Usmle 01 1415 Manual DG

Gastroenterology
American Manual
of Examination
in Medicine
(2CK)
DISCLAIMER
Medicine is a science subject to constant change. As research and clinical experience widen our
knowledge, treatments and pharmacotherapy changes are necessary. The editors of this work have
veried their results against reliable sources, in an eort to provide general and complete information,
according to the accepted criteria at the time of publication. Nevertheless, given the fact that human
error may occur or that some changes may take place in medical sciences, neither the editor nor any
of the contributors involved in the preparation or publication- of this work can guarantee that the
content herein is accurate and complete in each and every aspect. The editors and the contributing
sources cannot be held responsible for any errors, omissions or the outcome derived from the use
of the information provided herein. Therefore, readers are recommended to verify the content of this
work against other sources. As an example, it is especially advisable to read the package insert of any
drug to be administered to ensure that the information furnished by this publication is accurate and no
modications were made either to the recommended dose or to the contraindications for administering
said drug. This recommendation is particularly signicant in relation to new or seldom used drugs.
Readers should also check with their own laboratory about normal values.
No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any
means, electronic, mechanical, photocopying, recording, or otherwise without prior permission of the
holders of the copyright.
CTO EDITORIAL, S.L. 2015
Design and layout: CTO Editorial
C/ Francisco Silvela, 106; 28002 Madrid
Phone no.: (0034) 91 782 43 30 - Fax: (0034) 91 782 43 43
E-mail address: ctoeditorial@ctomedicina.com
Website: www.grupocto.es
ISBN full edition: 978-84-16276-21-9
Author
Beatriz Merino Rodrguez
Gastroenterology
American Manual
of Examination
in Medicine
(2CK)
A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)
Index
01. Esophageal Pathology..................................................................... 1
1.1.
1.2.
1.3.
1.4.
1.5.
1.6.
Dysphagia ........................................................................................................................................ 1
Gastroesophageal Reflux Disease ................................................................ 3
Infectious Esophagitis .................................................................................................... 5
Esophageal Diverticula................................................................................................. 5
Hiatal Hernia ................................................................................................................................. 6
Squamous Cell Carcinoma of the Esophagus ............................. 6
02. Gastric Pathology ................................................................................... 7

2.1.
2.2.
2.3.
2.4.
2.5.
Gastritis ............................................................................................................................................... 7
Peptic Ulcer .................................................................................................................................... 8
NSAID-Associated Ulcers ....................................................................................... 11
Zollinger-Ellison Syndrome................................................................................ 12
Gastric Tumors ....................................................................................................................... 12
03. Pathology of the Small

and Large Intestine........................................................................... 13
3.1.
3.2.
3.3.
3.4.
3.5.
3.6.
3.7.
3.8.
3.9.
3.10.
3.11.
3.12.
3.13.
3.14.
3.15.
3.16.
Diarrhea ........................................................................................................................................... 13
Acute Infectious Diarrhea ..................................................................................... 14
Malabsorption ....................................................................................................................... 19
Disaccharidase Deficiency ................................................................................... 20
Carcinoid Syndrome ..................................................................................................... 20
Irritable Bowel Syndrome ..................................................................................... 21
Inflammatory Disease................................................................................................. 21
Diverticular Disease ....................................................................................................... 25
Ileus........................................................................................................................................................ 26
Intestinal Obstruction ................................................................................................ 27
Acute Mesenteric Ischemia ................................................................................ 28
Chronic Mesenteric Ischemia or Intestinal Angina.......... 29
Ischemic Colitis ..................................................................................................................... 29
Gastrointestinal Bleeding...................................................................................... 30
Malignant Tumors of the Large Intestine ...................................... 30
Inguinal Hernias .................................................................................................................. 32
04. Liver Pathology ...................................................................................... 34

4.1.
4.2.
4.3.
4.4.
4.5.
4.6.
4.7.
Study of Patients with Hepatobiliary Disease ......................... 34

Hyperbilirubinemia ........................................................................................................ 35
Viral Hepatitis .......................................................................................................................... 35
Cirrhosis........................................................................................................................................... 37
Hepatocarcinoma ............................................................................................................. 39
Chronic Cholestasis ........................................................................................................ 43
Metabolic Liver Diseases ...................................................................................... 44
05. Biliary Pathology: Diseases

of the Gallbladder and Bile Ducts ............................... 46
5.1.
5.2.
5.3.
5.4.
Gallstones ..................................................................................................................................... 46
Acute Cholecystitis ......................................................................................................... 47
Gallstone Ileus........................................................................................................................ 47
Cholangitis .................................................................................................................................. 48
06. Pancreatic Pathology ..................................................................... 49

6.1. Acute pancreatitis ............................................................................................................ 49
6.2. Chronic Pancreatitis ........................................................................................................... 50
G astro e nte ro l ogy
Esophageal
Chapter 01
Pathology
1.1. Dysphagia
intrinsic esophagus narrowing or an extrinsic compression. The causes are many, but within this group of cancer, benign stenosis and
lower esophageal ring, should always be kept in mind.
2. Motor dysphagia. It can occur when there is a decrease or alteration in the normal peristalsis of the esophagus or when there is an
alteration in relaxation of upper and lower esophageal sphincters.
There are multiple causes, including primary or secondary achalasia
or diuse esophageal spasm.
Diagnosis
Concept
Dysphagia is diculty swallowing. Dysphagia does not have to be painful,
and if it is, it is called odynophagia. Aphagia means complete esophageal
obstruction, and its most common cause of it is food bolus impaction.
If obstructive lesion is suspected the diagnosis is made with oral endoscopy. If there is a motor disorder esophageal manometry is the method
of choice (Figure 1).
Dysphagia
Pathophysiology of Dysphagia
We can divide dysphagia into oropharyngeal dysphagia and esophageal
dysphagia; also, the latter may be divided into mechanical or motor dysphagia.
Difficulty initiating
swallowing
Oropharyngeal dysphagia
Esophageal dysphagia
Oropharyngeal Dysphagia
It is the inability to initiate swallowing.
Etiology
Bronchopulmonary aspiration is the most frequent cause of death in
these patients. Strokes are the most common cause of oropharyngeal
dysphagia, but there are many other causes: neuromuscular disorders,
peripheral nervous system diseases, diseases of the neuromuscular
junction diseases, striated muscle diseases involving hypopharynx or
upper esophagus muscles, inflammatory local structural lesions (tuberculosis, abscesses, etc.) neoplastic, congenital or acquired membranes,
or injuries causing extrinsic compression in that area (goiter, osteophytes, lymphadenopathy) and upper esophageal sphincter intrinsic
motility disorders (hypertensive upper esophageal sphincter, cricopharyngeal achalasia).
Diagnosis
Diagnosis of oropharyngeal dysphagia is performed by conventional
barium contrast radiology, endoscopy, and chest and spinal cord x-rays
to rule out organic lesions. A video-fluoroscopy study and manometry
can detect various motor function abnormalities at the level of the
pharynx, upper esophageal sphincter or cervical esophagus.
Treatment
Difficulty after
swallowing
Solids only
Solids or fluids
Mechanical obstruction
Neuromuscular
Disease
Intermittent
Progressive
Chronic Pyrosis Age > 50

