posterior pituitary Flashcards
oxytocin: effect on uterus
-Stimulates contraction of the smooth muscle cells of the uterus
-Uterine sensitivity increases throughout pregnancy
-Plasma levels do not increase sharply during parturition
-Role of oxytocin in the initiation of labor is unclear
oxytocin: effect on breast
-Myoepithelial cells
-Suckling stimulates the production of oxytocin
-Cells surround the alveoli of the mammary gland → contraction causes milk to move from the alveoli to large sinuses for ejection
-Letdown reflex
ADH action
action
- water conservation by increasing the permeability of the distal tubular epithelium to water
-At high concentrations: ADH causes vasoconstriction
Plays an important role in maintaining fluid homeostasis and vascular and cellular hydration
ADH stimulation and inhibition
Main stimulus for ADH release: Increased osmotic pressure of water in the body***
Other stimulus: Volume depletion
-Sensed by baroreceptors in the left atrium, pulmonary veins, carotid sinus, and aortic arch
-Transmitted to the CNS through the vagus and glossopharyngeal nerves
Other stimulants for ADH release include:
-Pain, stress, emesis, hypoxia, exercise, hypoglycemia, cholinergic agonists, β-blockers, angiotensin, and prostaglandins
Inhibitors of ADH release
- alcohol
- α-blockers
- glucocorticoids
Central diabetes insipidus
Deficiency of ADH due to a hypothalamic-pituitary disorder
-Primary
-Secondary
Pathology of CDI:
- always involves the supraoptic and paraventricular nuclei of the hypothalamus or a major portion of the pituitary stalk
- Hypothalamic nuclei and part of the neurohypophyseal tract need to be intact
Nephrogenic Diabetes Insipidus:
definition:
- Inability to concentrate urine due to impaired renal tubule response to ADH
- Inability of kidney to respond normally to ADH
-Inherited or secondary to impairment of renal concentration
Nephrogenic Diabetes Insipidus: sx, dx
sx:
-Excretion of large amounts of dilute urine
-Polyuria
- hypernatremia**
- dehydration but good thirst response**
Diagnosis :
– water deprivation test and/or administration of exogenous ADH
- DDx with CDI with exogenous ADH test
Lack of ADH: other pathologies
Vasopressinase-induced DI
Removal of the pituitary gland:
- does NOT result in permanent diabetes insipidus
- some of the remaining hypothalamic neurons produce small amounts of ADH
Nephrogenic Diabetes Insipidus: tx
- adequate free water intake (prevent dehydration)
- thiazide diuretics (reduces urine volume)
- NSAIDs
- low-salt, low-protein diet
Goal: reduce urine output and increase ability to concentrate urine
Differential for polyuria
Differential for polyuria:
-CDI
-NDI
- compulsive or habitual water drinking (psychogenic polydipsia)
-DM
diabetes insipidus (DI) main sx and dx
Sx:
-Polyuria
-Polydipsia
Diagnosis:
-Water deprivation test: Failure to maximally concentrate urine
-ADH levels and response to exogenous ADH help distinguish CDI from NDI
diabetes insipidus (DI) tx
-intranasal desmopressin or lypressin
-Nonhormonal treatment:
diuretics (MC: thiazides)
-ADH-releasing drugs: chlorpropamide
primary central diabetes insipidus
-Marked decrease in the hypothalamic nuclei of the neurohypophyseal system
- Genetic abnormalities of the ADH gene on chromosome 20
- Idiopathic
secondary (acquired) central diabetes insipidus
Various lesions:
-Hypophysectomy
-Cranial injuries (particularly basal skull fractures)
-Suprasellar & intrasellar tumors (primary or metastatic)
-Granulomas (sarcoidosis or TB),
-Vascular lesions (aneurysm and thrombosis)
-Infections (encephalitis or meningitis)
DI onset and sx of primary vs secondary
Onset:
- insidious or abrupt
-Occurring at any age
Primary CDI:
- ONLY SX: polydipsia & polyuria
Secondary CDI:
- S&S of the associated lesions
DI signs
Large quantities of fluid
ingested + Excreted
-3 to 30 L/day of dilute urine excreted
-Sp.gravity usually < 1.005 (nml 1.030)
-Osmolality < 200 mOsm/L (nml 280-285mOsm/L)
-Nocturia almost always occurs
-Dehydration and hypovolemia
tests for DI
-All tests for CDI &NDI based on the principle that:
-Increasing the plasma osmolality in normal people – will lead to decreased excretion of urine
-Water deprivation test:
-Simplest
-Most reliable method
-Patient needs constant supervision*
-Serious dehydration may result *
water deprivation test: what does it entail
Pt is weighed, Electrolyte concentrations are obtained from plasma and urine
Dehydration begins and urine is collected hourly with specific gravity or osmolality measured
Dehydration is continued until:
-Orthostatic hypotension
-Postural tachycardia appear
-≥ 5% of the initial body weight has been lost
-OR
-Urinary concentration does not increase > 0.001 sp gr or > 30 mOsm/L in sequentially voided specimens
After:
-Serum electrolytes and osmolality are obtained
-5 units of aqueous vasopressin injected sc.
