Download Disorders of Acid-Balance: Signs, Symptoms and Management of Metabolic Alkalosis and more Study notes Pathophysiology in PDF only on Docsity!
Disorders of Acid-Base Balance 6.
SIGNS AND SYMPTOMS OF METABOLIC ALKALOSIS
Central Nervous System Headache Lethargy Stupor Delirium Tetany Seizures Potentiation of hepatic encephalopathy
Cardiovascular System Supraventricular and ventricular arrhythmias Potentiation of digitalis toxicity Positive inotropic ventricular effect
Respiratory System Hypoventilation with attendant hypercapnia and hypoxemia
Neuromuscular System Chvostek’s sign Trousseau’s sign Weakness (severity depends on degree of potassium depletion)
Metabolic Effects Increased organic acid and ammonia production Hypokalemia Hypocalcemia Hypomagnesemia Hypophosphatemia
Renal (Associated Potassium Depletion) Polyuria Polydipsia Urinary concentration defect Cortical and medullary renal cysts
FIGURE 6-
Signs and symptoms of metabolic alkalosis. Mild to moderate metabolic alkalosis usually is accompanied by few if any symp- toms, unless potassium depletion is substantial. In contrast, severe metabolic alkalosis ([HCO 3 - ] > 40 mEq/L) is usually a symptomatic disorder. Alkalemia, hypokalemia, hypoxemia, hypercapnia, and decreased plasma ionized calcium concentration all contribute to
these clinical manifestations. The arrhythmogenic potential of alka- lemia is more pronounced in patients with underlying heart disease and is heightened by the almost constant presence of hypokalemia, especially in those patients taking digitalis. Even mild alkalemia can frustrate efforts to wean patients from mechanical ventilation [23,24].
Ingestion of large amounts of calcium
Augmented body content of calcium
Increased urine calcium excretion (early phase)
Urine alkalinization
Ingestion of large amounts of absorbable alkali
Augmented body bicarbonate stores
Increased renal H +^ secretion
Nephrocalcinosis
Decreased urine calcium excretion
Increased renal reabsorption of calcium
Renal vasoconstriction
Reduced renal bicarbonate excretion
Renal insufficiency
Metabolic Hypercalcemia alkalosis
FIGURE 6-
Pathophysiology of the milk-alkali syndrome. The milk-alkali syndrome comprises the triad of hypercalcemia, renal insufficiency, and metabolic alkalosis and is caused by the ingestion of large amounts of calcium and absorbable alkali. Although large amounts of milk and absorbable alkali were the culprits in the classic form of the syndrome, its modern version is usually the result of large doses of calcium carbonate alone. Because of recent emphasis on prevention and treatment of osteoporosis with calcium carbonate and the availability of this preparation over the counter, milk-alkali syndrome is currently the third leading cause
of hypercalcemia after primary hyper- parathyroidism and malignancy. Another common presentation of the syndrome origi- nates from the current use of calcium car- bonate in preference to aluminum as a phos- phate binder in patients with chronic renal insufficiency. The critical element in the pathogenesis of the syndrome is the devel- opment of hypercalcemia that, in turn, results in renal dysfunction. Generation and maintenance of metabolic alkalosis reflect the combined effects of the large bicarbon- ate load, renal insufficiency, and hypercal- cemia. Metabolic alkalosis contributes to the maintenance of hypercalcemia by increasing tubular calcium reabsorption. Superimposition of an element of volume contraction caused by vomiting, diuretics, or hypercalcemia-induced natriuresis can wors- en each one of the three main components of the syndrome. Discontinuation of calcium carbonate coupled with a diet high in sodi- um chloride or the use of normal saline and furosemide therapy (depending on the sever- ity of the syndrome) results in rapid resolu- tion of hypercalcemia and metabolic alkalo- sis. Although renal function also improves, in a considerable fraction of patients with the chronic form of the syndrome serum creatinine fails to return to baseline as a result of irreversible structural changes in the kidneys [27].