No weight weight
Peptic
Lower
esophageal Stenosis
ring
Carcinoma
Intermittent
Thoracic
pain
Diffuse
esophageal
spasm
Progressive
Chronic
pyrosis
Regurgitation
weight
Sclerodermia
Achalasia
Figure 1. Dierential diagnosis of dysphagia
Achalasia
The term achalasia means failure to relax. Thus, the lower esophageal
sphincter produces a functional obstruction of the esophagus, as it does
not relax properly when swallowing. The transition from the esophagus
to the stomach is also altered by a defect in the esophageal body resulting in abnormal contractions.
Treatment, in general, for the disease aecting this symptom.
Physiopathology
Esophageal Dysphagia
This is diculty swallowing once the bolus has traversed the pharynx
and upper esophageal sphincter. Esophageal dysphagia may, in turn, be
divided into mechanical and motor dysphagia.
1. Mechanical dysphagia. It occurs when there is diculty passing the
bolus. In general, it can result from an excessively large bolus, an
In the primary achalasia, there is an alteration in the esophageal

smooth muscle innervation. The most striking symptom is a significant
reduction in cell bodies of the myenteric plexus, especially inhibitory
neurons, but further alterations have been shown in branches of the
vagus, and even abnormalities in the dorsal motor nucleus of the vagus
in the brainstem. In vigorous achalasia, changes are milder.
Symptoms
Achalasia occurs at all ages and in both genders. The main symptoms
are dysphagia, chest pain and regurgitation. Dysphagia occurs early on
for solids and liquids, although dysphagia for solids is the most common
symptom of achalasia. Dysphagia worsens with stress and fast meals.
The course is usually progressive with weight loss over months or years.
The presence of GERD is against the diagnosis of achalasia.
Diagnosis
Chest x-rays can reveal the absence of gastric bubble and a widened
mediastinum with air-fluid level can be seen when the subject is standing. Radiology barium studies show a dilated esophagus, which in later
stages can have a sigmoid appearance and a sharp finish called birds
beak.
Manometry confirms the diagnosis by showing incomplete relaxation
of lower esophageal sphincter following swallowing, which is the most
important finding of achalasia; the basal pressure of the lower esophageal sphincter may be normal or increased; the basal pressure in the
esophageal body is usually increased and, during swallowing, simultaneous contractions of low amplitude take place (Figure 2).
prior myotomy, children, the existence of an epiphrenic diverticulum

or the existence of a large hiatal hernia.
Medical treatment. Nitrites and calcium antagonists have been the
main components used; of these, nifedipine is the most successful. Isosorbide dinitrate is more eective than nifedipine, but it has more side
eects. They should be taken immediately before meals. It is thought,
in general, that they are of little use and should be prescribed to patients who are not candidates for another treatment or while they are
preparing for another treatment. Currently, they are only indicated
temporarily and in extreme stages of life (children and elderly).
Botulinum toxin. Endoscopic injection of botulinum toxin in the
lower esophageal sphincter is a novel treatment that improves
symptoms, but its indications are not yet well established. Elderly
and patients with vigorous achalasia respond better. They require
repeated injections after symptoms reappear.
Surgical treatment. Currently this option has gained wide acceptance. Achalasia surgery is aimed at four groups of patients:
Young patients (where expansions are eective in less than 50%).
Patients with recurrent symptoms even after expansion.
High risk patients for expansion (short distal esophagus, diverticula, or previous surgery of the gastroesophageal junction).
Patients who choose surgery for best long-term results. Indeed,
the risk associated with laparoscopic myotomy is lower than the
risk associated with repeated dilatations.
Surgical Options
Modified heller myotomy (only anterior myotomy) plus antireflux
technique, via thorax or abdomen. Nowadays, the laparoscopic
technique is replacing open surgery. The most common early complication of Heller is pneumonia, and then GERD.
Esophageal resection and replacement with tubularized stomach enable definitive treatment of esophageal abnormality. It is used when
achalasia operations fail or in those patients with megaesophagus (sigmoid esophagus) that may not empty properly, even after esophagomyotomy.
Achalasia
Low surgical risk
High surgical risk
According to patients preference
Pneumatic
Dilation
Myotomy
Failure
Failure
Failure
dilation
Pneumatic
dilation
Failure
Failure
Myotomy
Esophageal resection
Pharmacologic treatment
or botulinium toxin
Figure 2. Achalasia: esophageal dilation
Treatment
Balloon dilation. Eective treatment in 85% of patients. Its long-term
results are lower than surgery, it is cheaper and has a similar incidence
of complications and mortality. In its favor, it should be noted that
surgery can be performed if expansion fails, although the existence
of previous expansions complicates surgery. Its major complications
are perforation and hemorrhage. Related contraindications are the
presence of a tortuous sigmoid shape of the esophagus, performing a
Failure
Gastrotomy
Figure 3. Therapeutic algorithm of achalasia
Diffuse Esophageal Spasm

and Related Disorders
It pharmacologic treatment fails, balloon dilation of the lower esophagus may be atempted, which is especially useful in patients who complain of dysphagia.
Diuse esophageal spasm is a disorder characterized by multiple spontaneous contractions induced by swallowing, which are repetitive and of
simultaneous start; they have wide amplitude and long duration.
If all of the above fails, it may be useful a longitudinal myotomy of the

