Acid-Base balanceAcid-Base balance

Acid-base balance refers to the mechanisms the Acid-base balance refers to the mechanisms the

body uses to keep its fluids close to neutral pH (that body uses to keep its fluids close to neutral pH (that

is, neither basic nor acidic) so that the body can is, neither basic nor acidic) so that the body can

function normally.function normally.

Arterial blood pH is normally closely regulated Arterial blood pH is normally closely regulated

to between 7.35 and 7.45.to between 7.35 and 7.45.

Acid Base balanceAcid Base balance

acidsacids ？？

basesbases ？？

Any ionic or molecular substance Any ionic or molecular substance that can act as a proton donor.that can act as a proton donor.

Strong acidStrong acid ：： HCl, HHCl, H22SOSO44, H, H33POPO44..

Weak acidWeak acid ：： HH22COCO33, CH, CH33COOH.COOH.

Any ionic or molecular substance Any ionic or molecular substance that can act as a proton acceptor.that can act as a proton acceptor.

Strong alkaliStrong alkali ：： NaOH, KOH.NaOH, KOH.Weak alkaliWeak alkali ：： NaHCONaHCO33, NH, NH33, ,

CHCH33COONa.COONa.

Lactic acid

Ketone bodies

Sulfuric acid

Phosphoric acid

Intracellular metabolism

Volatile acids

300~400L 300~400L COCO2 (15(15molmol

HH++) )

Fixed acids

50~100 50~100 mmol mmol HH++

NHNH33 , sodium citrate, sodium lactate

Origin of acids Much more

Origin of basesOrigin of bases less

CO2+H2O=H2CO3

pHpH- - pH of ECF is between 7.35 and 7.45.pH of ECF is between 7.35 and 7.45.

Deviations, outside this range affect Deviations, outside this range affect membrane function, alter protein membrane function, alter protein function, etc.function, etc.

- - You cannot survive with a pH <6.8 or You cannot survive with a pH <6.8 or >7.7>7.7

- Acidosis- below 7.35 Acidosis- below 7.35

Alkalosis- above 7.45Alkalosis- above 7.45

CNS function deteriorates, coma, cardiacCNS function deteriorates, coma, cardiac

irregularities, heart failure, peripheral irregularities, heart failure, peripheral

vasodilation, drop in Bp.vasodilation, drop in Bp.

Given that normal body pH is slightly alkaline and that normal metabolism produces acidic waste products such as carbonic acid (carbon dioxide reacted with water) and lactic acid, body pH is constantly threatened with shifts toward acidity.

In normal individuals, pH is controlled by two major and related processes; pH regulation and pH compensation. Regulation is a function of the buffer systems of the body in combination with the respiratory and renal systems, whereas compensation requires further intervention of the respiratory and/or renal systems to restore normalcy.

Buffer Systems in Body Fluids

Figure 27.7

Buffering systemBuffering system ECF

Plasma NaHCO3/ H2CO3 NaPr/HPr* Na2HPO4/NaH2PO4

intercellular NaHCO3/ H2CO3 Na2HPO4/NaH2PO4

fluid

ICF** KPr/HPr K2HPO4/KH2PO4 KHCO3 /H2CO3

organic acids

RBC KHb/HHb KHbO2/HHbO2 K2HPO4/KH2PO4

KHCO3/ H2CO3

* HPr ： protein ； ** muscle cells 。

Major buffer system in the Major buffer system in the bodybody

Carbonic acid/Bicarbonate(HCOCarbonic acid/Bicarbonate(HCO33--/H/H22COCO33)) : :

The major extracellular bufferThe major extracellular buffer ，， regulated regulated by lungs and by lungs and kidneyskidneys ，， effectiveeffective ，， determining the pH of determining the pH of plasma. plasma.

