Renal 21
Thur 03/20/03 9am
Dr. Mallet
Le Giang
Proscribe Samera Kasim
Page 1 of 7
Acid Base Balance II
Cont from 8am lecture….
I. Excretion of H+ (figure)
a. 2 options:
b. as a titratable acid
i. (berne & levy fig 44-4, p. 769)
ii. CO2 and water move into the cell, and carbonic anhydrase
combines them, making carbonic acid, which further dissociates
into H+ and HCO3-. This results in the secretion of H+.
iii. H+ combines with a filtered base such as HPO4, forming the
conjugate acid of that base, H2PO4.
iv. This is excreted in the urine
v. Bicarb is made in the kidneys from CO2 and H20 and returned to
the body
vi. This bicarb is used to replenish that used to buffer the H+ secreted.
vii. SO, an acid is being made somewhere in the body, increasing H+
conc. Bicarb buffers it, resulting in decr [bicarb]. When the
kidneys excrete the acid made, they actually make bicarb to
replace that which did the buffering.
c. as ammonium (NH4)
i. (Berne & Levy Fig 44-5, p. 770)
ii. ammonium is not filtered, but is generated from the metabolism of
glutamine, which is an important energy source in the renal tubular
epithelium.
iii. When oxidized, it releases 2 ammonia, which combine with 2 H+
to make ammonium, which carries a + charge. Thus if it leaves the
cell, it is exchanged with Na.
iv. OR the ammonia could diffuse through the lipid bilayer to the
lumen to form ammonium.
v. This is the major way by which the kidneys eliminate fixed
acids from the body.
vi. The rate at which this occurs can be adjusted as in chronic
acidemia
II. Chronic acidemia (graph)
i. In chronic acidemia, the kidneys up-regulate their ability to
oxidize glutamine and make ammonium, thus resulting in
increased urine ammonium at a given pH.
ii. Chronic academia also activates the genetic machinery that
stimulates the synthesis of glutaminase, which is the enzyme that
catalyzes the rate limiting step in glutamine. More glutaminase
Renal 21
Thur 03/20/03 9am
Dr. Mallet
Le Giang
Proscribe Samera Kasim
Page 2 of 7
increases the ability for the oxidation of glutamine and subsequent
release of the amino groups to make ammonium.
III. SUMMARY: Session 8
a. Henderson-Hasselbalch equation
b. First line of defense: buffer systems
c. Bicarbonate system is an ‘open’ buffer system
d. Second line of defense: ventilation (lungs remove acid by removing CO2)
e. Third line of defense: renal excretion of H+
f. Bicarbonate reabsorption adjustment
g. Excretion of H+ as titratable acids
h. Excretion of H+ as ammonium
i. Very little of free acid secreted as the free H+ ion.
IV. OVERVIEW: Session 9
a. Physiological control of renal H+ secretion: six factors influence epithelial
H+ secretion
b. Mechanisms that defend intracellular pH throughout the body
c. Acid-base disorders
d. Respiratory acidosis, respiratory alkalosis (change in PCO2)
e. Metabolic acidosis, metabolic alkalosis
f. Anion gap: differential diagnosis of metabolic acidosis
i. KNOW THIS
V. Alkalemia
a. collecting ducts secrete HCO3b. β-Intercalated cells actively secrete bicarb into the lumen
VI. Factors controlling renal H+ secretion
a. There’s 6 of them…
b. High H+ concentration in the cell means there’s more available to
secrete
c. PCO2 in the blood: as the partial pressure of CO2 increases during
pulmonary insufficiency, CO2 can diffuse into the blood, where it
combines with water to form H+ will.
i. CO2 is a source of H+ via the carbonic anhydrase reaction.
d. Carbonic Anhydrase (CA) activity: CA is an abundant enzyme;
diuretics can inhibit them and impede the reaction: CO2 + H2O  H2CO3
i. Normally not a limiting factor; it’s an abundant enzyme in the
tubular epithelium except in the presence of Carbonic anhydrase
inhibiting diuretics
ii. Tubular H+ secretions decrease, predisposing the pt to become
more acidemic.
Renal 21
Thur 03/20/03 9am
Dr. Mallet
Le Giang
Proscribe Samera Kasim
Page 3 of 7
iii. Bicarb reabsorption will decrease because H+ secretion is required
to capture the filtered bicarb
iv. A patient with alkylemia and edema, the CA inhibitory would be
an ideal diuretic
e. Na reabsorption: more Na reabsorption = more H+ secretion.
i. The entry of one cation favors the entry of another to maintain
neutrality
ii. Diuretics decrease Na reabsorption in the proximal tubule. Thus
there is a lot of Na in the lumen upon arriving at the collecting
duct. That increases Na reabsorption there, resulting in increased K
secretion and H+ secretions
iii. Diuretics can predispose a person to developing alkylemia.
