Water and Salt Flashcards
Vasopressin is far more sensitive to changes in _______ rather than changes in ________
- Osmolality
- Pressure/volume
How does vasopressin act?
Acts on V2 receptors in the principal cells in the collecting duct to simulate the expression of intracellular water channels (aquaporin-2). Adenylate cyclase is then activated to produce cAMP, which stimulates the production of new aquaporin-2 and transfer of existing aquaporin to the cell membrane.
List the types of vasopressin receptors
- V1 receptors: on blood vessels, causes contraction of vascular smooth muscle to raise BP
- V2 receptors: in collecing duct, causes increased production and expression of aquaporin-2 channels to concentrate urine
- V3 receptors: in pituitary gland, stimulates ACTH
List 4 etiologies for central diabetes insipidus
- AD mutation in vasopressin gene
- DIDMOAD (Wolfram syndrome)
- Midbrain malformations
- Solid tumors or hematologic malignancies (ex. craniopharyngioma, suprasellar germinoma, pinealoma, metastatic disease to the pituitary/hypothalamus from breast/lung CA)
- Trauma/surgery
- Granulomaous and infectious disease
- Lymphocytic infundibulohypophysitis
- Essential hypernatremia (adipsic hypothalaic DI)
- Cerebral anoxia/brain death
Describe the triphasic DI response following pituitary surgery
- Initial axonal shock inhibits release of any vasopressin (5-10 days)
- Severed axons in the posterior pituitary become necrotic and there is uncomtrolled release of vasopressin –> SIADH (5-10 days)
- Return of diabetes insipidus
Note: if there is partial damage, you may only see second phase followed by recovery of axis
List 3 etiologies for nephrogenic diabetes insipidus
- X-linked recessive mutation of V2 receptor (90%).
- Type 1: normal receptors but don’t go to basal surface
- Type 2: receptors midfold and degrade
- Type 3: transcription issue (unstable mRNA)
- Autosomal recessive or dominant mutation of aquaporin-2 water channels
- Acquired nephrogenic DI (renal disease that distorts the vascular architecture of the kidney and washes out the inner medulla, ex. polycystic renal disease, infarcts, sickle cell anemia, drugs- lithium and demeclocycline and amphotericin B)
Describe how the following would present on water deprivation test:
- Normal physiology
- Partial central DI
- Primary polydipsia
- Complete central DI
- Nephrogenic DI
How do you calculate serum osmolality?
2x Na+ (mEq/L) + glucose (mmol/L) + BUN (mmol/L)
List a differential diagnosis for hyponatremia
- Low fluid status (dehydration):
- Urine Na <20 mEq/L: total body Na depleted, normal renal response (hemorrhage, GI losses)
- Urine Na >25 mEq/L: renal Na loss (renal disease, diuretics, CSW, Addisons disease)
Normal or fluid overload:
- Urine Na <20 mEq/L: hyperaldosteronism secondary to inadequate perfusion (ex. CHF ascites)
- Urine Na >25 mEq/L: SIADH (Na loss secondary to volume expansion)
List a differential diagnosis for SIADH
- Ectopic production of vasopressin by tumors
- Bronchogenic cardinoma
- Carinoma of the duodenum and pancreas
- Urethral, prostate, bladder carcinoma
- Thymoma
- Mesothelioma
- Lymphoma/leukemia
- Drug induced
- Desmopressin, oxytocin
- SSRIs, TCAs, MAOIs
- Chlorpropamide, carbamazepine, clofibrate, ecstacy
- Vinca alkaloids, cisplatin, cyclophsophamide
- Disrupt neural pathways
- Pulmonary disorders (pneumonia, TB, fungal infections, empyema, PPV)
- CNS disorders (infection, trauma, surgery, hemorrhage, inflammatory disorders, degenerative diseases, porphyria)
- Nephrogenic SIADH
- Extremely rare mutation of V2 receptor producing chronic activation
What is the risk of rapidly correcting chronic hyponatremia?
Central pontine myelinolysis (loss of intracellular osmocytes to maintain brain volume from a sudden shift of intracellular to extracellular fluid with acute increase in osmolality of ECF)
