PDFPGs 955-962

Appendicitis-Hepatic Encephalopathy

Appendicitis
Appendicitis is an inflammation of the vermiform appendix, which is a projection from
the apex of the cecum. It is the most common surgical emergency of the abdomen and
affects 7% to 12% of the population. It generally occurs between 20 and 30 years of age,
although it may develop at any age.

PATHOPHYSIOLOGY The exact mechanism of the cause of appendicitis is

controversial. Obstruction of the lumen with stool, tumors, or foreign bodies with
consequent bacterial infection is the common theory. The obstructed lumen does not
allow drainage of the appendix, and as mucosal secretion continues, intraluminal pressure
increases. The increased pressure decreases mucosal blood flow, and the appendix
becomes hypoxic. The mucosa ulcerates, promoting bacterial or other microbial invasion
with further inflammation and edema. Inflammations may involve the distal or entire
appendix. Gangrene develops from thrombosis of the luminal blood vessels, followed by
perforation.

CLINICAL MANIFESTATIONS Gastric or periumbilical pain is the typical

symptom of an inflamed appendix. The pain may be vague at first, increasing in intensity
over 3 to 4 hours. It may subside and then recur in the right lower quadrant, indication
extension of the inflammation to the surrounding tissues. Nausea, vomiting and anorexia
follow the onset of pain, and a low-grade fever is common. Diarrhea occurs in some
individuals, particularly children; others have a sensation of constipation, Perforation,
peritonitis and abscess formation are the most serious complications of appendicitis.

EVALUATION AND TREATMENT In addition to clinical manifestations, the

clinician can usually locate the painful site with one finger. Rebound tenderness is
usually referred to the right lower quadrant. The white blood cell count ranges from
10,000 to 16,000 cells/mm³ with increased neutrophils. Ultransonography and computed
tomography (CT) scans can assist in differentiating appendicitis from perforated ulcer of
cholecystitis. Laparoscopy may be necessary.
Appendectomy is the treatment for simple or perforated appendicitis. Surgery
provides quick recovery for simple appendicitis. Recovery is more complicated in cases
of perforation or abscess formation.

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with no specific
structural or biochemical alterations as a cause of disease. It is broadly characterized by
abdominal pain and discomfort associated with altered bowel habits. About 20% of the
world’s population is estimated to have the disorder, and it is more common in women
with a higher prevalence during youth and middle age. Individuals with symptoms of
IBS are also more likely to have anxiety and depression. Symptoms of IBS can
negatively affect quality of life and activity and present a significant economic burden.

PATHOPHYSIOLOGY The pathophysiology of IBS is complex, but there is

increasing evidence for organic disease, Several mechanisms are proposed to explain the
causes for the symptoms listed here.

1. Visceral hypersensitivity or hyperalgesia particularly with distention of the

rectum but also other areas of the gut. The mechanism may be related to a
dysregulation of the “brain-gut-axis” the role of serotonin in the enteric nervous
system or alterations in autonomic or central nervous system processing of
information.
2. Abnormal gastrointestinal motility and secretion. Individuals with diarrhea type
IBS have more rapid colonic transit times, whereas those with bloating and
constipation have delayed transit times. The mechanism may also be related to
visceral hypersensitivity as wells as dysregulation of the brain-gut axis or to the
role of serotonin in the function of the enteric nervous system.
3. Intestinal infection (bacterial eneritis) has been associated with symptoms of IBS,
and postinfectious IBS appears to be related to ongoing low-grade inflammation
and an abnormal immune response in gut tissues.
4. Overgrowth of intestinal flora (normal gut bacteria) may precipitate IBS
symptoms, and it is proposed that methane gas may slow intestinal transit time
resulting in constipation and bloating.
5. Food allergy or food intolerance. Food antigens may activate the mucosal
immune system mediating hypersensitivity reactions and IBS symptoms. Food
elimination approaches are helpful in some cases.
6. Psychosocial factors including emotional stress influence brain-gut interactions
including neuroendocrine, autonomic nervous system and pain modulatory
responses contributing to the symptoms of IBS.

CLINICAL MANIFESTATIONS IBS is characterized by lower abdominal pain or

discomfort, diarrhea-predominant, constipation-predominant, or alternating
diarrhea/constipation, gas bloating, and nausea. Symptoms are usually relieved with
defecation and do not interfere with sleep.

