S.M. Gorbatkin MD, PhD Emory Board Review in Internal Medicine July Renal Division Department of Veterans Affairs Medical Center Atlanta

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1 S.M. Gorbatkin MD, PhD Emory Board Review in Internal Medicine July 2016 External Industry Relationships * Equity, stock, or options in biomedical industry companies or publishers Board of Directors or officer Company Name None None Role Renal Division Department of Veterans Affairs Medical Center Atlanta Royalties from Emory or from external entity Industry funds to Emory for my research None None Associate Professor Emory University Other < 4% Share in 2 Davita Dialysis Units Use Systematic Approach for Acid Base Disorder Analysis 2. Analyze Mixed Acid Base Disorders 3. Use Urine Anion Gap when Appropriate 4. Clinical Correlation with Elevated Anion Gap 5. Recognize Renal Tubular Acidoses 6. Understand Utility of Urine Na 130 mmol/l Cl 108 mmol/l BUN 31 mg/dl K 5.0 mmol/l HCO 3 12 mmol/l Cr 1.4 mg/dl BG 100 mg/dl Albumin 4.0 mg/dl ph 7.46, pco 2 32 mm Hg, po 2 90 mm Hg (obtained at same time as metabolic profile) Which best describes the above? A. Metabolic Acidosis B. Metabolic Acidosis and Respiratory Alkalosis C. Metabolic Acidosis and Respiratory Acidosis D. Not possible 3 4 Na 130 mmol/l Cl 108 mmol/l BUN 31 mg/dl K 5.0 mmol/l HCO 3 12 mmol/l Cr 1.4 mg/dl BG 100 mg/dl Albumin 4.0 mg/dl ph 7.46, pco 2 32 mm Hg, po 2 90 mm Hg (obtained at same time as metabolic profile) Answer: Not possible If HCO 3 12 mmol/l is primary disorder: metabolic acidosis ALWAYS CALCULATE ANION GAP: NaClHCO 3 = =10(normal) Expected CO 2 = 1.5(12) = (Winter s) or add 15 to HCO 3 : = is above expected compensation: respiratory acidosis Choice C was: Metabolic Acidosis and Respiratory Acidosis 5 Na 130 mmol/l Cl 108 mmol/l BUN 31 mg/dl K 5.0 mmol/l HCO 3 12 mmol/l Cr 1.4 mg/dl BG 100 mg/dl Albumin 4.0 mg/dl ph 7.46, pco 2 32 mm Hg, po 2 90 mm Hg (obtained at same time as metabolic profile) Answer: Not possible If low pco 2 =32 is primary (to cause ph 7.46): respiratory alkalosis Expected HCO 3 for compensation depends on chronicity: Acute D [HCO 3 ] = 0.2 x DpCO 2 =.2 (4032) = 1.6 HCO 3 = 22.4 Chronic D [HCO 3 ] = x DpCO 2 =.4.5(4032)=3.2 4 HCO 3 = For either acute or chronic, HCO 3 =12 mmol/l < compensation: Also Metabolic Acidosis Choice B was: Metabolic Acidosis and Respiratory Alkalosis 6 1

2 Na 130 mmol/l Cl 108 mmol/l BUN 31 mg/dl K 5.0 mmol/l HCO 3 12 mmol/l Cr 1.4 mg/dl BG 100 mg/dl Albumin 4.0 mg/dl ph 7.46, pco 2 32 mm Hg, po 2 90 mm Hg (obtained at same time as metabolic profile) Why is Answer: Not possible? HendersonHasselbalch Equation: Expected ph is 7.19, Not internally consistent: ph, HCO 3, pco 2 cannot exist together Know: 1. Board Exam should not expect numeric calculations using HendersonHasselbalch. Know may not be internally consistent and know general trends (see slide 15). Check for internal consistency Check Anion Gap Correct anion gap for low albumin if needed Check for mixed metabolic disorder Decide which abnormalities primary, secondary Calculate expected compensation for primary disorder Identify additional acid base disorders by comparing values to expected compensation Correlate with other clinical information 2. Compensation for metabolic and respiratory disorders 3. It matters which