Renal tubular acidosis – causes, symptoms, diagnosis, treatment, pathology

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much more. Try it free today! With renal tubular acidosis, renal refers
to the kidney, tubular refers to the main tube-portion of the nephron, and acidosis
refers to having too many protons or increased acidity in blood, so renal tubular acidosis
or RTA describes increased acidity in the blood because the renal tubules can’t get
rid of protons. The kidneys contain millions of nephrons,
each of which has a renal corpuscle, and a renal tubule that ends in a collecting duct. The renal corpuscle filters large amounts
of solutes that go from the blood into the filtrate and eventually the urine, and the
renal tubule and collecting duct are responsible for fine tuning the reabsorption and secretion
of solutes to adjust the amount that ultimately gets retained by or removed from the body. Broadly speaking, renal tubular acidosis can
develop in either the proximal convoluted tubule, sometimes called just the proximal
tubule, or the distal convoluted tubule, or distal tubule, and the nearby collecting duct. The proximal tubule is lined by brush border
cells which have two surfaces. One is the apical surface that faces the tubular
lumen and is lined with microvilli, which are tiny little projections that increase
the cell’s surface area to help with solute reabsorption. The other is the basolateral surface, which
faces the peritubular capillaries, which run alongside the nephron. Now – when a molecule of bicarbonate approaches
the apical surface of the brush border cell it binds to hydrogen to form carbonic acid. At that point, an enzyme called carbonic anhydrase
type 4 which lurks in tubule among the microvilli like a shark, swims along and splits the carbonic
acid into water and carbon dioxide. The overall equation looks like this: H+ + HCO3- <-> H2CO3 <-> H2O + CO2 The water and carbon dioxide happily diffuse
across the membrane into the cells where carbonic anhydrase type 2 facilitates the reverse reaction
– combining them to form carbonic acid, which dissolves into bicarbonate and hydrogen. A sodium bicarbonate cotransporter on the
basolateral surface snatches up the bicarbonate and a nearby sodium, and shuttles both into
the blood. Meanwhile, a sodium-hydrogen exchanger on
the apical surface, pulls sodium into the cell, while pushing hydrogen back into the
tubule. So at the end of the day, there’s a movement
of bicarbonate from the tubule to the blood. Okay – so now let’s shift over to the distal
tubule and collecting duct which we’ll talk about together. First off, one type of cell these are lined
with are the alpha-intercalated cells. Like the brush border cells, the alpha intercalated
cells move bicarbonate and hydrogen from the tubule into the cell using carbonic anhydrase. The alpha intercalated cells have two major
ways to get rid of that hydrogen across the apical surface. First, they have a H+/ATPase which simply
pushes hydrogen into the tubule. Second, they have a hydrogen potassium ATPase
(H+K+ATPase) which pushes hydrogen into the tubule in exchange for potassium. With regard to bicarbonate, there is a bicarbonate/chloride
antiporter which moves bicarbonate into the blood in exchange for chloride. To prevent chloride from piling up within
the cell, there’s a potassium/chloride symporter on the basolateral surface that moves both
of these ions into the blood. In addition, there’s a chloride channel
on the basolateral surface that allows chloride to passively move down its concentration gradient
into the blood. Finally, it’s worth mentioning that like
all cells – sodium and potassium levels are controlled by Na/K ATPase pumps on the basolateral
surface which move two potassium ions into the cell and three sodium ions out of the
cell. So overall, there’s a net movement of sodium,
chloride, and bicarbonate into the blood, while hydrogen is pushed into the tubule. Once in the lumen, hydrogen binds to phosphate
or ammonia to form relatively weak acids like dihydrogen phosphate or ammonium, which then
get peed out in the urine. This allows protons to get removed without
making the urine too acidic and damaging the cells lining the tubules and the rest of the
urinary tract. The other group of cells are the principal
cells.These cells have two channels on the apical surface, a potassium channel that allows
potassium into the lumen and an epithelial sodium channel called ENaC that allows sodium
into the cell. The flow of positively charged sodium ions
into cell helps drive the positively charged potassium ions out of the cell against their
concentration gradient. There’s also a Na/K ATPase pump on the basolateral
surface that again moves 2 potassium ions in for every 3 sodium ions out. All three of these are stimulated by aldosterone,
and the combined effect is resorption of sodium and loss of potassium. In RTA type I or distal renal tubular acidosis,
the main issue is that alpha intercalated cells of the distal tubule and collecting
duct are unable to secrete hydrogen. The buildup of hydrogen in those cells leads
to a buildup of hydrogen in the blood – resulting in acidemia. The underlying cause could be a genetic mutation
in the H+ATPase pump or the H+K+ATPase pump of alpha intercalated cells. Alternatively it could be due to an acquired
defect from a medication like lithium or amphotericin B, both of which can make cells permeable,
allowing hydrogen to simply diffuse from the tubule right back into the cell. A less common mechanism, is a defect in the
bicarbonate/chloride antiporter, which causes a decrease in bicarbonate reabsorption, and
less bicarbonate in the blood, also leads to an acidemia. In RTA type II or proximal renal tubular acidosis,
the main issue is that brush border cells of the proximal tubule are unable to reabsorb
bicarbonate. As a result, bicarbonate gets lost in the
urine and it means that there is nothing to counterbalance the hydrogen ions – resulting
in acidemia. One known cause is a genetic mutation in the