EVALUATION AND TREATMENT The diagnosis of IBS is based on signs and

symptoms and includes the exclusion of structural or biochemical causes of disease.
Diagnostic procedures to rule out other causes of symptoms may include endoscopic
evaluations, CT scans or abdominal ultrasound, blood tests, and tests for lactose
intolerance, celiac disease, or other disorders. The patient may be evaluated for food
allergies, parasites, or bacterial growth. The Rome III criteria for diagnosing IBS have
been released to guide evaluation (see Box 34-1).
There is no cure for IBS, and treatment is individualized. Treatment of symptoms
may include laxatives and fiber, antidiarrheals, antispasmodics, low-dose antidepressants,
visceral analgesics, and serotonin agonists or antagonists. For more severe constipation,
5-hydrosytryptomine 4 agonists (e.g., tegaserod) may be used, and for more severe
diarrhea, 5 hydroxytryptomine 3 antangonists (e.g., alosetron) may be used to normalize
bowel habits. Alternative therapies including probiotics, hypnosis, and psychotherapy
are treatment options. Research continues to advance the management of this complex
syndrome.

Vascular Insufficiency
Three branches of the abdominal aorta supply the stomach and intestines: the celiac axis
and the superior and inferior mesenteric arteries. Because of the rich collateral
circulation, at least two of the supplying vessels must be compromised to cause ischemia.
Atherosclerotic lesions, thrombi, and emboli can develop in these vessels, occluding
blood flow and causing ischemia or necrosis in the gastrointestinal tract.

Box 34-1 Rome III-Diagnostic Criteria for Irritable Bowel Syndrome

For a disorder to be diagnosed as irritable bowl syndrome, at least two or more of the
following conditions will have existed for at least 3 months, with onset occurring at least
6 months before the beginning of the recurrent abdominal pain or discomfort (an
uncomfortable sensation not described as pain):
1. Improvement with defecation
2. Onset associated with a change in frequency of stool
3. Onset associated with a change in form (appearance) of stool

Chronic mesenteric arterial insufficiency is rare but can develop secondary to congestive
heart failure, acute myocardial infarction, hemorrhage, stenosis, thrombus formation, or
nay condition that decreases arterial blood flow. Elderly individuals with arteriosclerosis
are particularly susceptible. Chronic occlusion is often accompanied by formation of
collateral circulation. The collateral vessels may be able to nourish the resting intestine,
but after eating, when the intestine requires more blood, the arterial supply may be
insufficient. Ischemia develops, causing a cramping abdominal pain (abdominal angina).
Progressive vascular obstruction eventually causes continuous abdominal pain and
necrosis of the intestinal tissue.
Acute mesenteric arterial insufficiency results from dissecting aortic aneurysms
(rare) or emboli. Embolic obstruction is associated with atrial fibrillation, mitral valve
disease, and heart valve prostheses. The superior mesenteric artery has a more direct line
of flow from the aorta; therefore, emboli enter it more readily that the inferior branch,
causing ischemia and necrosis of the small intestine. Ischemia and necrosis alter
membrane permeability. Increased motility followed by absence of motility result. The
damaged intestinal mucosa cannot produce enough mucus to protect itself from digestive
enzymes. Fluid moves from the blood vessels into the bowel wall and peritoneum, and
its loss causes hypovolemia and further decreases intestinal blood flow. As intestinal
infarction progresses, shock, fever, bloody diarrhea, leukocytosis, and abdominal
distention develop. Abdominal pain may be severe.
Colicky abdominal pain after eating is a cardinal symptom of chronic mesenteric
insufficiency. Some individuals suffer significant weight loss because they stop eating to
control the pain. Acute mesenteric insufficiency causes severe continuous pain, rigid
abdomen, and bloody diarrhea. Manifestations of enrelieved acute obstruction are
distended abdomen, loss of bowel sounds, shock, peritonitis, fever, and tachycardia.
Diagnosis of mesenteric artery occlusion is based on clinical manifestations,
mesenteric artery angiography, and abdominal imaging. Oftern a bruit can be heard over
the occluded artery. After angiography, a vasodilating agent may be injected into the
vessels to improve the circulation. Surgery is required to remove necrotic tissue or repair
sclerosed vessels. Mortality is high for individuals with acute occlusion, compromised
cardiac output, coexisting systemic disease, or delayed diagnosis.

