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Flashcards in Pathophysiology of Water Handling Deck (43):

True or False: Serum osmolality is mostly determined by Na


Normal serum osmolality is 280-295 mOsm/kg and in a normal person about 280 mOsm of that is from the Na.


Osmoregulation is achieved by changes in _____ balance


Excretion, retention, and intake


What 2 things trigger ADH release?

High plasma osmolality and low blood volume.


True or False: In severe volume depletion, the hypovolemic stimulus can override the osmolality stimulus and release ADH even in states of hyponatremia.

True. It is more important to the body to preserve blood volume in cases of severely low 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.


Explain the mechanism of vasopressin in the kidney principal cells

Vasopressin arrives at the principal cells from the peritubular capillaries. It attaches to the V2R receptor (vasopressin 2 receptor) on the basolateral membrane of the principal cell which stimulates adenylyl cyclase which makes cAMP which stimulates PKA which leads to exocytosis of aquaporin water channels which insert into the apical membrane. This allows water to be absorbed.


What causes isotonic hyponatremia?

It is usually a lab artifact but can happen in severe hyperlipidemia or hyperproteinemia.


What causes hypertonic hyponatremia?

It is most often due to uncontrolled diabetes which causes a water shift.

Sosm = (2x Na meq/L) + (BUN mg/dL / 2.8) + (Glucose mg/dL / 18)

You can see that if glucose gets really high from uncontrolled diabetes, the osmolality of the serum will increase. Water will shift from the extracellular space into the blood stream to try to reduce the osmolality but this addition of water dilutes the Na. This causes a state of hypertonic hyponatremia.


True or False: Hypotonic hyponatremia is the most clinically significant hyponatremia and is even called "True" hyponatremia.



What is the first step in evaluating patients with hypotonic hyponatremia?

Determine their volume status: hypovolemic, euvolemic, or hypervolemic.

This can be done by...

History: trauma/blood loss, diarrhea, vomitting, etc.

BP and HR

Orthostatics is a sign of volume depletion

Weight changes

Physical exam: Edema, rales, etc


What are causes of hypovolemic hyponatremia?

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


What is osmotic diuresis and how can is cause hypovolemic hyponatremia?

It is when the urine is high is osmolarity (common in uncontrolled diabetes). High glucose in urine will drag water and electrolytes with it which can cause days to weeks of diuresis which can cause volume depletion.


How do you treat hypovolemic hyponatremia?

Normal saline.


In hypovolemia, there is decreased total body sodium. Total body water is decreased but to a lesser extent because of appropriate ADH release. Restoring plasma volume with saline will cause normonatremia and fall in ADH.


What are 2 categories of causes for hypervolemic hyponatremia?

  • ADH-mediated
    • Congestive heart failure
    • Liver cirrhosis
  • Independent from ADH
    • Severe renal failure causing kidneys to be unable to excrete excess water


Why is ADH released in CHF and liver cirrhosis?

In severe heart failure, cardiac output and tissue perfusion is very low which is sensed by the baroreceptors and the kidney as reduced "effective" blood volume. Counterregulatory hormones (e.g. renin-angiotensin-aldosterone system, sympathetic nervous system, and ADH) lead to salt and water retention by the kidneys causing edema.

In liver cirrhosis, there is excessive vasodilation in the splanchnic vasculature, which is also sensed by baroreceptors as reduced "effective" blood volume, stimulating ADH.

ADH release in these settings can cause hyponatremia which is a poor prognostic sign.


Explain hypervolemic hyponatremia independent from ADH and a therapy that is a frequent cause of hyponatremia, particularly in the elderly.

When hypervolemic hyponatremia is independent from ADH, it means that the mechanism is intrinsic to the kidney. Either the diluting mechanism in the distal tubules does not work or renal blood flow and glomerular filtration rate are too low, as in cases of advanced chronic kidney disease.

Thiazide diuretics impair dilution and are a frequent cause of hyponatremia, particularly in the elderly.


How do you treat hypervolemic hyponatremia?

Water and salt restriction

Loop diuretics

Stop thiazides

Inotropes for CHF


True or False: Euvolemic hyponatremia is usually due to ADH secretion



What stimuli can cause excessive ADH release resulting in euvolemic hyponatremia? (7)

  1. Hypothyroidism
  2. Adrenal insufficiency
  3. Nausea
  4. Pain
  5. Psychosis
  6. Many medications (SSRIs, antipsychotics, NSAIDS, and others)
  7. SIADH (syndrome of inappropriate ADH secretion)


What is SIADH?

Syndrome of inappropriate ADH secretion. It is a diagnosis of exclusion and is when a patient has euvolemic hyponatremia and urine that is not maximally dilute (greater than 50-100 mOsm/kg)


What causes SIADH?

SIADH is commonly caused by carcinomas which cause ectopic ADH production. It can also be caused by CNS disorders of the hypothalamus or pituitary or pulmonary diseases.


Symptoms of hyponatremia depend on what 2 things?

Speed of onset and severity.

If it develops slowly (days to weeks), sometimes patient don't even have symptoms.


