Systemic diseases associated with disorders of water homeostasis

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Systemic diseases associated with disorders of
water homeostasis

• Lisa L. Wong, MD, Endocrinol Metab Clin N Am, 2002

Reading by ???, 92-3-7
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normal water homeostasis

• Maintain within narrow limits (275 to 295 mOsm/kg
  H2O)
• Osmoreceptor anterior hypothalamus
• Thirst osmoreceptor organum vasculosum of the
  lamina terminalis and the anterior wall fo the
  third ventricle
• Arginine vasopressin synthesize supraoptic
  (SON) and paraventricular nuclei (PVN)
• Secretion only 1 to 2 leads to an increase in
  AVP of approximately 1 pg/ml
• Maximum antidiuresis approximately 5 pg/ml

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• Osmotic threshold for thirst 5 to 10 mOsm/kg H2O
  above that for AVP releaseonly activated by
  larger and more threatening osmotic perturbation
• Baroreceptors located in the cardiac atria and
  large arteries, reduction in effective
  circulating volume (hypotension and volume
  depletion) 10 to 20 is required before a
  significant AVP response occurs
• Nonosmotic stimuli nausea, hypoxia, hypercapnia,
  hypoglycemia, and various medications

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AVP V2 receptor

• basolateral membrane of renal collecting duct
  cells
• family of G protein-coupled seven-transmembrane
  domain
• linked to adenylyl cyclase signaling pathway
  shuttling aquaporin-2 (AQP2) water channels from
  intracellular vesicles into the apical plasma
  membrane of the renal collecting duct cells

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Systemic disorders associated with excess AVP
secretion or effects

• SIADH clinical criteria
• true hypo-osmolality with a urine osmolality that
  is greater than maximally dilute (i.e., gt100
  mOsm/kg H2O) and an elevatd utine Na exctetio
  (i.e., gt30 mmol/L).
• clinical euvolemia also must be demonstrated
• absence of hypothyroidism, hypocortisolism, renal
  insufficiency, and recent diuretic use

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Systemic disorders associated with excess AVP
secretion or effects

• SIAD about 10 to 20 meet above criteria
  without lelvated AVP level another circulating
  antidiuretic substance, or to increased AVP V2
  receptor sensitivity

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tumors

• Pulmonary or mediastinal
• bronchogenic carcinoma
• Mesothelioma
• Thymoma
• Hodgkins lymphoma
• Nonchest
• Nasopharyngeal carcinoma
• Duodenal carcinoma
• Pancreatic carcinoma
• Ureteral /prostatic carcinoma
• Uterine carcinoma
• leukemia

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tumors

• Most common
• Small cell lung carcinoma (SCLC)
• SIADH occur approximately 15
• culture tumor tissue synthesize not only AVP but
  also the entire AVP prohormone
• only half possess AVP immunoreactivity
• elevated mRNA for atrial natriuretic peptide
  (ANP) contribute to hypo-osmolality in patients
  with low AVP level

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Reset osmostat

• Tuberculosis
• Malnutrition
• Gastric carcinoma
• Pneumonia
• encephalitis

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Reset osmostat

• 15 to 20 regulates his plasma osmolality
  appropriately, but around a reduced set point
• normal diluting capacity defined as the ability
  to excrete more than 80 of a standard water
  load within 4 hours and to decrease urine
  osmolality to less than 100 mOsm/kg H2O.
• chronic hyponatremia dose not appear to alter the
  osmotic threshold for AVP secretion

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Reset osmostat

• placental hormone relaxin causes a stimulation of
  AVP and oxytocin secretion that closely resembles
  the reset osmostat pattern
• some represent tumor-stimulated pituitary AVP
  secretion rather than paraneoplastic AVP
  secretion
• hyponatremia only mild, asymptomatic, chronic,
  and fairly stable
• no specific therapy is required, otherwise, may
  overwhelm urinary diluting capacity, resulting in
  lower and more dangerous levels of hyponatremia

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CNS disorder

• Mass lesion
• Infectious/inflammatory
• Demyelinative/degenerative

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CNS disorder

• No apparent common denominator linking them
• Any diffuse CNS disorder potentially can disrupt
  inhibit pathway from the brainstem to the
  hypothalamus

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Pulmonary disorders

• Infections
• Tuberculosis
• Aspergillosis
• Pneumonia
• Empyema
• Mechanical/ventilatory
• Acute respiratory failure
• Chronic obstructive pulmonary disease
• Positive pressure ventilation

