Acid-base Balance and its Disorders

Prof. Dr. Meltem Pekpak

For optimal functioning of cells..

• Acids and bases in the body must be in balance.

• We all consume every day food and drinks which contain acids, metabolism produces also acids...

Body pH Balance

• Chemical blood buffers:

• Lungs,

• Cells,

• Kidneys

• Defences against changes in hydrogen concentration (getting acidotic..)

You get acidotic every day !

• While living, eating and drinking...there is..

• Production of 1 mmol of fixed acid/kg body weight per day (60 kg=60 mmol/day)

Buffers

• Extracellular:• Hemoglobin

– (‘Chloride shift’-for each chloride leaving the cell-one bicarbonate ion enters)

• Plasma protein – (with the liver, varying the amount of H-ions in the

protein structure)• Bicarbonate system:

– Normal acid to base ratio is 20:1– 20 parts bicarbonate to 1 part carbonic acid

(H2CO3=CO2),– Neutralizing a strong acid bicarb. will be lost

Human Acid-base Homeostasis

• Tight regulation:• CO2 tension

– by respiratory excretion (of volatile acids)

• Plasma bicarbonate [HCO3-]

– By renal HCO3- reabsorption and

– Elimination of protons produced by metabolism

• pH is determined by CO2 tension and [HCO3

-]

Physiology of Buffering:

• Ability of a solution containing a weak or poorly dissociated acid and its anion (a base) to resist change in pH when strong acid or alkali is added

• 1 ml of 0.1 M HCl to 9 ml distilled water =• [H+] from 10 -7 M to 10 -2 M= pH from 7 to 2• 1 ml of 0.1 M HCl to 9 ml of phosphate buffer:

dissoc. H+ combines with [HPO42-] = (H2PO4

-)

• pH fall of only 0.1= to 6.9

Bicarbonate Buffer

• Extracellular most important buffer

• Proteins and phosphate buffer less important

• Intracellular phosphate- most important b.

• Equilibrium conditions because abundant carbonic anhydrase in blood

• H+ + HCO3- H2CO3 H2O + CO2

• [H+ ]= Keq x [H2CO3 ]/[HCO3-]

Equations

• H+ + HCO3- H2CO3 H2O + CO2

• Equilibrium

• [H+ ]= Keq x [H2CO3 ]/[HCO3-]

Total Acid- base Metabolism Henderson-Hasselbalch 1909,1916

HCO3 -

• pH = pK + log ------------

PaCO2

Result of Metabolic and RespiratoryInterplay

Primary RespiratoryDisorders Altered by

RespiratoryCompensation for Metabolic Disorders

Metabolic comp.

Respiratorycomponent

Altered byBuffering

Primarily Altered in Metabolic Disorders

Normal Values• [HCO3

-] ~ 24 mM

• PaCO2 = 38 torr

• pH ~ 7.42

• Plasma HCO3- regulation by

– reclaiming filtered HCO3- and

– generating new HCO3- (carboanhydrase)

– ( to replace the lost internally titrating metabolic acid and externally from the GI tract)

• Production of 1 mmol of acid/kg body weight per day (60 kg=60 mmol/day)

Renal Acid -base Handling

• Two seperate functions:

• Bicarbonate reabsorption

• Net acid secretion

Proximal Tubular BicarbonateReclamation Process (90 %)

Two vehicles for apical H+ secretion (Na+/H+ exchanger), H+ATPase.Basolateral ion pumps: Na+/K+ ATPase, (Na+HCO3-)symporter,HCO3-/Cl-

Exchanger. The role of carbonic anhydrase (CA) in tubular cell and brush border

Net Acid Excretion

• Urine is acid = pH~ 4.5• Buffer salts are in the tubular fluid• Phosphate is the most important buffer in urine:

HPO42- + H+ = H2PO4

-

• Nonvolatile (fixed) acids (anions= sulfates, phosphates) must be accompanied in the urine by equivalent cations (Na +, K +, Ca + +) for maintenance of electrical neutrality

• In acid urine ammonium helps to keep

[H+ ] (ammonia NH3+ to NH4

+)

Clinical Evaluation

• Patient history• Clinical presentation• Acidemia Hyperventilation• Alkalemia Paresthesias and Tetany• Laboratory: Blood acid-base status:• Blood pH (4 º C, with anticoagulant, promptly), • Urine pH• Plasma and urine electrolyte concentration• Lactate concentration

Acidosis

• Clinical effects of severe acidosis: pH <7.2• Cardiovascular system effects:• Decreased myocardial contractility• Decreased cardiac output• Cardiac failure• Hypotension• Decreased hepatic and renal blood flow• Centralization of effective blood volume• Tissue hypoxia • Pulmonary edema

Metabolic acidosis• Hallmark is [HCO3

-] • 1. Acid production net acid intake

above net renal excretion (ketoacidosis, lactic acidosis, ammonium chloride loading)

• 2. failure of renal net excretion (chronic renal failure, renal tubular acidosis)

• 3. Bicarbonate loss via the gastroinestinal tract (diarrhea, gastrointestinal fistula)

• 4. Nonbicarbonate solutions added to ECF (dilutional acidosis)

Steps of evaluation• 1. Examine pH= Reduction ( 7.2) Acidosis

• Increase (7.5) Alkalosis• 2. Examine directional change of PCO2

• and [HCO3

-] , • pH acid, HCO3

- low Metabolic acidosis

• pH alkal., HCO3- high Metabolic alkalosis

• 3. Assess degree of compensation: Mixed acid-base disorder?• Metabolic acidosis PCO2 • Metabolic alkalosis PCO2• Failure of respiratory compenstion= primary respiratory acid-base

disorder• Never to initial pH through compensation !!