Disorders of Nutrition
Obesity
Obesity is an increase in body fat mass and a metabolic disorder that has increased in rate
of incidence significantly since the 1980s. Over 60% of adults are overweight or obese in
the United States, and the rate is rapidly increasing among children and adolescents.
Obesity generally develops when caloric intake exceeds caloric expenditure. Obesity is
defined as a body mass index (body mass index [BMI]=kg/m²) that exceeds 30. Obesity
is a major risk for morbidity and death.
The causes and consequences of obesity are multiple and complex with rapidly
advancing research regarding risk factors, causal mechanisms, and complications. Obsity
is known to occur in families and genotypes, and gene-environment interactions are
important predisposing factors. Environmental factors include culture, socioeconomic
status, food intake habits, and exercise. Metabolic abnormalities associated with obesity
include Cushing Syndrome, Cushing disease, polycystic ovarian syndrome,
hypothyroidism, and hypothalamic injury.

PATHOPHYSIOLOGY Adipocytes (fat cells) secrete a number of hormones and

cytokines known as adipocytokines (Box 34-2). These adipocytokines are signaling
molecules and participate in the neuroendocrine regulation of food intake, lipid storage,
metabolism, insulin sensitivity, and female reproduction. Adipocytokines also influence
the alternative complement system, vascular homeostasis, blood pressure regulation,
angiogenesis, and the inflammatory and immune responses. Excessive increase in fat cell
mass causes dysfunction in the regulation and interaction of these hormones and
contributes to the complications and consequences of obesity.
Neuroendocrine regulation of appetite, eating behavior, energy metabolism, and
body fat mass is controlled by a dynamic circuit of signaling molecules from the
periphery acting on the hypothalamus. An imbalance in this system is usually associated
with excessive caloric intake in relation to exercise with the consequence of weight gain
and obesity.

Box 34-2 Examples of Adipocytokines and Hormones From Adipose Tissue

Adipocytokines
Leptin: Hunger/appetite suppression at hypothalamus;
promotes insulin sensitiviy
Adiponectin: Insulin sensitizing for regulation of blood glucose;
promotes anti-inflammatory vascular effects and reduces atherosclerosis.
Resistin: Promotes insulin resistance and increases blood
glucose levels.
Vistatin: mimics insulin and binds to insulin receptors

Other Hormones
Tumore necrosis factor alpha (TNFα): A
proinflammatory hormone
Angiotensinogen: regulates blood pressure
and blood volume
Plasminogen activator inhibitor-1 (PAI-1): Promotes clot
formation by inhibiting plasminogen and urokinase
Interleukins 6 and 8: Proinflammatory hormones

Many different hormones and signaling systems control appetite and body weight.
The sources include indulin from the beta cells of the pancreas; ghrelin from the stomach;
peptide YY from the intestines; and leptin, adiponectin, and resistin from adipose tissue.
These hormones circulate in the blood at concentrations proportional to body fat mass
and severe as peripheral signals to the hypothalamus where appetite and metabolism are
regulated. Obesity is associated with increased circulating plasma levels of leptin,
insulin, ghrelin, and peptide YY and decreased levels of adiponectin. Interaction of these
hormones with neuropeptides at the level of the hypothalamus may be an important
determinant of excessive fat mass.
Leptin, a product of the obesity gene (Ob gene), is a hormone that is being studied
in relation to obesity. One of the functions of leptin is to act on the hypothalamus to
suppress appetite and function to regulate body weight within a fairly narrow range.
Leptin increases as adipocytes increase; however, for unknown reason, high leptin levels
are ineffective at decreasing appetite and energy expenditure, a condition is known as
leptin resistance. Leptins resistance disrupts hypothalamic satiety signaling and
promotes overeating and excessive weight gain and may be a factor in the development
of obesity (Figure 34-10). Leptin also may be associated with the cardiovascular
complications of obesity. Decreases in adiponectin are associated with insulin resistance,
coronary artery disease, and hypertension and also may contribute to the complications of
obesity.

