Pathobiochemistry and diagnostics of acid -base and ...Astrup pH – glass electrode Partial...

11

DisordersDisorders ofof acidacid--base base equilibriumequilibrium

PathobiochemistryPathobiochemistry and and diagnosticsdiagnostics ofof

acidacid--base and base and mineralmineral metabolismmetabolism

22

MaintainingMaintaining acidity acidity ofof innerinner

environmentenvironment

COCO22

NHNH33

HH++

HCOHCO33--

formation of

ureaglutamine

©© Martin VejraMartin Vejražžka, 2007ka, 2007

33

BicarbonateBicarbonate bufferbuffer

H2O + CO2HH22O + COO + CO22 H2CO3

HH22COCO33 HCO3– + H+HCOHCO33–– + H+ H++

44

HendersonHenderson--HasselbalchHasselbalch equationequation

][

][log

32

3

COH

HCOpKpH a

−

+=][

][log

32

3

COH

HCOpKpH a

−

+=

•• pKpKaa = 6.1= 6.1

•• [HCO[HCO33--] = 24 ] = 24 mmolmmol.L.L--11

•• [H[H22COCO33] = 1.2 ] = 1.2 mmolmmol.L.L--1120

COH

HCO=

−

][

][

32

3

55

HendersonHenderson--HasselbalchHasselbalch equationequation

•• pKpKaa = 6.1= 6.1

•• [HCO[HCO33--] = 24 ] = 24 mmolmmol.L.L--11

•• αα = 0,224 = 0,224 mmolmmol.L.L--1 1 / / kPakPa pCOpCO22 = 5.3 = 5.3 kPakPa

2

3

p

][log

COα

HCOpKpH a

⋅+=

−

2

3

p

][log

COα

HCOpKpH a

⋅+=

−

66

BicarbonateBicarbonate bufferbuffer

H2O + CO2HH22O + COO + CO22 H2CO3

HH22COCO33 HCO3– + H+HCOHCO33–– + H+ H++

tissuetissuetissue

lungslungslungs kidneykidneykidney

77

HydrogencarbonateHydrogencarbonate bufferbuffer

HH22COCO33

COCO22

H2OHH22OOHCOHCO33

--

HH++

NB: NB: sizesize ofof boxesboxes doesdoes not not exactlyexactly correspondcorrespond to to concentrationconcentration!!

