Chapter 4(1) Acid – Base DisordersChapter 4(1) Acid – Base Disorders

§1. Acid- Base balance 1.Concept of acid and base

Acid: Acid is a proton donor. (HCl, NH4+)

HCl → H+ + Cl-

NH4+ → H+ + NH3

Base: Base is a proton acceptor. (OH-, HCO3-, NH3)

OH- + H+ → H2O

HCO3- + H+ → H2CO3

NH3 + H+ → NH4+

2.Origins of acid and base in the body Source of acid: 1) origins of volatile acid

It results from an end-product of oxidative metabolism namely CO2. CO2+H2O = H2CO3

Normally produced CONormally produced CO2 2 300-400 L/d or H300-400 L/d or H++ 15 mol/ 15 mol/d.d.

2) origins of nonvolatile acid ( fixed acid )

It comes from metabolic processes or incomplete oxidation of glucose or fats and so on. as: H2SO4, H3PO4, lac

tic acid, acetoacetic acid, β-hydroxybutyric acid.

Sulfuric acid:Sulfuric acid: Catabolism of sulfur-containing amino acids. Catabolism of sulfur-containing amino acids.

Phosphoric acid; Phosphoric acid; Catabolism of phosphoesters ,phosphoprotei Catabolism of phosphoesters ,phosphoprotein ,nucleotide.n ,nucleotide.

Lactic acid: Lactic acid: Incomplete oxidation of carbohydrate. Incomplete oxidation of carbohydrate.

Beta-hydroxybutyric acid, acetoacetic acid:Beta-hydroxybutyric acid, acetoacetic acid:

Incomplete oxidation of fatty acid.Incomplete oxidation of fatty acid.

Normally produced HNormally produced H++ 50-100 mmol/d . 50-100 mmol/d .

3) Exogenous acid intake

Salicin intoxication

Hydrochloric acid

Origin of bases:

1) NH3: It is formed by deamination of amines, amino acid, purines and so on. 2) Eatting salt of organic acid: Sodium citratc and sodium lactate come from vegetable and fruits.

3. Regulation of acid – base balance

1) Chemical buffers: Buffer system is composed by weak acid and weak acid salt. It may convert strong acid into weak acid or strong alkali into weak alkali.

NaHCO3+HCl → NaCl+H2CO3

H2CO3+NaOH → H2O+NaHCO3

Major buffer system in the bodyMajor buffer system in the bodyCarbonic acid/Bicarbonate(HCOCarbonic acid/Bicarbonate(HCO33

--/H/H22COCO33)) : :

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

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

-- )) : Intracellular : Intracellular

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

Hemoglobin (HbHemoglobin (Hb--/HHb/HHb and and HbOHbO22--/HHbO/HHbO22 )) : : 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 excludFast / effectively / only excludes volatile acides volatile acid

PaCOPaCO22(40-80 mmHg)(40-80 mmHg)Blood-brain barrier permeBlood-brain barrier permeable to COable to CO22: CO: CO22+H+H22OOHH22COCO33 HH+++HCO+HCO33

--(in cerebr(in cerebrospinal fluid, CSF)ospinal fluid, CSF) [H[H++] ] Central chemoreceptorCentral chemoreceptor(beneath the ventral surface of the medulla oblong(beneath the ventral surface of the medulla oblongata)ata) Respiratory center Respiratory center VentilationVentilation (Main) (Main)

PCOPCO22 80 mmHg, inhibition of respiratory cente80 mmHg, inhibition of respiratory center.r.

PaOPaO22 (30-60 mmHg) /pH (30-60 mmHg) /pH / PCO / PCO22Peripheral chPeripheral chemoreceptoremoreceptor (Carotid bodies, aortic bodies) (Carotid bodies, aortic bodies) Resp Respiratory center iratory center Ventilation Ventilation (Minor) (Minor)

Pa OPa O2 2 30 mmHg, inhibition of respiratory cente30 mmHg, inhibition of respiratory centerr

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 excludeEffectively ( fixed acid may be excluded ) / slowlyd ) / slowly

