Acid

1
Acid Base

• John R. Foringer, M.D.
• Division of Renal Diseases and Hypertension
• Section of Critical Care Nephrology
• john.r.foringer_at_uth.tmc.edu
• [phone]

2
152 104 30
ABG 7.42/24/115
3.6 15 1.0
Why do we call Normal Saline normal?
What is the Na concentration of ½ NS with 2 Amps
of NaHCO3?
3
Simple Acid-Base Disturbances

• pH pK log10 HCO3
• (0.0301)(paCO2)
• pH 6. 1 log ( metabolic component)
• (respiratory component)
• HCO3_ CO2 pH
• CO2 HCO3_ pH

4
Understanding Normal Acid-Base Handling

• Metabolic processes in the body lead to the
  production of acid
• The catabolism of glucose and fatty acids
  produces CO2 and H2O,
• effectively carbonic acid.
• About 1 mEq/Kg body weight of H is produced a
  day in the body.
• Respiratory elimination of CO2 and cellular
  buffers handle this acid load.
• Renal excretion of acid must be maintained.

5
Understanding Normal Acid-Base Handling

• The Kidney
• Reabsorbs 4500 mEq of HCO3 per day
• Generates new HCO3 to replenish buffer stores
• The Proximal tubule does most of the work
• Luminal membrane carbonic anhydrase

This is stimulated by an ? PCO2
6
Understanding Normal Acid-Base Handling

• The Kidney
• The Distal tubule reclaims the remainder of the
  HCO3
• Uses cytoplasmic carbonic anhydrase
• Also eliminates H to the nonvolatile acid
  production

Stimulated by aldosterone and ? PCO2
The Kidney will excrete NH4 to eliminate the H
7
Normal renal processes of acid handling
Proximal tubule
Distal Nephron / Collecting Duct
H HCO3- CO2 H2O
HCO3-
HCO3-
HCO3-
H secretion and HCO3- regeneration
H
Urine
8
CO2 H2O HCO3- H
To Blood
Kidney
Bicarbonate reabsorption
HCO3
H
HCO3-
CO2
CO2 H2O HCO3- H
Titratable acid formation
HPO42-
H2PO4-
HCO3-
H
Glutamine HCO3- NH4
Ammonium excretion
HCO3-
NH4
9
Understanding Normal Acid-Base Handling

• Other organs involved in acid-base regulation
• The Gut
• Stomach adds H to the gut lumen
• Below the pylorus - HCO3 is added to the gut

Proton-secreting cell
Bicarbonate-secreting cell
Gut Lumen
HCO3
H
CO2 H2O ? HCO3 H
CO2 H2O ? HCO3 H
H
HCO3
Blood
10
Understanding Normal Acid-Base Handling

• Other organs involved in acid-base regulation
• The Liver
• Detoxification of NH4
• Hepatic synthesis of urea then urinary secretion
  (consumes HCO3-).
• Hepatic synthesis of glutamine from NH4 then
  conversion of glutamine in the kidney to NH4
  (renal ammoniagenesis) and secretion in the urine
  (no HCO3- consumption).

11
Simple Acid-Base Disorders

• Metabolic Acidosis
• Metabolic Alkalosis
• Respiratory Acidosis
• Respiratory Alkalosis

12
Mixed Acid-Base Disturbances

• Definition
• Combination of two or more of the 4 simple
  disturbances (primary)
• Examples
• Mixed respiratory-metabolic disorders
• Mixed metabolic disorders

13
Compensatory Responses in Simple Acid-Base
Disorders
14
What is the Base Excess?

• Proposed as an indicator of acid-base status that
  was not influenced by PaCO2
• It is the sum of the concentration of buffer
  anions
• HCO3 and hemoglobin
• Problem is this only works in vitro
• In vivo as the PCO2 rises the ? HCO3 is
  attenuated by flux into the interstitial fluid
  compartment
• Now to overcome this Standard Base Excess
• SBE 0.93 (HCO3 -24.4) 13.79 (pH -7.4)
• Estimates the amount of base needed to restore
  the metabolic acid-base status to normal in the
  entire extracellular fluid compartment

