Gas transport and pH regulation dr.Syazili Mustofa

pH regulationdr.Syazili MustofasensorBiochemistry departement of medical faculty lampung university

ASAM BASA..pH

[H+]

pH

AcidBaseNotasi pH diciptakan oleh seorang ahli kimia dari Denmark yaitu Soren Peter Sorensen pada thn 1909, yang berarti log negatif dari konsentrasi ion hidrogen. Dalam bahasa Jerman disebutWasserstoffionenexponent (eksponen ion hidrogen) dan diberi simbol pH yang berarti: potenz (power) of Hydrogen. pH

pH Regulation4Maintenance of relatively constant blood pH value is essential for health, since changes in blood pH will affect intracell pH alter : - metabolism - protein conformation - enzyme activity - equilibria of reaction that consume / generate H+(oxidation - reduction reaction)Maintenance of a constant blood pH is, in part, achieved by - buffer system in the blood control short - term changes in acid - base metab. - in long term : balancing proton loss & proton gainSyazili Mustofa

5pH value of plasma may be affected by :- malfunctioning of buffer system or- disturbance of acid base balance e.g. due to - kidney disease or - altered breathing frequency ( hypo / hyperventilation)Normal alterial plasma pH : 7.40 0.05- pH < 7.35 acidosis- pH > 7.45 alkalosisSyazili Mustofa

Buffer System63 major body water components : - plasma : within circulating system - interstitial fluid : fluid that bathes cells - intracellular fluidComposition : - plasma : - major kation : Na+ - small amounts : K+, Ca2+, Mg2+- dominant anions : HCO3-, Cl-- small amount anion : protein, HPO42-, SO42-- mixture organic anions - interstitial fluid : - similar - contain less protein plasma & interst. fluid extracell. Fluid

- intracell fluid : - major kation : K+- major anions : - organic P (ATP, BPG, glycolitic intrmd) - protein

Syazili Mustofa

7Each fluid makes a different contribution to buffering* Major buffer of extracell fluid : HCO3- / CO2 system- not very effective in resisting pH changes from changes in pCO2- effective in controlling pH changes caused by other than pCO2 changes* Intracell fluid : responsible for buffering pCO2 changes ( Hb buffering within RBC)* Extracell fluid & intracell fluid : equal in buffering strong organic / inorganic acids Plasma : excellent indicator to handle additional loads of acids

Syazili Mustofa

8Every buffer consist of : - a weak acid : H A - conjugate base : A- e.g. acetate-/acetic acid, NH3 / NH4+, HPO42- / H2PO4- weak acid : neutral, (+) charged, (-) charged conjugate base : 1 less (+) charge / 1 more (-) charge than weak acid Henderson - Hesselbalch equation :pH = pK + log

direct relationship between pH & ratio .

[conj. base ] [acid]Syazili Mustofa

9

[HCO3-] / [CO2] buffer system :Blood pH : 7,4 p.k. : 6,1

[HCO3-] / [CO2] ratio = 20/1 at normal blood pH = 7,4Every changes in [HCO3-] or [CO2] changes the ratio changes pH compensation to normalize blood pH.7,4 = 6,1 + log 20/1

Syazili Mustofa

10Blood plasma is a mixed buffer system :HCO3- / CO2 , HPO42- / H2PO4-, protein / H proteinMajor buffer of plasma : bicarbonate buffer system an open system : pCO2 is adjusted to meet the bodys needsIf respiration can not accomplish this adjustment pCO2 changes strikingly bicarbonate syst. would be ineffective.Syazili Mustofa

Acid - base balance & its maintenance11Acidosis : excess acid or def. of alkali in the bodyAlkalosis : excess alkali or def. of acid in the bodyThere exist mechanisms where the body normally rids itself of excess acid or alkali

Individuals produce large amounts of acids* Major acid : CO2 volatile : normally excreted by the lungs Inability of the lungs respiratory acidosis or alkalosisSyazili Mustofa

12

* Respiratory acidosis : result of hypoventilation of alveoli CO2 accumulates Alv. hypoventilation : occur when depth or rate of respiration - airway obstruction - neuromuscular disorders- diseases of CNS

- chronic resp. acidosis : chronic obstructive lung disease (emphyema)- inhalation of gas mixture with high pCO2 resp. acidosisIncrease the PCO2 ------> the pH goes down. Hypoventilation.

Acute resp. acidosisSyazili Mustofa

13

* Respiratory alkalosis : arises from decreased alv. pCO2 Hyperventilation : - anxiety : most common cause - CNS injury involving resp. center - salicylate poisoning - fever - artificial ventilation High altitude alv. pCO2 chronic resp. alkalosis

Decrease the PCO2 ------> the pH goes up. Hyperventilation.

