality:
 Normal: 400-500 mM
▫ Maximal dilution 50-100 mM
▫ Maximal concentration 900-1200 mM

18. Hyponatremia
Serum OSM
LOW NORMAL HIGH
Marked
Hypotonic hyperlipidemia Hyperglycemia
hyponatremia Hyperproteinemia Mannitol

19. Pseudohyponatremia
Pseudohyponatremia is laboratory error
due to high content of plasma proteins
and lipids
Expansion of nonaqueous portion of the
plasma sample
Errant report of a low ECF [Na+]

20. Hyponatremia
Serum OSM
LOW NORMAL HIGH
Marked
Hypotonic hyperlipidemia Hyperglycemia
hyponatremia Hyperproteinemia Mannitol

21. Hyperosmolar hyponatremia
Osmotically active solute other than sodium
accumulates in the ECF, drawing water into
the ECF and diluting the Na+ content.
 Glucose
 Glycine
100 MG/DL RISE IN FALL IN PLASMA [NA+]
Mannitol
PLASMA GLUCOSE OF 1.6 TO 2.4 MEQ/L
Sorbitol

22. Hyponatremia
Serum OSM
LOW NORMAL HIGH
Marked
Hypotonic hyperlipidemia Hyperglycemia
hyponatremia Hyperproteinemia Mannitol

23. RESET OSMOSTAT
Set point for plasma osmolality is reduced.
ADH and thirst responses maintain osmolality
at this lower level.
 This phenomenon occurs in almost all
pregnant women

24. PSYCHOGENIC POLYDIPSIA
Urine cannot be diluted to an osmolality less
than ~50 mosm/l
 A small amount of solute is required in even
the most dilute urine.

26. Assessment of
volume status
hypovolemia Euvolemia hypervolemia
U na >20
Una <20
RENAL LOSSES
Diuretic excess EXTRA RENAL LOSSES
Mineralocorticoid deficiency Vomiting
Salt losing deficiency DIARRHOEA
Ketonuria THIRD SPACING
Osmotic diuresis BURNS,PANCREATITIS,TRAUMA
Cerebral salt wasting syndrome

27. HYPOVOLEMIC HYPONATREMIA
Develops as sodium and free water are lost
and/or replaced by inappropriately
hypotonic fluids

28. Assessment of volume
status
hypovolemia Euvolemia hypervolemia
Acute or chronic renal
U Na >20 failure
NEPHROTIC
SYNDROME
U Na<20 CIRRHOSIS
Cardiac failure

29. Assessment of
volume status
hypovolemia Euvolemia hypervolemia
U Na >20
Glucocorticoid deficiency
Hypothyroidism
Stress
Drugs
Syndrome of inappropriate ADH secretion

30. WHAT is inappropriate about
SIADH?
Despite the absence of osmotic or volume-related stimuli
Nonphysiologic release of vasopressin from the posterior
pituitary or an ectopic source

36. Cerebral salt-wasting
 Hyponatremia in cns disease particularly in
patients with subarachnoid hemorrhage
Characterized by hyponatremia & extracellular
fluid depletion due to inappropriate sodium
wasting in the urine

37. Cerebral Salt Wasting
• Cerebral disease (particularly SAH)
• Mimics SIADH with hyponatremia except
primary defect is salt wasting not water
retention.
• Treatment is NS to correct ECFv contraction

38. SIADH CSW
Urine Output decreased polyurea
Serum Na low low
Urine Na high high
Serum osm low low
Urine osm high high
CVP high low

39. Treatment
• Distinction between CSW & SIADH is critically
important since the two disorders are managed
differently
▫ fluid restriction, the usual first-line therapy for
SIADH, may increase the risk of cerebral infarction
among patients who actually have CSW
▫ Volume repletion with isotonic saline is the
recommended therapy in CSW, since it will suppress
the release of ADH, thereby permitting excretion of the
excess water and correction of the hyponatremia

40. Diagnostic Testing for classification
 Plasma osmolality
 Urine osmolality
 Urine sodium concentration
 Diagnosis of underlying cause
 CT head, EKG, CXR if symptomatic
 CT scan
 Urea ,Creatinine
 Serum potassium levels
 Uric acid
 TFT

41. Treatment of Hyponatremia
• Issues to be addressed
 Asyptomatic vs. Symptomatic
 Acute (within 48 hours) vs. Chronic (>48
hours)
 Volume status
 Monitoring response to intervention

