abg und re standing the principles
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ACID BASE EVALUATION:ACID BASE EVALUATION:
Nauman Tarif, MDNauman Tarif, MD
Associate ProfessorAssociate Professor
SIMSSIMS
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ACIDS AND BASESACIDS AND BASES
Using the definitions proposed byUsing the definitions proposed by
BronstedBronsted
An acid is a substance that canAn acid is a substance that candonate H+ ionsdonate H+ ions
A base is a substance that canA base is a substance that can
accept H+ ionsaccept H+ ions
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H2CO3 H+ + HCO3-
HCl H+ + Cl-
NH4+ H+ + NH3
H2PO4- H+ + HPO42-
Acid Base
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pHpH
What is pH ?What is pH ?
P French word Pvissance (power)P French word Pvissance (power)
Meaning power of hydrogenMeaning power of hydrogen
Def: -ve log of [H+] conc. i.e.minus no. toDef: -ve log of [H+] conc. i.e.minus no. to
which 10 must be raised to get that no.which 10 must be raised to get that no.
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pH ScalepH Scale
7 (neutral)7 (neutral)
||0 --------------------------------------------------140 --------------------------------------------------14
|| alkalinealkaline
7.40(Blood)7.40(Blood)pH< 7.35Acidosis
pH > 7.45
Alkalosis
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Acid-Base DisordersAcid-Base Disorders
Blood PH 7.4Blood PH 7.4
HH++ = 40 x 10= 40 x 10-9-9 = 40 nmol/L= 40 nmol/L
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AcidsAcidsHH++ ionsions or proton donoror proton donor
Two types of acids are formed byTwo types of acids are formed by
metabolic processesmetabolic processes
Volatile acids:Volatile acids: liquidliquid gas. COgas. CO22eliminated by lungs.eliminated by lungs.
COCO22 + H+ H22OO HH22COCO33 HH++ + HCO+ HCO33 NonvolatileNonvolatile or fixed acids: are eliminatedor fixed acids: are eliminated
by the kidneysby the kidneysExamples: SOExamples: SO44, PO, PO44, lactic acid, ketoacids, lactic acid, ketoacids
TheThe non-volatile portion is trivialnon-volatile portion is trivial whenwhen
compared to the volatile COcompared to the volatile CO22.About 50-100.About 50-100
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H+ isH+ is maintained within narrowmaintained within narrowlimits.limits.
Normal LevelNormal Level approx.40 nanomol/Lapprox.40 nanomol/LLow Conc.Low Conc. Essential for normalEssential for normalcellular fxn.cellular fxn.
Changes in the H+ conc.,Changes in the H+ conc., proteinsproteinsgain or lose H+ ions.gain or lose H+ ions.
resulting in:resulting in:
alteration in charge distributionalteration in charge distributionmolecular configurationmolecular configuration
protein functionprotein function
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pH change RegulationpH change Regulation
The bodyThe body constantly produces acidsconstantly produces acids throughthroughmetabolismmetabolism
These acids must beThese acids must be constantly eliminatedconstantly eliminatedfrom the bodyfrom the body
BuffersBuffersChemical substance that prevents largeChemical substance that prevents largechanges in pHchanges in pH
VentilationVentilation
Can handle ~75% of most pH disturbancesCan handle ~75% of most pH disturbances
Renal regulationRenal regulation of Hof H++ & HCO& HCO33--
slow but very effectiveslow but very effective
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Acid-Base LoadAcid-Base Load
Addition from extrinsic source:Addition from extrinsic source:
Infusions [eg HCl, NH4Cl]Infusions [eg HCl, NH4Cl]
Intrinsic sources:Intrinsic sources: Acid generation: ketoacidosis, LacticAcid generation: ketoacidosis, Lacticacidosisacidosis
Acid loss: VomitingAcid loss: Vomiting
Base loss: DiarrheaBase loss: Diarrhea
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HENDERSON-HASSELBACHHENDERSON-HASSELBACH
EQUATIONEQUATION
pH = pKa + logpH = pKa + log basebase
acidacid
When ph and pKa are equal: 50% exists as Base
& 50% as Acid
HA H+ + A-Law of Mass Action: at Equilibrium reactions are equal
Strong Acid: Completely ionized at ph= 7.4
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weak acids, are able to
take up or release H+ sothat changes in the free H+
concentration areminimized
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HPO4(2-) + H+ H2PO4-