abnormality is primary 7 8 EMIA: In Blood Acidemia (ph < 7.35) Alkalemia (ph > 7.45) OSIS: Process Acidosis Alkalosis Normal arterial pco 2 = 40 mm Hg (range 3644) Increase in pco 2 : Respiratory Acidosis Decrease in pco 2 : Respiratory Alkalosis Normal Bicarbonate (HCO 3 ) = 24 mmol/l > 28 Metabolic alkalosis < 22 Metabolic acidosis 9 10 ph 7.46 Alkalemia pco 2 = 32 Below normal of 40 Could be resp alkalosis, or expected compensation, or if above expected compensation resp acidosis HCO 3 = 12 Metabolic acidosis or at lower limit of compensation for severe chronic respiratory alkalosis Caution: If HCO 3 normal could have elevated anion gap acidosis and metabolic alkalosis (See Self Study Case 8) ALWAYS CALCULATE ANION GAP for acid base question

3 If HCO 3 = 16 mmol/l is the primary disorder: Metabolic Acidosis Expected compensation pco 2 = 1.5(16) = or = 31 HCO 3 = 16 mmol/l and pco 2 31: metabolic acidosis or, metabolic acidosis with appropriate compensation. IS NOT METABOLIC ACIDOSIS and RESPIRATORY ALKALOSIS HCO 3 = 16 mmol/l and pco 2 38 mm Hg: metabolic acidosis and respiratory acidosis HCO 3 = 16 mmol/l and pco 2 26 mm Hg: metabolic acidosis and respiratory alkalosis H + [10 9 moles/liter]=24(pco 2 )/HCO 3 pco 2 in mm Hg HCO 3 in mmol/l ph = log 10 [H + ] Case 1: ph = log 10 [24(32)/12 x 10 9 ] = 7.19 Not CONSISTENT with ph 7.46 Boards: Should not expect to use for numerical result H + [10 9 moles/liter]=24(pco 2 )/HCO 3 Higher H + = lower ph Know: High pco2 and/or low HCO3 Will lower ph below 7.4 (pco 2 = 50, HCO 3 12, ph 7.5): Not consistent Low pco2 and/or high HCO3 Will raise ph above 7.4 (pco 2 = 20, HCO 3 30, ph 7.3): Not consistent Lack of Internal Consistency: Drawn at Different Times, Wrong Patient, Dilution or Lab Error mmol/l Potassium 5.7 mmol/l 80 mmol/l Bicarbonate 8 mmol/l BUN 35 mg/dl Cr 1.5 mg/dl Glucose > 500 mg/dl ABG room air: 7.22/pCO 2 =20/pO 2 =105, Albumin 4 mg/dl ph = log 10 [H + ] = log 10 [(24 x pco 2 /HCO 3 ) x 10 9 ] = log 10 [(24 x 20/8)x 10 9 ] = log 10 [60 x 10 9 ] = 7.22 Is Internally Consistent mmol/l 80 mmol/l Bicarbonate 8 mmol/l Glucose > 500 mg/dl ABG room air: 7.22/pCO 2 =20/pO 2 =105, Albumin 4 mg/dl The acid base disorder is: A. High AG acidosis + respiratory alkalosis B. High AG acidosis + appropriate respiratory compensation C. High AG acidosis + metabolic alkalosis + appropriate respiratory compensation D. High AG acidosis + nonag acidosis + appropriate respiratory compensation 17 Check for internal consistency Check Anion Gap Correct anion gap for low albumin if needed Check for mixed metabolic disorder Decide which abnormalities primary, secondary Calculate expected compensation for primary disorder Identify additional acid base disorders by comparing values to expected compensation Correlate with other clinical information 18 3

4 AG = plasma [Na + ] [Cl ] [HCO3 ] Normal approx 10 mmol/l For low albumin: add [2.5 (4.0albumin)] to anion gap Case 2: AG = = 44 Do not correct Na for Hyperglycemia All components of AG are affected Check for internal consistency Check Anion Gap Correct anion gap for low albumin if needed Check for mixed metabolic disorder Decide which abnormalities primary, secondary Calculate expected compensation for primary disorder Identify additional acid base disorders by comparing values to expected compensation