CLINICAL MANIFESTATIONS Obesity usually presents with two different forms

of adipose tissue distribution. Central Obesity (also known as intra-abdominal, visceral,
or masculine obesity) occurs when the distribution of body fat is localized around the
abdomen and upper body, resulting in an apple shape. Central obesity has an increased
risk for hyperlipidemia, cardiovascular disease, and insulin resistance with the
development of type 2 diabetes mellitus. This combination of traits, also known as
metabolic syndrome, is discussed in detail in Chapters 17 and 23. Peripheral obesity
(also known as gluteal-femoral or feminine obesity) occurs when the distribution of body
fat is around the thighs and buttocks, resulting in a pear shape.
Three leading causes of death in the United States are associated with obesity:
coronary artery disease, type 2 diabetes mellitus, and cancer (colon, breast in
postmenopausal women, endometrial, prostate, kidney, and esophagus). Obesity is also a
risk factor for hypertension, stroke, hepatobiliary disease (gallstones and nonalcoholic
steatohepatitis), and osteoarthritis. Pulmonary function can be compromised by a large
amount of adipose tissue overlying the chest cage, and obstructive sleep apnea syndrome
can occur as a consequence (see Chapter 13).

Figure 34-10

Increased appetite Decreased appetite and food intake Leptin resistance and other
Decreased temperature Increased metabolism hormone action:
Decreased metabolism Increased sympathetic activity (G) Increased appetite and food
Decreased reproductive function intake
Increased parasympathetic activity Decreased metabolism
(Y) Sustained sympathetic
activity (O)
Hypothalamus

Leptin level increased excessively

Leptin level decreases (Y) Leptin level normal (G) (O)

Loss of fat cell mass (Y) Normal fat cell mass (G) Increased in fat cell mass (O)

Starvation or weight loss (Y) Normal body weight (G) Obesity (O)

Fig 34-10 Leptin Theory of Obesity. The hypothalamus controls appetite, fat cell mass, and energy expenditure by responding to
circulating levels of leptin and other hormones. Regulation of normal body weight is presented in the green boxes (G). Changes
occurring with obesity are presented in the orange boxes (O), and changes occurring with starvation or weight loss are presented in
the yellow boxes (Y)
EVALUATION AND TREATMENT There are several methods for measuring or
estimating body fat mass, including computed tomography (CT) and magnetic resonance
imaging (MRI) techniques; bioimpedance analysis; underwater weighing; and
anthropometric measurements, such as skinfold thickness, circumferences, and various
body diameters (i.e., waist-to-hip ratios and waist circumference, and body mass index
[BMI-kg/m²] tables). The BMI and waist-to-hip ratios are most commonly used because
they are the easiest to measure. Overweight is defined as a BMI greater that 25 and
obesity is a BMI greater than 30. BMI charts are available for children ages 2 to 20
years; these can be used for comparison during adulthood because obese children
generally become obese adults. No specific diagnostic criteria for obesity have been
established.
Obesity is a chronic disease for which various approaches to treatment have been
used; these include correction of metabolic abnormalities, individually tailored weight
reduction diets, and exercise programs. A combination of weight reduction and exercise
are the most effective treatments. Self-motivation and support systems are critical
aspects of treatment. Additional treatments, such as psychotherapy, behavioral
modification, medications, and bariatric surgery (i.e., the Roux-en-Y gastric bypass or
gastric banding) are also prescribed and when successful significantly reduce
comorbidities and decrease insulin resistance. Unraveling the causes of obesity will lead
to more specific prevention and pharmacotherapeutic strategies.

Anorexia nervosa and bulimia nervosa

Many young adults and adolescents- 5 to 10 million young and adult women and 1
million males- are affected by two complex and related eating disorders: anorexia
nervosa and bulimia nervosa. Both conditions have a familial tendency and may by
associated with other disorders such as anxiety, depression, and obsessive compulsive
disorder.
Anorexia nervosa is a psychologic and physiologic syndrome characterized by
the following:
1. Fear of becoming obese despite progressive weight loss
2. Distorted body image: the perception that the body is fat when it is actually
underweight
3. Body weight 15% less than normal for age and height because of refusal to eat
4. In women and girls, absence of three consecutive menstrual periods
Persons with anorexia nervosa often deny they have an eating problem. As the
disease progresses, muscle and fat depletion give the individual a skeleton-like
appearance. Postural hypotension, edema, bradycardia, hypothermia, constipation, and
sleep disturbances may ensue. The loss of 25% to 30% of ideal body weight can
eventually lead to death caused by starvation-induced cardiac failure. Diagnosis of
anorexia nervosa involves a thorough medical history, a physical and psychologic
examination, and ruling out other causes of anorexia and malnutrition.
Treatment objectives for anorexia nervosa include reversing the compromised
physical state, promoting insights and knowledge about the disorder, setting mutual
goals, promoting interaction with family members, restoring developmental growth,
modifying food habits, and restoring weight. Correction of nutritional status can require
hospitalization. When the individual demonstrates the willingness to eat food for
nourishment, dietary protein, carbohydrate, and fat are introduced in tolerable amounts.
Psychotherapy begins as soon as the physical symptoms are stabilized and may continue
for several years.