• 4. Calculate the serum anion gap• Is the acid-base disorder organic or

mineral in origin??• We use venous sample blood electrolytes:• Electroneutrality demands:• Serum anion gap, that means:• [Na+] + [UC]= [Cl-] +[Total CO2] + [UA]• (U means: unmeasured)

Steps of evaluation

Normally the serum anion gap is about 9 (6-12 mEq/l), a major increase inAnion gap > 26 mEq/l always implies existence of an organic acidosis

Differential Diagnosis of Metabolic Acidosis

• Normal anion gap Increased anion gap• (hyperchloemic) (organic)_________

• GI loss of HCO3- acid production

• Diarrhea Lactic acidosis• Renal tub. Acidosis Diab. Ketoacidosis• Parenteral alimentation Toxic alcohol,salicy. • Carbonic anhydr. İnh. Acute renal failure• K-sparing diuretics Chronic renal failure

Increased anion gap Metabolic acidosis

• Ketoacidosis (diabetic)• Uremia (renal failure)• Salicylate intoxication• Starvation• Methanol intoxication• Alcohol ketoacidosis• Unmeasured osmoles (intoxication)• Lactic acidosis

Simple decompensatedAcid-base Disorders

• Acid Base Dis.: pH pCO2 HCO3-

• Metabolic acidosis • Respiratory acidosis • Metabolic alkalosis • Respiratory alkalosis

Compensatory Response one half of acid load is buffered by nonbicarbonate

buffers= Bone, protein, red cells.. • PCO2 (Kussmaul)• compensatory response after 15-30 minutes, • 5 days up to maximal• Kidney:• Metabolic acidosis processing of glutamine into NH4

+ (ammonia to ammonium for better H-excretion)and

• Bicarbonate generation (and reclaiming)

Respiratory Acidosis• Acute increase in pCO2• Buffered primarily by intracellular buffers• Chronic state:• Kidneys compensation:• Increase net acid excretion,• (48 hours for fully development)• Underlying cause:• Central nervous system disease,• lung (COPD)and heart disease, • sedatives and opiates depressing the

respiratory center• Hypercapnic encephalopathy can develop

Metabolic Alkalosis

• Plasma bicarbonate [HCO3-] = pH

• 1) H+ GI loss or shift into cells• 2) Excess HCO3

- Administration of bicarbonate, or precursors: lactate, acetate, citrate orFailure to excrete: mineralocorticoid effect

• 3) Loss of fluid with Diuretic therapy

[Cl-], [K+] and [H+] loss from plasma- extracellular volume contraction

Alkalosis

Volume Depletion and Metabolic Alkalosis

• Absolute volume depletion:• Loss of salt by bleeding or vomitting or

• Effective volume depletion:

• Heart failure, cirrhosis, nephrotic syndrome whenever

GFR Tubular HCO3

- reabsorption • Because proximal tubule reabsorption is enhanced

forNa and water

Compensatory Respiratory Response

• Alveolar hypoventilation(hypercapnia)

• (limited pCO2 rise to 50-60 mm Hg)

• Kidneys:

• Excretion of HCO3- proportional to GFR

(excessive)

pCO2 , pH due to:Hypoxia (compensatory hyperventilation)• Acute: pulmonary edema or emboli, pneumonia, • Chronic: severe anemia, high altitude,

hypotensionRespiratory center stimulation• Pregnancy, Anxiety, Fever, heat stroke, sepsis,

salisylate intox., cerebral disease, hepatic cirrhosis,

Increased mechanical ventilation

Respiratory Alkalosis

Respiratory Alkalosis

• Most common acid-base disorder• Physiologic in pregnancy and high altitude• Bad prognosis in critically ill patients

(the higher hypocapnia, the higher mortality)• Hyperventilation,• Perioral and extremity paresthesias,• Light-headedness,• Muscle cramps,• Hyperreflexia, seizures, ionized Ca tetany

Metabolic Alkalosiswith and without Volume Depletion • Volume depleted- Chloride responsive

metabolic acidosis:

• Urine chloride is low (<10 mmol/l)

• Due to:

• Gastric fluid losses

• Stool losses

• Diuretic therapy

Metabolic AlkalosisExcessive Mineralocorticoids

• Mineralocorticoids stimulate hydrogen ion secretion

• And this bicarbonate reabsorption• Urinary chloride is normal (<20 mmol/l)• Hypokalemia• Primary aldosteronizm, • Bartter’s Syndrome,• Cushing Syndrome• Renovascular hypertension

The proximal tubulus cells form carbonic acid from carbon dioxide and waterunder the influence of the enzyme carboanhydrase (CA). Carbonic acid ionizes to yield hydrogen and bicarbonate . Hydrogen formed in the cellexchanges with sodium in the tubular fluid (dashed circle). As a net effect Sodium bicarbonate is reabsorbed, and the hydrogen ion secreted into thetubular lumen is buffered by filtered bicarbonate.

Proximal Tubular Bicarbonate Reclamation Process (90 %)

Henderson-Hasselbach 1909,1916

• H2CO3 = p CO2 + solubility in physiol. Fluids

• [H+ ]= K x [S x pCO2 ]/[HCO3-]

Antilog of both sides:

pH= pK + log10 [HCO3-] / [S x PCO2]

In blood at 37º C, pK =6.1 and S is 0.03

pH= 6.1+ log10 [HCO3-] / [0.03 x PaCO2]