Metabolic acidosis

Last updated
Metabolic acidosis
Bicarbonate Levels in Metabolic Acidosis.jpg
The calculated level of bicarbonate in the blood (HCO3−) reflects the severity of acidosis.
Specialty Nephrology
Complications Acute: poor morbidity and mortality outcomes;
Chronic: adverse outcomes on kidney function, musculoskeletal system, possible cardiovascular effects
TypesAcute Metabolic Acidosis
Chronic Metabolic Acidosis
CausesAcute: Excessive amounts of organic acids;
Chronic: Impaired kidney function
Diagnostic method Level of bicarbonate (HCO3-) in the blood
TreatmentAcute: Mitigation of the underlying cause for the metabolic problem, such as administration of insulin in cases of diabetic ketoacidosis or restoration of effective circulating intravascular volume in cases of lactic acidosis. The administration of IV bicarbonate, although intellectually appealing, is rarely indicated or administered Chronic: Diet rich in fruits and vegetables, oral alkali therapy [1]
FrequencyAcute: Most often presented during critical illnesses, and hospitalizations: incidence ranging 14–42%. [2] [3]
Chronic: Highly prevalent in people with Chronic Kidney Disease: 9.4% CKD Stage 3a; 18.1% CKD Stage 3b; 31.5% CKD Stage 4 and 5 [4]

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 to excrete excess acids. [5] Metabolic acidosis can lead to acidemia, which is defined as arterial blood pH that is lower than 7.35. [6] Acidemia and acidosis are not mutually exclusive – pH and hydrogen ion concentrations also depend on the coexistence of other acid-base disorders; therefore, pH levels in people with metabolic acidosis can range from low to high.

Contents

Acute metabolic acidosis, lasting from minutes to several days, often occurs during serious illnesses or hospitalizations, and is generally caused when the body produces an excess amount of organic acids (ketoacids in ketoacidosis, or lactic acid in lactic acidosis). A state of chronic metabolic acidosis, lasting several weeks to years, can be the result of impaired kidney function (chronic kidney disease) and/or bicarbonate wasting. The adverse effects of acute versus chronic metabolic acidosis also differ, with acute metabolic acidosis impacting the cardiovascular system in hospital settings, and chronic metabolic acidosis affecting muscles, bones, kidney and cardiovascular health. [7]

Signs and symptoms

Acute metabolic acidosis

Symptoms are not specific, and diagnosis can be difficult unless patients present with clear indications for blood gas sampling. Symptoms may include palpitations, headache, altered mental status such as severe anxiety due to hypoxia, decreased visual acuity, nausea, vomiting, abdominal pain, altered appetite and weight gain, muscle weakness, bone pain, and joint pain. People with acute metabolic acidosis may exhibit deep, rapid breathing called Kussmaul respirations which is classically associated with diabetic ketoacidosis. [8] Rapid deep breaths increase the amount of carbon dioxide exhaled, thus lowering the serum carbon dioxide levels, resulting in some degree of compensation. Overcompensation via respiratory alkalosis to form an alkalemia does not occur.[ citation needed ]

Extreme acidemia can also lead to neurological and cardiac complications:[ citation needed ]

Physical examination can occasionally reveal signs of the disease, but is often otherwise normal. Cranial nerve abnormalities are reported in ethylene glycol poisoning, and retinal edema can be a sign of methanol intoxication.[ citation needed ]

Chronic metabolic acidosis

Chronic metabolic acidosis has non-specific clinical symptoms but can be readily diagnosed by testing serum bicarbonate levels in patients with chronic kidney disease (CKD) as part of a comprehensive metabolic panel. Patients with CKD Stages G3–G5 should be routinely screened for metabolic acidosis. [9] [10]

Diagnostic approach and causes

Metabolic acidosis results in a reduced serum pH that is due to metabolic and not respiratory dysfunction. Typically the serum bicarbonate concentration will be <22 mEq/L, below the normal range of 22 to 29 mEq/L, the standard base will be more negative than -2 (base deficit) and the pCO2 will be reduced as a result of hyperventilation in an attempt to restore the pH closer to normal. Occasionally in a mixed acid-base disorder where metabolic acidosis is not the primary disorder present, the pH may be normal or high. [5] In the absence of chronic respiratory alkalosis, metabolic acidosis can be clinically diagnosed by analysis of the calculated serum bicarbonate level.[ citation needed ]