circular muscular layer of the esophagus may be useful, together with
an antireflux technique if LES pressure is low.
There are some variants that show only some of the changes, these being
more frequent. Diuse esophageal spasm may be an isolated condition
or associated with other diseases such as collagen disease, diabetic neuropathy, reflux esophagitis, radiation esophagitis, esophageal obstruction.
1.2. Gastroesophageal Re lux Disease
Pathologic anatomy
Gastroesophageal reflux disease (GERD) is defined as any clinical symptoms or histopathologic alterations resulting from GER episodes.
It is shown that there is a localized patchy degeneration in the nerve,

rather than in the cell bodies (contrary to what occurred in achalasia).
Symptoms
The average onset is about 40 years. The most common symptoms are
chest pain, dysphagia, or both. Dysphagia occurs both for solids and liquids, it is intermittent and varies in intensity throughout the day; it is generally not progressive and it is not severe enough to cause weight loss.
Pain is usually retrosternal and may radiate the same as ischemic heart
disease; it appears both at rest and triggered by swallowing or stress.
Diagnosis
An esophagogram barium fluoroscopy can reveal the typical corkscrew
esophagus caused by abnormal contractions; lower esophageal sphincter opens normally.
An esophangeal manometry also shows typical repetitive, simultaneous contractions with large amplitude, starting at the bottom of the
esophagus. It should be noted that the conditions may be episodic and
therefore, manometric findings may be normal at the time of study.
Treatment
Treatment is aimed primarily at reducing symptoms. Several drugs are
used to relax the smooth muscle fiber before meals; sublingual nitroglycerin, isosorbide dinitrate, and calcium antagonists such as nifedipine and diltiazem have been used (Table 1).
ACHALASIA
DIFFUSE
ESOPHAGEAL SPASM
LES
Incomplete LES relaxation

after swallowing
Relaxation during
swallowing
Basal LES
pressure
Normal or increased
Increased
Esophageal
body during
swallowing
Low-amplitude simultaneous
contractions, in case
of classic achalasia,
and of great amplitude
and duration, in case
of vigorous achalasia
Large-amplitude
repetitive contractions
that start at the lower
part of the esophagus
Table 1. Dierential diagnosis of esophagus motor disorders
Pathophysiology
GERD occurs when the balance between aggressive factors (acid
reflux, power flow) and defensive factors of the esophageal mucosa (esophageal acid clearance, mucosal resistance) is upset. In the
pathophysiology of this disease three aspects should be considered:
pathogenesis of GERD episode, the amount of reflux and esophagitis
pathogenesis.
Symptoms
Reflux is usually asymptomatic in the absence of esophagitis. Heartburn
is the most common symptom, acid regurgitation, chest pain or dysphagia may also occur. Dysphagia can be caused by a peptic stenosis, a
Schatzki ring or a peristaltic dysfunction induced by Gastroesophageal
reflux (GER). Sore throat is a rare symptom in GERD, and if it is prominent, you should suspect the presence of an esophageal ulcer or deep
erosion. Reflux esophagitis is the most common cause of chest pain of
esophageal origin.
In the case of mucosa ulceration or Barrett s ulcer, bleeding may occur. If there is progressive dysphagia and weight loss, adenocarcinoma
should be ruled out. There may be extraesophageal manifestations such
as pharyngitis, posterior laryngitis and, as a result of microaspirations,
bronchospasm, aspiration pneumonia, pulmonary fibrosis or chronic
asthma, which can be caused by microaspirations or by a vagal reflex
from the esophagus to the lung.
Diagnosis
When the symptoms are typical of reflux with heartburn, with or without acid regurgitation, the probability that there is GERD is very high,
and therefore an empirical treatment is directly justified. In cases with
onset of symptoms suggestive of a complication (dysphagia, odynophagia, chest pain, etc.) diagnostic tests should be performed, starting with
an endoscopy. This should also be indicated in patients refractory to
treatment. Any esophageal stenosis should undergo biopsy and cytology, regardless of the macroscopic appearance it may have. The edges
of any esophageal ulcer should also be observed through biopsy.
pH measurements using a small electrode placed 5 cm above the
LES allow to diagnose the presence of acid GER and to quantify it by
means of 24-hour ambulatory measurements. It is useful in the preop and postop evaluation of anti-GERD surgery, when symptoms are
extraesophageal, and also to assess the ecacy of drug treatment if

symptoms persist.
Complications of GERD
Esophageal ulcers and upper gastrointestinal bleeding. They are
more common if Barrett s esophagus is present. Diagnosis is by endoscopy and biopsies should be taken to rule out malignancy. They
usually occur with severe forms of esophagitis.
Peptic stenosis. It is usually manifested by dysphagia and sometimes occurs with no prior symptoms. The peptic stenosis unrelated to Barrett s esophagus is usually short and located immediately above the gastroesophageal junction. Biopsies should
always be taken to rule out malignancy, and the treatment is dilation.
Barretts esophagus. This term refers to the presence of intestinal
type columnar epithelium (metaplasia) coating the esophagus at a
variable distance above the gastroesophageal junction.
The diagnosis is made by endoscopy and biopsy still requiring multiple biopsies at intervals of 1 or 2 cm from the gastroesophageal
junction.
Respiratory symptoms. Chronic asthma, hoarseness, bronchitis,
aspiration pneumonia, bronchiectasis, atelectasis, hemoptysis and
even pulmonary fibrosis.
Neoplasms. Patients with Barrett s esophagus have an increased
risk of suering adenocarcinoma of the esophagus and proximal
stomach.
Figure 4. Esophagitis (endoscopy)
Medical treatment
First it includes a lifestyle modification that involves raising the head
of the bed, dietary changes increasing protein and decreasing fat,
chocolates, alcohol; avoid having big meals and lying down immediately after them, tobacco and drugs that relax the lower esophageal
sphincter. Regarding pharmacotherapy, patients with mild symptoms
may improve just by taking antacids when symptomatic and H2 antagonists at normal dosages. In general, if there are symptoms of
GER disease or confirmed erosive esophagitis proton pump inhibitors (PPI) such as omeprazole, lansoprazole, pantoprazole and rabeprazole in standard doses are used, as they are more eective than
the H2 antagonists. If symptoms do not disappear or the esophagitis
is severe, high doses of PPIs are used. In general, treatment is sustained, depending on severity of the disease, about eight weeks in
mild cases, or between 6 and 12 months in severe cases, and then a
gradual withdrawal is attempted. If there is relapse, treatment with
PPI is prolonged, even indefinitely.
Figure 5. Barretts esophagus
Surgical Treatment of GERD

