Metabolic and Respiratory Acidosis ebook

Siobhan A. Corbett, MD
1
Acid-Base Physiology

The state of systemic acid-base balance is estimated clinically by use if the bicarbonate-
carbon dioxide buffering system.

The normal H
+
concentration is 40 nEq/L
The amount of acid produced per day is about 50-100 meq/L. If this were added to
the blood, the hydrogen content in the blood would rise 2 meq/L (one million times
normal) and the pH would be below 3.
Acidemia does not occur because free H
+
combines with HCO
3
-
, HPO
4
2-
, protein
anions, and carbonate in the bone.

Renal Acid Excretion

The dietary acid load must be excreted in the urine
H+ excretion occurs by secretion by the tubule cells in the proximal tubule, loop of Henle
and collecting tubules.
The minimum urine pH is 4.5 (40 mol/L)- you would need 2500 L of urine to
secrete 100 meq of H+.
H+ ions are buffered by HPO
4
2-
and ammonium (NH
4
+
)
All of the filtered HCO3- must be reabsorbed before H+ can be excreted.
Na
+
- H
+
exchanger secretes H
+
to the apical lumen (Na
+
- K
+
ATPase driven)
H
+
combines with filtered HCO
3
- to generate carbonic acid (H
2
CO
3
)
H
2
CO
3
dissipates in to CO
2
and H
2
O - which is absorbed back into the cell
H
2
CO
3
is reformed, generating H+ and HCO
3
-
which leaves the cell via a Na
+
-3HCO
3
-

Reabsorption of filtered HCO3- does not result in acid secretion

Titratable Acidity

Excretion of dietary acids requires the combination of secreted acid with buffers (e.g.
monobasic phosphate) or the formation of ammonium to generate a free intracellular
HCO3- that is returned to the systemic circulation
Phosphate buffering increases distally as the urine pH falls.
Buffering by phosphate is titratable acidity

Ammonium Excretion

Ammonium excretion is the major adaptive response to an acid load because it can be
varied according to metabolic needs (30-300 meq/day)- ammonium is generated within
the cell from the metabolism of glutamine to glutamate and ketoglutarate. It can then be
actively secreted or diffuse into the lumen of the proximal tubule.




Metabolic and Respiratory Acidosis ebook
Siobhan A. Corbett, MD
2
What determines how much H+ is excreted?

Na
+
-H
+
exchange in the PT and LOH can be increased (H+ is also exchanged for K+ to
maintain electroneutrality)
Ammonium production and secretion in the PT can be enhanced by increasing
glutamine uptake and metabolism
H
+
-ATPase activity can increase in the collecting tubules
There is increased activity of the Na
+
-3HCO
3
-
exchanger. As HCO
3
-
drops
systemically due to increased H
+
, the low bicarbonate concentration is sensed by the
tubule cells. Increased HCO
3
-
then leaves the cell, intracellular pH drops and signals
the increased secretion of H
+
.

In addition to the renal response, the
extracellular pH in metabolic acidosis is
protected by a rise in alveolar ventilation,
thereby lowering the P
CO2
. The pH in the plasma
is proportional to the ratio of the plasma
bicarbonate concentration to the P
CO2
not the absolute values.

The P
CO2
falls about 1.2mm Hg for every 1-meq/L decline in the plasma bicarbonate


Metabolic Acidosis

Metabolic acidosis is characterized by a fall in extracellular pH that is induced by:
A reduction in plasma bicarbonate concentration
Decreased renal acid excretion
Bicarbonate loss in the GI tract or in the urine
Increased acid retention

Etiology

Increased Acid Production
o Lactic Acidosis
o Ketoacidosis (most often due to DM)
o Ingestions
Aspirin
Ethylene glycol
Methanol
o Loss of bicarbonate
GI loss- diarrhea (primary); pancreatic, biliary or intestinal fistulae
Renal- type 2 (proximal) renal tubular acidosis (RTA)

Decreased Acid Excretion (we will not review this now- more to come in renal block)
o Renal Failure decreased NH4+ excretion
Metabolic and Respiratory Acidosis ebook
Siobhan A. Corbett, MD
3
o Type 1 (distal) RTA
o Type 4 RTA

Increased Acid Production

Acute and severe metabolic acidosis can occur when there is a marked increase in acid
production. The two major mechanisms of increased acid generation leading to metabolic
acidosis are those that reduce bicarbonate and chloride concentrations (anion gap
acidosis) and those in which bicarbonate alone is reduced, but chloride becomes elevated.