6.26 Disorders of Water, Electrolytes, and Acid-Base
Clinical syndrome
Bartter's syndrome
Type 1 NKCC2 15q15-q
Gitelman's syndrome
TSC 16q
TAL
Type 2 ROMK 11q
TAL
CCD
DCT
Affected gene Affected chromosome Localization of tubular defect
3HCO^ – 3
2K +
Na +
Thick ascending limb (TAL) Distal convoluted tuble (DCT)
Cl– Loop diuretics Thiazides
K+^ ,NH + 4
H +
Ca2+
Ca2+ Ca2+
Mg 2+
K+
Cell Cell
Peritubular space
Tubular lumen
Peritubular space
Tubular lumen
ATPase 3Na +
2K +
K+
K+
Na + Cl–
Cl–
Cl–
ATPase 3Na +
3Na +
Cortical collecting duct (CCD)
Cell
Peritubular space
Tubular lumen
2K +
Cl–
ATPase
3Na +
Na +
K+
K+
Na +
FIGURE 6-
Clinical features and molecular basis of tubular defects of Bartter’s and Gitelman’s syn- dromes. These rare disorders are characterized by chloride-resistant metabolic alkalosis, renal potassium wasting and hypokalemia, hyperreninemia and hyperplasia of the jux- taglomerular apparatus, hyperaldosteronism, and normotension. Regarding differentiat- ing features, Bartter’s syndrome presents early in life, frequently in association with growth and mental retardation. In this syndrome, urinary concentrating ability is usual- ly decreased, polyuria and polydipsia are present, the serum magnesium level is normal,
and hypercalciuria and nephrocalcinosis are present. In contrast, Gitelman’s syn- drome is a milder disease presenting later in life. Patients often are asymptomatic, or they might have intermittent muscle spasms, cramps, or tetany. Urinary con- centrating ability is maintained; hypocal- ciuria, renal magnesium wasting, and hypomagnesemia are almost constant fea- tures. On the basis of certain of these clin- ical features, it had been hypothesized that the primary tubular defects in Bartter’s and Gitelman’s syndromes reflect impairment in sodium reabsorption in the thick ascending limb (TAL) of the loop of Henle and the distal tubule, respectively. This hypothesis has been validated by recent genetic studies [28-31]. As illustrat- ed here, Bartter’s syndrome now has been shown to be caused by loss-of-function mutations in the loop diuretic–sensitive sodium-potassium-2chloride cotransporter (NKCC2) of the TAL (type 1 Bartter’s syndrome) [28] or the apical potassium channel ROMK of the TAL (where it recy- cles reabsorbed potassium into the lumen for continued operation of the NKCC cotransporter) and the cortical collecting duct (where it mediates secretion of potas- sium by the principal cell) (type 2 Bartter’s syndrome) [29,30]. On the other hand, Gitelman’s syndrome is caused by mutations in the thiazide-sensitive Na-Cl cotransporter (TSC) of the distal tubule [31]. Note that the distal tubule is the major site of active calcium reabsorption. Stimulation of calcium reabsorption at this site is responsible for the hypocalci- uric effect of thiazide diuretics.
6.28 Disorders of Water, Electrolytes, and Acid-Base
- Sabatini S, Kurtzman NA: Metabolic alkalosis: biochemical mecha- nisms, pathophysiology, and treatment. In Therapy of Renal Diseases and Related Disorders Edited by Suki WN, Massry SG. Boston: Kluwer Academic Publishers; 1997:189–210.
- Galla JH, Luke RG: Metabolic alkalosis. In Textbook of Nephrology. Edited by Massry SG, Glassock RJ. Baltimore: Williams & Wilkins; 1995:469–477.
- Madias NE, Adrogué HJ, Cohen JJ: Maladaptive renal response to secondary hypercapnia in chronic metabolic alkalosis. Am J Physiol 1980, 238:F283–289.
- Harrington JT, Hulter HN, Cohen JJ, Madias NE: Mineralocorticoid- stimulated renal acidification in the dog: the critical role of dietary sodium. Kidney Int 1986, 30:43–48.
- Beall DP, Scofield RH: Milk-alkali syndrome associated with calcium carbonate consumption. Medicine 1995, 74:89–96.
- Simon DB, Karet FE, Hamdan JM, et al .: Bartter’s syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. Nat Genet 1996, 13:183–188.
- Simon DB, Karet FE, Rodriguez-Soriano J, et al .: Genetic heterogene- ity of Bartter’s syndrome revealed by mutations in the K+^ channel, ROMK. Nat Genet 1996, 14:152–156.
- International Collaborative Study Group for Bartter-like Syndromes. Mutations in the gene encoding the inwardly-rectifying renal potassi- um channel, ROMK, cause the antenatal variant of Bartter syndrome: evidence for genetic heterogeneity. Hum Mol Genet 1997, 6:17–26.
- Simon DB, Nelson-Williams C, et al .: Gitelman’s variant of Bartter’s syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet 1996, 12:24–30.