Causes

Generally, metabolic acidosis occurs when the body produces too much acid (e.g., lactic acidosis, see below section), there is a loss of bicarbonate from the blood, or when the kidneys are not removing enough acid from the body.[ citation needed ]

Chronic metabolic acidosis is most often caused by a decreased capacity of the kidneys to excrete excess acids through renal ammoniagenesis. The typical Western diet generates 75–100 mEq of acid daily, [11] and individuals with normal kidney function increase the production of ammonia to get rid of this dietary acid. As kidney function declines, the tubules lose the ability to excrete excess acid, and this results in buffering of acid using serum bicarbonate, as well as bone and muscle stores. [12]

There are many causes of acute metabolic acidosis, and thus it is helpful to group them by the presence or absence of a normal anion gap. [13]

Increased anion gap

Causes of increased anion gap include:

Normal anion gap

Causes of normal anion gap include: [24]

To distinguish between the main types of metabolic acidosis, a clinical tool called the anion gap is very useful. The anion gap is calculated by subtracting the sum of the serum concentrations of major anions, chloride and bicarbonate, from the serum concentration of the major cation, sodium. (The serum potassium concentration may be added to the calculation, but this merely changes the normal reference range for what is considered a normal anion gap)

Because the concentration of serum sodium is greater than the combined concentrations of chloride and bicarbonate an 'anion gap' is noted. In reality serum is electoneutral because of the presence of other minor cations (potassium, calcium and magnesium) and anions (albumin, sulphate and phosphate) that are not measured in the equation that calculates the anion gap.[ citation needed ]

The normal value for the anion gap is 8–16 mmol/L (12±4). An elevated anion gap (i.e. > 16 mmol/L) indicates the presence of excess 'unmeasured' anions, such as lactic acid in anaerobic metabolism resulting from tissue hypoxia, glycolic and formic acid produced by the metabolism of toxic alcohols, ketoacids produced when acetyl-CoA undergoes ketogenesis rather than entering the tricarboxylic (Krebs) cycle, and failure of renal excretion of products of metabolism such as sulphates and phosphates.[ citation needed ]

Adjunctive tests are useful in determining the aetiology of a raised anion gap metabolic acidosis including detection of an osmolar gap indicative of the presence of a toxic alcohol, measurement of serum ketones indicative of ketoacidosis and renal function tests and urinanalysis to detect renal dysfunction.[ citation needed ]

Elevated protein (albumin, globulins) may theoretically increase the anion gap but high levels are not usually encountered clinically. Hypoalbuminaemia, which is frequently encountered clinically, will mask an anion gap. As a rule of thumb, a decrease in serum albumin by 1 G/L will decrease the anion gap by 0.25 mmol/L[ citation needed ]

Pathophysiology

Compensatory mechanisms

Metabolic acidosis is characterized by a low concentration of bicarbonate (HCO−
3), which can happen with increased generation of acids (such as ketoacids or lactic acid), excess loss of HCO−
3 by the kidneys or gastrointestinal tract, or an inability to generate sufficient HCO−
3. [25] Thus demonstrating the importance of maintaining balance between acids and bases in the body for maintaining optimal functioning of organs, tissues and cells.[ citation needed ]

The body regulates the acidity of the blood by four buffering mechanisms.[ citation needed ]

Buffer

The decreased bicarbonate that distinguishes metabolic acidosis is therefore due to two separate processes: the buffer (from water and carbon dioxide) and additional renal generation. The buffer reactions are:

The Henderson–Hasselbalch equation mathematically describes the relationship between blood pH and the components of the bicarbonate buffering system: where pKa ≈ 6.1. In clinical practice, the CO2 concentration is usually determined via Henry's law from PaCO2, the CO2 partial pressure in arterial blood:

For example, blood gas machines usually determine bicarbonate concentrations from measured pH and PaCO2 values. Mathematically, the algorithm substitutes the Henry's law formula into the Henderson-Hasselbach equation and then rearranges: At sea level, normal numbers might be pH ≈ 7.4 and PaCO2 ≈ 40 mmHg; these then imply

Consequences

Acute metabolic acidosis

Acute metabolic acidosis most often occurs during hospitalizations, and acute critical illnesses. It is often associated with poor prognosis, with a mortality rate as high as 57% if the pH remains untreated at 7.20. [2] At lower pH levels, acute metabolic acidosis can lead to impaired circulation and end organ function.[ citation needed ]

Chronic metabolic acidosis

Chronic metabolic acidosis commonly occurs in people with chronic kidney disease (CKD) with an eGFR of less than 45 ml/min/1.73m2, most often with mild to moderate severity; however, metabolic acidosis can manifest earlier on in the course of CKD. Multiple animal and human studies have shown that metabolic acidosis in CKD, given its chronic nature, has a profound adverse impact on cellular function, overall contributing to high morbidities in patients.

The most adverse consequences of chronic metabolic acidosis in people with CKD, and in particular, for those who have end-stage renal disease (ESRD), are detrimental changes to the bones and muscles. [26] Acid buffering leads to loss of bone density, resulting in an increased risk of bone fractures, [27] renal osteodystrophy, [28] and bone disease; [26] as well, increased protein catabolism leads to muscle wasting. [29] [30] Furthermore, metabolic acidosis in CKD is also associated with a reduction in eGFR; it is both a complication of CKD, as well as an underlying cause of CKD progression. [31] [32] [33] [34]

Treatment

Treatment of metabolic acidosis depends on the underlying cause, and should target reversing the main process. When considering course of treatment, it is important to distinguish between acute versus chronic forms.[ citation needed ]

Acute metabolic acidosis

Bicarbonate therapy is generally administered In patients with severe acute acidemia (pH < 7.11), or with less severe acidemia (pH 7.1–7.2) who have severe acute kidney injury. Bicarbonate therapy is not recommended for people with less severe acidosis (pH ≥ 7.1), unless severe acute kidney injury is present. In the BICAR-ICU trial, [35] bicarbonate therapy for maintaining a pH >7.3 had no overall effect on the composite outcome of all-cause mortality and the presence of at least one organ failure at day 7. However, amongst the sub-group of patients with severe acute kidney injury, bicarbonate therapy significantly decreased the primary composite outcome, and 28-day mortality, along with the need for dialysis.[ citation needed ]

Chronic metabolic acidosis

For people with chronic kidney disease (CKD), treating metabolic acidosis slows the progression of CKD. [36] Dietary interventions for treatment of chronic metabolic acidosis include base-inducing fruits and vegetables that assist with reducing the urine net acid excretion, and increase TCO2. Recent research has also suggested that dietary protein restriction, through ketoanalogue-supplemented vegetarian very low protein diets are also a nutritionally safe option for correction of metabolic acidosis in people with CKD. [37]

Currently, the most commonly used treatment for chronic metabolic acidosis is oral bicarbonate. The NKF/KDOQI guidelines recommend starting treatment when serum bicarbonate levels are <22 mEq/L, in order to maintain levels ≥ 22 mEq/L. [9] [10] Studies investigating the effects of oral alkali therapy demonstrated improvements in serum bicarbonate levels, resulting in a slower decline in kidney function, and reduction in proteinuria – leading to a reduction in the risk of progressing to kidney failure. However, side effects of oral alkali therapy include gastrointestinal intolerance, worsening edema, and worsening hypertension. Furthermore, large doses of oral alkali are required to treat chronic metabolic acidosis, and the pill burden can limit adherence. [38]

Veverimer (TRC 101) is a promising investigational drug designed to treat metabolic acidosis by binding with the acid in the gastrointestinal tract and removing it from the body through excretion in the feces, in turn decreasing the amount of acid in the body, and increasing the level of bicarbonate in the blood. Results from a Phase 3, double-blind placebo-controlled 12-week clinical trial in people with CKD and metabolic acidosis demonstrated that Veverimer effectively and safely corrected metabolic acidosis in the short-term, [39] and a blinded, placebo-controlled, 40-week extension of the trial assessing long-term safety, demonstrated sustained improvements in physical function and a combined endpoint of death, dialysis, or 50% decline in eGFR. [40]