Correlate with other clinical information Normal Hyperchloremic Acidosis Increased, HCO 3 decreased nonag or normal AG Acidosis Normal Anion Gap Acidosis Delta AG = 2610 = Delta AG = 24 Cations 10 AG 10 Anions 20 HCO 3 24 Cations 10 AG 10 Anions 20 HCO 3 8 Cations 10 AG 10 Anions 20 HCO 3 24 Cations 10 Anions 34 AG HCO HCO Imagine before Anions Added Case 2 Delta AG = 4410 = Delta AG = 8+34 = 42: Elevated AG Acidosis + Alkalosis (HCO 3 42 before add delta AG to replace) Cations AG 10 Anions 20 HCO Cations 10 Anions AG 44 HCO HCO Add Excess AG (Delta AG) to the HCO 3 in the metabolic profile Delta AG + HCO 3 > 28: High AG Metabolic Acidosis + Metabolic Alkalosis Alternative: Delta AG/ Delta HCO 3 > 2 Delta AG + HCO 3 < 22: High AG Metabolic Acidosis + Normal AG Acidosis Alternative: Delta AG/ Delta HCO 3 < 0.8 (Some references: <1, less specific)

5 (Delta Anion Gap)/(Delta HCO 3 )> 2 = high AG metabolic acidosis+ metabolic alkalosis More than one Anion Required to Replace One HCO 3 Metabolic Elevated AG Acidosis + Metabolic Alkalosis if Delta AG + HCO 3 > 28 or (Delta Anion Gap) / (Delta HCO 3 ) > 2 Less Sensitive, More Specific than Delta AG + HCO 3 > 28 But Same Concept or stick with your own variation 25 Case 2: Delta AG + HCO 3 = = 42 Delta AG = 4410 = 34 Delta HCO 3 = I824I = 16 (Delta Anion Gap) / (Delta HCO 3 ) = 34/16 26 Check for internal consistency Check Anion Gap Correct anion gap for low albumin if needed Check for mixed metabolic disorder Decide which abnormalities primary, secondary Calculate expected compensation for primary disorder Identify additional acid base disorders by comparing values to expected compensation Correlate with other clinical information Acidemia must have at least one primary Acidosis Alkalemia must have at least one primary Alkalosis Elevated Anion Gap Acidosis: always primary rather than compensatory Can have two primaries, for example Primary Respiratory Alkalosis and Primary Elevated AG Acidosis (See Case 12 on Aspirin Ingestion) Primary Disorder Adaptive Response Limits of Adaptation Met Acidosis pco 2 = 1.5 [HCO 3 ] (Winters) pco 2 not < 10 mm Hg Shortcut: pco 2 = [HCO 3 ] +15 (close to Winters if [HCO 3 ] > 9) Met Acidosis pco 2 = 1.5 [HCO 3 ] (Winter s Formula) pco 2 = 1.5 (8) = Met Alkalosis DpCO 2 = 0.7 x D [HCO 3 ] pco 2 not > 55 mm Hg Resp Acidosis Acute D [HCO 3 ] = 0.1 x DpCO 2 [HCO 3 ] not > 30 mmol/l Chronic D [HCO 3 ] = 0.35 x DpCO 2 [HCO 3 ] not > 45 mmol/l Resp Alkalosis Acute D [HCO 3 ] = 0.2 x DpCO 2 [HCO 3 ] not < 1718 mmol/l Chronic D [HCO 3 ] = x DpCO 2 [HCO 3 ] not < 1215 mmol/l 29 Shortcut: pco 2 = 8+15 = 23, outside range but close, closer if HCO 3 >9 ABG: pco 2 = 20 is appropriate compensation for metabolic acidosis If pco 2 were 12: Respiratory Alkalosis If pco 2 were 30: Respiratory Acidosis (despite pco 2 < 40) 30 5

6 132 mmol/l 80 mmol/l Bicarbonate 8 mmol/l Glucose > 500 mg/dl ABG room air: 7.22/pCO 2 =20/pO 2 =105, Albumin 4 mg/dl The acid base disorder is: A. High AG acidosis + respiratory alkalosis B. High AG acidosis + appropriate respiratory compensation ANSWER: C. High AG acidosis + metabolic alkalosis + appropriate respiratory compensation D. High AG acidosis + nonag acidosis + appropriate respiratory compensation mmol/l 80 mmol/l Bicarbonate 8 mmol/l Glucose > 500 mg/dl ABG room air: 7.22/pCO 2 =20/pO 