is a diuretic used to alkalinize the urine or treat metabolic alkalosis as it inhibits carbonic anhydrase.
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 20-year-old man comes to the clinic because of muscle cramps and fatigue for the past year. He has experienced muscle cramps his entire life, but they have now become more frequent and painful. He has always awoken several times per night to urinate. His medical history includes chronic mild hypokalemia and hypomagnesemia. Family history is significant for similar symptoms in one of his four older sisters. He takes no medications. His temperature is 37.0°C (98.6°F), pulse is 76/min, respirations are 14/min, and blood pressure is 126/78 mm Hg. Physical examination shows a tired-appearing male with no other abnormalities. In addition to his chronic electrolyte deficits, laboratory studies show a mild metabolic alkalosis. Which of the following is the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH
With metabolic alkalosis, “alkalosis” refers to a process that raises blood pH above 7.45, and “metabolic” refers to the fact that it’s caused by an increase in the concentration of bicarbonate HCO3− in the blood.
Normally, blood pH depends on the balance or ratio between the concentration of bases, mainly bicarbonate HCO3−, which increases the pH, and acids, which decrease the pH.
The blood pH needs to be constantly between 7.35 and 7.45.
Now, metabolic alkalosis can typically happen from two main causes - loss of hydrogen H+ ions and gain of HCO3− bicarbonate ions, or, most often, a combination of these two.
Loss of hydrogen H+ ions can occur either from the gastrointestinal tract or from the kidneys.
The first case most commonly happens during vomiting, because the gastric secretions are very acidic, meaning that they have lots of hydrogen H+ ions.
On top of that, normally, as gastric secretions flow into the pancreas, they’re met with HCO3− bicarbonate secretions which neutralize the acid so that the various pancreatic enzymes like trypsin and chymotrypsin, can work effectively.
So during vomiting, not only is the stomach acid lost, but in addition the pancreas doesn’t secrete HCO3− bicarbonate into the intestines, and so it builds up in the blood instead.
Another way that hydrogen H+ ions can be lost is through the urine, in the context of having too much of the hormone aldosterone.
This can happen, when there’s an adrenal tumor that secretes excess aldosterone.
The aldosterone makes the α- intercalated cells of the distal convoluted tubule and collecting duct dump out hydrogen H+ ions and reabsorb more bicarbonate HCO3− ions.
The result is that the urine becomes more acidic and the blood becomes more basic.
Now, the second cause - a primary gain of HCO3− bicarbonate ions - is usually caused by an increased reabsorption of HCO3− bicarbonate ions from the kidneys.
There are various things that could stimulate the kidneys to do that.
The resulting alkalosis is called a contraction alkalosis.
Another stimulus is hypokalemia, or decreased levels of potassium in the blood, which can be due to excessive loss from the gastrointestinal tract, like in diarrhea, or from the kidneys due to diuretic use.
In any case, when there’s less volume or less potassium in the extracellular space, it triggers the renin-angiotensin-aldosterone mechanism.
As a result, angiotensin II and aldosterone levels rise, and the kidneys start to retain water and reabsorb more bicarbonate HCO3− ions in the proximal convoluted tubule.
In addition, the α- intercalated cells of the distal convoluted tubule and the collecting ducts secrete some hydrogen H+ ions into the urine, but, most importantly, also make new bicarbonate HCO3− ions, which will again get reabsorbed.
Now, in other cases, excess bicarbonate HCO3− ions don’t come from within our bodies at all, but are ingested in large amounts, usually in the form of antacids, like NaHCO3 sodium bicarbonate.
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