sodium bicarbonate cotransporter on the basolateral surface that makes it less functional. Being able to move less bicarbonate out of
the cell, alters the intracellular bicarbonate concentration and makes it imore difficult
for bicarbonate to get brought across the apical surface into the cell. As a result, less bicarbonate gets reabsorbed
by the brush border cells, and more is left behind in the lumen of the tubule. Eventually losing bicarbonate in the urine,
means that there’s less bicarbonate in the blood – resulting in an acidemia. Unlike RTA type I, the distal intercalated
cells are still functional and can produce hydrogen ions, and can therefore can generally
still acidify the urine. RTA type II can happen independently or can
be part of a broader dysfunction of the proximal tubular cells called Fanconi syndrome. In Fanconi syndrome, in addition to the loss
of bicarbonate, there is also phosphaturia, glycosuria, aminoaciduria, uricosuria, and
proteinuria – the loss of phosphate, glucose, amino acids, uric acid, and protein in the
urine. Fanconi syndrome can be inherited, but can
also be acquired, for example, it can be a side effect of taking certain medications
like tetracycline class antibiotics. In RTA type III there is a defect in both
the distal and proximal tubule, a fairly uncommon situation. The causes are not well understood, but some
cases have been associated with congenital carbonic anhydrase deficiency, this is because
carbonic anhydrases are present in both distal and proximal tubule. Finally, there’s RTA type IV, sometimes
called hyperkalemic acidosis, and it’s classically due to aldosterone deficiency or aldosterone
resistance in the collecting ducts, which would affect both the principal and alpha
intercalated cells. Aldosterone has an important role in the regulation
of sodium, potassium,, and hydrogen levels. An example of aldosterone deficiency is Addison’s
disease, where the adrenal gland doesn’t produce enough of it. An example of aldosterone resistance is a
mutation in the epithelial sodium channel (ENaC), so that it doesn’t respond well
to normal levels of aldosterone. Either way – a reduced effect of aldosterone
can decrease the function of the Na+K+ATPase, making sodium levels fall and potassium levels
rise in the blood. A reduced effect of aldosterone on the H+/ATPase
in the intercalated cells, means that more hydrogen gets retained in the cells and eventually
in the blood, causing the acidemia. Overall, this causes high potassium, hyperkalemia,
and high levels of hydrogen ions, acidemia, in the blood. Also, since hydrogen usually combines with
ammonia in the tubule to form ammonium, with less hydrogen there’ll be less ammonium
formed and excreted in the urine. There are some other causes of RTA type IV
as well. One of them is severe hypovolemia. Or low fluid, which means less sodium is available
for reabsorption in the principal cells. The result is lower sodium levels in the cell,
which alters the ion exchange between sodium and potassium – resulting in low sodium and
high potassium levels in the blood, and the hyperkalemia contributes to the acidosis. Another cause of RTA type IV is systemic lupus
or medications like lithium and amphotericin B, all of which can make the distal tubule
and collecting duct cells more permeable to hydrogen ions, allowing them to diffuse into
the blood and causing acidosis. Initially, symptoms of renal tubular acidosis
include gastrointestinal problems like decreased appetite, vomiting, and abdominal pain. But, if left untreated, severe metabolic acidosis
can lead to vasodilation of peripheral arterioles which can cause shock. Like other causes of metabolic acidosis, there
is a compensatory pattern of breathing called Kussmaul breathing– where a person initially
takes rapid shallow breaths that become more deeper over time – in order to blow off the
carbon dioxide. Also, the urine tends to be more alkaline
than normal, typically greater than a pH of 6; this especially happens in RTA type I and
sometimes in the acute setting for RTA type II. This causes hypercalciuria and leads to the
precipitation of calcium phosphate which can cause painful kidney stones. Renal tubular acidosis is a metabolic acidosis
– a pH below 7.35 and a low bicarbonate level – with a normal anion gap. That means that the difference between measured
anions –Cl- and HCO3- and cations — Na+ and K+– is between 8 mEq/L and 12 mEq/L.
In addition, blood potassium and urine pH are typically done to identify the exact type
of RTA. Low levels of HCO3- in the blood also lead
to elevated levels of chloride, so hyperchloremia is a classic finding in RTA. In RTA type I and II, the main goal is to
replenish bicarbonate and correct hypokalemia with potassium citrate. In RTA type II, this can be achieved with
thiazide diuretics which cause water loss and increased reabsorption of bicarbonate. For RTA type IV, the goal is to treat hypoaldosteronism
with fludrocortisone or loop diuretics, which increases sodium delivery to the collecting
duct and increases potassium hydrogen exchange. Alright, as a quick recap, renal tubular acidosis
describes a condition in which the kidney is unable to secrete acids or reabsorb bicarbonate
from the body. And this most commonly results in metabolic
acidosis with a normal anion gap. If left untreated, the acidemia can cause
peripheral vasodilation and shock.


  1. An other great video! I love the way you explain everything! It is clear, compact and entertaining. I hope to one day make such good videos!

  2. Sir, can you pls make videos on metabolic acidosis and alkalosis, respiratory acidosis and alkalosis

  3. Small but important addition is that hyperkalemia causes acidosis by inhibiting ammoniagenesis in the prox tubule. The limits buffer delivery and limits acid excretion. Type 4 RTA can happen by this mechanism when there is ANY cause for hyperkalemia – hypoaldosteronism is just one of many causes of this form of acidosis

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