a Precious

Acid Base
Asst Prof Medicine Oakland Beaumont Med School

Joel M.

Acid-Base Physiology! !

Joel M. Topf, MD

Introduction

At the beginning of every episode of ER, as the impossibly attractive patient is being rolled from the ambulance bay to the resuscitation room, the equally attractive doctor barks orders, I need a chem-20, CBC, chest x-ray, and blood gas! The list may have a few other items but those four belong on the diagnosticians Mount Rushmore of tests. Despite being common, learning to fully interpret any one of those tests means torturing the results to extract the vary last byte of signal from the data. This handbook will guide you through the full extraction of the blood gas.

Goals
Understand how pH is like an earthquake The use and uselessness of the Henderson Hasselbalch formula Identify the 4 primary acid-base disorders Calculate appropriate compensation for all four primary acid-base disturbances Understand and calculate the anion gap Trash MUDPILES Know: GOLDMARK Non-anion gap metabolic acidosis Delta-gap or gap-gap Osmolar gap
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Acid-Base Physiology! !

Joel M. Topf, MD

Table of Contents
pH and the hydrogen ion concentration! ..........................................................................4 Henderson-Hasselbalch equation ! .....................................................................................5 There are four primary acid-base disturbances!..............................................................9 Compensation ! ......................................................................................................................9 Rapid interpretation of ABGs!............................................................................................12 Multiple primary acid-base disturbances ! ........................................................................13 Looking for second primary acid base disturbances the old timey way !....................14 Using the prediction equations!.........................................................................................15 The anion gap!......................................................................................................................18 Anion gap metabolic acidosis (AGMA) ! ...........................................................................19 Diabetic Ketoacidosis! ..........................................................................................................20 Non-Anion Gap Metabolic Acidosis (NAGMA)!............................................................22 Osmolar Gap!........................................................................................................................24 Additional metabolic acid-base conditions!.....................................................................26 Answers!................................................................................................................................28

Acid-Base Physiology! !

Joel M. Topf, MD

pH and the hydrogen ion concentration

Acid base physiology is the regulation of hydrogen ion concentration

Hydrogen ions are similar and different from other physiologically important electrolytes. Like other electrolytes, hydrogen ion concentrations need to be regulated. If the concentration rises too high or falls too low there are physiologic consequences and illness. A normal hydrogen ion concentration is 40 nmol/L and that leads to the principle difference from other ions. 40 nmol/L is 0.00004 mmol/L

Hydrogen ions exist at such minute concentrations that inorganic chemists decided to measure them on a negative log-rhythmic scale so 0.00004 mmol/L converts to 7.4. Every move of one point is a factor of ten. a pH of 6.4 is 400 nmol/L and 8.4 is 4 nmol/ L. On this scale every change of 0.3 pH units changes the hydrogen concentration by a factor of two.

pH

H+ concentration (nmol/L)

6.8 7.1 7.4 7.7

160 80 40 20

Acid-Base Physiology! !

Joel M. Topf, MD

Henderson-Hasselbalch equation
The primary buffer in the body is bicarbonate which is in equilibrium with carbon dioxide and water. The relationship between hydrogen ions, bicarbonate and carbon dioxide is governed by the law of mass action. This mass action formula can be simplied to a simple relationship called the Henderson-Hasselbalch formula.

Acid-Base Physiology! !

Joel M. Topf, MD

The Henderson Hasselbalch formula provides a critical relationship that governs all of acid base physiology. It is the Mantra of Acid Base physiology.

Acid-Base Physiology! !

Joel M. Topf, MD

Use the Henderson Hasselbalch formula to calculate the normal pH from a normal bicarbonate of 24 and a normal pCO2 of 40 mmHg.

You are taking boards and they give you the following ABG: pH = 6.8 / pCO2 = 50 / HCO3 = 15

You have been told that one question on the boards will require you to use the HendersonHasselbalch equation to determine if the ABG is possible. Use the Henderson-Hasselbalch equation to determine if this ABG is possible.

Do the same for this ABG: pH = 8.1 / pCO2 = 10 / HCO3 = 30

I guarantee you will get one of these questions on the boards. There will be one acid-base question where the right answer is some variance of: E) There is a lab error. or B) This ABG is impossible. One of the keys to the math on these problems is realizing that no one has a calculator and it is rather difcult to do logs in your head so the test writers try to keep the numbers easy to handle. The pCO2 x 0.03 will always be a tenth of the bicarbonate (so the log is 1 and the pH should be 6.1+1=7.1) or a hundredth of the bicarbonate (so the log is 2 and the pH should be 6.1+2=8.1).

Acid-Base Physiology! !

Joel M. Topf, MD

The pH is proportional to the serum bicarbonate over carbon dioxide. An increase in the numerator, bicarbonate, increases pH. A decrease in the denominator, carbon dioxide, also increases the pH. This relationship of bicarbonate, CO2 and pH is critical and you must have perfect knowledge of it to understand even the basics of acid-base physiology.

If the quantitative approach is not helpful one can understand the relationship from a simple qualitative approach. Bicarbonate is alkaline so increases in its concentration occur with increases in pH. The carbon dioxide is the acid so as its concentration rises the pH falls.
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Acid-Base Physiology! !