See also

Related Research Articles

<span class="mw-page-title-main">Arterial blood gas test</span> A test of blood taken from an artery that measures the amounts of certain dissolved gases

An arterial blood gas (ABG) test, or arterial blood gas analysis (ABGA) measures the amounts of arterial gases, such as oxygen and carbon dioxide. An ABG test requires that a small volume of blood be drawn from the radial artery with a syringe and a thin needle, but sometimes the femoral artery in the groin or another site is used. The blood can also be drawn from an arterial catheter.

Acidosis is a biological process producing hydrogen ions and increasing their concentration in blood or body fluids. pH is the negative log of hydrogen ion concentration and so it is decreased by a process of acidosis.

<span class="mw-page-title-main">Kidney disease</span> Damage to or disease of a kidney

Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can be diagnosed by blood tests. Nephrosis is non-inflammatory kidney disease. Nephritis and nephrosis can give rise to nephritic syndrome and nephrotic syndrome respectively. Kidney disease usually causes a loss of kidney function to some degree and can result in kidney failure, the complete loss of kidney function. Kidney failure is known as the end-stage of kidney disease, where dialysis or a kidney transplant is the only treatment option.

<span class="mw-page-title-main">Respiratory acidosis</span> Decrease in blood pH due to insufficient breathing

Respiratory acidosis is a state in which decreased ventilation (hypoventilation) increases the concentration of carbon dioxide in the blood and decreases the blood's pH.

<span class="mw-page-title-main">Respiratory alkalosis</span> Increase in blood pH due to rapid breathing

Respiratory alkalosis is a medical condition in which increased respiration elevates the blood pH beyond the normal range (7.35–7.45) with a concurrent reduction in arterial levels of carbon dioxide. This condition is one of the four primary disturbances of acid–base homeostasis.

The anion gap is a value calculated from the results of multiple individual medical lab tests. It may be reported with the results of an electrolyte panel, which is often performed as part of a comprehensive metabolic panel.

<span class="mw-page-title-main">Metabolic alkalosis</span> Abnormally high tissue pH due to metabolic dysfunction

Metabolic alkalosis is an acid-base disorder in which the pH of tissue is elevated beyond the normal range (7.35–7.45). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations. The condition typically cannot last long if the kidneys are functioning properly.

In physiology, base excess and base deficit refer to an excess or deficit, respectively, in the amount of base present in the blood. The value is usually reported as a concentration in units of mEq/L (mmol/L), with positive numbers indicating an excess of base and negative a deficit. A typical reference range for base excess is −2 to +2 mEq/L.

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. Although plasma anion gap is normal, this condition is often associated with an increased urine anion gap, due to the kidney's inability to secrete ammonia.

<span class="mw-page-title-main">Renal tubular acidosis</span> Higher blood acidity due to failure of the kidneys to fully acidify urine

Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. In renal physiology, 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 insufficient secretion of hydrogen ions into the latter portions of the nephron or by failure to reabsorb sufficient bicarbonate ions from the filtrate in the early portion of the nephron. Although a metabolic acidosis also occurs in those with chronic kidney disease, 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.

Acid–base homeostasis is the homeostatic regulation of the pH of the body's extracellular fluid (ECF). The proper balance between the acids and bases in the ECF is crucial for the normal physiology of the body—and for cellular metabolism. The pH of the intracellular fluid and the extracellular fluid need to be maintained at a constant level.

<span class="mw-page-title-main">Renal compensation</span> Regulation of blood plasma acidity by kidneys

Renal compensation is a mechanism by which the kidneys can regulate the plasma pH. It is slower than respiratory compensation, but has a greater ability to restore normal values. Kidneys maintain the acid-base balance through two mechanisms: (1) the secretion of H+ ions into the urine (from the blood) and (2) the reabsorption of bicarbonate HCO−
3 (i.e., bicarbonate moves from urine back into the blood). The regulation of H+ ions and bicarbonate HCO−
3 is determined by the concentration of the two released within the urine. These mechanisms of secretion and reabsorption balance the pH of the bloodstream. A restored acid-base balanced bloodstream thus leads to a restored acid-base balance throughout the entire body.