88


HH22COCO33

COCO22

H2OHH22OOHCOHCO33

--

HH++

99


HH22COCO33

COCO22

H2OHH22OOHCOHCO33

--

HH++

1010

COCO22


HH22COCO33

H2OHH22OOHCOHCO33

--

HH++lungslungs

1111

COCO22


HH22COCO33

H2OHH22OOHCOHCO33

--

HH++lungslungs

1212

ABE ABE andand potassiumpotassium

�� Exchange Exchange ofof KK++ & H& H++ on cell on cell

membranemembrane

–– acidemiaacidemia →→ hyperkaliemiahyperkaliemia

–– alkalemiaalkalemia →→ hypokaliemiahypokaliemia

–– hyperkaliemiahyperkaliemia →→ acidemiaacidemia

–– hypokaliemiahypokaliemia →→ alkalemiaalkalemia

1313

ABE ABE andand calciumcalcium

�� Exchange Exchange ofof HH++ andand CaCa2+2+ on plasma on plasma

proteinsproteins

�� acidemiaacidemia →→→→→→→→ hypercalcemiahypercalcemia

�� alkalemiaalkalemia →→→→→→→→ hypocalcemiahypocalcemia

1414

ABE and ABE and ionsions

�� ElectroneutralityElectroneutrality mustmust bebe keptkept

�� thusthus: ABE : ABE influencesinfluences mineralmineral

metabolismmetabolism

�� DeviationsDeviations in ion in ion

concentrationsconcentrations are most are most easilyeasily

compensatedcompensated by HCOby HCO33--

CaCa2+2+

Na+

K+

MgMg2+2+

Cl–

HCO3-

prot-

SOSO4422--, HPO, HPO44

22--, ,

lactatelactate, , ketoacidsketoacids

1515

HypochloremicHypochloremic alkalosisalkalosis

�� LackLack ofof ClCl-- isis compensatedcompensated by by

increasedincreased HCOHCO33--

�� ChangedChanged ratioratio bicarbonatebicarbonate / /

COCO22 causes alkalosis

� E.g. in vomiting

CaCa2+2+

Na+

K+

MgMg2+2+

Cl–

HCO3-

prot-


22--, ,


1616

HypochloremicHypochloremic alkalosisalkalosis

H+

Cl-

HCl

CO2

H2CO3

HCO3-

• Chlorides replaced with bicarbonates

• HCO3- rises, pCO2 constant


1717

KetoacidosisKetoacidosis

�� ExcessExcess ofof ββ--hydroxybutyrichydroxybutyric

and acetoacetic and acetoacetic acidacid leadsleads to to

decreaseddecreased bicarbonatebicarbonate

�� E.g. E.g. decompenseddecompensed diabetes diabetes

mellitusmellitus, , starvationstarvation……

CaCa2+2+

Na+

K+

MgMg2+2+

Cl–

HCO3-

prot-


22--, ,


1818

AcidAcid--base base equilibriumequilibrium

DonDon‘‘t t thinkthink aboutabout changechange in in

HH++ oror OHOH--

butbut aboutabout changeschanges in in

concentrationconcentration ofof major major ionsions

pH pH changechange isis secondarysecondary to to changechange ofof

HCOHCO33-- / pCO/ pCO22 ratioratio


1919

ABE ABE disordersdisorders

�� AcidemiaAcidemia, , alkalemiaalkalemia

–– deviationdeviation ofof bloodblood pHpH

�� AcidosisAcidosis, , alkalosisalkalosis

–– excessexcess//lacklack ofof acidsacids//basesbases

2020

AlkalemiaAlkalemia

�� ↓↓↓↓↓↓↓↓ CaCa2+2+ →→→→→→→→ ↑↑↑↑↑↑↑↑ neuromuscularneuromuscular excitabilityexcitability

�� ↓↓↓↓↓↓↓↓ KK+ + →→→→→→→→ heartheart arrhythmiasarrhythmias

�� Shift Shift ofof hemoglobin hemoglobin dissociationdissociation curvecurve

→→→→→→→→ tissuetissue hypoxiahypoxia

2121

ABE ABE disordersdisorders

�� CompensationCompensation

–– MetabolicMetabolic disorderdisorder isis compensatedcompensated by by

respirationrespiration and v.v.and v.v.

�� CorrectionCorrection

–– MetabolicMetabolic disorderdisorder isis correctedcorrected

metabolicallymetabolically

•• respirationrespiration: 12 : 12 -- 24 24 hourshours

•• kidneykidney: : aboutabout 5 5 daysdays

2222

MetabolicMetabolic acidosisacidosis (MAC)(MAC)

�� LactateLactate acidosisacidosis

–– hypoxiahypoxia, , poorpoor lactatelactate degradationdegradation

�� KetoacidosisKetoacidosis

–– diabetes, diabetes, starvationstarvation, , alcoholismalcoholism……

�� Renal Renal acidosisacidosis

–– accumulationaccumulation ofof sulphatessulphates, , phosphatesphosphates……

�� IntoxicationIntoxication

2323

MAC in MAC in lossloss ofof HCOHCO33--

�� Diarrhoea and Diarrhoea and otherother lossloss fromfrom GITGIT

�� Renal Renal tubulartubular acidosisacidosis

–– disorderdisorder ofof HCOHCO33-- reabsorptionreabsorption in tubuliin tubuli

�� DilutionDilution acidosisacidosis

–– largelarge amountamount ofof infusionsinfusions lackinglacking bufferingbuffering

systemsystem

(pCO(pCO22 constantconstant, HCO, HCO33-- quicklyquickly diluteddiluted))

2424

TreatmentTreatment ofof MACMAC

�� NaHCONaHCO33

�� saltssalts ofof organicorganic acidsacids

–– metabolisedmetabolised to COto CO2 2 in in KrebsKrebs cyclecycle

RingerRinger solutionsolution withwith lactatelactate

2525

MetabolicMetabolic alkalosisalkalosis (MAL)(MAL)

�� ExcessiveExcessive lossloss ofof chlorideschlorides

–– vomitingvomiting, , diureticsdiuretics

�� DehydratationDehydratation ((concentrationconcentration

alkalosisalkalosis))

�� HypoproteinemiaHypoproteinemia

�� HyperaldosteronismHyperaldosteronism

–– retentionretention ofof NaNa++ atat the expense the expense ofof KK++ & H& H++

2626

ParadoxicalParadoxical aciduriaaciduria

alkalosisalkalosis EC KEC K++ ⇔⇔ IC HIC H++

↓↓KK++

kidneykidney::

NaNa++ ⇔⇔ HH++

exchangedexchanged insteadinstead ofof

NaNa++ ⇔⇔ KK++

↑↑ lossloss ofof HH++ to urineto urine

(and HCO(and HCO33-- reabsorptionreabsorption))