Joel M. Topf, MD

There are four primary acid-base disturbances

Looking at The Mantra it becomes apparent there are four disturbances which can occur: 1. an increase in bicarbonate 2. a decrease in bicarbonate 3. an increase in carbon dioxide 4. a decrease in carbon dioxide Any alteration of acid-base physiology requires at least one of these changes. The acid-base disturbances are categorized by Acid-Base disorder Metabolic acidosis the initial (i.e. primary) disturbance to The Mantra: 1. An increase in bicarbonate is a metabolic alkalosis 2. A decrease in bicarbonate is a metabolic acidosis 3. An increase in carbon dioxide is a respiratory acidosis 4. A decrease in the carbon dioxide is a respiratory alkalosis

Primary disturbance

compensation

pH =
pH = pH =

HCO3 CO2
HCO3 CO2 HCO3 CO2

pH =
pH = pH =

HCO3 CO2
HCO3 CO2 HCO3 CO2

Metabolic alkalosis

Respiratory acidosis

Respiratory alkalosis

pH =

HCO3 CO2

pH =

HCO3 CO2

Compensation
In order to remain in health, the body attempts to minimize changes in pH. Faced with a change in one component of The Mantra, the other factor changes in the same direction so that the fraction remains nearly constant. For example, the body responds to a fall in bicarbonate by decreasing carbon

dioxide. This minimizes changes in the ratio that determines the pH.

Acid-Base Physiology! !

Joel M. Topf, MD

The important thing to recognize is that carbon dioxide (respiratory alkalosis) will the primary disturbance without any comincrease the pH. pensation is a theoretical construct. In real The quick method patients, Since bicarbonate is proportional to compenpH, any ABG with pH and bicarsation ocIn metabolic disorders: pH, HCO3 and bonate moving in concordant direccurs sipCO2 all move in the same directions tions will be a primary metabolic multanedisease. Then all you need to do is ously with determine if the pH is elevated, the primary defect. This complicates trying metabolic alkalosis, or decreased, metabolic to sleuth out what is disease and what is acidosis. Additionally, since the compensacompensation. tory changes in carbon dioxide are in the For example: a decrease in bicarbonate same direction as the bicarbonate, all three and carbon dioxide could be due to a priHenderson-Hasselbalch variables will move mary decrease in bicarbonate with a comin the same direction in a metabolic acidpensatory decrease in carbon dioxide or a base disturbance. primary decrease in carbon dioxide with a Conversely, since carbon dioxide is incompensatory decrease in bicarbonate. versely related to pH, in a respiratory acidThe key to this mystery is the fact that base disturbance the carbon dioxide and pH compensation does not move in discordant completely erase the pridirections. Again In respiratory disorders: pH, HCO3 and mary change in pH. In since compensation pCO2 move in discordant directions metabolic acidosis the pH is always in the falls, and the compensasame direction as tory decrease in carbon the primary disorder, dioxide minimizes the change in pH but in a respiratory acid-base disturbance the does not erase it. So, a primary decrease in three Henderson-Hasselbalch variables will bicarbonate (metabolic acidosis) will demove in discordant directions. crease the pH while a primary decrease in

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Acid-Base Physiology! !

Joel M. Topf, MD

Determine the primary acid-base disturbance: 1. pH = 7.27 / pCO2 = 34 / HCO3 = 15 normal values pH=7.4 2. pH = 7.34 / pCO2 = 50 / HCO3 = 26 pCO2=40 HCO3=24 3. pH = 7.45 / pCO2 = 48 / HCO3 = 32

4. pH = 7.32 / pCO2 = 28 / HCO3 = 14

5. pH = 7.37 / pCO2 = 50 / HCO3 = 28

6. pH = 7.36 / pCO2 = 80 / HCO3 = 44

7. pH = 7.32 / pCO2 = 36 / HCO3 = 18

8. pH = 7.36 / pCO2 = 48 / HCO3 = 26

9. pH = 7.43 / pCO2 = 45 / HCO3 = 29

10. pH = 7.47 / pCO2 = 54 / HCO3 = 38

11. pH = 7.45 / pCO2 = 18 / HCO3 = 12

12. pH = 7.57 / pCO2 = 18 / HCO3 = 16

13. pH = 7.27 / pCO2 = 36 / HCO3 = 16

14. pH = 7.34 / pCO2 = 49 / HCO3 = 26

15. pH = 7.45 / pCO2 =50 / HCO3 = 33

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Acid-Base Physiology! !

Joel M. Topf, MD

Rapid interpretation of ABGs

A pH of 7.1 in methanol intoxication is an ominous sign. A pH of 7.1 following a grand-mal seizure is routine and without signicant morbidity. A pH of 7.6 due to anxiety-hyperventilation syndrome is benign. A pH of 7.6 in patients on digoxin and diuretics predisposes to serious arrhythmia. From the above examples it should be clear that it is the disease, not the pH that determines morbidity. Because of this, it is imperative to rapidly determine the etiology of an acid-base disturbance. The ABG and electrolyte panel allow one to easily narrow the differential diagnosis. It also allows the cagey physician to detect and categorize multiple, simultaneous, primary acid-base disorders. To fully characterize an acid-base disorder there are as many as 5 steps: 1. Determine the primary acid-base disorder 2. Determine if there is a second primary disorder affecting compensation 3. If the patient has a metabolic acidosis, determine the anion gap 4. If the patient has an anion gap metabolic acidosis (AGMA), determine if there is an osmolar gap 5. If the patient has an AGMA, look for a pre-existing non-anion gap metabolic acidosis or metabolic alkalosis

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Acid-Base Physiology! !

