Anion GapAnion Gap

The difference between [NaThe difference between [Na++] and ] and the sum of [HC0the sum of [HC033

--] and [Cl] and [Cl--].].

[Na[Na++] – ([HC0] – ([HC033--] + [Cl] + [Cl--]) = ]) =

140 - (24 + 105) = 11140 - (24 + 105) = 11 Normal = 12 Normal = 12 ++ 2 2

Clinicians use the anion gap to Clinicians use the anion gap to identify the cause of metabolic identify the cause of metabolic acidosis. acidosis.

Types of Acids in the BodyTypes of Acids in the Body

Volatile acids:Volatile acids: Can leave solution and enter the Can leave solution and enter the

atmosphere.atmosphere. HH22C0C033 (carbonic acid). (carbonic acid). PcoPco22 is most important factor in pH of is most important factor in pH of

body tissues.body tissues.

Buffer: any substance which reversibly consumes or releases H+. Buffers minimize or attenuate changes in pH by consuming or adding H+ in such a way to minimize discrete changes.

Valence does not matter, ie for buffer “B”

Protonated form in equilibrium with deporotonated form

Weak acid Weak base

HB (n+1) = B (n) + H (+)

The buffers distribute themselves via their dissociation constant (K) defined as the ratio [B(n)] [H+] = K

[HB(n=1)]

Most important physiological buffer pair is CO2 (carbon dioxide) and HCO3

- (bicarbonate).

Since the lung can expire volatile CO2, it can regulate and stablize the balance of CO2. If CO2 is in solution, it can dissociate to carbonic acid (a slow reaction)

CO2 + H2O H2CO3

Formed carbonic acid can quickly dissociate to hydrogen ions and bicarbonate:

H2CO3 H+ + HCO3

-

Note that the formation of H+ will decrease pH. The net reaction is

CO2 + H2O H+ + HCO3-

ProteinsProteins

COOH or NHCOOH or NH22.. Largest pool of buffers in the body.Largest pool of buffers in the body. pk. close to plasma.pk. close to plasma. Albumin, globulins such as Hb.Albumin, globulins such as Hb.

6

Other important buffersOther important buffers

The phosphate buffer system (HPOThe phosphate buffer system (HPO442-2-/H/H22POPO44

--) plays a role in plasma ) plays a role in plasma

and erythrocytes.and erythrocytes.

HH22POPO44-- + H + H22O O ↔ H↔ H33OO++ + HPO + HPO44

2-2-

Any acid reacts with monohydrogen phosphate to form dihydrogen Any acid reacts with monohydrogen phosphate to form dihydrogen

phosphatephosphate

dihydrogen phosphate monohydrogen phosphatedihydrogen phosphate monohydrogen phosphate

HH22POPO44-- + H + H22OO ← ← HPOHPO44

2-2- + H + H33OO++

The base is neutralized by dihydrogen phosphateThe base is neutralized by dihydrogen phosphate

dihydrogen phosphate dihydrogen phosphate monohydrogen phosphatemonohydrogen phosphate

HH22POPO44-- + OH + OH-- → → HPOHPO44

2-2- + H + H33OO++

Respiratory SystemRespiratory System

2nd line of defense.2nd line of defense. Acts within min. maximal in 12-24 Acts within min. maximal in 12-24

hrs.hrs. HH22COCO33 produced converted to CO produced converted to CO22, ,

and excreted by the lungs.and excreted by the lungs. Alveolar ventilation also increases as Alveolar ventilation also increases as

pH decreases (rate and depth).pH decreases (rate and depth). Coarse , CANNOT eliminate fixed Coarse , CANNOT eliminate fixed

acid.acid.

Renal Acid-Base RegulationRenal Acid-Base Regulation

Kidneys help regulate blood pH by Kidneys help regulate blood pH by excreting Hexcreting H++ and reabsorbing HC0 and reabsorbing HC033

--.. Most of the HMost of the H++ secretion occurs across secretion occurs across

the walls of the PCT in exchange for Nathe walls of the PCT in exchange for Na++.. Antiport mechanism.Antiport mechanism.

Moves NaMoves Na++ and H and H++ in opposite directions. in opposite directions.

Normal urine normally is slightly acidic Normal urine normally is slightly acidic because the kidneys reabsorb almost all because the kidneys reabsorb almost all HC0HC033

-- and excrete H and excrete H++.. Returns blood pH back to normal range.Returns blood pH back to normal range.