<span class="mw-page-title-main">Bicarbonate buffer system</span> Buffer system that maintains pH balance in humans

The bicarbonate buffer system is an acid-base homeostatic mechanism involving the balance of carbonic acid (H2CO3), bicarbonate ion (HCO−
3), and carbon dioxide (CO2) in order to maintain pH in the blood and duodenum, among other tissues, to support proper metabolic function. Catalyzed by carbonic anhydrase, carbon dioxide (CO2) reacts with water (H2O) to form carbonic acid (H2CO3), which in turn rapidly dissociates to form a bicarbonate ion (HCO−
3 ) and a hydrogen ion (H+) as shown in the following reaction:

<span class="mw-page-title-main">Acid–base disorder</span> Abnormality of the human bodys normal balance of acids and bases

Acid–base imbalance is an abnormality of the human body's normal balance of acids and bases that causes the plasma pH to deviate out of the normal range. In the fetus, the normal range differs based on which umbilical vessel is sampled. It can exist in varying levels of severity, some life-threatening.

<span class="mw-page-title-main">High anion gap metabolic acidosis</span> Medical condition

High anion gap metabolic acidosis is a form of metabolic acidosis characterized by a high anion gap. Metabolic acidosis occurs when the body produces too much acid, or when the kidneys are not removing enough acid from the body. Several types of metabolic acidosis occur, grouped by their influence on the anion gap.

In clinical chemistry, the urine anion gap is calculated using measured ions found in the urine. It is used to aid in the differential diagnosis of metabolic acidosis.

Winters's formula, named after R. W. Winters, is a formula used to evaluate respiratory compensation when analyzing acid-base disorders in the presence of metabolic acidosis. It can be given as:

<span class="mw-page-title-main">Distal renal tubular acidosis</span> Medical condition

Distal renal tubular acidosis (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 cells of the distal tubule and cortical collecting duct of the distal nephron. This failure of acid secretion may be due to a number of causes. It leads to relatively alkaline urine, due to the kidney's inability to acidify the urine to a pH of less than 5.3.

Proximal renal tubular acidosis (pRTA) or type 2 renal tubular acidosis (RTA) is a type of RTA 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 syndrome where there is also phosphaturia, glycosuria, aminoaciduria, uricosuria and tubular proteinuria.

In nephrology, the delta ratio, or "delta-delta", is a formula that can be used to evaluate whether a mixed acid–base disorder is present, and if so, assess its severity. The anion gap (AG) without potassium is calculated first and if a metabolic acidosis is present, results in either a high anion gap metabolic acidosis (HAGMA) or a normal anion gap acidosis (NAGMA). A low anion gap is usually an oddity of measurement, rather than a clinical concern.