42. calculations
• Calculation: Total Body Water (TBW)
▫ Men
 TBW = 0.6 x (kilograms Lean Body Mass)
▫ Women
 TBW = 0.5 x (kilograms Lean Body Mass)
• Calculations based on Total Body Water
(TBW)
▫ Total Body Water Excess (Hyponatremia)
 Normal TBW = TBW x (Serum Sodium / 140)
 Excess TBW = TBW - Normal TBW
▫ Free Water Deficit (Hypernatremia)
 FWD = TBW x (Serum Sodium - 140) / 140
• Calculations: Total Body Sodium Deficit
▫ Sodium deficit = TBW x (140 - Serum Sodium)

43. EXAMPLE
A 70 years old women is having seizure,her serum sodium is 100 Meq/l.her
body wt is 60 kg.
INITIAL GOAL-
Increase the sodium concentation to 116 meq or symptoms resolution
ESTIMATE TOTAL BODY WATER
O.45 * 60=27
ESTIMATE CHANGE IN SERUM SODIUM
(USING one liter of 3% hypertonic saline)
(531-110)/(27+1)=14.39
SYMPTOMATIC PATIENT SO RATE IS 1 MEQ/L/HR FOR NEXT THREE
HOUR
For 14.39 meq change - lt. of hypertonic saline 1 lt.
For 3 meq change –lt.of hypertonic saline used is (1/14.39)*3
Rate of administration for 3 hours
208/3=69.33 ml/hr

44. Rx Hyponatremia
• When do you need to treat quickly?
▫ Acute (<24h)
▫ severe (< 120 meq/L)
▫ Symptomatic hyponatremia (seizures, coma, etc.)
• “Quickly” by:
▫ 3% NS, 1-2 mEq/L/h until:
 Till Symptoms stops
 3-4h elapsed and/or Serum Na has reached 120 mEq/L
• Then SLOW down correction to 0.5 mEq/L/h with
0.9% NS or simply fluid restriction.
• Aim for overall 24h correction to be < 10-12 mEq/L/d
to prevent myelinolysis

45. Treatment Hyponatremia
• Act slowly (correct < 0.5 mEq/L/h, 10-12 mEq/L/d)
▫ Symptomatic/Acute: rapid Rx has resolved symptoms and
brought serum Na up to 120 mEq/L
▫ Asymptomatic, mild, chronic hyponatremia
▫ Want to prevent myelinolysis
 Increased risk: Women, alcoholics, malnourished
• ECFv contracted
 Bolus NS until BP, HR, JVP stable
 Then correct slowly with 0.9% NS or salt tablets

46. SIADH
Treatment
• Fluid Restriction
• Oral Salt, Hi-protein diet or Urea(30 g/d
• Lasix 20 mg po od-bid
• Demeclocycline 300-600 mg bid)
• Lithium

47. • Tolvaptan
• Most appropriate for significant and persistant
SIADH not responding to furesomide, salt
tablets and water restriction

48. • WATER RESTRICTION.
• The amount of fluid restriction necessary depends on the extent
of water elimination.
▫ If (Urine Na + Urine K)/Serum Na < 0.5, restrict to 1 L/d.
▫ If (Urine Na + Urine K)/Serum Na is 0.5 to 1.0, restrict to
500 mL/d.
▫ If (Urine Na + Urine K)/Serum Na is >1, the patient has a
negative renal free water clearance and is actively
reabsorbing water.

49. Osmotic Demyelination Syndrome
due to Rapid correction
Neurologic Features
 flaccid paralysis
 Dysarthria
 dysphagia.
Diagnosis
 suspected clinically
 can be confirmed by neuroimaging .
Treatment
 No effective therapy
 aggressive plasmapheresis

50. Osmotic Demyelination Syndrome
 chronic hyponatremia
 most susceptible to ODS
 Administration of hypertonic saline
 sudden osmotic shrinkage of brain cells.
 Risk factors
▫ prior cerebral anoxic injury,
▫ hypokalemia,
▫ Malnutrition
▫ chronic alcoholism.
• Prognosis
▫ 50% mortality

52. Hypernatremia
(Na+ > 145 mEq)

53. Introduction
• Caused by a relative deficit of water in
relation to sodium which can result from-
Iatrogenic
sodium
loading
Net water
loss

54. Causes of Hypernatremia
Net water loss
Pure water loss
•Unreplaced insensible losses (dermal and respiratory)
• 10ml/kg per day
•Exercise
•Fever
•heat exposure
•mechamical ventilation

