Acid Base Disorders in Medicine. Case 1. Objectives

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1 Acid Base Disorders in Medicine Jonathan J. Taliercio, DO Department of Nephrology and Hypertension Glickman Urological and Kidney Institute Case 1 A hospitalized 62-year-old woman has a 2 day history of SBO manifesting with profuse vomiting requiring NGT suction. Exam BP 80/50, HR 115/min, skin turgor, and diffuse abdominal pain. The BMP indicates serum Na 135 meq/l, K 3.5 meq/l, Cl 85 meq/l, HCO 3 25 meq/l, BG 90 mg/dl, BUN 110 mg/dl, creatinine 4.5 mg/dl. ABG: ph 7.40, pco 2 40 mm Hg. Which one of the following best applies to this patient? A. There is no significant acid-base disorder because the blood ph and HCO 3 are normal B. The patient does not have metabolic acidosis because of the normal blood ph C. The patient has metabolic alkalosis D. The patient has metabolic acidosis and respiratory acidosis E. The patient has a mixed metabolic acidosis and metabolic alkalosis Objectives Relevant, high yield information for boards and clinical practice Basic Concepts Acid Base Nomenclature Stepwise approach to Acid Base Problem solving Questions and Answers Conclusions

2 Basic Concepts Carbohydrate and lipid metabolism generates 15,000 mmol/day of CO 2 Volatile acid CO 2 + H 2 0 H 2 CO 3 H + + HCO 3 CO 2 is effectively eliminated via respiration Protein metabolism generates amino acid Nonvolatile acids (sulfur, phosphorus) 1 mmol H + per kg ~ ( mmol/day) Kidney must excrete H+ with urinary buffers (ammonia = NH 3 ) and replenish HCO 3 that is consumed via the neutralization of nonvolatile acids Consequences of Acidosis Cardiovascular Cardiac contractility and BP Risk for dysarrhythymias Respiratory Hyperventilation Cerebral Obtundation and coma Metabolic Hyperkalemia, insulin resistance, ATP synthesis Basic Concept A simultaneous ABG and a BMP is required for the determination of an acid base disorder HCO 3 measurement on the ABG is calculated using the henderson-hasselbalch equation HCO 3 (total PCO 2 ) on a venous sample is a true measurement

3 Normal Values for Acid-Base Parameters in Arterial and Venous Blood ph [H + ] PCO 2 [HCO 3 ] nanoeq/l mmhg meq/l Arterial Venous Henderson-Hasselbalch What is the expected ph in a patient with HCO 3 15 and PCO 2 40? HCO 3 ph = log (0.03) PCO 2 ph = log (40) ph = 7.2 Clinical Use What is the expected ph in a patient with HCO 3 15 and PCO 2 40? PCO [H + 2 ] neq/l = 24 x HCO 3 [H + 40 ] neq/l = 24 x 15 [H + ] neq/l = 63 ph [H+]

4 Acid-base Nomenclature Simple acid-base disturbance The presence of one primary abnormality coupled with its anticipated secondary response Mixed acid-base disturbance The simultaneous presence of two or more primary abnormalities Acid Base Nomenclature Acidemia - ph < 7.36 [ H + ] ( ph) Alkalemia- ph > 7.44 [ H + ] ( ph) Acidosis- a pathophysiological process which decreases extracellular fluid ph Metabolic acidosis initial disturbance [HCO 3 ] Respiratory acidosis initial disturbance [PCO 2 ] Alkalosis - a pathophysiological process which increases extracellular fluid ph Metabolic alkalosis initial disturbance [HCO 3 ] Respiratory alkalosis initial disturbance [PCO 2 ] Patterns of Simple Acid Base Disorders Primary Disorder ph Compensatory Change (PCO 2) Primary Change (HCO 3 ) Metabolic Acidosis Metabolic Alkalosis Primary Disorder ph Primary Change (PCO 2 ) Compensatory Change (HCO 3 ) Respiratory Acidosis Respiratory Alkalosis