Syazili Mustofa

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* Metabolic acidosis The body produced nonvolatile acids H+ + SO42-- hydrolysis of phosphate- esters phosphoric acid- metabolism - lactic acid - acetoacetic acid - - hydr. butyric acid- administration of : NH4Cl / Arg hydrochloride / Lys hydrochloride urea + HCl

Decrease the HCO3------> the pH goes down

produced in excess accumulation acidosisSyazili Mustofa

15- ingestion of salicylate, methyl alcohol, ethylene glycol production of strong organic acid accumulation of nonvolatile acids metabolic acidosis- abnormal loss of base ;- renal tubular acidosis : abnormal amount of HCO3- escape from blood into urine- severe diarrhea HCO3-

Syazili Mustofa

16

* Metabolic alkalosis - intake excess alkali :- NaHCO3- salt of organic acid : Na - lactate NaHCO3- fruits & vegetables : contain mixture of organic acids - metabolized to CO2 + H2O no long term. effect on acid base balance - salt of organic acids [HCO3-] - abnormal loss of acids : vomiting, gastric lavage (Lose enough stomach acid to produce alkalosis) - rapid loss of body water :diuresis temporary [HCO3-]Increase the HCO3------> the pH goes up

Syazili Mustofa

17Causes of acid base imbalanceAcidosis : Respiratory : alveolar hypoventilation Metabolic : - H+ overproduction - HCO3- overexcretionAlkalosis : Respiratory : alveolar hyperventilation Metabolic : - alkali ingestion - H+ overexcretionSyazili Mustofa

18Normal

Acidosis- Respiratory- Metabolic

Alkalosis- Respiratory- MetabolicBlood pH

7,4

Urine pH

6 7

[HCO3- ]/ [H2CO3

20/1

20 / > 1< 20 / 1

20 / < 1>20 / 1 Cause

HypoventilationH+ productionor HCO3- excretion

HyperventilationAlkali ingestionor H+ excretion

Syazili Mustofa

RespirasiHiperventilasiPenurunan kekuatan otot nafas dan menyebabkan kelelahan ototSesakMetabolikPeningkatan kebutuhan metabolismeResistensi insulinMenghambat glikolisis anaerobPenurunan sintesis ATPHiperkalemiaPeningkatan degradasi proteinOtakPenghambatan metabolisme dan regulasi volume sel otakKomaKardiovaskularGangguan kontraksi otot jantung

Dilatasi Arteri,konstriksi vena, dan sentralisasi volume darahPeningkatan tahanan vaskular paruPenurunan curah jantung, tekanan darah arteri, dan aliran darah hati dan ginjalSensitif thd reentrant arrhythmia dan penurunan ambang fibrilasi ventrikelMenghambat respon kardiovaskular terhadap katekolaminManagement of life-threatening Acid-Base Disorders, Horacio J. Adrogue, And Nicolaos EM: Review Article;The New England Journal of Medicine;1998AKIBAT DARI ASIDOSIS BERAT

KardiovaskularKonstriksi arteriPenurunan aliran darah koronerPenurunan ambang anginaPredisposisi terjadinya supraventrikel dan ventrikel aritmia yg refrakterRespirasiHipoventilasi yang akan menjadi hiperkarbi dan hipoksemiaMetabolicStimulasi glikolisis anaerob dan produksi asam organikHipokalemiaPenurunan konsentrasi Ca terionisasi plasmaHipomagnesemia and hipophosphatemiaOtakPenurunan aliran darah otakTetani, kejang, lemah delirium dan stuporAKIBAT DARI ALKALOSIS BERATManagement of life-threatening Acid-Base Disorders, Horacio J. Adrogue, And Nicolaos EM: Review Article;The New England Journal of Medicine;1998

Essentially, the difference between the concentrations of cations (Na+ primarily) and anions (Cl-, HCO3-) in the blood.

Anion gap= ( Na + K ) ( Cl + HCO)

= 4-17 mmol l

ANION GAP:

High Anion Gap: It is high in any condition with reduced clearance or excess production of any unmeasured anions. Metabolic Acidosis. It indicates that you have added acids to the blood: salicylic acid, formic acid, lactic acid, oxalic acid, sulfuric acid.Normal Anion Gap: Respiratory Acidosis. It occurs when you ultimately become acidotic because of losing HCO3

It is low in hyperalbuminaemia, liver disease and paraproteinaemias

Item valuepH7,4[HCO3-]22 - 28 mEq / LPaCO233 - 44 mEq / LPaO290 - 100 mEq / L

Normal value of arterial blood gasInget brho.

DUA VARIABELpH atau [H+] DALAM PLASMA DITENTUKAN OLEHVARIABELINDEPENDEN

VARIABEL DEPENDENMenurut Stewart ;MenentukanStewart PA. Can J Physiol Pharmacol 61:1444-1461, 1983.

