Lactic Acidosis in Liver Cirrhosis

02 January, 2024

Love your liver this January with Fortress Diagnostics. The liver is the largest organ in the body. It is an incredible organ with a multitude of crucial functions essential for maintaining overall health. Despite its significance, it often doesn’t receive as much attention as other vital organs, like the lungs or heart 1. Acute and chronic hepatic insufficiency can lead to lactate accumulation and subsequently result in lactic acidosis 2.

 

Lactic Acid

Lactic acid, or lactate, is produced when cells break down carbohydrates for energy. During intense physical activities or situations where the body requires energy faster than the oxygen supply available (anaerobic conditions), such as during vigorous exercise, the muscles produce lactic acid as a by-product of cellular metabolism. Lactic acid production isn’t exclusive to exercising muscles. Any activity that demands increased oxygen usage can lead to its production. This includes various physical exertions like yard work or carrying heavy items. This temporary rise in lactic acid levels typically isn’t harmful and is usually processed and removed by the liver and kidneys 3.

Lactic acid, or lactate, serves several roles within the body:

  1. Energy production: During times of intense physical activity or when oxygen availability is limited (anaerobic conditions), cells, particularly muscle cells, can produce energy quickly by breaking down glucose without the need for oxygen. This process, called anaerobic glycolysis, generates lactate as a by-product. Lactate can be used as a temporary energy source within the muscle cells themselves or transported to other tissues, like the heart or liver, where it can be converted back into glucose and used as fuel.
  2. Regulation of pH: Lactate also plays a role in maintaining the body’s acid-based balance. When produced in excess, it can contribute to changes in pH. The body has mechanisms to regulate this, such as converting lactate back into glucose in the liver, which helps stabilise pH levels.
  3. Metabolic fuel: Lactate produced in one tissue can be transported via the bloodstream to other tissues where it can serve as an energy source. For instance, the heart can use lactate as an energy substrate.
  4. Intermediary metabolite: Lactate is an intermediary metabolite in various metabolic pathways. It can be converted to pyruvate and then used in the Krebs cycle (citric acid cycle) to produce energy aerobically.
  5. Gluconeogenesis: After its production in tissues, lactic acid can be filtered out of the blood by the liver and kidneys. These organs play a crucial role in converting lactate back into glucose through gluconeogenesis. The newly synthesised glucose can then be stored or used by the body as an energy source when needed, helping to maintain blood sugar levels.
  6. Molecular Signalling: Lactic acid can act as a signalling molecule in the body. It functions as a signalling agent involved in various processes, including would healing and immune response. Lactic acid can attract immune cells to sites of tissue damage or infection, aiding in the healing process and fighting off infections. It serves as a kind of marker or signal for cells involved in the immune response.

While historically considered a waste product or a substance causing fatigue during exercise, recent research suggests lactate has a more complex role in metabolism and exercise physiology than previously thought. It’s an important metabolic intermediate that can be utilised by various tissues in the body. The multifaceted role of lactic acid extends beyond being solely a by-product of anaerobic metabolism. It demonstrates its significance as both an energy substrate and a signalling molecule involved in various physiological processes within the body, contributing to energy production, metabolic regulation, and immune response 3.

 

Lactic Acidosis

Lactic acidosis occurs when there’s an accumulation of lactic acid in the bloodstream beyond the body’s capacity to clear it. The liver and kidneys play crucial roles in metabolising and removing excess lactic acid from the body. However, if there’s an excessive production of lactic acid or if the liver or kidneys are impaired and cannot adequately process and clear the lactate, it can lead to lactic acid build-up in the blood. A moderate increase in blood lactate levels is termed hyperlactatemia, which might not necessarily lead to significant changes in pH levels. However, when the accumulation of lactic acid reaches a point where it disrupts the body’s acid-base balance, causing a decrease in blood pH (acidosis), it is then termed lactic acidosis 4.

Lactic acidosis can result from various conditions or factors, such as:

  1. Sepsis or infections: Severe infections can lead to a state of shock, impairing oxygen delivery to tissues and causing lactic acid build-up.
  2. Hypoperfusion or shock: Conditions where there is decreased blood flow or oxygen delivery to tissues, such as in shock states or heart failure, can result in lactic acidosis.
  3. Liver disease: Liver dysfunction or failure can hinder the breakdown and clearance of lactate, contributing to lactic acidosis.
  4. Medications and toxins: Some medications or toxins can interfere with cellular metabolism, leading to increased lactate production and subsequent lactic acidosis.
  5. Metabolic disorders: Certain inherited metabolic disorders can disrupt the body’s ability to metabolise lactate, leading to its accumulation and lactic acidosis.

The symptoms of lactic acidosis can range from mild to severe and might include: abdominal pain, confusion, lethargy, nausea, rapid breathing, vomiting, and in severe cases, shock or organ failure. Treatment involves addressing the underlying cause, providing supportive care, and correcting the acid-base imbalance. Prompt medical attention is crucial in managing lactic acidosis 4.