2 =105, Albumin 4 mg/dl ANSWER: C. High AG acidosis + metabolic alkalosis + appropriate respiratory compensation Could also see following wording (appropriate compensation understood): Answer: C. High AG acidosis + metabolic alkalosis 32 Check for internal consistency Check Anion Gap Correct anion gap for low albumin if needed Check for mixed metabolic disorder Decide which abnormalities primary, secondary Calculate expected compensation for primary disorder Identify additional acid base disorders by comparing values to expected compensation Correlate with other clinical information Fatigue, Polyuria, Elevated BG, High AG Acidosis: Diabetic Ketoacidosis Elevated Anion Gap Acidosis plus Metabolic Alkalosis: Contraction Alkalosis, vomiting Low pco 2 = Appropriate Respiratory Compensation: Natural respiratory response to Metabolic Acidosis YO Male with Short Gut Syndrome after a large portion of his small bowel was removed following trauma. He takes no medications. He presents with confusion, dysarthria, ataxia, abnormal gait after eating at a spaghetti/lasagna buffet. 132 mmol/l 98 mmol/l Bicarbonate 12 mmol/l The most likely diagnosis is: A. DLactic Acidosis B. 5Oxoproline (Pyroglutamic Acid) C. Bicarbonate loss due to diarrhea D. Starvation Ketoacidosis YO Male with Short Gut Syndrome after a large portion of his small bowel was removed following trauma. He takes no medications. He presents with confusion, dysarthria, ataxia, abnormal gait after eating at a spaghetti/lasagna buffet. 132 mmol/l 98 mmol/l Bicarbonate 12 mmol/l Anion Gap = 132(98+12) = = 22 Delta AG = 2210 = 12, Delta HCO 3 = I1224I = 12 Delta AG + HCO 3 = = 24 (Delta Anion Gap) / (Delta HCO 3 ) = 12/12 = 1 Pure Elevated AG acidosis Answer: DLactic Acidosis 36 6

7 Short Gut Syndrome (missing small bowel, jejunal bypass): Increased Delivery of Carbohydrates to Gut Bacteria Especially after high carbohydrate loads: DLactic Acidosis Altered Mental Status, Dysarthric Speech, Ataxia, Gait Disorder Antibiotics can be used to Treat, Low carbohydrates helpful Antibiotics can sometimes precipitate by lactobacilli overgrowth 52 YO Female with depression, weight loss, poor nutrition, and chronic pain presents for fatigue. She is on a chronic SSRI and acetaminophen. She takes occasional cough syrup at recommended doses. 132 mmol/l 98 mmol/l Bicarbonate 12 mmol/l Cr 1.4 mg/dl The most likely diagnosis is: Seen in Cows MidGeorgia Cattleman s Association (Reference for picture only) A. LLactic Acidosis B. 5Oxoproline (Pyroglutamic Acid) C. Bicarbonate loss due to diarrhea D. Propylene Glycol E. Renal Tubular Acidosis YO Female with depression, weight loss, poor nutrition, and chronic pain presents for fatigue. She is on a chronic SSRI and chronic acetaminophen. She takes occasional cough syrup at recommended doses. 132 mmol/l 98 mmol/l Bicarbonate 12 mmol/l Cr 1.4 mg/dl Same labs as Case 3: Elevated Anion Gap Acidosis Answer: 5Oxoproline (Pyroglutamic Acid) Propylene Glycol: Considered Safe as Food, Tobacco, Cosmetic, and Oral Medication Additive Military Smoke Screen Case 4: Cough syrup may have propylene Glycol, but at normal doses would not cause Lactic acidosis Risk of DLactic Acidosis with prolonged IV infusions: Anticonvulsants, antibiotics, others prolonged and extensive skin application/burns COMMON EXAMPLES: