Updated: 2/24/2018

Proximal Tubule Diuretics

Topic
Review Topic
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Questions
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Evidence
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Overview
 

 
Snapshot
  • A 32-year-old previously healthy man develops headache, fatigue, vomiting, and shortness of breath about 12 hours after arriving to Mt. Everest Base Camp. Over the next day, he develops mild difficulty walking, and confusion. He is seen by a physician who administers a medication and advises him to rest. His symptoms improve over the next 24-48 hours. (Acetazolamide)
Mannitol
  • Mechanism 
    • osmotic diuretic
      • increases osmotic pressure of the glomerular filtrate
        • this in turn impairs tubular reabsorption of water and electrolytes
  • Clinical use
    • oliguria
      • which can result from shock and trauma
    • drug overdose
      • promotes urinary excretion of toxic substances
    • glaucoma
      • ↓ intraocular pressure
    • increased intracranial pressure
      • especially in the setting of cerebral edema
  • Toxicity 
    • pulmonary edema 
    • congestive heart failure (CHF) exacerbation
    • hypovolemia
  • Contraindications
    • anuria
    • CHF
Acetazolamide
  • Mechanism
    • carbonic anhydrase inhibitor
      • blocks reabsorption of bicarbonate
        • dissociation of carbonic acid into water and carbon dioxide in the proximal tubule prevented
      • bicarbonate in the lumen then binds to sodium to form sodium bicarbonate which is excreted
    • results in sodium bicarbonate diuresis and ↓ total body bicarbonate
      • loss of bicarbonate results in metabolic acidosis
  • Clinical use
    • glaucoma
    • urinary alkalinization
    • metabolic alkalosis
    • altitude sickness
    • increased intracranial pressure
      • especially for idiopathic intracranial hypertension
  • Toxicity
    • hyperchloremic metabolic acidosis (non-anion gap)
    • type 2 renal tubular acidosis
    • hypokalemia
    • neuropathy/parasthesias
    • ↑ renal stone production
      • calcium phosphate stones
    • ammonia toxicity
    • sulfa allergy
 

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Questions (2)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
Calculator

(M1.RL.6) A 56-year-old male with history of CHF presents to a trauma center following a motor vehicle accident. On arrival, his Glasgow Coma Scale score is 8, and he is found to have increased intracranial pressure. Mannitol is administered. Which of the following side effects of the drug would you most likely observe in this patient? Review Topic

QID: 100960
1

Blood dyscrasias

8%

(36/460)

2

Seizures

21%

(95/460)

3

Pulmonary edema

47%

(217/460)

4

Arrhythmias

20%

(94/460)

5

Restrictive cardiomyopathy

3%

(13/460)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M1.RL.48) A 61-year-old male is given acetazolamide to treat open-angle glaucoma. Upon diuresis, his urine is found to be highly alkaline. Which of the following accounts for the alkaline nature of this patient’s urine? Review Topic

QID: 101002
1

Inhibition of chlorine reabsorption in the thick ascending loop of Henle

6%

(7/108)

2

Inhibition of chlorine reabsorption in the distal convoluted tubule

12%

(13/108)

3

Inhibition of acid secretion in alpha-intercalated cells

6%

(7/108)

4

Inhibition of bicarbonate reabsorption in the proximal tubule

55%

(59/108)

5

Inhibition of bicarbonate reabsorption in beta-intercalated cells

13%

(14/108)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 4
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