pKa= 6.8
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[HPO4-]
pH = PKa [H2PO4
(2-) ]
10
= 160 x = 160 nanomol/L (pH=6.80)
10
pKa= 6.8 At pH=7.4[HPO4-] : 80%
[H2PO4-]: 20%
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Addition of Acid:Large changes in H+
concentration are prevented by:
Buffering
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HCl + Na2HPO4 > NaCl + NaH2PO4
It was possible because the Na2HPO4 can beionized as pk is close to the physiological Ph 7.4
pK= 6.8 and so can bind the H ions and make aweaker acid and thus nullify the effect of HCL
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12
H + = 6.8 x = 240 nanomol/L (pH =6.62)8
pH = 2.7
If all H+ taken up by HPO4 then
[HPO4-][H2PO4
(2-) ]
If No Buffer
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[CO2]dis + H2O H2CO3 H+ + HCO3-
[H+] [HCO3-]
Ka =
[CO2]dis [H2O]
[H+] [HCO3-]
K'a =
[CO2]dis
PCO2
pH = 24 x
[HCO3-]
pKa x [CO2]dis
pH =
[HCO3-]
At Physiological pH
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BufferBuffer
There are four main buffer systems inThere are four main buffer systems inthe body:the body: Bicarbonate buffer system. (the MAIN one)Bicarbonate buffer system. (the MAIN one)
64%64%
NaHCONaHCO33 HH22COCO33COCO22
Hemoglobin buffer system. 29%Hemoglobin buffer system. 29%
HbOHbO22-- HHbHHb
Protein buffer system. 6%Protein buffer system. 6%PrPr-- HPrHPr
Phosphate buffer system. 1%Phosphate buffer system. 1%
NaNa22
HPOHPO44
NaHPONaHPO44
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Open buffer systemOpen buffer system
[CO2]dis + H2O H2CO3 H+ + HCO3-
Add AcidExpired Gas
At physiologic pH of 7.4: HCO3 : H+ 20:1
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Primary and Secondary DisordersPrimary and Secondary Disorders
Primary:Primary: Respiratory:Respiratory: AcidosisAcidosis
AlkalosisAlkalosis
Metabolic:Metabolic: AcidosisAcidosisAlkalosisAlkalosis
Secondary:Secondary: Respiratory:Respiratory: AcidosisAcidosis
AlkalosisAlkalosis Metabolic:Metabolic: AcidosisAcidosis
AlkalosisAlkalosis
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Two classes of acids are physiologically
important:
Carbonic acid (H2CO3) &
non-carbonic acids.
Metabolism ofcarbohydrates and fats
results in the generation of
approximately 15,000 mmol ofCO2/Day
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COCO22 + H+ H22OOHH22COCO33 H+ + HCOH+ + HCO33
This is prevented by the loss of CO2 via
Via lungs
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Noncarbonic acids:
Primarily derived from themetabolism of proteins
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CO2 + H2O H2CO3 H+ + HCO3 HCO3-
H2CO3 : HCO3= 1 : 6800
At Physiological pH
H2CO3 : PCO2= 1: 340
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The primary intracellular buffers are proteins,
organic and inorganicphosphates,
and,
in the erythrocyte, hemoglobin (Hb-):
H+ + Hb- HHb
H+ + Pr- HPr
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H+ + Hb- HHb
H+ + Pr- HPr
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Bone:
Important site of acid and base buffering
Exchange for surface Na+ and K+,Dissolution of bone mineralRelease of buffer compounds:
NaHCO3 & KHCO3 initiallyThen CaCO3 and CaHPO4,
This buffering reaction appears to be initiated
in part by the fall in the plasma HCO3-concentration
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Methionine > glucose + urea + SO4(2-) + 2 H+
Arginine+ > glucose (or CO2) + urea + H+
R-H2PO4 + H2O > ROH + 0.8 HPO42- / 0.2 H2PO4- + 1.8 H+
Glutamate- + H+ > glucose + urea
Citrate- + 4.5 O2 > 5 CO2 + 3 H2O + HCO3-
Lactate- + H+ > glucose + CO2
Increasing the pH/ Alkalosis/ Decreasing H+
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Glutamate- + H+ > glucose + urea
Citrate- + 4.5 O2 > 5 CO2 + 3 H2O + HCO3-
Lactate- + H+ > glucose + CO2
Increasing the pH/ Alkalosis/ Decreasing H+
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(1)Reabsorption of the filtered HCO3-
(1)Excretion of the 50 to 100 meq of H+
produced per day
Renal Actions
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A normal subject
GFR: 180 L/day (125 mL/min)
plasma HCO3- concentration of24 meq/L
filters & then must reabsorb
approximately 4300 meq of HCO3- each day
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The lowest urine pH that can be achieved inhumans is 4.5.