 

Liver Cirrhosis

Cirrhosis is a condition characterised by severe scarring of the liver tissue. This scarring occurs as a result of chronic liver injury, which can stem from various causes, such as: autoimmune liver diseases, chronic alcohol abuse, non-alcoholic fatty liver disease (NAFLD), viral hepatitis, or other factors that lead to ongoing liver damage 5.

The liver has a remarkable ability to regenerate and repair itself. However, when the liver is repeatedly injured or experiences chronic inflammation due to conditions like hepatitis or ongoing exposure to toxins (alcohol), the healing process leads to the formation of scar tissue. This scarring, also known as fibrosis, gradually replaces healthy liver tissue and disrupts the liver’s structure and function 5.

As cirrhosis progresses, the liver’s capacity to perform its vital functions, such as processing nutrients, filtering toxins, producing proteins, and regulating various metabolic processes, becomes increasingly impaired. Advanced cirrhosis can result in complications like portal hypertension (increase pressure in the portal vein system), ascites (accumulation of fluid in the abdomen), hepatic encephalopathy (brain dysfunction due to liver failure), and an increase risk of liver cancer 5.

Unfortunately, the damage caused by cirrhosis is often irreversible. However, early diagnosis and management of the underlying cause, such as treating viral hepatitis, addressing alcohol dependency, managing complication, and adopting lifestyle changes, can slow down or half the progression of cirrhosis. In some rare cases, such as when cirrhosis is diagnosed early and the underlying cause is effectively treated, it is possible for some degree of liver function to be restored or further damage to be limited. Regular monitoring, adherence to treatment plans, and lifestyle modifications are crucial for individuals with cirrhosis to manage the condition and prevent complications. Ultimately, advanced cirrhosis is a serious and potentially life-threatening condition, requiring ongoing medical care and support 5.

 

Lactic Acidosis in Liver Cirrhosis

Several studies support the positive correlation between lactic acidosis and liver cirrhosis.

  1. Acid-based status and its clinical implication in critically ill patients with cirrhosis, acute-on-chronic liver failure and without liver disease (2018) 6

A post hoc analysis of prospectively collected data of 178 critically ill patients with liver cirrhosis compared to 178 matched controls. The study found that hyperchloremic acidosis and hypoalbuminemic alkalosis coexist in the critically ill patients, including those with liver cirrhosis. The study found that in cirrhosis, particularly acute-on-chronic liver failure (ACLF), the net acidosis was caused by lactate and unmeasured ions (BEUMA). Lactate was linked to hepatic function and vasopressor use, whereas the unmeasured ions were strongly associated with acute kidney injury. The metabolic differences between cirrhosis and non-cirrhosis critically ill patients increased with the severity of the disease, resulting in pronounced academia in cirrhosis patients with ACLF. Lactate and BEUMA were identified as independent predictors of 28-day mortality in critically ill patients with liver cirrhosis and ACLF.

 

  1. Metabolic acidosis in critically ill patients with cirrhosis: Epidemiology and short-term mortality risk factors (2019) 7

A Chinese study prospectively evaluated 975 patients with cirrhosis to explore the epidemiology and risk factors of metabolic acidosis in critically ill patients with cirrhosis with a follow-up for at least 28 days. Of these 975 patients with liver cirrhosis, 506 had metabolic acidosis, including 275 patients who had decompensated metabolic acidosis at intensive care unit admission. The study concluded that critically ill patients with cirrhosis have a high mortality rate and poor prognosis due to the high prevalence of metabolic acidosis. It was found that lactic acidosis was the worst prognosis of all the different types of metabolic acidosis.  

 

  1. Liver cirrhosis affects serum lactate level measurement while assessing disease severity in patients with sepsis (2021) 8

A Chinese study retrospectively evaluated 12,281 cases of infection, with initial serum blood lactate drawn during January 2007-December 2013 to determine the predictive ability of serum lactate in patients with liver cirrhosis and sepsis. The study concluded that serum lactate levels can be used to predict the severity of sepsis in patients with liver cirrhosis.

 

  1. Serum lactate levels in cirrhosis and non-cirrhosis patients with septic shock (2022) 9

A retrospective cohort study conducted at a referral, university-affiliated medical centre in Thailand between 2012 and 2018 who satisfied the septic shock diagnostic criteria of the Surviving Sepsis Campaign: 2012. 777 patients were enrolled of which 91 had previously been diagnosed with cirrhosis with lactate levels reviewed on arrival and at 6 hours. The study concluded that the initial lactate level and lactate at 6 hours were significantly higher in cirrhosis patients than in non-cirrhosis patients.

 

How Fortress Can Help

At Fortress diagnostics, we offer a few lactate assays.

Description

Cat Code

Kit Size

Category

Lactate (Lyo.)

