Acid-Base Balance Flashcards
Acids
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
Bases
chemicals that combine with (accept) H+: [e.g.- monobasic phosphoric acid, bicarbonate, ammonia]
Chemical buffer systems
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
Volatile acid:
carbonic acid: H2CO3
In chemical equilibrium with CO2, a volatile gas: H2CO3 CO2 + H2O
Pulmonary ventilation controls H2CO3 concentration in body fluids
Fixed acids
non-carbonic acids generated metabolically (e.g. sulfuric, phosphoric acids)
Initially neutralized by buffers in body fluids
Ultimately excreted in urine
Metabolic sources of H+
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
3 lines of defense against pH changes
- Chemical buffers
- Respiration
- Kidneys
1st line defense
Chemical Buffers Expand: Table slide 17
Bicarbonate system is the major EC buffer
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]
CO2 concentration is related to PCO2
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.
Why is bicarbonate buffer system so powerful?
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
Urine pH range:
4.5 - 8.0
Renal response to excess acid:
All of filtered HCO3- is reabsorbed
Additional H+ is secreted into lumen, excreted primarily as ammonium (NH4+)
Renal response to excess base:
Incomplete reabsorption of filtered HCO3-
Decreased H+ secretion
Secretion of HCO3- in collecting duct
urinary buffers. Two types:
Titratable acid: conjugate bases of metabolic acids (phosphate, creatinine, urate) accept H+ in lumen
Ammonia, generated by tubular epithelium
mEq H+ are excreted in urine
Each day
40-80 mEq H+
Total renal H+ excretion
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)
Luminal pH along nephron
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.
Collecting ducts can secrete H+ or HCO3-
-intercalated cells actively secrete H+:
H+-ATPase
up to 900 fold [H+] gradient
-intercalated cells secrete HCO3- to eliminate excess base
Acidification of urine begins in proximal tubule
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
Tubular reabsorption of filtered HCO3-
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-
Important features of HCO3- reabsorption
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
Excretion of H+ as titratable acid
Filtered HPO42- is the most important buffer converted to titratable acid
Excretion of H+ as ammonium
Two NH4+ are generated by glutamine oxidation within the tubular epithelial cells. Two HCO3- are produced by glutamine oxidation.
Chronic acidemia (elevated H+ conc.)
up-regulates renal NH4+ production, excretion
In alkalemia (reduction in H+ conc.),
collecting ducts secrete HCO3-
B intercalated cell
Factors controlling renal H+ secretion
- intracellular pH
- plasma PCO2
- carbonic anhydrase activity (affecting H+ & HCO3)
- Na+ reabsorption (ECF volume changes due to angiotensin/aldosterone)
- extracellular [K+]
- aldosterone
Simple acid-base disorders
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
Respiratory acidosis: increased arterial PCO2
CO2 + H2O H+ + HCO3-
Renal response: increased H+ secretion restores extracellular pH, increases HCO3- further
Respiratory alkalosis: decreased arterial PCO2
CO2 + H2O H+ + HCO3-
Renal response: less H+ secretion, more HCO3-excretion in urine
Metabolic acidosis
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-
Metabolic alkalosis
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-
Anion gap (A.G.)
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
Hyperchloremic acidosis
A.G. is unchanged:
HCl + HCO3- Cl- + H2O + CO2
Loss of HCO3- is matched by gain of Cl-
High anion gap acidosis (normochloremic):
HCO3- is replaced by unmeasured anion (lactate, ketoacidosis, poisoning):
HA + HCO3- A- + H2O + CO2
In this case, anion gap increases
Causes of high anion gap acidosis
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)
