Transcript Metabolic Acidosis

Metabolic Acidosis
Residents’ Conference
11/1/01
Romulo E. Colindres, MD
Primary Acid-Base Disorders
Disorder
Metabolic Acidosis
Metabolic Alkalosis
Respiratory Acidosis
Respiratory Alkalosis
pH
HCO3-
pCO2
Compensatory Responses to
Primary Acid-Base Disorders
Disorder
Metabolic acidosis
Primary Change
Fall in plasma bicarbonate
Metabolic alkalosis
Rise in plasma bicarbonate
Respiratory acidosis
Rise in pCO2
Respiratory
alkalosis
Fall in pCO2
Compensatory Response
For every 1 mEq/L decrease in
bicarbonate,
the pCO2 falls by 1.2 mmHg
For every 1 mEq/L rise in bicarbonate,
the pCO2 rises 0.6-0.7 mmHg
Acute:
For every 10 mmHg rise in pCO2, the
bicarbonate rises 1 mEq/L
Chronic:
For every 10 mmHg rise in pCO2, the
bicarbonate rises 3.5 mEq/L
Acute:
For every 10 mmHg fall in pCO2, the
bicarbonate falls 2 mEq/L
Chronic:
For every 10 mmHg fall in pCO2, the
bicarbonate falls 4 mEq/L
SERUM ANION GAP
[Na + K] + Unmeasured Cations =
[Cl + HCO3] + Unmeasured Anions
[Na + K] - [Cl + HCO3] =
Unmeasured Anions (UC) - Unmeasured Cations
(UC) .
CAN OMIT K.
[Na] - [Cl + HCO3) = UA-UC; Normal Value:
10+/- 2mEq/L. Increase in anion gap usually
indicates an increase in unmeasured anions:
albumin, PO4, SO4, anions of organic acids.
Anion Gap
Proteins 16
K5
Ca 5
Mg 2
Organic Acids 5
PO4 SO4 3
AG 12
HCO324
Na+
140
HCO324
Na+
140
Cl104
Cations Anions
Cl104
AG = Na+ - (Cl+HCO3)
CAUSES OF METABOLIC ACIDOSIS
1 Excessive Acid Production
• Endogenous
• Exogenous
2 Bicarbonate Wasting
• Diarrhea
• Renal (Type 2 RTA)
3 Decreased Excretion of
Acid (Impaired NH4+
excretion)
• Renal Failure
• Impaired Distal Acidification
(RTA 1)
• Hypoaldosteronism (RTA 4)
4 Combination of Above
METABOLIC ACIDOSIS:
INDICIS OF SEVERITY
•
•
•
•
pH <7.2
[HCO3] < 10mEq/L
Massive continuous production of acid
Poor respiratory compensation ( pCO2
fall less than 1.25 mm Hg for each
mEq/L fall in HCO3 concentration)
Acid Production
• Carbohydrates/Fats  15,000 mmol/d CO2 (Volatile acid)
CO2 + H20  H2CO3  H+ + HCO3-
Lungs
• Proteins  50-100 mEq/d H2SO4 (Fixed Acid)
– H+ + HCO3-  H2CO3
– H+ + Intracellular Base-  HBase
– H+ excretion in the kidney
Limits rise in [H+]
RENAL EXCRETION OF ACID
• The kidneys must excrete 50 to 100 mEq of acid to
regenerate the bicarbonate used to buffer the fixed acid
generated from metabolism each day
• The daily acid load cannot be excreted unless all of the
filtered HCO3 is reabsorbed
• Excretion of an acid urine is a necessary but not sufficient
condition to excrete the daily acid load: free H+
concentration in the urine is very low (<0.05mEq/L) in a
maximally acid urine
• Acid excretion comes from H+ secretion and binding to
NH4+ and phosphate
Proximal Tubule: Bicarbonate Reabsorption
Tubular lumen
Na+
Peritubular
capillary
3Na+
HCO3- + H+
H+
ATPase
2K+
H 2O
H2CO3
CA
CO2 + H2O
OH- + CO2
HCO3CA
Na+
HCO3Na+
Proximal Tubule: Titratable Acid
Tubular lumen
Na+
Peritubular
capillary
3Na+
HPO42- + H+
