Milk-alkali syndrome
Encyclopedia
In medicine
, milk-alkali syndrome, also called Burnett's syndrome in honour of Charles Hoyt Burnett, the American physician who first described it, is characterized by hypercalcemia caused by repeated ingestion of calcium
and absorbable alkali
(such as calcium carbonate
, or milk
and sodium bicarbonate
). If untreated, milk-alkali syndrome may lead to metastatic calcification
and renal failure
.
It was most common in the early 20th century, but there has been a recent increase in the number of cases reported.
, as prescribed by the "Sippy regimen", leading to overingestion of two key ingredients that lead to the disorder, excess calcium and excess base. Ingesting over two grams of elemental calcium
per day produces this disorder in susceptible individuals. Gastrointestinal
absorption of such a large amount of calcium leads to hypercalcemia. This inhibits parathyroid hormone
secretion by the parathyroid gland
and may also lead to diabetes insipidus
. The body's attempt to rid itself of the excess base in the urine may cause bicarbonaturia and subsequent hypovolemia
due to transport of sodium ions to accompany the bicarbonate.
Hypovolemia may increase the reabsorption of calcium and bicarbonate
in the proximal convoluted tubules of the kidney. Elevated bicarbonate levels in the blood raises the pH
, producing an alkalemia. In this state, excess bicarbonate eventually begins to reach the distal convoluted tubule
, leading to sodium retention in the lumen
, an effect similar to the action of thiazide
diuretics, hence increasing lumen positivity and driving calcium through the passive calcium channels to bind intracellular calbindin
. Finally, because of the decreased intracellular sodium, there is an increased driving force for the basolateral Na+/Ca++ antiporter, thus facilitating calcium reabsorption. Basically, hypovolemia is the culprit that prevents correction of the hypercalcemia.
The understanding of this mechanism led to the development of a simple yet elegant treatment for hypercalcemia. The first and most important step is intravenous infusion of normal saline
to restore the intravascular volume, which reverses the calcium and bicarbonate retention in the PCT. Then a loop diuretic
is used, but only after the volume replacement is complete, otherwise volume contraction would result, which would further exacerbate the hypercalcemia. The loop diuretics inhibit the Na-K-2Cl symporter
and hence eliminate passive diffusion of potassium into the lumen via the ROMK
channel. This effectively removes the net positive charge from the lumen, one of the main driving forces for calcium reabsorption via the paracellular pathway. In addition, loop diuretics increase the flow of luminal contents, which helps flush the calcium to the distal nephron.
, vomiting
, constipation
and a host of psychiatric effects, including weakness, fatigue and altered mental status. Thus, a level of serum
calcium
must be obtained, but a full workup must include total/ionized calcium
, albumin
, phosphate
, PTH
, PTHrP, vitamin D
and TSH
. In addition, evaluation of hypercalcemia must include an ECG, which may show a short QT interval.
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, milk-alkali syndrome, also called Burnett's syndrome in honour of Charles Hoyt Burnett, the American physician who first described it, is characterized by hypercalcemia caused by repeated ingestion of calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
and absorbable alkali
Alkali
In chemistry, an alkali is a basic, ionic salt of an alkali metal or alkaline earth metal element. Some authors also define an alkali as a base that dissolves in water. A solution of a soluble base has a pH greater than 7. The adjective alkaline is commonly used in English as a synonym for base,...
(such as calcium carbonate
Calcium carbonate
Calcium carbonate is a chemical compound with the formula CaCO3. It is a common substance found in rocks in all parts of the world, and is the main component of shells of marine organisms, snails, coal balls, pearls, and eggshells. Calcium carbonate is the active ingredient in agricultural lime,...
, or milk
Milk
Milk is a white liquid produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals before they are able to digest other types of food. Early-lactation milk contains colostrum, which carries the mother's antibodies to the baby and can reduce the risk of many...
and sodium bicarbonate
Sodium bicarbonate
Sodium bicarbonate or sodium hydrogen carbonate is the chemical compound with the formula Na HCO3. Sodium bicarbonate is a white solid that is crystalline but often appears as a fine powder. It has a slightly salty, alkaline taste resembling that of washing soda . The natural mineral form is...
). If untreated, milk-alkali syndrome may lead to metastatic calcification
Metastatic calcification
Metastatic calcification is deposition of calcium salts in otherwise normal tissue, because of elevated serum levels of calcium in blood, which can occur because of deranged metabolism as well as increased absorption or decreased excretion of calcium and related minerals.It occurs as opposed to...
and renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
.
It was most common in the early 20th century, but there has been a recent increase in the number of cases reported.