Joel M. Topf, MD

Multiple primary acid-base disturbances

Patients are complex and often have multiple simultaneous primary acid-base disturbances. Think of the patient with gastroenteritis with diarrhea causing metabolic acidosis and vomiting causing metabolic alkalosis. Uncovering these complex cases can be done mathematically or graphically. My suggestion to you is to get a computer. Patients are too important and you are too bad at math to do the calculation reliably, especially late at night. On the iPhone and iPod Touch there is a free program called ABG which will do this for you. Alternatively one can use an AcidBase nomogram which are accurate and easy to use. Just draw a line connecting the pH and pCO2 or connect the pCO2 and the bicarbonate (the diagonal lines). Unfortunately neither computers nor nomograms are available on the boards. For this reason you need to be able to fully interpret an ABG on your own.

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Acid-Base Physiology! !

Joel M. Topf, MD

Looking for second primary acid base disturbances the old timey way
As discussed earlier, compensation occurs in every acid-base disturbance. In the absence of a second primary-disorder the degree of compensation can be determined solely by the severity of the primary disturbance (and by the duration in the case of metabolic compensation). We use the predictability of compensation to determine if additional primary disorders are present. If the degree of compensation falls in the predicted range then there is no additional acid-base disturbance. Each primary acid-base disturbance has its own equation to calculate the predicted degree of compensation. See the table below. How to predict compensation

Disorder

Primary disturbance / Compensation decrease in bicarbonate decrease in carbon dioxide increase in bicarbonate increase in carbon dioxide increase in carbon dioxide increase in bicarbonate

Metabolic acidosis Metabolic alkalosis Respiratory acidosis

CO2 = 1.5 x HCO3 + 8 2 Winters formula CO2 increases 0.7 for every 1 mmol increase in HCO3 Acute: HCO3 increases 1 for every 10 mmHg of CO2

Chronic: HCO3 increases 3 for every 10 mmHg of CO2 Respiratory alkalosis decrease in carbon dioxide decrease in bicarbonate Acute: HCO3 decreases 2 for every 10 mmHg of CO2

Chronic: HCO3 decreases 4 for every 10 mmHg of CO2

If the prediction equation explains the compensation then you have a simple acidbase disorder. If the prediction equation does not explain the compensation then a second primary disorder exists. In metabolic disorders, if the actual pCO2 is less than the predicted pCO2 there is an additional respiratory alkalosis. If the actual

pCO2 is greater than the predicted pCO2 there is an additional respiratory acidosis. In respiratory disorders, if the actual HCO3 is greater than the predicted HCO3 there is an additional metabolic alkalosis. If the actual HCO3 is less than the predicted HCO3 there is an additional metabolic acidosis.
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Acid-Base Physiology! !

Joel M. Topf, MD

Using the prediction equations

Metabolic acidosis Suppose a patient has a pH of 7.37, HCO3 of 10 and a pCO2 of 18. All three variables are lower than normal so the patient has a metabolic disturbance. The pH is decreased so this is metabolic acidosis. To look for a second primary condition the rst step is to use Winters formula to see if the compensation is appropriate. With a bicarbonate of 10, Winters formula predicts a pCO2 of ______. The actual pCO2 is 18, below the predicted pCO2 so this patient has an additional primary respiratory __________. If the actual pCO2 was 24, then the patient would have physiologically compensated metabolic acidosis without a second primary ____________ disorder. If the actual pCO2 was 28 then the patient would have a pCO2 that was higher than predicted or an additional primary respiratory _____________. Metabolic alkalosis Suppose a patient has a pH of 7.50, HCO3 of 36 and pCO2 of 48. All three variables are higher than normal so the patient has a __________ disturbance. The pH is ____________ so this is metabolic alkalosis. To look for a second primary condition rst determine what the expected compensation should be. In metabolic alkalosis the pCO2 rises 0.7 for every 1 mmol/L increase in HCO3. An HCO3 of 36 is an increase of 12 from normal. This should be compensated by an increase in pCO2 of _______. The actual pCO2 is 48, so this patient has an isolated metabolic alkalosis with ____________ respiratory compensation. If the pCO2 was 58, the patient would have an additional respiratory ____________. If the pCO2 was 42, the patient would have an additional primary respiratory ____________. Respiratory acidosis Suppose a patient has a pH of 7.35, HCO3 of 30 and a pCO2 of 56. The pH is decreased and both the HCO3 and pCO2 are elevated. Since the variables move in discordant direction it is a _____________ disturbance. The pH is decreased so this is respiratory ______________. To look for a second primary condition the rst step is to determine the expected bicarbonate. The pCO2 is 16 above normal which corresponds to an expected increase in HCO3 of 2 in ________ respiratory acidosis and 5 in _______ respiratory acidosis. So the expected bicarbonate is 26 if the respiratory acidosis is acute and 29 if it is chronic. The actual HCO3 is 30 so there is an additional _________ _______ if the patient has acute disease and a pure res-

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Acid-Base Physiology! !