BXC0621A

R1: 1x105ml; R2: 16x6ml; R4: 1x5ml

Clinical Chemistry Reagent

Lactate (Monoliquid) Enzymatic (Colorimetric

BXC0622A

R1: 2x50ml; R2: 1x5ml

Clinical Chemistry Reagent

Lactate Dehydrogenase P-L (L.S)

BXC0242A

R1: 5x20ml; R2: 1x20ml

Clinical Chemistry Reagent

Lactate Dehydrogenase L-P (L.S)

BXC0243A

R1: 5x20ml; R2: 1x20ml

Clinical Chemistry Reagent

Lactate

HIT0621B

R1: 1 x 100ml R2: 16 X 6ml

Analyser Specific Reagent

Lactate (Mono)

HIT0622A

R1: 5 x 20ml

Analyser Specific Reagent

Lactate Dehydrogenase P-L

HIT0242A

R1: 12 x 20ml R2: 3 x 20ml

Analyser Specific Reagent

Lactate Dehydrogenase P-L

HIT0242C

R1: 2 x 20ml R2: 1 x 8ml

Analyser Specific Reagent

Lactate Dehydrogenase L-P

HIT0243A

R1: 12 x 20ml R2: 3 x 20ml

Analyser Specific Reagent

Lactate Pyruvate

HIT0243C

R1: 2 x 20ml R2: 1 x 8ml

Analyser Specific Reagent

Lactate (Mono)

OLY0622B

R1: 2 x 30ml

Analyser Specific Reagent

Lactate (Mono)

BXCF622A

R1: 4 x 20.5ml

Analyser Specific Reagent

 

Fortress Diagnostics Hepatic Panel

Description

Category

Alanine Aminotransferase (ALT)

Clinical Chemistry Reagent

Alanine Aminotransferase (ALT)

Analyser Specific Reagent

Aspartate Aminotransferase (AST)

Clinical Chemistry Reagent

Aspartate Aminotransferase (AST)

Analyser Specific Reagent

Albumin

Clinical Chemistry Reagent

Albumin

Analyser Specific Reagent

Ammonia

Clinical Chemistry Reagent

Ammonia

Analyser Specific Reagent

Ammonia

Controls & Calibrators

Alcohol/Ammonia/Carbonate

Controls & Calibrators

Bile Acids

Clinical Chemistry Reagent

Bile Acids

Analyser Specific Reagent

Bilirubin

Clinical Chemistry Reagent

Bilirubin

Analyser Specific Reagent

Bilirubin

Controls & Calibrators

Hepatitis A

ELISA

Hepatitis B

ELISA

Hepatitis C

ELISA

Hepatitis D

ELISA

Hepatitis E

ELISA

Urine Strips

Urinalysis

Blood Alcohol

Clinical Chemistry Reagent

Blood Alcohol

Analyser Specific Reagent

Blood Alcohol

Controls & Calibrators

Gamma-Glutamyltransferase (GGT)

Clinical Chemistry Reagent

Gamma-Glutamyltransferase (GGT)

Analyser Specific Reagent

PT High Sensitivity

Haemostasis

PT Low Sensitivity

Haemostasis

Total Protein

Clinical Chemistry Reagent

Total Protein

Analyser Specific Reagent


References

  1. British Liver Trust. Love Your Liver awareness month. https://britishlivertrust.org.uk/love-your-liver-month/ (accessed 14 December 2023).
  2. Cheng CY, Kung CT, Wu KH, Chen FC, Cheng HH, et al. Liver cirrhosis affects serum lactate level measurement while assessing disease severity in patients with sepsis. European Journal of Gastroenterol Hepatol 2021; 33(9): . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322043/ (accessed 18 December 2023).
  3. Cleveland Clinic. What is lactic acid?. https://my.clevelandclinic.org/health/body/24521-lactic-acid (accessed 18 December 2023).
  4. Cleveland Clinic. Lactic Acidosis. https://my.clevelandclinic.org/health/diseases/25066-lactic-acidosis (accessed 18 December 2023).
  5. Mayo Clinic.  https://www.mayoclinic.org/diseases-conditions/cirrhosis/symptoms-causes/syc-20351487 (accessed 18 December 2023).
  6. Drolz A, Horvatits T, Roedl K, Rutter K, Brunner R, et al. Acid–base status and its clinical implications in critically ill patients with cirrhosis, acute-on-chronic liver failure and without liver disease. Annals of Intensive Care 2018; 48(8): . https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-018-0391-9 (accessed 18 September 2023).
  7. Gao F, Lin MT, Yang XY, Cai MX, Nan H, et al. Metabolic acidosis in critically ill patients with cirrhosis: Epidemiology and short-term mortality risk factors. Turkish Journal of Gastroenterology 2019; 30(10): . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812953/ (accessed 18 December 2023).
  8. Cheng CY, Kung CT, Wu KH, Chen FC, Cheng HH, et al. Liver cirrhosis affects serum lactate level measurement while assessing disease severity in patients with sepsis. European Journal of Gastroenterology and Hepatology 2021; 33(9): . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322043/ (accessed 18 December 2023). Tongyoo S, Sutthipool K, Viarasilpa T, Permpikul C. Serum lactate levels in cirrhosis and non-cirrhosis patients with septic shock. Acute and Critical Care 2022; 37(1): . chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.accjournal.org/upload/pdf/acc-2021-00332.pdf (accessed 18 December 2023).

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