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The Liver - Part 2: physiology

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VOL: 101, ISSUE: 49, PAGE NO: 22

Helen L. Day, MSc, BSc, RGN, RSCN, DipN, is paediatric critical care clinical educator and outreach facilitator

Rachel M. Taylor, MSc, RGN, RSCN, DipRes, is nurse researcher, Paediatric Liver Centre; both at King’s College Hospital, London

The second article in this series on the liver examines its physiology, which any practitioner caring for a patient with a liver disorder will need to understand to identify presenting symptoms and deliver effective care. The functions of the liver can be grouped into three areas: metabolic, secretory and immunological.

The second article in this series on the liver examines its physiology, which any practitioner caring for a patient with a liver disorder will need to understand to identify presenting symptoms and deliver effective care. The functions of the liver can be grouped into three areas: metabolic, secretory and immunological.

Bile synthesis

Bile is formed in the hepatocytes and comprises water, electrolytes, bilirubin, steroid hormones, salts of bile acids, cholesterol, lecithin and many other substances. Bile secretion is stimulated by increased hepatic blood flow, vagus stimulation, elevated levels of bile salts in the blood and the hormone secretin.

The liver synthesises primary bile salts from cholesterol, providing the major route of cholesterol removal from the body. Secondary bile acids are formed from primary bile acids in the intestine by bacterial action. They are absorbed and returned to the liver in the enterohepatic circulation. If the bile salt level in the portal vein rises (via the enterohepatic circulation), the production of bile salts in the liver is slowed down (negative feedback) and their secretion into the bile is increased.

Bile serves to excrete several waste products from the blood. These include bilirubin, an end product of haemoglobin destruction, and excess cholesterol synthesised in the liver. Bile also plays an important role in fat digestion (Guyton and Hall, 2005; Ganong, 2003; Moseley, 2000; Pocock and Richards, 1999).

Red blood cells become less active and more fragile with time. The cell membrane ruptures and the haemoglobin released from the cells is phagocytosed by macrophages in many parts of the body, particularly in the liver by Kupffer cells, and in the spleen and bone marrow. The macrophages release the iron from haemoglobin - it is stored in the liver and other tissues as ferritin. The porphyrin portion of the haemoglobin is converted by macrophages into the bile pigment bilirubin. This is released by the macrophages into plasma where it is tightly bound to albumin and is called free or unconjugated bilirubin. Unconjugated bilirubin is absorbed through the hepatocyte membrane, released from albumin and then conjugated, mostly with glucuronide, before being excreted into the bile canaliculi (Guyton and Hall, 2005; Ganong, 2003; Moseley, 2000; Pocock and Richards, 1999).

Lipid metabolism

The liver receives lipids from the gastrointestinal tract - fatty acids, triglycerides and cholesterol. Triglycerides are the most abundant fats in the diet and are broken down to fatty acids by lipolysis. Cholesterol is an important component of cell membranes and is a precursor of steroid hormones and bile acids. When saturated fat is broken down the liver uses some of the products to make cholesterol. Lipoproteins are the product of a combination of proteins produced in the liver and triglycerides or cholesterol. Cholesterol and triglycerides are not water-soluble so are unable to pass through the bloodstream unless combined with proteins (Guyton and Hall, 2005; Ganong, 2003; Moseley, 2000; Pocock and Richards, 1999).

Carbohydrate metabolism

The liver plays an important role in glucose control. Following ingestion, all sugars pass to the liver and are converted to glucose. Some glucose remains in the circulation, maintaining normal blood glucose concentrations. Glucose that is not required is converted to the insoluble polysaccharide glycogen in the liver and muscles, through a process called glycogenesis. Glucose stored as glycogen in the liver can be released for liver activity and to meet the energy demands of other tissues by maintaining blood glucose levels. Excess carbohydrates are converted to fat through a process called lipogenesis and stored in fat depots (Guyton and Hall, 2005; Ganong, 2003; Moseley, 2000; Richards, 1999).

Lactate metabolism

Glucose and glycogen can be oxidised anaerobically, which is useful in exercising muscle. An end product of the complex reaction is lactate, which accumulates, representing an ‘oxygen debt’. When oxygen becomes available, lactate is metabolised in the liver and can then be converted to glucose in the liver by gluconeogenesis. The majority of lactate ions are removed in this way, so hepatic metabolism plays an important part in maintaining the acid-base balance (Ganong, 2003; Murphy et al, 2001; Moseley, 2000).

Protein metabolism

Amino acids are the basic materials for protein synthesis and are a major source of energy. The liver removes amino acids from the blood for protein synthesis and gluconeogenesis.

It is the major site for interconversion of non-essential amino acids, releases amino acids into the blood for use by the peripheral tissues, especially skeletal muscle, and plays a major role in amino acid breakdown, removing their nitrogen as urea. Urea formation also removes ammonia from body fluids, which is created during deamination and by bacteria in the gut.

The majority of plasma proteins are formed by the hepatocytes (Guyton and Hall, 2005; Ganong, 2003).


The liver is able to detoxify and excrete exogenous substances such as alcohol, drugs and poisons. In a similar manner, many hormones secreted by the endocrine system are either chemically altered or excreted by the liver, including thyroxine and all steroid hormones. The liver metabolises drugs to render them more hydrophilic for excretion. Excretion can occur via the bile, where first-pass metabolism or intra-hepatic recycling occurs. Some of the drug is excreted while some may re-enter the gastrointestinal tract via the sphincter of Oddi and return to the liver in the portal circulation. Excretion also occurs by elimination in urine. The liver metabolises alcohol by converting it to water and carbon dioxide (Guyton and Hall, 2005; Ganong, 2003).


The liver stores fat-soluble vitamins A, B12, D, E and K, and certain minerals such as iron and copper. The activation of vitamin D involves the skin, liver and kidneys (Guyton and Hall, 2005; Ganong, 2003).

Kupffer cells make up about 10 per cent of all cells in the liver. Their principal functions are shown in Table 1. Many of these materials are mediators of infection and/or tissue injury, so normal Kupffer cell activity is necessary for health. Kupffer cell activity may be depressed in liver disease owing to reduced perfusion, ischaemia, reduced plasma recognition factors or intrinsic dysfunction of the Kupffer cells, as seen in acute liver failure (Ganong, 2003; Rolando et al, 1996).


Coagulation is a complex mechanism involving two pathways (intrinsic and extrinsic), which meet to form a common pathway and produce fibrin, which facilitates the conversion of a loose aggregation of platelets to a definitive clot. The formation of fibrin involves a cascade of reactions to convert the soluble plasma protein fibrinogen to insoluble fibrin. With the exception of von Willebrand factor, all clotting factors are synthesised in the hepatocytes (Pereira et al, 1996).

Liver failure can be characterised by failure to synthesise these factors, resulting in coagulopathy and a tendency to bleed. The liver also synthesises many inhibitors of coagulation, which further complicate coagulopathy in liver disease and can lead to disseminated intravascular coagulation (Guyton and Hall, 2005; Ganong, 2003; Moseley, 2000).

- This article has been double-blind peer-reviewed.

For related articles on this subject and links to relevant websites see

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