Fundoplications. They are the most common antireflux techniques.
They are usually performed through the abdomen (laparoscopic or
open), although some techniques are performed by thoracotomy. In
the case of Nissens (fundoplication 360), the esophagus is completely
surrounded by a sleeve of gastric fundus, while in the partial fundoplications (Toupet, Dor) it is only partially surrounded. The fundoplications
can fail for being too lax (recurrence of reflux) or being too tight (causing dysphagia and gas-bloat syndrome, consisting of not being able to
burp or vomit). In the presence of impaired esophageal motility a partial
fundoplication is prescribed, since esophageal propulsive strength may
be insucient to cross a complete fundoplication (Figures 4, 5 and 6).
Figure 6. Erosions in Barretts esophagus
1.3. Infectious Esophagitis
diagnosis is the observation of the fungus in properly dyed brushing

samples or biopsy of specimens obtained by endoscopy. The treatment
of choice is fluconazole, and if it fails, amphotericin B is used.
Viral Esophagitis
The Herpes simplex virus type I may cause esophagitis in immunocompetent patients, and both type I and type II may aect those immunocompromised, with chest pain, dysphagia, and sore throat, which may
result in bleeding. Diagnosis is made by brushing or biopsy of small
resulting vesicles or ulcers, showing multinucleated epithelial cells with
intranuclear inclusions (Cowdry type A). Treatment is with acyclovir,
and in cases of resistance, with foscarnet.
Cytomegalovirus (CMV) can result in esophagitis in the immunocompromised, and it may lead to giant ulcers, especially in the lower esophagus; diagnosis is made with a biopsy of the ulcers core. Treatment is
with ganciclovir or foscarnet (Figure 7).
1.4. Esophageal Diverticula

Diverticula are sacculations of the esophageal wall. Barium radiology is
used for diagnosis.
Zenker Diverticulum
It is located in the back of the hypopharynx, above the cricopharyngeal
muscle and below the lower pharyngeal constrictor muscle. It is caused
by compulsion, due to lack of coordination of the pharyngeal muscles.
It may cause halitosis, regurgitation, oropharyngeal dysphagia, and
even complete obstruction by compression.
Possible complications are episodes of bronchoaspiration, fistula formation between the diverticulum and the trachea, intradiverticular
bleeding (especially with aspirin) and, more rarely, the appearance of
an epidermoid carcinoma in the diverticulum. The placement of a nasogastric tube or performing endoscopy in these patients involves the risk
of perforation of the diverticulum. Treatment is surgical, performing a
cricopharyngeal myotomy and removing the diverticulum. If it is small,
myotomy is sucient (Figure 8).
Thyrohyoideus
membrane
Thyroid
cartilage
Figure 7. Digestive endoscopy revealing CMV pathology
Esophagitis Candida
It is the most common cause of infectious esophagitis, Candida albicans being the most common species that produces esophagitis, although it can also
be caused by C. tropicalis, Torulopsis glabrata. Esophageal infections by other fungi such as Aspergillus, Histoplasma, Cryptococcus or Blastomyces are
much more rare and only seen in severely immunocompromised individuals.
Many species of Candida are normal commensals in the flora of the mouth,
but occasionally they may be pathogenic in normal subjects and, especially,
in immunocompromised individuals, such as: HIV patients, patients with
tumors, patients receiving corticosteroid treatment or other immunosuppressive treatments, patients with broad spectrum antibiotics, diabetes
mellitus, hypoparathyroidism, systemic lupus erythematosus, or patients
with hemoglobinopathies or prior esophageal disease, such as erosive
esophagitis or esophageal food stasis, wich may be diverticula, achalasia.
The most common symptoms are dysphagia and odynophagia, although
subjects with this condition may be asymptomatic. Complications such
as bleeding, perforation or stenosis may result. The safest method of
Lower constrictor
muscle of the
pharynx
Cricothyroid
membrane
Zenkers
diverticulum
Cricothyroid
muscle
Cricoid
cartilage
Fibrous arch
Cricopharyngeal
muscle
Trachea
Esophagus
Figure 8. Zenkers diverticulum
Mid-Section Diverticulum
It may be caused by traction or drive in patients with motor abnormalities
of the esophagus. It is usually asymptomatic, appearing incidentally in radiologic studies performed for some other reason and needs no treatment.
Epiphrenic Diverticulum
It occurs above the LES, and is frequently associated with esophageal motor disorders, particularly achalasia; a fairly typical symptom is regurgitation of large amounts of fluid, usually at night. If symptomatic, treatment,
is surgical; a diverticulectomy is performed with wide extramucosal myotomy plus antireflux technique if a hiatal hernia is associated.
1.5. Hiatal Hernia
(Figure 9)
A hiatal hernia is a herniation of an abdominal organ, usually the stomach, through the esophageal hiatus. Diagnosis is based on radiographic
contrast studies. There are two main types: sliding and paraesophageal.
Sliding Hernia or Type I (90%)
The most common complication is recurrent, chronic, asymptomatic

and hidden gastrointestinal bleeding. The second most common, but
more serious complication is gastric volvulus. Gastric volvulus consists
of the stomach rotating on its longitudinal axis (most often) or on about
its transverse axis. Clinically it causes severe abdominal pain and Brochardt triad: retching and inability to vomit, epigastric distention and
inability to insert a NG tube. It requires emergency laparotomy and repairing of the hiatal hernia. Gastric ischemia may require gastric resection and intestinal anastomosis.
Because of the risk of complications, surgical treatment of type II hiatal
hernia is prescribed, even if asymptomatic. A reduction of the hernia sac,
resection of the sac and reparing of the hiatus is performed. An antireflux
technique is also associated, as GER frequently occurs after surgery, and
because up to two-thirds of paraesophageal hernias are mixed.
1.6. Squamous Cell Carcinoma
of the Esophagus
The esophagogastric junction is displaced through the hiatus. There is no

hernial protrusion. They are usually asymptomatic. They require treatment only when there is symptomatic gastroesophageal reflux.
It is the most common type of neoplasia worldwide.
Paraesophageal Hernia or Type II (10%)
Incidence and etiology
Type I
Hernia because of sliding
Squamocylindrical joint
Diaphragm
Type II
Paraesophageal hernia
Diaphragm
Squamocylindrical joint
Figure 9. Types of Paraesophageal hiatal hernies

