Pathophysiology of Water Handling

Question 1

Plasma sodium definition

Answer 1

• concentration term; not a measure of total body sodium content
• [ECF Na] = ECF Na / ECF H₂O
• low plasma sodium ==> deficit of sodium and/or relative excess of water

Question 2

Serum osmolality definition/relationship to sodium

Answer 2

• Sodium = most abundant cation in ECF ==> concentration is major determimnant of tonicity/osmolality
• Sosm (mosm/kg) = 2xNa + (BUN/2.8) + (Glucose/18)
• tonicity of ECF reflects the tonicity of cells bc water flows freely accross cellular membranes

Question 3

Normal urine diluting system

Answer 3

• normal fxn of the diluting segment: dilution @ water-imp. ascending LOH + distal convoluted tubule via reabsorption of NaCl
• normal delivery to diluting segment: normal GFR + proximal reabsorption
• absence of vasopressin ==> collecting duct remains impermeable to water ==> water remains and dilutes urine

Question 4

Normal maximal ability to dilute urine

Answer 4

• maximal free water excretion + ~20% of GFR
  
  • normal renal fxn ==> 24L/day
  • impaired renal fxn (e.g. 20% of normal GFR) ==> 4 L/day
• **excessive water intake alone does not cause hyponatremia unless it exceeds 1L/hr (in patients w/normal renal fxn)

Question 5

Normal renal concentrating mechanism

Answer 5

• allows for excretion of urine concetration = 4 x plasma ==> 1200 mOsm/kg H₂O
• ability to generate hypertonic interstitium: LOH active transport of chloride
• secretion of ADH: renders collecting duct permeable to water
• collecting duct response to ADH

Question 6

ADH: osmoregulation vs. volume regulation

Answer 6

• increases collecting duct permeability ==> water reabsorption
• is released in response to hyperosmolality and volume depletion
• **after about 6-7% volume depletion, the “volume response” dominates the “osmolality response.” **
• ADH is normally osmoregulatory, but during stress becomes a volume regulatory hormone.

Question 7

Characteristics of Hypertonic Hyponatremia

Answer 7

• shift of water from cells in response to a non-sodium solute ==> e.g. glucose
• hyperglycemia, mannitol or glycerol
• per 100 mg/dL serum glucose increase, serum sodium falls 1.6 mEq/L

Question 8

Characteristics of Isotonic Hyponatremia

Answer 8

• =hyponatremia w/normal plasma osmolality
• caused by [lab artifiact] in association with hyperlipidemia or hyperproteinemia (i.e. multiple myeloma)

Question 9

Type of hypotonic hyponatremia

Answer 9

• Hypervolemic: TB Na+; TB water ++
• Euvolumemic: TB Na; TB water+
• Hypovolemic: TB Na - -; TB water -

Question 10

Characteristics of hypovolemic hypotonic hyponatremia

Answer 10

• =low total body sodium (+clinical low ECF volume)
• renal loss (U_Na>20)
  
  • diuretic overuse
  • salt-losing nephritis
  • osmotic diuresis
• extrarenal loss (U_Na<20)
  
  • GI loss

Question 11

Characteristics of Hypervolemic Hypotonic Hyponatremia

Answer 11

• =increased total body sodium + clinically increased ECF volume
• CHF, cirrhosis, nephrotic syndrome, advanced chronic or acute renal failure
  
  • decreased in effective vascular volume ==> release of ADH ==> excess volume
• characterised by edema

Question 12

Characteristics of Euvolemic Hypotonic Hyponatremia

Answer 12

• =normal total body sodium + clinically normal ECF volume
• ADH secretion is increased despite absence of stimuli
• Hypothyroidism
• Drugs: Nicotine, SSRI, antipsychotics
• adrenal insufficiency
• primary polydipsia
• SIADH (syndrome of inappropriate ADH)

Question 13

Diseases that may cause SIADH

Answer 13

• carcinomas
  
  • lung (small cell)
  • duodenum
  • pancreas
• Pulmonary diseases
  
  • pneumonia
  • abcess
  • TB
  • ventilation
• CNS disorders
  
  • meningitis
  • enchephalitis
  • psychosis
  • trauma

Question 14

Signs of hyponatremia

Answer 14

• GI complaints: anorexia, nausea, vomiting
• altered sensorium
• seizures

Question 15

Treatment of hyponatremia

Answer 15

• dietary water restriction
• correct causative disorder
• hypertonic NaCl w/ or w/out furosemide (not too quickly)

Question 16

Main root causes of hypernatremia

Answer 16

• =elevated sodium plasma concentration
• ADH is decreased/ineffective
• Daily water intake is less than required to compensate for normal losses

Question 17

Types of hypernatremia

Answer 17

• Decreased TB Na
• Normal TB Na
• Increased TB Na

Question 18

Hypernatremia w/decreased total body Na

Answer 18

• total body water loss >> TB salt loss
• GI loss (diarrhea), skin loss (burns), diuretics w/out sufficient water intake

Question 19

Hypernatremia w/increased total body Na

Answer 19

• rare
• usually due to hypertonic fluid e.g. sodium bicarbonate or hypertonic saline

Question 20

Hypernatremia w/normal total body Na

Answer 20

• Central diabetes insipidus = ADH deficiency
  
  • most cases = idiopathic
  • other causes: head trauma, surgery, neoplasm
  • urine volume = 3-15L/day
  • kidneys respond to exogenous ADH
  • complete ==> [urine] < 200 mOsm/kg
  • partial can concentrate but not maximally
• Nephrogenic DI = collecting duct does not respond to ADH
  
  • will not respond to exogenous ADH
  • congenital or acquired
  • causes: chronic renal failure, hypercalcemia, hypokalemia, drugs

Question 21

Clinical presentation of hypernatremia

Answer 21

• cellular dehydration = water out of cells
• neuromuscular irritability = twitches, hyperreflexia, seizures
• ==> coma, death

Question 22

Tx of hypernatremia

Answer 22

• aim = restore serum tonicity to normal + correct sodium imbalance
• water needed (L) = 0.6 x weight (kg) x [(actual Na/desired Na) - 1]
• restore water slowly to avoid cerebral edema