Phosphate (HPOPhosphate (HPO442-2-/H/H22POPO44

-- ) : Intracellular ) : Intracellular

Protein (PrProtein (Pr--/HPr) : Plasma/Intracellular/HPr) : Plasma/Intracellular

Hemoglobin (HbHemoglobin (Hb--/HHb and HbO/HHb and HbO22--/HHbO/HHbO2 2 ) : ) :

RBCRBC

*A buffer system cannot buffer itself.*A buffer system cannot buffer itself. fast / no permanencefast / no permanence

2) Respiratory control:

Expelling more CO2 through respiration→to exclude volatile acid.

H+→chemoreceptor → excite respiratory centre → hyperventilation → exclude volatile acid

Fast / effectively / only Fast / effectively / only excludes volatile acidexcludes volatile acid

PaCOPaCO22(40-80 mmHg)(40-80 mmHg)Blood-brain barrier Blood-brain barrier permeable to COpermeable to CO22: CO: CO22+H+H22OOHH22COCO33 HH++

+HCO+HCO33--(in cerebrospinal fluid, CSF)(in cerebrospinal fluid, CSF) [H[H++] ]

Central chemoreceptorCentral chemoreceptor(beneath the (beneath the ventral surface of the medulla oblongata)ventral surface of the medulla oblongata) Respiratory center Respiratory center VentilationVentilation (Main) (Main)

3) Role of kidney (exclusion of acid with conservation of base)

hydrogen ion secreted ammonium excreted by renal tubular cell bicarbonate reabsorbed

Effectively ( fixed acid may be Effectively ( fixed acid may be excluded ) / slowlyexcluded ) / slowly

Kidney tubules and pH Regulation

Figure 27.10a, b

An acid base disorder is a change in the a change in the normal value of extracellular pHnormal value of extracellular pH that may result when renal or respiratory function is abnormal or when an acid or base load overwhelms excretory capacity.

Definition of acid-base disordersDefinition of acid-base disorders

Figure 27.6

Animation: Relationship Between PCO2 and Plasma pHPLAY

Simple acid-base disorder1. Metabolic acidosis

1) concept: primary disturbance [HCO3

-] ↓ ; PH . PaCO2 ↓

2) clasification:

Normal AG High AG

3) pathogenesis and mechnisms: (1) lose of bases (2) gaining acids

Metabolic acidosisMetabolic acidosis

CausesCauses:: (1) lose of bases (bicarbonate decreased)

Gastrointestinal lossesGastrointestinal losses: diarrhea : diarrhea Renal lossesRenal losses: proximal renal tubular acidosis : proximal renal tubular acidosis and distal renal tubular acidosisand distal renal tubular acidosis

(2) gaining acids (bicarbonate consumed in buffering) Lactic acidosisLactic acidosis: tissue hypoxia, impaired oxygen utilization, : tissue hypoxia, impaired oxygen utilization, severe liver dysfunction, and shocksevere liver dysfunction, and shock KetoacidosisKetoacidosis: diabetic,hepatic cirrhosis, alcoholic : diabetic,hepatic cirrhosis, alcoholic poisoning, or starvation poisoning, or starvation Renal failure: conservation of acids Renal failure: conservation of acids

Exogenous acid intakeExogenous acid intake: ammonium chloride, salicylate, : ammonium chloride, salicylate, ethylene glycol(commonly used in antifreeze), or methanol ethylene glycol(commonly used in antifreeze), or methanol intoxication intoxication

4) CompensationCompensation:all regulation system take part in5) Effects Effects: (1) Depression of central neural system a Elevated activities of glutamate decarboxylase →GABA ↑

b.ATP ↓ (2) Depression of heart and vessel(Ca2+ transport disorder; hyperkalemia;ATP↓): cardiac output ↓ ; cardiac arrhythmias; peripheral vasodilation.(3) Skin: warm and flashed(4) Alteration of skeleton: decacification, retarding growth and osteodystrophy6) TreatmentTreatment: administration of 5%NaHCO3, sodium lactate, THAM.