HEALTH ALERT
Refeeding Syndrome
Refeeding syndrome occurs in severely malnourished individuals when parenteral or
enteral nutritional therapy is initiated. During starvation, loss of body minerals
causes the movement of phosphates, magnesium and potassium out of the cells and
into the plasma. When refeeding starts, an increase in insulin levels stimulates the
intracellular movement of glucose and these ions and the plasma concentrations can
decrease to dangerously low levels causing hypophosphatemia, hypomagnesaemia,
and hyposkalemia. Rapid expansion of the extracellular fluid volume can also occur
with carbohydrate refeeding and may cause fluid overload. Hypophosphatemia
contributes to alterations in red blood cell shape and function contributing to tissue
hypoxia and increased respiratory drive. The consequence of these alterations
includes life-threatning dysrhythmias, congestive heart failure, muscle weakness
(including respiratory muscles), and death. Individuals at greatest risk are those with
starvation from any cause including anorexia nervosa, chronic alcoholism, morbid
obesity with massive weight loss, and prolonged fasting. Refeeding syndrome is
prevented by slowly reinstituting feeding (about 20kcal/kg/day for the first few days)
and monitoring plasma phosphate, potassium, magnesium, and calcium.

Bulimia nervosa is characterized by bingeing- the consumption of normal to large

amounts of food, often several thousand calories at a time-followed by self-induced
vomiting or purging of the intestines with laxatives. The group at risk is the same as that
for anorexia nervosa, except that bulimia nervosa tends to occur in slightly older, less
affluent women. Approximately 50% of individuals with anorexia nervosa are bulimic as
well. Many young women stimulate vomiting inappropriately to control weight but are
not classified as bulimic unless the pattern is obsessional of normal health or activity is
interrupted. Diagnosis of bulimia nervosa is based on the following findings:
1. Recurrent episodes of binge eating during which the individual fears not being
able to stop
2. Self-induced vomiting, use of laxatives, or fasting to oppose the effect of binge
eating
3. Two binge-eating episodes per week for at least 3 months
Although individuals with bulimia nervosa are afraid of gaining weight, their
weight usually remains within normal range. Because of negative connotations
associated with self-stimulated vomiting and purging, individuals who have bulimia
nervosa binge and purge secretly. They may binge and purge as often as 20 times each
day. Continual vomiting of acidic chime can cause pitted teeth, pharyngeal and
esophagated inflammation, and tracheoesophageal fistulae. Overuse of laxatives can
cause rectal bleeding. Secret bingeing isolates the bulimic individual and leads to
depression and anger that is turned inward. A vicious cycle of depression, overeating to
try to feel better, vomiting and purging to maintain a normal weight, and returning
depression perpetuates this eating disorder.
 Because persons with bulimia are usually older that individuals with anorexia
nervosa and have usually separated from a family core, individual or group counseling is
the treatment focus. Individuals with bulimia nervosa rarely have physical problems
requiring hospital care.