References

  1. ↑ Navaneethan, Sankar D.; Shao, Jun; Buysse, Jerry; Bushinsky, David A. (5 July 2019). "Effects of Treatment of Metabolic Acidosis in CKD: A Systematic Review and Meta-Analysis". Clinical Journal of the American Society of Nephrology. 14 (7): 1011–1020. doi:10.2215/CJN.13091118. PMC   6625635 . PMID   31196951.
  2. 1 2 Kraut, Jeffrey A.; Madias, Nicolaos E. (4 September 2012). "Treatment of acute metabolic acidosis: a pathophysiologic approach". Nature Reviews Nephrology. 8 (10): 589–601. doi:10.1038/nrneph.2012.186. PMID   22945490. S2CID   34657707.
  3. ↑ Jung, Boris; Rimmele, Thomas; Le Goff, Charlotte; Chanques, Gérald; Corne, Philippe; Jonquet, Olivier; Muller, Laurent; Lefrant, Jean-Yves; Guervilly, Christophe; Papazian, Laurent; Allaouchiche, Bernard; Jaber, Samir (2011). "Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. A prospective, multiple-center study". Critical Care. 15 (5): R238. doi: 10.1186/cc10487 . PMC   3334789 . PMID   21995879.
  4. ↑ Inker, Lesley A.; Coresh, Josef; Levey, Andrew S.; Tonelli, Marcello; Muntner, Paul (1 December 2011). "Estimated GFR, Albuminuria, and Complications of Chronic Kidney Disease". Journal of the American Society of Nephrology. 22 (12): 2322–2331. doi:10.1681/ASN.2010111181. PMC   3279937 . PMID   21965377.
  5. 1 2 Emmett, Michael; Szerlip, Harold. "Approach to the adult with metabolic acidosis".
  6. ↑ Costanzo, Linda (2010). Physiology. Philadelphia, Pennsylvania: Elsevier. ISBN   978-1-4160-6216-5.
  7. ↑ Kraut, Jeffrey A.; Madias, Nicolaos E. (2010-05-01). "Metabolic acidosis: pathophysiology, diagnosis and management". Nature Reviews Nephrology. 6 (5): 274–285. doi:10.1038/nrneph.2010.33. ISSN   1759-5061. PMID   20308999. S2CID   205512465.
  8. ↑ Gallo de Moraes, Alice; Surani, Salim (2019-01-15). "Effects of diabetic ketoacidosis in the respiratory system". World Journal of Diabetes. 10 (1): 16–22. doi: 10.4239/wjd.v10.i1.16 . ISSN   1948-9358. PMC   6347653 . PMID   30697367.
  9. 1 2 "National Kidney Foundation: K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease" (PDF). Am J Kidney Dis. 42 (Suppl 3): S1–S201.
  10. 1 2 "CKD Evaluation and Management – KDIGO". kdigo.org. Retrieved 2019-12-31.
  11. ↑ Weaver, Connie M. (2013-05-06). "Potassium and Health123". Advances in Nutrition. 4 (3): 368S–377S. doi:10.3945/an.112.003533. ISSN   2161-8313. PMC   3650509 . PMID   23674806.
  12. ↑ Kovesdy, Csaba. "Pathogenesis, consequences, and treatment of metabolic acidosis in chronic kidney disease". UpToDate.
  13. ↑ Stern, Scott D. C.; Cifu, Adam S.; Altkorn, Diane (2015). Symptom to diagnosis: an evidence-based guide (3rd ed.). New York: McGraw-Hill Education. ISBN   9780071803441. OCLC   896866189.
  14. ↑ Quinn, Gene R.; Gleason, Nathaniel W.; Papadakis, Maxine A.; McPhee, Stephen J., eds. (2016). Current medical diagnosis & treatment study guide (2nd ed.). New York: McGraw-Hill. ISBN   9780071848053. OCLC   910475681.
  15. 1 2 DeGowin's diagnostic examination. LeBlond, Richard F.,, Brown, Donald D., 1940-, Suneja, Manish,, Szot, Joseph F. (Tenth ed.). New York. 2014-09-05. ISBN   9780071814478. OCLC   876336892.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  16. ↑ Morgan & Mikhail's clinical anesthesiology. Butterworth, John F., IV,, Mackey, David C.,, Wasnick, John D.,, Morgan, G. Edward,, Mikhail, Maged S.,, Morgan, G. Edward. (Sixth ed.). New York. 2018-08-21. ISBN   9781259834424. OCLC   1039081701.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  17. ↑ Smollin, Craig (2022). "Chapter 2-1: Acetaminophen". In Olson, Kent R.; Smollin, Craig G.; Anderson, Ilene B.; Benowitz, Neal L.; Blanc, Paul D.; Kim-Katz, Susan Y.; Lewis, Justin C.; Wu, Alan H.B. (eds.). Poisoning & Drug Overdose. The Faculty, Staff, and Associates of the California Poison Control System (Eighth ed.). McGraw Hill Lange. ISBN   978-1-264-25908-3.
