Metabolic AcidosisResidents Conference11/1/01Romulo E. Colindres, MD

Primary Acid-Base DisordersDisorder pHHCO3- pCO2

Metabolic Acidosis

Metabolic Alkalosis

Respiratory Acidosis

Respiratory Alkalosis

Compensatory Responses toPrimary Acid-Base Disorders

Disorder

Primary Change

Compensatory Response

Metabolic acidosis

Fall in plasma bicarbonate

For every 1 mEq/L decrease in bicarbonate,

the pCO2 falls by 1.2 mmHg

Metabolic alkalosis

Rise in plasma bicarbonate

For every 1 mEq/L rise in bicarbonate,

the pCO2 rises 0.6-0.7 mmHg

Respiratory acidosis

Rise in pCO2

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

Respiratory alkalosis

Fall in pCO2

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 GapNa+140HCO3-24

Cl-104Proteins 16Organic Acids 5 PO4 SO4 3K 5Ca 5Mg 2Cations AnionsNa+140HCO3-24

Cl-104AG 12AG = Na+ - (Cl+HCO3)

CAUSES OF METABOLIC ACIDOSISExcessive Acid ProductionEndogenousExogenous

Bicarbonate WastingDiarrheaRenal (Type 2 RTA)

Decreased Excretion of Acid (Impaired NH4+ excretion)Renal FailureImpaired Distal Acidification (RTA 1)Hypoaldosteronism (RTA 4)

Combination of Above

METABOLIC ACIDOSIS: INDICIS OF SEVERITYpH

Acid ProductionCarbohydrates/Fats 15,000 mmol/d CO2 (Volatile acid)CO2 + H20 H2CO3 H+ + HCO3-LungsProteins 50-100 mEq/d H2SO4 (Fixed Acid)H+ + HCO3- H2CO3H+ + Intracellular Base- HBaseH+ excretion in the kidneyLimits rise in [H+]

RENAL EXCRETION OF ACIDThe kidneys must excrete 50 to 100 mEq of acid to regenerate the bicarbonate used to buffer the fixed acid generated from metabolism each dayThe 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 (

Proximal Tubule: Bicarbonate Reabsorption3Na+2K+PeritubularcapillaryTubular lumenATPaseH+OH- + CO2H2O HCO3-CANa+Na+H+ HCO3- +H2CO3CO2 + H2OCANa+HCO3-

Proximal Tubule: Titratable Acid3Na+2K+PeritubularcapillaryTubular lumenATPaseH+OH- + CO2H2O HCO3-CANa+Na+H+Na+HCO3-HPO42- +H2PO4-

Collecting Duct -Intercalated Cell: Titratable Acid

Peritubularcapillary

Tubular lumen

ATPase

H+

OH- + CO2

H2O

HCO3-

CA

Cl-

HPO42- + H+

H2PO4-

HCO3-

Cortical Collecting Duct-Ammonium Trapping

3Na+

2K+

Peritubularcapillary

Tubular lumen

ATPase

ATPase

H+

NH3

+NH3

NH4+

H+

OH- + CO2

H2O

HCO3-

CA

Cl-

3Na+2K+PeritubularcapillaryTubular lumenNH4+Na+NH4+GlutamineGlutamate-GlutaminaseNa+NH4+2Cl-NH4+NH3ATPaseH+ NH3 +NH4+Ammonia Synthesis and TransportATPase

Renal Acid-Base Regulation4000 mEq HCO3- filtered in proximal tubule must be reabsorbed - no net acid excretionMinimal 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/dayH+ is excreted in the form of urinary buffers, H2PO4- and NH4+

METABOLIC ACIDOSIS WITH INCREASED ANION GAPNaHCO3 + 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 KetoacidsNa+140Cl-105HCO3 10Ketoacid 13Pr, OA, P,S12Anion Gap = 25pH = 7.25HCO3 = 10pCO2= 25AG = 25

Differential Diagnosis of AG Metabolic Acidosis Methanol poisoningUremia (advanced, SO4, PO4)Diabetic ketoacidosis-Other ketoses EtOH StarvationParaldehyde (rare)Ischemia-LactateEthylene glycolSalicylate 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

