1. Anion Gap

The difference between [Na+] and the sum of
[HC03-] and [Cl-].
 [Na+] – ([HC0 -] + [Cl-]) =
3


140 - (24 + 105) = 11
 Normal = 12 + 2
Clinicians use the anion gap to identify the cause
of metabolic acidosis.

2. Types of Acids in the Body

Volatile acids:
Can leave solution and enter the atmosphere.
 H C0 (carbonic acid).
2
3


Pco2 is most important factor in pH of body
tissues.

3. 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
HB (n+1)
Weak base
B (n) + H (+)
=
The buffers distribute themselves via their dissociation constant (K) defined as the ratio
[B(n)] [H+] = K
[HB(n=1)]

4. 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+ + HCO3Note that the formation of H+ will decrease pH. The net reaction is
CO2 + H2O   H+ + HCO3-

5. Proteins

COOH or NH2.

Largest pool of buffers in the body.
pk. close to plasma.
Albumin, globulins such as Hb.



6. Other important buffers

The phosphate buffer system (HPO42-/H2PO4-) plays a role in plasma and erythrocytes.

H2PO4- + H2O ↔ H3O+ + HPO42-

Any acid reacts with monohydrogen phosphate to form dihydrogen phosphate
dihydrogen phosphate monohydrogen phosphate

H2PO4- + H2O ← HPO42- + H3O+

The base is neutralized by dihydrogen phosphate
dihydrogen phosphate

monohydrogen phosphate
H2PO4- + OH- → HPO42- + H3O+
6

7. Respiratory System





2nd line of defense.
Acts within min. maximal in 12-24 hrs.
H2CO3 produced converted to CO2, and
excreted by the lungs.
Alveolar ventilation also increases as pH
decreases (rate and depth).
Coarse , CANNOT eliminate fixed acid.

8. Renal Acid-Base Regulation


Kidneys help regulate blood pH by excreting H+ and
reabsorbing HC03-.
Most of the H+ secretion occurs across the walls of
the PCT in exchange for Na+.

Antiport mechanism.


Moves Na+ and H+ in opposite directions.
Normal urine normally is slightly acidic because the
kidneys reabsorb almost all HC03- and excrete H+.

Returns blood pH back to normal range.

9. Simple Acid-Base Disturbances

When compensation is appropriate
Metabolic acidosis (↓ HCO3, ↓ pCO2)
Metabolic alkalosis (↑ HCO3, ↑ pCO2)
Respiratory acidosis (↑ pCO2, ↑ HCO3)
Respiratory alkalosis (↓ pCO2, ↓ HCO3)

10. Organ dysfunction

CNS – respiratory acidosis (suppression) and alkalosis
(stimulation)





Pulmonary – respiratory acidosis (COPD) and
alkalosis (hypoxia, pulmonary embolism)
Cardiac – respiratory alkalosis, respiratory acidosis,
metabolic acidosis (pulmonary edema)
GI – metabolic alkalosis (vomiting) and acidosis
(diarrhea)
Liver – respiratory alkalosis, metabolic acidosis (liver
failure)
Kidney – metabolic acidosis (RTA) and alkalosis (1st
aldosteone)

11. Metabolic (Nonrespiratory) Acidosis:
H+ ↑ pH ↓



Symptoms: Increased ventilation, fatigue, confusion
Causes: Renal disease, including hepatitis and cirrhosis;
increased acid production in diabetes mellitus,
hyperthyroidism, alcoholism, and starvation; loss of
alkali in diarrhea; acid retention in renal failure
Treatment: Sodium bicarbonate given orally, dialysis for
renal failure, insulin treatment for diabetic ketosis
11

12. Organ Dysfunction

Endocrine

Diabetes mellitus – metabolic acidosis

Adrenal insufficiency – metabolic acidosis
Cushing’s – metabolic alkalosis
Primary aldosteronism – metabolic alkalosis



Drugs/toxins



Toxic alcohols – metabolic acidosis
ASA – metabolic acidosis and respiratory alkalosis
Theophylline overdose – respiratory alkalosis

13. Generation of Metabolic Acidosis
Administration of
HCl, NH4+Cl, CaCl2, lysine HCl
Exogenous acids
ASA
Toxic alcohol
H+
Compensations
Buffers
Endogenous acids
ketoacids
DKA
starvation
alcoholic
Lactic acid
L-lactic
D-lactate
High gap
Loss of HCO3
diarrhea
Lungs
Kidneys
HCO 3
Normal gap
If kidney function is normal, urine anion gap Neg

14. Respiratory acidosis
PCO2 greater than expected
Acute or chronic
Causes
 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)

15. Metabolic 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)

16. Respiratory alkalosis
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)

17. Metabolic alkalosis
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 NaHCO 3
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)

18. Metabolic (Nonrespiratory) Acidosis:
H+ ↑ pH ↓



Symptoms: Increased ventilation, fatigue, confusion
Causes: Renal disease, including hepatitis and cirrhosis;
increased acid production in diabetes mellitus,
hyperthyroidism, alcoholism, and starvation; loss of
alkali in diarrhea; acid retention in renal failure
Treatment: Sodium bicarbonate given orally, dialysis for
renal failure, insulin treatment for diabetic ketosis
18

19. Loss of H+ from GI
Vomiting, NG suction
Congenital Cl diarrhea
Loss of H+ from kidney
1st & 2nd aldosterone
ACTH
Diuretics
Bartter’s, Gitelman’s, Liddle’s
Inhibition of β – OH steroid deh
Gain of HCO3
Administered HCO3,
Acetate, citrate, lactate
Plasma protein products
H
Compensations
Buffer
Respiratory
HCO3
Forget the kidney

20. Vomiting vs Diuretic

Active vomiting





ECF depletion
Metabolic alkalosis
High UNa, UK, low UCl
Urine pH > 6.5
Remote vomiting





ECF depletion
Metabolic alkalosis
Low UNa, high UK, low
Cl
Urine pH 6
Active diuretic





ECF depletion
Metabolic alkalosis
High UNa, UK and Cl
Urine pH 5-5.5
Remote diuretic




ECF depletion
Metabolic alkalosis
Low UNa, high UK, low
Cl
Urine pH 5-6

21. Treatment of Respiratory Alkalosis


Correct the underlying disorder.
Hyperventilation Syndrome: Best treated by
having the patient rebreathe into a paper bag to
increase pCO2, decrease ventilator rate

22. 血红蛋白缓冲对的缓冲作
用
CO2+H2O
CO2
C.A.
H2CO3
HCO-3
H+--Hb-