H+
ATPase
2K+
H 2O
H2PO4-
OH- + CO2
HCO3CA
Na+
HCO3Na+
Collecting Duct -Intercalated Cell: Titratable Acid
Tubular lumen
HPO 42- + H+
ATP ase
Peritubular
capillary
H+
H 2O
OH- + CO 2
HCO3 CA
H 2PO 4-
HCO3 Cl -
Cortical Collecting Duct-Ammonium “Trapping”
Tubular lumen
H+
+
NH3
ATP ase
Peritubular
capillary
H+
3Na+
ATP ase
H 2O
2K+
OH- + CO 2
HCO3 CA
NH4+
NH3
Cl-
Ammonia Synthesis and Transport
Na+
NH4 +
2ClTubular lumen
Na+
NH4
+
NH4
+
Peritubular
capillary
3Na+
ATPase
2K+
GlutamateGlutaminase
Glutamine
NH4+
NH3
NH3
+
H+ ATPase
NH4+
Renal Acid-Base Regulation
• 4000 mEq HCO3- filtered in proximal tubule must
be reabsorbed - no net acid excretion
• Minimal urine pH is 4.5 only 40-80 mol per
day can be excreted as free H+; Excretion of the
daily acid load as free H+ would require 2000
liters of urine output/day
– H+ is excreted in the form of urinary buffers,
H2PO4- and NH4+
METABOLIC ACIDOSIS
WITH INCREASED ANION
GAP
NaHCO3 + Lactic acid--->Na Lactate +
CO3H2----> [Na] - [Cl +HCO3 + Lactate]
• Usually caused by increased production of
endogenous or exogenous organic acid
• Salt (anion) may be quickly metabolized or
excreted yielding a hyperchloremic acidosis
 Gap Metabolic Acidosis
Due to Presence of Ketoacids
pH
HCO3
pCO2
AG
= 7.25
= 10
= 25
= 25
Pr, OA, P,S
12
Ketoacid 13
HCO3 10
Na+
140
Cl105
Anion Gap = 25
Differential Diagnosis of
AG Metabolic Acidosis
Methanol poisoning
Uremia (advanced, SO4, PO4)
Diabetic ketoacidosis -Other ketoses
EtOH
Starvation
Paraldehyde (rare)
Ischemia-Lactate
Ethylene glycol
Salicylate toxicity
DIFFERENTIAL DX OF  ANION
& OSMOLAR GAP ACIDOSES
Anion Gap >16
Alcoholic Ketoacidosis
Diabetic Ketoacidosis
Lactic Acidosis
Salicilate Toxicity
Methanol/Ethylene Glycol
Osmolar Gap < 25 mOsm/Kg
Alcoholic Ketoacidosis
Diabetic Ketoacidosis
Lactic Acidosis
Salicylate Toxicity
Methanol/Ethylene Glycol in Late Phase
Osmolar Gap >25 mOsm/Kg
Methanol Intoxication
Ethylene Glycol
KETOACIDOSIS
EVOLVES FROM HIGH AG  NL. AG ACIDOSIS
Na + H2O
W/out Cl
AG,Cl
LIVER
H+ Ket
+
Na HCO3
BLOOD
Na Ket
MUSCLE
URINE
Na Ket
+
H2O Excretion
Na Ket Reabsorption
Maintains High AG
Na Ket NaHCO3
 S HCO3,
but not to nl
 S AG 
to nl
HYPERCHLOREMIC
METABOLIC ACIDOSIS
HCL + NaHCO3---> NaCl and H2CO3--->
CO2 +H2O Therefore: anion gap unchanged since
[Na] - (increased [Cl] + decreased [HCO3]).
• Loss of HCO3 in stool
• Loss of HCO3 in urine (RTA 2)
• Decreased excretion of NH4 (RTA 1 and 4 and
renal failure)
• Increased production of acid but prompt excretion
of anion (treatment of DKA, toluene)
Normal Anion Gap Metabolic Acidosis in a
Patient with Diarrhea
AG 12
pH
HCO3pCO2
AG
= 7.32
= 15
= 30
= 12
HCO3 15
Na+
140
Cl113
URINE ANION GAP:AN INDIRECT
MEASUREMENT OF NH4+
EXCRETION IN HYPERCHLOREMIC
METABOLIC ACIDOSIS
Urine Anion Gap: [Na] + [K] - [Cl]
Since: [Na] + [K] + Unmeasured (U) Cations =
[Cl] + Unmeasured (U) Anions
Therefore, [Na] + [K] - [Cl]= U Anions- U Cations
U Anions = Sulfates, Phosphates, etc.