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Pulmonary disorders

• Hypoxia induced antidiuresis mediated by way of
  baroreceptor-stimulated AVP release by a fall in
  PaO2 to less than 50 mmHg
• Hypercapnia decreasing systemic resistance, and
  only secondarily

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Pulmonary disorders

• Pneumonitis and advanced COPD, other than TB,
  only in sporadic case reports
• Occur on the setting of respiratory failure
• Limited to the initial days, once clinical
  improvement has begun, free water excretion
  generally spontaneously improves
• Mechanical ventilation decreases pulmonary blood
  volume and left atrial pressure resulting
  activation of carotid baroreceptors

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Edema-forming states

• Occur in advanced stage
• Decrease intravascular volume
• Decrease distal delivery of glomerular filtrate
  and secondarily elevated AVP levels
• Activating renin-angiotensin-aldosterone system,
  the sympathetic nervous system and AVP secretion

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Systemic disorders associated with insufficient
AVP secretion or effects

• Central diabetes insipidus
• Granulomatous
• Neurosarcoidosis
• Langerhans cell histiocytosis
• Tumors
• Germinoma craniopharyngioma
• Meningioma
• Lymphoma
• Infections
• Meningitis
• Encephalitis
• Ischemic
• Sheehans syndrome
• Nephrogenic diabetes insipidus
• Metabolic
• Hypercalcemia
• Hypokalemia
• Infiltrative
• Amyloidosis

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Central diabetes insipidus

• 90 fo magnocellular neurons lost before
  clinically CDI develops
• destruction of the posterior pituitary alone
  generally does not result in CDI
• transient CDI following neurosurgery and
  reorganize their terminals from higher in the
  hypothalamus median eminence
• Permanent CDI injury in level og pituitary stalk
  to cause retrograde neuronal degeneration

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neurosarcoidosis

• Noncaseating granulomata can involve the cranial
  nerves, the floor of the third ventricle and
  basal meninges, region of the hypothalamus and
  optic chiasm
• Partial or total destruction of the pituitary
• Extensive infiltration of the hypothalamus by
  later autopsiespredominant site of functional
  disturbance

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• Less than one third of patients lacked sufficient
  AVP level
• Destruction of magnocellular

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Dipsogenic DI

• Some patient reset thirst osmostat despite
  adequate AVP release in response to osmotic
  stimuli
• Not respond to desmopressin therapy until Na
  concentration below the new thirst threshold

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• No definitive diagnostic test specific for
  NSremain a diagnosis of exclusion
• Tx Corticosteroids
• Pituitary hormone replacement

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LCH

• CDI occurring in 5 to 50
• Manifestation of CNS involvement
• Water metqabolism similar to NS
• Aggressive chemotherapy may prevent to CDI
• Radiotherapyresponse to therapy? Or spontaneous
  regression

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Nephrogenic diabetes insipidus

• Metabolic
• Hypercalcemia
• Hypokalemia
• Infiltrative
• Amyloidosis
• Vascular
• Sickle cell disease
• Granulomatous
• Sarcoidosis
• Infectious
• Pyelonephritis
• Obstruction
• Obstructive uropathy

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Nephrogenic diabetes insipidus

• Collecting duct permeability reflect to AVP
• AVP regulates the transport of NaCl at thick
  ascending limb (TAL) of the loop of Henle
• Decrease AQP2 expression

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Hypercalcemia

• Clinically apparent until calcium concentration
  gt11 mg/dl
• Inhibition of NaCl reabsorption in the
  TALtubulointerstitial damage play the role
• Berl et al found the TAL impaired adenylyl
  cyclase activation
• Decrease AQP2 expression

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• Activation of renal calcium-sensing receptors can
  impair concentrating ability of loop of Henle and
  collecting tubules
• Familial hypocalciuric hypercalcemia preserve
  normal urinary concentrating ability
• Prostaglandin E2, angiotensin II may also inhibit
  TAL NaCl reabsorption

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• General is reversible
• Hydration usually needed (Vicious cycle of
  dehydration exacerbating hypercalcemia and
  hypercalcemia worsening dehydration continues)

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hypokalemia

• Usually requires K deficit of greater than 200
  mEq and plasma lt3 mEq/L
• Mechanism similar to hypercalcemia and general
  less severe
• Reversible once electrolyte imbalance correction

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summary

• Disorder of AVP secretion and action sometimes
  present as the first manifestation of a variety
  systemic diseases
• Much of the pathophysiology is not understood
  completely
• Further investigation likely will allow
  physicians to offer more effective treatment,
  such as the AVP V2 antagonist for SIADH and
  edema-forming states