Lactate is a substance produced during normal cellular metabolism. Measuring blood lactate provides valuable information about the body's metabolic state and can help clinicians identify impaired tissue perfusion, increased metabolic demand and potentially life-threatening illness. Lactate is commonly measured in patients with suspected sepsis, shock, major trauma, seizures and other conditions associated with physiological stress.
Although lactate is frequently associated with inadequate oxygen delivery, elevated lactate levels do not always indicate tissue hypoxia. Lactate can also increase when the body accelerates glucose metabolism, when lactate clearance is impaired or when medications and other conditions alter normal metabolic processes. Understanding how lactate is produced and metabolised is essential for interpreting results accurately and recognising their clinical significance.
What You Need to Know
Lactate is continuously produced by cells as part of glucose metabolism. During glycolysis, glucose is broken down into pyruvate, which can then be converted into lactate by the enzyme lactate dehydrogenase. This reaction regenerates nicotinamide adenine dinucleotide (NAD⁺), allowing glycolysis to continue producing energy.
Importantly, lactate production occurs even when adequate oxygen is available. Under normal physiological conditions, the body maintains a balance between lactate production and clearance, keeping circulating lactate concentrations relatively low.
The liver is responsible for much of the body's lactate clearance, converting lactate into glucose through gluconeogenesis or using it in other metabolic pathways. The kidneys and other tissues also contribute to lactate metabolism.
Blood lactate concentrations increase when production exceeds the body's capacity to utilise or clear it. This may occur because of impaired oxygen delivery, increased metabolic activity, reduced clearance or a combination of these mechanisms.
Key points:
Lactate is a normal product of cellular metabolism and is continuously produced, even when oxygen is available.
Elevated lactate is known as hyperlactataemia.
Increased lactate may indicate impaired tissue perfusion, but it is not specific to tissue hypoxia or sepsis.
Lactate concentrations reflect the balance between production, utilisation and clearance.
The liver and kidneys play important roles in lactate metabolism.
Elevated lactate is associated with increased illness severity in many clinical conditions, but it does not identify the underlying cause.
Serial lactate measurements and the patient's clinical presentation are generally more informative than a single isolated result.
Common causes of elevated lactate:
Shock and impaired tissue perfusion
Sepsis and severe infection
Major haemorrhage
Severe hypoxaemia
Generalised tonic-clonic seizures
Intense muscular activity
Adrenergic stimulation, including some medication effects
Liver dysfunction and impaired lactate clearance
Certain medications and toxins
Thiamine deficiency
Beyond the Basics
Lactate
Reference range
Approximately 0.5–2.0 mmol/L (varies between laboratories and sampling methods)
Lactate is produced when pyruvate is converted into lactate during glycolysis. This process helps maintain the availability of NAD⁺, which is required for continued glucose metabolism and energy production.
Lactate is often described as a waste product of anaerobic metabolism. However, this is an oversimplification. Lactate is also an important metabolic fuel that can be transported between tissues and used for energy production or glucose synthesis.
During periods of physiological stress, lactate production may increase because cells are metabolising glucose more rapidly. In other circumstances, lactate accumulates because tissues are not receiving sufficient oxygen to meet metabolic demands or because the body cannot clear lactate efficiently.
Decreased lactate: Low lactate concentrations are generally not clinically significant. They usually reflect normal metabolic balance and do not require investigation in isolation.
Elevated lactate: Increased lactate may occur with shock, sepsis, tissue hypoperfusion, seizures, intense exercise, adrenergic stimulation, impaired hepatic clearance or medication-related metabolic disturbances. The clinical significance depends on the degree of elevation, the underlying cause and the patient's overall condition.
A lactate concentration of 4.5 mmol/L in a patient with hypotension, altered consciousness and suspected infection is concerning for significant physiological dysfunction. However, a similar result immediately following a generalised tonic-clonic seizure may be due to temporarily increased muscular metabolism rather than persistent tissue hypoperfusion.
The number alone does not explain why lactate is elevated.
How Lactate Is Produced
To understand why lactate levels increase, we first need to understand how cells produce energy. Cells use glucose (sugar) to produce adenosine triphosphate (ATP), which provides the energy needed for normal cellular functions.
Glucose is initially broken down through a process called glycolysis, which occurs in the cell's cytoplasm. During glycolysis, glucose is converted into two molecules of pyruvate, a three-carbon molecule, producing a small amount of ATP in the process. When sufficient oxygen is available, pyruvate can enter the mitochondria, where it is converted into acetyl-CoA and enters the Krebs cycle. This supports further energy production through the electron transport chain, which requires oxygen to generate large amounts of ATP.