15
A New Trend in Trauma Surgery
In 3,102 trauma patients. Serum HCO3 measurement
shows a strong linear correlation and similar
predictive ability compared with the arterial BD.
Serum HCO3 may be safely and accurately
substituted for arterial BD measurement in
critically injured patients.
FitzSullivan et al., Am J of Surg. Volume 190,
Issue 6, Pages 827-994 (December 2005)
16
Metabolic Acidosis
17
Why Acidosis is Bad
18
Changes in Cardiac Output with Declining pH
Kraut et al., AJKD, 38 Pages 703-727 (October
2001)
19
Evaluating a Low HCO3

• No acid/base disorder can be diagnosed without
  an ABG
• With every Chem 7 there is an anion gap and a
  calculated osm

Anion Gap Na - (HCO3 Cl) Serum Osm 2(Na)
BUN Glc 2.8 18
20
Assessment of a Low Serum HCO3
21
Classification of Metabolic Acidosis
22
Lactic Acid

• Type I proportional increase in lactate and
  pyruvate
• Type II Lactate higher than pyruvate
• Type A tissue hypoxia
• Type B arises from malignancy, liver disease,
  inborn errors of metabolism, or ingestion of
  toxins

23
Treatment of Metabolic (Lactic) Acidosis

• Treatment with NaHCO3
• An estimate of replacement
• Dose of bicarbonate (0.5 X BW) X (desired HCO3
  current HCO3)
• Goal of replacement is a pH above 7.2

24
Treatment of Lactic Acidosis

• Should we treat lactic acid with HCO3 ?
• ?PFK activity (rate limiting enzyme of
  glycolysis)
• Acidosis ?and alkalosis ? lactate production
• ? CO2 production
• Impairs cardiac performance
• Large fluid load

• What about Dialysis?
• Add HCO3
• Remove lactic acid (MW 90.08 vs ß2-microglobulin
  11,815)

25
Treatment of Lactic Acidosis with HCO3
Kraut et al., AJKD, 38 Pages 703-727 (October
2001)
26
Treatment of Ketoacidosis with HCO3
Kraut et al., AJKD, 38 Pages 703-727 (October
2001)
27
Treatment of Lactic Acidosis

• Dichloroacetate
• Promotes oxidation of lactate (pyruvate
  dehydrogenase) ?? acetyl-coenzyme A carbon
  dioxide
• 252 patients with lactic acidosis,
  placebo-controlled, randomized trial of
  intravenous sodium dichloroacetate
• Only 12 percent of the dichloroacetate-treated
  patients and 17 percent of the placebo patients
  survived to be discharged
• Statistically significant but clinically
  unimportant changes in arterial-blood lactate
  concentrations and pH and fails to alter either
  hemodynamics or survival

Stacpoole P., et al. N Engl J Med 1992
3271564-1569, Nov 26, 1992.
28
Treatment of Lactic Acidosis

• THAM (0.3 N tromethamine) Tris-Hydroxymethyl
  Aminomethane
• Sodium-free solution
• Buffers both metabolic acids (THAM H ??
  THAM)
• and respiratory acids (THAM H2CO3 ?? THAM
  HCO3-)
• proton and CO2 scavenger
• Limits carbon dioxide generation and increases
  both extracellular and intracellular pH
• Serious side effects
• including hyperkalemia, hypoglycemia,
  ventilatory depression, local injury in cases of
  extravasation, and hepatic necrosis in neonates
• Renal excretion

29
Treatment of Lactic Acidosis

• Carbicarb
• Equimolar concentrations of sodium bicarbonate
  and sodium carbonate
• Carbonate is a stronger base (CO32- H ??
  HCO3-)
• Carbonate ion can react with carbonic acid,
  thereby consuming carbon dioxide
• (CO32- H2CO3 ?? 2HCO3-).
• Increased blood and intracellular pH with little
  or no rise in the arterial or venous partial
  pressure of carbon dioxide
• Risks of hypervolemia and hypertonicity

