Summary
The milk-alkali syndrome was initially described within the early twentieth century when sufferers developed hypercalcemia, metabolic alkalosis, and renal failure after ingesting giant portions of milk, cream, and absorbable alkali to deal with peptic ulcer illness (1, 2). For a time frame after the introduction of histamine-2 blockers and proton pump inhibitors, this syndrome was just about eradicated. Nonetheless, a brand new type of milk-alkali syndrome, that some have proposed must be known as calcium-alkali syndrome, has extra lately emerged as a comparatively widespread trigger for hypercalcemia and metabolic alkalosis (3). The calcium-alkali syndrome is triggered partly by the ingestion of huge portions of calcium carbonate, which is on the market over-the-counter. Using calcium carbonate has steadily elevated as an antacid and as a calcium complement to deal with or forestall osteoporosis (3). We report a case of calcium-alkali syndrome.
CASE REPORT
A 78-year-old Caucasian lady offered to the emergency division after falling and injuring her proper arm. She complained of common malaise, weak spot, and dizziness for a number of days. She denied fevers, chills, weight adjustments, bone pains, dyspnea, chest pains, palpitations, or urinary signs. Her previous medical historical past was vital for continual obstructive pulmonary illness, hypertension, atrial fibrillation, and continual kidney illness with a baseline creatinine of 1.3 mg/dL. Her common drugs included verapamil 180 mg twice every day, ramipril 5 mg every day, warfarin 5 mg every day, ibandronate 2.5 mg every day, and calcium with vitamin D over-the-counter dietary supplements. The affected person lived in an impartial residing facility. She had a earlier 15 pack-year historical past of tobacco use however give up 17 years in the past. She denied any alcohol or leisure drug use.
On preliminary examination, her blood strain was 215/90 mm Hg, pulse 100 beats/minute, respiratory charge 20 breaths/minute, and temperature 97°F. She was alert and oriented to particular person, place, and time; nevertheless, she was irritable, drowsy, and sluggish to reply questions. She had dry mucous membranes and poor pores and skin turgor. Her chest was clear to auscultation bilaterally. On precordial examination, no murmurs have been heard. Her stomach was gentle, nontender, and nondistended. Her extremities had full vary of movement and regular power.
Preliminary laboratory outcomes included hemoglobin, 16.2 g/dL; hematocrit, 48.2%; sodium, 138 mEq/L; potassium, 4.2 mEq/L; chloride, 96 mEq/L; bicarbonate, 32 mEq/L; blood urea nitrogen, 35 mg/dL; creatinine, 2.9 mg/dL; calcium, 14.4 mg/dL; albumin, 4.0 g/dL; ionized calcium, 1.52 mmol/L; phosphorus, 5.2 mg/dL; intact parathyroid hormone, 21.0 pg/dL; thyroid-stimulating hormone, 2.66 microIU/L; free thyroxine, 1.26 ng/dL; and 25-hydroxy-vitamin D, 11.0 pg/dL. Serum and urine protein electrophoreses didn’t reveal any monoclonal proteins.
Her chest radiograph was regular. Renal sonography confirmed bilateral elevated echogenicity and cortical thinning, according to continual renal illness.
Upon additional questioning, the affected person reported that she had ingested about one bottle (>50 tablets) of calcium carbonate tablets (500 mg) over the earlier 3 days to deal with heartburn signs. Throughout this time she additionally continued taking her common calcium and vitamin D dietary supplements. The prognosis of calcium-alkali syndrome was made.
Intravenous regular saline was administered, and all calcium and vitamin D dietary supplements have been discontinued. On day 2, the affected person was extra lucid, awake, and capable of readily talk. Calcium and creatinine ranges dropped to 12.8 mg/dL and a couple of.7 mg/dL, respectively. On day 5, the calcium and bicarbonate ranges have been regular at 9.6 mg/dL and 27 mEq/L. The creatinine and blood urea nitrogen have been at her baseline values of 1.3 mg/dL and 16 mg/dL, respectively.
The affected person was educated on the correct use and dosing of all over-the-counter drugs, together with calcium and vitamin D dietary supplements. She was discharged house on the fifth day of hospitalization.
DISCUSSION
The calcium-alkali syndrome is the third main explanation for hypercalcemia in hospitalized sufferers after major hyperparathyroidism and malignant neoplasms (4). The present model of this syndrome has a number of biochemical and epidemiological variations from the standard milk-alkali syndromes described within the early to mid 1900s. The historic situations have been extra widespread in middle-aged males with peptic ulcer illness and have been as a result of hourly ingestion of sodium bicarbonate, magnesium carbonate, and bismuth subcarbonate (“Sippy Powder”) along with cream and milk. In 1949, Burnett et al described a continual, extra persistent variant of this dysfunction (5). The introduction of histamine-2 receptor blockers (in 1976) and proton pump inhibitors (in 1989) to dam acid secretion, in addition to therapies directed at eradicating Helicobacter pylori, just about eradicated the basic acute and continual types of the milk-alkali syndrome. Over the past a number of many years, the “modern” model was acknowledged. This way extra generally impacts postmenopausal ladies who ingest giant quantities of calcium dietary supplements, generally along with vitamin D and infrequently with thiazide diuretics to stop or deal with osteoporosis (6–8). It has additionally occurred in transplant sufferers taking excessive doses of calcium carbonate to stop osteoporosis associated to continual steroid use (6). Using calcium-containing antacids to deal with dyspepsia additionally could happen, as was the case within the present report. It has been steered that the trendy syndrome be known as the calcium-alkali syndrome as a result of it is because of ingestion of soluble calcium salts as an alternative of milk, cream, and the opposite alkali sources listed above (3).
