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PATHOPHYSIOLOGY
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Chapter 36: Alterations of Digestive Function – Part 2
Accessory Organs and Cancers of the Digestive System
I. Vascular Insufficiency

Vascular insufficiency in the intestine is most often associated with occlusion or obstruction of
the mesenteric vessels or insufficient arterial blood flow.

Acute insufficiency is usually due to emboli dislodged from the heart.

The resulting ischemia and necrosis produce abdominal pain, fever, bloody diarrhea,
hypovolemia, and shock.
II. Disorders of Nutrition
A. Obesity

Obesity is a metabolic disorder with an increase in body fat mass and a BMI greater than 30.

The causes of obesity are complex and involve the interaction of adipokines produced by fat cells
and other body weight control signals at the level of the hypothalamus.

o
Hypothalamic resistance to leptin increases body fat mass.
o
The gene for leptin is mutated in some obese people.
Central obesity increases the risk of developing hypertension, coronary artery disease, type 2
diabetes mellitus, cancer, and pulmonary disorders.
B. Anorexia Nervosa and Bulimia Nervosa

Both involve abnormal eating behavior, weight regulation, and disturbed attitudes toward body
weight, body shape, and size.
1. Anorexia nervosa

Anorexia nervosa is a psychologic and physiologic syndrome characterized by the following:
o
Fear of becoming obese despite progressive weight loss.
o
Distorted body image: the perception that the body is fat when it is actually underweight.
o
Body weight 15% less than normal for age and height because of refusal to eat.
o
In women and girls, absence of three consecutive menstrual periods.

Primarily occurs in adolescent and young women.

Anorexic patients can lose 25% to 30% of their ideal body weight.

Clinical manifestations:
o
Without adequate nutrition, muscle and fat depletion lead to hypotension, edema,
bradycardia, hypothermia, and constipation.

o
Can lead to starvation-induced cardiac failure.
o
Death may occur if weight loss exceeds 25% of ideal body weight.
Treatment - intensive psychologic intervention; may require hospitalization to restore
nutritional balance.
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2. Bulimia nervosa

Bulimia nervosa, or binging and purging, involves eating normal or large amounts of food
and then purging by inducing vomiting or abusing laxatives.
o
Severe weight loss is rare.
o
Frequent vomiting and laxative use result in pathological effects.

Often accompanies anorexia nervosa and may have similar psychological causes.

Clinical manifestations:
o
Continual vomiting of acidic chyme can cause pitted teeth, pharyngeal and esophageal
inflammation, and tracheoesophageal fistulas.
o
Overuse of laxatives can cause rectal bleeding.
III. Disorders of the Accessory Organs of Digestion
A. Clinical Manifestations of Liver Disorders
1. Portal hypertension

Portal hypertension is an elevation of portal venous pressure to at least 10mm Hg.

Results from increased resistance to venous flow in the portal vein and its tributaries,
including the sinusoids and hepatic vein.

Causes - cirrhosis of the liver (most common); can be seen in congestive heart failure, hepatic
vein thrombosis, and infection of the liver.

Pathophysiology:
o
The portal system consists of a large network of collateral veins that come together to
form the portal vein before it enters the liver.
o
When flow in the portal vein is obstructed, pressures rise and are reflected back to these
collateral veins, causing them to dilate and become prone to rupture and hemorrhage.

Consequences:
o
Esophageal varices - often cause bleeding; rupture can be life-threatening.
o
Hemorrhoids - varices of the rectum.
o
Splenomegaly - from increased pressures reflected into the splenic vein.
o
Ascites - increased pressures in the veins in the abdomen cause translocation of fluid
from the vessels into the peritoneal space.
o
Hepatic encephalopathy - CNS disturbances and alterations of consciousness due to
toxins in blood that are not removed by the liver.
2. Ascites

Ascites is accumulation of protein-rich fluid in the peritoneal space.

Causes - hepatic cirrhosis (most common), malignancies, and conditions characterized by
reduced intravascular oncotic pressure such as nephrotic syndrome and malnutrition.
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
Pathophysiology of ascites:
o
Liver damage reduces the production of albumin and increases portal venous pressures.
o
Together these cause capillary hydrostatic pressure to exceed capillary osmotic pressure.
o
This imbalance pushes water into the peritoneal cavity.
o
Conditions that impair excretion of sodium by the kidneys promote water retention and
add to the volume of fluid that accumulates.

Clinical manifestations - weight gain due to fluids and increased abdominal girth, dyspnea
due to pressure on diaphragm, and vulnerability to peritoneal infection.
3. Hepatic encephalopathy

Hepatic encephalopathy is impaired cerebral function caused by blood-borne toxins
(particularly ammonia) not metabolized by the liver.

