Page 275 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

266 ACID-BASE DISORDERS

BOX 10-2 Causes of L-Lactic Acidosis*

Type A: Hypoxic Type B: Nonhypoxic
Increased oxygen demand Drugs and toxins
Severe exercise Phenformin
Convulsions Salicylates
Decreased oxygen availability Ethylene glycol
144
Reduced tissue perfusion Many others
Cardiac arrest, cardiopulmonary resuscitation Diabetes mellitus
Shock Liver failure
Hypovolemia Neoplasia (e.g., lymphosarcoma)
Left ventricular failure Sepsis
Low cardiac output Renal failure
Acute pulmonary edema Hypoglycemia
Reduced arterial oxygen content Hereditary defects
Hypoxemia (PO 30 mm Hg) Mitochondrial myopathies
2
Extremely severe anemia (packed cell volume <10%) Defects in gluconeogenesis

*D-Lactic acidosis occurs with short bowel syndrome in humans and has been reported in a cat with intestinal bacterial overgrowth secondary to
pancreatic insufficiency. 184 It also has been observed in cats with diabetic ketoacidosis 47 and in those fed propylene glycol. 45,46

concentration of pyruvate and the NADH/NAD ratio, adenosine triphosphate (ATP) is synthesized from adeno-
þ
both of which are affected by mitochondrial oxidative sine diphosphate (ADP) and when NADH is oxidized to
function. NAD þ in the mitochondria. 136,144 Protons are released
Pyruvate is produced in the cytosol by anaerobic glycol- by hydrolysis of ATP to ADP and by reduction of NAD þ
ysis (Embden-Meyerhof pathway). Under aerobic to NADH, reactions that occur mainly in the cytosol.
conditions, NADH is oxidized to NAD þ in the The protons do not arise from dissociation of lactic acid
mitochondria and pyruvate enters the mitochondria for because the anion lactate is the predominant metabolite
conversion to acetylcoenzyme A (CoA) and use in the tri- atnormalhepatocytepH i (pH i ¼ 7.00to7.20).Thus,lactic
carboxylic acid (Krebs) cycle, or it is converted to oxaloac- acidosis reflects the imbalance between ATP hydrolysis and
etate and used for gluconeogenesis in the liver and renal synthesis and between reduction and oxidation of NAD .
þ
cortex. Under anaerobic conditions (e.g., tissue hypoxia), The protonsproducedduringanaerobicglycolysisare buff-
oxidative pathways in the mitochondria are disrupted, and ered by bicarbonate and nonbicarbonate buffers. Protons
þ
NAD must be replenished by reduction of pyruvate to are consumed and the buffers replenished when lactate is
lactate in the cytosol. Thus, lactate accumulation is the metabolized to glucose or oxidized to CO 2 and water.
price to be paid for maintaining energy production under
anaerobic conditions.
Pathophysiology
At rest, skin, red cells, brain, skeletal muscle, and gut
Lactic acidosis occurs when production of lactate by mus-
all produce lactate. During tissue hypoxia, skeletal muscle
cle and gut exceeds its use by liver and kidneys. Both
and gut become the major producers of lactate. The liver
pathways of lactate use depend on intact mitochondrial
and kidneys are the main consumers of lactate, using it for
oxidative function, and clinical settings characterized by
gluconeogenesis (primarily in the liver) or oxidizing it to
tissue hypoxia are the most common causes of lactic
CO 2 and water. Protons are consumed when lactate is
acidosis (see Box 10-2). Hepatic uptake of lactate is
metabolized:
decreased when arterial PO 2 decreases to approximately
Gluconeogenesis 30 mm Hg. 225 Severe acidosis further impairs hepatic
uptake of lactate, and the liver eventually becomes a
þ 140
2CH 3 CHOHCOO þ 2H ! C 6 H 12 O 6 producer rather than a consumer of lactate.
In an experimental model of hypoxic lactic acidosis
Oxidative metabolism (type A) induced by ventilating dogs with 8% O 2 , lactate
concentration was more than 5 mEq/L, pH was less than

þ

CH 3 CHOHCOO þ H þ 3O 2 ! 3CO 2 þ 3H 2 O 7.2, HCO 3 concentration was less than 12 mEq/L, PO 2
was less than 30 mm Hg, and hepatocyte pH i was less than
Both of these reactions require normal mitochondrial 7.00. 11 When a similar degree of acidosis was created by
oxidative function. The protons are consumed when infusing lactic acid into dogs with normal PO 2 , hepatocyte