LORAZEPAM, DIAZEPAM, PHENOBARBITOL, PENTOBARBITOL Would have normal anion gap for: Bicarbonate loss due to diarrhea Renal Tubular Acidosis 39 Agency for Toxic Substances and Disease Registry: 40 Lactate > 4 meq/l (Most lactate labs measure Llactate, not Dlactate) Of Many Possible Causes, Know: Type A: Tissue Hypoperfusion Type B: No evidence of hypoperfusion Metformin Linezolid Propofol Nucleoside Reverse Transcriptase Inhibitors for HIV DLactic Acidosis: Short Gut Syndrome (less small bowel) Propylene Glycol Metformin: Risk formerly defined for Cr > mg/dl FDA (April82016): Chance of Lactic Acidosis from Metformin very low Contraindicated for GFR < 30 ml/min/1.73 m 2 Not recommend to start if GFR 3045 ml/min/1.73 m 2 If GFR falls to < 45, assess benefit/risk of continuing, DC if GFR < 30 Review Criteria for when to stop before IV contrast: not just GFR

8 Case 4: 52 YO Female with depression, weight loss, poor nutrition, and chronic pain presents for fatigue. She is on a chronic SSRI and chronic acetaminophen. She takes occasional cough syrup at recommended doses. Chronic Acetaminophen Ingestion High AG Acidosis FEMALES (80%) malnourished/chronic Illness Agency for Toxic Substances and Disease Registry: MUDPILES Methanol Uremia DKA/AKA Paraldehyde Iron/INH Lactic Acidosis Ethylene Glycol Salicylates NEW Mnemonic for the 21 st Century GOLDMARK Glycols(Ethylene and Propylene) Oxoproline (=pyroglutamic acid) LLactate DLactate Methanol Aspirin Renal Failure Ketones Salicylate: Elevated Anion Gap Acidosis and Respiratory Alkalosis Ethylene Glycol: Calcium Oxalate Crystals Two crystal forms: Methanol: Impaired Vision (usually), Also: Papilledema, Mydriasis (Dilated Pupils), Putamen Lesions Ethylene Glycol and Methanol: Osmolal gap early, Anion Gap Increases with time Tx Fomepizole, May need dialysis Mehta A. Emmett M. Emmitt J. The Lancet Vol Tx for Salicylate: Systemic Alkalinization, May need dialysis YO white male presents for evaluation of kidney stones, with his first stone appearing as a child. Hx of severe muscle weakness & cardiac arrythmias. Labs: = 139, Potassium= 2.8, =117, Bicarbonate = 12, BUN=31, Cr = 1.8; Albumin 4.0. Room air ABG : ph = 7.29, pco 2 = 25; Urine: sodium = 130, potassium = 20, chloride = 110. KUB: Calcium deposits in periphery of both kidneys. The most likely diagnosis is: A. Type II RTA (RTA = Renal Tubular Acidosis) B. Type I distal RTA C. Type IV RTA D. Chronic Diarrhea E. Salicylate intoxication 47 = 139, Potassium= 2.8, =117 Bicarbonate = 12, BUN=31, Cr = 1.8, Albumin 4.0. Room air ABG: ph = 7.29, pco 2 = 25 Urine: sodium = 130, potassium = 20, chloride = 110 Internally consistent Anion Gap = 139 ( ) = = 10 (Albumin normal) Normal anion gap acidosis, primary (no mixed metabolic) Expected compensation is pco 2 = 1.5 (12) = Shortcut: pco 2 = =

9 Urine Anion Gap = [(Na + ) + (K + ) (Cl )] Estimate of Renal Ammonium Cation (NH 4+ ) If Kidneys Working Properly: Excrete acid as NH 4 + Urine Anion Gap is negative Details not needed for board review: Invalid if large number of unmeasured anions such as HCO 3 or ketones. Inaccurate if volume depleted and urine Na < 25 mmol/l (Cl reabsorbed and cannot secrete NH 4 Cl) Urine Anion Gap = [(Na + ) + (K + ) (Cl )] = 40 mmol/l Positive Urine Anion Gap Kidneys Not Working Properly Insufficient Acid Excretion as NH Finding Type I RTA