Hyperlactatemia and Lactic Acidosis

I recently came across a young patient with unexplained hyperlactatemia. He came in with severe abdominal pain and was found to have a normal CT Abdomen with a background of ethanol related chronic pancreatitis . He was eventually admitted for pain relief and unexplained hyperlactatemia. So I went back and did a bit of reading on LACTATE...

What is Lactate?

Lactate is the normal endpoint of the anaerobic breakdown of glucose. Most of the lactate production occurs in skeletal muscle, bowel, brain, and RBCs. The lactate generated can be taken up by the liver and converted to glucose (via gluconeogenesis) or can be used as a primary oxidative fuel. In the setting of decreased tissue oxygenation, lactic acid is produced as the anaerobic cycle is utilized for energy production.

Evidence suggests increased morbidity and mortality for patients with  increasing lactate levels or a decreased rate of lactate clearance.

How is lactate cleared from our body?

Lactate is cleared from blood by thru liver, kidneys (10-20%) and skeletal muscles. The ability of the liver to consume lactate is concentration-dependent and progressively decreases as the level of blood lactate increases. 

Lactate producers: skeletal muscle, the brain, the gut, and the erythrocytes. 

Lactate metabolizers: Liver, the kidneys, and the heart.

Lactate v/s Lactic Acid and Hyperlactatemia v/s Lactic Acidosis.

Lactate is not synonymous with lactic acid, and hyperlactatemia is not synonymous with lactic acidosis.

Hyperlactatemia is defined as a persistent, mild to moderate (upto 4-5 mmol/L) increase in blood lactate concentration without metabolic acidosis. It can occur in the setting of adequate tissue perfusion, intact buffering systems, and adequate tissue oxygenation.

Lactic acidosis is characterized by persistently increased blood lactate levels (usually >5 mmol/L) in association with metabolic acidosis. Also, lactic acidosis may not necessarily produce acidemia in a patient. The development of lactic acidosis depends on the magnitude of hyperlactatemia, the buffering capacity of the body, and the coexistence of other conditions that produce tachypnea and alkalosis (eg, liver disease, sepsis). Thus, hyperlactatemia or lactic acidosis may be associated with acidemia, a normal pH, or alkalemia.

D-Lactate and L-lactate

L-lactate and D-lactate are the two isomeric forms of lactate.

L-lactate is the most commonly measured level, as it is the only form produced in human metabolism.

D-lactate is a byproduct of bacterial metabolism and may accumulate in patients with short-gut syndrome or in those with a history of gastric bypass or small-bowel resection

What causes an elevated lactate?

1.   Tissue Hypoxia and Anaerobic Metabolism (Traditional school of thought)
2.   Due to decreased clearance rather than increased production in sepsis
3.   Secondary to down-regulating of pyruvate dehydrogenase in skeletal muscles by inflammatory mediators (Cytokines) and Catecholamines.

Is it possible to have hypoperfusion but a normal lactate level?

Short Answer- YES

For significant increase in blood lactate to occur, lactate must be released into the systemic circulation and the rate of production must exceed hepatic, renal, and skeletal muscle uptake. Therefore, regional hypoperfusion of tissues may be present despite normal blood lactate concentrations.

Types of Lactic Acidosis

• Type A – Poor tissue perfusion or oxygenation of blood (eg, hypotension, cyanosis, cool and mottled extremities). It can be caused by the overproduction of lactate or the underutilization of lactate. For instance, muscular activity, seizures, ischemia, shock, hypoxemia, anemia, CO poisoning.

• Type B - no clinical evidence of poor tissue perfusion or oxygenation exists.

1. Type B1 occurs in association with systemic disease, such as renal and hepatic failure, diabetes and malignancy, thiamine deficiency, infection, pancreatitis, short bowel syndrome. 
2. Type B2 is caused by several classes of drugs and toxins, including biguanides, alcohols, iron, isoniazid, zidovudine, and salicylates.
3. Type B3 is due to inborn errors of metabolism.

List of Possible Causes

•       Sepsis related Hypoperfusion and Mitochondrial Dysfunction
•       Bowel ischemia
•       Severe iron-deficiency anemia, Diabetes mellitus
•       Liver disease, Kidney Disease
•       Alcoholic Ketoacidosis, Pancreatitis
•       Malignancy (leukemia, lymphoma, lung cancer)
•       Seizures
•       Heat stroke, Pheochromocytoma
•       Thiamine deficiency (Remember this one during ICU rounds!)
•       Inborn errors of metabolism - von Gierke disease, fructose-1,6-diphosphatase  deficiency, pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency, oxidative phosphorylation deficiency, and methylmalonic aciduria.
•       MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke like episodes) - Characterized by migraine like headaches, dementia, hearing loss, ataxia, and episodic vomiting

What drugs can cause an elevated lactate?

•   Acetaminophen

•   Alcohols and glycols (ethanol, ethylene glycol, methanol, propylene glycol)

•   Antiretroviral nucleoside analogs (zidovudine, didanosine, lamivudine)

•   Beta-adrenergic agents (epinephrine, ritodrine, terbutaline, salbutamol)

•   Biguanides (phenformin, metformin)

•   Cocaine

•   Cyanogenic compounds (cyanide, nitroprusside)

•   5-FU

•   Iron, Isoniazid

•   Propofol

•   Salicylates

•   Sulfasalazine

•   Valproic acid

Click here to listen to Scott Weingart talking about Lactate

Take Home:

• Get familiar with Type B causes of an elevated lactate
• See the medication list and co-morbities while evaluating elevated lactate

Other Resources:
EMCrit/Pulmcrit on Lactate
Resus.me 

Author:

              

     Lakshay Chanana
     
     Speciality Doctor
     Northwick Park Hospital
     Department of Emergency Medicine
     England

     @EMDidactic