Polyuria and hypernatremia

Question 1

Water and Na balance

Answer 1

• Abnormal total body water generates hyponatremia (too much water) or hypernatremia (too little water)
• Regulated by ADH
• D/o of Na balance leads to volume contraction (too little Na) or volume expansion (too much Na) and is regulated by RAAS
• Hypernatremia almost always due to too little TBW (too much water loss, or not enough water consumption)

Question 2

Total body water

Answer 2

• TBW is 60% of body mass for men and 50% body mass for women
• 2/3rds of TBW in cells
• 1/3rd of TBW in ECF (25% of this in plasma, 75% in ISF)

Question 3

Regulation of total body sodium

Answer 3

• RAAS regulates Na reabsorption in distal tubule (increases it)
• RAAS activated due to low ECFV, low renal perfusion
• ADH regulates amount of total body water (increases H2O reabsorption), and is activated by small increases in serum osmolality and large decreases in blood volume
• Other factors can activate ADH release: emotion, CHF, liver disease, drugs, nausea/vomiting, pain/stress, ATII

Question 4

ADH production and release

Answer 4

• Produced and released by paraventricular and supra ventricular nuclei of the hypothalamus (incl. supraoptic nucleus)
• Enters the hypothalamus capillaries to be moved to post pituitary, then enters systemic circulation
• ADH uses the osmotic Na gradient set up by TAL to increase H2O reabsorption by increasing AQP expression in CD

Question 5

Polyuria

Answer 5

• Urine output >3L/day and excess loss of free water
• Causes: osmotic (uncontrolled DM, hyperosmolar contrast, osmotic diuretics like manitol, excess electrolytes) and water-genic (psychogenic polydipsia, central diabetes insipidus, nephrogenic diabetes indipidus)

Question 6

Diabetes insipidus

Answer 6

• Very low Na content in urine, lots of excess water excreted
• Urine Na is low, but serum Na can be normal or high
• Causes can be central or nephrogenic

Question 7

Central diabetes insipidus

Answer 7

• Decreased ADH production due to hypothalamic or post pituitary lesion
• Will have low ADH levels
• Possible causes: surgery, trauma, tumors, CVA, infection, mutations

Question 8

Nephrogenic diabetes insipidus

Answer 8

• Inability of kidney to respond to ADH
• Will have high ADH levels
• Causes: electrolyte d/o (hypokalemia, hypercalcemia), tubulointerstitial nephropaties (SCD, myeloma, obstructions, Li Rx, acute kidney injury)
• Familial mutations can cause it (V2 receptor, AQP2)

Question 9

Water deprivation test and exogenous ADH 1

Answer 9

• To distinguish btwn causes of water diuresis, deprive pt of water then administer ADH
• If psychogenic there is no point in giving ADH, since the body is already overloaded with water that ADH levels are near zero as they should be, leading to a very dilute urine
• The body is working fine (i.e. getting rid of the excess water normally since ADH response is appropriately turned off), but the pt is drinking too much water
• Psychogenic polydipsia does not cause hypernatremia, but does cause hyponatremia (too much water)

Question 10

Water deprivation test and exogenous ADH 2

Answer 10

• In central DI, administration of DDAVP will increase urine osm since the kidneys can respond to the DDAVP normally, but the brain is not producing its own ADH (ADH levels are inappropriately low- whats causing the polyuria)
• Thus administration of DDAVP will cause water retention as expected and increase Uosm
• If nephrogenic DI, the DDAVP will not affect urine osm, since the kidneys cannot respond to the DDAVP properly and will not reabsorb the water (urine remains dilute)
• Since kidneys cannot respond to ADH must find alternative way to reabsorb water (thiazides)

Question 11

Rx of polyuria

Answer 11

• Psychogenic: decrease water consumption
• Central DI: give DDAVP plus adequate H2O intake
• Nephrogenic: increase proximal water reabsorption by low Na diet and thiazide diuretic plus adequate H2O intake
• If osmotic diuresis: remove osmolar load

Question 12

Thiazide diuretics in nephrogenic DI pts

Answer 12

• Thiazides reduce free water excretion in two ways
• They cause mild volume contraction by increasing excretion of Na, which increases H2O reabsorption in PT
• They impair urinary dilution by increasing expression of AQP2 in CD

Question 13

Hypernatremia 1

Answer 13

• Serum Na > 145mEq/L
• Pathogenesis is water intake less than water excretion: net water loss
• Decreased water intake plus water loss stimulates osmoreceptors (increases serum osmolality), results in posterior pituitary ADH release
• ADH binds to CD V2 receptors and leads to insertion of AQP2 to increase water reabsorption
• This increases urine osm and decreases free water excretion

Question 14

Hypernatremia 2

Answer 14

• This process can be interfered w/ at various stages to cause hypernatremia, it could be renal (osmotic diuresis, DI), or extra renal (GI/sweat)
• Central DI prevents ADH release
• Nephrogenic DI prevents ADH from binding to V2 and/or inserting AQP2

Question 15

Central affects of ADH

Answer 15

• As ADH is released due to small increases in serum osm, there is stimulation of thirst
• Hypothalamic lesions can prevent the thirst response
• Even if thirsty, there may be no access to water which will prevent correcting hypernatremia

Question 16

Hospitalized pts

Answer 16

• They may be receiving IV hypertonic solutions containing Na w/o adequate H2O administration
• This increases Sosm and leads to shift of H2O from ICF to ECF

Question 17

Clinical manifestations of hypernatremia

Answer 17

• As high [Na] in ECF pulls H2O from ICF, cells in the brain begin to shrink b/c they are losing water
• There can be rupture of cerebral veins and intracranial hemorrhage leading to neuro damage
• There can be lethargy, weakness, seizures, coma, and death

Question 18

Compensatory mechanisms for hypernatremia

Answer 18

• As the brain shrinks the cells begin to increase intracellular organic osmoles, which increase ICosm
• This shifts the water back to ICF to normalize brain volume

Question 19

Dx the cause of hypernatremia

Answer 19

• Hx: Sx of thirst, decreased access to water, polyuria/polydipsia, diarrhea, diuretics
• Break down Dx based on Urine osm
• Either the Uosm is 800 (H2O loss from elsewhere- extra renal problem) + decreased water intake

Question 20

Renal causes of hypernatremia

Answer 20

• Either central or nephrogenic DI, use water restriction + DDAVP to Dx (also ADH levels ?)
• Can also be osmotic diuresis (due to glc, urea, mannitol, contrast)

Question 21

Calculation of free water deficit

Answer 21

• First calculate TBW: 60% or 50% (man vs women) of Kg body weight
• then TBW x (Na - 140)/140
• Ex: 42 x (172 - 140)/140 = 9.6 L water deficit
• Replace 1/2 free water deficit every 24 hrs plus ongoing losses
• Do not decrease Sna more than .5 mEq/L per hour or 8-10 per day to avoid cerebral edema
• Ongoing losses: all insensible losses, all vomiting and suction, and 1/2 diarrhea and 1/2 urine output

Question 22

Management of hypernatremia

Answer 22

• Rx underlying cause (water intake less than water loss)
• CDI: demopressin
• NDI: Na restriction, thiazides, amiloride, desmopressin

Question 23

Key points of hypernatremia

Answer 23

• Always intake < output
• Decreased water intake secondary to impaired thirst or limited access to water
• DI does not normal cause hypernatremia unless water intake is limited
• Rapid correction of hypernatremia may induce cerebral edema