  18. ↑ Critical care. Oropello, John M.,, Pastores, Stephen M.,, Kvetan, Vladimir. [New York]. 2016-11-22. ISBN   9780071817264. OCLC   961480454.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  19. ↑ Current medical diagnosis & treatment 2020. Papadakis, Maxine A.,, McPhee, Stephen J.,, Rabow, Michael W. (Fifty-eighth ed.). New York. 2019-09-02. ISBN   9781260455281. OCLC   1109935506.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  20. ↑ Harrison's principles of internal medicine. Jameson, J. Larry,, Kasper, Dennis L.,, Longo, Dan L. (Dan Louis), 1949-, Fauci, Anthony S., 1940-, Hauser, Stephen L.,, Loscalzo, Joseph (20th ed.). New York. 2018-08-13. ISBN   9781259644030. OCLC   1029074059.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  21. ↑ Morgan & Mikhail's clinical anesthesiology. Butterworth, John F., IV,, Mackey, David C.,, Wasnick, John D.,, Morgan, G. Edward,, Mikhail, Maged S.,, Morgan, G. Edward. (Sixth ed.). New York. 2018-08-21. ISBN   978-1259834424. OCLC   1039081701.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  22. ↑ Katzung, Bertram G. (2018-09-05). Katzung & Trevor's pharmacology : examination & board review. Kruidering-Hall, Marieke,, Trevor, Anthony J. (Twelfth ed.). New York. ISBN   978-1259641022. OCLC   1052466341.{{cite book}}: CS1 maint: location missing publisher (link)
  23. ↑ Levitzky, Michael G. (2007). Pulmonary physiology (7th ed.). New York: McGraw-Hill Medical. ISBN   9780071437752. OCLC   75713147.
  24. ↑ Field, Michael J.; Pollock, Carol A.; Harris, David C. (2010). The renal system: basic science and clinical conditions (2nd ed.). Edinburgh: Churchill Livingstone/Elsevier. ISBN   9780702033711. OCLC   319855752.
  25. ↑ Costanzo, Linda S. (2017-03-15). Physiology (6th ed.). Philadelphia, PA: Elsevier. ISBN   9780323511896. OCLC   965761862.
  26. 1 2 Kraut, Jeffrey A.; Madias, Nicolaos E. (2017). "Adverse Effects of the Metabolic Acidosis of Chronic Kidney Disease". Advances in Chronic Kidney Disease. 24 (5): 289–297. doi:10.1053/j.ackd.2017.06.005. PMID   29031355.
  27. ↑ Kato, Akihiko; Kido, Ryo; Onishi, Yoshihiro; Kurita, Noriaki; Fukagawa, Masafumi; Akizawa, Tadao; Fukuhara, Shunichi (2014). "Association of serum bicarbonate with bone fractures in hemodialysis patients: the mineral and bone disorder outcomes study for Japanese CKD stage 5D patients (MBD-5D)". Nephron Clinical Practice. 128 (1–2): 79–87. doi:10.1159/000365089. ISSN   1660-2110. PMID   25378374. S2CID   20320396.
  28. ↑ Lefebvre, A.; de Vernejoul, M. C.; Gueris, J.; Goldfarb, B.; Graulet, A. M.; Morieux, C. (1989). "Optimal correction of acidosis changes progression of dialysis osteodystrophy". Kidney International. 36 (6): 1112–1118. doi: 10.1038/ki.1989.309 . ISSN   0085-2538. PMID   2557481.
  29. ↑ Hanna, Ramy M.; Ghobry, Lena; Wassef, Olivia; Rhee, Connie M.; Kalantar-Zadeh, Kamyar (2020). "A Practical Approach to Nutrition, Protein-Energy Wasting, Sarcopenia, and Cachexia in Patients with Chronic Kidney Disease". Blood Purification. 49 (1–2): 202–211. doi: 10.1159/000504240 . ISSN   0253-5068. PMID   31851983. S2CID   209418220.
