posterior pituitary Flashcards
if you drink too much water what would happen
decrease body fluid osmolarity (via increasing H20 concentration), decreased firing by hypothalamic osmoreceptors, decreased vasopressin secretion in the posterior pituitary, decreased plasma vasopressin–> Collecting ducts decrease the permeability to H20, which decrease H20 reabsorption, increases H20 excretion
If your plasma volume decreases
decreased venous, atrial and arterial pressures, reflexes mediated by cardiovascular baroreceptors, posterior pituitary increases vasopressin secretion–> increases plasma vasopressin–> collecting ducts increase tubular permeability to H20–> increased H20 reabsorption–> decreased H20 excretion
Vasopressin/ antidiuretic hormone MOA
Vasopressin activates the vasopressin receptor (aGPCR), which activates adenylate cyclase–> ATP activates cAMP–> PKA–> Protein phosphorylation–> Membrane fusion –> Aquaporins move to the plasma membrane on the tubular lumen
Diabetes Insipidus
Diabetes basically means too much urine
Osmotic diarrhea bc of too much glucose in the urine, and non osmotic diarrhea (very dilure)
polyuria (dilute urine) with high normal or high plasma sodium - why do they get hypernaterima- lost water, what behavioral pattern- drinking more water
Central (neurogenic, pituitary)- insufficient production of vasopressin, can be partial- AVP is present but attenuated relatice to plasma hyperosmolality (type 1, not making any)
Nephrogenic- unresponsiveness of the renal tubules ot vasopressin (type 2, receptors dont responD)
Physical findings and clinical presentations
Central Diabetes insipidus is usually abrupt in onset, primary polydipsia and lithium-induced DI have a vague history of onset
Nocturia is common in Central diabetes insipidus, Polyruria- urinary volumes ranging from 2.5 to 6L a day
Polydipsia- predilectation for cold or iced drinks
Neurologic manifestations (seizures, headaches)
Evidence of volume contraction
Causes of central and nephrogenic Diabetes insipidus
Central causes: Autoimmune injury to hypothalamus/pituitary, head trauma or surgery, cerebral hypoperfusion, tumors (metastases to hypothalamus and/or pituitary, craniopharyngioma, meningioma), infiltrative disorders (sarcoidosis, histiocytosis)
Nephrogenic diabetes insipidus: vasopressin receptor mutations or AQP mutations (hereditary nephrogenic diabetes insipidus), hypokalemia, hypercalcemia, renal diseases, drugs (Lithium)
diagnosis of di
patient presents with complaint of polyuria (look for water bottle sign)
rule out DM and hyper calcemia (chem panel) if normal
20min
Pt collects urine at home if <2 liters/day probably not DI
if >2 L then
Overnight water deprivation (if plasma sodium and plasma osmolality are increased and urine osmolality is not >100 mosm/L then DI), the urine should be super concentrated
Poly uria and polydipsia eval
Dehydration if serum osmolarity is high and urine osmolarity is also high
Primary polydipsia if serum osmolarity is normal but urine osmolarity is low (increases with water restriction)- drinking too much water
DI if serum osmolarity is normal (high if water restricted), but the urine osmolarity is low (much lower than serum, absent or attenuated increase with water restriction
Desmopressin is a analog of vasopressin, nephrogenic DI doesnt respond
In central DI, they respond to desmopressin (but still not perfect)- complete
Formal water deprivation test
Primary polydipsia - adequate response to H20 deprivation
Nephrogenic- no response to H20 deprivation/desmopresstion
Central- no response to h20 deprivation, but a response to desmopressin
Why doesnt the Urine osmolarity maximally increase with desmopressin in central DI- Wash out of medullary gradient, solute gradient is washed out
Why doesnt Urine osmolarity maximally increase in primary polydipsia
Di treatment
for central diabetes insipidus, replase the mising hormone with a synthetic form of ADH called desmopressin
Nephrogenic DI- recommend a low salt, low protein diet, limiting solute potentially lowers GFR, stop offending drug if possible (lithium), start a thiazide diuretic to induce natriuresis enhanced with amiloride, NSAIDs inhibit renal prostaglandin synthesis, reduces prostaglandin interference with AVP (amplifies effect of AVP)
Syndrome of inappropriate antidiuretic hormone (SIADH)
Excessive secretion of antidiuretic hormone (ADH aka AVP)
Absence of normal osmotic or physiologic stimuli, absence of increased serum osmolarity, absence of decreased plasma volume / hypotension
usually normovolemic- no edema
Hyponatremia- if severe, CNS findings
Common etiologies of SIADH
Tumor secreting AVP, CNS (mass lesions, Inflammatory diseases, degenerative/demyelinative diseases, nausea (particularly post op)
Drug related; (stimulate release of AVP, nicotine, phenothiazines, tricyclic andidepressants, SSRIs, carbamazepine), Direct renal effects and/or potentiation of AVP antidiuretic effects (AVP), oxytocin, prostaglandin synthesis inhibitors
Pulmonary ( chemo, baro, mechanoreceptor afferent input to the hypothalamus, infections, mechanical/ventilatory causes
Differential diagnosis of SIADH
Hyponatremia associated with hypervolemia ( CHF, Cirrhosis, nephrotic syndrome)
Hyponatremia associated with hypovolemia (burns, GI fluid losS)
Euvolemic
Absence of other endocrine diseases
SIADH criteria
inability to excrete a water load and/or failure to dilute urine osmolality to <100 mosm/kg
Plasma vasopressin level inappropriately elevated relative to the plasma osmolality
Patient is clinically euvolemic (normal blood volume)
Serum sodium and serum osmolality are low
A urine osm>100 mM
Hypothryrodism and 1’ or 2’ adrenal insufficieny 9cortisol defect) have both been ruled out
SIADH management
Fluid restriction, IV salt solution (rate of correction is an important caveat), vasopressin receptor Antagonists (Conivaptan and tolvaptan)- block V2 receptors therby limiting AQP2 channel activity and reducing water permeability
Loop diuretics (furosemide and bumetanide)- directly diminish the renal medullary gradient, demeclocycline (tetracycline antibiotic), inhibits the collecting tubules response to AVP
