Page 487 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Fluid, Electrolyte, and Acid-Base Disturbances in Liver Disease 475

sites of lactate removal, with the liver predominating at (Figure 19-12). Lactate generation by RBCs, brain, and
rest (see Table 19-2). The normal dog liver can extract skin with subsequent gluconeogenesis by liver and
at least 19% of a physiologic lactate load per hour. 168 Lac- kidneys is known as the Cori cycle, an important mecha-
tate use is governed by conversion to pyruvate via lactate nism of energy provision during starvation.
dehydrogenase (LDH), and the pyruvate formed is either Pyruvate, an intermediate common to several meta-
metabolized to glucose or oxidized in the tricarboxylic bolic pathways, is the immediate precursor of lactic acid.
acid (Krebs) cycle to carbon dioxide and water Glucose and alanine are the physiologically important
pyruvate precursors. Pathologic conditions stimulating
conversion of glucose or alanine to pyruvate predispose
TABLE 19-2 Rates of Basal Lactate to lactic acidosis. The enzyme pyruvate dehydrogenase
Production and Use (PDH) plays an integral role in lactate metabolism,
(mmol/day/kg) in catalyzing the intramitochondrial conversion of pyruvate
Humans to acetyl coenzyme A (acetyl CoA), which enters the
Krebs cycle (see Figure 19-12).
Basal Basal Removal of lactic acid normally occurs through three
Lactate Lactate pathways: two depend on hepatic function and the third
Tissue Production Tissue Use on renal excretion. 121 At rest, the liver metabolizes 40%
to 60% of endogenously produced lactate by oxidation
Skin 5.0 Liver 10.3 in the mitochondrial tricarboxylic acid cycle or by conver-
Red blood cells 4.3 Kidney 5.5 sion of lactate to glucose in the cytosolic Cori cycle (see
Brain 3.4 Heart 1.1
Muscle 3.1 Other 1.5 Figure 19-12). Each mechanism of lactate metabolism
Intestinal mucosa 1.6 regenerates bicarbonate. Hepatic use of lactate depends
White blood cells, 1.0 on substrate uptake, hepatic gluconeogenic capacity,
platelets and hepatic blood flow. In the absence of metabolic aci-
Total 18.4 Total 18.4 dosis or tissue perfusion deficits, hyperlactatemia usually
is associated with conditions that favor glycolysis (e.g.,
From Park R, Arieff AI. Lactic acidosis. Adv Intern Med 1980;25:33–68. high catecholamine concentrations, alkalosis) and an

Mitochondria
Conditions increasing Oxygen-dependent
lactate accumulation Triglyceride
Ketone cholesterol
Citrate
Hypoxia bodies
Systemic hypoperfusion TCA Cycle
Tissue ischemia TCA Cycle
Severe anemia Acetyl-CoA Amino
Cardiovascular insufficiency Oxaloacetate acids
Hepatic failure PDH Acetate
Metabolic alkalosis Lactate Pyruvate Alanine
↑ Catecholamines
Thiamine deficiency PFK
(PFK activity) Cori cycle P-enolpyruvate
Renal failure
Seizures Glucose
Hypoglycemia Cytosol
Oxygen-independent
A
Hepatic Failure

↑ Epinephrine Hypoglycemia

↑ Extrahepatic
lactate production

↓ Lactate uptake

B Lactic Acidosis
Figure 19-12 Metabolic generation and interactions of lactate (A) and the mechanisms leading to lactic
acidosis in liver failure (B). PFK, Phosphofructokinase; PDH, pyruvate dehydrogenase.