Renal tubular acidosis
Encyclopedia
Renal tubular acidosis is a medical condition that involves an accumulation of acid in the body due to a failure of the kidney
s to appropriately acidify the urine
. When blood is filtered by the kidney, the filtrate passes through the tubules of the nephron
, allowing for exchange of salts, acid equivalents, and other solutes before it drains into the bladder
as urine
. The metabolic acidosis
that results from RTA may be caused either by failure to recover sufficient (alkaline) bicarbonate
ions from the filtrate in the early portion of the nephron (proximal tubule
) or by insufficient secretion of (acid
) hydrogen ions into the latter portions of the nephron (distal tubule). Although a metabolic acidosis also occurs in those with renal insufficiency, the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys. Several different types of RTA exist, which all have different syndromes and different causes.
The word acidosis
refers to the tendency for RTA to lower the blood's pH. When the blood pH is below normal (7.35), this is called acidemia. The metabolic acidosis caused by RTA is a normal anion gap acidosis
.
An overview of types 1, 2, and 4 is presented below (type 3 is usually excluded from modern classifications):
Distal RTA (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cell
s of the cortical collecting duct of the distal nephron
. This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a pH
of less than 5.3. Because renal excretion is the primary means of eliminating acid from the body, there is consequently a tendency towards acidemia. There is an inability to excrete while cannot be reabsorbed, leading to acidemia (as builds up in the body) and hypokalemia (as cannot be reabsorbed).
This leads to the clinical features of dRTA;
, aminoaciduria, uricosuria and tubular proteinuria
.
The principal feature of Fanconi's syndrome is bone demineralization (osteomalacia
or rickets
) due to phosphate wasting.
Combined dRTA and pRTA is also observed as the result of inherited carbonic anhydrase
II deficiency. Mutations in the gene encoding this enzyme give rise to an autosomal recessive syndrome of osteopetrosis
, renal tubular acidosis, cerebral calcification
, and mental retardation. It is very rare and cases from all over the world have been reported, of which about 70% are from the Magreb region of North Africa, possibly due to the high prevalence of consanguinity
there.
The kidney problems are treated as described above. There is no treatment for the osteopetrosis or cerebral calcification.
Type 3 is rarely discussed. Most comparisons of RTA are limited to a comparison of types 1, 2, and 4.
Type 4 RTA is not actually a tubular disorder at all nor does it have a clinical syndrome similar to the other types of RTA described above. It was included in the classification of renal tubular acidoses as it is associated with a mild (normal anion gap) metabolic acidosis due to a physiological reduction in proximal tubular ammonium
excretion, which is secondary to hypoaldosteronism
, and results in a decrease in urine buffering capacity. Its cardinal feature is hyperkalemia
, and measured urinary acidification is normal, hence it is often called hyperkalemic RTA or tubular hyperkalemia.
Causes include:
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s to appropriately acidify the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
. When blood is filtered by the kidney, the filtrate passes through the tubules of the nephron
Nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....
, allowing for exchange of salts, acid equivalents, and other solutes before it drains into the bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
as urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
. The metabolic acidosis
Metabolic acidosis
In medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
that results from RTA may be caused either by failure to recover sufficient (alkaline) bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
ions from the filtrate in the early portion of the nephron (proximal tubule
Proximal tubule
The proximal tubule is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.-Structure and appearance:...
) or by insufficient secretion of (acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
) hydrogen ions into the latter portions of the nephron (distal tubule). Although a metabolic acidosis also occurs in those with renal insufficiency, the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys. Several different types of RTA exist, which all have different syndromes and different causes.
The word acidosis
Acidosis
Acidosis is an increased acidity in the blood and other body tissue . If not further qualified, it usually refers to acidity of the blood plasma....
refers to the tendency for RTA to lower the blood's pH. When the blood pH is below normal (7.35), this is called acidemia. The metabolic acidosis caused by RTA is a normal anion gap acidosis
Normal anion gap acidosis
In renal physiology, normal anion gap acidosis, and less precisely non-anion gap acidosis, is an acidosis that is not accompanied by an abnormally increased anion gap....
.