It is a true herniation of the stomach within the hernial sac in the mediastinum. The gastroesophageal junction remains in place, although
over time it is frequently associated with a sliding component (com-
bined hernias or type III). Most are asymptomatic. When symptoms and
complications occur, they are due to an anatomic defect, and not to a
physical disorder of the esophagogastric competence.
As for its etiology, the most clearly related factors are alcohol and tobacco, having also been related to ingestion of certain carcinogens like
nitrites, smoked opiates and certain mycotoxins; in situations of physical
damage to the mucosa, such as ingestion of hot food following sequels
of caustic ingestion (it increases risk by 40 being the most potent precancerous conditioning), stenosis by radiation, chronic achalasia and, although it is not proven, there is a suspicion that GERD without Barrett s
esophagus can also increase the risk. There is individual susceptibility in
the Plummer-Vinson syndrome, in tylosis (hyperkeratosis of palms and
plants) and thyroid diseases; it seems that in certain nutritional deficiencies (molybdenum, zinc, vitamin A) and celiac sprue, there may be a
slight increased risk of squamous cell esophageal cancer.
Symptoms and diagnosis

Approximately 10% to 15% are located in the cervical esophagus, 50%
in the middle third of the esophagus and 35% in the lower third. Progressive dysphagia of mechanical characteristics and weight loss are the
most common symptoms. In practice, it is assumed that the onset of
dysphagia means that the disease is incurable and may further result
in chest pain, vomiting, regurgitation, aspiration episodes, hiccup and
hoarseness. Paraneoplastic presentations such as hypercalcaemiaby
production of PTH-rP or hypokalemic alkalosis by ACTH production have
also been noted. Tracheoesophageal fistulas may occur in 6% to 12%
of patients. The disease spreads to nearby and supraclavicular lymph
nodes as well as to the liver, lungs and pleura.
Regarding diagnosis, radiographic barium contrast studies (mostly using
double contrast techniques) can identify most malignant lesions and dier-
entiate them from benign lesions; however, smaller lesions may hardly be
seen with radiologic studies, so it is always mandatory, when esophageal
cancer is suspected, to perform an esophagoscopy (with biopsy and brushing of the injury for cytologic study. It is mandatory to always see the gastric
fundus on endoscopy. CT is used to assess the local extent of the tumor
and to study metastasis in chest and abdomen. Endoscopic ultrasonography
has been recently introduced for the study of the local extent of the tumor,
now considered the best method for T and N staging. Bronchoscopy should
be performed in tumors of upper and middle third to assess resectability,
since the presence of tracheobronchial invasion contraindicates a resection
(Figure 10).
Esophageal Adenocarcinoma
It is the most prevalent type of cancer in the USA, Europe and Australia.
It is related to Barrett s esophagus (intestinal metaplasia).
It is characterized by the existence of progressive dysphagia, weight
loss and odynophagia.
Diagnosis is made by endoscopy and biopsies.
Treatment is based on resection and chemotherapy, if possible.
Gastric
Chapter 02
Pathology
2.1. Gastritis
Gastritis is a term denoting histologic inflammation of the gastric mucosa, and, a biopsy is thus required for diagnosis.
Acute Gastritis
Stress Gastritis
Understood as a severe case, stress may result in a range of lesions from
superficial erosions to complicated peptic ulcers. Erosions are more
frequently found in the body and fundus, while ulcers themselves are
more frequently found in the antrum and duodenum. This type of acute
gastritis is particularly seen in hospitalized patients who are severely ill,
such as those with severe trauma or infections, severe liver, kidney or
respiratory failure, etc. The main mechanism which they result from is
unknown, but the two most important pathogenic factors are probably
mucosa ischemia and heartburn, the former probably being the most
important triggering factor for most patients.
Figure 10. Epidermoid carcinoma of the upper third of the esophagus
Treatment
Histologically, there is loss of gastric mucosa with erosions and diused

bleeding. These gastric erosions do not, by definition, go beyond the
mucosa muscle layer.
Few patients are candidates for surgery and, of those who survive it,
less than 20% will be alive after five years.
The most frequent clinical case is upper gastrointestinal bleeding with

dierent severities. Endoscopy is the best diagnosis method.
Resection (esophagectomy) and chemotherapy are performed whenever possible.
Treatment consists of improving the underlying illness, steps adopted

for upper gastrointestinal bleeding, and use of IBP, anti-H2 or sucralfate
as needed to maintain gastrointestinal pH over 4. These drugs should
be used both for prevention and treatment. More aggressive steps such
as embolization are occasionally needed to control bleeding. Given the
high mortality in this clinical scenario, surgery is the last resource, although it may occasionally be required (when resections are made).
In the frequent cases of unresectable disease, mitigation techniques are

applied, whether surgical (exclusions, gastrostomy) or endoscopic (laser,
photodynamic, expansion, brachytherapy, expandable prosthesis). Radiation therapy alone for the same type of patients provides similar results, although it is less eective at relieving the obstruction it prevents
perioperative mortality and morbidity. In some cases resectability may be
improved with preoperative radiotherapy (although it does not improve
survival). The overall survival rate for this cancer is less than 5% five years
after diagnosis.
There are two types of stress ulcers which are separate entities:
Cushings ulcer. It is a true stress ulcer associated with a central nervous system pathology or increase of intracranial pressure; characteristically, the main pathogenic factor is acid hypersecretion.
Curlings ulcer. This type of ulcer is associated with severe burns, and
it is caused by hypovolemia. Hypovolemia reduces stomach flow interfering with the clearance mechanism of hydrogen ions, which remain longer in contact with mucosa resulting in this type of ulcer.
Drug-Induced Gastritis
Various agents may result in lesions to the gastric mucosa similar to
those from stress gastritis. Acetylsalicylic acid (ASA), NSAID, bile acids,
pancreatic enzymes or alcohol are among them. Among drugs, ASA and
NSAID, with inhibition activity of cyclooxygenase-1, are the most common causes of reactive gastropathy.
Toxic Gastritis
The disease is more common in northern Europe and it predominates