Role of the kidneysRole of the kidneys

powerfully, slowpowerfully, slowlyly## Proximal tubuleProximal tubule: : H H+ + secretion coupled with secretion coupled with HCHCOO33

-- reabsorption reabsorption

# # Collecting tubuleCollecting tubule H H+ + secretion and excretion cousecretion and excretion coupled with the addition of pled with the addition of newnew HCOHCO33

-- to the plasmato the plasma

Secreted ammonia once the noSecreted ammonia once the normal urinary phosphate buffermal urinary phosphate buffers are saturated.rs are saturated. NH NH3 3 + H+ H+ + NHNH44

++

4) Role of tissue and cell

cell: intra and extra ions exchange across the cellular membrane buffering in the cell or titrating base in ECF

bone: Ca3(PO4)2+4H+ 3Ca2++2H2PO4 Decalcification, osteoporosis. Decalcification, osteoporosis.

• Effectively / but need timeEffectively / but need time

Acid-base balance: Acid and bases are continuously produced in the body, PH is maintained 7.35-7.45 by four regulation of the body, This condition is termed as acid-base balanceacid-base balance.

§2. Laboratory parameters of acid-base balance 1. PH ： pH= pH= log [Hlog [H++]]=log1/ [H=log1/ [H++] (The logarithm to the ] (The logarithm to the base 10 of the reciprocal of the [Hbase 10 of the reciprocal of the [H++])])

HCO3-(metabolic factor)

pH= pKa+ log ——————————— H2CO3 (respiratory factor)

= pKa + logHCO3-/α×PCO2 ＝ 6.1+1.3=7.4

Normal plasmaNormal plasma pH 7.35-7.45 ( average 7.pH 7.35-7.45 ( average 7.4 )4 )

2. PaCO2( respiratory parameter ):

Partial pressure of COPartial pressure of CO22dissolved in arterial plasma(dissolved in arterial plasma(The pressure is produced by CO2 dissolved in arterial plasma).

Normal range: 4.39~6.25kPa(33~46mmHg)Normal range: 4.39~6.25kPa(33~46mmHg) Average: 5.32kPa(40mmHg) Average: 5.32kPa(40mmHg)

PaCO2 ＞ Normal (hypoventilation) a.primary change: RAC b.secondary change: MAL with respiratory compensation

PaCO2 ＜ Normal (hyperventilation) a.primary change: RAL b.secondary change: MAC with respiratory compensation

3. SB AB BB BE (metabolic parameter): SB: HCO3

- in plasma under standard condition 22~27 mmol/L AB: HCO3

- in plasma under actual condition 22~27 mmol/L

　　 Average : 24 m mol/LAverage : 24 m mol/L

BB: BB = HCO3- + Pr - + Hb - 45~55 mmol/L

BE: BE = ΔBB = BB-NBB -3~+3 mmol/L

MAC: primary decreased

MAL: primary elevated

Normal condition : PaCO2 ＝ 5.32Kpa( 40mmHg )

AB ＝ SB ＝ 24 mmol/L 24 mmol/L ( average)( average)

AB ＞ SB → CO2 retention: RAC (primary change)

MAL with respiratory compensation

AB ＜ SB → CO2 expiration:RAL (primary change)

MAC with respiratory compensation AB↑ ＝ SB↑→ MAL without respiratory compensation

4. AG( anion gap ):

AG=UA(undetermined anion – UC(undetermined cation ) [HCO3

- ]+[Cl- ]+UA= [Na+]+UC AG=UA-UC=[Na+]-([HCO3

-]+[Cl-])=140-(24+104)=12mmol/L±2

§3. Simple acid-base disorder1. Metabolic acidosis

1) concept: primary disturbance [HCO3

-] ↓ ; PH . AB↓ , SB↓ , BB↓ , BE ↓ ; PaCO2 ↓ ; AB ＜ SB

2) clasification:

Normal AG MAC High AG MAC

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, fistulae and so on. : diarrhea, fistulae and so on. Renal lossesRenal losses: proximal renal tubular acidosis and distal r: proximal renal tubular acidosis and distal renal tubular acidosisenal tubular acidosis

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

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

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↑ ; AB↑ SB↑ BB ↑ BE ↑ ; AB ＞ SB