Almost 1000 times (3 log units) more acid thanthe extracellular pH,
Still extremely low free H+ concentration of lessthan 0.04 meq/L.
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Secretion of each H+ ion is associated with
the generation of one HCO3- ion in the plasma.
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steady state, the net amount of H+ excreted is equal to the
normal H+ load of50 to 100 meq/day
This value can exceed 300 meq/day (primarily due to enhanced
NH4+ excretion) if acid production is increased
Secretion of each H+ ion is associated with
the generation of one HCO3- ion in the plasma.
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Proximal Tubular CellProximal Tubular Cell
2K
H2O OH + CO2
H+H+ CA
3HCO3 HCO3
BloodTubular Lumen
Na+
Na+
3Na+
2K
Na K AtPase
HCO3 +
H2O + CO2
Renal Tubular Acidosis: Proximal RTA
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Distal acidification
H+ secretion in the distal nephron primarily
occurs in the
intercalated cells in the cortical collecting
tubule
and in the cells in the outer and innermedullary collecting tubules
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-Intercalated Cells of Cortical-Intercalated Cells of CorticalCollecting Collecting TubuleCollecting Collecting Tubule
H+ H+
K K
H2O OH
H+H+
H-ATPase
CA
HCO3
Cl
Cl
HCO3
BloodTubular Lumen
Cl
Renal Tubular Acidosis: Distal RTA
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H2OOH
H+H+
H-ATPase
CA
HCO3
Cl
HCO3
BloodTubular Lumen
Cl Cl
-Intercalated Cells of Cortical-Intercalated Cells of CorticalCollecting Collecting TubuleCollecting Collecting Tubule
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Glutamine NH4+ + glutamate-
NH4+ + alpha-ketoglutarate(2-)
AMMONIUM EXCRETION
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AcidosisAcidosis
So what kind of metabolic acidosis is it?So what kind of metabolic acidosis is it?
LossLoss of HCO3 orof HCO3 orgaingain of intrinsic orof intrinsic or
extrinsic Acidsextrinsic Acids
CalculateCalculate anion gapanion gap: 8-16(normal): 8-16(normal)
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Anion Gap [AG]
Na= 139 Cl= 103 HCO3=24
AG = [+VE] [-VE]
Ca, Mg, K= So4 , PO3
Na - [Cl+HCO3] =
139 - [103+ 24] =
139 - 127 = 12
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What is AG of 12 ?
All charges POSITIVE = Negative
Some other [ ve] charges
that we could not estimate from our lab
These [ ve] charges are forAlbumin
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Causes of High AG MA:
M
U
D
P
I
L
E
S
Methanol [Formate]
Uremia [SO4, Pho3, other]
DKA [Acetoacetate, -OH Butyrate]
Paraldehyde [unknown/Acetic Acid]
Isopropyl Alcohol [Lactate]
Lactic Acidosis [Lactate]
Ethylene Glycol [Oxalate, Glycolate]
ASA [Lactate & Ketoacids]
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Osmolal Gap:
Addition of solute the P Osmolality
Measured Osmol - Calculated Osmol = < 20[Nml]
Calculated Osmol =
2 x Na + Urea + Glucose= mmol/L
Causes ofCauses ofOsmol GapOsmol GapEthanol
Methanol
Ethylene Glycol
Isopropyl Alcohol
B i R l f thAcid Base Evaluation: Summary
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Basic Rules of the game
AG, CO2, HCO3, pH
1: PH=7.4 CO2 =40 HCO3 =24
2: HCO3 < 13 Definitely Metabolic Acidosis
3: Anion Gap [AG]
AG >20 Metabolic Acidosis Definitely
AG 12-20 MA Or MAlk
IF YOU FOLLOW THE RULES
Mixed Acid Base Disorder evaluation is easy!