Malnutrition and starvation

Malnutrition is lack of nourishment from inadequate amounts of calories, protein,
vitamins, or minerals and is caused by improper diet, alterations in digestion or
absorption, or a combination of these factors. Starvation is a state of extreme
malnutrition and hunger from lack of nutrients. Short-term starvation (1 to 14 days of
fasting) and long term starvation (14 to 60 days of fasting) have different effects.
Therapeutic short-term starvation is part of many weight-reduction programs because it
causes an initial rapid weight loss that reinforces the individual’s motivation to diet.
Therapeutic long-term starvation is used in medically controlled environments to
facilitate rapid weight loss in morbidly obese individuals. Pathologic long-term
starvation can be caused by poverty (particularly among those living in third world
countries); chronic diseases of the cardiovascular, pulmonary, hepatic, renal and digestive
systems; malabsorption syndromes; and cancer. Cachexia is physical wasting with loss
of weight and muscle atrophy, fatigue, and weakness. Inflammatory mediators (i.e.,
TNFα, interferon gamma, or interleukin 6) associated with advanced cancer (see chapter
10), AIDS, tuberculosis, and other major chronic progressive diseases contribute to
cachexia. Anorexia and cachexia often occur together. Cachexia is not the same as
starvation. A healthy person’s body can adjust to starvation by slowing metabolism, but
in cachexia the body does not make this adjustment.
Short-term starvation, or extended fasting, consists of several days of total dietary
abstinence or deprivation. Once all available energy has been absorbed from the
intestine, glycogen in the liver is converted to glucose through glycogenolysis, the
splitting of glycogen into glucose. This process peaks within a 4 to 8 hours, and
gluconeogenesis begins. Gluconeogenesis is the formation of glucose from
noncarbohydrate molecules: lactate, pyruvate, amino acids, and the glycerol portion of
fats. Like glycogenolysis, gluconeogenesis takes place within the liver. Both of these
processes deplete stored nutrients and thus cannot meet the body’s energy needs
indefinitely. Proteins continue to be catabolized to a minimal degree, providing carbon
for the synthesis of glucose. The kidney converts glutamine to glucose, significantly
contributing to glucose production. Fatigue decreases physical activity and energy
expenditure.
Long-term starvation begins after several days of dietary abstinence and
eventually causes death. The major characteristic of long-term starvation is a decreased
dependence on gluconeogenesis and an increased use of ketone bodies (products of lipid
and pyruvate metabolism) as a cellular energy source. Depressed insulin and glucagon
levels promote lipolysis in adipose tissue. Lipolysis liberates fatty aids, which supply
energy to cardiac and skeletal muscle cells, as well as ketone bodies, which sustain brain
tissue. Fatty acid or ketone body oxidation meets most energy needs of the cells. (Some
glucose is still needed as fuel for brain tissue.) Once the supply of adipose tissue is
depleted, proteolysis begins. The breakdown of muscle protein is the last process to
supply energy for life. Death results from severe alterations in electrolyte balance and
loss of renal, pulmonary, and cardiac function.
Adequate ingestion of appropriate nutrients is the obviousl treatment for
starvation. In medically induced starvation, the body is maintained in a ketotic state until
the desired amount of adipose tissue has been lysed. Starvation imposed by chronic
disease, long-term illness, or malabsorption is treated with enteral or parenteral nutrition.

DISORDERS OF THE ACCESSORY

ORGANS OF DIGESTION
The accessory organs of digestion (liver, gallbladder, pancreas) secrete substance
necessary for digestion and, in the case of the liver, carry out metabolic functions needed
to maintain life. Causes are inflammatory disease, obstruction of ducts, and tumors.
(Cancers of the digestive tract are described at the end of this chapter.)

Clinical Manifestations of Liver

Disorders
Of all the accessory organ disorders, acute or chronic liver disease leads to significant
systemic, life-threatning complications. These complications include portal
hypertension, ascites, hepatic encephalopathy, jaundice, and hepatorenal syndrome.

Portal hypertension
Portal hypertension is abnormally high blood pressure in the portal venous system.
Pressure in this system is normally 3 mm Hg; portal hypertension is an increase to at least
10 mm Hg.

