Lec 61. Acid Base Balance, Dr. Yuri Zagvazdin - FS.pdf

Acid-Base Balance Lecture highlights 1. Acids in the body: homeostatic role of buffers, lungs and kidneys 2. Acid-base disorders and compensatory responses 3. Bicarbonate reabsorption, H+ secretion and urinary buffers 4. Types of renal tubular acidosis 5. Anion Gap Objectives: 1. Identify the nor...

Acid-Base Balance Lecture highlights 1. Acids in the body: homeostatic role of buffers, lungs and kidneys 2. Acid-base disorders and compensatory responses 3. Bicarbonate reabsorption, H+ secretion and urinary buffers 4. Types of renal tubular acidosis 5. Anion Gap Objectives: 1. Identify the normal range of pH values, and Ddescribe the role of buffers, and respiratory and renal mechanisms in maintaining pH. 2. Describe the respiratory and renal regulation of the CO2 /HCO3 - buffer system. Discuss the significance of Henderson-Hasselbalch equation 3. Distinguish between CO2 -derived volatile and nonvolatile acids and the normal routes of their loss from the body. 4. Identify simple metabolic and respiratory acid-base diseases using values of arterial blood gases (ABG). Understand the difference between simple and mixed acid-base disturbances and between acute and chronic disturbances. 5. Describe processes that lead to acid-base disturbances and their common causes. 6. Predict the direction and time course of the compensatory reactions to acidbase disturbances. 7. Identify the major sites and mechanisms of HCO3 - reabsorption and H + secretion along the nephron. 8. Explain the physiological effects of carbonic anhydrase inhibition at the proximal tubule and other inhibitors of renal tubular transport on acidbase balance; give specific examples. 9. Describe the significance of urinary buffers (phosphate and ammonia) and contrast them with the blood buffers. Distinguish between the reclamation of filtered bicarbonate and the formation of new bicarbonate. 10. Distinguish between different types of renal tubular acidosis; explain the use of increased and normal anion gap for diagnostic purposes. Many cellular functions are sensitive to the blood pH [H+] nEq/L Normal arterial blood pH is close to 7.4 1. Blood pH < 7.38 – Acidosis 2. Blood pH > 7.44 – Alkalosis The pH range that is compatible with life is 6.8 to 7.8 Acidemia 80 60 40 20 pH = - log [H+] – Note reverse relationship: Increased [H+] = decreased pH Logarithmic “distortion” Large changes in [H+] appear as small changes in pH, e.g., an increase of [H+] from 40 to 80 nmol/L will decrease pH from 7.4 to 7.1 pH 7.55 Mortality rate? ~ 50% if metabolic alkalosis Physiological concentration of [H+] are very low compared to other ions Distilled water [H+] = 0.000000155 mole/L, pH = 6.8; Plasma [H+] = 0.000000040 mole/L, pH = 7.4 Alkalemia 7.0 7.4 7.6 pH pH value [H+]; nmol/L 7.6 25 7.5 32 7.4 40 7.3 50 7.2 60 7.1 80 7.0 100 6.9 125 6.8 160 Normal tissue metabolism results in production of acids Adequate tissue perfusion and O2 supply results in generation of 15-20 moles of CO2. Accumulation of CO2 in the body should be viewed as acidification because hydration of CO2 generates a volatile carbonic acid (CO2 can be eliminated via lungs) H2CO3 Acids that don’t derive from CO2 hydration are non-volatile, e.g. lactic acid. Oxygen and Carbon Dioxide Transport and Control of Respiration Mulroney, Susan E., PhD, Netter's Essential Physiology, Chapter 16, 185-199 Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. A regular Western diet generates a daily nonvolatile metabolic acid load of approximately 50 to 100 mEq/day that must be excreted by the kidneys. Food and Acid Production Relatively alkaline urine (above pH 6 may be induced by a diet high in certain fruits and vegetables Alkaline producing Neutral Acid producing vegetables fruits meat asparagus banana eggs barley grass broccoli blueberry cantaloupe milk butter cabbage cranberry fish Very alkaline urine (pH>7.0) is suggestive of? infection