Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of
acid
In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a se ...
in the body due to a failure of the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
s to appropriately
acidify the
urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra.
Cellul ...
.
In
renal physiology, when
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
is
filtered by the kidney, the
filtrate passes through the
tubules
In biology, a tubule is a general term referring to small tube or similar type of structure. Specifically, tubule can refer to:
* a small tube or fistular structure
* a minute tube lined with glandular epithelium
* any hollow cylindrical body stru ...
of the
nephron, allowing for exchange of
salts, acid equivalents, and other
solutes
In chemistry, a solution is a special type of homogeneous mixture composed of two or more substances. In such a mixture, a solute is a substance dissolved in another substance, known as a solvent. If the attractive forces between the solven ...
before it drains into the
bladder
The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine en ...
as
urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra.
Cellul ...
. The
metabolic acidosis
Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys ...
that results from RTA may be caused either by insufficient
secretion 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classic ...
of
hydrogen ions (which are acidic) into the latter portions of the nephron (the
distal tubule) or by failure to
reabsorb sufficient
bicarbonate
In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula .
Bicarbonate serves a crucial biochemi ...
ions (which are
alkaline
In chemistry, an alkali (; from ar, القلوي, al-qaly, lit=ashes of the saltwort) is a basic, ionic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a ...
) from the filtrate in the early portion of the nephron (the
proximal tubule). Although a metabolic acidosis also occurs in those with
chronic kidney disease
Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...
, 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. RTA is usually an incidental finding based on routine blood draws that show abnormal results. Clinically, patients may present with vague symptoms such as dehydration, mental status changes, or delayed growth in adolescents.
The word ''
acidosis
Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma.
The term ''acidemia'' describe ...
'' refers to the tendency for RTA to cause an excess of
acid
In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a se ...
, which lowers 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.
Types
An overview of types 1, 2, and 4 is presented below (type 3 is usually excluded from modern classifications):
Type 1: distal
Distal RTA (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalated
cells of the
medullary collecting duct of the
distal
Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...
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 from the body, there is consequently a tendency towards
acidemia. There is an inability to excrete H
+ while cannot be reclaimed by the cell, leading to acidemia (as builds up in the body) and hypokalemia (as cannot be reabsorbed by the alpha cell).
This leads to the clinical features of dRTA;
[ In other words, the intercalated cells' apical H+/K+ antiporter is non-functional, resulting in proton retention and potassium excretion. Since calcium phosphate stones demonstrate a proclivity for deposition at higher pHs (alkaline), the substance of the kidney develops stones bilaterally; this does not occur in the other RTA types.
* Normal anion gap ]metabolic acidosis
Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys ...
/acidemia
* Hypokalemia, Hypocalcemia, Hyperchloremia
* Urinary stone
A bladder stone is a stone found in the urinary bladder.
Signs and symptoms
Bladder stones are small mineral deposits that can form in the bladder. In most cases bladder stones develop when the urine becomes very concentrated or when one is ...
formation (related to alkaline urine, hypercalciuria
Hypercalciuria is the condition of elevated calcium in the urine. Chronic hypercalciuria may lead to impairment of renal function, nephrocalcinosis, and chronic kidney disease. Patients with hypercalciuria have kidneys that put out higher levels o ...
, and low urinary citrate).
* Nephrocalcinosis (deposition of calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
in the substance of the kidney)
* Bone
A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
demineralisation (causing rickets in children and osteomalacia in adults)
* Growth deficiency
* Medullary cysts
* Sensorineural hearing loss
Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear or sensory organ (cochlea and associated structures) or the vestibulocochlear nerve (cranial nerve VIII). SNHL accounts for about 90% of re ...
* Hereditary hemolytic anemia
Distal RTA has also been linked to specific genetic mutations that will alter when the disease will present in the patient's life. Patient's with mutations in ''ATP6V1B1'' and ''ATP6V0A4'' will present with symptoms within the first year of life, while those with mutation of the ''SLC4A1'' have delayed onset around 10 years of age. Electrolyte imbalances remain the same, while in severe cases symptoms can advance to amino aciduria and hyperammonemia
Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to brain injury and death. It may be primary or secondary.
Ammonia is a substance that contains nitrogen. I ...
. In a large Asian series of Distal renal Tubular Acidosis in Sjogren's Syndrome, late diagnosis is a rule in spite of overt hypokalemic periodic paralysis in a vast majority of them
dRTA is the most common form of RTA diagnosed in Western countries, and can be classified as either hereditary (primary) or acquired (secondary). Primary RTA generally results from systemic and autoimmune diseases or drug and toxin exposure in adults, whereas pediatric RTA results from genetic defects in the proteins that facilitate urine acidification at the distal tubule. Hereditary dRTA generally presents as failure to thrive during the first several months of life. Other common clinical manifestations in children include a variety of gastrointestinal and urinary symptoms, including polyuria, polydipsia, constipation, diarrhea, bouts of dehydration, and decreased appetite.
