Causes of Lactate Elevation, Lactic Acidosis - Differential Diagnosis



The most common causes of hyperlactatemia are usually: 

 - hypoxemia

 - tissue hypoperfusion

 - toxic-induced impairment of cellular metabolism,

 - regional ischemia or the mechanism is unknown

 - Many other causes are listed as Type A and B categories



Lactate levels depend on:

 - ongoing production

 - removal from the blood by excretion (e.g., urine, sweat) 

 - its metabolism (e.g., uptake by cells as a direct source of energy, conversion to glucose by the liver)



Why do we emphasize this parameter? The use of lactate as a clinical prognostic tool was suggested in 1964 by Broder and Weil - they observed that a lactate excess of > 4 mmol/L was associated with poor outcomes in patients with undifferentiated shock. ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975915/ )

Therefore, time and time again we might see an urgency to bolus these values as we somehow equate that an elevated lactate means the patient is in impending shock.



What we should be teaching is that elevated lactate is encountered in a multitude of clinical presentations and disease states one of which is the critically ill patient with shock/hypoxemia/Sepsis etc. Persistent hyperlactatemia is particularly difficult to interpret.



Causes of elevated lactate apart from tissue hypoperfusion have been recognized and should be considered in the appropriate clinical context.

One of these is the contribution of liver or renal injury in the production and clearance of Lactate. Both of these organs can ↑ lactate



With ↑ Lactate, our response should be to  determine the underlying cause. 

 - hypoperfusion/ hypoxemia -> focus on improving perfusion 

 - shock->treatments include fluid administration, vasopressors, or inotropes. 

 - regional ischemia, surgery may be needed to restore circulation



If drugs, seizures, malignancy, or thiamine deficiency are the cause: stop, reverse and treat the offending agent.



Multiple conditions can contribute to lactic acidosis, therefore carefully: 

 - evaluate the patient’s complete medical history

 - conduct a thorough physical assessment

 - assess other laboratory or diagnostic tests before beginning treatment.



Join the resistance simply to bolus!



Causes of Lactate Elevation



Type A Lactic Acidosis: Hypoxic/Failure of Circulatory System

 • Increased Oxygen Demand:

	- Heavy exercise

	- Seizures

	- Severe asthma - accessory muscle use

 • Decreased Oxygen Availability:

	- Reduced tissue perfusion

		- Cardiac arrest

		- Shock

		- Hypovolemia

		- LV failure

		- Low cardiac output

		- Acute pulmonary edema

		- Mesenteric ischemia (90% sensitivity/98% specific)

		- Compartment syndrome

		- Sepsis

		- Bacterial peritonitis

		- Acute pancreatitis

		- Gangrene/Fournier’s

 • Reduced Arterial Oxygen Content:

	- Hypoxemia (PaO2 < 30mmHg)

	- Severe anemia

	- Carbon monoxide

	- Methemoglobinemia



Type B Lactic Acidosis: Nonhypoxic

 • Type B1:

	- Diabetes mellitus/DKA

	- Liver failure

	- Neoplasia/Warburg effect

	- Thiamine deficiency

	- Renal failure

	- Hypoglycemia

	- Alcohol

 • Type B2: Drugs and Toxins:

	- Metformin

	- Salicylates

	- Ethylene glycol

	- HIV/HAART medications

	- Beta agonists

	- Cocaine

	- Cyanide

	- Propofol

 • Type B3: Hereditary Defects:

	- Mitochondrial myopathies

	- Defects in gluconeogenesis



Liver Injury:

 • Reduced clearance of lactate and can act as source of lactate production

Renal Failure:

 • Diminished lactate clearance



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