PATHOPHYSIOLOGY Portal hypertension is caused by disorders that obstruct or

impede blood flow through any component of the portal venous system of vena cava.
Intrahepatic causes result from thrombosis, inflammation, or fibrosis of the sinusoids, as
occurs in cirrhosis of the liver, viral hepatitis, or schistosomiasis (a parasitic infection).
Posthepatic causes occur from hepatic vein thrombosis or cardiac disorders that impair
the pumping ability of the right heart. This causes blood to back up and increases
pressure in the portal system. The most common cause of portal hypertension is
obstruction caused by cirrhosis of the liver (see p. 697).
 Long-term portal hypertension causes several problems that are difficult to treat
and can be fatal:
1. Varices (distended, tortuous, collateral veins), Prolonged elevation of pressure in
collateral veins causes their transformation into varices, particularly in the lower
esophagus and stomach, but also in the rectum (figure 34-11). Rupture of varices
can cause life-threatning hemorrhage.
2. Splenomegaly (enlargement of the spleen) caused by increased pressure in the
splenic vein, which branches from the portal vein.
3. Ascites (the accumulation of fluid in the peritoneal cavity) caused by increased
pressure in the mesenteric tributaries of the portal vein. Hydrostatic pressure
forces water out of these vessels and into the peritoneal cavity.
4. Hepatic encephalopathy, also called portal-systemic encephalopathy, which is
characterized by central nervous system disturbances, particularly reversible
alterations of consciousness. Blood that is shunted through collateral vessels to
the systemic veins bypasses the liver, where toxins, hormones, and other harmful
substances normally are removed. Hepatic encephalopathy results from the
presence of these substances, particularly ammonia, in blood that reaches the
brain.

CLINICAL MANIFESTATIONS Vomiting of blood from bleeding esophageal

varices is the most common clinical manifestation of portal hypertension. Slow, chronic
bleeding from varices causes anemia and the presence of digested blood in the stools.
Usually the bleeding is from varices that have developed slowly over a period of years.
Rupture of esophageal varices causes hemorrhage and voluminous vomiting of
dark-colored blood. The ruptured varices are usually painless. Rupture is caused by a
combination of erosion by gastric and elevated venous pressure. Mortality from fuptured
esophageal varices ranges from 30% to 60%. Recurrent bleeding of esophageal varices
indicates a poor prognosis. Most individuals die within 1 year.

EVALUATION AND TREATMENT Portal hypertension is often diagnosed at the

time of variceal bleeding and confirmed by endoscopy and evaluation of portal venous
pressure. Distended collateral veins may radiate over the abdomen, giving rise to the
description of caput medusae (Medusa Head). The individual usually has a history of
jaundice, hepatitis, of alcoholism.
Emergency management of bleeding varices includes use of vasopressors and
compression of the varices with and inflatable Sengstaken-Blakemore tube,
sclerotherapy, or variceal ligation. Surgical shuts may decompress the varices, but this
treatment can precipitate encephalopathy or liver failure. Liver transplant is an
alternative with endstage liver disease.

Ascites
Ascites is the accumulation of fluid in the peritoneal cavity. Ascites traps body fluid in a
“third space” from which it cannot escape. The effect is to reduce the amount of fluid
available for normal physiologic functions. Cirrhosis is the most common cause ascites,
but others include heart failure, constrictive pericarditis, abdominal malignancies,
nephritic syndrome, and malnutrition. Of individuals who develop ascites caused by
cirrhosis, 25% die within 1 year. Continued heavy drinking of alcohol is associated with
this mortality.
PATHOPHYSIOLOGY Several factors contribute to the development of ascites.
Impaired excretion of sodium by the kidneys promotes water retention. Portal
hypertension and reduced serum albumin levels cause capillary hydrostatic pressure to
exceed capillary osmotic pressure. This imbalance pushes water into the peritoneal
cavity. Portal hypertension also increases the production of hepatic lymph, which
“weeps” into the peritoneal cavity. Peripheral vasodilation associated with increased
nitric oxide “underfills” the vascular system with hormonal stimulation that promotes
renal sodium and water retention.
With cirrhosis, both portal hypertension and decreased production of albumin by
hepatocytes contribute to the ascites. Besides reducing albumin synthesis, deranged liver
metabolism permits the accumulation of hormones that regulate sodium and water
balance. As ascites sequesters more and more body fluid, the kidneys respond by
retaining sodium and water in amounts exceeding intake, particularly in response to
increased aldosterone and antidiuretic hormone. This expands plasma volume, thereby
accelerationg portal hypertension and ascites formation.
Ascites can be complicated by bacterial peritonitis, an inflammatory response that
increases mesenteric capillary permeability. As plasma seeps out of the permeable
mesenteric capillaries, it adds to the volume of ascitic fluid. Figure 34-12 summarizes
the mechanisms by which cirrhosis of the liver causes ascites.

