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Acetazolamide Induced Metabolic Acidosis

Pathogenic Mechanism, Prophylaxis, And Therapy Of Symptomatic Acidosis Induced Byacetazolamide.

Pathogenic Mechanism, Prophylaxis, And Therapy Of Symptomatic Acidosis Induced Byacetazolamide.

1. J Investig Med. 2002 Mar;50(2):125-32. doi: 10.2310/6650.2002.31297. Pathogenic mechanism, prophylaxis, and therapy of symptomatic acidosis induced byacetazolamide. Filippi L(1), Bagnoli F, Margollicci M, Zammarchi E, Tronchin M, Rubaltelli FF. (1)Department of Critical Care Medicine, University of Florence, Careggi Hospital, Italy. [email protected] BACKGROUND: Acetazolamide, a noncompetitive carbonic anhydrase inhibitor, canproduce symptomatic acidosis and bone marrow suppression by a mechanism that isstill unknown. This presentation occurs in the elderly, patients with renal orliver failure, people with diabetes, and newborns. The objective of this studywas to understand the pathogenic mechanism of these adverse effects and topropose a possible prophylaxis and therapy.METHODS: Four human clinical cases were studied, and one animal experiment wasperformed. Four preterm newborns with posthemorrhagic ventricular dilationdeveloped severe metabolic acidosis after treatment with acetazolamide. Theacidosis suddenly disappeared after a packed red blood cell transfusion.Metabolic studies were performed in one patient and in newborn guinea pigstreated with 200 mg/kg acetazolamide.RESULTS: Acetazolamide can produce severe lactic acidosis with an increasedlactate-to-pyruvate ratio, ketosis with a lowbeta-hydroxybutyrate-to-acetoacetate ratio, and a urinary organic acid profiletypical of pyruvate carboxylase deficiency. The acquired enzymatic injuryresulting from the inhibition of mitochondrial carbonic anhydrase V that providesbicarbonate to pyruvate carboxylase can produce tricarboxylic acid cycle damage. We demonstrate that the dramatic disappearance of metabolic acidosis andnormalizing metabolism after blood transfusion were due to the citrate contained in the pack Continue reading >>

Acetazolamide For Metabolic Alkalosis In Ventilated Patients

Acetazolamide For Metabolic Alkalosis In Ventilated Patients

Topf , Acetazolamide , AcidBase , Electrolytes Patients in the ICU with pulmonary disease primarily have respiratory acidosis and/or metabolic alkalosis. The respiratory acidosis is due to the primary disease and the metabolic alkalosis is due to our attempts to manage that disease, in this case with diuretics. Compensation for metabolic alkalosis is suppression of respiration to allow the carbon dioxide to accumulate reducing the change in pH. Suppressing respiration is obviously a concern in patients on the vent. One option in this situation is to treat the metabolic alkalosis. Although I have read about giving hydrochloric acid infusions, that is a bit nuts. The conventional choice is to cause a drug induce proximal (Type 2) RTA with acetazolamide. The proximal tubule reabsorbs the vast majority of filtered bicarbonate, but it does it through a complex process, where bicarbonate is metabolized to CO2 and water (catalyzed by carbonic anhydrase). The carbon dioxide diffuses into the proximal tubule cell where bicarbonate is reconstituted (again catalyzed by carbonic anhydrase) and then secreted into the circulation. So bicarbonate is destroyed in the tubules and reformed in the tubule cells. Carbonic anhydrase inhibitors slow this and cause the patient to pee bicarbonate. The loss of bicarbonate causes metabolic acidosis, or alternatively, improvement in pre-existing metabolic alkalosis. The carbonic anhydrase inhibitor of choice is acetazolamide. Other carbonic anhydrase inhibitors include Methazolamide,Dorzolamide,Brinzolamide,Topiramate. The pomegranate contains natural carbonic anhydrase activity. This is a nice theory but in February JAMA published a clinical trial to provide empiric data for this time honored strategy. This is a multi center, double-blind, paral Continue reading >>