VARIABEL INDEPENDENCO2STRONG ION DIFFERENCEWEAK ACIDpCO2SIDAtot

Controlled by the respiratory systemThe electrolyte composition of the blood (controlled by the kidney)The protein concentration (controlled by the liver and metabolic state)

Changes in H+ occur not as a result of how much H+ is added or removed, but as a consequence of water dissociation.

H2OH+OH-

MECHANISMEH20H++OH

SIDAtotCO2

DISSOCIATION & ASSOCIATION OF PURE WATER

Hubungan antara SID, H+ & OH-

SID()(+)[H+][OH-]Dalam cairan biologis (plasma) dgn suhu 370C, SID hampir selalu positif, biasanya berkisar 30-40 mEq/LiterAsidosisAlkalosisKonsentrasi [H+]

Strong IonsDifferencepCO2ProteinConcentrationPHYSICOCHEMICAL RxCONSERVATION of MASSELECTRONEUTRALITYH+HCO3-OH-tCO2A-CO3=

INDEPENDENT VARIABLESDEPENDENT VARIABLES

Stewart PA How to Understand Acid-Base. A Quantitative Acid-Base Primer for Biology and Medicine 1981 Edward Arnold. ISBN 0-7131-4390-8

pCO2 SID [weak acid]H2O

H+ OH-

30We are looking at an alternative approach first described by the late Peter Stewart which states that pH is determined by only 3 independent variables

CARBON DIOXIDEA MEASUREMENT CALLED THE STRONG ION DIFFERENCE(a strong ion being one that completely dissociates in solution)THE TOTAL AMOUNT OF WEAK ACID

Only these 3 things can independently affect pH

They do this by affecting the dissociation of the largest source of Hydrogen ion in the body and that is plasma water.Water itself being a weak acid.

Rx dominan dari CO2 adalah rx absorpsi OH- hasil disosiasi air dengan melepas H+.Semakin tinggi pCO2 semakin banyak H+ yang terbentuk.Ini yg menjadi dasar dari terminologi respiratory acidosis, yaitu pelepasan ion hidrogen akibat pCO2CO2OH- + CO2 HCO3- + H+CA

STRONG ION DIFFERENCEDefinisi: Strong ion difference adalah ketidakseimbangan muatan dari ion-ion kuat.

SID adalah jumlah konsentrasi basa kation kuat dikurangi jumlah dari konsentrasi asam anion kuat.

Untuk definisi ini semua konsentrasi ion-ion diekspresikan dalam ekuivalensi (mEq/L).

GamblegramNa+140K+ 4Ca++Mg++Cl-102

KATIONANION

SIDSTRONG ION DIFFERENCE[Na+] + [K+] + [kation divalen] - [Cl-] - [asam organik kuat-][Na+] + [K+] - [Cl-] = [SID] 140 mEq/L + 4 mEq/L - 102 mEq/L = 34 mEq/L

Kombinasi protein dan posfat disebut asam lemah total (total weak acid) [Atot]. Reaksi disosiasinya adalah:[Atot] (KA) = [A-].[H+][Protein H][Protein-] + [H+]

WEAK ACIDdisosiasi

GamblegramNa+140K+ 4Ca++Mg++Cl-102HCO3-24

KATIONANION

SIDWeak acid(Alb-,P-)WEAK ACID

DEPENDENT VARIABLESH+OH-CO3=A-AHHCO3-

Strong IonsDifferencepCO2ProteinConcentrationpH

INDEPENDENT VARIABLESDEPENDENT VARIABLES

[H+]OH-HCO3-S I DCO2Weak AcidsISF,RBC & PLASMAH2OH+.OH-pHCO3=DETERMINANTS OF BLOOD pHLiver

KLASIFIKASI

ASIDOSIS

ALKALOSIS

I. Respiratori

PCO2

PCO2

II. Nonrespiratori (metabolik)

1. Gangguan pd SID

a. Kelebihan / kekurangan air

[Na+], SID

[Na+], SID

b. Ketidakseimbangan anion kuat:

i. Kelebihan /kekurangan Cl-

[Cl-], SID

[Cl-], SID

ii. Ada anion tak terukur

[UA-], SID

2. Gangguan pd asam lemah

i. Kadar albumin

[Alb]

[Alb]

ii. Kadar posphate

[Pi]

[Pi]

Fencl V, Jabor A, Kazda A, Figge J. Diagnosis of metabolic acid-base disturbances in critically ill patients. Am J Respir Crit Care Med 2000 Dec;162(6):2246-51

RESPIRASIM E T A B O L I KAbnormal pCO2AbnormalSIDAbnormalWeak acidAlbPO4-AlkalosisAsidosisTurunMeningkatTurunkelebihankekuranganPositifmeningkat

