Ross & Wilson Anatomy and Physiology in Health and Illness (154 page)

Circulatory disturbances

The intensely active hepatocytes are particularly vulnerable to damage by hypoxia, which is usually due to impaired blood supply caused by:

•
fibrosis in the liver following inflammation

•
compression of the portal vein, hepatic artery or vein by a tumour

•
acute general circulatory failure and shock

•
venous congestion caused by acute or chronic right-sided heart failure (
Ch. 5
).

Chronic hepatitis

This is defined as any form of hepatitis which persists for more than 6 months. It may be caused by viruses, alcohol or drugs, but sometimes the cause is unknown.

Mild, persistent inflammation may follow acute viral hepatitis. There is usually little or no fibrosis.

There may be continuing progressive inflammation with cell necrosis and the formation of fibrous tissue that may lead to cirrhosis of the liver. There is distortion of the liver blood vessels and hypoxia, leading to further hepatocyte damage. This condition is commonly associated with Types B and C viral hepatitis, some forms of autoimmunity and unpredictable (idiosyncratic) drug reactions.

Cirrhosis of the liver

This is the result of long-term injury caused by a variety of agents. The most common causes are:

•
excessive alcohol consumption

•
hepatitis B and C virus infections

•
recurrent obstruction of the biliary tract.

As the inflammation subsides, destroyed liver tissue is replaced by fibrous tissue. There is hyperplasia of hepatocytes adjacent to damaged areas, in an attempt to compensate for the destroyed cells. This leads to the formation of nodules consisting of hepatocytes confined within sheets of fibrous tissue.

As the condition progresses portal hypertension develops, leading to congestion in the organs drained by the tributaries of the portal vein, to ascites and to the development of oesophageal varices (
p. 313
).

Liver failure may occur when hyperplasia is unable to keep pace with cell destruction, and there is increased risk of liver cancer developing.

Liver failure

This occurs when liver function is markedly impaired. It can be acute or chronic and may be the outcome of a wide variety of disorders, e.g.:

•
acute viral hepatitis

•
extensive necrosis due to poisoning, e.g. some drug overdoses, hepatotoxic chemicals, adverse drug reactions

•
cirrhosis of the liver.

Liver failure has serious effects on other parts of the body.

Hepatic encephalopathy

The cells affected are the astrocytes in the brain. The condition is characterised by apathy, disorientation, muscular rigidity and confusion, progressing to coma. Several factors may be involved, e.g.:

•
nitrogenous bacterial metabolites absorbed from the colon, which are normally detoxified in the liver, reach the brain via the blood

•
other metabolites, normally present in trace amounts, e.g. ammonia, may reach toxic concentrations and change the permeability of the cerebral blood vessels and the effectiveness of the blood–brain barrier

•
hypoxia and electrolyte imbalance.

Blood coagulation defects

The liver fails to synthesise substances needed for blood clotting, i.e. prothrombin, fibrinogen and factors II, V, VII, IX and X. Purpura, bruising and bleeding may occur.

Oliguria and renal failure

Portal hypertension may cause the development of oesophageal varices (
p. 313
). If these rupture, bleeding may lead to a fall in blood pressure sufficient to reduce the renal blood flow, causing progressive oliguria and renal failure.

Oedema and ascites

These may be caused by the combination of two factors:

•
portal hypertension raises the capillary hydrostatic pressure in the organs drained by the tributaries of the portal vein (see
Fig. 5.46, p. 103
)

•
diminished production of serum albumin and clotting factors reduces the plasma osmotic pressure.

Together these changes cause the movement of excess fluid into the interstitial spaces where it causes
oedema
. Eventually free fluid accumulates in the peritoneal cavity and the resultant
ascites
may be severe.

Jaundice

The following factors may cause jaundice as liver failure develops:

•
inability of the hepatocytes to conjugate and excrete bilirubin

•
obstruction to the movement of bile through the bile channels by fibrous tissue that has distorted the structural framework of liver lobules.

Tumours of the liver

Benign tumours are very rare.

Malignant tumours

Cancer of the liver is frequently associated with cirrhosis but the relationship between them is not clear. It may be that both cirrhosis and cancer are caused by the same agents or that the carcinogenic action of an agent is promoted by cirrhotic changes. Malignancy sometimes develops following acute hepatitis caused by Types B and C viruses. The most common sites of metastases are the abdominal lymph nodes, the peritoneum and the lungs.

Secondary malignant tumours (metastases) in the liver are more common than primary liver tumours. They usually spread there from primary tumours in the gastrointestinal tract, the lungs and the breast. They tend to grow rapidly and are often the cause of death.

Diseases of the gall bladder and bile ducts

Learning outcomes

After studying this section, you should be able to:

describe the causes and consequences of gallstones

compare and contrast acute and chronic cholecystitis

briefly outline the common sites and consequences of biliary tract tumours

discuss the main causes and effects of jaundice.

Gallstones (cholelithiasis)

Gallstones consist of deposits of the constituents of bile, most commonly cholesterol. Many small stones or one or more large stones may form but they do not necessarily produce symptoms. Predisposing factors include:

•
changes in the composition of bile that affect the solubility of its constituents

•
high blood cholesterol levels

•
diabetes mellitus

•
female gender

•
obesity

•
several pregnancies in young women, especially when accompanied by obesity.

Acute cholecystitis

This is acute inflammation of the gall bladder usually associated with gallstones, and occurs when a gallstone becomes impacted (stuck) in the cystic duct, often after a fatty meal. Strong peristaltic contractions of the smooth muscle in the wall of the cystic duct that occur in an attempt to move the stone onwards result in
biliary colic
, severe acute pain in the right hypochondrium. This does not cause jaundice because bile from the liver can still pass directly into the duodenum. Bile is unable to leave the gall bladder and an inflammatory reaction follows. This may be complicated by bacterial infection and distension of the gall bladder, which carries the risk of perforation and peritonitis.