An overview of types 1, 2, and 4 is presented below (type 3 is usually excluded from modern classifications):
| Type | Type 1 | Type 2 | Type 4 |
|---|---|---|---|
| Location | Distal tubules | Proximal tubules | Adrenal |
| Acidosis? | Yes (severe) | Yes | Mild when present |
| Potassium Potassium Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are... |
Hypokalemia Hypokalemia Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low... |
Hypokalemia | Hyperkalemia Hyperkalemia Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated... |
| Pathophys | H+ secretion | Bicarb reabsorption | hypoaldosteronism Hypoaldosteronism In medicine , hypoaldosteronism refers to decreased levels of the hormone aldosterone.The term "isolated hypoaldosteronism" is used to describe lowered aldosterone without corresponding changes in cortisol... /pseudohypoaldosteronism Pseudohypoaldosteronism Pseudohypoaldosteronism is a condition that mimics hypoaldosteronism. However, the condition is due to a failure of response to aldosterone, and levels of aldosterone are actually elevated, due to a lack of feedback.... |
Type 1-Distal RTA
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s of the cortical collecting duct of the distal nephron
Nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....
. This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a 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...
of less than 5.3. Because renal excretion is the primary means of eliminating acid from the body, there is consequently a tendency towards acidemia. There is an inability to excrete while cannot be reabsorbed, leading to acidemia (as builds up in the body) and hypokalemia (as cannot be reabsorbed).
This leads to the clinical features of dRTA;
- Normal anion gapAnion gapThe anion gap is the difference in the measured cations and the measured anions in serum, plasma, or urine. The magnitude of this difference in the serum is often calculated in medicine when attempting to identify the cause of metabolic acidosis...
metabolic acidosisMetabolic acidosisIn medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
/acidemia - HypokalemiaHypokalemiaHypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
- Urinary stoneKidney stoneA kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
formation (related to alkaline urine, hypercalciuriaHypercalciuriaHypercalciuria or hypercalcinuria is the condition of elevated calcium in the urine. Chronic hypercalcinuria may lead to impairment of renal function, nephrocalcinosis, and renal insufficiency....
, and low urinary citrate). - NephrocalcinosisNephrocalcinosisNephrocalcinosis, once known as Albright's calcinosis after Fuller Albright, is a term originally used to describe deposition of calcium salts in the renal parenchyma due to hyperparathyroidism. It is now more commonly used to describe diffuse, fine, renal parenchymal calcification on radiology...
(deposition of calciumCalciumCalcium 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...
in the substance of the kidney) - BoneBoneBones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
demineralisation (causing ricketsRicketsRickets is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium , phosphorus or calcium, potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries...
in children and osteomalaciaOsteomalaciaOsteomalacia is the softening of the bones caused by defective bone mineralization secondary to inadequate amounts of available phosphorus and calcium, or because of overactive resorption of calcium from the bone as a result of hyperparathyroidism...
in adults)
Type 2-Proximal RTA
Proximal RTA (pRTA) is caused by a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the urine can acidify to a pH of less than 5.3. pRTA also has several causes, and may occasionally be present as a solitary defect, but is usually associated with a more generalised dysfunction of the proximal tubular cells called Fanconi's syndrome where there is also phosphaturia, glycosuriaGlycosuria
Glycosuria or glucosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because the kidneys are able to reclaim all of the filtered glucose back into the bloodstream. Glycosuria is nearly always caused by elevated blood glucose levels, most commonly due to...
, aminoaciduria, uricosuria and tubular proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
.
The principal feature of Fanconi's syndrome is bone demineralization (osteomalacia
Osteomalacia
Osteomalacia is the softening of the bones caused by defective bone mineralization secondary to inadequate amounts of available phosphorus and calcium, or because of overactive resorption of calcium from the bone as a result of hyperparathyroidism...
or rickets
Rickets
Rickets is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium , phosphorus or calcium, potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries...
) due to phosphate wasting.
Type 3 RTA-Combined proximal and distal RTA
In some patients, their RTA shares features of both dRTA and pRTA. This rare pattern was observed in the 1960s and 1970s as a transient phenomenon in infants and children with dRTA, possibly in relation with some exogenous factor such as high salt intake, and is no longer observed. This form of RTA has also been referred to as juvenile RTA.Combined dRTA and pRTA is also observed as the result of inherited carbonic anhydrase
Carbonic anhydrase
The carbonic anhydrases form a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons , a reversible reaction that occurs rather slowly in the absence of a catalyst...