However, pyruvate can also be converted into lactate by an enzyme called lactate dehydrogenase (LDH). This reaction is important because it regenerates a molecule called NAD⁺, which is needed for glycolysis to continue. Without enough NAD⁺, cells cannot keep breaking down glucose to produce ATP.
When oxygen delivery is inadequate, such as during haemorrhagic shock, the mitochondria cannot produce ATP as efficiently. Cells become more reliant on glycolysis for energy, increasing the conversion of pyruvate into lactate to regenerate NAD⁺. If lactate production exceeds the body's ability to use or remove it, blood lactate levels rise.
However, lactate can also increase when oxygen is available. For example, during severe physiological stress, adrenaline stimulates glycolysis, increasing the production of pyruvate and consequently lactate. Lactate may also accumulate when its clearance is impaired, such as in severe liver dysfunction.
This is why elevated lactate does not automatically indicate tissue hypoxia. It may reflect inadequate oxygen delivery, increased cellular metabolism, reduced lactate clearance or a combination of these processes.
Type A and Type B Hyperlactataemia
Elevated lactate is traditionally classified into two broad categories based on the underlying mechanism.
Type A: Associated with tissue hypoxia or hypoperfusion
Type A hyperlactataemia occurs when oxygen delivery is insufficient to meet tissue metabolic requirements. This may result from reduced circulating blood volume, impaired cardiac output, severe hypoxaemia or disruption of tissue perfusion.
Common causes include:
Hypovolaemic shock, including major haemorrhage
Cardiogenic shock
Septic shock with impaired tissue perfusion
Obstructive shock
Severe hypoxaemia
Regional tissue ischaemia
In these circumstances, elevated lactate may indicate an imbalance between oxygen supply and metabolic demand. However, lactate is not a direct measurement of tissue oxygenation.
Type B: Not primarily caused by tissue hypoxia
Type B hyperlactataemia occurs when lactate production increases or clearance decreases without tissue hypoxia being the primary mechanism.
Common causes include:
Generalised seizures and intense muscular activity
Adrenaline and beta-adrenergic medication effects
Liver dysfunction (the liver clears up to 70% of body’s circulating lactate, converting it back into glucose via the Cori cycle)
Certain medications, including metformin in relevant clinical circumstances (Metformin can reduce lactate clearance by inhibiting mitochondrial respiration and hepatic gluconeogenesis, decreasing the liver’s ability to convert lactate into glucose)
Thiamine deficiency (thiamine (vitamin B1) is needed to convert pyruvate into acetyl-CoA for energy production, so when thiamine is deficient, more pyruvate is converted into lactate instead, increasing blood lactate levels)
Malignancy and some metabolic disorders
Type A and Type B mechanisms can coexist. For example, a patient with sepsis may have impaired tissue perfusion, increased adrenergic stimulation and reduced lactate clearance simultaneously.
The classification is therefore useful for understanding possible mechanisms but should not be treated as a definitive diagnostic distinction.
Lactate and Sepsis
Lactate is frequently measured during the assessment of patients with suspected sepsis because elevated concentrations may indicate significant physiological stress, circulatory dysfunction or impaired tissue perfusion.
However, sepsis-associated hyperlactataemia is complex. During sepsis, the body's inflammatory response triggers the release of stress hormones, including adrenaline, which accelerates glycolysis and increases lactate production. This means cells may produce more lactate even when they are receiving sufficient oxygen. Sepsis can also disrupt blood flow through the smallest blood vessels (microcirculation), meaning some tissues may receive inadequate oxygen despite relatively normal blood pressure.
Mitochondrial dysfunction may further affect how efficiently cells produce energy, while impaired liver function can reduce the body's ability to clear lactate. These mechanisms can occur simultaneously, contributing to elevated lactate concentrations.
Consequently, an elevated lactate does not necessarily establish that the patient has inadequate oxygen delivery, and it should not be used as a standalone diagnostic test for sepsis. Lactate is a marker of physiological stress and illness severity, rather than a specific marker of infection.
A lactate concentration above 2 mmol/L in a patient with suspected infection warrants careful clinical assessment, particularly when accompanied by hypotension, altered mental status, reduced urine output or other signs of deterioration. Higher or persistently elevated lactate concentrations are generally associated with poorer outcomes, making repeat measurements useful for monitoring the patient's response to treatment.
Importantly, a normal lactate does not exclude sepsis or serious infection, as patients can develop significant infection and organ dysfunction without substantial lactate accumulation.