in women. In some cases, there is an autosomal dominant inheritance.
First-degree relatives of these patients have a higher risk of developing
the disease.
It is usually atrophic gastritis. Inflammation and posterior atrophy predominates in fundus and body, with parietal cells being destroyed by an
immune mechanism. A profound hypochlorhydria occurs which determines a significant hypergastrinemia with hyperplasia of antral G cells,
sometimes becoming real carcinoid tumors. As a consequence of the
destruction of parietal cells, there is also a decreased secretion of intrinsic factor, which sometimes results in pernicious anemia by vitamin B12
deficiency (megaloblastic) with or without neurologic symptoms.
Alcohol. Following ingestion, subepithelial bleeding is frequently

seen during endoscopic analysis with no major mucosa swelling.
The eects of combining alcohol and ibuprofen (NSAID) were noted
in endoscopic studies with greater mucosa damage than that observed for each agent in isolation.
Cocaine. There has been a relationship between the use of crack cocaine and gastrointestinal bleeding because of diuse exudative erosion throughout the gastric fundus, body, antrum, and duodenal bulb.
Bile reflux. Frequently there is bile reflux in the stomach after partial gastrectomy with anastomosis of the duodenum (Billroth I) or
jejunum (Billroth II). Bile reflux gastritis may also occur following
a cholecystectomy or sphincteroplasty. Endoscopy reveals edema,
congestion, erosions and bile impregnation in the gastric mucosa.
Gastric atrophy may occur and increase the risk of gastric stump carcinoma. Treatment of choice is sucralfate or aluminum hydroxide.
Sometimes, it is necessary to perform a Roux-en-Y bypass to remove
biliopancreatic secretions from gastric remnant.
Atrophic gastritis without pernicious anemia is more common than the

previous condition; this is explained because some parietal cells secreting intrinsic factor remain harmless, enabling the absorption of B12.
In over 50% of these patients antiparietal cells may also appear, and it
is speculated that over time, these patients will progress to pernicious
anemia. There is no treatment, except for pernicious anemia (consisting
of administering intramuscular vitamin B12). There is a greater risk of
gastric adenocarcinoma than in the general population.
Acute Gastritis Because of H. Pylori
H. Pylori-Associated Gastritis. Type B Gastritis
Although most frequently the H. pylori infection is asymptomatic, it

may occasionally cause nonspecific symptoms and histologically there
is polymorphonuclear infiltration in the gastric mucosa. Some studies
with healthy volunteers in whom the bacteria was probably transmitted
among one other have noted small epidemics of what has been called
acute epidemic gastritis as a result of H. pylori.
It is the most common. Although it was initially considered that the antrum
was the main residence of H. pylori, now we know that it can be found almost with the same frequency in the body and fundus. It primarily causes
lesions of active chronic gastritis. Virtually 100% of the population over 70
years of age has some degree of gastritis of this type. In young people, it
is mainly antral, and in the elderly it aects, probably by progression, a
large part of the stomach. It is usually associated with some degree of hypochlorhydria and the gastrin level in these patients is highly variable, but
it is often normal. Multiple biopsies are taken for diagnosis. There are no
therapeutic recommendations for this type of injury.
Enteropathic Erosive Gastritis

It is a rare clinical entity with multiple erosions on the crests of gastric folds found in the absence of recognized precipitating factors for
these lesions. Patients usually have anorexia, nausea, vomiting, and
nonspecific abdominal discomfort. Diagnosis is by means of endoscopy and biopsy, and there is no specific therapeutic recommendation.
Other noted causes have been nasogastric tube erosion, radiotherapy
on the area, vasculitis, duodenogastric reflux, idiopathic scenarios and
marathon runners.
Autoimmune Gastritis. Atrophic Gastritis Type A
Parietal cell antibodies appear in 90% of patients with atrophic gastritis type A and pernicious anemia, and intrinsic antifactor Ac appears in
40% of patients; they are more specific and also collaborate with intrinsic factor deficiency. In other autoimmune disorders such as hypoparathyroidism, autoimmune thyroiditis, Addisons disease and vitiligo,
antiparietal cell Ac may also appear, however, it may also be detected
in healthy people.
Diagnosis is made by endoscopy with biopsy (and urease test or histology for the diagnosis of H. pylori).
Treatment is with eradication therapy (amoxicillin, clarithromycin and
omeprazole) and proton pump inhibitors.
Chronic Gastritis
2.2. Peptic Ulcer
This occurs when when the inflammatory infiltrate is mainly constituted

by mononuclear cells. If there are polymorphonuclear cells as well, we
are looking at active chronic gastritis; it is almost always associated with
infection by H. pylori (70% to 95% of cases).
This refers to a group of ulcerative disorders of the upper gastrointestinal tract, aecting primarily the proximal duodenum and stomach. Very
often, the causative agent is Helicobacter pylori. Although knowledge
of the etiopathogenesis is incomplete, it is accepted that it is the result