  30. ↑ Foley, Robert N.; Wang, Changchun; Ishani, Areef; Collins, Allan J.; Murray, Anne M. (2007). "Kidney Function and Sarcopenia in the United States General Population: NHANES III". American Journal of Nephrology. 27 (3): 279–286. doi:10.1159/000101827. ISSN   0250-8095. PMID   17440263. S2CID   2847009.
  31. ↑ Shah, Samir N.; Abramowitz, Matthew; Hostetter, Thomas H.; Melamed, Michal L. (2009-08-01). "Serum bicarbonate levels and the progression of kidney disease: a cohort study". American Journal of Kidney Diseases. 54 (2): 270–277. doi:10.1053/j.ajkd.2009.02.014. ISSN   1523-6838. PMC   4354889 . PMID   19394734.
  32. ↑ Dobre, Mirela; Yang, Wei; Chen, Jing; Drawz, Paul; Hamm, L. Lee; Horwitz, Edward; Hostetter, Thomas; Jaar, Bernard; Lora, Claudia M.; Nessel, Lisa; Ojo, Akinlolu (2013-10-01). "Association of Serum Bicarbonate With Risk of Renal and Cardiovascular Outcomes in CKD: A Report From the Chronic Renal Insufficiency Cohort (CRIC) Study". American Journal of Kidney Diseases. 62 (4): 670–678. doi:10.1053/j.ajkd.2013.01.017. ISSN   0272-6386. PMC   3701754 . PMID   23489677.
  33. ↑ Menon, Vandana; Tighiouart, Hocine; Vaughn, Nubia Smith; Beck, Gerald J.; Kusek, John W.; Collins, Allan J.; Greene, Tom; Sarnak, Mark J. (2010-11-01). "Serum Bicarbonate and Long-term Outcomes in CKD". American Journal of Kidney Diseases. 56 (5): 907–914. doi:10.1053/j.ajkd.2010.03.023. ISSN   0272-6386. PMID   20605301.
  34. ↑ Raphael, Kalani L.; Wei, Guo; Baird, Bradley C.; Greene, Tom; Beddhu, Srinivasan (2011-02-01). "Higher serum bicarbonate levels within the normal range are associated with better survival and renal outcomes in African Americans". Kidney International. 79 (3): 356–362. doi:10.1038/ki.2010.388. ISSN   0085-2538. PMC   5241271 . PMID   20962743.
  35. ↑ Jaber, Samir; Paugam, Catherine; Futier, Emmanuel; et al. (2018). "Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial" (PDF). The Lancet. 392 (10141): 31–40. doi:10.1016/S0140-6736(18)31080-8. PMID   29910040. S2CID   49276138.
  36. ↑ Goraya, Nimrit; Wesson, Donald E. (2019). "Clinical evidence that treatment of metabolic acidosis slows the progression of chronic kidney disease". Current Opinion in Nephrology and Hypertension. 28 (3): 267–277. doi:10.1097/MNH.0000000000000491. ISSN   1062-4821. PMC   6467553 . PMID   30681417.
  37. ↑ Garneata, Liliana; Stancu, Alexandra; Dragomir, Diana; Stefan, Gabriel; Mircescu, Gabriel (2016-07-01). "Ketoanalogue-Supplemented Vegetarian Very Low–Protein Diet and CKD Progression". Journal of the American Society of Nephrology. 27 (7): 2164–2176. doi:10.1681/ASN.2015040369. ISSN   1046-6673. PMC   4926970 . PMID   26823552.
  38. ↑ Chen, Wei; Abramowitz, Matthew K. (2019). "Advances in management of chronic metabolic acidosis in chronic kidney disease". Current Opinion in Nephrology and Hypertension. 28 (5): 409–416. doi:10.1097/MNH.0000000000000524. ISSN   1473-6543. PMC   6677263 . PMID   31232712.
  39. ↑ Wesson, Donald E.; Mathur, Vandana; Tangri, Navdeep; Stasiv, Yuri; Parsell, Dawn; Li, Elizabeth; Klaerner, Gerrit; Bushinsky, David A. (2019-04-06). "Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial". The Lancet. 393 (10179): 1417–1427. doi:10.1016/S0140-6736(18)32562-5. ISSN   0140-6736. PMID   30857647. S2CID   72332908.
  40. ↑ Wesson, Donald E.; Mathur, Vandana; Tangri, Navdeep; Stasiv, Yuri; Parsell, Dawn; Li, Elizabeth; Klaerner, Gerrit; Bushinsky, David A. (2019-08-03). "Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension". The Lancet. 394 (10196): 396–406. doi:10.1016/S0140-6736(19)31388-1. ISSN   0140-6736. PMID   31248662. S2CID   195339720.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.