The calcium-alkali syndrome, much like the standard model, is characterised by hypercalcemia, metabolic alkalosis, and renal harm. Nonetheless, serum phosphorus ranges have been normally excessive within the historic kinds as a result of excessive phosphorus load from cream and milk and the event of acute and continual renal harm. The present calcium-alkali syndrome extra usually presents with a traditional and even low serum phosphorus focus ensuing from the dietary phosphate-binding properties of calcium carbonate (6–8).
Though serum vitamin D is normally suppressed in sufferers with calcium-alkali syndrome, it could be regular and even elevated if vitamin D dietary supplements have contributed to the dysfunction (8). Serum parathyroid hormone ranges, which might be anticipated to be low, are generally regular. This can be on account of renal insufficiency or associated to a speedy fall in serum calcium quickly after initiation of aggressive intravenous saline infusion (7).
The pathogenesis of calcium-alkali syndrome entails the interaction of a number of organ programs, together with bone, intestines, and the kidney. The ingestion of huge quantities of calcium-containing compounds will increase intestinal absorption of calcium and causes hypercalcemia. Hypercalcemia will constrict the renal arterioles, scale back the glomerular filtration charge, and reduce renal calcium excretion (9). Calcium-sensing receptors (CaSRs) are positioned in lots of tissues all through the physique, together with the renal tubules, the intestines, and the parathyroid and thyroid glands. When excessive calcium ranges activate the CaSRs within the thick ascending loop of Henle, sodium chloride reabsorption at this website is inhibited, inflicting diuresis and rising renal calcium excretion (i.e., a loop diuretic-like impact). This impact additionally contributes to quantity depletion and metabolic alkalosis (10). CaSRs are additionally current on the luminal membrane of the distal convoluted tubules, and activation of those receptors (by excessive renal tubule calcium concentrations) will increase calcium reabsorption through TRVP5 channels (10). As well as, CaSRs are discovered on the luminal membranes of the amassing duct cells, and their activation reduces expression of aquaporin 2 water channels. This reduces renal tubule water reabsorption and causes the excretion of dilute urine (10). The online impact is a salt and water diuresis with variable impression on renal calcium excretion. Metabolic alkalosis helps to perpetuate this cycle by rising the affinity of the CaSRs to calcium, which reinforces the natriuresis. An alkaline pH additionally stimulates the exercise of an essential calcium selective receptor known as the transient receptor potential vanilloid member 5 (TRPV5); this enhances calcium reabsorption and results in worsening hypercalcemia (10, 11). To the extent hypercalcemia suppresses serum parathyroid hormone, renal bicarbonate reabsorption is promoted. Moreover, hypercalcemia could generate nausea and vomiting, which worsens the quantity depletion and alkalosis (9).
The prognosis of calcium-alkali syndrome must be thought-about when a affected person presents with acute renal harm, metabolic alkalosis, hypercalcemia, and a historical past of extreme calcium (± vitamin D) consumption. Usually, the primary and most essential remedy for calcium-alkali syndrome is extracellular quantity enlargement with intravenous saline. This may hopefully enhance renal perform and improve renal calcium and bicarbonate excretion. It’s also important to establish all calcium salt and vitamin D–containing drugs that the affected person is taking and to offer schooling about applicable dosing. It could be troublesome to find out the suitable dose of calcium salts for a given affected person. The syndrome has been reported after ingestion of doses as little as 1 g of elemental calcium every day (11). Nonetheless, most reported circumstances of the syndrome doc ingestion of a minimum of 4 g of elemental calcium per day. Though a every day consumption of two g of calcium is taken into account secure for the overall inhabitants, smaller doses of 1.2 to 1.5 g every day must be used when sufferers have danger components that improve their probability of growing the calcium-alkali syndrome (3, 8, 9). For instance, the aged and sufferers with continual kidney illness are extra inclined as a result of they may have a decrease glomerular filtration charge and decreased calcium clearance (9, 11). Moreover, the skeleton of aged topics doesn’t buffer calcium hundreds in addition to that of youthful topics (9).
Thiazide diuretic use can also predispose to the event of this situation by enhancing renal tubule calcium absorption and by selling quantity depletion and alkalosis. Moreover, any drugs that scale back glomerular filtration charge, similar to nonsteroidal antiinflammatory medicine and angiotensin-converting enzyme inhibitors, can contribute to the event of the syndrome (9).
References – “calcium alkaline”
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