3ddesign Bmw F30 328i N20b20a , 3ddesign

3ddesign Bmw F30 328i N20b20a , 3ddesign

3DDesign BMW F30 328i N20B20A , 3DDesign [3DDesign]BMW F30 328i(N20B20A), 3DDesign SWAGE-LINE 30mm 250SB, 250SB SWAGE-LINE CARB531GOODRIDGE Z2, Z2 GOODRIDGE 20671350 :ET-1057 H24/5H28/12 5 , ELEVEN FY 187.0J 53 114.3-5 3HSMC, DR17V AT 2015.03, AWESOME317 VRX-2 155 55R14 4 14 4 155 55R14 1993 YFM400 Kodiak ATV Carburetor Repair (), 1993 YFM400 Kodiak ATV Carburetor Repair () SWAGE-LINE 100mm GSX-R750, GSX-R750 SWAGE-LINE PARB402TOYO OBSERVE GARIT GIZ 215/55R17 ( ) 1, 1TOYO OBSERVE GARIT GIZ 215/55R17 P24055C 733-0634 () 2X4 55mm, sw :ET-0296 H18/6H20/12 8 , ELEVEN TM Ignite REV DY5W DY5R :ED-0689 H20/8H24/3 4 , ELEVEN Brembo AUDI Q5 8RCTVF 12/11 P85 099S , T.M. Designworks Dirt Polifibar Rear Guide - RCG-SRM-YL (), T.M. Designworks Dirt Polifibar Rear Guide - RCG-SRM-YL ()FUJITSUBO/ AUTHORIZE S DAA-AVV50 H26.09 360-24461, FUJITSUBO/ AUTHORIZE S DAA-AVV50 H26.09 360-24461 [H20.05H28.08] 3, [H20.05H28.08] Fit CVT MT GK 12 2 19:00 12 7 1:59 MPVH11.06H15.10LW#W 02P05Nov16, CAN AM DOO DECAL-WINDSCREEN GENUINE OEM 204901373 (), CAN AM DOO DECAL-WINDSCREEN GENUINE OEM 204901373 ()CMS KNUCKLERH, CMS 391860004[3DDesign]BMW F11 528i(N20B20A), SSR Professor MS1R 7.0J-16 1, SSR & H22A H27A Microlon 32oz946cc, Microlon Continue reading >>

Acetazolamide (pim 005)

Acetazolamide (pim 005)

2. SUMMARY 2.1 Main risks and target organs Overdoses of diuretics are rare and problems most frequently involve chronic overmedication or poor monitoring of effects or drug-drug interactions that are not anticipated by the clinician. Main toxic effects are on the kidneys with diuresis of water, sodium, potassium, and most importantly bicarbonate with resultant dehydration. More caution is warranted with patients at higher risk for renal abnormal function including patients with any renal disease, diabetes mellitus, exposure to nephrotoxic contrast agents and borderline fluid and/or electrolyte status. Patients with either acute or chronic overdosage with acetazolamide may show signs of dehydration with thirst, lethargy, confusion, poor skin turgor, and prolonged capillary refill time, but may have a paradoxical continued diuresis. Electrolyte abnormalities include hyponatremia, hypokalemia, and a non-anion gap hyperchloremic metabolic acidosis in the more than mild ingestion which may lead to further deterioration in mental status, production of seizures, electrocardiographic abnormalities, and arrhythmias. Prior renal insufficiency will lead to increased toxicity at a given dose. There are idiosyncratic reactions producing bone marrow suppression with hepatic and renal insufficiency. Acetazolamide may also precipitate in the renal tubules producing calculi with renal colic. Hypokalemia may lead to muscular weakness, hyporeflexia, and hypochloremic metabolic alkalosis. In chronic therapy, especially in geriatric patients, a chronic metabolic acidosis may lead to a chronic compensatory hyperventilation which increases pulmonary vascular resistance and decreases left ventricular function. This can be especially significant in patients on concurrent beta-blocker or calci Continue reading >>