with a ureasplitting organism, such as Proteus mirabilis Most fluids which we consume have pH lower than 7.4 Solution 1 M HCL pH 0 Lemons 2.3 Soft drinks 3.0 Oranges 3.5 Tomatoes 4.2 Rainwater Milk 6.2 6.5 Pure water 7.0 Ocean water 8.5 Our body must retain an alkaline environment despite constant acid production Three lines of defense: 1. Buffers - intracellular, extracellular and urinary, rapid action 2. Lungs – changes in ventilation to remove CO2, rapid action – minutes 3. Kidneys – changes in H+ secretion and HCO3 reabsorption, slow action - days Action of buffers: response to addition of NH4Cl in water The most common acid-loading test is and plasma administration of ammonium chloride (NH Cl). + NH4Cl = H + NH3 + Cl pH 7.4 7.0 6.0 Plasma Urine Buffering: (“H+ sponge”) Urine pH 6 hours later 5.0 4.0 3.0 2.0 4 Urine is collected hourly 2-8 hours later. A healthy person excretes acid decreasing urine pH. Failure of urine pH to shift below 5.2 after NH4 Cl suggest renal tubular acidosis (RTA), i. e. impaired H+ secretion in the distal renal tubule Distal RTA Healthy While normal physiological range of urine pH is 4.5 – 8 with an average close to 6 in healthy individuals without acid-base disturbance, patients with normal kidney function and normal renal acidification mechanisms who develop metabolic acidosis usually have a urine pH of 5.3 or less. Water 1.0 1 min Extracellular buffers: 1. Bicarbonate - carbonic acid = most important physiologically. Lungs can independently regulate CO2, and kidneys can independently regulate H+ and HCO3- secretion and reabsorption. Insignificant as a buffer in urine!; urine HCO3concentration is negligible in the physiological range of urine pH Adrenal Gland H+ + HCO3- = H2CO3= H2O + CO2 Extracellular bicarbonate neutralizes most of H+ load Kidney Lungs 2. Plasma Proteins 3. Phosphate, small amount in blood, important urinary buffer Intracellular buffers – hemoglobin, phosphate air Acid – Base Balance in Plasma Base excess (positive or negative) H2O + CO2 = H2CO3= H+ + HCO3Acid (releases H+) Base (accepts H+) unstable Carbonic anhydrase catalyze the reaction Ratio [HCO3-] / CO2 determines plasma pH Pco2 or [HCO3-] - pH (acidosis) [HCO3-] or Pco2 - pH (alkalosis) normally ratio [HCO3-] / H2CO3 = 20 / 1 Acid Base Disorders Four primary simple acid base disorders: a. respiratory acidosis b. respiratory alkalosis c. metabolic acidosis d. metabolic alkalosis Acid base disturbances due to a change in arterial partial pressure of carbon dioxide Pco2 are respiratory. All other disturbances are referred to as metabolic. How is acid-base status assessed? Acid base status is assessed by arterial blood gases (ABG = pH, pCO2, bicarbonate, pO2*). ABG’s can show not only the original problem, but also a compensatory attempt by the body. * pO2 is used for assessment of oxygenation status, but may be also informative for acid base status The ABL800FLEX blood gas analyser. (Courtesy of Radiometer Medical ApS.) Additional equipment used in anaesthesia and intensive care Al-Shaikh, Baha, FCARCSI, FRCA, Essentials of Anaesthetic Equipment, Chapter 13, 219-239 Copyright © 2013 Copyright © 2013 Elsevier Ltd. All rights reserved Respiratory acid base disorders indicate inadequate lung ventilation. Compensatory reaction: only the kidneys (3rd line of defense). In contrast, both kidneys and lungs (if their functions are intact) or only lungs can attempt to compensate metabolic disturbances. Compensatory reactions do not provide complete normalization unless the underlying problem is corrected. An exception may be chronic respiratory acidosis in which healthy kidneys can with time elevate pH up to normal level. The patient experiences anxiety, shortness of breath and feels as though she is unable to fill her lungs. Hyperventilation Buttaravoli, Philip, MD FACEP, Minor Emergencies, Chapter 3, 8-10 Copyright © 2012 Copyright © 2012 by Saunders, an imprint of Elsevier Inc. If