Joel M. Topf, MD

piratory acidosis if the condition is _______. It is important to understand that the compensation equation can not tell you if the patient has acute or chronic disease. The physician must determine that. Respiratory alkalosis Suppose a patient has a pH of 7.56, HCO3 of 23 and a pCO2 of 22. The pH is increased and the HCO3 and pCO2 are both ________. Since the variables move in discordant direction it is a __________ disturbance.

The pH is increased so this is respiratory alkalosis. To look for a second primary condition the rst step is to determine the expected bicarbonate. The pCO2 is 18 below normal which corresponds to an expected _________ in HCO3 of 4 in acute respiratory alkalosis and 8 in chronic respiratory alkalosis. So the expected bicarbonate is 20 if the respiratory alkalosis is acute and 16 if it is chronic. The actual HCO3 is 23 so this is a respiratory alkalosis with ________ ___________ regardless if it is acute or chronic.

Respiratory acidosis Acute Chronic

Respiratory alkalosis

10:1 10:3
For every rise of 10 in the pCO2 the HCO3 will rise by 1 or 3

10:2 10:4
For every fall of 10 in pCO2 the HCO3 will fall by 2 or 4.

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Acid-Base Physiology! !

Joel M. Topf, MD

Brittany Spears has been out partying and wakes up vomiting. After six hours she is still vomiting and calls her personal concierge physician who gets the following ABG: 7.71 / 33 / 94 with a HCO3 of 40 on the electrolyte panel.

John Daley presents to the ED stuporous. His caddie says he has been taking nips from a little bottle all day. His labs reveal the following: 7.22 / 17 / 112 ! ! ! ! 147! 4.2! 104! 7! 38 1.8

Hunter Thompson is dragged in to your ofce by his attorney. Mr. Thompson is incomprehensible but does not appear toxic. There is no history of diarrhea. An ABG and lytes are drawn: 7.28 / 36 / 88 ! ! ! ! 136! 2.8! 116! 14! 16 0.8

John Wayne is admitted to a surgery center for a colonoscopy. During the procedure the oxygen saturation monitor malfunctions so the gastroenterologist gets an ABG to conrm good oxygenation. 7.32 / 60 / 145 / 31

Aretha Franklin is undergoing chemotherapy for pancreatic cancer. She develops nausea and vomiting and is admitted for IVF. In the ER a blood gas and labs are drawn: 7.54 / 45 / 104 ! ! ! ! 144! 3.2! 91! 35! 36 1.3

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Acid-Base Physiology! !

Joel M. Topf, MD

The anion gap

In respiratory acidosis the acid is known, by denition its carbon dioxide. In metabolic acidosis the acid (anion) can be anything and what it is can have profound implications for your patient. Metabolic acidosis is categorized by the In metabolic acidosis bicarbonate (an antype of acid which is consuming the bicarion) is decreased, so to keep the anions in bonate. The acid has two components: a probalance with the unchanged cations another ton, which reacts with bicarbonate and an anion must ll the void. This is either chloride anion which can accumulate in the body. The as seen on the left or an other anion as seen identity of the anion is how we name the difon the right. ferent metabolic acidosis. The anion gap is a way to quantify this In all of clinical medicine there are only two types of anions: Its either chloride or Its not chloride The anion-gap is a simple calculation which allows you to determine if the excess anion is chloride or not. The total number of anions in the blood must equal the total number of cations (otherwise touching blood would give you a shock). relationship:
Cl + HCO3 + Other anions = Na+ + Other cations

Then rearrange it to solve for the other ions:

Other anions Other cations = Na+ (Cl + HCO3 )

Dene anion gap as the difference between other anions and other cations:
Anion gap = Na+ (Cl + HCO3 )

On average the anion gap is 63 with the upper limit of normal being 12. With metabolic acidosis, if the anion gap is less than twelve then the increased hydrogen ions are associated with excess chloride and if the anion gap is greater than twelve the excess anion is something else.
Abnormally low anion gap Though not related to an acid-base disturbance, a low anion gap can also signal disease. Causes include: Increased chloride Hypertriglyceridemia Bromide Iodide Decreased Unmeasured anions Albumin Phosphorous Increased Unmeasured cations Hyperkalemia Hypercalcemia Hypermagnesemia Lithium IgG
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Acid-Base Physiology! !

Joel M. Topf, MD

Anion gap metabolic acidosis (AGMA)

Anion gap metabolic acidosis cause the most serious acute metabolic acidosis. The most important causes of AGMA are: Lactic acidosis Ketoacidosis Toxic alcohols Renal failure Lactic acid is produced during anaerobic metabolism. The production of lactic acid restores NAD+ needed for glycolysis. Two types of lactic acidosis: Type A: decreased perfusion causing ischemia resulting in anaerobic metabolism and lactic acidosis. Shock. Type B: anaerobic metabolism due to mitochondrial dysfunction. Aspirin toxicity, NNRTI, metformin, malignancy Ketones are produced as an alternative energy supply when glucose is unavailable: starvation ketosis alcohol induced hypoglycemia diabetic ketoacidosis Insulin is a potent suppressor of ketogenesis so treatment requires supplying insulin. In starvation or alcohol ketosis administering glucose allows the secretion of endogenous insulin. In DKA patients require an insulin drip. The toxic alcohols can cause AGMA and will be discussed more in the section on osmolar gap. Renal failure variably causes AGMA. Early in the course of CKD patients develop NAGMA but in late CKD stage 4 and CKD stage 5, sulfur based anions accumulate and cause AGMA.

