Milk-alkali syndrome pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
The exact [[pathogenesis]] of milk-alkali syndrome is unknown. Hypercalcemia in milk-alkali syndrome involves several mechanisms including: [[Intestine|intestinal]] absorption of [[calcium]] is increased, [[bone]] buffering of [[calcium]] becomes saturated, and [[Kidney|renal]] excretion of [[calcium]] is decreased. Several factors that increase [[bicarbonate]] [[reabsorption]] and contribute to the [[alkalosis]] in milk-alkali syndrome include: [[Hypovolemia|volume depletion]] due to increased [[sodium]] and free water [[excretion]] caused by increased [[calcium]] intake, suppression of [[Parathyroid hormone|PTH]], direct [[Nephron|tubular]] effects of [[calcium]] and other factors that cause [[Hypovolemia|volume depletion]] or [[alkalosis]] such as [[Nausea and vomiting|vomiting]] or [[thiazide]] use. | The exact [[pathogenesis]] of milk-alkali syndrome is unknown. Hypercalcemia in milk-alkali syndrome involves several mechanisms including: [[Intestine|intestinal]] absorption of [[calcium]] is increased, [[bone]] buffering of [[calcium]] becomes saturated, and [[Kidney|renal]] excretion of [[calcium]] is decreased. Several factors that increase [[bicarbonate]] [[reabsorption]] and contribute to the [[alkalosis]] in milk-alkali syndrome include: [[Hypovolemia|volume depletion]] due to increased [[sodium]] and free water [[excretion]] caused by increased [[calcium]] intake, suppression of [[Parathyroid hormone|PTH]], direct [[Nephron|tubular]] effects of [[calcium]] and other factors that cause [[Hypovolemia|volume depletion]] or [[alkalosis]] such as [[Nausea and vomiting|vomiting]] or [[thiazide]] use. | ||
== Pathophysiology == | == Pathophysiology == | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]
Overview
The exact pathogenesis of milk-alkali syndrome is unknown. Hypercalcemia in milk-alkali syndrome involves several mechanisms including: intestinal absorption of calcium is increased, bone buffering of calcium becomes saturated, and renal excretion of calcium is decreased. Several factors that increase bicarbonate reabsorption and contribute to the alkalosis in milk-alkali syndrome include: volume depletion due to increased sodium and free water excretion caused by increased calcium intake, suppression of PTH, direct tubular effects of calcium and other factors that cause volume depletion or alkalosis such as vomiting or thiazide use.
Pathophysiology
- The exact pathogenesis of milk-alkali syndrome is unknown.
- Consumption of excessive amounts of calcium and absorbable alkali causes milk-alkali syndrome.[1]
Pathogenesis
The pathogenesis of milk-alkali syndrome involves the kidneys, bones, and intestines.[2]
Hypercalcemia
- Hypercalcemia involves the following:[3]
- Intestines absorb the high quantities of consumed calcium and cause hypercalcemia.
- Bones have a limited capacity of calcium buffering and the variations in this capacity may contribute to hypercalcemia.
- Hypercalcemia causes vasoconstriction in the kidneys, which decreases glomerular filtration rate (GFR) and calcium excretion in the kidneys.[3]
- Hypercalcemia activates calcium-sensing receptors (CaSRs) in different areas and the following effects happen:[4]
- Renal tubules
- Thick ascending loop of Henle:
- Reabsorption of sodium chloride is blocked, which leads to diuresis and an increase in calcium excretion in the kidneys. These, in turn, result in volume depletion and metabolic alkalosis.
- Distal convoluted tubules (luminal membrane) :
- Calcium reabsorption through transient receptor potential vanilloid member 5 (TRPV5) channels is increased.
- Collecting duct (luminal membranes):
- Expression of aquaporin 2 water channels is decreased, and that decreases water reabsorption and dilutes the urine.
- Thick ascending loop of Henle:
- Renal tubules
- 25-hydroxylation of vitamin D in the kidneys is reduced by excessive calcium consumption, which decreases calcium absorption in the intestine.[1]
- Hypercalcemia inhibits parathyroid hormone (PTH) which decreases bone turnover and the capacity of the bone for calcium buffering and increases the excretion of calcium in the kidneys.[3]
- Hypercalcemia causes nausea and vomiting, which in turn deteriorate volume depletion and metabolic alkalosis.[3]
Metabolic Alkalosis
- Increases the affinity of the CaSRs to calcium, which increases natriuresis.