5 Respiratory Compensation for Primary Metabolic Disturbances Primary Compensatory Disorder Change Response Metabolic [HCO 3 ] * Expected PaCO 2 : 1.2 mmhg in PaCO 2 Acidosis for every 1 mmol/l fall in HCO 3 Time adaptation *Expected PaCO 2 : 1.5 X HCO 3 + (8 +/- 2) (Winters Formula) * Expected PaCO 2 : HCO * Expected PaCO 2 : last digits of ph ~ 30 mins - 24 hours Respiratory Compensation for Primary Metabolic Disturbances Primary Compensatory Disorder Change Response Metabolic [HCO 3 ] * Expected PaCO 2 : 0.7 mmhg in PaCO 2 Alkalosis for every 1 mmol/l rise in HCO 3 Time adaptation ~ 30 mins - 24 hours Renal Compensation for Primay Respiratory Disturbances Disorder Compensatory Response Acute Respiratory Acidosis 1 meq/l increase in [HCO 3- ] for (mins- hours) every 10 mmhg rise in PCO 2 Acute Respiratory Alkalosis 2 meq/l decrease in [HCO 3- ] for (mins- hours) every 10 mmhg fall in PCO 2 Chronic Respiratory Acidosis 3.5 meq/l increase in [HCO 3- ] for (3-5 days) every 10 mmhg rise in PCO 2 Chronic Respiratory Alkalosis 4 meq/l decrease in [HCO 3- ] for (3-5 days) every 10 mmhg fall in PCO 2

6 Key Concept In primary acid base disorders, the compensatory response does not fully correct the underlying disorder (ph) but rather reduces the magnitude of the change in ph Metabolic Acidosis Primary defect is fall in serum HCO 3 Accumulation of metabolic acids caused by: 1. Excess acid production which overwhelms renal capacity for acid excretion (e.g., diabetic ketoacidosis) 2. Renal excretory failure: normal total acid production in face of poor renal function (e.g., chronic renal failure) 3. Loss of alkali: leaves un-neutralized acid behind (e.g., diarrhea) Serum Anion Gap Anion Gap = Na + - (Cl - + HCO 3 ) Normal range 8-16 meq/l The gap simply reflects the differences between the unmeasured anions and unmeasured cations The expected anion gap should be reduced by 2.5 meq/l for every 1 g/dl reduction in albumin below 4 g/dl Example: Expected AG is 5 in a patient with a albumin of 2 g/dl (10 (2 x 2.5) = 5)

7 Serum Anion Gap SO 4 - = 2 HPO 4 - = 3 Mg ++ = 2 Protein = 16 Cl - = 105 Cl - = 105 Causes of AGMA Methanol Uremia Diabetic (ETOH starvation ketosis) Propylene glycol Isoniazid Lactic acidosis Ethylene glycol Salicylates Glycols (ethylene, propylene) Oxoproline L-lactate D-lactate Methanol Aspirin Renal failure Ketosis (ETOH or DKA) Case 1 A hospitalized 62-year-old woman has a 2 day history of SBO manifesting with profuse vomiting requiring NGT suction. Exam BP 80/50, HR 115/min, skin turgor, and diffuse abdominal pain. The BMP indicates serum Na 135 meq/l, K 3.5 meq/l, Cl 85 meq/l, HCO 3 25 meq/l, BG 90 mg/dl, BUN 110 mg/dl, creatinine 4.5 mg/dl. ABG: ph 7.40, pco 2 40 mm Hg. Which one of the following best applies to this patient? A. There is no significant acid-base disorder because the blood ph and HCO 3 are normal B. The patient does not have metabolic acidosis because of the normal blood ph C. The patient has metabolic alkalosis D. The patient has metabolic acidosis and respiratory acidosis E. The patient has a mixed metabolic acidosis and metabolic alkalosis

8 Step Wise Approach to Acid Base Problem Solving 1. Is there a acidemia or alkalemia present? 2. Identify the primary disturbance (-oses) Examine HCO 3 and PCO 2 levels 3. Calculate the expected compensation If inappropriate, identify the 2 nd disorder 4. Is an AGMA present? 5. If an AGMA is present, check the delta-delta Case 1 Answer Serum: Na 135 meq/l, K 3.5 meq/l, Cl 85 meq/l, HCO 3 25 meq/l, BG 90 mg/dl, BUN 110 mg/dl, creatinine 4.5 mg/dl. ABG: ph 7.40, pco 2 40 mm Hg. Which one of the following best applies to this patient? 1. Is there a acidemia or alkalemia present? No 2. What is the primary disturbance? pco 2 = 40, HCO 3 = 25 (None) 3. Calculate the expected compensation? Not required 4. Is an AGMA present? AG = Na + - (Cl - + HCO 3 ) 135 ( ) = 25. Yes 5. If an AGMA is present, check the delta-delta AGMA with Metabolic Alkalosis Delta Ratio or Gap

