Pathophysiology of H20 Handling

Question 1

Na is the main determinant of serum osmolality. What is the normal range for serum osmolality?

What is the equation to calculate it?

Answer 1

Range: 280-295 mOsm/kg

Equation:

• Sosm = 2x Na (mEq/L) + BUN (mg/dL)/2.8 + Glucose (mg/dL)/18
• Sodium contributes like 240 of this

Question 2

Osmoregulation is achieved by changes in water balance: water excretion or retention by the kidneys, and water intake stimulated by thirst.

What hormone is used to regulated renal water handling? When is it stimulated?

Answer 2

ADH (or vasopressin, AVP)

See image below:

• Osmolality over ~280 causes ADH to be released and causes thirst
• ALSO- HYPOVOLEMIA causes high levels of ADH to be released (more important to maintain fluid volume levels)

Question 3

To drill that last point home, which two types of receptors send signals to the pituitary to release ADH?

What is the end physiologic result?

Answer 3

Osmoreceptors + Baroreceptors

=> Causes increase in blood volume/ pressure and to a lower osmolality

Question 4

If you have a low osmolarity and low blood, which stimulus is stronger for ADH?

Answer 4

Blood volume: ADH increases exponentially if blood volume decreases by more than 6-8%, despite a decrease in serum osmolality.

• Thus, severe volume depletion can cause hyponatremia

Question 5

Water balance determines hypo/hypernatremia (serum osmol.), not total body sodium. How does ADH cause reabsorption of water in the collecting duct?

Answer 5

Causes aquaporins from cytoplasm to be inserted in endothelial cell membrane and become permeable to water.

• When serum osmol. goes up, then ADH gets released > V2receptor > Gs > adenylil cyclase > cAMP > aquaporins insert on membrane

Question 6

What effect would uncontrolled diabetes/ glucose in the blood have on serum osmolality?

Answer 6

=> Hypertonic hyponatremia

• causes water shift into blood from ECF and dilutes sodium

Question 7

Hypotonic (lower solutes outside cells) Hyponatremia is clinically the most significant hyponatremia because of brain complications. What is your first step in care?

Answer 7

Determine their volume status! [History, BP, HR, orthostatics, weight, physical exam (edema, rales, etc)]

1. Hypovolemic
2. Euvolemic
3. Hypervolemic

Question 8

In hypovolemic hyponatremia you have sodium and fluid loss (but more sodium) and ADH is released. Besides diabetes, what else can cause this?

Answer 8

• Hemorrhage
• Plasma volume and EC fluid losses:
  
  • Gastrointestinal loss
  • Renal loss (excessive use of diuretics, osmotic diuresis, mineralocorticoid deficiency)
  • Excessive sweating
  • Loss of sodium and water

Question 9

In hypervolemic hyponatremia you get increased body sodium and water (edema), but more water. What can cause this? Why?

Answer 9

ADH-mediated:

• CHF: Decreased perfusion, sensed as reduced “effective” blood volume > hormones to cause salt/ water retention and edema
• Cirrhosis: Portal hypertension > vasodilation, sensed as reduced “effective” blood volume > hormones to cause salt/ water retention and edema

Independent from ADH:

• Severe renal failure (kidneys unable to secrete excess water or low GFR or thiazide diuretics in old people)

Question 10

Free water excretion capacity is about 20% of GFR. Maximal urinary dilution: ~ 50 mOsm/kg. What are the requirements for a normal diluting system?

Answer 10

1. Normal function of ascending limb of Henle’s loop and of distal convoluted tubule
2. Normal delivery of tubular fluid to the distal diluting segment of the nephron (GFR)
3. Normal suppression of ADH (vasopressin)

Note: can’t get hyponatremia from just drinking water in normal person

Question 11

What is the treatment for hypovolemic hypernatremia? What about hypervolemic hypernatremia?

Answer 11

Hypovolemic hyponatremia:

• Restore plasma volume by giving normal saline, ADH will fall, and normonatremia will follow

Hypervolemic hyponatremia:

• Water/ salt restriction, loop diuretics (stop thiazides), inotropes for CHF,
• DONT GIVE SALT (makes edema worse)

Question 12

Hyponatremia is usually due to ADH secretion. What stimuli cause excessive ADH release?

