3. The relation between salt and water
Definitions
• Too much salt – EDEMA
– Appropriate response: increase sodium excretion
• Tool little sodium – VOLUME DEPLETION
– Appropriate response: reduce sodium excretion
• Too much water – HYPONATREMIA
– Appropriate response: suppress ADH to increase water
excretion
• Too little water – HYPENATREMIA
– Appropriate response: enhance ADH release and thirst
Elhassan, FACP
4. Osmo-regulation vs. Volume Regulation
Osmo‐regulation Volume regulation
What is sensed Plasma osmolality, primarily Effective tissue perfusion
Plasma Na
Sensors Hypothalamic osmoreceptors Glomerular AA
Carotid sinus
Atria
Effectors ADH Renin‐AII‐Aldo
Thirst SAS
ANP, BNP
What is affected Water excretion Urine Na
Water intake ADH, thirst
Elhassan, FACP
5. Effect of Plasma Osmolality on ADH
Release and Thirst
Elhassan, FACP
6. Hormonal and Urinary Responses to
Cheese and Potato Chips
• Salt intake raises the P Na, which initiates the following responses:
– P Na increases, raising P osmolality
– The increase in P osm pulls water out of cells, increasing the
extracellular fluid volume
– The rise in Posm stimulates both ADH release and thirst, increasing
both urine osmolality and water intake
– The increase in ECF volume raises ANP and reduce the activity of the
renin‐angiotensin‐aldosterone system, raising Na excretion
• The final urine has a lot of Na in a small volume, similar to intake
(steady state achievement)
Elhassan, FACP
8. Major Causes
• Intake of water that cannot be excreted
– Hypovolemic states
– True volume depletion
– Diuretics, particularly thiazides
– CHF and cirrhosis
• SIADH
– CNS disorders
– Malignancy, primarily small cell ca
– Drugs: SSRI, carbamazepine
– Pulmonary infection
– Post‐surgery
– Adrenal insufficiency or hypothyroidism
• Advanced renal failure
• Primarily polydipsia, e.g marathon runners
Elhassan, FACP
9. Initial evaluation of hyponatremia:
Step 1
• Measure P osm – largely determined by P Na
– Low:
• True hyponatremia
– Normal or elevated:
• Pseudohyponatremia (milky serum, hyperproteinemia)
• Hyperglycemia
• Renal Failure
Elhassan, FACP
10. Initial evaluation of hyponatremia:
Step 2
• Urine osmolality
– Less than 100 mosmol/L
• Primary polydipsia with normal water excretion
• Reset osmostat
– Greater than 150 mosmol/L
• Other causes of true hyponatremia in which water
excretion is impaired
Elhassan, FACP
11. Initial evaluation of hyponatremia:
Step 3
• Volume status and urine Na concentration
– Less than 10 mEq/L
• True volume depletion
• CHF or cirrhosis (EABV depletion)
– Greater than 20 mEq/L
• Other causes of hyponatremia in which euvolemia (SIADH)
or renal salt wasting is present
Elhassan, FACP
14. Presentation
• Symptoms:
– Nausea, malaise (120‐125 meq/L)
– Headache, lethargy, obtundation ( 115‐120
meq/L)
– Seizures, coma (<115 meq/L)
• Chronic hyponatremia cause few if any symptoms
Elhassan, FACP
15. Pathophysiology of Hyponatremia
Normotremia: equilibrium
Extracellular fluid ECF
Acute hyponatremia Na/H2O
K, Na, osmolytes / H2O
ECF hypo‐osmolality
K, Na, osmolytes
Na↓/H2O↑ H2O↑
Movement down Chronic hyponatremia
osmotic gradient
ECF hypo‐osmolality K↓, Na↓, osmolytes↓
Na↓/H2O↑ H2O ↓
Brain adapted to new
osmotic equilibrium
Elhassan, FACP
16. Rx of Hyponatremia
• Hypovolemic hyponatremia:
– Volume replacement with isotonic (0.9%) saline
• Hypervolemic hyponatremia:
– Water restriction (1‐1.5 L/d) and diuretics
– Specific treatment for CHF, cirrhosis and advanced
renal failure
Elhassan, FACP
17. Euvolemic Hyponatremia
• Treat the underlying disease
• Fluid restriction (~50‐60% of daily fluid intake to
achieve negative water balance)
• Measures to augment water diuresis
– Salt tablets
– Demeclocycline
– Urea
– V2 receptor antagonists
Elhassan, FACP
18. Long term
management
Identification and Rx of reversible etiologies
Water restriction
Demeclocycline mg BID (allow two weeks for full effect)
Urea 15‐60 g/day
2 receptor antagonists
V
Elhassan, FACP
19. Treating Hyponatremia
Based on acuity and presence vs. absence of symptoms:
– severe neurologic manifestations: (seizures, impaired
mental status or coma)
• hypertonic saline
– Less severe (fatigue, nausea, dizziness, gait disturbances,
forgetfulness, confusion, lethargy, muscle cramps):
• measures above
– “Asymptomatic" with subtle neurologic manifestations
Elhassan, FACP
20. Treatment principles
• Avoid overly rapid correction
– (<10 meq/L 1st 24 hr/<18 meq/L 1st 48 hr)
• Estimate Na deficit
Na deficit = TBW x (desired serum Na ‐ actual serum Na)
• Determine need for urgent correction, if using Hypertonic
saline:
– Contains 513 mEq/L
– 100 mL of as IV bolus to reduce cerebral edema.
