Diabetes insipidus is due to absolute or relative deficiency in the circulating levels or bioactivity of ADH (vasopressin).


How does it happen?]







Content 9




Complications of Injecting Drug Use

  • Local problems—Abscess (Figures 240-2 
    Image not available.

    A 32-year-old woman with type 1 diabetes developed large abscesses all over her body secondary to injection of cocaine and heroin. Her back shows the large scars remaining after the healing of these abscesses. (Courtesy of ­Richard P. Usatine, MD.)

    and 240-3; Abscess), cellulitis, septic thrombophlebitis, local induration, necrotizing fasciitis, gas gangrene, pyomyositis, mycotic aneurysm, compartmental syndromes, and foreign bodies (e.g., broken needle parts) in local areas.2
    • IDUs are at higher risk of getting methicillin-resistant Staphylococcus aureus(MRSA) skin infections that the patient may think are spider bites (Figure 240-4).
    • Some IDUs give up trying to inject into their veins and put the cocaine directly into the skin. This causes local skin necrosis that produces round atrophic scars (Figure 240-5).
  • IDUs are at risk for contracting systemic infections, including HIV and hepatitis B or hepatitis C.
    • Injecting drug users are at risk of endocarditis, osteomyelitis (Figures 240-6and 240-7), and an abscess of the epidural region. These infections can lead to long hospitalizations for intravenous antibiotics. The endocarditis that occurs in IDUs involves the right-sided heart valves (see Chapter 50, Bacterial Endocarditis).2 They are also at risk of septic emboli to the lungs, group A β-hemolytic streptococcal septicemia, septic arthritis, and candidal and other fungal infections.


Content 3

Content 13

A 54-year-old man presents to his clinician complaining of polyuria. He states that he must get up three or four times each night to urinate. He also notes frequent thirst. He denies polyphagia, urinary urgency, difficulty initiating urination, or postvoid dribbling. His medical history is notable only for bipolar disease. He has a long-standing history of noncompliance with medications for this disease, with frequent hospitalizations for both mania and depression, but has been stable on lithium for the past 6 months. He denies any symptoms of mania or depression at this time. He takes no other medications. Family history is notable for depression and substance abuse. The patient has a history of polysubstance abuse but has been “clean and sober” for the past 6 months. On examination, the patient's vital signs are within normal limits. Head-neck examination reveals slightly dry mucous membranes. Rectal examination reveals a normal prostate without masses. The remainder of his examination is unremarkable. Urinalysis reveals dilute urine without glycosuria or other abnormality. Serum electrolytes reveal a mildly increased sodium level. A diagnosis of diabetes insipidus is entertained.
1. What clues would suggest diabetes insipidus in a new patient?
  • Both central and nephrogenic diabetes insipidus result in the same symptoms and signs: polyuria, polydipsia, hypotonic urine, and hypernatremia
  • Another clue would be the rapid onset of dehydration and hypernatremia progressing to coma if the patient is deprived of access to sufficient fluid intake

2. How would you make a definitive diagnosis of diabetes insipidus?

  • The hallmark of diabetes insipidus is dilute urine, even in the face of hypernatremia
  • Dipstick testing of the urine for glucose can exclude diabetes mellitus
  • Conditions in which osmotic diuresis is responsible for polyuria can be distinguished from diabetes insipidus by their normal or elevated urine osmolality
  • Primary polydipsia is distinguished by low instead of normal or elevated serum sodium

3. What are the pathophysiologic differences between central and nephrogenic diabetes insipidus?

  • Central diabetes insipidus results from lack of synthesis or secretion of antidiuretic hormone (ADH) or vasopressin
  • It often results from acute injury (eg, post-infarction or post-trauma), leading to transient cessation of ADH secretion followed by gradual recovery
  • Familial nephrogenic diabetes insipidus results from a generalized defect in either the V2 class of vasopressin receptors or the aquaporin-2 water channel of the renal collecting ducts
  • Drug-induced nephrogenic diabetes insipidus results from the effect of lithium, fluoride, and other salts on the activity of the vasopressin receptor. It occurs in 12–30% of patients treated with these drugs





Mr. Matherli is a 54-year-old man with nephrogenic diabetes insipidus (NDI) from lithium therapy. Usually, he is excellent about keeping up his free water intake to control his sodium level. However, he was involved in a car accident requiring operation at an outside hospital. There, they did not know about his NDI, and after being NPO for 48 hours, he was found to have a serum sodium of 160 mEq/dL. He is a 100-kg man. To correct his serum sodium over the next 24 hours, at what approximate rate should the physician run intravenous 5% dextrose in water (D5W; for free water)?

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The correct answer is E. You answered C.