Type 2 RTA Type 4 RTA GI (Distal) (Proximal) (Distal) Minimum Urine ph > 5.5 < 5.5 < %Filtered NaHCO 3 Excreted <10 >15 <10 <10 Serum Potassium Low Low HIGH Low Fanconi Syndrome No Yes No No Stones/Neprocalcinosis YES NO NO No Daily Acid Excretion Low Normal Low High Urine Anion Gap Positive Positive* Positive Neg NaHCo3 Replace/Day < 4 mmol/kg >4 mmol/kg <4mmol/kg Variable *RECENT REFERENCES: URINE ANION GAP for Proximal Type 2 RTA Negative [Adapted from Harrison s Principles of Internal Medicine 16th Ed Table 2652] Characteristics of TYPE IV RTA Distal Hyperkalemic (Aldosterone Deficiency or resistance) Normal Anion Gap Acidosis with Positive Urine Anion Gap Common Causes: DM, Obstruction, Drugs I and IV Distal I and II Hypokalemic Type I: Stones/Nephrocalcinosis, AUTOIMMUNE (SLE, Sjogren s) Type II: Fanconi Syndrome: UA Glucose+ but normal Blood Glucose (renal loss of glucose, phosphate, amino acids, uric acid, bicarbonate) PARAPROTEINEMIA (Myeloma), Wilson s 29 YO white male presents for evaluation of kidney stones, with his first stone appearing as a child. Hx of severe muscle weakness & cardiac arrythmias. Labs: = 139, Potassium= 2.8, =117, Bicarbonate = 12, BUN=31, Cr = 1.8; Albumin 4.0. Room air ABG: ph = 7.29, pco 2 = 25; Urine: sodium = 130, potassium = 20, chloride = 110. KUB: Calcium deposits in periphery of both kidneys. Normal AG Acidosis, Positive Urine Anion Gap, Stones/Calcinosis A. Type II RTA ANSWER: B. Type I distal RTA C. Type IV RTA (Would have high K) D. Chronic Diarrhea (would have neg urine anion gap) E. Salicylate intoxication (would have high AG acidosis)

10 A patient is very obese and it is difficult to tell volume status by exam. His blood pressure is normal. The patient has a metabolic alkalosis. Which is most useful to determine volume status? A. Urine B. Urine C. Urine Urea D. Urine Bicarbonate A patient is very obese and it is difficult to tell volume status by exam. His blood pressure is normal. The patient has a metabolic alkalosis. Which is most useful to determine volume status?. A. Urine B.Urine = correct answer C. Urine Urea D. Urine Bicarbonate A 47 YO male reports he has no significant medical history, no medications. Presents with 4 days of intermittent vomiting. BP = 146/94 P92 = 139, Potassium= 2.9, =96, Bicarbonate = 34, BUN=22, Cr = 1.1; Albumin 4.0. Urine chloride = 55 mmol/liter. ABG: 7.50/pCO 2 =45/pO 2 =104 = 139, Potassium= 2.9, =96, Bicarbonate = 34, BUN=22, Cr = 1.1; Albumin 4.0. Urine chloride = 55 mmol/liter. ABG 7.48/47/104 Check for internal consistency Check Anion Gap Correct anion gap for low albumin if needed Check for mixed metabolic disorder Decide which abnormalities primary, secondary Calculate expected compensation for primary disorder Identify additional acid base disorders by comparing values to expected compensation Correlate with other clinical information = 139, Potassium= 2.9, =96, Bicarbonate = 34, BUN=22, Cr = 1.1; Albumin 4.0. Urine chloride = 55 mmol/liter. ABG 7.48/47/104 Internally consistent, primary metabolic alkalosis. Anion Gap = 139 ( ) = = 9 (normal) Respiratory Compensation for Primary Metabolic alkalosis: DpCO 2 = 0.7 x D [HCO 3 ] =.7 (10) = 7 For metabolic alkalosis: Measure Urine Urine < 1020 mmol/liter: responsive Urine > 2030 mmol/liter: resistant Appropriate respiratory compensation. Etiology?

