24

24 CASE 24


A 48-year-old woman in an inpatient psychiatric hospital reports passing a high volume of urine and experiencing excessive thirst.


The patient was admitted to the hospital 1 year ago and was diagnosed with bipolar affective disorder. Lithium has been used successfully for the past year to control the psychiatric problems.



PHYSICAL EXAMINATION



VS: T 37°C, P 80/min, R 17/min, BP 100/70 mm Hg, BMI 22

PE: Patient appears dehydrated.


LABORATORY STUDIES



Plasma analysis:
• Sodium: 150 mEq/L (normal: 135 to 145 mEq/L)

• Potassium: 4.8 mEq/L (normal: 3.5 to 5 mEq/L)

• Chloride: 115 mEq/L (normal: 101 to 112 mEq/L)

pH: 7.48 (normal venous: 7.31 to 7.41)

Osmolality: 320 mOsm/kg (normal: 275 to 293 mOsm/kg)

Urinalysis:
• Urine osmolality: 200 mOsm/kg (normal: 100 to 900 mOsm/kg)

• 24-hour sample: 4.8 L (normal: <2 L/24 hr)

Water deprivation test: Little increase in urine osmolarity after 6 hours of water deprivation. Desmopressin injection had little effect.


DIAGNOSIS


Nephrogenic diabetes insipidus



PATHOPHYSIOLOGY OF KEY SYMPTOMS


Antidiuretic hormone (ADH, vasopressin) is synthesized in the hypothalamus and released in the posterior pituitary in response to an increase in plasma osmolarity. ADH binds to two subtypes of vasopressin receptors: (1) V1 on the vasculature causing vasoconstriction and prostaglandin release and (2) V2 in the collecting duct of the kidney that mediates the response to ADH.


The major biologic action of ADH is to stimulate water reabsorption in the distal tubule, which is why the term “antidiuretic hormone” is replacing “vasopressin” for this peptide. Binding of ADH to the V2 receptor stimulates the production of cyclic adenosine monophosphate, leading to the insertion of aquaporin water channels into the apical surface of the collecting duct cells.


The renal glomerulus, proximal tubule, distal tubule, and cortical collecting duct are all in the cortex of the kidney. Only the loop of Henle, the medullary collecting duct, and the vasa recta pass through the renal medulla.


The osmolarity of the renal medullary interstitium is the driving force for the osmotic reabsorption of water from the collecting duct. Normal plasma osmolarity is 300 mOsm/L. Renal medullary interstitium osmolarity varies from a low of about 600 mOsm/L in a well-hydrated individual to a high of about 1400 mOsm/L in an individual who is dehydrated. About half of the renal medullary interstitium is due to urea accumulation, and the remainder is due to NaCl. ADH stimulates urea reabsorption from the medullary portions of the collecting duct, leading to its accumulation within the renal medulla. NaCl accumulation is the result of the Na+/K+/2Cl− transporter of the thick ascending limb of the loop of Henle.


The tight junctions of the ascending limb of the loop of Henle, the distal tubule, and the collecting duct are all impermeable to water. Consequently, tubular filtrate osmolarity can be different from that of the interstitial osmolarity. The filtrate of the ascending limb of the loop of Henle becomes dilute owing to the active transport of Na+/K+/2Cl−. In the absence of ADH, there is little further water reabsorption and the body produces a large volume of dilute urine (see Fig. 19-2).


In the presence of ADH, aquaporin channels are inserted into the apical membrane, allowing the osmotically driven reabsorption of water. ADH increases filtrate osmolarity in the distal tubule to 300 mOsm/L, equal to the renal cortex interstitium osmolarity. In the medullary collecting duct, ADH increases filtrate osmolarity up to the level of the renal medullary interstitium osmolarity, up to 1400 mOsm/L in a dehydrated individual. ADH results in the production of a small volume of highly concentrated urine (see Fig. 19-2).


Lithium diminishes the ability of V2 receptors to generate cyclic adenosine monophosphate. Consequently, the biologic action of ADH is diminished, resulting in an inability to reabsorb water and urea. Chronically, lithium may also diminish the transcription of aquaporin channels. If the disease is not too severe, this effect can be reversed if the patient is taken off of lithium. If lithium is necessary, the use of amiloride or thiazide and a low sodium diet is recommended. This combination allows a reduction in urinary volume and urinary dilution independent of ADH actions.


Impaired water reabsorption because of a defect in the kidney is termed “nephrogenic diabetes insipidus.” “Nephrogenic” indicates the problem is the renal response to ADH, not the production of ADH. Plasma ADH levels are usually high, reflecting the ADH-releasing stimulus, high plasma osmolarity. “Diabetes” refers to the large volume of urine. “Insipidus” refers to the absence of glucose in this urine and is used to distinguish the disease from another polyuria, diabetes mellitus.


Excessive water loss leads to an increase in plasma osmolarity and an increase in plasma electrolyte concentration. The increase in osmolarity stimulates thirst, leading to a polydipsia. Excessive water ingestion is physiologically appropriate, allowing the patient to partially compensate for the inability of the kidney to conserve water. Over time, the body fluid osmolality stabilizes at a higher level, changing the osmotic threshold for thirst.


If the 24-hour urine collection shows a dilute urine, the diagnosis is confirmed with the water deprivation test. Because of the impairment of ADH, an individual can become severely dehydrated in a few hours, so the test must be carefully monitored. A normal individual should increase the urine osmolarity when water is withheld. The absence of an increase in urine osmolarity indicates impairment in water reabsorption. Injection of desmopressin should result in an increase in urine osmolarity if the kidneys are able to respond to ADH and is used to distinguish central diabetes insipidus from nephrogenic diabetes insipidus.

< div class='tao-gold-member'>

Related posts:

  1. 28
  2. 23
  3. 58
  4. 71

Stay updated, free articles. Join our Telegram channel
Tags:
Jul 4, 2016 | Posted by in PHYSIOLOGY | Comments Off on 24

Full access? Get Clinical Tree
Get Clinical Tree app for offline access