The answer is E. This patient has severe hypernatremia after being denied free water. In the state of nephrogenic diabetes insipidus, the kidneys fail to respond to ADH and excrete dilute urine regardless of serum osmolality. To correct this hyponatremia, you must first calculate the patient’s total free water deficit. This is calculate as: ([Na] – 140/140) × (total body water) where total body water is roughly 50%–60% of body weight (60% in men, or 60 kg for Mr. Matherli). Thus, Mr. Matherli’s free water deficit is ~8.5 L (or 8500 mL). To replace this in 24 hours requires approximately 350 mL/hr of free water administration.


A 75-year-old triathlete complains of gradually worsening vision over the past year. It seems to be involving near and far vision. The patient has never required corrective lenses and has no significant medical history other than diet-controlled hypertension. He takes no regular medications. Physical examination is normal except for bilateral visual acuity of 20/100. There are no focal visual field defects and no redness of the eyes or eyelids. Which of the following is the most likely diagnosis?

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The correct answer is A. You answered A.

Age-related macular degeneration is a major cause of painless, gradual bilateral central visual loss. It occurs as nonexudative (dry) or exudative (wet) forms. Recent genetic data have shown an association with the alternative complement pathway gene for complement factor H. The mechanism link for that association is unknown. The nonexudative form is associated with retinal drusen that leads to retinal atrophy. Treatment with vitamin C, vitamin E, beta-carotene, and zinc may retard the visual loss. Exudative macular degeneration, which is less common, is caused by neovascular proliferation and leakage of choroidal blood vessels. Acute visual loss may occur because of bleeding. Exudative macular degeneration may be treated with intraocular injection of a vascular endothelial growth factor antagonist (bevacizumab or ranibizumab). Blepharitis is inflammation of the eyelids usually related to acne rosacea, seborrheic dermatitis, or staphylococcal infection. Diabetic retinopathy, now a leading cause of blindness in the United States, causes gradual bilateral visual loss in patients with long-standing diabetes. Retinal detachment is usually unilateral and causes visual loss and an afferent pupillary defect.


Mr. Jenson is a 40-year-old man with a congenital bicuspid aortic valve who you have been seeing for more than a decade. You obtain an echocardiogram every other year to follow the progression of his disease knowing that bicuspid valves often develop stenosis or regurgitation requiring replacement in middle age. Given his specific congenital abnormality, what other anatomic structure is important to follow on his biannual echocardiograms?

Aortic root size

Left atrial size

Pulmonary artery pressures

Pulmonic valve function

Tricuspid valve regurgitation

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The correct answer is A. You answered A.

The answer is A. (Chap. 282) Bicuspid aortic valve is among the most common of congenital heart cardiac abnormalities. Valvular function is often normal in early life and thus may escape detection. Due to abnormal flow dynamics through the bicuspid aortic valve, the valve leaflets can become rigid and fibrosed, leading to either stenosis or regurgitation. However, pathology in patients with bicuspid aortic valve is not limited to the valve alone. The ascending aorta is often dilated, misnamed “poststenotic” dilatation; this is due to histologic abnormalities of the aortic media and may result in aortic dissection. It is important to screen specifically for aortopathy because dissection is a common cause of sudden death in these patients.


Several families were studied whose affected individuals have nephrogenic diabetes insipidus. This disease causes childhood symptoms of polyuria (frequent urination), polydipsia (constant thirst and frequent drinking), poor growth, and hypernatremia (increased serum sodium concentration). Administration of antidiuretic hormone was not curative, focusing attention on a renal water loss due to a transport defect. A gene named aquaporin-2 was cloned from renal tubular epithelium, its amino acid sequence derived, and structural domains hypothesized to facilitate separation of mutations from benign variants. The hypothesized structure contained several transmembrane domains demarcated by β-turns, and these potential water channels were found to be mutated in affected individuals. Which of the following amino acids is most suggestive of β-turns?

  1. Arginine and lysine

  2. Aspartic acid and glutamic acid

  3. Glycine and proline

  4. Leucine and valine

  5. Tryptophan and tyrosine

The answer is C. A β-turn structure consists of four amino acids in which the first residue is hydrogen bonded to the fourth residue of the turn (see Figure 1-5C). Glycine residues are small and flexible, whereas proline residues assume a cis or flattened conformation, making these residues amenable to tight turns. Transport proteins often have several membrane-spanning domains demarcated by β-turns that allow them to exit and return back into the membrane. These transmembrane domains form channels that regulate transport of ions and water in organs such as lung, gut, and kidney. Nephrogenic diabetes insipidus results when the kidney is less responsive to antidiuretic hormone excreted by the posterior pituitary, causing abnormal water excretion, dehydration, and electrolyte disturbances.


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