Chapter 172

### INTRODUCTION

The liver has numerous functions, including glucose homeostasis, protein metabolism, bilirubin formation and excretion, carbohydrate and lipid metabolism, blood filter, blood reservoir, drug metabolism, and excretion.

### GLUCOSE HOMEOSTASIS

The liver is the major site for glucose formation from lactate, amino acids (mainly alanine), and glycerol (derived from fat metabolism). Hepatic gluconeogenesis is primarily responsible for maintaining a normal blood glucose concentration. It should be noted that gluconeogenesis is inhibited by general anesthesia.

Glucose absorbed following a meal is stored in the liver as glycogen. When the liver’s capacity to store glycogen is exceeded, excess glucose is converted into fat. Insulin enhances glycogen synthesis, while epinephrine and glucagon enhance glycogenolysis. Normal glycogen stores about 65 g/kg of liver tissue in total. Average daily glucose consumption is 150 g/day, so glycogen stores are depleted within 48 hours of fasting.

### PROTEIN METABOLISM

The liver is responsible for four primary aspects of protein metabolism: (1) deamination of amino acids, (2) formation of urea to eliminate the ammonia, (3) interconversion between nonessential amino acids, and (4) formation of plasma proteins. Deamination occurs via enzymes (usually transaminases) as part of the metabolic process of converting excess amino acids into carbohydrates and fats. The deamination of alanine is critically important to hepatic gluconeogenesis. Ammonia is formed as a byproduct of deamination and is highly toxic to tissues. The liver combines two molecules of ammonia with CO2 to form urea which is then excreted by the kidneys.

Virtually all plasma proteins, with the exception of immunoglobulins, are formed by the liver. The most important of these proteins is albumin. Roughly, 10-15 g of albumin per day are synthesized by the liver to maintain the plasma albumin concentration between 3.5 and 5.5 g/dL. Albumin is responsible for maintaining plasma oncotic pressure as well as serving as the principal binding and transport protein for drugs and hormones. In fact, when plasma albumin concentration falls below 2.5 g/dL, there is increased drug sensitivity. In addition, the liver produces nearly all coagulation factors (I, II, and V-XIII) as well as plasma cholinesterase, antithrombin III, alpha-1 antitrypsin, transferrin, haptoglobin, and ceruloplasmin.

### CARBOHYDRATE AND LIPID METABOLISM

When carbohydrate stores are saturated, the liver converts excess ingested carbohydrates (and proteins) into fat, as well as storing fat. In addition, the liver is responsible for the synthesis of all lipoproteins which are used for the transport of lipids in the blood. Further, the liver is responsible for the synthesis of cholesterol and phospholipids, necessary components of cellular membranes.

### BILIRUBIN METABOLISM AND EXCRETION

Bilirubin is formed in the reticuloendothelial system from the breakdown of hemoglobin and then bound to albumin for transport to the liver. The liver then conjugates bilirubin with glucuronic acid via glucuronyl transferase into a water-soluble form where it is excreted ...

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