CO2 goes up – pH decreases = respiratory acidosis Decreased ventilation rate Reduced expiration of CO2 Hypoventilation - Pco2 exceeds 45 mm Hg Increase in plasma Pco2 Causes: pulmonary insufficiencies such as COPD, lung edema, respiratory muscle weakness, drugs (anesthetics, CNS depressants, Decrease in plasma pH Respiratory acidosis morphine, etc.) Respiratory [H+] pH Pco2 HCO3 Compensation Acidosis slow Alkalosis slow If CO2 goes down–pH increases = respiratory alkalosis Hyperventilation - Pco2 is below 35 mm Hg Causes: high altitude, fever, anxiety, heat exposure, etc. The metabolic compensation for respiratory acidosis is H+ secretion by the kidney; the elevated serum bicarbonate is a byproduct of H+ secretion and does not play a role in buffering the respiratory acid. If HCO3- goes down – pH decreases = metabolic acidosis It is either loss of bicarbonate or gain of hydrogen HCO3- is less than 22 mEq/L Causes: acid overproduction in diabetes, loss of alkali in acute diarrhea or failure to adequately reabsorb HCO3- (type II proximal tubular acidosis), or failure to excrete H+ (type I and IV distal tubular acidosis) Metabolic [H+] pH Pco2 HCO3 Compensation Acidosis fast or slow Alkalosis fast or slow If HCO3- goes up – pH increases = metabolic alkalosis HCO3- is greater than 28 mEq/L It is either gain of bicarbonate or loss of hydrogen Causes: ingestion of alkali (antacids), loss of acid with vomiting, hyperaldosteronism, diuretics. Metabolic alkalosis is frequently associated with circulatory volume depletion and hypokalemia. Compensatory reaction of the intercalated cells to acidosis Alpha intercalated cells are involved in the compensatory reaction to acidosis (increased H+ secretion), but no full compensation unless the underlying cause of the condition is fixed. Acidosis may coexist with hyperkalemia (decreased K+ secretion) or hypokalemia. By contrast, metabolic alkalosis often coexists with hypokalemia. Bicarbonate secretion via beta intercalated cells can occur in alkalosis . Normal Acid-Base Balance Palmer, Biff F., Comprehensive Clinical Nephrology, Chapter 11, 142-148 Copyright © 2015 Copyright © 2015, 2010, 2007, 2003, 2000 by Saunders, an imprint of Elsevier Inc. Acid Base Disturbances Disturbance PCO2 H+ pH HCO3- Acidosis Respiratory Metabolic Normal or Alkalosis Respiratory Metabolic Normal or Determination of whether appropriate respiratory compensation of metabolic acidosis has taken place These rules work well for mild to moderately severe metabolic acidosis (HCO3 7-22 mEq/L) ● Winter's formula: pCO2 = 1.5 x HCO3 + 8 ± 2 ●pCO2 = HCO3 + 15. ●The pCO2 should approximate the decimal digits of the arterial pH. Example: if the pH is 7.25, then the pCO2 should be approximately 25 mmHg Walter Cannon, Department of Physiology, Harvard Medical School, coined the term “Fight or Flight response” DOI: (10.1152/advan.00187.2017) Fig. 3. Left to right: Captains John Fraser and A. N. Hooper of the Royal Army Medical Corps with Captain Walter B. Cannon of the U.S. Army Medical Service at Casualty Clearing Station No. 33, Béthune, France, October 1917. [From Benison et al. (2), reproduced with permission.] Sodium bicarbonate for treatment of metabolic acidosis Snatched from death Walter Cannon to his wife Cornelia, 1914: A poor fellow was brought in with terrible wounds… After operation his blood pressure was 68, his pulse 148, his respiration 34 and over. About ten o’clock he was much worse….He was gasping for breath at the rate 48 per minute. … “ I can’t breathe. Give me air…” We ran 35 ounces of the warm sodium bicarbonate solution in his arm vein. I have never saw anything in my life so dramatic as the change that occurred. His respirations promptly fell from 48 to 26 per minute, and his pulse from 148 to 126. And in ten minutes he was quietly sleeping. … Next day blood pressure rose 86, 102, 114… Wolfe E., Barger A.C., Benson S. 2000 Walter B. Cannon, Science and Society. Soldier