Type 2: proximal
Proximal RTA (pRTA) is caused by a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate
In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula .
Bicarbonate serves a crucial biochemi ...
wasting and subsequent acidemia. Reabsorption of bicarbonate is typically 80-90% in the proximal tubule and failure of this process leads to decreased systemic buffer and metabolic acidosis
Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys ...
. The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the alpha intercalated cells can produce H+ to acidify the urine 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 generalized dysfunction of the proximal tubular cells called Fanconi syndrome, in which there is also phosphaturia, glycosuria, aminoaciduria, uricosuria, and tubular proteinuria.
The principal feature of Fanconi syndrome is bone demineralization ( osteomalacia or rickets) due to phosphate wasting.
Type 3: combined proximal and distal
In some patients, 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
The carbonic anhydrases (or carbonate dehydratases) () form a family of enzymes that catalyze the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions). The active sit ...
II deficiency. Mutations in the gene encoding this enzyme give rise to an autosomal recessive syndrome of osteopetrosis, renal tubular acidosis, cerebral calcification
Calcification is the accumulation of calcium salts in a body tissue. It normally occurs in the formation of bone, but calcium can be deposited abnormally in soft tissue,Miller, J. D. Cardiovascular calcification: Orbicular origins. ''Nature M ...
, and mental retardation. It is very rare and cases from all over the world have been reported, of which about 70% are from the Maghreb
The Maghreb (; ar, الْمَغْرِب, al-Maghrib, lit=the west), also known as the Arab Maghreb ( ar, المغرب العربي) and Northwest Africa, is the western part of North Africa and the Arab world. The region includes Algeria, ...
region of North Africa, possibly due to the high prevalence of consanguinity
Consanguinity ("blood relation", from Latin '' consanguinitas'') is the characteristic of having a kinship with another person (being descended from a common ancestor).
Many jurisdictions have laws prohibiting people who are related by blood fr ...
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: absolute hypoaldosteronism or aldosterone insensitivity
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
The ammonium cation is a positively-charged polyatomic ion with the chemical formula or . It is formed by the protonation of ammonia (). Ammonium is also a general name for positively charged or protonated substituted amines and quaterna ...
excretion (impaired ammoniagenesis), which is secondary to hypoaldosteronism
Hypoaldosteronism is an endocrinological disorder characterized by decreased levels of the hormone aldosterone. Similarly, isolated hypoaldosteronism is the condition of having lowered aldosterone without corresponding changes in cortisol. (The ...
, and results in a decrease in urine buffering capacity. Its cardinal feature is hyperkalemia
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occa ...
, and measured urinary acidification is normal, hence it is often called hyperkalemic RTA or tubular hyperkalemia.[
Causes include:
* Aldosterone deficiency (]hypoaldosteronism
Hypoaldosteronism is an endocrinological disorder characterized by decreased levels of the hormone aldosterone. Similarly, isolated hypoaldosteronism is the condition of having lowered aldosterone without corresponding changes in cortisol. (The ...
): Primary vs. hyporeninemic (including diabetic nephropathy)
* Aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
resistance
# Drugs: NSAIDs, ACE inhibitors and ARBs, Eplerenone, Spironolactone
Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood press ...
, Trimethoprim, Pentamidine
# Pseudohypoaldosteronism
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.
Donald L. Lewis postulated the character Tiny Tim, of ''A Christmas Carol
''A Christmas Carol. In Prose. Being a Ghost Story of Christmas'', commonly known as ''A Christmas Carol'', is a novella by Charles Dickens, first published in London by Chapman & Hall in 1843 and illustrated by John Leech. ''A Christmas ...
'', was suffering from renal tubular acidosis.
Researchers published in PLOS ONE in 2009 speculated that the infamously afflicted Charles II of Spain may have suffered from renal tubular acidosis in tandem with combined pituitary hormone deficiency
Hypopituitarism is the decreased (''hypo'') secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain. If there is decreased secretion of one specific pituitary hormone, the condition is kno ...
.
See also
* Charles II of Spain, who is speculated to have suffered with dRTA
* Hyperchloremic acidosis
Hyperchloremic acidosis is a form of metabolic acidosis associated with a normal anion gap, a decrease in plasma bicarbonate concentration, and an increase in plasma chloride concentration (see anion gap for a fuller explanation). Although plasma a ...
* Hypokalemic acidosis
* Lightwood–Albright syndrome
References
External links
{{Water-electrolyte imbalance and acid-base imbalance
Kidney diseases