– If neurologic symptoms persist or worsen, bolus can be
repeated X1‐2 at 10 min intervals.
Elhassan, FACP
22. Example I
• A 60 years old man has a tumor of the lung and is admitted to
the hospital with a 2 weeks history of progressive lethargy and
obtundation. The physical examination is within normal limits
except for obtundation. The following lab studies were
obtained:
• Na= 105 meq/L, K= 4 meq/L, Cl=72 meq/L, HCO‐3=21 meq/L
• POSM= 222mosmol/L
• UOSM= 604 mosmol/L, UrineNa= 78 meq/L
• What is the most likely diagnosis?
• How would you correct it?
Elhassan, FACP
23. Example II
• A 68 years old diabetic man with congestive
heart failure is seen in the outpatient clinic
with mild peripheral edema. Lab
investigations revealed a plasma Na= 123
meq/L, K=3.7 meq/L and a plasma osmolality
of 268 mosm/kg.
• What is correct therapy?
Elhassan, FACP
26. Hypernatremia
• Symptoms:
Lethargy, Weakness, Irritability, Seizure, Coma,
and Death
• Severity of symptoms depends on:
– The rate of rise in the POSM
– Chronic hypernatremia is asymptomatic due to cerebral
adaptation
Elhassan, FACP
27. Major causes of Hypernatremia
• Impaired thirst or impaired access to water
– Water loss:
• Insensible losses: most common. Seen primarily in
adults with impaired mental status
• Central or nephrogenic DI: urine should be dilute unless
marked hypovolemia
• Osmotic diuresis or osmotic diarrhea
– Sodium retention
• Administration of hypertonic solution
Elhassan, FACP
29. Determine volume status
Hypovolemic or euvolemic Hypervolemic
Water Loss Na retention
Urine osm <300 Urine osm 300- Urine osm
600 >600
Complete DI Renal water losses: Extra-renal water Exogenous NaCl infusion
Diuretics losses: Mineralocorticoid excess
Osmotic diuresis: (glucose, GI
mannitol) Insensible losses
Partial DI
Reset osmostat
Elhassan, FACP
31. Treatment-II
• Replace volume (based on clinical judgment) and replace free water
deficit:
Free water deficit = 0.6 X BW [(Na /140) – 1] (x 0.85 in females)
• D5W, or ½ or ¼ NS to simultaneously provide volume and free
water.
• Replace free water deficit (50% in first 24 h) + ongoing free
water loss
• Slow correction (0.5 meq/L per hour or 12 meq/L per day)
Elhassan, FACP
32. Treatment-III
• Hypervolemic hypernatremia:
– Loop diuretics and dextrose 5% in water.
• Diabetes insipidus (DI):
– Central DI: desmopressin (dDAVP), a long‐acting vasopressin
analog.
– Nephrogenic DI: treat underlying cause; salt and protein
restriction + thiazide diuretics (reduces delivery of filtrate to
diluting segments of kidney).
Elhassan, FACP
33. Why salt/protein restriction in DI for
polyuria and NOT water restriction?
