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
Primarily Altered
in Metabolic Disorders

Altered by
Buffering

HCO3 pH

= pK + log
Primary
Respiratory
Disorders

Result of Metabolic
and Respiratory
Interplay

-----------PaCO2

Metabolic comp.

Respiratory
component

Altered by
Respiratory
Compensation for
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 Bicarbonate

Reclamation Process (90 %)
Two vehicles for apical H+ secretion (Na+/H+ exchanger), H+ATPase.
Basolateral ion pumps: Na+/K+ ATPase, (Na+HCO3-)symporter,HCO3-/ClExchanger. 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 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 !!

Steps of evaluation
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)

Normally the serum anion gap is about 9 (6-12 mEq/l), a major increase in
Anion 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

Lactic acidosis
Diab. Ketoacidosis
Toxic alcohol,salicy.
Acute renal failure
Chronic renal failure

Diarrhea
Renal tub. Acidosis
Parenteral alimentation
Carbonic anhydr. nh.
K-sparing diuretics

Increased anion gap

Metabolic acidosis

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

Simple decompensated
Acid-base Disorders

Acid Base Dis.:

pH

Metabolic acidosis
Respiratory acidosis
Metabolic alkalosis
Respiratory alkalosis

pCO2 HCO3

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 HCO3Administration of bicarbonate, or precursors:
lactate, acetate, citrate or
Failure to excrete: mineralocorticoid effect
3) Loss of fluid with
Diuretic therapy
[Cl-], [K+] and [H+] loss from plasmaextracellular 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
for
Na and water

Compensatory Respiratory
Response

Alveolar hypoventilation(hypercapnia)
(limited pCO2 rise to 50-60 mm Hg)
Kidneys:
Excretion of HCO3- proportional to GFR
(excessive)

Respiratory Alkalosis
pCO2 , pH due to:
Hypoxia (compensatory hyperventilation)
Acute: pulmonary edema or emboli, pneumonia,
Chronic: severe anemia, high altitude,
hypotension
Respiratory center stimulation
Pregnancy, Anxiety, Fever, heat stroke, sepsis,
salisylate intox., cerebral disease, hepatic
cirrhosis,
Increased mechanical ventilation

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 Alkalosis
with 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 Alkalosis
Excessive Mineralocorticoids
Mineralocorticoids stimulate hydrogen ion
secretion
And this bicarbonate reabsorption
Urinary chloride is normal (<20 mmol/l)
Hypokalemia
Primary aldosteronizm,
Bartters Syndrome,
Cushing Syndrome
Renovascular hypertension

Proximal Tubular Bicarbonate Reclamation Process (90 %)

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

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 37 C, pK =6.1 and S is 0.03
pH= 6.1+ log10 [HCO3-] / [0.03 x PaCO2]