9 Alternative to Delta Ratio or Gap HCO 3 expected = HCO3 normal (24) - AG 1.If HCO 3 expected ~ HCO 3 measured = pure AGMA If the expected and measured HCO 3 are similar than no other hidden acidosis or alkalosis are present 2.If HCO 3 expected > HCO 3 measured = AGMA with NAGMA A measured HCO 3 much less than expected HCO 3 in AGMA is a clue that a hidden NAGMA is present 3. If HCO 3 expected < HCO 3 measured = AGMA with metabolic alkalosis A measured HCO 3 much higher than expected HCO 3 in AGMA is a clue that a hidden metabolic alkalosis is present Case 2 Answer : Delta Delta Serum: Na 135 meq/l, Cl 85 meq/l, HCO 3 25 meq/l. ABG: ph 7.40, pco 2 40 mm Hg. Which one of the following best applies to this patient? AG = 25 HCO 3 expected = HCO 3 normal (24) - AG [24 - (25-10)] = 9 HCO 3 expected HCO 3 measured is 25 For every 1 AG : 1 HCO 3 expected HCO 3 expected 9 < HCO 3 measured (25) than there is a hidden metabolic alkalosis in the presence of an AGMA Treatment of Metabolic Acidosis 1. Treat underlying cause (e.g., hypotension, sepsis, DKA) 2. Administration of sodium bicarbonate ALWAYS if ph < 7.2 Avoid overzealous administration of HCO 3 Modest increment in plasma HCO 3, (e.g., 4-6 meq/l) BEWARE of overshoot alkalemia BEWARE of worsening CNS status HCO 3 + H+ H 2 CO 3 CO 2 + H 2 O

10 Key Concept If the ph is normalized than a mixed disorder is present It is impossible to have a simultaneous respiratory acidosis and respiratory alkalosis Case 2 22 year old man is found unconscious in the street and brought to an OSH ED. He is only responsive to pain. His neurological exam is non focal. Serum: Na 130, K 4, Cl 94, HCO 3 11, BUN 56, SC~ 2, Glucose 72, serum osmoles 320. ABG ph 7.27, PCO Serum lactate, ketones, and ethanol levels are normal. What is the most appropriate first step in the management of this patient? A. Transfer him to the Cleveland Clinic B. Forced alkaline diuresis C. Fomepizole D. Hemodialysis Case 2 Answer Serum: Na 135, K 4, Cl 100, HCO 3 11, BUN 56, SC~ 2, Glucose 72, serum osm 320. ABG: ph 7.27, PCO Serum lactate, ketones, and ethanol levels are normal. What is the most appropriate first step in the management of this patient? 1. Is there a acidemia or alkalemia present? ph < 7.36 = Acidemia 2. What is the primary disturbance? Metabolic Acidosis 3. Calculate the expected compensation? Winters Formula : Expected PaCO 2 : 1.5 X HCO 3 + (8 +/- 2) Expected PaCO 2 : 1.5 X (11) + (8 +/- 2) ~ Is an AGMA present? AG = ( ) = 24. Yes 5. If an AGMA is present, check the delta-delta HCO 3 expected = HCO 3 normal (24) - AG 24 - (24-10) = HCO 3 expected = 10 HCO 3 expected is 10 and HCO 3 measured is 11 so pure AGMA

11 Osmolar Gap Serum: Na 135, K 4, Cl 100, HCO 3 11, BUN 56, SC~ 2, Glucose 72, serum osm 320. ABG ph 7.27, PCO Serum lactate, ketones, and ethanol levels are normal. Calculated Osmolality (Na x 2) + (BUN/2.8) + (Glucose/18) = mos/kg Osmolar gap = measured calculated osmolality > 10 positive, presence of an osmotically active substance > 20 is almost always due to a toxic alcohol ETOH/4.6, methanol, ethylene/propylene glycol Calculated osm: (135 x 2) + (56/2.8) + (72/18) = 294 mos/kg Osmolar gap: = 26 Causes of AGMA Methanol Uremia Diabetic (ETOH starvation ketosis) Propylene glycol Isoniazid Lactic acidosis Ethylene glycol Salicylates Glycols (ethylene, propylene) Oxoproline L-lactate D-lactate Methanol Aspirin Renal failure Ketosis (ETOH or DKA) Case 2 Answer AGMA with + Osmolar gap Ethylene glycol Methanol What is the most appropriate first step in the management of this patient? A. Transfer him to the Cleveland Clinic B. Forced alkaline diuresis C. Fomepizole D. Hemodialysis