II deficiency. Mutations in the gene encoding this enzyme give rise to an autosomal recessive syndrome of osteopetrosis
Osteopetrosis
Osteopetrosis, literally "stone bone", also known as marble bone disease and Albers-Schonberg disease is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis, in which the bones become less dense and more brittle,...
, renal tubular acidosis, cerebral calcification
Calcification
Calcification is the process in which calcium salts build up in soft tissue, causing it to harden. Calcifications may be classified on whether there is mineral balance or not, and the location of the calcification.-Causes:...
, and mental retardation. It is very rare and cases from all over the world have been reported, of which about 70% are from the Magreb region of North Africa, possibly due to the high prevalence of consanguinity
Consanguinity
Consanguinity refers to the property of being from the same kinship as another person. In that respect, consanguinity is the quality of being descended from the same ancestor as another person...
there.
The kidney problems are treated as described above. There is no treatment for the osteopetrosis or cerebral calcification.
Type 3 is rarely discussed. Most comparisons of RTA are limited to a comparison of types 1, 2, and 4.
Type 4 RTA
Ammonium
The ammonium cation is a positively charged polyatomic cation with the chemical formula NH. It is formed by the protonation of ammonia...
excretion, which is secondary to hypoaldosteronism
Hypoaldosteronism
In medicine , hypoaldosteronism refers to decreased levels of the hormone aldosterone.The term "isolated hypoaldosteronism" is used to describe lowered aldosterone without corresponding changes in cortisol...
, and results in a decrease in urine buffering capacity. Its cardinal feature is hyperkalemia
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
, and measured urinary acidification is normal, hence it is often called hyperkalemic RTA or tubular hyperkalemia.
Causes include:
- Aldosterone deficiency (hypoaldosteronismHypoaldosteronismIn medicine , hypoaldosteronism refers to decreased levels of the hormone aldosterone.The term "isolated hypoaldosteronism" is used to describe lowered aldosterone without corresponding changes in cortisol...
): Primary vs. hyporeninemic - AldosteroneAldosteroneAldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
resistance
- Drugs: AmilorideAmilorideAmiloride is a potassium-sparing diuretic, first approved for use in 1967 , used in the management of hypertension and congestive heart failure. Amiloride was also tested as treatment of cystic fibrosis, but it was revealed inefficient in vivo due to it's short time of action, therefore...
, SpironolactoneSpironolactoneSpironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...
, TrimethoprimTrimethoprimTrimethoprim is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections.It belongs to the class of chemotherapeutic agents known as dihydrofolate reductase inhibitors...
, PentamidinePentamidinePentamidine is an antimicrobial medication given for prevention and treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii , a severe interstitial type of pneumonia often seen in patients with HIV infection... - PseudohypoaldosteronismPseudohypoaldosteronismPseudohypoaldosteronism is a condition that mimics hypoaldosteronism. However, the condition is due to a failure of response to aldosterone, and levels of aldosterone are actually elevated, due to a lack of feedback....
History
Renal tubular acidosis was first described in 1935 by Lightwood and 1936 by Butler et al. in children. Baines et al. first described it in adults in 1945.See also
- Hyperchloremic acidosisHyperchloremic acidosisHyperchloremic acidosis is a form of metabolic acidosis associated with a normal anion gap, a decrease in plasma bicarbonate concentration, and in an increase in plasma chloride concentration .-Causes:...
- HypokalemiaHypokalemiaHypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
- Kidney stoneKidney stoneA kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
- Fanconi syndromeFanconi syndromeFalconi syndrome is a disease of the proximal renal tubules of the kidney in which glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed. Fanconi syndrome affects the proximal tubule, which is the first part of the tubule to process fluid...
- Tiny TimTiny Tim (A Christmas Carol)Timothy Cratchit, called "Tiny Tim", is a fictional character from the 1843 novella A Christmas Carol by Charles Dickens. He is a minor character, the young son of Bob Cratchit, and is seen only briefly, but serves as an important symbol of the consequences of the protagonist's choices...
, who might have had RTA - Charles II of SpainCharles II of SpainCharles II was the last Habsburg King of Spain and the ruler of large parts of Italy, the Spanish territories in the Southern Low Countries, and Spain's overseas Empire, stretching from the Americas to the Spanish East Indies...
, who is also speculated to have suffered with dRTA