11 Urine High (>2030 mmol/l) Concentrate On Top 3 causes In left Column Plus: Urine High while Diuretics Active A 47 YO male reports no significant medical history, no medications. Presents with 4 days of intermittent vomiting. BP = 146/94 P92 = 139, Potassium= 2.9, =96, Bicarbonate = 34, BUN=22, Cr = 1.1; Albumin 4.0. Urine chloride = 55 mmol/liter. ABG 7.50/45/104 Primary metabolic alkalosis with appropriate respiratory compensation. Urine > 2030 mmol/l Etiology: resistant metabolic alkalosis Hypertension even after vomiting: Mineralicorticoid excess (real or apparent) Low CO 2 (<35) with ph > 7.45: Primary Respiratory Alkalosis 1. Hypoxemia or Tissue Hypoxia 2. Pain 3. Exercise 4. Pregnancy 5. Drugs (Salicylates, also have metabolic elevated AG acidosis) Compensation: Acute D [HCO 3 ] = 0.2 x DpCO 2 [HCO 3 ] not < 1718 mmol/l Chronic D [HCO 3 ] = x DpCO 2 [HCO 3 ] not < 1215 mmol/l (Case 1 was numerical example but was not internally consistent: HCO 3 was too low to match the ph) See Supplemental Case High CO2 (>45) with ph < 7.35: Primary Respiratory Acidosis Acute Respiratory Acidosis: 1. Respiratory Depression (Central Nervous System of DrugInduced) 2. Neuromuscular Disease or Paralysis 3. Acute Airway Obstruction (Asthma or COPD) Compensation: Acute D [HCO 3 ] = 0.1 x DpCO 2 See Supplemental Case 11 [HCO 3 ] not > 30 mmol/l High CO2 (>45) with ph < 7.35: Primary Respiratory Acidosis Chronic Respiratory Acidosis: 1. COPD with hypoventilation 2. Obesity Hypoventilation Syndrome, Central Sleep Apnea 3. Chronic Neuromuscular Disorders 4. Restrictive Ventilation (interstitial fibrosis, thoracic skeletal problems) Compensation: Chronic D [HCO 3 ] = 0.35 x DpCO 2 See Supplemental Cases 10 [HCO 3 ] not > 45 mmol/l

12 1. Use Systematic Approach for Acid Base Disorder Analysis 2. Analyze Mixed Acid Base Disorders 3. Use Urine Anion Gap when Appropriate 4. Clinical Correlation with Elevated Anion Gap 5. Recognize Renal Tubular Acidoses 6. Understand Utility of Urine Supplementary Cases: Mixed Metabolic: Cases 8,9 Respiratory Acidosis: Cases 10,11 Respiratory Alkalosis with metabolic acidosis from Aspirin: Case In the figures, the electrolytes on the right hand side with the elevated anion gap are the measured values. The electrolytes on the left hand side of the figures correspond to adding the Delta AG to HCO 3 for analysis of whether there is a mixed metabolic acid base disorder. 