Simple Acid-Base DisturbancesSimple Acid-Base Disturbances

When compensation is appropriateWhen compensation is appropriate

Metabolic acidosis (Metabolic acidosis (↓ HCO↓ HCO33, ↓ pCO, ↓ pCO22))

Metabolic alkalosis (Metabolic alkalosis (↑ HCO↑ HCO33, ↑ pCO, ↑ pCO22))

Respiratory acidosis (Respiratory acidosis (↑ pCO↑ pCO22, ↑ HCO, ↑ HCO33))

Respiratory alkalosis (Respiratory alkalosis (↓ pCO↓ pCO22, ↓ HCO, ↓ HCO33))

Organ dysfunctionOrgan dysfunction

CNSCNS – – respiratory acidosis (suppression) and alkalosis respiratory acidosis (suppression) and alkalosis (stimulation)(stimulation)

PulmonaryPulmonary – – respiratory acidosis (COPD) and alkalosis respiratory acidosis (COPD) and alkalosis (hypoxia, pulmonary embolism)(hypoxia, pulmonary embolism)

CardiacCardiac – – respiratory alkalosis, respiratory acidosis, respiratory alkalosis, respiratory acidosis, metabolic acidosis (pulmonary edema)metabolic acidosis (pulmonary edema)

GIGI – – metabolic alkalosis (vomiting) and acidosis metabolic alkalosis (vomiting) and acidosis (diarrhea)(diarrhea)

LiverLiver – respiratory alkalosis, metabolic acidosis (liver – respiratory alkalosis, metabolic acidosis (liver failure)failure)

KidneyKidney – metabolic acidosis (RTA) and alkalosis (1 – metabolic acidosis (RTA) and alkalosis (1stst aldosteone)aldosteone)

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Metabolic (Nonrespiratory) Metabolic (Nonrespiratory) Acidosis: HAcidosis: H++ ↑ pH ↑ pH ↓↓

Symptoms:Symptoms: Increased ventilation, fatigue, Increased ventilation, fatigue, confusionconfusion

Causes:Causes: Renal disease, including hepatitis Renal disease, including hepatitis and cirrhosis; increased acid production and cirrhosis; increased acid production in diabetes mellitus, hyperthyroidism, in diabetes mellitus, hyperthyroidism, alcoholism, and starvation; loss of alkali in alcoholism, and starvation; loss of alkali in diarrhea; acid retention in renal failurediarrhea; acid retention in renal failure

Treatment:Treatment: Sodium bicarbonate given Sodium bicarbonate given orally, dialysis for renal failure, insulin orally, dialysis for renal failure, insulin treatment for diabetic ketosistreatment for diabetic ketosis

Organ DysfunctionOrgan Dysfunction

EndocrineEndocrine Diabetes mellitus – Diabetes mellitus – metabolic acidosismetabolic acidosis Adrenal insufficiency – metabolic acidosisAdrenal insufficiency – metabolic acidosis Cushing’s – metabolic alkalosisCushing’s – metabolic alkalosis Primary aldosteronism – metabolic alkalosisPrimary aldosteronism – metabolic alkalosis

Drugs/toxinsDrugs/toxins Toxic alcohols – metabolic acidosis Toxic alcohols – metabolic acidosis ASA – metabolic acidosis and respiratory alkalosisASA – metabolic acidosis and respiratory alkalosis Theophylline overdose – respiratory alkalosisTheophylline overdose – respiratory alkalosis

Generation of Metabolic AcidosisGeneration of Metabolic Acidosis

H+

HCO3

-

Exogenous acids ASA Toxic alcohol

Endogenous acids ketoacids DKA starvation alcoholic Lactic acid L-lactic D-lactate

Administration of HCl, NH4

+Cl, CaCl2, lysine HCl

Loss of HCO3

diarrhea

Compensations

Buffers

Lungs

Kidneys

High gap Normal gap If kidney function is normal, urine anion gap Neg

Respiratory Respiratory acidosisacidosis

PCO2 greater than expectedAcute or chronicCauses

excess CO2 in inspired air(rebreathing of CO2-containing expired air, addition of CO2 to inspired air, insufflation of CO2 into body cavity)

decreased alveolar ventilation(central respiratory depression & other CNS problems, nerve or muscle disorders, lung or chest wall defects, airway disorders, external factors)

increased production of CO2

(hypercatabolic disorders)

