**3.1 Primary (type B)**

308 Perioperative Considerations in Cardiac Surgery

and oxidized nicotine adenine dinucleotide, respectively) (Phypers, 2006). Under aerobic conditions, pyruvate is converted to acetyl CoA to enter the Kreb's cycle. Under anaerobic conditions, pyruvate is converted by lactate dehydrogenase (LDH) to lactic acid. In aqueous solutions, lactic acid dissociates almost completely to lactate and H**+**þ (Phypers, 2006). Once having been believed to be the consequence of oxygen lack in contracting skeletal muscle, it is now known that lactate is also formed and utilized continuously under fully aerobic

Normal plasma lactate concentration is 0.3–1.3 mmol/liter (3-12 mg/dL), and normal basal lactate production is 0.8 mmol/kg/hour (1300 mmol/day) (Phypers, 2006). Normal subjects produce between 15 to 20 mmol/kg of lactic acid/day, most of which is generated either from glucose via the glycolytic pathway or from the deamination of alanine (Huckabee, 1961). Its concentration can rise to over 20 mmol/L (180 mg/dL ) during intense exertion or

Lactate has two chemical isomers in nature. The first, D-lactate, is produced from nonabsorbed carbohydrates by colonic bacteria (which may also proliferate in the ileum). The D isomer is mostly exogenous from Ringer's lactate solution infusion, and its non-iatrogenic presence in humans is uncommon. In the blood, it is a reflection of bacterial overgrowth in the gastrointestinal tract. Its clearance is much slower than the other chemical isomer, Llactate, with the clearance mainly depending on liver function (Uribarri et al., 1998). Llactate is the product of anaerobic glycolysis in humans and has been used as a marker of cellular hypoxia and tissue malperfusion. It can only be produced or consumed from pyruvate via the enzyme LDH in the cytosol, by means of a process of fermentation during normal metabolism and exercise (Mizock, 1989). It does not increase in concentration until the rate of lactate production exceeds the rate of lactate removal, a process which is governed by a number of factors, including monocarboxylate transporters, concentration

Both the production and the removal of lactate are active functions of every tissue of the body. Tissue sources of lactate production include erythrocytes, perivenous hepatocytes, skeletal myocytes and skin. The liver is the major organ of lactate utilization, followed by the kidneys (Huckabee, 1961; Mizock, 1989). The liver removes 70% of lactate and less than 5% of lactate is renally excreted. Liver uptake involves both a monocarboxylate transporter and the less efficient process of diffusion, while renal fraction may increase and become more clinically significant during hyperlactatemia. Following the liver, skeletal muscle, brain, erythrocytes, and the renal medulla are considered to be the most important sources

Hyperlactatemia is usually defined as more than >4 mmol/liter or 40 mg/dL, a result of conditions in which production exceeds utilization. Hyperlactatemia can be associated with acidosis, alkalosis and normal blood pH, and can also be found in conditions of normoxia,

Since lactate is a byproduct of anaerobic metabolism, it becomes elevated in hypoperfusion states when pyruvate cannot enter the Krebs cycle due to insufficient oxygen supply and is converted to lactate. Lactate-producing tissues include the skin, erythrocytes, brain, skeletal muscles, leukocytes and the renal medulla. Lactate-consuming tissues include the liver,

conditions (Brooks, 2002).

severe illness (Mizock & Falk, 1992).

of lactate in the body (Phypers, 2006).

**3. Causes for hyperlactatemia** 

hypoxia and anoxia (Handy, 2006).

and isoform of LDH, and oxidative capacity of the tissues.

The more clinically prevalent hyperlactatemia is not associated with poor tissue perfusion (i.e., alkalosis or increased metabolic activity). In such cases, body-buffering mechanisms can compensate for the decreasing pH (Smith et al., 2001). Among the mechanisms that may be involved are a toxin-induced impairment of cellular metabolism or regional areas of ischemia. Primary hyperlactatemia is usually associated with an underlying disease (e.g., diabetes mellitus, liver disease, malignancy, sepsis, pheochromocytoma, and thiamine deficiency), with drugs or toxins (e.g., ethanol, methanol, ethylene glycol, fructose, sorbitol, xylitol, salicylates, acetaminophen, epinephrine, terbutaline, cyanide, nitroprusside, isoniazid and propylene glycol), and with inborn errors of metabolism (e.g., glucose + phosphatase deficiency [van Gierke's disease], fructose-l + diphosphatase deficiency, pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency, and oxidative phosphorylation defects), or following hypoglycemia (Mizock, 1989). D-lactic acidosis is a unique form of acidosis that occurs in patients with short bowel syndrome or other forms of malabsorption.