The classic mnemonic MUD PILES sucks. The new mnemonic is GOLD MARK. Know it. G! O! Glycols: ethylene glycol Oxoproline: Pyroglutamic Acid is a rare cause of high anion gap (30s) metabolic acidosis. It is seen with acetaminophen, hypotension and infection. L-lactic acidosis. D-Lactic acidosis: Bacteria metabolize carbohydrate to the isomer D-lactate. LDH only recognizes L-lactate so Dlactate must be cleared by the kidney. The anion gap is usually small and transient because D-lactate is rapidly cleared by the kidneys. M! A! R! K! Methanol Aspirin. The anion is actually lactate in ASA toxicity. Renal failure Ketoacidosis: DKA, starvation, hypoglycemia

L! D!

AN Mehta, JB Emmett , M Emmett, Lancet, 372, 9642, p 892, 2008

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Acid-Base Physiology! !

Joel M. Topf, MD

Diabetic Ketoacidosis
The most exciting diagnosis in internal medicine In diabetic ketoacidosis, just about every lab value that can go wrong has gone wrong. DKA occurs when there is an absolute or relative lack of insulin. In the absolute case, the patient with DM1 forgets or fails to take their insulin, in the relative case, patients on a stable dose of insulin undergo a crisis that requires additional insulin and if her insulin prescription does not account for this, they have a relative paucity of insulin and go into ketoacidosis. Triggers of DKA: a 7 eyed monster initial (new diagnosis) infection illicit drug use insulin (lack of, non-compliance) infarction (myocardial) incision (surgery) infant (pregnancy) Patients who present with DKA are typically quite toxic with hypovolemic shock, altered mental status, abdominal pain, vomiting. Acetone can cause a fruity odor on the breath. Diagnosis can be made from the combination of an anion gap metabolic acidosis, hyperglycemia (500-800) and positive serum ketones. The ketones can be acetoacetate, hydroxybutyrate or acetone. Only acetoacetate is detected by the routine serum ketone assay. There is no role of serial ketone assays in the management of DKA The lab abnormalities are ubiquitous in DKA: Sodium is decreased due to pseudohyponatremia. To estimate the corrected Na+ add 1.6 mEq/L to the measured Na+ for every 100 mg/dL the glucose is above 100 mg/dL. Some 2.4 per 100 of glucose. Potassium is usually increased due to solute drag. The lack of insulin prevents a shift of K+ back into cells. Despite high plasma levels, total body potassium is decreased due to increased renal losses. Bicarbonate is decreased. Duh, metabolic acidosis. BUN and creatinine are elevated due to pre-renal acute renal failure. Glucose is elevated, usually above 300 mg/dL. Duh, diabetes. Anion gap is increased due to the presence of ketone anions. The gap is often greater than 20 mEq/L. Phosphorous is decreased. Amylase is increased because ketones interfere with the laboratory assay. Lipase is usually normal. pH is decreased. PCO2 is decreased due to compensatory hyperventilation (Kussmauls respiration). White blood cell count is increased due to demargination. The most profound abnormality is volume depletion. The osmotic diuresis vomiting ( a common symptom of DKA) can result in life-threatening hypovolemic shock.

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Acid-Base Physiology! !

Joel M. Topf, MD

The three core medicines used to treat DKA are: 1. Insulin. Insulin will lower the glucose but it is used to reverse the ketosis. The insulin drip should be continued until the anion gap has closed (indicating complete reversal of the ketosis) even if that means starting continuing the insulin after the hyperglycemia is resolved. You made need to start a dextrose infusion to prevent hypoglycemia. 2. 0.9 Normal Saline. Saline is used to reverse the volume loss. 3. Potassium. Patients on initial presentation will usually be hyperkalemic despite total body potassium depletion. When the insulin is started, potassium will shift into the cells and rapidly uncover the hypokalemia. Potassium replacement should be started when the potassium falls below 4 mmol/L. Potassium should be frequently assessed during therapy. Bicarbonate has been tested and should not be used as it can prolong the ketosis and promotes hypophosphatemia without improving patient outcomes.
accucheck: high ABG 7.20 / 16 / 96 / 6 128 6.4 94 44 7 1.8

A 14 year old actress has been having increasing fatigue for the past few weeks. Her school performance has slipped and her parents are worried that she may have gotten into drugs. She has been waking at night to go to the bathroom 2-3 times a night. Today, her mother found her unconscious on the oor in a puddle of urine. In her purse the mom found a bag of dried plant-matter and a bottle of unidentied pills. Blood pressure is 80/P, HR 146, RR 32, Wt 40 kg. Skin is cool, lungs are clear, heart is tachy,cardic, abdomen is rm without rebound. She has no edema. She is nonresponsive. What are rst steps in resuscitation? Initial diagnostic procedures?