Drug-induced Metabolic Acidosis

Drug-induced Metabolic Acidosis

Go to: Introduction Metabolic acidosis is defined as an excessive accumulation of non-volatile acid manifested as a primary reduction in serum bicarbonate concentration in the body associated with low plasma pH. Certain conditions may exist with other acid-base disorders such as metabolic alkalosis and respiratory acidosis/alkalosis 1. Humans possess homeostatic mechanisms that maintain acid-base balance ( Figure 1). One utilizes both bicarbonate and non-bicarbonate buffers in both the intracellular and the extracellular milieu in the immediate defense against volatile (mainly CO 2) and non-volatile (organic and inorganic) acids before excretion by the lungs and kidneys, respectively. Renal excretion of non-volatile acid is the definitive solution after temporary buffering. This is an intricate and highly efficient homeostatic system. Derangements in over-production, under-excretion, or both can potentially lead to accumulation of excess acid resulting in metabolic acidosis ( Figure 1). Drug-induced metabolic acidosis is often mild, but in rare cases it can be severe or even fatal. Not only should physicians be keenly aware of this potential iatrogenic complication but they should also be fully engaged in understanding the pathophysiological mechanisms. Metabolic acidosis resulting from drugs and/or ingestion of toxic chemicals can be grouped into four general categories ( Figure 2): Some medications cannot be placed into one single category, as they possess multiple mechanisms that can cause metabolic acidosis. In suspected drug-induced metabolic acidosis, clinicians should establish the biochemical diagnosis of metabolic acidosis along with the evaluation of respiratory compensation and whether there is presence of mixed acid-based disorders 2, then convert the bioche Continue reading >>

Acetazolamide And Symptomatic Metabolic Acidosis In Mild Renal Failure.

Acetazolamide And Symptomatic Metabolic Acidosis In Mild Renal Failure.

Acetazolamide and symptomatic metabolic acidosis in mild renal failure. This article has been cited by other articles in PMC. Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (419K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . These references are in PubMed. This may not be the complete list of references from this article. Maren TH. Carbonic anhydrase: chemistry, physiology, and inhibition. Physiol Rev. 1967 Oct;47(4):595781. [ PubMed ] CAMPBELL DA. Diuretics and the eye. Br Med J. 1961 Aug 19;2(5250):467474. [ PMC free article ] [ PubMed ] Heuser D, Astrup J, Lassen NA, Betz BE. Brain carbonic acid acidosis after acetazolamide. Acta Physiol Scand. 1975 Mar;93(3):385390. [ PubMed ] O'Sullivan PJ, Crowley JG, Muldowney FP. A case of acetazolamide induced (Diamox) acidotic coma in polycystic renal disease. J Ir Med Assoc. 1967 Oct;60(364):382384. [ PubMed ] Higenbottam T, Ogg CS, Saxton HM. Acute renal failure from the use of acetazolamide (Diamox). Postgrad Med J. 1978 Feb;54(628):127128. [ PMC free article ] [ PubMed ] Ferry AP, Lichtig M. Gouty arthritis as a complication of acetazolamide (Diamox) therapy for glaucoma. Can J Ophthalmol. 1969 Apr;4(2):145147. [ PubMed ] NADELL J. The effects of the carbonic anhydrase inhibitor 6063 on electrolytes and acid-base balance in two normal subjects and two patients with respiratory acidosis. J Clin Invest. 1953 Jul;32(7):622629. [ PMC free article ] [ PubMed ] COUNIHAN TB, EVANS BM, MILNE MD. Observations on the pharmacology of the carbonic anhydrase inhibitor diamox. Clin Sci. 1954 Nov;13(4):583598. [ PubMed ] Epstein DL, Grant WM. Carbonic anhydrase inhibitor side effects. S Continue reading >>

