Acid Base Disorders Cases Prof Dr. Chew Keng Sheng Faculty of Medicine and Health Sciences Universiti Malaysia Sarawak

Case 1 4 years old referred from klinik kesihatan c/o generalized tonic clonic seizure for about 30 minutes associated with fever On arrival to ED, the child developed continuous seizure lasting more than 30 minutes Decided for intubation and mechanical ventilation

Case 1 Post intubation ABG on ventilator pH 7.084 HCO3- 11.9 mmol/l BE -15.2 What should be the expected PaCO2 if the patient had metabolic acidosis only?

Winter’s Equation In metabolic acidosis, If the measured PaCO2 is less than the expected → concurrent respiratory alkalosis If the measured PaCO2 is more than the expected → concurrent respiratory acidosis PaCO2 = (1.5 * [HCO3-]) + 8 (+/- 2)

Case 1 Expected PaCO2: (1.5 * [11.9]) + 8 = 26 mmHg The measured PaCO2 was 44.8 mmHg Concurent respiratory acidosis

Case 2 61 years old man came presented with chest pain since 2 hours prior to admission associated with sweatings and palpitation ECG consistent with Acute Inferior myocardial infarction On arrival to ED, unarousable; BP 50/15 mmHg, heart rate 45 /min Intubated and ventilated in ED; TCP applied

Case 2 pH 7.350 pCO2 26.2 mmHg pO2 67.2 mmHg SaO2 92.7% HCO3- 16.8 mmol/l What is the primary disorder? What should be the expected PaCO2?

Case 2 Metabolic Acidosis with concurrent respiratory alkalosis (expected PaCO2 should be 33.2 mmHg) Is it normal anion gap or wide anion gap? Na 133; K 3.3; Cl 116; HCO3- 16.8

Case 2 Anion gap ([Na+] + [K+]) –([HCO3-] + [Cl-]) = 3.5 Normal anion gap = 3 – 11 mmol/l (or 7 mmol +/- 4)

Normal and Wide Anion Gap Metabolic Acidosis

Case 3 A 44 year old moderately dehydrated man was admitted with a two day history of acute severe diarrhea. Electrolyte results: Na+ 134, K+ 2.9, Cl- 108, HCO3- 16, BUN 31, Cr 1.5. ABG: pH 7.31; pCO2 33 mmHg; HCO3 16; pO2 93 mmHg What is the acid base disorder?

Answer Case 3 Normal Anion Gap Metabolic Acidosis Partial respiratory compensation (expected PaCO2 = 32; measured = 33)

Case 4 A 22 year old female with type I DM, presents to the emergency department with a 1 day history of nausea, vomiting, polyuria, polydypsia and vague abdominal pain. On examination, she was noted for deep sighing breathing, orthostatic hypotension, and dry mucous membranes.

Case 4 Labs: Na 132 , K 6.0, Cl 93, HCO3- 11 Glucose 720 mg/dl, BUN 38 mg/dl, Cr 2.6 mg/dl. Urine Analysis: pH 5, SG 1.010, ketones negative, glucose positive . Plasma ketones trace ABG: pH 7.27 HCO3- 10  PCO2 23

Answer Case 4 Wide Anion Gap Metabolic Acidosis (AG ~ 28) Partial respiratory compensation Note the absence of ketones in the urine. This is sometimes seen in early DKA. Why? This is sometimes seen in early DKA due to the predominance of beta-hydroxybutyrate. The nitroprusside reaction in dipstick test for ketones detect acetoacetates but not beta-hydroxybutyrate

Delta Gap Metabolic acidosis can co-exist with metabolic alkalosis Example: 28-year-old man who presents to the ED with several days of vomiting, nausea and abdominal pain There is both a wide anion gap metabolic acidosis (from dehydration and poor perfusion) and a metabolic alkalosis (from vomiting and loss of stomach acid)

Delta Gap Delta Gap = Measured AG – normal AG (taken as 11) Delta gap + measured HCO3- MUST BE equal back to the normal HCO3- If Delta Gap + measured HCO3- > than normal HCO3-, this means there are too much HCO3-, therefore there is co-existing metabolic alkalosis

Delta Gap If Delta Gap + measured HCO3- < than normal HCO3, there is co-existing normal anion gap metabolic acidosis (besides the wide anion gap metabolic acidosis) If Delta Gap + measured HCO3- = normal HCO3-, it is a simple wide anion gap acidosis

Paradoxical Results in Serum Ketones Testing in DKA The nitroprusside reaction in serum ketone testing is positive only for acetoacetate Therefore, patient with severe DKA or alcoholic ketoacidosis may have predominantly β-hydroxybutyrate (BHB) as the ketone species in their blood – this lack the methyl group to be detected As patient clinically improved, more BHB be oxidized to acetoacetates, and the results seems paradoxically rising! The nitroprusside reaction used to measure serum ketones is positive only for species whose carbonyl moiety has an α-methyl group. The major ketones present in pt with untreated DKA or alcoholic ketoacidosis is B-hydroxybutyrate acid, which has no methyl group. This can be a paradox, as initial serum ketone testing maybe weakly positive in the beginning, but rising despite clear clinical improvement. This occurs because appropriate treatment alters the hepatic ratio of nicotinamide adenoside dinucleotide (NAD) to NADH2 and the restoration of NAD allows concentrations allows oxidation of B-hydroxybutyrate to acetoacetate.