Related Article: Sepsis: Dysregulated Immune Response and Organ Failure
Lactate and Lactic Acidosis
Hyperlactataemia and lactic acidosis are related but are not interchangeable terms.
Hyperlactataemia refers to an elevated blood lactate concentration, which does not necessarily mean the blood has become too acidic.
Lactic acidosis occurs when elevated lactate is associated with metabolic acidosis, meaning the blood has become more acidic than normal (typically a pH below 7.35). This is often accompanied by reduced bicarbonate levels, as bicarbonate helps buffer excess acidity in the blood. Lactic acidosis can develop during severe circulatory dysfunction, such as shock, when normal cellular metabolism is disrupted.
However, lactate itself is not simply responsible for making the blood acidic. The relationship involves changes in cellular energy metabolism and the accumulation of hydrogen ions.
A patient can have elevated lactate without developing acidosis, particularly if the body's buffering mechanisms are maintaining a normal blood pH. Conversely, metabolic acidosis can occur with normal lactate levels when another process is responsible, such as renal dysfunction or bicarbonate loss.
Lactate concentrations must therefore be interpreted alongside the patient's acid–base status, rather than assuming that an elevated lactate automatically indicates lactic acidosis.
Lactate Clearance and Trends
A single lactate measurement provides information about the patient's metabolic state at one point in time. Repeated measurements help clinicians assess whether the underlying physiological disturbance is improving, persisting or worsening.
A decreasing lactate concentration may suggest that lactate production is falling, utilisation is increasing or clearance is improving. However, it does not independently confirm that tissue perfusion has normalised.
Similarly, a persistently elevated or increasing lactate may indicate ongoing physiological stress, impaired perfusion, reduced clearance or another unresolved cause.
Lactate trends should be interpreted alongside:
Blood pressure and haemodynamic status
Heart rate and respiratory rate
Level of consciousness
Peripheral perfusion and capillary refill
Urine output
Oxygenation and respiratory function
The patient's response to treatment
Lactate reduction is sometimes described clinically as lactate clearance, although changes in measured concentrations reflect both production and removal rather than clearance alone.
Factors That Can Affect Lactate Results
Lactate results can be influenced by how the blood sample is collected, handled and processed. This is important because an incorrectly elevated result may suggest a physiological problem that is not actually occurring.
Several factors can affect lactate measurements:
Prolonged tourniquet application: Extended restriction of blood flow may increase local lactate production, particularly when combined with repeated fist clenching.
Repeated fist clenching: Contracting the hand muscles increases their energy requirements and can cause local lactate production, potentially affecting the sample.
Delayed sample processing: Blood cells continue metabolising glucose after collection, producing lactate. If the sample is not processed promptly or handled according to laboratory requirements, the measured lactate may increase.
Recent physical activity or seizures: Intense muscular activity increases glycolysis and lactate production. This can temporarily elevate lactate even when tissue perfusion is adequate.
Medications: Drugs such as salbutamol and adrenaline can stimulate glycolysis and increase lactate production independently of tissue hypoxia.
In clinical practice, lactate samples should be collected and handled according to local laboratory requirements. When a result is unexpectedly elevated or inconsistent with the patient's clinical presentation, clinicians should consider potential sampling errors, recent activity and medication effects, and whether repeat testing is appropriate.
In Practice
Understanding lactate production is only the first step. In clinical practice, lactate is interpreted alongside the patient's observations, medical history, medications and other investigations. The following scenarios demonstrate how similar lactate elevations can arise through different mechanisms and why clinical context is essential.
Scenario 1: Septic shock
A 72-year-old woman presents with fever, confusion and increasing weakness. She has a history of recurrent urinary tract infections and has become progressively unwell over the previous 24 hours.
Clinical findings:
Blood pressure: 82/46 mmHg
Heart rate: 124 beats/min
Respiratory rate: 28 breaths/min
Temperature: 39.2°C
Lactate: 5.6 mmol/L
Urine output: Reduced
Interpretation:
The markedly elevated lactate, together with hypotension, tachycardia, altered mental status and reduced urine output, raises significant concern for circulatory dysfunction associated with severe infection.
Reduced tissue perfusion may be contributing to increased lactate production, while the inflammatory and adrenergic responses associated with sepsis may also increase glycolysis.
This patient requires immediate escalation and assessment for septic shock, with time-critical management according to local sepsis protocols. Serial lactate measurements may help assess the physiological response to treatment, but they must be interpreted alongside haemodynamic status and other indicators of organ perfusion.