Anion Gap 27 glucose 764 adjusted Na 138.6

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Acid-Base Physiology! !

Joel M. Topf, MD

Non-Anion Gap Metabolic Acidosis (NAGMA)

Non-anion gap metabolic acidosis occurs in three clinical scenarios: 1. Excessive chloride intake, usually as normal saline 2. Increased lower GI losses, usually as diarrhea 3. Failure of the kidney to excrete the daily hydrogen load, renal tubular acidosis.
Chloride intake

matic losses of bicarbonate. This causes a NAGMA. In GI disturbances the pH follows the food, with vomiting the food and pH rises, with diarrhea the food and pH falls
Renal tubular acidosis

Normal saline has a pH of 5.5. It also is a massive source of chloride. How would you compare the relative acidity of saline versus plasma? How much chloride is in all of the plasma? How much chloride is found in a liter of 0.9% normal saline. Almost all of the cases of excessive chloride intake causing NAGMA are due to saline infusions, often erroneously called dilutional acidosis. Hydrochloric acid intoxication or chlorine gas poisoning can also cause NAGMA via excessive chloride.
GI losses

The kidneys role in regard to maintaining a normal bicarbonate can be neatly divided into three tasks: Reabsorb all of the ltered bicarbonate. Like other valuable small molecules and electrolytes that are freely ltered at the glomerulus, the kidney avidly scavenges these particles and reabsorbs them. Synthesize new bicarbonate. The kidney must also synthesize new bicarbonate to replace bicarbonate consumed in daily metabolism. Creating new bicarbonate requires excretion of hydrogen ions from the body. Excrete hydrogen as ammonium (NH4+). In order to synthesize de novo bicarbonate, the kidney must excrete hydrogen ions in the urine. These hydrogen ions make up the daily acid load (approx. 1 mmol/Kg body weight). The kidney cannot excrete the daily acid load as free hydrogen and must excrete the hydrogren as either titratable acids or ammonia. Failure in the rst bullet point results in type 2 or proximal RTA. Failure of the second bullet point results in RTA type 1. Failure of the third bullet point results in hyperkalemic or type 4 RTA.

GI secretions, distal to the highly acidic stomach, have relatively high bicarbonate concentrations:
Bile! .................................................30-40 mEq/L Pancreatic secretions!.................80-100 mEq/L Small intestine !..........................80-100 mEq/L Large intestine !............................30-50 mEq/L

It should be apparent that diarrhea or a surgical drain could result in rapid and dra-

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Acid-Base Physiology! !

Joel M. Topf, MD

Disorder GI losses Proximal RTA < 6.0

urine pH

Plasma K Hypokalemia, variable Hypokalemia during treatment Hyperkalmia

urine anion gap negative at Tm negative above Tm positive positive

at Tm < 6.0 above Tm, > 6.0

Electrogenic distal RTA Classic distal RTA Hyperkalemic RTA (type 4)

> 5.5

>5.5

Hypokalemia

positive

< 6.0

Hyperkalmia

positive

The ideal laboratory test to diagnose RTA would be a urinary ammonium assay. Outside of specialized laboratories this does not exist. We can infer the presence of ammonium by looking at the urinary anion gap. We used the serum anion gap to look for non-specic anions causing the metabolic acidosis. We will now use the urinary anion gap to look for increased cations, namely ammonium cations.
Urine Anion gap = (Na+ + K+) Cl

Normally, with urinary acidication, there is increased ammonium in the urine which adds to the unmeasured cations. Unmeasured cations exceed unmeasured anions so there are excess unmeasured cations so the anion gap will be negative. A negative urinary anion gap means good urinary ammonia levels. In distal RTA, there is no urinary acidication. Without acidic urine there is nothing to drive the formation of NH4+ from NH3. In type 4 RTA, the urine pH is low enough but the hyperkalemia blocks the release of NH3, so there is no substrate to produce NH4+.

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Acid-Base Physiology! !

Joel M. Topf, MD

Osmolar Gap
In patients with metabolic acidosis and a large anion gap, consideration should be given to ethylene glycol and methanol toxicity. Laboratory conrmation may take 24 hours. The osmolar gap allows one to infer the presence of these low molecular weight toxins. If a patient has ingested ethylene glycol or methanol, treatment must be initiated rapidly. Usually therapy is begun prior to conrming the diagnosis with a specic assay for the alcohol. One of the keys to building the clinical suspicion is demonstrating an osmolar gap.

The osmolar gap demonstrates an increase in the serum osmolality that can not be explained by the usual suspects: electrolytes, glucose, urea and ethanol. Because the molecular weight of methanol and ethylene glycol are low, a few grams equals many osmoles and will increase the measured osmolality without affecting the calculated osmolality. This provides the gap. Calculated Osmolality:

If the calculated osmolality is more than 10 mosm/Kg H2O less than the measured osmolality you have an abnormal osmolar gap. Elevated osmolar gaps are found with: Ethylene glycol Methanol Isopropyl alcohol Ketoacidosis Lactic acidosis Mannitol infusion Pseudohyponatremia

2 x Na + glucose/18 + BUN/2.8 + EtOH/4.6

The glucose, BUN and ethanol levels are divided by their molecular weight (180, 28 and 46) to convert mg/dL to mmol/dL and then multiplied by ten to get mmol/L
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Acid-Base Physiology! !