Acetazolamide Disease Interactions

Acetazolamide Disease Interactions

Get key facts and figures about chronic dry eye Carbonic Anhy. Inhibitors (Includes Acetazolamide) Bone Marrow Depression/Blood Dyscrasias Severe Potential Hazard, Moderate plausibility Applies to: History - Blood Dyscrasias, Bone Marrow Depression/Low Blood Counts The use of carbonic anhydrase inhibitors may rarely cause bone marrow suppression and blood dyscrasias at recommended dosages. Aplastic anemia, thrombocytopenia or thrombocytopenia purpura, leukopenia, agranulocytosis, and hemolytic anemia have been reported. Extreme caution should be exercised if carbonic anhydrase inhibitors are administered to patients with these preexisting conditions. A baseline CBC and platelet count is recommended, as well as monitoring at regular intervals during therapy. McWhae JA, Chang J, Lipton JH "Drug-induced fatal aplastic anemia following cataract surgery." Can J Ophthalmol 27 (1992): 313-5 Lubeck MJ "Aplastic anemia following acetazolamide therapy." Am J Ophthalmol 69 (1970): 684-5 Rentiers PK, Johnston AC, Buskard N "Severe aplastic anemia as a complication of acetazolamide therapy." Can J Ophthalmol 5 (1970): 337-42 Keisu M, Wiholm BE, Ost A, Mortimer O "Acetazolamide-associated aplastic anaemia." J Intern Med 228 (1990): 627-32 Englund GW "Fatal pancytopenia and acetazolamide therapy." JAMA 210 (1969): 2282 Gangitano JL, Foster SH, Contro RM "Nonfatal methazolamide-induced aplastic anemia." Am J Ophthalmol 86 (1978): 138-9 "Product Information. Diamox (acetazolamide)." Lederle Laboratories, Wayne, NJ. Wisch N, Fischbein FI, Siegel R, Glass JL, Leopold I "Aplastic anemia resulting from the use of carbonic anhydrase inhibitors." Am J Ophthalmol 75 (1973): 130-2 Kristinsson A "Fatal reaction to acetazolamide." Br J Ophthalmol 51 (1967): 348-9 Carbonic Anhyd. Inhibitors (Incl Continue reading >>

Preretinal Neovascularization Associated With Acetazolamide-induced Systemic Acidosis In The Neonatal Rat | Iovs | Arvo Journals

Preretinal Neovascularization Associated With Acetazolamide-induced Systemic Acidosis In The Neonatal Rat | Iovs | Arvo Journals

Preretinal Neovascularization Associated with Acetazolamide-Induced Systemic Acidosis in the Neonatal Rat From the Departments of Ophthalmology and From the Departments of Ophthalmology and Anesthesiology, Mayo Clinic, Rochester, Minnesota; and Department of Anatomy/Cell Biology/Ophthalmology, Wayne State University, Detroit, Michigan. From the Departments of Ophthalmology and Investigative Ophthalmology & Visual Science April 2001, Vol.42, 1066-1071. doi: Preretinal Neovascularization Associated with Acetazolamide-Induced Systemic Acidosis in the Neonatal Rat You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account Shuichen Zhang, David A. Leske, William L. Lanier, Bruce A. Berkowitz, Jonathan M. Holmes; Preretinal Neovascularization Associated with Acetazolamide-Induced Systemic Acidosis in the Neonatal Rat. Invest. Ophthalmol. Vis. Sci. 2001;42(5):1066-1071. ARVO (1962-2015); The Authors (2016-present) purpose. NH4Cl gavage in the neonatal rat produces a metabolicacidosis-induced retinopathy which serves as a model for retinopathy ofprematurity (ROP). Acetazolamide induces a metabolic acidosis via analternative biochemical mechanism (bicarbonate loss versus hydrogen ionload). In the present study, the following hypothesis was tested:acetazolamide-induced acidosis is associated with preretinalneovascularization in the neonatal rat. methods. All studies used newborn SpragueDawley rats raised in expandedlitters of 25. Arterial blood pH was measured to determine the level ofacidosis induced by intraperitoneal (IP) acetazolamide (50 or 200mg/kg) or saline. In a separate retinopathy study, newborn rats(n = 75) were randomized to either IPacetazolamide, 50 mg/kg (low-dose), or Continue reading >>