f. Change in extracellular pH
i. K+ can influence H+ secretion; they generally move in opposite
directions
ii. If you decrease the extracellular K+ conc, K leaves the cell down
its cg and H+ enters
iii. H+ intracellular conc and secretions increase
iv. Hypokalemia leads to increased H+ secretion
g. Aldosterone:
i. Stimulates Na reabsorption and K and H+ secretion
ii. Activates H+ ATPases in the luminal membrane, directly
stimulating H+ secretion
iii. **Conn’s disease (hyperaldosteronism) leads to alkylemia
(because too much H+ is being excreted) and hypokalemia
iv. **Addision’s diseases is opposite Conn’s
VII. Diuretic abuse
a. Again, can cause alkalemia
b. causes K+ depletion (by secretion)
c. this favors H+ secretion
d. causes extracellular volume to become depleted: decreased Blood pressure
e. Incr. renin, Angiotensin and Aldosterone secretions
f. Aldosterone Stimulates H+ secretion directly and via K+ depletion
VIII. Disturbances in acid-base balance
a. Normal arterial plasma pH range: 7.35-7.45
b. Definitions:
c. Acidemia: a reduction in arterial pH below 7.35
d. Acidosis: any abnormal condition that produces acidemia
e. Alkalemia: an increase in arterial pH above 7.45
f. Alkalosis: any abnormal condition that produces alkalemia
IX. Respiratory acid-base disturbances
Renal 21
Thur 03/20/03 9am
Dr. Mallet
Le Giang
Proscribe Samera Kasim
Page 4 of 7
a. Caused by change in PCO2
b. Respiratory acidosis: increased arterial PCO2
↑ CO2 + H2O ↔ ↓H+ + ↑ HCO3i. If the lungs are not eliminating CO2 at the same rate of metabolic
metabolism (pulmonary insufficiency, emphysema), levels rise
and the above reaction occurs
ii. The pH falls even though bicarb is being produced because pH
specifically refers to the H+ concentration; it is independent of
HCO3 by definition.
iii.
iv. Renal response: increased H+ secretion restores extracellular pH
by up-regulating the production of ammonium, resulting in further
increases in HCO3c. Respiratory alkalosis: decreased arterial PCO2
↓ CO2 + H2O ↔ ↑H+ + ↓HCO3i. Occurs in hyperventilation
ii. Renal response: less H+ secretion, more HCO3-excretion in urine
d. The changes in bicarb may seem counterintuitive.
X. Metabolic acidosis
a. NOT because of problems with the lungs
b. Low plasma pH due to:
i. gain of fixed acid in body fluids, or
ii. loss of HCO3iii. In either case, [HCO3-] falls
1. remember bicarb incr in RESPIRATORY acidosis
c. Renal compensation: increased H+ secretion (more ammonium in urine);
production of new HCO3d. Respiratory compensation: increased ventilation (peripheral
chemoreceptors stimulated), decreases PCO2 which eliminates a source of
H+ from the body
e. Metabolic acidosis can be causes by diarrhea. Why?
i. Bicarb is being lost from the GI tract.
ii. As bicarb conc falls, the equilibrium is shifted right
iii. More H+ ions are made = acidosis.
f. Lactic acid from anaerobic metabolism (indicative of a hypoxic
environment) breaks down to lactate and H+.
g. Bicarb tries to neutralize the excess H+, resulting in a decrease in bicarb
concentration
XI. Metabolic alkalosis
a. Abnormally high plasma pH, due to
i. Excessive gain of strong base or HCO3ii. Excessive loss of fixed acid
Renal 21
Thur 03/20/03 9am
Dr. Mallet
Le Giang
Proscribe Samera Kasim
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b. HCO3- concentration rises due to shift in carbonic anhydrase equilibrium
toward HCO3c. Respiratory compensation: decreased ventilation (increases PCO2)
d. Renal compensation:
i. Incomplete reabsorption of filtered HCO3- (which spills into urine)
ii. β-intercalated cells secrete HCO3e. vomiting increases bicarb because acid is being lost; Resp decreases
XII. Davenport diagram depicts changes in acid-base metabolites
a. The graph will not be on the exam, but it’s important that you understand
the concepts of the carbonic anhydrase reaction.
b. “A” is indicative of the normal bicarb concentration and pH of
extracellular fluid.
c. EX: Respiratory acidosis and renal compensaton: increasing PCO2; If
you move Left along the horizontal axis, indicating a drop in the pH, the
bicarb concentration increases along the vertical axis to restore the normal
pH of 7.4 by response of the kidneys. More ammonium will be in the
urine.
d. The opposite is true for an increase in the pH (bicarb conc decr)
e. Understand these concepts for both metabolic and respiratory acid-base
imbalances with compensation
f. Renal failure: results in acidosis. kidneys should compensate to the
acidosis and results in increased ammonium in the urine.
g. the lungs should compensate as well: an increase in ventilation by
stimulation of peripheral chemoreceptors will decrease the PCO2, and
elimination of H+ from the body.
h. There will be a scenario on the Exam for Acid-Base disorders.