Toxin-bearing blood may bypass the liver in collateral vessels dilated as a result of portal
hypertension, or diseased hepatocytes may be unable to carry out their metabolic functions.

Clinical manifestations - range from memory loss, confusion and asterixis (flapping tremor of
the hands) to loss of consciousness, coma, and death.

The condition develops rapidly during fulminant hepatitis or slowly during chronic liver disease.
4. Jaundice (icterus)

Jaundice (icterus) is a yellow or greenish pigmentation of the skin or sclera of the eyes
caused by increases in plasma bilirubin concentration (hyperbilirubinemia).

Unconjugated bilirubin (UCB) - bilirubin that has not been processed by the liver.

Conjugated bilirubin (CB) - bilirubin that has been linked to glucuronic acid by liver cells.
a. Obstructive jaundice
1) Intrahepatic obstructive jaundice - caused by obstructed bile canaliculi in the liver.
o
Due to liver disease (e.g., hepatitis, cirrhosis).
o
Results in increased levels of both unconjugated (UCB) and conjugated bilirubin (CB)
which build up in the blood.
o
Stool and urine tend to be light in color because less bilirubin is converted to
urobilinogen, which normally gives urine (and to a lesser extent, feces) a yellow color.
2) Extrahepatic obstructive jaundice - caused by obstructed bile ducts outside the liver.
o
Due to gallstones or tumors.
o
Results in elevation of conjugated bilirubin (CB).
o
Bilirubin accumulates proximal to sites of obstruction, enters the bloodstream, and is
carried to the skin and deposited, causing yellow color and pruritis (itching).
o
Stools tend to be light because bile is not entering small intestine, but urine tends to
be darker than normal.
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b. Hemolytic jaundice

Also called prehepatic jaundice.

Caused by excessive red blood cell destruction (hemolysis).

Results from hemolytic crisis (as in sickle cell disease) or hemolytic drugs.

Produces elevated levels of unconjugated bilirubin (UCB).

Higher levels of UCB in the stool and urine cause them to have a darker color.
ACTIVITY 1: Match each sign, symptom or characteristic to the associated type of jaundice.
a. Intrahepatic obstructive
b. Extrahepatic obstructive
c. Hemolytic
1. High UCB.
4. Light stool and urine.
7. Pruritis
2. High CB.
5. Dark stool and urine.
8. Anemia
3. High CB and UCB.
6. Light stool, dark urine.
9. Alcoholism
10. Gallstones
5. Hepatorenal Syndrome

Hepatorenal syndrome is functional kidney failure caused by advanced liver disease,
particularly cirrhosis with portal hypertension.
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Renal failure is caused by a sudden decrease in blood flow to the kidneys, usually caused by
massive gastrointestinal hemorrhage or liver failure.

Clinical manifestations - oliguria, ascites, hypotension, jaundice, and gastrointestinal
bleeding.
B. Disorders of the Liver
1. Viral Hepatitis

Hepatitis - any inflammatory process affecting the liver.
o

Most commonly describes viral infection of the liver by one of five viruses.
Causes hepatic cell necrosis, Kupffer cell hyperplasia, and infiltration of liver tissue by
mononuclear phagocytes.
o
These changes obstruct bile flow and impair hepatocyte function.

Most acute infections are followed by regeneration and recovery.

Persistent infection and inflammation, fulminant hepatitis, and even death can occur.
a. Hepatitis A Virus (HAV) Infection

Formerly known as infectious hepatitis.

Results from ingestion of contaminated water or food.
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Relatively short incubation period (30 days).

Causes an acute, relatively mild illness, usually followed by complete recovery.
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
Clinical manifestations - predictable phases that depend on the stage of infection.
o
Prodromal phase - fever, malaise, anorexia, and liver enlargement and tenderness.
o
Icteric phase - jaundice, enlarged liver, hyperbilirubinemia (causes dark urine and stools).
o
Recovery phase - symptoms resolve. Recovery takes several weeks.
b. Hepatitis B Virus (HBV) Infection

Formerly known as serum hepatitis.

Results from exposure to contaminated blood and body fluids, often through sexual
contact, needlestick injury, or intravenous drug use.
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Incubation period 60-180 days.

The initial phase of infection can be acutely symptomatic or insidious.