55. Central diabetes insipidus
•Post-traumatic
 Tumors
Cysts
Histiocytosis
Tuberculosis
Sarcoidosis
 Idiopathic
 Aneurysms, meningitis, encephalitis

56. Nephrogenic diabetes insipidus
• Congenital
• Mutation
•
▫ X-linked V2 receptors
▫ aquaporin 2 water channel
▫ Aquaporin one channel

58. • Acquired
Renal disease (e.g. medullary cystic disease)
Hypercalcemia
Hypokalemia
Drugs (lithium, demeclocycline, foscarnet,
methoxyflurane, amphotericin B, vasopressin V2-
receptor antagonists)

59. • Adipsic diabetes insipidus
• Central defect in osmoreceptor function
• Both AVP secretion and thirst
• Gestational diabetes insipidus
• Late pregnancy
• Placental protenease have vasopressinase activity

60. Causes of Hypernatremia (cont’d)
 Hypotonic fluid loss
• Renal causes
Loop diuretics
Osmotic diuresis (glucose, urea, mannitol)
Post-obstructive diuresis
Intrinsic renal disease

61. Hypotonic Fluid Loss (cont’d)
• Gastrointestinal
Vomiting
Nasogastric drainage
Enterocutaneous fistula
Diarrhea
Use of osmotic cathartic agents (e.g.,lactulose)
• Cutaneous
Burns
Excessive sweating

62. Causes of Hypernatremia (cont’d)
Hypertonic sodium gain
Cushing’s syndrome
Primary hyperaldosteronism
Hypertonic sodium bicarbonate infusion
Ingestion of sodium chloride
Ingestion of sea water
Sodium chloride-rich emetics
Hypertonic dialysis

63. Clinical Manifestations
• CNS dysfunction
▫ Depend on large or rapid increases in serum
Na+ concentration (acute and chronic)
▫ Few symptoms until Na+ > 160
▫ Affects extremes of ages
▫ Altered mental status
▫ seizures
• confusion
• coma
• Subarachnoid hemorrhages
• Rabdomyoslsis

64. Diagnostic approach
• Presence of thrist?
• Polyuria?
• Source of extra-renal loss
• Deatiled neurological examination
• Extracellular fluid volume Assesment

65. ECF VOLUME
INCREASED NOT INCREASED
ADMINISTRATION ?MINIMUM VOLUME
OF MAXIMALLY
OF HYPERTONIC CONCENTRATED
NACL OR NACO3 URINE

66. MINIMUM VOLUME OF MAXIMALLY CONCENTRATED
URINE
Insensible water loss URINE OSMOLE no
Gastrointestinal water
loss EXCERTION RATE<750
Remote renal water loss
mosoml/day
yes Renal response to
Diuretic no
Osmotic diuresis desmopressin
Unire osmolality Urine
increase osmolality
unchanged
Central diabetes insipidus Nephrogenic diabetes insipidus

67. DIAGNOSIS FOR HYPERNATREMIA
• Renal response to hypernatremia is small volume of concentrated
(urine osmolality > 800 mOsm/L) urine.
can occur from
urine osmolality <300 A suggests complete
mOsm forms of CDI and NDI
Urine osmolality between Partial forms of DI as well
300 and 800 mosm/L as osmotic diuresis.
The two can be differentiated by quantifying the daily solute excretion
(estimated by the urine osmolality × urine volume in 24 hours).
 A daily solute excretion > 900 mOsm defines an osmotic diuresis.

68. DIAGNOSIS FOR HYPERNATREMIA
RESPONSE TO to hypernatremia is a small volume of concentrated
The appropriate renal response
DDAVP
(urine osmolality > 800 mOsm/L) urine.
Submaximal urine osmolality (<800 mOsm/L) suggests a defect in renal water
Complete forms of CDI and NDI can be distinguished
conservation. by
administering the vasopressin analog dDAVP (10 mcg
intranasally) after careful mOsm in the setting of hypernatremia suggests
A urine osmolality <300 water restriction.
complete forms of CDI and NDI.
Urine osmolality between 300 and 800 mOsm/L can occur from partial
The urine as well as osmotic diuresis.
forms of DI osmolality should increase by at least 50% in
complete CDI and does not change in NDI. The diagnosis is
sometimes difficult when partial defectsdaily solute excretion (estimated by
The two can be differentiated by quantifying the are present.
the urine osmolality × urine volume in 24 hours).
A daily solute excretion > 900 mOsm defines an osmotic diuresis.