-- worseningworsening ofof alkalosisalkalosis

2727

MAL MAL treatmenttreatment

�� ArgininArginin chloridechloride

�� NaClNaCl

–– ClCl-- refillrefill

–– NaNa22HPOHPO4 4 excretedexcreted isteadistead ofof NaHNaH22POPO44

–– HCOHCO33-- dilutiondilution

�� KClKCl

–– additionalyadditionaly: : hypokalemiahypokalemia correctedcorrected

2828

AstrupAstrup

7,47,4

5,3 5,3

24,024,0

24,024,0

0,00,0

12,012,0

98,098,0

27,027,0

2929

AstrupAstrup

7,47,4

5,3 5,3

24,024,0

24,024,0

0,00,0

12,012,0

98,098,0

27,027,0

pHpH �� ActualActual pH pH ofof bloodblood

NV: 7,40 NV: 7,40 ±± 0,040,04

3030

AstrupAstrup

7,47,4

5,35,3

24,024,0

24,024,0

0,00,0

12,012,0

98,098,0

27,027,0

pHpH

pCOpCO22 kPakPa �� PartialPartial COCO2 2 pressurepressure

NV: 5,3 NV: 5,3 ±± 0,5 0,5 kPakPa

–– RespirationRespiration

3131

AstrupAstrup

7,47,4

5,3 5,3

24,024,0

24,024,0

0,00,0

12,012,0

98,098,0

27,027,0

pHpH

pCOpCO22 kPakPa

HCOHCO33-- actact.. mmol.lmmol.l--11 �� ActualActual bicarbonatesbicarbonates

NV: 24 NV: 24 ±± 2 mmol.l2 mmol.l--11

3232

AstrupAstrup

7,47,4

5,3 5,3

24,024,0

24,024,0

0,00,0

12,012,0

98,098,0

27,027,0

pHpH

pCOpCO22 kPakPa

HCOHCO33-- actact..

HCOHCO33-- stdstd..

mmol.lmmol.l--11

mmol.lmmol.l--11 �� Standard HCOStandard HCO33--

whatwhat wouldwould HCOHCO33-- bebe in in bloodblood

saturatedsaturated to 5.3 to 5.3 kPakPa COCO22

NV: 24 NV: 24 ±± 2 mmol.l2 mmol.l--11

3333

AstrupAstrup

7,47,4

5,3 5,3

24,024,0

24,024,0

0,00,0

12,012,0

98,098,0

27,027,0

pHpH

pCOpCO22 kPakPa

HCOHCO33-- actact..

HCOHCO33-- stdstd..

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11BEBE

�� Base Base excessexcess

howhow much much strongstrong acidacid shouldshould bebe

addedadded to to bloodblood atat

pCOpCO22 = 5,3 = 5,3 kPakPa

in in orderorder to to getget pH = 7,4pH = 7,4

NV: 0 NV: 0 ±± 2,5 mmol.l2,5 mmol.l--11

–– MetabolicMetabolic

3434

AstrupAstrup

7,47,4

5,3 5,3

24,024,0

24,024,0

0,00,0

12,012,0

98,098,0

27,027,0

pHpH

pCOpCO22 kPakPa

HCOHCO33-- actact..

HCOHCO33-- stdstd..

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11

kPakPa

BEBE

pOpO22

�� PartialPartial pressurepressure ofof OO22

NV: 10,0 NV: 10,0 -- 13,3 13,3 kPakPa

–– RespirationRespiration

3535

AstrupAstrup

7,47,4

5,3 5,3

24,024,0

24,024,0

0,00,0

12,012,0

98,098,0

27,027,0

pHpH

pCOpCO22 kPakPa

HCOHCO33-- actact..

HCOHCO33-- stdstd..

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11

%%

kPakPa

BEBE

pOpO22

satsat. O. O22

�� Hemoglobin Hemoglobin saturationsaturation

withwith oxygenoxygen

NV: 94 NV: 94 -- 99 %99 %

–– UsefulUseful to to checkcheck resultsresults

3636

AstrupAstrup

7,47,4

5,3 5,3

24,024,0

24,024,0

0,00,0

12,012,0

98,098,0

27,027,0

pHpH

pCOpCO22 kPakPa

HCOHCO33-- actact..

HCOHCO33-- stdstd..

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11%%

kPakPa

BEBE

pOpO22

satsat. O. O22

tottot. CO. CO22

�� TotalTotal carbonatecarbonate, i.e. , i.e.