Metabolic acidosisMetabolic acidosis

Plasma HCO3- less than expected

Gain of strong acid or loss of base

Alternatively, high anion gap or normal anion gap metabolic

acidosis

Causes high anion-gap acidosis (normochloremic)

(ketoacidosis, lactic acidosis, renal failure, toxins) normal anion-gap acidosis (hyperchloremic)

(renal, gastrointestinal tract, other)

Respiratory Respiratory alkalosisalkalosis

PCO2 less than expected

Acute or chronic

Causes increased alveolar ventilation

(central causes, direct action via respiratory center; hypoxaemia, act via peripheral chemoreceptors; pulmonary causes, act via intrapulmonary receptors; iatrogenic, act directly on ventilation)

Metabolic Metabolic alkalosisalkalosis

Plasma HCO3- greater than expected

Loss of strong acid or gain of base

Causes (2 ways to organize) loss of H+ from ECF via kidneys (diuretics) or gut (vomiting) gain of alkali in ECF from exogenous source (IV NaHCO3

infusion) or endogenous source (metabolism of ketoanions)or addition of base to ECF (milk-alkali syndrome) Cl- depletion (loss of acid gastric juice) K+ depletion (primary/secondary hyperaldosteronism) Other disorders (laxative abuse, severe hypoalbuminaemia)

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Metabolic (Nonrespiratory) Metabolic (Nonrespiratory) Acidosis: HAcidosis: H++ ↑ pH ↑ pH ↓↓

Symptoms:Symptoms: Increased ventilation, fatigue, Increased ventilation, fatigue, confusionconfusion

Causes:Causes: Renal disease, including hepatitis Renal disease, including hepatitis and cirrhosis; increased acid production and cirrhosis; increased acid production in diabetes mellitus, hyperthyroidism, in diabetes mellitus, hyperthyroidism, alcoholism, and starvation; loss of alkali in alcoholism, and starvation; loss of alkali in diarrhea; acid retention in renal failurediarrhea; acid retention in renal failure

Treatment:Treatment: Sodium bicarbonate given Sodium bicarbonate given orally, dialysis for renal failure, insulin orally, dialysis for renal failure, insulin treatment for diabetic ketosistreatment for diabetic ketosis

H

HCO3

Loss of H+ from GIVomiting, NG suctionCongenital Cl diarrhea

Loss of H+ from kidney1st & 2nd aldosteroneACTHDiureticsBartter’s, Gitelman’s, Liddle’sInhibition of β – OH steroid deh

Gain of HCO3 Administered HCO3, Acetate, citrate, lactatePlasma protein products

Compensations

Buffer

Respiratory

Forget the kidney

Vomiting vs DiureticVomiting vs Diuretic

Active vomitingActive vomiting ECF depletionECF depletion Metabolic alkalosisMetabolic alkalosis High UNa, UK, High UNa, UK, low UCllow UCl Urine pH > 6.5Urine pH > 6.5

Remote vomitingRemote vomiting ECF depletionECF depletion Metabolic alkalosisMetabolic alkalosis Low UNa, high UK, low Low UNa, high UK, low

ClCl Urine pH 6Urine pH 6

Active diureticActive diuretic ECF depletionECF depletion Metabolic alkalosisMetabolic alkalosis HighHigh UNa, UK and UNa, UK and ClCl Urine pH 5-5.5Urine pH 5-5.5

Remote diureticRemote diuretic ECF depletionECF depletion Metabolic alkalosisMetabolic alkalosis Low UNa, high UK, low Low UNa, high UK, low

ClCl Urine pH 5-6Urine pH 5-6

Treatment of Respiratory Treatment of Respiratory AlkalosisAlkalosis

Correct the underlying disorder. Correct the underlying disorder. Hyperventilation Syndrome: Hyperventilation Syndrome: Best Best

treated by having the patient treated by having the patient rebreathe into a paper bag to rebreathe into a paper bag to increase pCO2, decrease ventilator increase pCO2, decrease ventilator raterate

血红蛋白缓冲对的缓冲作用血红蛋白缓冲对的缓冲作用

COCO22

ClCl--

CO2+H2O

C.A.

H2CO3

HCO-3

H+--Hb-

RBC