Diagnosed by presence of hepatitis B surface antigens (HBsAg).
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Pathophysiology:
o
Hepatic injury is due to immune response to viral antigen in hepatocytes.
o
A vigorous immune response increases acute symptoms but decreases chronic infection.
o
Weakened immunity causes fewer acute symptoms but a greater risk of chronic infection
and being a carrier.

Chronic active hepatitis B is characterized by continued inflammation and the risk for the
development of cirrhosis and hepatocellular carcinoma.
c. Hepatitis C Virus (HCV) Infection

HCV is acquired through the same routes as hepatitis B.
o
Responsible for most cases of hepatitis due to blood transfusion and IV drug use.

Rarely causes acute illness.

Up to 80% of infected individuals develop chronic HCV infection, and up to 20% of
these progress to cirrhosis and liver failure.

HCV infection is a common reason for liver transplantation.

HCV is directly cytopathic to hepatocytes and results in persistent inflammation and
progressive scarring.
2. Fulminant hepatitis

Clinical syndrome of severe impairment or necrosis of liver cells and potential liver failure.

Complication of hepatitis B or C virus, congenital disorders or toxic reactions to drugs or poisons.

Causes widespread hepatic necrosis and is often fatal.

Clinical manifestations - initially: anorexia, vomiting, abdominal pain, and progressive
jaundice; followed by ascites, gastrointestinal bleeding and hepatic encephalopathy; renal
failure and pulmonary distress can occur.
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3. Cirrhosis

Cirrhosis is an irreversible inflammatory disease of the liver that disrupts liver function.

Results in disorganization of lobular structure, fibrosis, and nodular regeneration.

Cirrhosis obstructs biliary channels and causes portal hypertension.
o
Hypertension shunts blood away from the liver, and a hypoxic necrosis develops.

Causes - hepatitis or toxins, such as acetaldehyde (product of alcohol metabolism).

Progressive irreversible liver damage occurs, usually over a period of years.
a. Alcoholic liver disease

Acetaldehyde damages hepatocytes and impairs their ability to oxidize fatty acids, synthesize
enzymes and proteins, degrade hormones, and clear portal blood of ammonia and toxins.

The inflammatory response includes excessive collagen formation, fibrosis, and scarring,
which obstruct bile canaliculi and sinusoids.
o
Bile obstruction causes jaundice.
o
Vascular obstruction causes portal hypertension, shunting, and varices.
o
Hepatocyte damage interferes with production of clotting factors, causing bleeding.

Fatty liver is a mild form of alcoholic liver disease. Asymptomatic and reversible.

Damage in severe disease is irreversible, and often requires liver transplant.
b. Biliary cirrhosis

Cirrhosis that begins in the bile canaliculi and ducts.
1) Primary biliary cirrhosis - autoimmune inflammation results in destruction of
intrahepatic bile ducts.
2) Secondary biliary cirrhosis - develops from prolonged obstruction of bile flow.
o
Obstruction increases pressure in the hepatic bile ducts, causing pooling of bile and
necrosis of tissue.
o
Relief of obstruction allays symptoms of jaundice and pruritus.
o
Continued obstruction causes cirrhosis and liver failure.
ACTIVITY 2: Match each characteristic to the type of cirrhosis it is associated with.
a. Alcoholic cirrhosis
b. Primary biliary cirrhosis
c. Secondary biliary cirrhosis
1. Caused by autoimmune disorder.
4. Fatty liver is early stage.
2. Caused by toxins like acetaldehyde.
5. Involves destruction of liver bile ducts.
3. Caused by blockage of bile flow.
6. Reversible if obstruction is relieved.
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B. Disorders of the Gallbladder
1. Cholelithiasis
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Cholethiasis is the accumulation of gallstones in the gallbladder.

Affects up to 20% of individuals in developed countries.

Risk factors - obesity, middle age, female gender, Native American ancestry, and gallbladder,
pancreas, or ileal disease.

Gallstones form in the bile as a result of the aggregation of cholesterol crystals (cholesterol
stones; most common) or precipitates of unconjugated bilirubin (pigmented stones).
o
Gallstones that fill the gallbladder or obstruct the cystic or common bile duct cause
abdominal pain and jaundice.

Clinical manifestations - colicky abdominal pain that is intermittent and often associated with
fatty food intake; jaundice occurs if stone lodges in common bile duct.
2. Cholecystitis

Cholecystitis is an inflammation of the gallbladder wall.

It is usually associated with obstruction of the cystic duct by gallstones.
C. Disorders of the Pancreas
1. Acute pancreatitis

Inflammation of the pancreas.

Causes - obstruction of the pancreatic duct by a gallstone (most common); heavy alcohol intake.

