Disturbances in Tonicity

Question 1

What is serum Na concentration (osmolality) indicitave of?

Answer 1

total body WATER content

Question 2

Hypernatremia

Answer 2

Too little water relative to salt

Question 3

Hyponatremia

Answer 3

Too much water relative to salt

Question 4

How do you calculate serum osmolality?

Answer 4

]Na]*2+[gluc]+[BUN]

it’s approximately 2*[Na]+10

Question 5

Where is ADH made? secreted? in response to what?

Answer 5

Made in hypothalamus

Secreted from pituitary

It’s released in response to high plasma osmolality –> production of concentrated urine

Question 6

What are the 4 requirements for maintaining water balance?

Answer 6

1. Deliver H2O
2. Diluting segment intact (i.e. not poisoned by diuretics)
3. Functional medullary gradient (i.e. also not poisoned by diuretics)
4. Vasopressin action intact (no mutations in vasopressin receptor or aquaporin receptor)

Question 7

What are the 2 vasopressin receptors?

Answer 7

Antidiuretic hormone V2 receptor: collecting duct

Vasopressor hormone V1 receptor: vascular smooth muscle

Question 8

What are the 2 main stimuli for vasopressin release?

Answer 8

1. osmolality
2. volume

they interplay with each other: if you’re hypovolemic, you’re less sensitive to changes in plasma osmolality

Question 9

Response to ECF volume loss

Answer 9

Decreased ECF Volume —>

(1) Decreased RBF, hemodynamic changes to increase FF, increase prox tubular salt reabsorption, increase renin, AngII, increase aldosterone, increased sympathetic activity –> increased NaCl reabsorption
(2) Decreased renal BF and H2O delivery, increased vasopressin release, increased water reabsorption, increased thirst due to vasopressin and Ang II–> increased water reabsorption

Question 10

What determines osmolality?

Answer 10

Oral and IV free H2O intake

vs.

Free H2O excretion (urine) and losses (respiratory, IV, GI)

Question 11

What does it mean if the [Na] is high?

Answer 11

It is not Na overload!!!

It is hypernatremia: Free water loss >> Na loss

Question 12

What can cause hypernatremia?

Answer 12

Most common cause: unreplaced water loss: sweat loss, GI loss, renal loss (diabetes insipidus, osmotic diuresis)

Defectiv thirst or osmoreceptor function, damaged osmoreceptor function

Administration of hypertonic Na solution

Question 13

Treatment of hypernatremia

Answer 13

Replace water loss: PO, IV

Treatment is based on magnitude of water defifit

Water deficit = current TBW x (serum [Na]/140) - 1

Slow correction if chronic hypernatremia: reduce by 12 meq/24h

Question 14

Example of marathon rummer that collapsed & has no volume depletion, weight gain, hyponatremia (low serum Na), hypoosmolarity, and more concentrated urine (suggesting ADH action)

What’s going on?

Answer 14

Run marathon –> start sweating –> ADH release

+

excess hypotonic fluid intake during marathon

+ Failure to make dilute urine due to vasopressin

=

Net free water gain in setting of Na loss –> hyponatremia

Question 15

How do you treat acute hyponatremia?

Answer 15

If asymptomatic and the stimulus of vasopressin release is self-limited, no treatment

You can treat underlying volume depletion to suppress ADH: give normal saline

If CNS symptoms, treat with hypertonic saline or vasopressin antagonists

Question 16

What can cause hypovolemic hyponatremia?

Answer 16

Extrarenal losses: diarrhea, vomiting, burns, pancreatitis, insensible fluid loss, 3rd spacing of fluids

Renal losses: diuretics, osmotic diuresis (hyperglycemia), mineralocorticoid deficiency

Question 17

CHF patient with high serum Na (hyponatremia), low serum osmolarity (hypoosmolarity), low BP, weight gain, S3 (volume overload due to HF, based on history/exam), high urine osmolarity: more concentrated than serum

What’s going on with this pt?

Answer 17

CO decreased –> LVEDP increasese to compensate

Decreased effective arterial volume –> same response as volume loss: result is increased NaCl reabsorption, increased water reabsorption

Note that with CHF, hyponatremic have much worse outcome

Question 18

What can cause hypervolemic hyponatremia?

Answer 18

CHF, cirrhosis, nephrotic syndrome, renal failure

Syndrome of inappropriate ADH

Endocrinopathies, hypothyroidism, glucocorticoid deficiency

Question 19

How do you treat hypervolemic hyponatremia?

Answer 19

Treat underlying dz i.e. ionotropes to improve cardiac function, diuretics, reduce afterload

Fluid restriction: can be hard bc patient will feel thirsty due to ADH and AngII

Vasopressin antagonists can be used to produce aquaresis in severe hyponatremia but you have to be careful not to correct chronic hyponatremia too rapidly

Question 20

What are possible subcategories of syndromes of inappropriate ADH (SIADH)?

Answer 20

Ectopic production: tumors - lung, pancreas

Pulm dz: pneumonia, lung abscess

Drugs: SSRIs, chloropropamide, thiazide, diuretics, carbamazepine, oxcarbazepine, cyclophosphamide, etc

CNS disturbances: stroke, hemorrhage, infection, trauma, psychosis

Surgery: abdominal or thoracic surgery, due to stimulation of pain afferents

Question 21

Treatment of SIADH

Answer 21

Treat underlying etiology

Fluid restriction

Severe symptomatic hyponatremia: hypertonic saline, vasopressin antagonists, correct chronic hyponatremia slowly due to concern for central pontine myelinolysis

Question 22

What are the subcategories of volumes in hypoosmolar hyponatremia?

Answer 22

• *Hypovolemia**: low BP, orthostasis = total body water decreased, total body Na very low
• extrarenal losses, renal losses
• *Euvolemia**: total body water up, total body Na normal
• hypothyroidism, glucocortiocoid deficiency, drugs, SIADH
• *Hypervolemia** = edema, total body water increased, total body Na increased
• CHF, cirrhosis, nephrotic syndrome, chronic renal failure