U Cation = Mainly NH4+
Normal Value: 0
Hyperchloremic Metabolic Acidosis: -20 to -50 =
Appropriately Increased NH4+ Excretion
Practical Approach
(Hyperchloremic metabolic acidosis)
Urine Anion Gap
Negative
Positive
Type 2 RTA
Diarrhea
DKA/Toluene
HCl (Hyperalimentation)
Urine pH and Plasma K
Urine pH < 5.5, K 
Urine pH > 5.5, K nl/low
Urine pH > 5.5, K 
Type 4 RTA
Early CRF
Type 1 (secretory defect
or back-leak)
Type 1 (voltage)
METABOLIC
ACIDOSIS:BICARBONATE
THERAPY
• Avoid if metabolic acidosis is transient and
moderate and renal function is adequate,
particularly with increased anion gap acidosis,
since anions of organic acids can regenerate
HCO3
• Only a small inmediate increase (2-3 mEq/L) in
plasma [HCO3] is necessary to get patient out of
danger if there is normal respiratory compensation
Relationship Between pH and [HCO3-]
[HCO3-] meq/L
25
20
15
Small changes in [HCO3-] cause
large changes in pH
10
5
7.10
7.20
pH
7.30
7.40
Therapy in Patients with Severe Acidosis
• Initial goal is to raise the pH to ~7.20
– decreased risk of arrhythmias
– improved cardiac contractility and responsiveness
to catecholamines
• Further correction is generally not necessary acutely
– may cause volume overload
– may reduce O2 delivery to the tissues
– may result in hypercarbia
METABOLIC
ACIDOSIS:BICARBONATE
THERAPY
• Rapid I.V. administration of HCO3 is
important only in patients with severe
metabolic acidosis
• Serial Measurements of [HCO3]
• Give oral HCO3 if possible
• Assume volume of distribution of HCO3 to
be 50% of lean body weight
METABOLIC ACIDOSIS:
BICARBONATE THERAPY
• Chronic renal failure: HCO3, not citrate to avoid
Aluminum absorption. Give a large dose for
several days to achieve a [HCO3] of
approx.20mEq/L. Maintenance dose of about 40
mEq/day
• Chronic RTA 1: 1-2 mEq/Kg/day of Na-K citrate
after increasing [HCO3] to desired level
• RTA 2: 10-15 mEq/Kg/day
• RTA 4: Correct hyperkalemia
Normal [H+]
40 nanoequivalents per liter
 One-millionth the concentration of
sodium, potassium and chloride
Modified Henderson-Hasselbach Equation
[H+] = 24
pCO2
[HCO3-]
Bicarb-CO2 System in Response to H+ Load
30 mEq H+
ECF
24 mEq/L
HCO3-
ECF
22 mEq/L
HCO3-
30 mmol CO2 = 2 mmol/L CO2
Dissolved CO2 1.2 mmol/L + 2 mmol/L = 3.2 mmol/L  pCO2 107 mmHg
.
107
No change in VE [H+] = 24 22 = 116 nEq/L  pH = 6.94
37 = 39 nEq/L  pH = 7.396
 VE [H+] = 24
22
.
Change in Tubular Fluid pH
Distal Ureteral
convolution, urine
%
0
100
0 20 40 60 80 100
Proximal Tubule, %
D pH
0.2
0
0.2
0
0.4
0.4
0.8
0.8
1.2
1.2
D pH
1.6
2.0
2.4
Gottschalk CW, Lassiter WE, Mylle M, Am J Physiol, 198:581, 1960.
Decreased Efficacy of Respiratory
Compensation with Worsening Acidosis
HCO3-
pCO2
H+
pH
Normal
24
40
40
7.40
Moderately
Severe
15
30
50
7.30
Life Threatening
5
20
100
7.00
Condition