Case 5 A previously well 55 year old woman is admitted with a complaint of severe vomiting for 5 days. Physical examination reveals postural hypotension, tachycardia, and diminished skin turgor. The laboratory finding include the following: Na+ 140 , K+ 3.4, Cl 77 HCO3- 9, Cr 2.1 ABG: pH 7.23 , PCO2 22mmHg

Answer Case 5 Wide Anion Gap metabolic acidosis (AG 54) Partial respiratory compensation (expected PaCO2 = 21.5) Delta Gap = Measured AG – Normal AG = 43 Delta Gap + Measured HCO3- definitely more than normal HCO3- Therefore, there is concomitant metabolic alkalosis Mixed elevated anion gap metabolic acidosis and metabolic alkalosis likely due to lactic acidosis and vomiting

Case 6 A 70 year old man with history of CHF presents with increased shortness of  breath and leg swelling. ABG: pH 7.24, PCO2 60 mmHg, PO2  52 HCO3- 27 Is this an acute or chronic respiratory acidosis?

Answer Case 6 PaCO2 in that patient 60 mmHg. Therefore, there is a change of (60 – 40) mmHg = 20 mmHg of PaCO2 In acute setting, expected change of HCO3- would be 20/10 * 1 - 2 = 2 – 4 mmol/l only HCO3- would be 24 + 2 or 4 = 26 – 28 mmol/l (measured HCO3- in this pt 27 mmol/l) Expected change of pH would be 0.08 * 2 = 0.16 (pH 7.40 – 0.16 = 7.24)

Case 7 A 50 year old insulin dependent diabetic woman was brought to the ED by ambulance. She was semi-comatose and had been ill for several days. Current medication was digoxin and a thiazide diuretic for CHF. Se Na 132, K 2.7, Cl 79, HCO3- 19, Glu 815 Lactate 0.9 Urine ketones 3+ ABG:  pH 7.41, PCO2 32, HCO3- 19, pO2 82 What is the acid base disorder?

Answer Case 7 pH may be normal in the presence of a mixed acid base disorder pCO2 is low indicating a possible respiratory alkalosis. The HCO3- is also low indicating a possible metabolic acidosis. Because the pH is normal, we are unable to distinguish the initial, primary change from the compensatory response.

Answer Case 7 The anion gap is Na - (Cl + HCO3-) = 132 -(79 + 19) = 34 The presence of very high AG (>20) suggests wide anion gap metabolic acidosis EVEN IN THE PRESENCE OF NORMAL pH!!! The body DOES NOT generate an elevated anion gap JUST TO COMPENSATE for alkalosis Mixed elevated anion gap metabolic acidosis and metabolic alkalosis likely due to DKA and thiazide diuretics.

Answer Case 7 Delta Gap = 34 – 11 = 23 Delta Gap + 19 = 23 + 19 > normal HCO3- Therefore there was concurrent metabolic alkalosis

Case 8 A 78 year old woman was admitted comatose after her daughter complained that her conscious state had deteriorated over the last few hours. 2 empty bottles of “minyak cap kapak” were found by her bedside. On examination, she was found to be tachypnoeic with a respiratory rate of 55.

Case 8 pH 7.50; pCO2 17; pO2 103; bicarbonate 13 Na 152; K 3.5; Cl 118; urea 13.0 What are the abnormalities in this patient?

Answer Case 8 Respiratory alkalosis AG = 152 – 118 – 13 = 21 Concurrent wide anion gap metabolic acidosis

Salicylate Poisoning Methyl salicylate is hydrolysed to salicylate, conjugated with glycine / glucuronic acid and excreted in the urine. Salicylates directly stimulate respiratory centers in the medulla, causing hyperventilation and, subsequently, respiratory alkalosis. Metabolic acidosis is caused by : inhibition of enzymes in the citric acid cycle leading to raised lactate and pyruvate concentration; stimulation of the fatty acid oxidation and ketogenesis leading to ketoacidosis; and increased concentration of salicylic acid. In salicylate toxicity, as salicylate levels increase, the acid-base disturbance progresses from respiratory alkalosis to mixed respiratory alkalosis and metabolic acidosis. In children, the progression to metabolic acidosis occurs more rapidly. Salicylates directly stimulate respiratory centers in the medulla, causing hyperventilation and, subsequently, respiratory alkalosis. Salicylates also cause the uncoupling of oxidative phosphorylation, which leads to decreased adenosine triphosphate production, increased oxygen consumption, increased carbon dioxide production, and increased heat production. Derangement in the Krebs cycle and in carbohydrate metabolism leads to an accumulation of organic acids, including pyruvate, lactate, and acetoacetate, causing metabolic acidosis.

Salicylate Poisoning Dehydration and low plasma potassium & bicarbonate are caused by increased excretion of bicarbonate, potassium, sodium and free water. Hyperpyrexia (fever) and sweating are caused by the uncoupling of oxidation phosphorylation – energy used for ATP synthesis is dissipated as heat because ATP-depending enzymes are inhibited.