Acetazolamide, Metabolic Acidosis, And Intraocular Pressure

Acetazolamide, Metabolic Acidosis, And Intraocular Pressure

In order to investigate whether or not there is a causal relationship between the metabolic acidosis and the ocular hypotension induced by acetazolamide, we undertook to correlate over a period of time the blood-acidifying and ocular-hypotonizing effects of administering the lowest intravenous effective dose of acetazolamide; to treat the metabolic acidosis induced by acetazolamide by means of the intravenous introduction of bases, and pulmonary hyperventilation (respiratory alkalosis); to evaluate the effects on the intraocular pressure (IOP) by neutralizing the acetazolamide-induced metabolic acidosis by means of a continuous infusion of sodium bicarbonate; to determine the relationship between the metabolic acidosis induced by blood-acidifying agents, which do not inhibit carbonic anhydrase, and the IOP; and to determine the changes in the acid-base status of the aqueous humor induced by acetazolamide and other blood-acidifying drugs. We found that the hypertonic buffering solution of sodium bicarbonate could reduce the IOP by itself through an osmotic mechanism. On the basis of our results, we believe that a causal relationship exists between the metabolic acidosis induced by acetazolamide, and by other drugs that have a blood-acidifying effect as the result of other mechanisms, and ocular hypotension, bothin the animal and in the glaucomatous patient. Do you want to read the rest of this article? ... Various studies suggest that carbonic anhydrase , pH, endothelium and perivascular retinal tissue are involved [8,3536373839. It was suspected that the AZ effect is mainly based on the pH decrease caused by the carbonic anhydrase inhibition and its effect on the acidbase balance 4142. There is evidence that other mechanisms play a role in the vascular response to AZ. Continue reading >>

Acetazolamide - An Overview | Sciencedirect Topics

Acetazolamide - An Overview | Sciencedirect Topics

Acetazolamide is a carbonic anhydrase inhibitor that causes a metabolic acidosis that increases the stimulus to breathe while lowering the arterial Pco2 apneic threshold.133 Jeffrey K. Aronson, in Side Effects of Drugs Annual , 2011 Acetazolamide causes a metabolic acidosis, which is usually mild, but can be associated with hypokalemia. In nine subjects who took acetazolamide 250mg or placebo every 8hours for 3days in a double-blind, randomized, crossover design, metabolic acidosis due to acetazolamide was accompanied by a rise in ventilation, a substantial fall in PaCO2, and a parallel leftward shift of the ventilatory CO2 response curve [27c]. Acetazolamide shifted the concentrationeffect curve relating hypoxic sensitivity to arterial hydrogen ion concentration to the left, without altering its slope, showing that it did not affect the interaction of O2 and CO2. There was no specific inhibitory effect of acetazolamide on hypoxic sensitivity. In a 9-year-old girl recombinant human growth hormone 6mg/week caused idiopathic intracranial hypertension (pseudotumor cerebri), which was treated with acetazolamide [28A]. After 4days the dose was increased to 30mg/kg/day, and 2days later she developed a severe metabolic acidosis, with a pH of 7.29. There has been a previous report of metabolic acidosis in a 1-year-old girl who took 5001250mg of acetazolamide [29A]. Jean-Pierre Guignard MD, in Nephrology and Fluid/Electrolyte Physiology: Neonatology Questions and Controversies (Second Edition) , 2012 Acetazolamide increases the urinary excretion of HCO3, Na+, and K+, promoting alkaline diuresis with consequent systemic metabolic acidosis. Acetazolamide may be useful to alkalinize the urine when necessary, such as when chemotherapy is given. Acetazolamide can also be used to ass Continue reading >>

Metabolic Alkalosis Treatment & Management: Approach Considerations, Chloride-responsive Alkalosis, Chloride-resistant Metabolic Alkalosis

Metabolic Alkalosis Treatment & Management: Approach Considerations, Chloride-responsive Alkalosis, Chloride-resistant Metabolic Alkalosis