- Stimulates TRPV5 which increases calcium reabsorption and worsens hypercalcemia.[5][4]
- Several factors that increase bicarbonate reabsorption and contribute to the alkalosis in milk-alkali syndrome include:[6]
Histopathology
- There is limited evidence on the renal histopathological findings of milk-alkali syndrome.[1]
- The following findings on autopsies have been reported:[7][8][9][10]
- Nephrocalcinosis
- Glomerulus hyalinization (partial to complete)
- Thickened Bowman's capsule
- Atrophy of the tubules
- Vascular changes
- Diffuse lymphocytic infiltration
- The following findings on biopsies have been reported:[11][12][13]
- Focal calcification in the renal tubules
- Degeneration of the tubular epithelium
- Granular material (presumably calcium laden) in and around the collecting tubules
- Hyalinization of some glomeruli
- Thickened basement membrane
- It has been suggested that the prognosis of milk-alkali syndrome is associated with the severity of the histologic changes on the biopsies and that renal calcium deposition are usually not detectable on x-ray.[13]
References
- ↑ 1.0 1.1 1.2 Medarov BI (2009). "Milk-alkali syndrome". Mayo Clin Proc. 84 (3): 261–7. doi:10.1016/S0025-6196(11)61144-0. PMC 2664604. PMID 19252114.
- ↑ Arroyo M, Fenves AZ, Emmett M (2013). "The calcium-alkali syndrome". Proc (Bayl Univ Med Cent). 26 (2): 179–81. doi:10.1080/08998280.2013.11928954. PMC 3603742. PMID 23543983.
- ↑ 3.0 3.1 3.2 3.3 Felsenfeld AJ, Levine BS (2006). "Milk alkali syndrome and the dynamics of calcium homeostasis". Clin J Am Soc Nephrol. 1 (4): 641–54. doi:10.2215/CJN.01451005. PMID 17699269.
- ↑ 4.0 4.1 Riccardi D, Brown EM (2010). "Physiology and pathophysiology of the calcium-sensing receptor in the kidney". Am J Physiol Renal Physiol. 298 (3): F485–99. doi:10.1152/ajprenal.00608.2009. PMC 2838589. PMID 19923405.
- ↑ Picolos MK, Lavis VR, Orlander PR (2005). "Milk-alkali syndrome is a major cause of hypercalcaemia among non-end-stage renal disease (non-ESRD) inpatients". Clin Endocrinol (Oxf). 63 (5): 566–76. doi:10.1111/j.1365-2265.2005.02383.x. PMID 16268810.
- ↑ Fiorino AS (1996). "Hypercalcemia and alkalosis due to the milk-alkali syndrome: a case report and review". Yale J Biol Med. 69 (6): 517–23. PMC 2589043. PMID 9436295.
- ↑ BURNETT CH, COMMONS RR (1949). "Hypercalcemia without hypercalcuria or hypophosphatemia, calcinosis and renal insufficiency; a syndrome following prolonged intake of milk and alkali". N Engl J Med. 240 (20): 787–94. doi:10.1056/NEJM194905192402001. PMID 18126919.
- ↑ WERMER P, KUSCHNER M, RILEY EA (1953). "Case reports; reversible metastatic calcification associated with excessive milk and alkali intake". Am J Med. 14 (1): 108–15. doi:10.1016/0002-9343(53)90362-3. PMID 13016590.
- ↑ HOLTEN C, LUNDBAEK K (1955). "Renal insufficiency and severe calcinosis due to excessive alkali-intake". Acta Med Scand. 151 (3): 177–83. doi:10.1111/j.0954-6820.1955.tb10281.x. PMID 14375805.
- ↑ DUFAULT FX, TOBIAS GJ (1954). "Potentially reversible renal failure following excessive calcium and alkali intake in peptic ulcer therapy". Am J Med. 16 (2): 231–6. doi:10.1016/0002-9343(54)90339-3. PMID 13124355.
- ↑ SCHOLZ DA, KEATING FR (1955). "Milk-alkali syndrome; review of eight cases". AMA Arch Intern Med. 95 (3): 460–8. doi:10.1001/archinte.1955.00250090098012. PMID 14349424.
- ↑ RANDALL RE, STRAUSS MB, McNEELY WF (1961). "The milk-alkali synfcmme". Arch Intern Med. 107: 163–81. doi:10.1001/archinte.1961.03620020013003. PMID 13739449.
- ↑ 13.0 13.1 Junor BJ, Catto GR (1976). "Renal biopsy in the milk-alkali syndrome". J Clin Pathol. 29 (12): 1074–6. doi:10.1136/jcp.29.12.1074. PMC 476303. PMID 1010876.