-Urine for sp gr or osmolality measurement collected one final time 60 min post injection
result interpretation
Normal:
- Urine is maximally concentrated after dehydration
- Specific gravity > 1.020, Osmolality > 700 mOsm/L
- Osmolality does not increase >5% s/p vasopressin injection
CDI
- unable to concentrate urine to greater than the plasma osmolality
-Able to increase their urine osmolality by > 50% after vasopressin administration
NDI
- unable to concentrate urine to greater than the plasma osmolality
- shows NO response to vasopressin**
Partial CDI
- Often able to concentrate urine to above the plasma osmolality *
- Show a rise in urine osmolality of > 9% after vasopressin administration
ADH measurement
Measurement of circulating ADH
-Plasma ADH levels are diagnostic after either dehydration or infusion of hypertonic saline
-Most direct method of diagnosing CDI
-ADH difficult to measure; test not routinely available
-Direct measurement of ADH unnecessary
Levels of ADH at the end of the water deprivation test (before the vasopressin injection)
-Low in CDI
-Appropriately elevated in NDI
psychogenic polydipsia
Compulsatory behavior (anxiety, boredom) to ingest high volumes of fluids (up to 6 L/day)
- Does not present with nocturia and thirst does not wake them up at night
-Life-threatening hyponatremia**
- no response to exogenous ADH after water deprivation
Acute phase:
- pt able to concentrate urine during water deprivation
Chronic phase:
- Long-standing water intake = ↓ tonicity of kidney medulla = kidneys unable to maximally concentrate urine
- No response to exogenous ADH after water deprivation
- Once fluid intake normalizes, concentrating ability returns to normal within weeks
tx of DI
Hormone replacement and treatment of any correctable cause
-Permanent renal damage can result
Desmopressin:
-Synthetic analog of ADH
-Minimal vasoconstrictive properties
-Prolonged antidiuretic activity lasting for 12 to 24 h
ADR:
– fluid retention; headache; ↑ BP; URI or allergic rhinitis
Diuretics: MC= thiazides
-Primarily as a consequence of reducing ECF volume and increasing proximal tubular resorption
-Urine volumes may fall by 25 to 50%
ADH-releasing drugs
-Chlorprpamide (hypoglycemia)
-Carbamazepine
-Clofibrate
Prostaglandin inhibitors:
-Reduce GFR and renal blood flow
-NOT effective in NDI
Restricting salt intake also ↓ urine output by reducing solute load
SIADH criteria
Excessive ADH release
Defined as:
-Less than maximally dilute urine in the presence of plasma hypo-osmolality + hyponatremia
-urine is not as dilute as it should be under these conditions
-50% of all diagnosed cases of hyponatremia are due to SIADH
WITHOUT:
-Volume depletion or overload
-Emotional stress
-Pain
-Diuretics or other drugs that stimulate ADH secretion,
-AND WITH normal cardiac, hepatic, renal, adrenal, and thyroid function
Before diagnosis of SIADH can be made, MUST R/O
MUST R/O:
- thyroid disease
- adrenal insufficiency
SIADH causes
Drugs
Post OP
Hormone administration
CNS infections
Pulm Disorders **
Malignancy= LUNG*
disorders associated with SIADH secretion
Malignancy:
-CNS
-Pancreas
-Duodenum
-Lung*
-Lymphoma
Pulmonary disorders:
-Aspergillosis
-Lung abscess
-Pneumonia
-Positive-pressure breathing
-TB
CNS disorders:
-Acute intermittent porphyria
-Acute psychosis
-Brain abscess
-Encephalitis
-Guillain-Barré syndrome
Head trauma:
-Meningitis
-Stroke
-Subdural or subarachnoid hemorrhage
Endocrine disorders:
-Addison’s disease
-Hypopituitarism
-Hypothyroidism
Miscellaneous causes:
-Protein-energy malnutrition
-Surgery
symptoms SIADH
-Patient may be asymptomatic, especially when the cause is indolent or subacute.
Severe or rapid onset hyponatremia may cause:
-Confusion
-Lethargy
-Vomiting
-Seizures
SIADH signs
-Hyponatremia*
-Hypo-osmolality (<275 mosm/kg)*
-Euvolemic: normal hydration
-Elevated urinary osmolality (>100 mosm/kg and often at least 300 mosm/kg)
-Normal plasma volume
-Serum uric acid <4 mg/dL
-Normal acid base and potassium balance
-Normal renal function
-Relatively normal creatinine concentration
-Normal adrenal and thyroid function
diff dx SIADH
-Hypervolemic hypotonic hyponatremia:
-An increase in total body water and sodium with a decrease in the circulating volume (impaired water excretion)
-Characterized by clinical fluid overload with edema
-CHF, liver cirrhosis with ascites, nephrotic syndrome, protein losing enteropathy
-Hypovolemic hypotonic hyponatremia:
-Characterized by fluid volume loss due to underlying disorder
-Non-renal loss of electrolyte-containing fluid (diuretics, burns, severe diarrhea and vomiting)
-Salt losing renal diseases (interstitial nephritis, obstructive nephropathy)
-Mineralocorticoid deficiencies
SIADH management
First Line Therapy: Fluid Restriction !!!
Resolution of any CNS symptoms
- Achievement of safe Na+ levels (>120mEq/L), but GRADUALLY
Resolution of underlying cause of hypo-osmolality
Discontinue offending drugs
If Refractory to tx:
- Demeclocycline/saline infusion
- Tetracycline: Antagonizes ADH