in France. World War I. War! What is it good for? Mustard gas medicine Smith, Susan L., PhD, Canadian Medical Association Journal, Volume 189, Issue 8, E321-E322 Copyright © 2017 Joule Inc. or its licensors Cannon credited Sir Almroth Wright, who used Na2CO3 successfully to treat soldiers with acidosis accompanying gas gangrene infections. Since then, alkali was adopted for therapy of acidosis with low blood pressure regardless of pathogenesis. Severe and symptomatic acute metabolic acidemia can most rapidly be treated by the intravenous administration of sodium bicarbonate. Despite its potential adverse effects, sodium bicarbonate remains the most frequently used alkalinizing agent. Less severe acute metabolic acidosis does not usually require bicarbonate treatment and experts disagree on effectiveness of its outcomes. Sodium bicarbonate treatment may not be a good idea in respiratory acidosis. pH Pco2 (mm Hg) bicarbonate (mEq/L) mean 7.4 40 26 range 7.38 – 7.44 35 - 45 22-28 Which of the following is the disease of a patient with pH 7.29, Pco2 34 and HCO3 14 mEq/L? a. respiratory acidosis b. metabolic acidosis c. respiratory alkalosis d. metabolic alkalosis Renal compensatory response is slow (days). Consequently, respiratory acid-base disturbances can be divided into acute and chronic phases. Acute and chronic acid base disorders Respiratory acidosis The acute phase – not enough time for compensatory renal response – bicarbonate elevation is minimal (1 mEq/L per 10 mm Hg of CO2). The chronic phase – plasma bicarbonate is increased substantially (up to 4 mEq/L per 10 mm Hg of CO2), i.e. compensatory response is apparent. Acid-Base Regulation Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 31, 409-426 Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. Respiratory Acidosis CO2 is accumulated, Volatile acid formation Kidney compensation: H+ secretion and excretion Bicarbonate reabsorption Respiratory Alkalosis Kidney compensation: CO2 is exhaled excessively, H+ level H+ secretion and excretion Bicarbonate reabsorption Bicarbonate secretion and excretion mean range pH 7.4 7.38 – 7.44 Pco2 (mm Hg) 40 35 - 45 SBC (mEq/L) 26 22-28 SBC = serum bicarbonate A patient has low arterial pressure, reduced tissue turgor and the following ABG’s: pH 7.57, [HCO3] 47 mEq/l, pCO2 48 mm Hg. Which of the following is the expected diagnosis? a. respiratory alkalosis without compensation Analysis of blood gases and acid–base balance Smith, Andrew, Surgery, Volume 26, Issue 3, 86-90 Copyright © 2008 Elsevier Ltd b. respiratory alkalosis with compensation c. metabolic alkalosis without compensation d. metabolic alkalosis with compensation Common clinical states and associated acid-base disorders Clinical State Disturbance Pulmonary embolus Respiratory Alkalosis Pregnancy Respiratory Alkalosis Vomiting Metabolic Alkalosis Diuretics Metabolic Alkalosis Diarrhea Metabolic Acidosis (extrarenal origin) Renal tubular acidosis Metabolic Acidosis (renal origin) pH pCO2 pO2 Acid base status Example 7.56 20 90 Acute Respiratory Alkalosis Acute hyperventilation 7.56 20 50 Acute Respiratory Alkalosis Pulmonary embolism 7.44 25 90 Chronic Resp. Alk. w Comp. Chronic hyperventilation 7.24 60 80 Acute Respiratory Acidosis Sedative overdose 7.16 70 50 Acute Resp. Acid. w Hypoxia Resp. Failure from Hypoxia Generation and maintenance of metabolic alkalosis Metabolic alkalosis persists due to excessive gastrointestinal (vomiting) and/or renal H+ loss, and RAAS activation due to hypovolemia, low GFR or/and arterial blood volume (heart failure, cirrhosis) Acid-Base Physiology Costanzo, Linda S., PhD, Physiology, Chapter 7, 311-337 Copyright © 2018 Copyright © 2018 by Elsevier, Inc. All rights reserved. Reabsorption of bicarbonate by the nephron Most of bicarbonate reabsorption (70-80%) takes place in the proximal tubule and totally about 99% or more is reabsorbed Role of the Kidneys in the Regulation of Acid-Base Balance