Bersin RM. Circulation 198877227-233. Kucera
RR. Crit Care Med 1989171320-1323.
30
NaCl vs. NaHCO3 vs. Carbicarb vs. THAM
Arterial (Ha) and mixed venous (Hv)
hydrogen ion concentrations at baseline (B),
during ventricular fibrillation (VF), and during
cardiopulmonary resuscitation (CPR). Open
circles, sodium chloride (NaCl) controls solid
circles, bicarbonate solid squares, Carbicarb
open squares, THAM. up arrow Indicates the
timing of buffer dose administration.
Bar-Joseph, et al., Crit Care Med, Volume
26(8), August 1998, pp 1397-1408.
31
NaCl vs. NaHCO3 vs. Carbicarb vs. THAM
Arterial lactate, and arterial bicarbonate (HCO3)
concentrations during control measurements (C),
during ventricular fibrillation (VF), and during
cardiopulmonary resuscitation (CPR). Mean /- SEM
values. Open circles, sodium chloride (NaCl)
controls solid circles, bicarbonate solid
squares, Carbicarb open squares, THAM. up
arrowIndicates the timing of buffer dose
administration
Bar-Joseph, et al., Crit Care Med, Volume
26(8), August 1998, pp 1397-1408.
32
THAM in Acute Lung Injury
KALLET et al., Am. J. Respir. Crit. Care Med.,
Volume 161, Number 4, April 2000, 1149-1153.
33
THAM in Acute Lung Injury
KALLET et al., Am. J. Respir. Crit. Care Med.,
Volume 161, Number 4, April 2000, 1149-1153.
34

• Tromethamine Buffer Modifies the Depressant
  Effect of Permissive Hypercapnia on Myocardial
  Contractility in Patients with Acute Respiratory
  Distress Syndrome
• Several studies have indicated that at the same
  extracellular pH, hypercapnic acidosis induces
  more myocardial depression and decrease in
  intramyocardial pH than metabolic acidosis.
• Hypercapnia causes rapid diffusion of CO2 into
  myocytes, and the resultant intracellular
  acidosis impairs myocardial contractility.
• This explains why attempts to correct respiratory
  acidosis with CO2-generating buffers such as
  sodium bicarbonate may simply worsen
  intramyocardial acidosis.
• Only 12 patients
• THOMAS WEBER, Et al.
• Department of Anesthesiology and General
  Intensive Care, University of Vienna, Austria
  and Department of Anesthesiology, Division of
  Critical Care, College of Physicians and Surgeons
  of Columbia University, New York, New York
• Am. J. Respir. Crit. Care Med., Volume 162,
  Number 4, October 2000, 1361-1365

35
Evaluating a low serum HCO3

• Non-elevated Anion Gap acidosis
• Hyperchloremia
• Failure of the kidney to conserve bicarbonate or
  to secrete H?
• Renal tubular acidosis
• Gastro-intestinal loss of HCO3

36
Disorders Responsible for Hyperchloremic
Acidosis(Normal Anion Gap)

• Gastrointestinal Bicarbonate Loss
• Diarrhea
• Renal Acidification Defects
• Proximal, classical distal RTA, and hyperkalemic
  distal RTA
• Early chronic renal failure
• Ingestion or administration of acid,
  hyperalimentation
• Drugs

37
Evaluating a Low Serum HCO3

• Diarrhea
• Below the pylorus - HCO3 is added to the gut
  with a gain of H to the blood

Proton-secreting cell
Bicarbonate-secreting cell
Gut Lumen
HCO3
H
CO2 H2O ? HCO3 H
CO2 H2O ? HCO3 H
HCO3
H
To Blood
38
Evaluating a Low Serum HCO3