Fencl V, Am J Respir Crit Care Med 2000 Dec;162(6):2246-51 AIR Anion kuat

Cl-UA-

HipoHiper

pCO2 berbanding terbalik terhadap pH

pCO2pH40-45 mmHg7.35-7.45

pHpCO2

pHpCO2AlkalosisAcidosisHOMEOSTASIS

RESPIRASI

RESPIRASIM E T A B O L I KAbnormal pCO2AbnormalSIDAbnormalWeak acidAlbPO4-AlkalosisAcidosisTurunmeningkatturunkelebihankekuranganPositifmeningkat

AIR Anion kuat

Cl-UA-

HipoHiper

Na+ = 140 mEq/LCl- = 102 mEq/LSID = 38 mEq/L

140/1/2 = 280 mEq/L102/1/2 = 204 mEq/L SID = 76 mEq/L

1 liter literKEKURANGAN AIR - WATER DEFICITDiureticDiabetes InsipidusEvaporasiSID : 38 76 = alkalosis

ALKALOSIS KONTRAKSI

PlasmaPlasma

Na+ = 140 mEq/LCl- = 102 mEq/L SID = 38 mEq/L

140/2 = 70 mEq/L102/2 = 51 mEq/L SID = 19 mEq/L

1 liter2 literKELEBIHAN AIR - WATER EXCESS1 Liter H2O

SID : 38 19 = Acidosis

ASIDOSIS DILUSIPlasma

RESPIRASIM E T A B O L I KAbnormal pCO2AbnormalSIDAbnormalWeak acidAlbPO4-AlkalosisAcidosisturunmeningkatturunkelebihankekuranganPositifmeningkat

AIR Anion kuat

Cl-UA-

HipoHiper

Na+ = 140 mEq/L Cl- = 95 mEq/LSID = 45 mEq/L

2 literALKALOSIS HIPOKLOREMIK

SID ALKALOSIS

GANGGUAN PD SID:Pengurangan Cl-Plasma

Na+ = 140 mEq/L Cl- = 120 mEq/LSID = 20 mEq/L

2 literASIDOSIS HIPERKLOREMIK

SID ASIDOSIS

GANGGUAN PD SID:Penambahan/akumulasi Cl-Plasma

Na+ = 140 mEq/LCl- = 102 mEq/LSID = 38 mEq/L

Na+ = 154 mEq/LCl- = 154 mEq/LSID = 0 mEq/L

1 liter1 literPLASMA + NaCl 0.9%

SID : 38 PlasmaNaCl 0.9%

2 literASIDOSIS HIPERKLOREMIK AKIBAT PEMBERIAN LARUTAN Na Cl 0.9% =

SID : 19 AsidosisNa+ = (140+154)/2 mEq/L= 147 mEq/LCl- = (102+ 154)/2 mEq/L= 128 mEq/LSID = 19 mEq/LPlasma

Na+ = 140 mEq/L Cl- = 102 mEq/L SID= 38 mEq/L

Cation+ = 137 mEq/L Cl- = 109 mEq/LLaktat- = 28 mEq/L SID = 0 mEq/L

1 liter1 literPLASMA + Larutan RINGER LACTATE

SID : 38

PlasmaRinger laktatLaktat cepat dimetabolisme

2 liter=Normal pH setelah pemberian RINGER LACTATE

SID : 34 lebih alkalosis dibanding jika diberikan NaCl 0.9%Na+ = (140+137)/2 mEq/L= 139 mEq/L Cl- = (102+ 109)/2 mEq/L = 105 mEq/L Laktat- (termetabolisme) = 0 mEq/L SID = 34 mEq/LPlasma

Rapid Saline Infusion Produces Hyperchloremic Acidosis in Patients Undergoing Gynecological Surgery.(Scheingraber et al.: Anesthesiology 1999, 90)NaCl 0.9%(n = 12)Lact. Ringers (n = 12)Time of infusion (min)135 23138 20Volume after 120 min (ml/kg)71 1467 18Estimated blood loss (ml)962 332704 447Urine output (ml)717 4591 075 799

Scheingraber et al., Anesthesiology 90 (1999)NaCl 0.9%Lactated Ringers0 min120 min0 min120 minBicarbonate (mM)23.5 2.218.4 2.023.3 2.023.0 1.1Anion gap (mM)16.2 1.211.8 1.415.8 1.412.5 1.8Chloride (mM)104115104106

Scheingraber et al., Anesthesiology 90 (1999)NaCl 0.9%Lactated Ringers

7.50

7.45

7.40

7.35

7.30

7.25

7.200 30 60 90 120 min0 30 60 90 120 min0 30 60 90 120 min0 30 60 90 120 min50

46

42

38

34

30

264

0

-4

-8

-123.0

2.5

2.0

1.5

1.0

0.5

0.0mmHgmmol/lmmol/lpHCO2Base excessLactate#######*#*#*#********** P