Joel M. Topf, MD

Problems: gure out the anion gap, calculated osmolality, and osmolar gap in the following patients 1.! ! ! 2.! ! ! 3.! ! ! 4.! ! ! 5.! ! ! 6.! ! ! 7.! ! ! 8.! ! ! 9.! ! ! 10.! ! ! 148! 4.8! ! 146! 4.8! ! 138! 4.8! ! 146! 4.8! ! 141! 4.8! ! 135! 4.8! ! 138! 4.8! ! 146! 4.8! ! 130! 4.8! ! 148! 4.8! ! 111! 12! ! 105! 18! ! 112! 14! ! 106! 12! ! 95! 8! ! 105! 7! ! 112! 10! ! 114! 14! ! 94! 6! ! 120! 15! ! 10! 0.8! ! 14! 0.8! ! 28! 1.8! ! 196! 8.8! ! 85! 2.4! ! 45! 2.2! ! 62! 2.2! ! 127! 6.3! ! 8! 0.6! ! 18! 1.0! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! Ethanol: 0! Glucose: 40 ! ! Osmolality: 337! ! ! ! ! ! ! ! Ethanol: 0! Glucose: 80 ! ! Osmolality: 311! ! ! ! ! ! ! ! Ethanol: 0! Glucose: 120 ! ! Osmolality: 302! ! ! ! ! ! ! ! Ethanol: 0! Glucose: 335 ! ! Osmolality: 400! ! ! ! ! ! ! ! Ethanol: 0! Glucose: 165 ! ! Osmolality: 338! ! ! ! ! ! ! ! Ethanol: 48! Glucose: 223 ! ! Osmolality: 309! ! ! ! ! ! ! ! Ethanol: 86! Glucose: 40 ! ! Osmolality: 333! ! ! ! ! ! ! ! Ethanol: 112 ! Glucose: 48 ! ! Osmolality: 380! ! ! ! ! ! ! ! Ethanol: 0! Glucose: 90 ! ! Osmolality: 313! ! ! ! ! ! ! ! Ethanol: 0! Glucose: 656 ! ! Osmolality: 344! ! ! ! ! ! ! ! Anion gap: 25 Calculated Osm: 302 Osmolar gap: 35 Anion gap: 23 Calculated Osm: 301 Osmolar gap: 10 Anion gap: 12 Calculated Osm: 293 Osmolar gap: 9 Anion gap: 28 Calculated Osm: 381 Osmolar gap: 19 Anion gap: 38 Calculated Osm: 322 Osmolar gap: 16 Anion gap: 23 Calculated Osm: 309 Osmolar gap: 0 Anion gap: 16 Calculated Osm: 319 Osmolar gap: 14 Anion gap: 18 Calculated Osm: 364 Osmolar gap: 16 Anion gap: 30 Calculated Osm: 268 Osmolar gap: 45 Anion gap: 13 Calculated Osm: 339 Osmolar gap: 5
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Acid-Base Physiology! !

Joel M. Topf, MD

Additional metabolic acid-base conditions

There is a trick for patients with anion-gap metabolic acidosis that allows physicians to go back in time prior to developing the anion gap and see what the bicarbonate was at that time. From that you can deduce if the patient had either a pre-existing metabolic alkalosis or preexisting non-anion gap metabolic acidosis. Earlier we looked at compensation to deQuestions termine if a patient has a second primary An over-rated NFL quarteracid-base disorder. Now we will look at the back with a bad temper preanion gap to determine if the patient has an sents to the ER appearing additional primary acid-base disorder. toxic, hypotensive. His agent In order to use the anion gap to look for additional acid-base disorders we assume that for every increase in the anion gap over 12 the serum bicarbonate falls by one. reports that he initially developed diarrhea after eating some old chicken salad: 7.28 / 18 / 88 ! glucose: ! 875! ! ! 128! 5.6! 106! 8! 16 1.8

1. What is the primary acid-base disturbance? 2. Is there a second primary acid-base disturbance, affecting compensation? What is it? We can establish a formula to represent this:
! HCO3 = ! Anion Gap HCO3before HCO3now = AGcurrent AGnormal HCO3 before = HCO3now + (AGcurrent 12)

3. What is the anion gap? 4. What is the diagnosis? 5. Calculate the bicarbonate before 6. Did he have a pre-existing acid-base disorder? What is it and why does he have it?

By using the last formula we can actually infer what the bicarbonate was prior to developing the anion gap. If this bicarbonate is low we call this a pre-existing non-anion gap metabolic acidosis. If the bicarbonate is elevated then the patient had pre-existing metabolic alkalosis.

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Acid-Base Physiology! !