• Renal Tubular Acidosis
• Impaired ammonium excretion can be demonstrated
  by the urine net negative charge (anion gap)
• urine Na urine K urine NH4 urine
  Cl-
• UNa UK - UCl- -UNH4
• Normally UNa UK - UCl- -UNH4 lt -20 in
  the face of acidemia
• In RTAs ammonium excretion is impaired,
  therefore
• In RTAs UNa UK - UCl- -UNH4
  0
• ( range 20 to 80)

39
(No Transcript)
40
Normal physiology of acid excretion Proximal
tubule

• Responsible for reabsorption of the HCO3 filtered
  at the glomerulus bulk reabsorption

Tubular fluid
Blood
HCO3-

H2O
Carbonic anhydrase
Na
Na
CO2 OH-
H OH-
H2O
H
H
HCO3-
Carbonic anhydrase
H2CO3
41
Proximal Renal Tubular Acidosis
Proximal tubule
Distal Nephron / Collecting Duct
H HCO3- CO2 H2O
HCO3-
HCO3-
HCO3-
H secretion and HCO3- regeneration
Impaired (diminished) HCO3- absorption
H
HCO3-
42
Distal RTAs

• Impaired (diminished) H secretion by the distal
  nephron (CCT) will result in either

• Classic Distal RTA
• Direct impairment of H ion secretion or from
  H backleak
• Hyporeninemic Hypoaldosteronemic RTA (Type IV
  RTA)
• Inadequate aldosterone effect

43
Distal RTA
Proximal tubule
Distal Nephron / Collecting Duct
H secretion and HCO3- regeneration
HCO3-
HCO3- H CO2 H2O
HCO3-
HCO3-
A. Impaired (diminished) H secretion hence
diminished HCO3- regeneration
H
B. Back-leak can also diminish H secretion -
AMPHOTERICIN
? NH4 in urine
44
Metabolic Alkalosis
45
Evaluating an elevated Serum HCO3-

• Metabolic alkalosis
• Respiratory acidosis
• Therefore, diagnosis requires a concomitant
  arterial pH.

46
Evaluating an Elevated Serum HCO3-

• Causes of Metabolic Alkalosis
• Effective ECV Contraction resulting in secondary
  Hyperreninemic Hyperaldosteronism
• Hypermineralocorticoidism resulting in ECV
  expansion and Hypertension.
• Exogenous Alkali Loads

47
Evaluating an Elevated Serum HCO3-
Proximal tubule
Distal Nephron / Collecting Duct
Low GFR Impaired HCO3- filtration
H HCO3- CO2 H2O
-
HCO3-
Increased HCO3- absorption
H
HCO3-
48
Evaluating an Elevated Serum HCO3
49
Evaluating an Elevated Serum HCO3
50
Evaluating an Elevated Serum HCO3
51
Treatment of Metabolic Alkalosis

• Low Urine Cl- (lt 20 mEq/L)
• 0.9 NaCl
• Potassium Chloride
• High Urine Cl- (gt25 mEq/L)
• Cause specific (surgery, angioplasty, specific
  drug therapy)

52
Respiratory Acid-Base Disorders
53
Respiratory Acid-Base Disorders

• Alkalosis
• Central nervous system lesions, pregnancy,
  endotoxemia, salicylates, hepatic failure,
  hypoxemia, anxiety, pain

Compensation Respiratory alkalosis
Acute resp alkalosis HCO3 ? 2 mEq/L per 10 mmHg ?
PCO2 Chronic resp acidosis HCO3 ? 5 mEq/L per 10
mmHg? PCO2
54
Respiratory Acid-Base Disorders

• Respiratory Acidosis
• Central - drugs (anesthetics, morphine,
  sedatives), stroke, infection
• Airway - obstruction, asthma
• Parenchyma - emphysema, pneumoconiosis,
  bronchitis, adult respiratory distress
  syndrome
• Neuromuscular - poliomyelitis, kyphoscoliosis,
  myasthenia, muscular dystrophies
• Miscellaneous - obesity, hypoventilation
• Compensation
• Respiratory acidosis Acute respiratory
  acidosis
• HCO3 ? 1 mEq/L per 10 mmHg
  ? PCO2
• Chronic respiratory
  acidosis
• HCO3 ? 4 mEq/L per 10 mmHg
  ? PCO2