Clinical Picture
AG, HCO3, PCO2, pH, Osmolal Gap
Osmolal Gap: Addition of solute will the plasma OsmolalityMeasured Osmolality - Calculated Osmolality = Nml < 20
Calculated Osmolality=2Na + Urea + Glucose= All in mmol/L
Metabolic Acidosis
1. Last 2 digits of pH 7.25: CO2 = 25
2. Expected PCO2 = HCO3 X 1.2[Limit: Max PCO210 mm of Hg]
12-24 Hours for compensation
Metabolic Alkalosis
Expected PCO2 = 0.7 X HCO324-36 hrs for respiratory compensation
Limit: Max PCO2 55 mm of Hg
Chronic Respiratory Acidosis
10 PCO2 = 4 HCO3- [ Chronic RA]5-10 Days for Metabolic Compensation Max : 45 meq/L
Acute Respiratory Alkalosis
10 PCO2 = 2 HCO3 ,5-10 minutes for Compensation Max : 18 meq/L
Acute Respiratory Acidosis
10 PCO2 = by 1 HCO35-10 minutes for Compensation Max : 30 meq/L
Chronic Respiratory Alkalosis
10 PCO2 = 4 HCO32-3 Days for Metabolic Compensation Max : 14 meq/L
Acid Base Evaluation: Summary
Nauman Tarif, MD
AG / HCO3 = 1-1.6
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Primary Disorder
Acidosis or Alkalosis
If it is Respiratory thenRenal [metabolic] compensation
Respiratory Disorders:
Breathe Too MUCH!
Breathe Too LESS!
Respiratory Alkalosis
Respiratory Acidosis
H2O + CO2 H2CO3 H+ + HCO3
H+ + HCO3 H2CO3 H2O + CO2
M b li Di d
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Metabolic Disorders
Add Acid or Lose HCO3 Metabolic Acidosis
Add Alkali or Lose Acid Metabolic Alkalosis
If it is Metabolic then
Respiratory compensation
Compensatory responses
will not bring the pH to normal;
always close towards normal.
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In the presence ofNORMAL pH
IT IS A MIXED Disorder!
AT least 2 primary disorders
Human environment is Dynamic !
Abnormal CO2 or HCO3
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Pulmonary Embolus Respiratory Alkalosis
Shock Metabolicacidosis
Pulmonary edema RespiratoryAlkalosis
Renal Failure MetabolicAcidosis
Sepsis RespAlk+ MetAcid
COPD Respiratoryacidosis
Diuretic Use MetabolicAlkalosis
Cirrhosis RespiratoryAlkalosis
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42 y/o male found unconsciuos in the desert
[lost his way for the last 2 days] with an empty bottle
BP& bilateral chest creptsAG 144 -[97+10]= 37 HAGMA
PCO2 35 14 X 1.2 = 16.8 , [40-17 = 23 ]
So PCO2 should be 25 Here PCO2 is 35
So Something is keeping the PCO2RA
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In an unconscious pt with no clear cut history and MA
MUST Exclude: Ingestion [empty bottle!]
Gap: Osmolal Gap
Measured - Calculated Osmolality > 20 [Ingestion]
Methanol, Ethylene Glycol and Isopropyl Alcohol
Osmolal gap = 29 MSU : CaOxalate Crystals
Ethylene Glycol Intoxication
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Gap of the Gaps
Delta AG : Delta HCO3
37-12 : 24-10
25 : 14
1. 8 : 1 [ >1.6]
So Something is keeping the HCO3MAlkHe apparently had Vomiting after ingestion of EthGlycol
HAGMA + RA + MAlk
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pH 7.28
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Management Guidelines:
1. Treat the Clinical state
2. Metabolic Acidosis:
pH to 7.2 & HCO3 >10
[Prevent CVS Instability]
3. Metabolic Alkalosis
Fluid for Cl responsive
Acetazolamide
IV HCL, NH4Cl, ArgHCl
4. Respiratory Acidosis :
5. Respiratory Alkalosis
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Management Guidelines:
1. Treat the Clinical state
2. Metabolic Acidosis:
pH to 7.2 & HCO3 >10
[Prevent CVS Instability]
3. Metabolic Alkalosis
Fluid for Cl responsive
Acetazolamide
IV HCL, NH4Cl, ArgHCl
4. Respiratory Acidosis :
5. Respiratory Alkalosis