12 Case 3 A patient presents with a serum: Na 135 meq/l, potassium 2.5 meq/l, chloride 120 meq/l, HCO 3 5 meq/l. ABG: ph 7.15, PCO 2 17 mmhg. What is the metabolic disturbance? A. AGMA with appropriate respiratory compensation B. AGMA with inappropriate respiratory compensation C. NAGMA with appropriate respiratory compensation D. NAGMA with appropriate respiratory compensation Case 3 Answer Serum: Na 135 meq/l, potassium 2.5 meq/l, chloride 120 meq/l, HCO 3 5 meq/l. ABG: ph 7.15, PCO 2 17 mmhg. What is the metabolic disturbance? 1. Is there a acidemia or alkalemia present? Acidemia (ph < 7.36) 2. What is the primary disturbance? Metabolic acidosis 3. Calculate the expected compensation? Winters Formula : Expected PaCO 2 : 1.5 X HCO 3 + (8 +/- 2) Expected PaCO 2 : 1.5 X (5) + (8 +/- 2) ~ YES 4. Is an AGMA present? AG = Na + (Cl + HCO 3 ) ( ) = 10. No NAGMA with appropriate respiratory compensation Causes of Normal Anion Gap Metabolic Acidosis Hyperalimentation Excess NaCl Acetazolamide RTA, CKD 4 (CKD 29-15) Trotz (diarrhea), toluene Carbonic anhydrase inhibitors (topiramate) Cholestyramine Uretosigmoidostomy Recovering DKA Post hypocapnia ( CO 2 )

13 Case 3 continued Serum: Na 135 meq/l, potassium 2.5 meq/l, chloride 120 meq/l, HCO 3 5 meq/l. ABG: ph 7.15, PCO 2 17 mmhg. Urine: ph 6.5, U Na 28 meq/l, U K 50 meq/l, U Cl 57 meq/l. What is the diagnosis? A. Gitelmans B. Classic Distal RTA Type I C. Type IV RTA D. GI bicarbonate loss Urine Anion Gap in the Evaluation of NAGMA UAG (NH 4 Cl) = ([Na + ] + [K + ]) [Cl - ] Urinary ammonium (NH 4+ ) is a major unmeasured cation in the urine which binds to UCl UAG is a indirect estimate of urinary ammonium NH 4+ Cl UAG is variable without acidosis Urine Anion Gap Negative UAG means NH 4+ (acid) is present in the urine ( UpH) during systemic acidemia which is an appropriate renal response UAG should be negutive in diarrhea Positive UAG means NH 4+ (acid) is NOT present in the urine ( UpH) during systemic acidemia which is an INappropriate renal response UAG is positive in RTA

14 Case 3 continued Serum: Na 135 meq/l, potassium 2.5 meq/l, chloride 120 meq/l, HCO 3 5 meq/l. ABG: ph 7.15, PCO 2 17 mmhg. Urine: ph 6.5, U Na 28 meq/l, U K 50 meq/l, U Cl 57 meq/l. What is the diagnosis? UAG = ([Na + ] + [K + ]) [Cl - ] UAG = = +21 A. Gitelmans B. Classic Distal RTA Type I C. Type IV RTA D. GI bicarbonate loss Case 4 55 year old male with chronic small bowel obstruction requiring NGT for intermittent drainage comes to the hospital for abdominal pain. Serum: Na 145 meq/l, K 3 meq/l, Cl 95 meq/l, HCO 3 40 meq/l. ABG: ph 7.55, PCO 2 51 mmhg. Urine: U Na 45 meq/l, U K 23 meq/l, U Cl 9 meq/l. What is the metabolic disturbance and the treatment response? A. Respiratory Acidosis B. Respiratory Alkalosis C. Metabolic Alkalosis, not saline responsive D. Metabolic Alkalosis, saline responsive Case 4 Answer Serum: Na 145 meq/l, K 3 meq/l, Cl 95 meq/l, HCO 3 40 meq/l. ABG: ph 7.55, PCO 2 51 mmhg. Urine: U Na 45 meq/l, U K 23 meq/l, U Cl 9 meq/l What is the metabolic disturbance and the treatment response? 1.Is there a acidemia or alkalemia present? Alkalemia (ph > 7.44) 2.What is the primary disturbance? Metabolic alkalosis 3.Calculate the expected compensation? * Expected PaCO 2 : 0.7 mmhg in PaCO 2 for every 1 mmol/l rise in HCO 3 Expected pco2 (40-24)= 16 x 0.7 ~ 11. Yes 4.Is an AGMA present? AG = Na (Cl + HCO 3 ) ( ) = 10. No Metabolic Alkalosis with appropriate respiratory compensation with a low urinary chloride