Pathophysiology:
o
Damaged pancreas cells leak digestive proenzymes into pancreatic tissue.
o
Proenzymes become activated and begin the process of autodigestion, which causes
inflammation, and destruction of tissues.
o
Release of pancreatic enzymes and inflammatory mediators into the bloodstream or
abdominal cavity can result in the systemic inflammatory response syndrome (SIRS) with
renal, pulmonary, and myocardial dysfunction.
o

Release of vasoactive inflammatory mediators can cause systemic vasodilation and shock.
Clinical manifestations - severe epigastric pain, fever, nausea, and vomiting; elevated levels
of pancreatic enzymes in blood serum, including pancreatic lipase and amylase.

Treatment - often difficult; includes narcotic pain control, eliminating oral intake of food and
fluids, parenteral fluids and nutrition, antacids, and antibiotics.
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2. Chronic pancreatitis

Chronic pancreatitis results from repetitive inflammation of the pancreas.

Related to chronic alcohol abuse.

Chronic inflammation and scarring of the pancreas cause insulin deficiency and pancreatic
insufficiency, with associated digestive problems.

Clinical manifestations - severe abdominal pain, malabsorption of fat with steatorrhea, and
diabetes.

Chronic pancreatitis is a risk factor for pancreatic cancer.
IV. Cancer of the Digestive System
A. Esophageal cancer

Esophageal carcinoma is rare.

Risk factors - age older than 70; alcohol and tobacco use; reflux esophagitis, and nutritional
deficiencies.

Clinical manifestations - dysphagia and chest pain are the primary manifestations.

Early treatment of tumors that have not spread into the mediastinum or lymph nodes results in a
good prognosis.
B. Stomach cancer

Risk factors - H. pylori infection, high salt intake, food preservatives (nitrates, nitrites), alcohol
and tobacco use, and atrophic gastritis.

Approximately 50% of all gastric cancers are located in the prepyloric antrum.

Clinical manifestations - weight loss, upper abdominal pain, vomiting, hematemesis, anemia;
these develop only after the tumor has penetrated the wall of the stomach.
C. Colon and rectal cancer

Cancer of the colon and rectum (colorectal cancer) is the third most common cause of cancer
death in the United States.

Risk factors - advanced age; colon polyps and hereditary polyposis, smoking, high-fat low-fiber
diet, alcohol consumption, obesity, and ulcerative colitis.

Clinical manifestations - gradual onset of changes in bowel movements, melena or hematochezia,
weight loss, abdominal pain, and bowel obstruction.

Rectal tumors can spread transmurally to the vagina in women or prostate in men.
D. Liver cancer

Metastatic invasion of the liver is more common than primary cancer of the liver (hepatocellular
carcinoma).

Risk factors- ingestion of mycotoxins found in moldy grain, cirrhosis, hepatitis B and C virus,
and alcohol abuse.

Clinical manifestations - abdominal discomfort, nausea, and fullness in the right upper quadrant;
jaundice may occur early or late depending on the type of neoplastic changes.
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E. Pancreatic cancer

Pancreatic cancer is the most deadly form of cancer, with a mortality rate of almost 100%.

Risk factors - smoking, diabetes, and chronic pancreatitis.

Cancer usually arises from the exocrine cells and rapidly invades surrounding tissue and
abdominal structures.

If the tumor occurs in the head of the pancreas, individuals may present with bile duct obstruction
("painless jaundice").

Metastasis to other organs occurs early in the course of the disease.

Clinical manifestations - generally few symptoms until late in the course of the illness, though
abdominal or back pain may be present; symptoms more often result from metastases to the brain,
lungs, or lymph nodes.
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Answer Key to Activities
ACTIVITY 1: Match each sign, symptom or characteristic to the associated type of jaundice.
a. Intrahepatic obstructive
b. Extrahepatic obstructive
c. Hemolytic
C
1. High UCB.
A
4. Light stool and urine.
B
7. Pruritis
B
2. High CB.
C
5. Dark stool and urine.
C
8. Anemia
A
3. High CB and UCB.
B
6. Light stool, dark urine.
A
9. Alcoholism
B
10. Gallstones
ACTIVITY 2: Match each characteristic to the type of cirrhosis it is associated with.
a. Alcoholic cirrhosis
b. Primary biliary cirrhosis
c. Secondary biliary cirrhosis
B
1. Caused by autoimmune disorder.
A
4. Fatty liver is early stage.
A
2. Caused by toxins like acetaldehyde.
B
5. Involves destruction of liver bile ducts.
C
3. Caused by blockage of bile flow.
C
6. Reversible if obstruction is relieved.