The etiology of metabolic acidosis is often evident from the history. In addition, calculation
of the anion gap is a routine part of the evaluation because it divides the different causes of
metabolic acidosis into two categories. The anion gap is equal to the difference between
the plasma concentrations of the major cation (sodium) and the major measured anions
(bicarbonate and chloride):






The approximate normal values for these ions are 140, 24 and 108 meq/L respectively,
leading to a normal anion gap of 6 to 10 meq/L. The negative charges on most of the
plasma proteins comprises the gap

Increased Anion Gap Normal Anion Gap (Hyperchloremic)
Renal Failure- PO4-, SO4-, urate, hippurate Renal bicarbonate loss
Lactic Acidosis- lactate GI loss of bicarbonate (diarrhea)
Ketoacidosis- -hydroxybutyrate Renal dysfunction
Ingestions
Aspirin- ketones, lactate, salicylate
Ethylene Glycol- glycolate, oxalate
Methanol- formate
Paraldehyde- organic anions
Toluene- hippurate
Sulfur- SO4
2-

Ingestions
Ammonium chloride
Hyperalimentation fluids
Rhabdomyolysis

A clinically significant rise in anion gap is almost always due to a rise in the measurement
of unmeasured anions (see table).

If the acid that accumulates is HCl, then there is a meq/meq replacement of extracellular
HCO3- with choride. As a result, there is no increase in the anion gap since the sum of the
chloride and bicarbonate ions are unchanged. Gastrointestinal or renal loss of bicarbonate
indirectly produces the same result.

Anion Gap = [Na
+
] ([Cl
-
] + [HCO
3
-
])
Metabolic and Respiratory Acidosis ebook
Siobhan A. Corbett, MD
4
Respiratory Acidosis:

Pathophysiology and Etiology

Endogenous metabolism results in the production of approximately 15,000 mmol of CO
2

per day. Although CO
2
is not an acid, it combines with H
2
O in the blood stream, resulting in
the formation of H
2
CO
3
:






The ensuing elevation in the H
+
concentration is then minimized because the excess H
+
ions
combine with intracellular buffers, including hemoglobin in RBCs. The net effect is that
metabolically generated CO
2
is primarily carried in the blood stream as HCO
3
-
, with little
change in the extracellular pH. These processes are reversed in the alveoli. As HHb is
oxygenated, H
+
is released and combines with HCO
3
-
to form H
2
CO
3
and then CO
2
.

Control of Ventilation

Alveolar ventilation provides the oxygen necessary for oxidative metabolism and
eliminates CO
2
produced by these metabolic processes. It is therefore appropriate that the
main physiologic stimuli to respiration are:

A reduction in the arterial P
O2
(hypoxemia)
o Sensed by chemoreceptors in the carotid bodies
An elevation in arterial P
CO2
(hypercapnea)
o Sensed by chemosensitive areas in respiratory centers in the medulla

Carbon dioxide is a major stimulus to respiration and minute ventilation is enhanced by
even minor changes in the arterial P
CO2
. In contrast, hypoxemia does not begin to
substantially promote ventilation until the arterial P
O2
is less that 50 to 60 mmHg.

Development of Hypercapnea

Since the CO
2
stimulus to ventilation is so strong, hypercapnea and respiratory acidosis are
almost always due to a reduction in effective alveolar ventilation, NOT an increase in CO
2

production. Hypoventilation can occur when there is interference with any step in the
ventilatory process, which may be due to a generalized fall in alveolar ventilation (e.g.
neuromuscular dysfunction) or an imbalance between ventilation and perfusion (e.g.
intrinsic pulmonary disease).