Joel M. Topf, MD

A manic patient with fever and diarrhea presents to the ER, hypotensive with these initial labs:

Calculate the bicarb prior to the AGMA: 1.! ! 2.! 140! 4.8! 134! 4.8! 138! 4.8! 146! 4.8! 141! 4.8! 135! 4.8! 138! 4.8! 146! 4.8! 130! 4.8! 148! 4.8! 110! 18! 104! 12! 114! 6! 114! 16! 105! 18! 94! 19! 101! 14! 114! 16! 96! 6! 106! 14! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! Anion Gap: 2 Bicarb before: 8 Anion Gap: 18 Bicarb before: 18 Anion Gap: 18 Bicarb before: 12 Anion Gap: 16 Bicarb before: 20 Anion Gap: 18 Bicarb before: 24 Anion Gap: 22 Bicarb before: 29 Anion Gap: 23 Bicarb before: 25 Anion Gap: 16 Bicarb before: 20 Anion Gap: 28 Bicarb before: 22 Anion Gap: 28 Bicarb before: 30

7.28 / 28 / 88 ! glucose: ! 128!

! !

142! 3.2!

102! 18!

16 1.8

! 3.! ! 4.! ! 5.! ! 6.! ! 7.! !

1. What is the primary acid-base disturbance: 2. Is there a second primary acid-base disturbance affecting compensation? What is it? 3. What is the anion gap? 4. Calculate the bicarbonate before 5. Did he have a pre-existing acid-base disorder? What is it and why does he have it? A person of remarkable genetic luck returns from an African safari with a cyclical fever and nausea and vomiting. He appears toxic:

7.42 / 32 / 76 ! glucose: ! 56!

! !

148! 5.8!

98! 28!

43 2.3

8.! ! 9.! ! 10.! !

1. What is the primary acid-base disturbance: 2. Is there a second primary acid-base disturbance affecting compensation? What is it? 3. What is the anion gap? 4. Calculate the bicarbonate before 5. Did he have a pre-existing acid-base disorder? What is it and why does he have it?

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Acid-Base Physiology! !

Joel M. Topf, MD

Answers
Determine the primary acid-base disturbance: 1. 2. 3. 4. 5. 6. 7. 8. 9. Metabolic Acidosis Respiratory acidosis Metabolic alkalosis Metabolic Acidosis Respiratory acidosis Respiratory acidosis Metabolic Acidosis Respiratory acidosis Metabolic alkalosis

Ms. Spears: both a primary metabolic alkalosis and respiratory alkalosis Mr. Daley: isolated metabolic acidosis Mr. Thompson: metabolic acidosis and respiratory acidosis Mr. Wayne: isolated chronic respiratory acidosis or an acute respiratory acidosis and metabolic alkalosis Ms. Franklin: isolated metabolic alkalosis Problems: gure out the anion gap, calculated osmolality, and osmolar gap in the following patients 1. 2. 3. 4. 5. 6. 7. 8. 9. Anion gap: 25 Calc Osm: 302 gap: 35 Anion gap: 23 Calc Osm: 301 gap: 10 Anion gap: 12 Calc Osm: 293 gap: 9 Anion gap: 28 Calc Osm: 381 gap: 19 Anion gap: 38 Calc Osm: 322 gap: 16 Anion gap: 23 Calc Osm: 309 gap: 0 Anion gap: 16 Calc Osm: 319 gap: 14 Anion gap: 18 Calc Osm: 364 gap: 16 Anion gap: 30 Calc Osm: 268 gap: 45

5. Patient had pre-existing metabolic alkalosis. This patient has a triple disorder: metabolic acidosis, respiratory alkalosis and metabolic alkalosis. Alkalosis likely due to crack cocain being cut with bicarbonate. Prince William 1. metabolic alkalosis 2. respiratory alkalosis 3. 22 4. 18 5. Patient had pre-existing metabolic acidosis. The presence of an anion gap in metabolic alkalosis or a primary respiratory acid-base disorder indicates an additional metabolic acidosis. This patient also has a triple disorder. Lactic acidosis of fulminant malaria, Calculate the bicarb before: 1.Anion Gap: 12 Bicarb before: 18 2.Anion Gap: 18 Bicarb before: 18 3.Anion Gap: 18 Bicarb before: 12 4.Anion Gap: 16 Bicarb before: 20 5.Anion Gap: 18 Bicarb before: 24 6.Anion Gap: 22 Bicarb before: 29 7.Anion Gap: 23 Bicarb before: 25 8.Anion Gap: 16 Bicarb before: 20 9.Anion Gap: 28 Bicarb before: 22 10.Anion Gap: 28 Bicarb before: 30

10. Metabolic alkalosis 11. Respiratory alkalosis Using the prediction equations ! Metabolic Acidosis 232 alkalosis respiratory acidosis ! Metabolic alkalosis metabolic increased 8 appropriate acidosis alkalosis ! Respiratory acidosis respiratory acidosis acute chronic metabolic alkalosis chronic ! Respiratory alkalosis decreased respiratory decrease metabolic alkalosis Multiple Acid-base disturbances. Case vignettes

10. Anion gap: 13 Calc Osm: 339 gap: 5 Gap-Gap case vignettes: Jay Cutler 1. metabolic acidosis 2. None 3. 14 4. DKA 4. 10 5. Yes. Pre-existing NAGMA due to diarrhea Charlie Sheen. Winning! 1. metabolic acidosis 2. respiratory alkalosis 3. 22 4. 28

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