Methanol Intoxication

Ethylene Glycol

Osmolar Gap < 25 mOsm/Kg

Alcoholic Ketoacidosis

Diabetic Ketoacidosis

Lactic Acidosis

Salicylate Toxicity

Methanol/Ethylene Glycol in Late Phase

KETOACIDOSIS EVOLVES FROM HIGH AG NL. AG ACIDOSISGFRINSULIN

LIVER

H+ Ket

+

Na HCO3

Na Ket

URINE

BLOOD

MUSCLE

Na Ket Reabsorption

Maintains High AG

Na Ket

+

H2O Excretion

Na Ket (NaHCO3

(Na + H2O

W/out Cl

(AG,(Cl

S HCO3,(

but not to nl

S AG (

to nl

HYPERCHLOREMIC METABOLIC ACIDOSISHCL + NaHCO3---> NaCl and H2CO3--->CO2 +H2O Therefore: anion gap unchanged since [Na] - (increased [Cl] + decreased [HCO3]).Loss of HCO3 in stoolLoss 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 DiarrheaNa+140HCO3 15Cl-113AG 12pH= 7.32HCO3-= 15pCO2= 30AG= 12

URINE ANION GAP:AN INDIRECT MEASUREMENT OF NH4+ EXCRETION IN HYPERCHLOREMIC METABOLIC ACIDOSISUrine Anion Gap: [Na] + [K] - [Cl]Since: [Na] + [K] + Unmeasured (U) Cations =[Cl] + Unmeasured (U) AnionsTherefore, [Na] + [K] - [Cl]= U Anions- U CationsU Anions = Sulfates, Phosphates, etc.U Cation = Mainly NH4+Normal Value: 0Hyperchloremic Metabolic Acidosis: -20 to -50 = Appropriately Increased NH4+ Excretion

Practical Approach (Hyperchloremic metabolic acidosis)Urine Anion Gap

Negative PositiveType 2 RTADiarrheaDKA/TolueneHCl (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 RTAType 1 (secretory defect Type 1 (voltage)Early CRF or back-leak)

METABOLIC ACIDOSIS:BICARBONATE THERAPYAvoid 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-]2520151057.107.207.307.40pH[HCO3-] meq/LSmall changes in [HCO3-] cause large changes in pH

Therapy in Patients with Severe AcidosisInitial goal is to raise the pH to ~7.20decreased risk of arrhythmiasimproved cardiac contractility and responsiveness to catecholaminesFurther correction is generally not necessary acutelymay cause volume overloadmay reduce O2 delivery to the tissuesmay result in hypercarbia

METABOLIC ACIDOSIS:BICARBONATE THERAPYRapid I.V. administration of HCO3 is important only in patients with severe metabolic acidosisSerial Measurements of [HCO3]Give oral HCO3 if possibleAssume volume of distribution of HCO3 to be 50% of lean body weight

METABOLIC ACIDOSIS: BICARBONATE THERAPYChronic 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/dayChronic RTA 1: 1-2 mEq/Kg/day of Na-K citrate after increasing [HCO3] to desired levelRTA 2: 10-15 mEq/Kg/dayRTA 4: Correct hyperkalemia

Normal [H+]40 nanoequivalents per liter

One-millionth the concentration of sodium, potassium and chloride

Modified Henderson-Hasselbach Equation[H+] = 24pCO2[HCO3-]

Bicarb-CO2 System in Response to H+ Load30 mEq H+ ECF24 mEq/L HCO3-ECF22 mEq/L HCO3-30 mmol CO2 = 2 mmol/L CO2Dissolved CO2 1.2 mmol/L + 2 mmol/L = 3.2 mmol/L pCO2 107 mmHg[H+] = 2410722= 116 nEq/L pH = 6.94 [H+] = 243722= 39 nEq/L pH = 7.396No change in VE. VE.

Change in Tubular Fluid pHD pHD pH0.200.40.81.20.200.40.81.21.62.02.4 0 20 40 60 80 100Proximal Tubule, %Distalconvolution,%0 100UreteralurineGottschalk CW, Lassiter WE, Mylle M, Am J Physiol, 198:581, 1960.

Decreased Efficacy of Respiratory Compensation with Worsening AcidosisConditionHCO3-pCO2 H+pH

Normal 24 40407.40

Moderately 15 30507.30 Severe

Life Threatening 5 201007.00