Metabolic and Respiratory Acidosis ebook
Siobhan A. Corbett, MD
5
If ventilatory function is not restored, the decrease in pH produced by CO2 retention is
minimized by the cell buffers and by increased renal H+ secretion, both of which result in
an elevation in the plasma HCO
3
-
concentration- but this can take several days to occur.


CAUSES OF ACUTE AND CHRONIC RESPIRATORY ACIDOSIS

Inhibition of the medullary respiratory center
o Acute: Drugs (opiates), oxygen in chronic hypercapnea
o Chronic: Extreme Obesity

Disorders of respiratory muscles and chest wall
o Acute: Guillain-Barre; hypophosphatemia
o Chronic: spinal cord injury, ALS; kyphoscoliosis

Upper airway Obstruction
Aspiration of foreign body, sleep apnea

Disorders affecting gas exchange across the pulmonary capillary
o Acute: ARDS; Pulmonary edema; severe asthma; pneumonia
o Chronic: COPD


All patients with hypercapnea who are breathing room air experience a fall in alveolar and
arterial PO2. In most cases, hypoxemia occurs earlier and is more severe than the
hypercapnea. This is because CO
2
can diffuse faster than O
2
across the alveolar wall (20x)
and as patients attempt to increase ventilation in normal lung segments, more CO
2
can be
excreted but more O
2
cant be taken up.

Important note: Hypercapnea is a late finding, and even a small elevation in the P
CO2
of a
few mm Hg indicates advanced pulmonary dysfunction or an insult to ventilatory drive
(e.g.narcotics) because hypercapnea is such a powerful stimulus to ventilation.

Regulation of ventilation in Chronic Respiratory Acidosis

The respiratory centers become less sensitive to the CO2 and therefore the
academic drive to ventilation
As a result, hypoxemia becomes the primary stimulus to respiration.

Acute Respiratory Acidosis

The ability to acutely protect the extracellular pH is different in metabolic and respiratory
acidosis. In metabolic acidosis, extracellular and intracellular buffering and compensatory
hyperventilation all minimize the fall in pH. In contrast, the body is not so well adapted to
handle an acute elevation in the PCO2. There is virtually no extracellular buffering because
Metabolic and Respiratory Acidosis ebook
Siobhan A. Corbett, MD
6
HCO
3
-
cannot buffer for H
2
CO
3
. So, the only protection against acute hypercapnea are the
cell buffers, Hgb and proteins. Thus, there is an increase in the plasma HCO
3
-
concentration
averaging, 1 meq/L for every 10 mm Hg rise in P
CO2
.








If the P
CO2
were to acutely rise to 80 mm Hg, there would be a 4-meq/L rise in the plasma
HCO
3
-
to 28 meq/L and a potentially serious drop in the extracellular pH to 7.17
An even more severe drop in pH can occur when there is a combined respiratory and
metabolic acidosis.

Chronic Respiratory Acidosis

The acid-base picture is different with chronic hypercapnea because of the compensatory
renal response. The persistent elevation in the P
CO2
stimulates renal H
+
secretion, resulting
in the addition of HCO
3
-
to the ECF. The net effectis that after 3 to 5 days, a new steady-
state is attained in which there is roughly a 3.5-meq/L increase in the plasma HCO
3
-
concentration for every 10 mmHg increment in the P
CO2
. (What would the pH be if the P
CO2

was 80?). The extent of the rise in HCO3- in the plasma is determined solely by the
increase in renal H
+
secretion.

Symptoms of severe hypercapnea include:
Headache
Blurred vision
Restlessness
Anxiety
Tremors; asterixis; delirium
Somnolence


Metabolic and Respiratory Acidosis ebook
Siobhan A. Corbett, MD
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