68 Initial CASE 8 Initial + Add Anions 24 + Delta AG = = 38: Elevated AG Acidosis + Alkalosis Cations AG 10 Anions 20 HCO Cations 10 Anions AG 24 HCO HCO Example of HCO 3 =24 corresponding to elevated AG acidosis plus metabolic alkalosis Na 140 mmol/l Cl 92 mmol/l HCO 3 24 mmol/l Anion Gap (AG) = 140(92+24) = 24 Delta AG = 2410 = 14, Delta HCO 3 = I2424I = 0 HCO 3 + Delta AG = = 38, which is > 28 (Delta Anion Gap) / (Delta HCO 3 ) = 14/0 = infinity, which is > Cations Initial CASE 9 Initial + Add Anions 6 + Delta AG = 6+14 = 20: Elevated AG + normal AG Acidosis AG 10 Anions 20 HCO Cations 10 Anions AG 24 HCO HCO Example of Elevated AG acidosis plus metabolic nonag acidosis Na 132 mmol/l Cl 102 mmol/l HCO 3 6 mmol/l Anion Gap (AG) = 132(102+6) = 24 Delta AG = 2410 = 14, Delta HCO 3 = I624I = 18 HCO 3 + Delta AG = = 20, which is <22 (Delta Anion Gap) / (Delta HCO 3 ) = 14/18 = 0.78 which is <0.8 (some references say < 1, but much less specific)

13 65 YO Male with chronic COPD and no acute illness: Na 140 mmol/l Cl 101 mmol/l HCO 3 29 mmol/l ABG: ph 7.34/pCO2 55/pO2 65 Internally Consistent ph, HCO 3, pco 2, Anion Gap= = 10 (normal) ph < 7.35 and pco2 > 45: Primary Respiratory Acidosis Secondary to chronic COPD Compensation: Chronic D [HCO 3 ] = 0.35 x DpCO 2 [HCO 3 ] not > 45 mmol/l D [HCO 3 ] = 0.35 x (5540)= 0.35 x 15 = 5 Expected HCO 3 corresponding to compensation = 24+5 = 29 mmol/l This is a primary chronic respiratory acidosis 35 YO Male with drug overdose, acute depressed respiration: Na 140 mmol/l Cl 103 mmol/l HCO 3 27 mmol/l ABG: ph 7.21/pCO2 70/pO2 55 Internally Consistent ph, HCO 3, pco 2, Anion Gap= = 10 (normal) ph < 7.35 and pco2 > 45: Primary Respiratory Acidosis Secondary to drug overdose with acute respiratory depression Compensation: Acute: D [HCO 3 ] = 0.1 x DpCO 2 [HCO 3 ] not > 30 mmol/l D [HCO 3 ] = 0.1 x (7040)= 0.1 x 30 = 3 Expected HCO 3 corresponding to compensation = = 27 mmol/l This is a primary acute respiratory acidosis A 23 YO male ingested a large quantity of aspirin 6 hrs prior to presentation. ph 7.47 paco 2 20 mm Hg HCO 3 14 mmol/liter, Anion Gap elevated Internally Consistent ph, HCO 3, pco 2 Alkalemia with Acute primary respiratory alkalosis Expected compensation for ACUTE respiratory alkalosis D[HCO 3 ] = 0.2 x DpCO2 [HCO 3 ] not < 1718 meq/l D[HCO 3 ] = 0.2 (20) = 4 Expected HCO 3 = 20 Comprehensive Clinical Nephrology, 5th Edition, R.J. Johnson, J. Feehaly and J. Floege, eds., (Elsevier, 2015). Primer on Kidney Disease, 6th Edition, S.Gilbert and D. Weiner, (Elsevier, 2014). Harrison s Principles of Internal Medicine, 19 th Ed (McGrawHill, 2015). Brenner & Rector s The Kidney, 10 th Ed. (Elsevier, 2016). Acute primary respiratory alkalosis HCO 3 of 14 lower than expected for compensation: Also has Primary metabolic acidosis Anion gap elevated from Aspirin Biff F. Palmer Prim Care Clinic Office Prac 35 (2008)