Metabolic AlkalosisTreatment & Management Author: Christie P Thomas, MBBS, FRCP, FASN, FAHA; Chief Editor: Vecihi Batuman, MD, FASN more... The management of metabolic alkalosis depends primarily on the underlying etiology and on the patients volume status. In the case of vomiting, administer antiemetics, if possible. If continuous gastric suction is necessary, gastric acid secretion can be reduced with H2-blockers or more efficiently with proton-pump inhibitors. In patients who are on thiazide or loop diuretics, the dose can be reduced or the drug can be stopped if appropriate. Alternatively, potassium-sparing diuretics or acetazolamide can be added. Acetazolamide also appears safe and effective in patients with metabolic alkalosis following treatment of respiratory acidosis from exacerbations of chronic obstructive pulmonary disease (COPD). [ 10 , 11 ] However, one randomized trial found that the duration of mechanical ventilation in patients with COPD or obesity-hypoventilation syndrome with metabolic alkalosis was not significantly reduced in patients who received early administration of acetazolamide, compared with placebo. [ 12 ] For a discussion of metabolic alkalosis in children, see Pediatric Metabolic Alkalosis . For a general review of acid-base regulation, see Metabolic Acidosis . If chloride-responsive alkalosis occurs with volume depletion, treat the alkalosis with an intravenous infusion of isotonic sodium chloride solution. Because this type of alkalosis is usually associated with hypokalemia, also use potassium chloride to correct the hypokalemia. If chloride-responsive alkalosis occurs in the setting of edematous states (eg, congestive heart failure [CHF]), use potassium chloride instead of sodium chloride to correct the alkalosis and avoid volume ove Continue reading >>

Acetazolamide - Wikipedia

Acetazolamide - Wikipedia

Not to be confused with acetohexamide or methazolamide . Common side effects include numbness, ringing in the ears , loss of appetite, vomiting, and sleepiness. [2] It is not recommended in those with significant kidney problems , liver problems , or who are allergic to sulfonamides . [2] [4] Acetazolamide is in the diuretic and carbonic anhydrase inhibitor families of medication. [2] It works by decreasing the amount of hydrogen ions and bicarbonate in the body. [2] Acetazolamide came into medical use in 1952. [5] It is on the World Health Organization's List of Essential Medicines , the most effective and safe medicines needed in a health system . [6] Acetazolamide is available as a generic medication . [2] The wholesale cost in the developing world is about 1.40 to 16.93 USD per month. [7] In the United States the wholesale cost is about 125.34 USD per month. [8] It is used in the treatment of glaucoma , drug-induced edema , heart failure-induced edema, epilepsy and in reducing intraocular pressure after surgery. [9] [10] It has also been used in the treatment of altitude sickness , [11] Mnire's disease , increased intracranial pressure and neuromuscular disorders. [12] In epilepsy, the main use of acetazolamide is in menstrual-related epilepsy and as an add on to other treatments in refractory epilepsy. [9] [13] It has been demonstrated in drug trials to relieve symptoms associated with dural ectasia in individuals with Marfan's Syndrome . [14] A 2012 review and meta-analysis found that there was "limited supporting evidence" but that acetazolamide "may be considered" for the treatment of central (as opposed to obstructive) sleep apnea . [15] It has also been used to prevent methotrexate -induced kidney damage by alkalinalizing one's urine, hence speeding up methot Continue reading >>

Metabolic Acidosis And Hyperventilation Induced By Acetazolamide In Patients With Central Nervous System Pathology

Metabolic Acidosis And Hyperventilation Induced By Acetazolamide In Patients With Central Nervous System Pathology

ACETAZOLAMIDE, a carbonic anhydrase inhibitor, is used in patients with meningeal inflammation, mild intracranial hypertension, and basal skull fractures to decrease the formation of cerebrospinal fluid (CSF). It causes mild metabolic acidosis by inhibiting the reabsorption of bicarbonate (HCO−3) ions from renal tubules. This effect has been used successfully in the treatment of patients with chronic respiratory acidosis with superimposed metabolic alkalosis 1 and central sleep apnea syndrome. 2 Life-threatening metabolic acidosis during acetazolamide therapy has been observed only in patients with renal impairment or 3 diabetes 4 and in elderly patients. 5 Severe metabolic acidosis, associated with acetazolamide, in the absence of other predisposing factors has not been reported in patients with central nervous system disease. We report three cases of severe metabolic acidosis and hyperventilation during acetazolamide therapy in normal doses in adult patients without renal impairment. A 35-yr-old man with a head injury underwent craniotomy for evacuation of a traumatic left temporal extradural hematoma. Postoperatively, the patient underwent mechanical ventilation to maintain a partial pressure of arterial carbon dioxide (Paco2) of 30–35 mmHg. On the third postoperative day, 250 mg acetazolamide administered every 8 h through a nasogastric tube was started to treat a CSF leak from the operative wound. A T-piece trial of weaning was started on the fourth postoperative day. On the fifth postoperative day, patient respiratory rate increased to 40–44 breaths/min. Arterial blood gas analysis showed metabolic acidosis resulting in compensatory hypocapnia and a normal pH (table 1). The patient was sedated and underwent artificial ventilation for the next 6 days. Attempt Continue reading >>