Koeppen, Bruce M., MD, PhD, Berne and Levy Physiology, 37, 670-684 Copyright © 2018 Copyright © 2018 by Elsevier, Inc. All rights reserved. Reabsorption of filtered bicarbonate . Renal tubule is not permeable to bicarbonate ions. CA = carbonic anhydrase converts ions into molecules of water and CO2 which can diffuse across the cell membrane. What would be the effect of CA inhibitors? Hydrogen secretion in proximal and distal segments of nephron Proximal Distal H+ excreted (mEq/per day) 3,900 504 Maximum acidity of tubular fluid 6.8 4.4 Accomplishment Reabsorption of 3.900 mEq Reabsorption of 432 mEq of bicarbonate per day of bicarbonate per day and generation of 72 mEq of new bicarbonate Formation of “new” bicarbonate and two mechanisms for trapping H+ in urine (urinary buffers) Formation of new bicarbonate – trapping H+ in the lumen Two mechanisms: 1. Phosphate 2. Ammonia Role of the Kidneys in the Regulation of Acid-Base Balance Koeppen, Bruce M., MD, PhD, Berne and Levy Physiology, 37, 670-684 Copyright © 2018 Copyright © 2018 by Elsevier, Inc. All rights reserved. Phosphate plays an important role of urinary buffer by trapping H+ Na2HPO4 dibasic phosphate Secreted H+ is bound and excreted as monobasic phosphate Urine Excretion of H+ as titratable acid (any acid that can lose proton(s) in an acid-base reaction, in this case phosphoric acid) Acid-Base Regulation Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 31, 409-426 Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. Ammonia mechanism Accounts for about 50% of H+ buffering or more Secreted H+ ions combine with NH3 which diffuse from the tubular cell and ammonium ions NH4+ are formed. Cell membrane is impermeable to NH4+ , and trapped H+ is excreted The major adaptive kidney response to an acid load is to increase urinary excretion of NH 4 + produced from systemically derived glutamine. Creatinine contributes significantly as urinary buffer in severe metabolic acidosis at pH of urine below 5) Bicarbonate is not considered as a urinary buffer! Common clinical states and associated acid-base disorders Clinical State Disturbance Pulmonary embolus Respiratory Alkalosis Pregnancy Respiratory Alkalosis Vomiting Metabolic Alkalosis Diuretics Metabolic Alkalosis Diarrhea Metabolic Acidosis (extrarenal origin) Renal tubular acidosis Metabolic Acidosis (renal origin) The normal urine pH range is between 4.5 and 8. Any pH higher than 8 is basic or alkaline, and any under 6 is acidic Renal tubular acidosis Acidosis can be caused by various defects in the tubular transport: 1. Renal tubular acidosis type I – distal, hypokalemic Damage to the alpha intercalated cells (autoimmune disease = Sjogren’s syndrome, nephrocalcinosis) 2. Renal tubular acidosis type II – proximal hypokalemic Damage to the cells of the proximal tubule = Fanconi’s syndrome 3. Renal tubular acidosis type III – mixture of type I and type II 4. Renal tubular acidosis type IV – distal hyperkalemic as in hypoaldosteronism Type I distal tubular hypokalemic acidosis Renal tubular acidosis Acidosis can be caused by various defects in the tubular transport: 1. Renal tubular acidosis type I – distal, hypokalemic Damage to the alpha intercalated cells (autoimmune disease = Sjogren’s syndrome, nephrocalcinosis) 2. Renal tubular acidosis type II – proximal hypokalemic Damage to the cells of the proximal tubule = Fanconi’s syndrome 3. Renal tubular acidosis type III – mixture of type I and type II 4. Renal tubular acidosis type IV – distal hyperkalemic as in hypoaldosteronism Proximal tubule. Tubular acidosis type II, hypokalemic Can be caused by carbonic anhydrase inhibitors Solvent drag Renal tubular acidosis Acidosis can be caused by various defects in the tubular transport: 1. Renal tubular acidosis type I – distal, hypokalemic Damage to the alpha intercalated cells (autoimmune disease = Sjogren’s syndrome, nephrocalcinosis) 2. Renal tubular acidosis type II – proximal