Acid-Base Balance

Question 1

Acids

Answer 1

chemicals that release (donate) H+: [e.g.- carbonic acid, hydrochloric acid, ammonium, & dibasic phosphoric acid]

Acids dissociate to some extent in solution:
HA  H+ + A-
Strong acids dissociate more than weak acids

Question 2

Bases

Answer 2

chemicals that combine with (accept) H+: [e.g.- monobasic phosphoric acid, bicarbonate, ammonia]

Question 3

Chemical buffer systems

Answer 3

Mixture of weak acid and its conjugate base in aqueous solution

Chemical buffers minimize but don’t completely prevent pH changes caused by strong acid or base

Ability (‘strength’) of buffer to minimize pH changes depends on:
Concentrations of buffer system components
Nearness of buffer’s pKa to pH of solution

Question 4

Volatile acid:

Answer 4

carbonic acid: H2CO3
In chemical equilibrium with CO2, a volatile gas: H2CO3  CO2 + H2O
Pulmonary ventilation controls H2CO3 concentration in body fluids

Question 5

Fixed acids

Answer 5

non-carbonic acids generated metabolically (e.g. sulfuric, phosphoric acids)
Initially neutralized by buffers in body fluids
Ultimately excreted in urine

Question 6

Metabolic sources of H+

Answer 6

Oxidative metabolism: CO2 (c. 15,000 mEq/day)
CO2 + H2O  H2CO3  H+ + HCO3-

Nonvolatile (fixed) acids: 40-80 mEq/day
Glycolysis: lactic acid (pKa 3.9)
Incomplete oxidation of fatty acids: ketone acids (pKa c. 4.5)
Protein, nucleic acid, phospholipid metabolism: sulfuric, phosphoric, hydrochloric acids
Cannot be removed from body by ventilation

Question 7

3 lines of defense against pH changes

Answer 7

1. Chemical buffers
2. Respiration
3. Kidneys

Question 8

1st line defense

Answer 8

Chemical Buffers Expand: Table slide 17

Question 9

Bicarbonate system is the major EC buffer

Answer 9

Equilibrium between H2CO3 and HCO3- (pKa = 3.8):
[HCO3-]
pH = 3.8 + log [H2CO3]
H2CO3 is also in equilibrium with CO2 and H2O; CO2 conc is 400 x [H2CO3], thus
[HCO3-]
pH = 3.8 + log [CO2]/400 , or
[HCO3-]
pH = 6.1 + log [CO2]

Question 10

CO2 concentration is related to PCO2

Answer 10

CO2 concentration is related to PCO2. For each mmHg PCO2, 0.03 millimolar CO2 is in solution at 37ºC. Thus:

                                           [HCO3-]
        pH    =   6.1  +  log (0.03 · PCO2)

Advantage: [HCO3-] and PCO2 are easily measured.

Question 11

Why is bicarbonate buffer system so powerful?

Answer 11

Components (HCO3-, CO2) are abundant
Bicarbonate buffer system is ‘open’; concentrations of HCO3- and CO2 are readily adjusted by respiration and renal function:
oxidative
metabolism kidneys

                          CO2     HCO3-

ventilation kidneys

Question 12

Urine pH range:

Answer 12

4.5 - 8.0

Question 13

Renal response to excess acid:

Answer 13

All of filtered HCO3- is reabsorbed

Additional H+ is secreted into lumen, excreted primarily as ammonium (NH4+)

Question 14

Renal response to excess base:

Answer 14

Incomplete reabsorption of filtered HCO3-
Decreased H+ secretion
Secretion of HCO3- in collecting duct

Question 15

urinary buffers. Two types:

Answer 15

Titratable acid: conjugate bases of metabolic acids (phosphate, creatinine, urate) accept H+ in lumen

Ammonia, generated by tubular epithelium

Question 16

mEq H+ are excreted in urine

Each day

Answer 16

40-80 mEq H+

Question 17

Total renal H+ excretion

Answer 17

H+ excretion = urinary excretion of titratable acid + ammonium - HCO3-

Typical rates (mEq/day):
               24  +  48  -  2   =   70 mEq/day

Note: HCO3- excretion is equivalent to adding acid to body fluids (for each mEq of HCO3- lost, a free H+ is left behind)

Question 18

Luminal pH along nephron

Answer 18

Acidification of luminal fluid is rather modest (pH c. 6.7) before collecting duct. In collecting duct, fluid can be acidified to a pH as low as 4.5.