Patient A: extra‐ Patient B: DI
renal water loss
Serum Na 150 meq/L 150 meq/L
Daily Osmole intake 1200 mOsm/d 1200 mOsm/d
Maximum ability of 1200 mOsm/L Partial: 300‐800 mOsm/L
urine concentration Complete: 0‐300 mOsm/L
(Max C)
UOP= daily Osm intake 1200/1200= 1 L P: 1200/300‐800= 1.5‐4 L
Max C C: 1200/0‐300= ∞‐4 L
Elhassan, FACP
34. DDx of Renal Water Loss/Polyuria
Polyuria (UOP > 3 L/d)
UOSM < 800 mOsm/Kg
Osmolar excretion rate (UOP X Uosm)
> 1000 mOsm/d < 1000 mOsm/d
Osmotic diuresis Water diuresis
NaCl, Glucose, Urea, Mannitol DI, Primary Polydipsia
Elhassan, FACP
35. DDx of DI/polyuria
Water deprivation test
P OSM ≥295 mOsm/Kg
U OSM
300‐800 mOsm/kg < 300 mOsm/Kg
Partial DI Complete DI
Primary Polidipsia
DDAVP
~ 50% rise in UOSM No change in UOSM
Partial Central DI Nephrogenic DI
Primary Polydipsia
100‐800% rise in UOSM
Complete Central DI
Elhassan, FACP
40. Transtubular K Gradient (TTKG)
TTKG = UK/Pk X 300/Uosm
o TTKG is one method to assess the renal response to
hypoK or hyperK
o Distal tubule Na delivery is required for an appropriate
renal K response.
o Therefore also check the urine Na; it should be
>20mEq/l for adequate interpretation
TTKG should be >7 if pt is hyperkalemic
TTKG should be <3 if pt is hypokalemic
Elhassan, FACP
50. Hyperkalemia (serum (K+)>5.5 meq/L in the
absence of hemolysis in the blood sample taken)
Severe muscle Serum (K+) 7.0 meq/L or Marked ECG
weakness greater changes
Emergency treatment
Calcium Gluconate NaHCO3, 44‐88 Regular insulin, 5‐ Nebulized salbutamol, 10‐20
10%, 5‐30 ml IV; or meq (1‐2 10 units, plus mg in 4 ml normal saline,
Calcium Chloride 5%, ampules) IV dextrose 50%, 50 inhaled over 10 minutes
5‐30 ml IV ml if plasma
Increase K+ glucose is < 250 Increase K+ entry into cells
Stabilize membrane entry into cells mg/dl
excitability Increase K+ entry
into cells
Elhassan, FACP
51. Serum (K+) ≤6.5 Asymptomatic patient No ECG changes
Non‐urgent treatment
Furosemide, 40‐160 Cation‐exchange resin: Hemodialysis or
mg IV or orally Oral: 15‐30 g in 20% sorbitol (50‐100ml) Peritoneal dialysis
Removal of excess Rectal: 50 g in 20% sorbitol Removal of excess
K+ Removal of excess K+ K+
Dietary K+ restriction (chronically helpful)
Elhassan, FACP
59. Treatment
• Oral KCl supplements
• IV KCl (no more than 10 mEq/hr through
peripheral line, 40 mEq/hr through central line)
• Amiloride or spironolactone may be useful in
patients with hyperaldosteronism
Elhassan, FACP
66. S. Ca >12 mg/dL
NS at 200 to 300 Calcitonin (4 IU/kg) Zoledronic acid
ml/hr Remeasure s. (4 mg IV over 15
Adjust NS to calcium in several minutes)
maintain UO at 100‐ hours Or
150 ml/hr If a hypocalcemic pamidronate
Furoemide to response is noted (60 to 90 mg
patients who are, or may repeated over two hours)
who get fluid‐ calcitonin every six
overloaded on this to 12 hours
regimen
Check Ca frequently.
If persistent or recurring
hypercalcemia consider
Chemotherapy or Hemodialysis with little or no
radiation therapy calcium in the dialysate
for malignant Peritoneal dialysis
hypercalcemia
Consider early dialysis in patients with
severe malignancy‐associated
hypercalcemia CKD or CHF where
hydration cannot be safely administered
Elhassan, FACP