CLINICAL MANIFESTATIONS The accumulation of ascitic fluid causes weight

gain, abdominal distention, and increased abdominal girth (Figure 34-13). Large
volumes of fluid (10 to 20L) displace the diaphragm and cause dyspnea by decreasing
lung capacity. Respiratory rate increases, and the individual assumes a semi-Fowler
position to relieve the dyspnea. Approximately 10% of individuals with ascites develop
bacterial peritonitis, which causes fever, chills, abdominal pain, decreased bowel sounds,
and cloudy ascitic fluid.

EVALUATION AND TREATMENT Diagnosis is usually based on clinical

manifestations and identification of liver disease. Paracentisis is used to aspirate ascitic
fluid for bacterial culture, biochemical analysis, and microscopic examination. The goal
of treatment is to relieve discomfort. If the restoration of liver function is possible, the
ascites diminishes spontaneously. In the meantime, dietary salt restriction and
potassium-sparing diuretics can reduce ascites. Serum electrolytes are monitored
carefully because the individual is at risk for hyponatremia and hypoklaemia.
Palliative measures include paracentesis to remove 1 or 2 L of ascitic fluid and
relieve respiratory distress. However, the removal of too much fluid relieves pressure on
blood vessels and carries the risk of hypotension, shock, or death. Despite repeated
paracentesis, ascitic fluid reaccumulates in individuals with irreversible disease.
Paracentesis is also likely to cause peritonitis. Other procefures include pertoneovenous
shunt, transjugular intrahepatic protosystemic shunt, and liver transplant. Individuals
with ascites and portal hypertension have a poor prognosis.
Hepatic encephalopathy
Hepatic encephalopathy (portal-systemic encephalopathy) is a complex neurologic
syndrome characterized by impaired cerebral function, flapping tremor (asterixis), and
electroencephalogram (EEG) changes. The syndrome may develop rapidly during acute
fulminant hepatitis or slowly during the course of chronic liver disease and the
development of portal hypertension.

Figure 34-12

Cirrhosis

Incr. Lymph Portal Hepatocyte

Production Hypertension failure

Incr. Capillary Decr. Albumin Altered

Filtration synthesis metabolism
pressure

Decr. Capillary
oncotic pressure
Peripheral arterial
vasodilation
Incr. Renin
Decr. Effective aldosterone, and
plasma volume ADH
Bacterial
peritonitis

Ascites Incr. Renal

absorption of Na
Incr. Capillary Loss of and water
permeability Plasma

Figure 34-12 Mechanism of Ascites Caused by Cirrhoids

PATHOPHYSIOLOGY Hepatic encephalopathy probably results from a

combination of biochemical alterations that affect neurotransmission. Liver dysfunction
and collateral vessels that shunt blood around the liver to the systemic circulation both
permit toxins absorbed from the gastrointestinal tract to circulate freely to the brain. The
most hazardous substances are end products of intestinal protein digestion, particularly
ammonia. Ammonia that reaches the brain may alter cerebral energy metabolism or
interfere with neurotransmitters.
 Blood levels of ammonia do no account for all symptoms associated with hepatic
encephalopathy. The accumulation of short-chain fatty acids, serotonin, tryptophan, and
false neurotransmitters probably contributes to neural derangement. Infection,
hemorrhage, electrolyte imbalance including zinc deficiency, sedatives, and analgesics
also can precipitate stupor and coma in the presence of liver disease.

CLINICAL MANIFESTATIONS Subtle changes in personality, memory loss,

irritability, lethargy, and sleep disturbances are common initial manifestations of hepatic
encephalopathy. Symptoms then can progress to confusion, flapping tremor of the hands,
stupor, convulsions, and coma. Coma is usually a sign of liver failure and ultimately
results in death.

EVALUATION AND TREATMENT Diagnosis of hepatic encephalopathy is

based on a history of liver disease and clinical manifestations. Electroencephalography
and blood chemistry tests provide supportive data.
Corrective of fluid and electrolyte imbalances and withdrawal of depressant drugs
metabolized by the liver are first steps in the treatment of hepatic encephalopathy.
Restricting dietary protein intake and eliminating intestinal bacteria reduce blood
ammonia levels. Neomycin is effective in sterilizing the bowel, but it can be
nephrotoxic. Lactulose may be administered to present ammonia absorption in the colon.

(Huether, McCane 2008)