Respiratory acidosis

1) ConceptConcept:

Primary change : retention of CO2; pH . PaCO2↑

2) Classification Classification: Acute RAC Chronic RAC

3) CausesCauses : Disorder of external respiration - Overdosage of sedatives, narcotics,etc. Cerebrovascular accidents. Cardiopulmonary arrest Central nervous system trauma, infections Poliomyelitis Inhalation of foreign bodies Chronic obstructive pulmonary disease Asthma Pneumonia Increased CO2 inhalation –

4) CompensationCompensation:

In acute RAC: ion exchange across the membrane and buffering in cell

HCO3-

+

H+ H++A- HA

K+ K+

（ somatic cell）CO2+H2O

H2CO3

In chronic RAC: excretion of more H+ and ammonia ion reabsorption of more HCO3

- in kindneys

Figure 27.11a

The Central Role of the Carbonic Acid-Bicarbonate Buffer System in the Regulation of Plasma pH

5) Effects Effects: (1) Neurological effects: CO2 narcosis (2) Cardiovascular effects: arrhythmias; pulmonary artery hypertension; cardiac output decrease. (3) Inducting of hyerkalemia and hypochloremia

6) principle of treatment: improve ventilation

Metabolic alkalosis1) ConceptConcept: Primary disturbance [HCO3

-] ↑ ; PH . PaCO2 ↑

2) Classification: Classification:

Chloride – responsive

Chloride – resistant

3) Causes and mechanismCauses and mechanism: MechanismMechanism: a. Excessive gain of alkali (bicarbonate)

b. Excessive loss of hydrogen ions, chloride or potassium ions

Causes:Causes:aa.Excessive gain of alkali (bicarbonate)Bicarbonate intake:treatment of MACcitrate-containing blood transfusionsParenteral solution containing lactate

bb.Excessive loss of hydrogen ions, chloride or potassium ionsGastrointestinal H+ loss:vomiting,gastric suctionRenal H+ loss:Aldosteronism,cushing’s syndromethiazide

cc.Volume contraction DehydrationDiuretic therapy

4) CompensationCompensation: Blood buffer role limitation Respiratory regulation Ion exchange and H+ out cell to titrate bicarbonate Renal role: excluding bicarbonate and conserving H+

5) EffectsEffects: (1) Hypoventilation→ PaCO2 ↑, PaO2 ↓

(2) Agitation of central neural system: GABA↓ → seizures (3) Increase excitability of the neuromuscle: free [Ca2+] decrease → muscle tremors (4) Mental dysfunction: O2 dissociated curve leftshift → impairing O2 release → ATP ↓. At 6-8 hs, 2,3-DPG and curve shifts back towards the right. (5) Hypokalemia → reduced fibrillation threshold

6) Principle of treatmentPrinciple of treatment:

a. Etiology treatment

b. Administration of KCl. or spironolactone if K+ and Cl- deficits are present

c, Carbonic anhydrase inhibitor: acetazolamide

Respiratory alkalosis

1) ConceptConcept: Primary change : H2CO3 ↓ or PaCO2 ↓ ; pH

2) ClassificationClassification:

a. Acute RAL

b. Chronic RAL

3) Causes and mechanismsCauses and mechanisms: Mechanisms: Mechanisms: Hyperventilation Causes:Causes:a. Psychogenic hyperventilation:Hysteria

b. Stimulation of respiratory center: High altitude hypooxia Salicylate toxication Blood ammonia↑(Hepatic encephalopathy) Encephalitis Brain injury Feverc. Inappropriately high ventilator settings

4) CompensationCompensation: In acute RAC: Ion exchange, H+ out of cell to titrate base in ECF In chronic RAC: Decreased excretion of H+ and NH4

+ Decreased reabeorption of HCO3

-

5) EffectsEffects: (1) Increased excitability of the nerve and muscle (2) Mental dysfunction (3) Hypokalemia,hypochloridemia

6) Principle of treatmentPrinciple of treatment: a. Decreased ventilation by administration of sedative. b. Application of a plastic bag to inspire more amount of CO2 gas

Figure 27.11b

The Central Role of the Carbonic Acid-Bicarbonate Buffer System in the Regulation of Plasma pH