55
Normal Lab Values
Sodium (Na) 140 mEq/L Potassium (K)
4.0 mEq/L Chloride (Cl)
100 mEq/L Bicarbonate (HCO3) 24 mEq/L Blood
Gas pH 7.44 PaCO2 40 mmHg Normal
Anion Gap 12
56
35-year-old man admitted to the hospital with
pneumonia and the following lab values
ARTERIAL BLOOD GASES SERUM ELECTROLYTES pH
7.52 Na 145 mEq/L PaCO2 30 mm Hg K 2.9
mEq/L PaO2 62 mm Hg Cl- 98 mEq/L HCO3- 22
mEq/L
Does the patient have an Alkalosis or Acidosis?
Alkalemia, pH is ?
Respiratory the PaCO2 is low as is the HCO3
Is it respiratory or metabolic?
Is the disorder compensated or not?
The answer
57
35-year-old man admitted to the hospital with
pneumonia and the following lab values
ARTERIAL BLOOD GASES SERUM ELECTROLYTES pH
7.52 Na 145 mEq/L PaCO2 30 mm Hg K 2.9
mEq/L PaO2 62 mm Hg Cl- 98 mEq/L HCO3- 22
mEq/L
Does the patient have an Alkalosis or Acidosis?
Alkalemia, pH is ?
Respiratory the PaCO2 is low as is the HCO3
Is it respiratory or metabolic?
Yes, the predicted HCO3 is 22 mEq/L
Is the disorder compensated or not?
How do we know what the HCO3 should be? Remember,
the HCO3 will ? 2 mEq/L for every 10 mmHg the
PaCO2 ? as acute compensation.
Compensated Respiratory Alkalosis
The answer
58
The following values are found in a 65-year-old
patient who has had poor oral intake for the last
week. ARTERIAL BLOOD GASES Serum Electrolytes pH
7.51 Na 155 mEq/L PaCO2 53 mm Hg K 5.5
mEq/L Cl- 90 mEq/L HCO3- 40 mEq/L
Does the patient have an Alkalosis or Acidosis?
Alkalemia, the pH is ?
Metabolic the HCO3 is ? and the PaCO2 is ?
Is it respiratory or metabolic?
Is the disorder compensated or not?
Yes, the PaCO2 should be 55 mmHg
How do we now what the PaCO2 should be? The
predicted PaCO2 should be the HCO3 plus 15. In
this example the HCO3 is 40 thus the PaCO2 should
be near 55.
Compensated Metabolic Alkalosis
The answer
59
68-year-old man with emphysema Arterial blood
gas Serum Electrolytes pH 7.34 Na
138 PaCO2 70 mm Hg K 4.7 Cl-
91 HCO3- 36
Does the patient have an acidosis or alkalosis?
Acidemia
Is it metabolic or respiratory?
Respiratory
Yes, the HCO3 should be 36 mEq/L
Is the respiratory acidosis compensated for?
Remember the HCO3 will ? 4 mEq/L for every 10 mm
Hg ? the PaCO2 in chronic respiratory
acidosis. In this case the PaCO2 ?by 30 mmHg thus
the HCO3 ? by 12 mEq/L In acute respiratory
acidosis the HCO3 will ?1 mEq/L.
The answer
Compensated Respiratory Acidosis
60
What is (are) the acid-base disorder(s) evident
in the following values, from a 27-year-old woman
with acute renal failure? Arterial Blood
Gas Serum Electrolytes pH 7.32 Na 144
mEq/L PaCO2 23 mm Hg K 4 mEq/L Cl - 108
mEq/L HCO3- 10 mEq/L
Does the patient have an acidosis or alkalosis?
Acidemia
Metabolic
Is it metabolic or respiratory?
Now that we have determined a metabolic acidosis,
is the anion gap normal or elevated?
High Anion Gap at 26
Remember the anion gap Na - (HCO3 Cl) and
normal is 12
Now that we have determined a high anion gap what
made the anion gap go up?
The drop in HCO3