Recognize whether compensations are occurring for the given lab
values. Be able to recognize what kind of acid-base disorder the pt has.
XIII. Anion gap
a. Used in differential diagnosis of metabolic acidosis
b. A.G. = measured cation (Na+) - measured anions (Cl-, HCO3-)
c. Normal range: 5-12 mEq/l
i. Plasma proteins are anionic but are not measured in the lab, thus
the [Na] should be greater. There is normally only a 5-12 mEq/l
difference, which is the normal range.
d. Anion gap is either normal or increased, depending on cause of metabolic
acidosis
e. Hyperchloremic acidosis: A.G. is unchanged
HCl + HCO3-  Cl- + H2O + CO2
i. Loss of HCO3- is matched by gain of Clii. The increase in urine Cl- is excreted in the urine
Renal 21
Thur 03/20/03 9am
Dr. Mallet
Le Giang
Proscribe Samera Kasim
Page 6 of 7
iii. Seen in diarrhea: kidneys respond to the loss of volume by
retaining Cl- and Na+. over time there is an incr in Cl- because
less is being excreted in the urine. Cl- will replace the bicarb that
was lost (both anions).
f. High anion gap acidos is: HCO3- is replaced by unmeasured anion:
HA + HCO3-  A- + H2O + CO2
i. (“unmeasured” means that the lab doesn’t measure that anion)
ii. In this case, anion gap increases
iii. Bicarb is consumed to neutralize free H+
g. Causes of high anion gap acidosis:
i. You can find the anion gap in E. Elm Park:
ii. Ethanol
iii. Ethylene glycol
iv. Lactic acid
v. Methanol
vi. Paraldehyde
vii. Aspirin
viii. Renal failure
ix. Ketone bodies
XIV. Case: ethylene glycol intoxication
a. A 55 y.o. alcoholic man is found unconscious and taken to the ER by the
police. An open container of antifreeze is found next to the patient. On
physical exam, his blood pressure is 110/70, pulse 80/min, and respiratory
rate 30 breaths/min. Arterial plasma chemistries:
Normal
Na+, mEq/l
125
135-145
Cl-, mEq/l
80
96-106
K+, mEq/l
4.0
3.5-4.5
HCO3-, mEq/l
15
23-29
pH
7.20
7.35-7.45
XV. What is patient’s anion gap? Why is respiratory frequency so high? Why is HCO3so low? Will arterial PCO2 be above or below normal?
a. Anion gap = 125 – (80 + 15) = 30
b. Low bicarb because it’s buffering the excess H+ from the ethylene glycol
c. PCO2 will be above normal
i. He has acidosis
ii. Has increases respiratory rate
d. Gap metabolic acidosis
XVI. A bad case of the flu
a. A 40 y.o. woman presents with a 7 day history of fever, chills, and severe
vomiting. Physical exam: unsteady ambulation, weakness, poor skin
Renal 21
Thur 03/20/03 9am
Dr. Mallet
Le Giang
Proscribe Samera Kasim
Page 7 of 7
turgor, dry mucous membranes. Supine blood pressure 130/70, pulse 100;
upon standing, 105/60 and 120. Arterial plasma chemistries:
Normal
+
Na , mEq/l
142
135-145
Cl-, mEq/l
100
96-106
HCO3 , mEq/l
36
23-29
b.
c.
d.
e.
This pt is hypovolemic
Has orthostatic hypotension and tachycardia
Na and water are lost in proportion, thus Na levels look normal
Predict the changes in arterial plasma pH and PCO2 in this patient
compared to normal.
i. Vomiting results in the loss of acid, thus she’s alkalotic
ii. Also, extracellular volume is low, thus ADH, Angiotensin and
aldosterone are high. Aldosterone stimulates the secreation of H+
in the collecting ducts, further adding to the alkalosis.
f. Why is HCO3- so high?
i. Loss of acid during vomiting produces alkalosis
g. Is anion gap increased?
i. No, it’s small (6mEq/l)
h. Is her plasma K+ likely to be normal?
i. No, has hypokalemia
ii. Results in increased H+ secretion
XVII. SUMMARY: Session 9
a. Six factors control renal H+ secretion: Intracellular pH, plasma PCO2,
carbonic anhydrase, Na+ reabsorption, EC K+, aldosterone
b. Cellular defense mechanisms against pH changes
c. Respiratory acid-base disturbances: primary changes in PCO2 cause H+
and HCO3- to change ( secondary change)
d. Metabolic acid-base disturbances: gains or losses of H+ and HCO3-;
respiratory, renal responses
i. Respiration is secondary change to PCO2
e. Anion gap: differential diagnosis of metabolic acidosis