COCO22 + H+ H22COCO33 + HCO+ HCO33--

3737

AstrupAstrup

�� FullFull heparinisedheparinised bloodblood

–– capillarycapillary ((arterialisedarterialised))

–– arteriaryarteriary

–– venousvenous

3838

AstrupAstrup

�� pHpH–– glassglass electrodeelectrode

�� PartialPartial pressurepressure ofof COCO22

–– glassglass electrodeelectrode in in bicarbonatebicarbonate solutionsolution, , separatedseparated

withwith COCO22 permeablepermeable membranemembrane fromfrom samplesample

�� PartialPartial pressurepressure ofof OO22

–– ClarkClark‘‘s oxygen s oxygen electrodeelectrode ((polarographypolarography))

�� HaemoglobinHaemoglobin concconc. & . & satsat..–– directdirect photometryphotometry

3939

AstrupAstrup

7,47,4

2323

4,88 4,88

10,610,6

95,295,2

pHpH

pCOpCO22 kPakPa

HCOHCO33-- actact..

HCOHCO33-- stdstd..

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11%%

kPakPa

BEBE

pOpO22

satsat. O. O22

tottot. CO. CO22

4040

AstrupAstrup

7,4237,423

4,88 4,88

23,523,5

24,224,2

--0,10,1

10,610,6

95,295,2

20,320,3

pHpH

pCOpCO22 kPakPa

HCOHCO33-- actact..

HCOHCO33-- stdstd..

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11%%

kPakPa

BEBE

pOpO22

satsat. O. O22

tottot. CO. CO22

�� EmpiricalEmpirical equationsequations!!

4141

LiverLiver failurefailure

�� AlkalosisAlkalosis

–– hypoproteinemiahypoproteinemia

–– hyperaldosteronismhyperaldosteronism

–– ↓↓ ofof ureasynthesisureasynthesis fromfrom ammoniaammonia

4242

Renal Renal failurefailure

�� AcidosisAcidosis

–– phosphatephosphate and and sulphatesulphate retentionretention

–– poorpoor urine urine acidificationacidification

4343

CombinedCombined ABE ABE disordersdisorders

�� MAC + MALMAC + MAL

–– vomitingvomiting + + starvationstarvation

–– vomitingvomiting + diarrhoea+ diarrhoea

–– renal renal failurefailure + + uremicuremic vomitingvomiting

–– hepatorenalhepatorenal failurefailure

�� MAC + RALMAC + RAL

–– salicylatesalicylate intoxicationintoxication

4444

CombinedCombined ABE ABE disordersdisorders

�� 22×× MACMAC

–– decompensateddecompensated diabetes mellitusdiabetes mellitus

ketoacidosisketoacidosis + + hypovolaemiahypovolaemia →→ lactatelactate MACMAC

�� RAC + MACRAC + MAC

–– cardiopulmonarycardiopulmonary failurefailure

4545

CasuistryCasuistry 11

7,1567,156

4,154,15

11,111,1

12,412,4

--15,715,7

10,110,1

90,890,8

12,112,1

pHpH

pCOpCO22 kPakPa

HCOHCO33-- actact..

HCOHCO33-- stdstd..

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11%%

kPakPa

BEBE

pOpO22

satsat. O. O22

tottot. CO. CO22

Na Na 141141 mmol.lmmol.l--11

K K 6,26,2 mmol.lmmol.l--11

Cl Cl 110110 mmol.lmmol.l--11

TP TP 58,8 58,8 g.lg.l--11

4646


7,3787,378

4,494,49

19,419,4

20,720,7

--4,44,4

8,88,8

92,492,4

16,916,9

pHpH

pCOpCO22 kPakPa

HCOHCO33-- actact..

HCOHCO33-- stdstd..

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11%%

kPakPa

BEBE

pOpO22

satsat. O. O22

tottot. CO. CO22




TP TP 65,765,7 g.lg.l--11

4747


7,4547,454

5,05,0

25,925,9

26,126,1

2,62,6

5,25,2

76,476,4

22,422,4

pHpH

pCOpCO22 kPakPa

HCOHCO33-- actact..

HCOHCO33-- stdstd..

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11%%

kPakPa

BEBE

pOpO22

satsat. O. O22

tottot. CO. CO22




TP TP 48,8 48,8 g.lg.l--11

4848


7,397,39

3,943,94

17,517,5

19,619,6

--5,75,7

7,17,1

87,287,2

15,315,3

kPakPa

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11

mmol.lmmol.l--11%%

kPakPa

pHpH

pCOpCO22

HCOHCO33-- actact..

HCOHCO33-- stdstd..

BEBE

pOpO22

satsat. O. O22

tottot. CO. CO22



Cl Cl ?????? mmol.lmmol.l--11

TP TP 62,3 62,3 g.lg.l--11

4949

DisordersDisorders ofof acidacid--base base equilibriumequilibrium

PathobiochemistryPathobiochemistry and and diagnosticsdiagnostics ofof

acidacid--base and base and mineralmineral metabolismmetabolism

Pathobiochemistry and diagnostics of acid -base and ...Astrup pH – glass electrode Partial...

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