So does the drop in HCO3 equal the increase in
the anion gap?
Yes, the ? HCO3 (14) the ? Anion gap (14)
Is the respiratory compensation adequate?
Yes, the PaCO2 should be 23 mmHg
Use Winters Formula to predict the PaCO2 with a
metabolic acidosis 1.5 (HCO3) 8 (?2)
The answer
Compensated High Anion Gap Metabolic Acidosis
61
55-year-old-man seen for newly diagnosed renal
failure Arterial blood gas Serum
chemistries pH 7.38 Na 140 Cr
1.9 PaCO2 30 K 3.2 HGB
8.0 Cl- 115 HCO3- 14
Acidemia
Does the patient have an acidosis or alkalosis?
Is it metabolic or respiratory?
Metabolic
Now that we determined a metabolic acidosis what
do we check next?
The anion gap
The anion gap 11
Remember the anion gap Na - (HCO3 Cl) and
normal is 12
Thus this is a normal anion gap acidosis or a
hyperchloremic acidosis, notice the Chloride is
115 mEq/L.
Is the metabolic acidosis compensated?
Yes, the PaCO2 should be 29
Remember Winters Formula, 1.5 (HCO3) 8 (?2)
The answer
Compensated Hyperchloremic Metabolic Acidosis
62
27-year-old woman with acute renal
failure Arterial blood gas Serum
electrolytes pH 7.12 Na 140 PaCO2 13 mm
Hg K 4.0 Cl- 115 HCO3- 5
Does the patient have an acidosis or alkalosis?
Acidemia
Is it metabolic or respiratory?
Metabolic
So, what is the anion gap?
Anion gap 20
Is the ? anion gap to the ? HCO3?
NO, ? anion gap 8 ? HCO3 19
Thus the ? HCO3 gt the ? anion gap, this means the
HCO3 went down more than the anion gap went up.
Something made the HCO3 drop further, the two
disorders that decrease the HCO3 even further
are Hyperchloremic metabolic acidosis or
compensation for a respiratory alkalosis.
Is the respiratory compensation adequate?
Yes, the predicted PaCO2 15 mmHg
Compensated High Anion Gap Metabolic Acidosis
with a Hyperchloremic Metabolic Acidosis
The Answer
63
19yo college student was found by roommate on
floor. Diaphoretic and comatose. BP 150/80, P
155/min and regular, RR 40/min
152 104 30
ABG 7.42/24/115
3.6 15 1.0
Dont know the pH is normal
Does the patient have an acidosis or alkalosis?
A good place to start is the anion gap
So, where do we start?
The anion gap 33
Thus there is at least a high anion gap metabolic
acidosis
Check the ? HCO3 and ? anion gap
So, now what?
The ? HCO3 24 - 15 9 The ? anion gap 33 -
12 21 Thus they are not equal
The anion gap went up more than the HCO3 went
down. Thus there is something keeping the HCO3 up.
So, what does this mean?
64
19yo college student was found by roommate on
floor. Diaphoretic and comatose. BP 150/80, P
155/min and regular, RR 40/min
152 104 30
ABG 7.42/24/115
3.6 15 1.0
This suggest there is either a Metabolic
alkalosis or a Respiratory acidosis with
compensation, both will cause the HCO3 to be high
So, we determined the ? anion gap gt ? HCO3
So, check Winters formula to determine the
respiratory compensation. 1.5 (HCO3) 8
The predicted PaCO2 is 30 This is higher than the
measured PaCO2, thus the patient has a
respiratory alkalosis
High anion gap met acidosis with met alkalosis
with resp alkalosis
The answer