15 Metabolic Alkalosis Saline- Responsive (U Cl < 20) Saline- Resistant (U Cl > 20) 1. GI losses Vomiting or NGT drainage 2. Contraction alkalosis Massive diuresis Villous adenoma Factitious diarrhea (laxatives) *Treatment requires removing the offending agent, provide volume, K supplementation. 1. Hypertensive Mineralcorticoid excess 1º hyperaldosteronism Liddle s Cushings Licorice ingestion 2. Normotensive Bartter s or Gitelman s Severe hypokalemia < 2 Current diuretic use Exogenous alkali load *Treat the underlying disorder Case 5 65 year old female with PMH of CAD s/p CABG in 2010 is admitted to the hospital for SOB. CXR reveals RLL infiltrate. Serum: Na 141 meq/l, Cl 100 meq/l, HCO 3 31 meq/l. ABG: ph 7.25, PCO 2 60 mmhg. What is the metabolic disturbance? A. Acute Respiratory Acidosis B. Chronic Respiratory Acidosis C. NAGMA D. AGMA with Metabolic Alkalosis Case 5 Answer Serum: Na 141 meq/l, Cl 100 meq/l, HCO 3 31 meq/l. ABG: ph 7.25, PCO 2 60 mmhg. 1. Is there a acidemia or alkalemia present? ph < 7.36 = Acidemia 2. What is the primary disturbance? Respiratory Acidosis 3. Calculate the expected compensation? Acute Resp. Acidosis: 1 meq/l increase in [HCO 3- ] for every 10 mmhg rise in PCO 2 Expected in HCO 3 (60-40 = 20) 20/10 = 2 x 1 = 2 so expected HCO3= 26 Chronic Resp. Acidosis: 3.5 meq/l increase in [HCO 3- ] for every 10 mmhg rise in PCO 2 Expected in HCO 3 (60-40 = 20). 20 /10 = 2 x 3.5 = 7 so expected HCO3= 31. Yes 4. Is an AGMA present? AG = Na (Cl + HCO 3 ) ( ) = 10. No Chronic Respiratory Acidosis

16 Clinical Causes of Respiratory Acidosis ACUTE General anesthesia Sedative overdose Pulmonary embolism Pneumothorax Pulmonary edema Severe pneumonia Broncho/laryngospasm Angioedema Aspiration of foreign body Ventilator-induced CHRONIC Alveolar hypoventilation (ILD) COPD Brain tumor OSA Restrictive disease of the thorax (e.g., obesity-hypoventilation syndrome, scleroderma) Respiratory nerve damage (e.g., MS, ALS, phrenic nerve palsy) Myopathy involving respiratory muscles (e.g., poliomyelitis) Clinical Causes of Respiratory Alkalosis Anxiety Pain CNS disorders CVA Tumor Infection Hormones - Drugs Salicylates Catecholamines Progesterone Sepsis, gram (+) or (+) Fever Hyperthyroidsim Hypoxia Ventilator-induced Pregnancy Cirrhosis Pulmonary edema Lung disease ARDS Pulmonary emboli Pneumonia Pneumothorax Clues to Diagnosis of Acid-Base Disorders COPD History Acid-Base Disorder Respiratory Acidosis Renal failure Diarrhea Shock NAGM or AGMA NAGMA AGMA (lactic acid)

17 Clues to Diagnosis of Acid-Base Disorders History Cirrhosis Acid-Base Disorder Respiratory Alkalosis Diuretics Vomiting NG suction Metabolic Alkalosis Metabolic Alkalosis Metabolic Alkalosis Clues to Diagnosis of Acid-Base Disorders History COPD + diuretics Pulmonary edema Sepsis Salicylate intoxication Acid-Base Disorder Respiratory Acidosis and Metabolic Alkalosis Metabolic Acidosis and Respiratory Acidosis Respiratory Alkalosis and Metabolic Acidosis Respiratory Alkalosis and Metabolic Acidosis Conclusions Use Clinical Clues to help identify disorders Step Wise Approach to Acid Base Problem Solving Anion Gap Metabolic Acidosis Osmolar Gap Non Anion Gap Metabolic Acidosis Urine Anion Gap Metabolic Alkalosis Chloride-Sensitive vs. Chloride-Resistant Respiratory Acidosis or Alkalosis Acute versus Chronic Process

18 Bicarbonate meq/l Thank You and Good Luck pco 2 mm Hg

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