hypokalemic Damage to the cells of the proximal tubule = Fanconi’s syndrome 3. Renal tubular acidosis type III – mixture of type I and type II 4. Renal tubular acidosis type IV – distal hyperkalemic as in hypoaldosteronism Type IV renal hyperkalemic tubular acidosis All types of renal tubular acidosis are associated with normal anion gap in plasma There are several gaps in acid – base physiology: Anion gap in plasma Delta anion gap Osmole (osmolarity) gap Urine anion gap What is anion gap of plasma? Anion Gap of Plasma The equivalents of cations in plasma always balance the equivalents of anions. So, the true plasma anion gap is 0. However, not all ionic constituents are reported by the lab. The simplest reports may give only [Na+], [Cl-] and [HCO3-]. The “real” balance is given by equation: [Na+] + [other cations] = [Cl-] + [HCO3-] + [other anions] Anion Gap Unmeasured anions HCO3Na+ Cl- other cations rearranging: "Anion Gap" Cations Anions = [Na] - ([Cl] + [HCO3]) = [other anions] - [other cations] Normal values for the Anion Gap are 8-16 mEq/L plasma All Cations and Anions (mEq/L) Cations Anions Sodium 140 Chloride 104 Calcium 5 Bicarbonate 24 Potassium 4.5 Proteins 15 Magnesium 1.5 Organic acids 5 Phosphates 2 Sulfates 1 Total 151 Total 151 Cations and Anions used to calculate Anion Gap Cations Anions Na+ = 140 Cl- + HCO3- = 128 Plasma Anion Gap = unmeasured anions Anion gap can be used to diagnose different types of metabolic acidosis Metabolic acidosis is associated with decreased plasma HCO3Increased anion gap Accumulation of organic acids (ketoacids, lactate, salicylate, etc.). The decrease in plasma HCO3- is offset by an increase in the concentration of an unmeasured organic anions. Thus, anion gap is wider in diabetic ketoacidosis, salicylate poisoning and chronic uremic renal failure. Normal Anion profile Gap = 12 HCO3-= 24 Cl- = 104 Addition of acid H+ AGap = 20 AHCO3-= 16 Gap from 12 to 20 HCO3- from 24 to 16 Cl- = 104 H+ A- + HCO3- = A- + H2O + CO2 Causes of High Anion Gap Metabolic Acidosis (GOLD MARK) Glycols (glycolic acid, ethylene and propylene glycol) Oxoproline (pyroglutamic acid, the toxic metabolite of excessive acetaminophen, e.g. paracetamol) L-Lactate (endogenous lactic acid; lactic acidosis causes HELP: hypoxia, ethanol, liver failure, poisoning with ethylene glycol or methanol) D-Lactate (exogenous lactic acid produced by gut bacteria) Methanol (formic acid) Aspirin (salicylic acid) Renal Uremic Failure (phosphate, uric acid, azotemia, low ammonia production and ammonium excretion) Ketones (ketoacids; SAD: starvation, alcoholism, diabetes) Clinical Syndromes of Metabolic Acidosis Krapf, Reto, Seldin and Giebisch's The Kidney, Chapter 59, 2049-2111 Copyright © 2013 Copyright © 2013 Elsevier Inc. All rights reserved Ketone Formation Normal anion gap The anion gap can be used to classify different types of metabolic In some formsassociated of metabolic with acidosis, no organic anions bicarbonate are accumulated. The acidosis decreased plasma decrease in plasma HCO3- is offset by an increase in the concentration of Cl- hyperchloremic metabolic acidosis with a normal anion gap (diarrhea, carbonic anhydrase inhibitors, renal tubular acidosis) Normal Anion profile Loss of HCO3- or addition of HCl Gap = 12 Gap = 12 HCO3-= 24 Cl- = 104 HCO3-= 16 Gap from 12 HCO3- from 24 to 16 Cl- = 112 HCl + HCO3- = Cl- + H2O + CO2 A diabetic patient with vomiting as a chief complain has the following blood work ABG: pH 7.4, PCO2 40 mm Hg, PO2 98 mm Hg, HCO324 mEq/L Electrolytes: Na+ 135 mEq/L, K+ 3.3 mEq/L, Cl- 75 mEq/L After, giving a prescription for potassium supplements, a resident is ready to send him home because the ABG values are normal !? Mixed disorders - two or more underlying causes of acid-base disturbance The patient has a mixed acid base disorder – metabolic acidosis and metabolic alkalosis. Loss of acid with vomiting masked the metabolic acidosis caused by diabetes.