69. Lab measurements
• Serum and urine osmolality
• Urine electrolytes
• Water deprivation test
• Response to DDAVP

70. Management
A two-pronged approach:
• Addressing the underlying cause: stopping GI
loss, controlling pyrexia, hyperglycemia,
correcting hypercalcemia or feeding preparation,
moderating lithium induced polyuria
• Correcting the prevailing hypertonicity: rate of
correction depends on duration of
hypernatremia to avoid cerebral edema

71. Correction of Hypernatremia
• Hypernatremia that developed over a period of
hours (accidental loading)
▫ Rapid correction improves prognosis without
cerebral edema
▫ Accumulated electrolytes in brain rapidly
extruded
▫ Reducing Na+ by 1 mmol/L/hr appropriate

72. Rate of Correction (Cont’d)
• Hypernatremia of prolonged or unknown
duration
▫ A slow pace of correction prudent
▫ Full dissipation of brain solutes occurs over
several days
▫ Maximum rate 0.5 mmol/L/hr to prevent cerebral
edema
▫ A targeted fall in na+ of 10 mmol/L/24 hr

73. Goal of Treatment
• Reduce serum sodium concentration to 145
mmol/L
• Make allowance for ongoing obligatory or
incidental losses of hypotonic fluids that will
aggravate the hypernatremia
• In patients with seizures prompt anticonvulsant
therapy and adequate ventilation

74. Administration of Fluids
• Preferred route: oral or feeding tube
• IV fluids if oral not feasible
• Except in cases of frank circulatory
compromise, isotonic saline is unsuitable
• Only hypotonic fluids are appropriate-pure
water, 5% dextrose, 0.2 % saline, 0.45% saline-
the more hypotonic the infusate, the lower the
infusion rate required

75. ▫ CORRECTION OF HYPERNATREMIA IS
ACCOMPLISHED BY CALCULATING FREE
WATER DEFICIT BY THE EQUATION:
• The change in [Na+] from the administration of fluids can
be estimated as follows:
• Δ[Na+] = {[Na+i] + [K+i] - [Na+s]} ÷ {TBW + 1}

76. WATER DEFICIT
Ongoing water losses:- (kg) by
I. TBW is estimated by multiplying lean weight
Management of hypernatremia
0.5 in men (rather than 0.6) and 0.4 in women.
Insensible loss-
CALCULATE ELECTROLYTE FREE WATER CLEARANCE
• Water deficit + ongoing water loss +insensible
II.Free water deficit = ml/kg - 140)/140} × (TBW)
1o {([Na] per day
loss
C H2O= V(1-UNa+Uk)/PNa
• Correct the water deficit over 48 to 72 hours
• Avoid correction of plasma Na by >10 mM/day

77. Diabetes insipidus is best treated by removing the
underlying cause
I. CENTRAL DIABETES INSIPIDUS
Administration of dDAVP, a vasopressin
analog.
II. NEPROGENIC DIABETES INSIPIDUS.
A low-Na+ diet combined with thiazide diuretics will
decrease polyuria through inducing mild volume
depletion.
Decreasing protein intake will further decrease urine
output by minimizing the solute load that must be
excreted.

78. HOSPITAL COURSE
• PATIENT IMPROVED DURING HER COURSE
OF STAY IN HOSPITAL BUT HAD PERSITANT
HYPOKALEMIA AND WEAKNESS OF
PROXIMAL MUSCLE DESPITE POTASSIUM
SUPPLEMENT.
D5 D6 D7
SODIUM 130 140 145
POTASSIUM 3.1 3.1 3.8
UREA 49 10
CREATININ 1 O.7
E

79. • DUE TO PERSISTEN HYPOKALEMIA SERUM
MAGNESIUM LEVELS WAS EVALUATED
CALCIUM MAGNESIUM
DAY 7 6.9 O.41
DAY 8

80. Mechanism of Hypokalemia in
Magnesium Deficiency

81. DAY 8 ADMISSION
• SHE IMPROVED GRRADUALLY
• NO DIFFICULTING IN LIFTING HER HEAD
• NO DIFFICULTY IN WALKING
PATIENT WAS DISCHARGED ON DAY 9.

82. •Thank you

83. Refrences
• HarrisonsPrinciples.of.Internal.Medicine.18th.E
dition
• Raoof Manual of critical care
• Washington Manual® of Medical Therapeutics,
The, 34rd Edition.
• HYPONATREMIA REVIEW ARTICLE, Adrogué
HJ, Wesson DE. The New England Journal of
Medicine 2004:205-84