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 – Misoperation of mechanical ventilator Inhalation CO2 of high concentration

4) CompensationCompensation:

In acute RAC:

ion exchange across the membrane and buffering in cell

HCO3-

+

H+ H++A- HA

K+ K+

体细胞（ somatic cell ）CO2+H2O

H2CO3

Red blood cell

CO2 CO2+H2O H2CO3

H++Hb - HHb

+

HCO3-

-

Cl-

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

- in kindneys

5) Effects Effects: (1) Neurological effects: CO2 narcosis (2) Cardiovascular effects: arrhythmias; pulmonary artery hypertension; cardiac output decrease. (3) Mixed acid-base imbalance (RAC+MAC) (4) Inducting of hyerkalemia and hypochloremia

6) principle of treatment: improve ventilation

Metabolic alkalosis1) ConceptConcept: Primary disturbance [HCO3

-] ↑ ; PH . AB↑, SB↑, BB↑, BE↑; PaCO2 ↑ ; AB ＞ SB

2) Classification: Classification:

Chloride – responsive MAL

Chloride – resistant MAL

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 and loop diureticpotassium deficit

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. Replacing N.S or NH4Cl solution.

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

d. Carbonic anhydrase inhibitor: acetazolamide

Respiratory alkalosis

1) ConceptConcept: Primary change : H2CO3 ↓ or PaCO2 ↓ ; pH . PaCO2↓ ; AB↓ SB↓ BB↓ BE↓ ; AB<SB

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

Parameter changes of simple typesParameter changes of simple types

Disorder Primary Change Second Response pHDisorder Primary Change Second Response pH

Metabolic acidosis Metabolic acidosis HCOHCO33- - PaCO PaCO2 2 pH pH

Respiratory acidosis PaCORespiratory acidosis PaCO2 2 HCOHCO33- - pHpH

Metabolic alkalosis HCOMetabolic alkalosis HCO33- - PaCOPaCO2 2 pH pH

Respiratory alkalosis PaCORespiratory alkalosis PaCO2 2 HCO HCO33-- pH pH

Compensated XCompensated X ：： after compensation, pH still in normal. after compensation, pH still in normal. Uncompensated XUncompensated X ： ： after compensation, pH still abnormaafter compensation, pH still abnormal.l.

§4. Mixed acid –base disturbance

Definition : more than one primary acid-base disorder coexist in a patient.

Double disorders

1) MAC+RAC: diabetic ketosis with pulmonary disease 2) MAL+RAL: vomiting with hyperventilation 3) MAC+RAL: uremia with high fever 4) MAL+RAC: diuretics with respiratory failure 5) MAC+MAL: heart failure with hypokalemia

Triple disorders :

respiratory acidosis

+ MAC + MAL

respiratory alkalosis

§5. Diagnosis 1. According to pathogensis establishing primary change 2. Manifestation: excitation — alkalosis inhibition — acidosis 3. According to PH PH<7.35 —acidemia — acidosis PH>7.45 — alkalemia — alkalosis PH=7.35~7.45: normal condition complete compensation mixed acid-base disturbance 4. Condition of compensation:direction ； predicted compensative value ； compensative limit 5. Estabolilshed triple disorders: utilized AG

The patient was suffered from salicylate intoxication. His blood-gas parameters (lab. Value): PH = 7.45 PaCO2 = 2.6 kpa (20mmHg)

HCO3- =13mmol/L .what acid-base disorders presente

d in this patient ?

Causes: salicylate intoxication. Primary change is HCO3- decreased.

HCO3- =13mmol/L<24mmol/L MAC

pH: pH=7.45=N compensated MAC mixed acid-base imbalance (MAC+RAL) Compensatory condition: PaCO2 =2.6kpa(20mmHg)<5.32kpa(40mmHg) Calculate: 1.2×ΔHCO3±2=1.2 ×(24-13) ±2=13.2 ±2=11.2-15.2 Predicted PaCO2 value =40 - (11.2or15.2)=24.8-28.8mmHg Actual PaCO2=20mmHg < predicted PaCO2=24.8 –28.8mmHg

diagnosis: MAC+RAL