Question 19

Collecting ducts can secrete H+ or HCO3-

Answer 19

-intercalated cells actively secrete H+:
H+-ATPase
up to 900 fold [H+] gradient

-intercalated cells secrete HCO3- to eliminate excess base

Question 20

Acidification of urine begins in proximal tubule

Answer 20

Most of the H+ secreted by the proximal tubule is used to reabsorb filtered HCO3-, so luminal pH falls only slightly (~6.7) in this segment

Question 21

Tubular reabsorption of filtered HCO3-

Answer 21

At 25 mEq/l plasma concentration, c. 4500 mEq of HCO3- are filtered into nephrons per day
Excretion of HCO3- has same effects as gaining H+; excretion of even small fraction of filtered HCO3- would acidify body fluids
Normal individuals: essentially all of filtered HCO3- must be recaptured
If arterial pH is too high, kidneys respond by incompletely reabsorbing HCO3-

Question 22

Important features of HCO3- reabsorption

Answer 22

HCO3- is temporarily converted to CO2
Ultimately dependent on Na+,K+ ATPase
Process does not result in net secretion of H+
By this mechanism, ~ 80% of filtered HCO3- is reabsorbed in proximal tubule, most of remainder in thick ascending limb
A saturable process: at [HCO3-] > 26 mEq/l, some is excreted in urine

Question 23

Excretion of H+ as titratable acid

Answer 23

Filtered HPO42- is the most important buffer converted to titratable acid

Question 24

Excretion of H+ as ammonium

Answer 24

Two NH4+ are generated by glutamine oxidation within the tubular epithelial cells. Two HCO3- are produced by glutamine oxidation.

Question 25

Chronic acidemia (elevated H+ conc.)

Answer 25

up-regulates renal NH4+ production, excretion

Question 26

In alkalemia (reduction in H+ conc.),

Answer 26

collecting ducts secrete HCO3- | B intercalated cell

Question 27

Factors controlling renal H+ secretion

Answer 27

1. intracellular pH 2. plasma PCO2 3. carbonic anhydrase activity (affecting H+ & HCO3) 4. Na+ reabsorption (ECF volume changes due to angiotensin/aldosterone) 5. extracellular [K+] 6. aldosterone

Question 28

Simple acid-base disorders

Answer 28

Normal arterial plasma pH range: 7.35-7.45 Acidemia: a reduction in arterial pH below 7.35 Acidosis: any abnormal condition that produces acidemia Alkalemia: an increase in arterial pH above 7.45 Alkalosis: any abnormal condition that produces alkalemia

Question 29

Respiratory acidosis: increased arterial PCO2

Answer 29

 CO2 + H2O   H+ +  HCO3- | Renal response: increased H+ secretion restores extracellular pH, increases HCO3- further

Question 30

Respiratory alkalosis: decreased arterial PCO2

Answer 30

 CO2 + H2O   H+ +  HCO3- | Renal response: less H+ secretion, more HCO3-excretion in urine

Question 31

Metabolic acidosis

Answer 31

Low plasma pH (Lowered ratio of HCO3- to PCO2) due to: gain of fixed acid in body fluids (ketone bodies, lactic acid) or loss of HCO3- (diarrhea) In either case, [HCO3-] falls Respiratory compensation: increased ventilation (peripheral chemoreceptors) Renal compensation: increased H+ secretion; production of new HCO3-

Question 32

Metabolic alkalosis

Answer 32

Abnormally high plasma pH (increased ratio of HCO3- to PCO2) due to: Excessive gain of strong base or HCO3- (alkali ingestion) Excessive loss of fixed acid (loss of gastric acid through vomiting) HCO3- concentration rises due to shift in carbonic anhydrase equilibrium toward HCO3- Respiratory compensation: decreased ventilation Renal compensation: Incomplete reabsorption of filtered HCO3- -intercalated cells secrete HCO3-

Question 33

Anion gap (A.G.)

Answer 33

Used in differential diagnosis of metabolic acidosis A.G. = measured cation (Na+) - measured anions (Cl-, HCO3-) Gap is comprised of unmeasured anions including plasma albumin, phosphate, sulfate, citrate, lactate, ketoacids Normal range: 3-18 mEq/l – Method-Dependent!!!!! Anion gap is either normal or increased, depending on cause of metabolic acidosis

Question 34

Hyperchloremic acidosis

Answer 34

A.G. is unchanged: HCl + HCO3-  Cl- + H2O + CO2 Loss of HCO3- is matched by gain of Cl-

Question 35

High anion gap acidosis (normochloremic):

Answer 35

HCO3- is replaced by unmeasured anion (lactate, ketoacidosis, poisoning): HA + HCO3-  A- + H2O + CO2 In this case, anion gap increases

Question 36

Causes of high anion gap acidosis

Answer 36

``` You can find the anion gap in E. Elm Park: Ethanol Ethylene glycol Lactic acid Methanol Paraldehyde Aspirin Renal failure Ketone bodies Or…. MUDPILES (will be listed in CIS) ```