What are symptoms of hyponatremia? (8)

  1. Anorexia
  2. Nausea
  3. Vomiting
  4. Weakness
  5. Lethargy
  6. Confusion
  7. Seizures
  8. Death


Symptoms of hyponatremia are likely due to _____ edema

cerebral edema


How do you treat euvolemic hyponatremia that presents with seizures?

Hypertonic saline


How do you treat asymptomatic euvolemic hyponatremia?

Water restriction and correction of underlying disorder or removal of offending drugs.

If underlying causes cannot be treated, you can give ADH antagonists.


How do you treat chronic euvolemic hyponatremia (greater than 48 hours of duration) or unknown duration?

You have to slow the correction to avoid central pontine myelinolysis (osmotic demyelination syndrome).


The brain adapts over time to hyponatremia. Initially, when serum osmolality is low, water goes from the serum into the brain which causes brain edema. However, the brain adapts by reducing its intracellular sodium and osmoles so that water flows out of the brain and intercranial pressure goes back to normal. If you rapidly correct serum osmolality, then the brain cells are hypotonic to the serum plasma so the cells will lose even more water and the neuron cells will shrink and lead to demyelination.


True or False: Hypernatremia and hyponatremia are disorders of water balance and do not indicate anything about total body sodium.


Hypernatremia can have decreased, normal, or increased total body sodium and so can hyponatremia.


True or False: Hypernatremia causes severe thirst

True. It causes an increase in serum osmolality which causes severe thirst.


Hypernatremia only develops in 2 cases. What are they?

  1. Patients who do not have access to water (often hospitalized patients)
  2. Patients with CNS pathology impairing thirst


What are causes of hypernatremia?

  1. Renal or extrarenal water loss that exceeds sodium loss
  2. Addition of hypertonic fluids (hypervolemic hypernatremia). This is usually iatrogenic (caused by medical intervension e.g. hypertonic saline, TPN, or bicarbonate infusion)
  3. Lack of ADH effect in diabetes insipidus (water diuresis, very dilute urine)


What is Diabetes Insipidus? What are the 2 kinds?

Diabetes insipidus (DI) is a condition characterized by excessive thirst and excretion of large amounts of severely dilute urine, with reduction of fluid intake having no effect on the concentration of the urine.

DI can be central or nephrogenic.

Central DI is when there is no ADH secreted or if there is ADH deficiency.

Nephrogenic DI is when the kidneys do not respond to ADH or have ADH resistance.


What do patients with diabetes insipidus complain of?

Polyuria (excessive urine volume) and Polydipsia (excessive thirst)


What are causes of central DI?

30-50% of cases are idiopathic (hypothesized as autoimmune?)

Diseases of hypothalamus or pituitary gland (head trauma, surgery, tumors, encephalitis)



How do you treat central DI?

You give long-acting nasally administered vasopressin analogue (DDAVP). You don't give ADH because ADH has a short halflife.


What are causes of nephrogenic DI?


gene mutations in either V2R vasopressin receptor or Aquaporin water channels


caused by medications, electrolyte disorders, or chronic kidney disease




What age group does congenital nephrogenic DI typically appear in? How do these patients present? How is it treated?

It typically presents in infants who have failure to thrive, polyuria, fever, vomiting, seizures, and sometimes death.

Treatment is meticulous attention to water balance.


True or False: congenital nephrogenic DI is usually less severe than acquired nephrogenic DI and is much more common

False. Acquired nephrogenic DI is much more common than congenital disease and is typically less severe and at least partially reversible.


What are causes of acquired nephrogenic DI? (7)

  1. Hypercalcemia or chronic hypokalemia can damage the distal tubules and collecting ducts.
  2. Long term therapy with lithium
  3. Other drugs (cidofovir, foscarnet, amphotericin B, ifosfamide)
  4. Treatment with vasopressin receptor antagonists (tolvaptan)
  5. CKD causes a concentrating defect due to tubular dysfunction (medulla not maximally hypertonic) as well as ADH resistance
  6. Sickle cell anemia and PKD cause early concentrating defects by disrupting the medulla
  7. Chronic urinary obstruction also causes ADH resistance


What is gestational DI? Does it need to be treated? If so, how?

In the second half of pregnancy, the placenta creates vasopressinase. This degrades endogenous vasopressin which can cause polyuria and polydipsia. It's typically not that severe but if it is then it can be treated with synthetic DDAVP (which is resistant to vasopressinase).


What are symptoms of hypernatremia?

Extreme thirst

Neuromuscular irritability with twitches, hyperreflexia, and seizures.

Altered mental status, confusion coma

Failure to thrive in infants

High mortality rate in both adults and children as hypernatremia often indicates a serious underlying disease.


How do you treat hypernatremia?

Calculate water deficit and replace the deficit in addition to ongoing free water losses.

In most cases, D5W should be given not half-normal saline.

Slow correction is required if hypernatremia is present for more than 48 hours (because of the brain adapting to chronic states of hypo/hypernatremia)


True or False: For chronic management of nephrogenic DI, thiazide diuretics have been shown to reduce polyuria.

Yes. It seems counter-intuitive but it has been shown empirically to help.


True or False: The brain adapts to chronic (greater than 48 hours) hypo- or hypernatremia, so that overly fast correction can cause severe neurological damage.