Answer 12

• Hypothyroidism and adrenal insufficiency,
• nausea, pain,
• psychosis,
• many medications, some of them commonly used (SSRI’s and antipsychotics, NSAIDS, and others)
• Syndrome of inappropriate ADH secretion (SIADH)- If excluded everything else

Question 13

What effect does SIADH have on serum osmolality and urine? What can cause it?

Answer 13

=> Euvolemic hyponatremia and urine that is not maximally dilute (>50-100 mOsm/kg)

•Due to carcinomas (ectopic ADH production), CNS disorders, or pulmonary diseases

Question 14

If developed chronically, hyponatremia can be asymptomatic. But what are the usual symptoms?

Answer 14

• Anorexia, nausea, vomiting
• Weakness, lethargy, confusion
• Seizures, death
• Symptoms likely due to cerebral edema

Question 15

To treat euvolemic hyponatremia, you can give hypertonic saline to prevent seizures, give ADH antagonists, or restrict fluid and correct the underlying disorder (if asymptomatic).

What happens if you try to correct too quickly?

Answer 15

Central pontine myelinolysis (osmotic demyelination syndrome)- brain adapts to hyponatremia and saline causes water to leave brain and wreck the myelin

• If hyponatremia is chronic (> 48 hours) or unknown duration => slow correction

Question 16

Increasing serum osmolality causes thirst, and not drinking (hospital or CNS impairment) can cause hypernatremia.

What are some other causes of hypernatremia?

Answer 16

1. Renal or extrarenal water losses that exceed sodium loss (hypovolemic hypernatremia)
2. Addition of hypertonic fluids (hypervolemic hypernatremia), usually iatrogenic (hypertonic saline, TPN or bicarbonate infusion)
3. Lack of ADH effect: Diabetes insipidus (water diuresis, very dilute urine)

Question 17

What causes diabetes insipidus?

What would be the symptoms of a patient with DI?

Answer 17

Causes:

1. No ADH secreted: Central DI, ADH deficiency (partial or complete)
2. Kidneys do not respond to ADH: Nephrogenic DI, ADH resistance

Symptoms: polyuria (pee a lot), polydipsia (drink a lot)

Question 18

T/F: a patient with central DI will respond to exogenous ADH?

Answer 18

TRUE:

• Central DI: disease of pituitary or hypothalamus
• nephrogenic DI doesn’t respond to exog. ADH
• Tx: long-acting, nasally administered vasopressin analogue (DDAVP)

Question 19

What are some causes of congenital nephrogenic DI?

Answer 19

Due to mutation in AVP-receptor gene (X-linked recessive; 90%) or due to mutation in aquaporin 2 gene (autosomal recessive or dominant; 10%)

• Treatment: meticulous attention to water balance

Question 20

What are some medical conditions that could cause acquired nephrogenic DI?

Answer 20

-Chronic kidney disease causes a concentrating defect due to tubular dysfunction (medulla not maximally hypertonic) as well as ADH resistance

• Sickle cell anemia and polycystic kidney disease cause early concentrating defects by disrupting the medulla
• Urinary obstruction also causes ADH resistance

Question 21

What can cause a women to get gestational DI when pregnant? What is the treatment?

Answer 21

• Pregnancy: release of vasopressinase from the placenta during second half of pregnancy
• Tx synthetic: DDAVP is resistant to vasopressinase

Question 22

Symptoms of hypernatremia include: extreme thirst, neuromuscular irritability with twitches, hyperreflexia, seizures, altered mental status, confusion, coma….

What is the treatment?

Answer 22

• Calculate water deficit, replace deficit in addition to ongoing free water losses
• Give D5W in most cases, not half-normal saline
• Slow correction if hypernatremia is present for > 48 hours

Question 23

What’s the formula to calculate water deficit?

Answer 23

Water needed (L)

= 0.6 x body weight (kg) x [actual Na- desired Na/ desired Na]