Type 2 Renal Tubular Acidosis And Acetazolamide - Deranged Physiology

Type 2 Renal Tubular Acidosis And Acetazolamide - Deranged Physiology

Type 2 Renal Tubular Acidosis and Acetazolamide This form of renal tubular acidosis decreases the strong ion difference by interfering with bicarbonate resorption in the proximal tubule; the mechanism is analogous to the action of acetazolamide. Bicarbonate handling in the proximal tubule Behold, the familiar activity of carbonic anhydrase in the proximal tubule. Carbonic anhydrase converts the filtered bicarbonate into easily resorbed CO2, and then traps it again inside the cell. The filtered bicarbonate is essentialy completely reabsorbed. The concentration of chloride in the tubule is therefore expected to increase- if the bicarbonate has been reabsorbed, more chloride must remain in the tubule to maintain electroneutrality. However, the failure of carbonic anhydrase results in bicarbonate remaining trapped in the urine. This, of course, means that electroneutrality of the tubule is maintained without the excretion of any further chloride. Thus, the chloride which would otherwise be excreted, is retained. There is an excellent article which discusses the mechanisms of chloride retention in acetazolamide-intoxicated patients with metabolic alkalosis. Particularly, it contains a graph of urinary strong ion diference over time, after the administration of 500mg of acetazolamide. It looks a little like this : Causes of proximal renal tubular acidosis Isolated congenital Type 2 RTA is very rare, and would likely form a part of of a syndrome , being associated with a series of other tubular defects, or forming a part of a whole-proximal-tubule problem like Fanconi syndrome. Anong the elderly, a new onset of Type 2 RTA without any new medication changes can be due to a monoclonal gammopathy , where ligh chains selectively damage the proximal tubule. Similarly, amyloidosis Continue reading >>

Normal Anion Gap Metabolic Acidosis

Normal Anion Gap Metabolic Acidosis

Home | Critical Care Compendium | Normal Anion Gap Metabolic Acidosis Normal Anion Gap Metabolic Acidosis (NAGMA) HCO3 loss and replaced with Cl- -> anion gap normal if hyponatraemia is present the plasma [Cl-] may be normal despite the presence of a normal anion gap acidosis -> this could be considered a ‘relative hyperchloraemia’. Extras – RTA, ingestion of oral acidifying salts, recovery phase of DKA loss of bicarbonate with chloride replacement -> hyperchloraemic acidosis secretions into the large and small bowel are mostly alkaline with a bicarbonate level higher than that in plasma. some typical at risk clinical situations are: external drainage of pancreatic or biliary secretions (eg fistulas) this should be easily established by history normally 85% of filtered bicarbonate is reabsorbed in the proximal tubule and the remaining 15% is reabsorbed in the rest of the tubule in patients receiving acetazolamide (or other carbonic anhydrase inhibitors), proximal reabsorption of bicarbonate is decreased resulting in increased distal delivery and HCO3- appears in urine this results in a hyperchloraemic metabolic acidosis and is essentially a form of proximal renal tubular acidosis but is usually not classified as such. hyperchloraemic metabolic acidosis commonly develops during therapy of diabetic ketoacidosis with normal saline oral administration of CaCl2 or NH4Cl is equivalent to giving an acid load both of these salts are used in acid loading tests for the diagnosis of renal tubular acidosis CaCl2 reacts with bicarbonate in the small bowel resulting in the production of insoluble CaCO3 and H+ the hepatic metabolism of NH4+ to urea results in an equivalent production of H+ REASONS WHY ANION GAP MAY BE NORMAL DESPITE A ‘HIGH ANION GAP METABOLIC ACIDOSIS’ 1. Continue reading >>

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