Scenario 2: Elevated lactate following a seizure
A 24-year-old man is brought to the emergency department following a witnessed generalised tonic-clonic seizure lasting approximately three minutes. He is initially drowsy but gradually becomes alert.
Clinical findings:
Blood pressure: 128/76 mmHg
Heart rate: 108 beats/min
Respiratory rate: 22 breaths/min
Lactate: 6.2 mmol/L
Repeat lactate two hours later: 1.8 mmol/L
Interpretation:
The elevated lactate is consistent with the intense muscular activity and increased metabolic demand associated with a generalised tonic-clonic seizure.
During the seizure, skeletal muscles rapidly consume ATP and increase glycolytic activity, producing substantial amounts of lactate. Once the seizure ends and metabolic demand decreases, lactate concentrations often fall relatively quickly.
The reduction from 6.2 to 1.8 mmol/L supports a transient increase in lactate production rather than ongoing accumulation.
Although the initial result is markedly elevated, it does not independently indicate shock or sepsis. The patient's neurological assessment, recovery and investigation of the seizure remain important.
Scenario 3: Haemorrhagic shock
A 38-year-old man is admitted following a motor vehicle collision. He has abdominal tenderness, cool extremities and increasing restlessness.
Clinical findings:
Blood pressure: 86/52 mmHg
Heart rate: 138 beats/min
Respiratory rate: 30 breaths/min
Lactate: 7.1 mmol/L
Haemoglobin: 94 g/L
Capillary refill: 5 seconds
Interpretation:
The markedly elevated lactate, hypotension, tachycardia and delayed capillary refill are concerning for significant tissue hypoperfusion associated with haemorrhagic shock.
Acute blood loss reduces circulating blood volume and compromises oxygen delivery to tissues. When oxygen supply becomes insufficient to meet metabolic demands, mitochondrial ATP production is limited and lactate accumulation may increase.
This is a life-threatening presentation requiring immediate escalation, haemorrhage control and resuscitation according to local trauma and massive transfusion protocols.
Lactate trends may contribute to monitoring the response to treatment, although they should not replace assessment of haemodynamics, bleeding and tissue perfusion.
Scenario 4: Elevated lactate during asthma treatment
A 29-year-old woman presents with an acute asthma exacerbation. She receives repeated doses of inhaled salbutamol and initially demonstrates improvement in wheeze and air entry. However, she remains tachypnoeic.
Clinical findings:
Blood pressure: 126/78 mmHg
Heart rate: 118 beats/min
Respiratory rate: 30 breaths/min
Oxygen saturation: 97% on room air
Lactate: 4.3 mmol/L
Interpretation:
The elevated lactate may be associated with beta₂-adrenergic stimulation from repeated salbutamol administration.
Beta₂-agonists can increase glycolysis and lactate production even when tissue oxygen delivery is adequate. Lactate accumulation may contribute to metabolic acidosis and increased respiratory drive, potentially making the patient appear persistently breathless despite improvement in bronchospasm.
However, persistent tachypnoea in a patient with acute asthma must not automatically be attributed to medication-related lactate production. Ongoing airflow obstruction, fatigue and other causes of deterioration require assessment.
Recognising this mechanism helps clinicians interpret lactate in context and avoid assuming that every elevation indicates worsening tissue hypoxia.
Scenario 5: Impaired lactate clearance in liver disease
A 61-year-old man with advanced cirrhosis is admitted with abdominal discomfort and increasing fatigue. He is haemodynamically stable and has no obvious signs of acute circulatory shock.
Clinical findings:
Blood pressure: 116/72 mmHg
Heart rate: 88 beats/min
Respiratory rate: 18 breaths/min
Lactate: 3.4 mmol/L
Bilirubin: 78 µmol/L
Albumin: 24 g/L
Interpretation:
The elevated lactate may partly reflect impaired hepatic lactate clearance.
Because the liver plays a major role in metabolising lactate, advanced hepatic dysfunction can reduce the body's capacity to remove lactate from circulation.
However, liver disease does not automatically explain every lactate elevation. Infection, gastrointestinal bleeding, hypovolaemia and other causes of physiological deterioration must still be considered, particularly in patients with cirrhosis.
This scenario demonstrates why elevated lactate should not be interpreted as definitive evidence of tissue hypoperfusion without considering the patient's underlying conditions and overall clinical presentation.
Clinical note: Lactate reference intervals and sampling procedures vary between laboratories. Elevated lactate is a marker of physiological disturbance rather than a diagnosis, and management should be guided by the patient's clinical presentation, serial assessments and relevant local protocols.