Pathophysiology
The name "milk-alkali syndrome" derives from when patients would take in excessive amounts of milk and antacids to control their dyspepsiaDyspepsia
Dyspepsia , also known as upset stomach or indigestion, refers to a condition of impaired digestion. It is a medical condition characterized by chronic or recurrent pain in the upper abdomen, upper abdominal fullness and feeling full earlier than expected when eating...
, as prescribed by the "Sippy regimen", leading to overingestion of two key ingredients that lead to the disorder, excess calcium and excess base. Ingesting over two grams of elemental calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
per day produces this disorder in susceptible individuals. Gastrointestinal
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
absorption of such a large amount of calcium leads to hypercalcemia. This inhibits parathyroid hormone
Parathyroid hormone
Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...
secretion by the parathyroid gland
Parathyroid gland
The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the rear surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest...
and may also lead to diabetes insipidus
Diabetes insipidus
Diabetes insipidus is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine. There are several different types of DI, each with a different cause...
. The body's attempt to rid itself of the excess base in the urine may cause bicarbonaturia and subsequent hypovolemia
Hypovolemia
In physiology and medicine, hypovolemia is a state of decreased blood volume; more specifically, decrease in volume of blood plasma...
due to transport of sodium ions to accompany the bicarbonate.
Hypovolemia may increase the reabsorption of calcium and bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
in the proximal convoluted tubules of the kidney. Elevated bicarbonate levels in the blood raises the pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
, producing an alkalemia. In this state, excess bicarbonate eventually begins to reach the distal convoluted tubule
Distal convoluted tubule
The distal convoluted tubule is a portion of kidney nephron between the loop of Henle and the collecting duct system.- Physiology :It is partly responsible for the regulation of potassium, sodium, calcium, and pH...
, leading to sodium retention in the lumen
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
, an effect similar to the action of thiazide
Thiazide
Thiazide is a term used to describe a type of molecule and a class of diuretics often used to treat hypertension and edema ....
diuretics, hence increasing lumen positivity and driving calcium through the passive calcium channels to bind intracellular calbindin
Calbindin
Calbindin refers to several calcium-binding proteins. They were originally described as vitamin D-dependent calcium-binding proteins in the intestine and kidney in the chick and mammals...
. Finally, because of the decreased intracellular sodium, there is an increased driving force for the basolateral Na+/Ca++ antiporter, thus facilitating calcium reabsorption. Basically, hypovolemia is the culprit that prevents correction of the hypercalcemia.
The understanding of this mechanism led to the development of a simple yet elegant treatment for hypercalcemia. The first and most important step is intravenous infusion of normal saline
Saline (medicine)
In medicine, saline is a general term referring to a sterile solution of sodium chloride in water but is only sterile when it is to be placed intravenously, otherwise, a saline solution is a salt water solution...
to restore the intravascular volume, which reverses the calcium and bicarbonate retention in the PCT. Then a loop diuretic
Loop diuretic
Loop diuretics are diuretics that act on the ascending loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency...
is used, but only after the volume replacement is complete, otherwise volume contraction would result, which would further exacerbate the hypercalcemia. The loop diuretics inhibit the Na-K-2Cl symporter
Na-K-2Cl symporter
The Na-K-Cl cotransporter is a protein that aids in the active transport of sodium, potassium, and chloride into and out of cells. There are two varieties, or isoforms, of this membrane transport protein, called NKCC1 and NKCC2. NKCC1 is widely distributed throughout the body; it has important...
and hence eliminate passive diffusion of potassium into the lumen via the ROMK
ROMK
ROMK is an acronym for the Renal Outer Medullary Potassium channel. This is an ATP-dependent potassium channel that transports potassium out of cells. It plays an important role in potassium recycling in the thick ascending limb and potassium secretion in the cortical collecting duct of the...
channel. This effectively removes the net positive charge from the lumen, one of the main driving forces for calcium reabsorption via the paracellular pathway. In addition, loop diuretics increase the flow of luminal contents, which helps flush the calcium to the distal nephron.
Clinical
Effects due to hypercalcemia may be remembered by the mnemonic bones, stones, groans and psychiatric overtones [ or moans ] . This means an increased risk of kidney stones, bone fractures, anorexiaAnorexia (symptom)
Anorexia is the decreased sensation of appetite...
, vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
and a host of psychiatric effects, including weakness, fatigue and altered mental status. Thus, a level of serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
must be obtained, but a full workup must include total/ionized calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
, albumin
Human serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein...
, phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
, PTH
PTH
PTH may refer to:*Parathyroid hormone*Pin through hole, mounting scheme used in electronics with component leads inserted through drilled holes*Plated through hole, used in electronics to connect layers with plated through hole vias...
, PTHrP, vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
and TSH
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
. In addition, evaluation of hypercalcemia must include an ECG, which may show a short QT interval.
External links
- eMedicine.com - Milk-Alkali Syndrome (http://www.emedicine.com/med/topic1477.htm).