of an imbalance between aggressive factors and defenders of gastric
mucosa. Unlike gastric erosions, it is well defined and deep, sometimes
reaching the muscle layer. Histologically, it is an area of eosinophilic necrosis that rests on granulation tissue with chronic inflammatory cells
surrounded by a degree of fibrosis.
Duodenal Ulcer
Its prevalence is estimated at approximately 10% of the population. Its natural history is one of spontaneous healing and recurrence, with relapse within
two years from 80% to 90%. However, with the current therapeutic arsenal
prospects are, in most cases, a single disease outbreak. They are located in
more than 95%, in the first portion of the duodenum in more than 95% of
cases. They are small and diameters larger than 1 cm are unusual.
Etiopathogenesis
The most important factor is the association with Helicobacter pylori: in
95% of patients the existence of H. Pylori can be demonstrated, can be
verified with gastric biopsies. Most infected patients do not develop ulcer,
so the presence of other contributing factors is necessary. In second place
are those associated with the consumption of NSAID. However, there
may be other factors associated with this disease. Thus, it is known that:
1. The basal gastrin in these patients is normal but they secrete more
gastrin in response to food, they secrete more acid in response to
an injection of gastrin and they empty their stomach faster, aspects
that cannot be attributed entirely to infection by Helicobacter pylori.
2. Genetic factors. Between 20% and 50% of patients with duodenal
ulcers have a family history of duodenal ulcer. People with blood
type 0 have a 30% increased risk. An increased incidence of HLA
B5 has also been reported. It is speculated that some genetic factors for duodenal ulcer assumptions represent no more than the
intrafamiliar spread of infection by Helicobacter pylori. For example,
inherited hyperpepsinogenemia type 1, which was considered a potential genetic marker of familiar duodenal ulcer, is currently known
to be explained by Helicobacter pylori infection.
3. Tobacco. Tobacco consumption increases the incidence of duodenal
ulcer and it worsens ulcer scarring. Tobacco also favors recurrences
and increases the risk of complications and the need for surgery.
There are several mechanisms by which it may act: increase in gastric emptying, decrease in pancreatic secretion of bicarbonate, impaired blood flow or decrease prostaglandin synthesis.
Also, an increased risk of duodenal ulcer has been noted in: systemic mastocytosis, myeloproliferative disorders with basophilia, COPD, cystic fibrosis, lack of alpha-1 antitrypsin, kidney stones, chronic renal failure and renal transplantation, alcoholic cirrhosis, hyperparathyroidism, situations of
vascular insuciency and use of crack, radiotherapy and chemotherapy.
Symptoms
The most common symptom is epigastric pain, which occurs between one
and a half and three hours after meals and it is relieved by food or antacids. The most characteristic symptom, but still far from perfect, is pain
that awakens the patient at night, between midnight and 3 am. The pain
is induced by acid. However, epigastric pain is a symptom that is neither
sensitive nor specific: we must take into account that many patients with
duodenal ulcer have no symptoms. A change in pain patterns should suggest a complication.
Pyloric ulcers present clinically as duodenal ulcers. But symptoms are less
responsive to food and antacids, may even increase pain with food and,
most often, vomiting occurs by gastric obstruction. In general, surgery is
required more frequently in pyloric ulcers than in duodenal bulb ulcers.
Diagnosis
Gastroduodenal conventional contrast studies identify about 70% of
the cases. Double-contrast techniques are better and are closer to endoscopy. Endoscopy is the most reliable method and it should be recommended first. It is not justified if the diagnosis was obtained by radiology. Mandatory endoscopy should be prescribed if there is a strong
suspicion of duodenal ulcer that is not visible radiographically (possibly
very small or superficial), in patients with bulbar deformity and when
presented with upper gastrointestinal bleeding.
Diagnosis of infection with Helicobacter pylori could be performed at
the time of endoscopy, obtaining samples of gastric antral mucosa; or
with breath test, if performed by barium examination.
Treatment guidelines
It is based on eradicating Helicobacter pylori in patients with documented
infection and confirmed ulcer, either at present or in other previous episodes. This can speed up healing and especially avoid recurrences. If the
patient is asymptomatic at the end of the eradication therapy, it will not
require maintenance treatment, except if it had gastrointestinal bleeding
or if the ulcer was greater than 2 cm, in which case it is preferred to continue with anti-H2. If the source was NSAID or idiopathic, treatment with
anti-H2 is IBP for four to six weeks (Figure 11).
Duodenal ulcer
Oral endoscopy
Gastroduodenal
test with contrast
Diagnostic test
of H. pylori:
urease-histology
Diagnostic test
of H. pylori:
breath test
+
Eradication treatment
Do not maintain antisecretory treatment
Figure 11. Diagnostic-therapeutic algorithm of duodenal ulcer
Gastric Ulcer
Etiopathogenesis
In general, there are few dierences between etiopathogenic gastric
ulcers and duodenal ulcers, although it is thought that in the first, the
most important pathogenic data is an alteration in the defense mechanisms of gastric mucosa. Acid secretion is normal or decreased and the
level of gastrin is normal or elevated proportional to degree of heart-
burn. They tend to be larger and deeper than duodenal ulcers. Helicobacter pylori is found in approximately 60% to 80% of patients with
gastric ulcer. NSAIDs patients are the second source, causing gastric ulcer more frequently than duodenal ulcer. Gastric ulcer occurs mainly in
patients over 65, taking concomitant corticosteroids and in cases with a
history of peptic ulcer. A total of 10% of gastric ulcers are idiopathic, i.e.,
not associated with Helicobacter pylori or intake of NSAIDs.
it is a complicated gastric ulcer, treatment is recommended with 40 mg

of omeprazole (Figure 13).
Gastric ulcer
PEO + 6-8 biopsies of ulcer borders
and brush center of the lesion
Symptoms
The peak incidence of gastric ulcers is in the sixth decade of life. They
are most often located in the minor curvature, especially in antral mucosa. They are almost always accompanied by gastritis, when associated
with Helicobacter pylori. Benign ulcers in the fundus are rare. Epigastric
pain is the most common symptom, but it follows a less typical pattern
than duodenal ulcer. Vomiting appears more frequently, without needing mechanical obstruction. Recurrences are usually asymptomatic.
Diagnosis
Radiologic barium studies. Some criteria have been reported to try to
distinguish between benign and malignant. Folds radiation from the
ulcers edge is considered a criterion of benign nature. Size: in one
study, 10% of ulcers larger than 2 cm and 62% of those over 4 cm were
malignant. The presence of a mass indicates malignancy. In any case,
between 3% and 7% of ulcers with benign radiographic appearance are
malignant, so endoscopy for suspected gastric ulcer is always advisable.
Endoscopy. It is the diagnostic procedure of choice. A total of 6-8
biopsies should be taken from the edges of the ulcer and brushing
of ulcer bed for cytologic study, so to exclude malignant lesions.
You must also obtain biopsies of the gastric antrum to investigate
infection by Helicobacter pylori (Figure 12).
Heartburn studies. They are not usually performed. The presence
of achlorhydria after pentagastrin stimulation suggests tumor.
Diagnostic test of Helicobacter pylori:

urease and/or histology
+
Eradication treatment
Confirmation of scarring and eradication
Antisecretory treatment for four to eight weeks
Figure 13. Diagnostic-therapeutic algorithm of gastric ulcer
Gastrointestinal Bleeding
by Peptic Ulcer
Hemorrhage
It occurs in 20% to 25% of peptic ulcer cases. Duodenal ulcer is the most
frequent cause of upper gastrointestinal bleeding (UGA) (usually on the posterior side). Gastric ulcers bleed more often than duodenal ulcers (although
being less prevalent they are less frequently a cause for UGA; this explains
the apparent contradiction between the two aforementioned sentences).
Further, gastrointestinal bleeding has greater mortality. The latter is due to
its lower tendency to spontaneously stop and to its prevalence among elderly people.
Bleeding ulcers are more frequent in patients over 50 years of age. It is usually painless and diagnosis is performed by means of endoscopy (Figure 14).
The first step against gastrointestinal bleeding is hemodynamic stabilization
of the patient. A total of 80% of patients admitted for duodenal ulcer bleeding stop bleeding spontaneously within the first eight hours of admission. If
eradication therapy is required, it is commenced together with oral feeding.
Figure 12. Ulcer: erythematous border and brinous base
Medical treatment
In general, the treatment is similar to that of duodenal ulcer, but bear in
mind that gastric ulcers heal more slowly. Therefore, after eradication
therapy it may be recommended, for uncomplicated ulcers, H2-antagonist for eight weeks, or if larger than 2 cm, for 12 weeks. In uncomplicated gastric ulcers, omeprazole has little advantage over H2 antagonists. If
10
Figure 14. Hemorrhage because of peptic ulcer. A vessel bleeding

actively can be observed
Endoscopy has proven highly valuable to identify lesions responsible for

bleeding and to establish a prognosis. Furthermore, it allows applying
hemostatic therapy if prescribed. This procedure oers major advantages if performed early (before 24 hours since the bleeding episode)
as follows:
Endoscopy enables identifying patients with low risk lesions and apt
for early discharge.
Hemostatic therapy may be applied to patients with high risk lesions, decreasing bleeding recurrence, the need for surgery and
mortality.
It has a positive eect on healthcare costs, since endoscopy avoids
unnecessary admissions of low risk patients and shortens the stay of
patients with high risk lesions.
The available endoscopic classification in order to establish a risk
classification of bleeding peptic ulcers is Forrests classification (Table 2).
Figure 15. Bleeding ulcer: fresh adherent clot
CLASSIFICATION
ENDOSCOPIC
FINDINGS
RELAPSE
Active
hemorrhage
Ia
Spurting hemorrhage
55%
Ib
Oozing hemorrhage
50%
Recent
hemorrhage
IIa
Visible vessel
43%
IIb
Adherent clot
22%
IIc
Hematin
7%
III
Fibrin base
2%
Absence
of bleeding
signs
Table 2. Forrest endoscopic classication

Forrest I: active bleeding at the time of the endoscopy.
Ia: spurting or jet bleeding.
Ib: oozing or drooling bleeding.
Forrest II: absence of active bleeding at the time of endoscopy with
signs of recent hemostasis.
IIa: nonbleeding visible vessel.
IIb: adherent clot (Figure 15).
IIc: ulcer covered in fibrin with red dots (hematin).
Forrest III: absence of bleeding signs. Ulcer totally covered by fibrin.
Endoscopic therapy, for which the following may be used:

Adrenaline or sclerosing agents (substances that cause vasoconstriction once injected into the lesion with a needle).
Hemoclips (mechanical methods of hemostasis).
Thermal methods of hemostasis (such as electrocoagulation).
Any of them is valid as endoscopic therapy, but it has been proven that
the combination of two of them (adrenaline and sclerosing agents;
adrenaline and hemoclip; sclerosing agent and electrocoagulation; and
so on) is superior to individual-basis therapy.
2.3. NSAID-Associated Ulcers

NSAIDs mainly act by inhibiting cyclooxygenase (COX), resulting in
inhibition of prostaglandin synthesis. This inhibition also aects
prostaglandins gastric mucosa, this being the main mechanism of
gastric injury. However, NSAIDs are also toxic against mucosa due to
its weak acid nature. There are two forms of COX-1: type 1, which is
routinely observed in normal cells, and COX-2, which is induced in
inflammatory cells. Selective inhibition of COX-2 would theoretically
provide the advantages of analgesia or anti-inflammation, but, since
it does not inhibit COX-1, no gastric damage would occur.
Conversely, IIc and III are low risk lesions where endoscopic treatment
is not prescribed, therefore, patients are apt for early hospital discharge
with oral IBP treatment.
NSAIDs mainly favor the occurrence of gastric ulcers. Peptic ulcer predisposing factors by NSAID consumption are: history of peptic ulcer
or gastrointestinal bleeding at advanced age; high doses; prolonged
therapy; association with corticosteroids (although these alone are
not ulcerogenic), type of NSAID, or severe underlying disease (Salsalate and selective inhibitors of COX-2, rofecoxib and celecoxib, have
a lower risk).
For high risk lesions (Forrest Ia to IIB) prescribed treatment is as follows:

Administration of intravenous IBP (80 mg bolus followed by intravenous perfusion for three days), since it has been proven to decrease
rebleeding, need for surgery and mortality.
Hospital admission.
As for treatment, drugs should be discontinued, if possible. Moreover,

treatment is preferably administered with omeprazole (better than
misoprostol and both better than anti-H2). If treatment with NSAIDs
cannot be discontinued the use of proton pump inhibitors (PPIs) in a
higher dose than usual will be necesary although H2 antagonists may
also be useful in duodenal ulcers (Table 3).
Forrests high risk lesions range from Ia to IIb and endoscopic therapy is
prescribed for all of them.
11
Guidelines for treatment for NSAID-induced ulcer

Suspend NSAID
Antisecretory (anti-H2/IBP)
- Duodenal ulcer eight weeks
- Gastric ulcer 12 weeks
If H. pylori positive: eradication
If NSAID cannot be suspended: keep IBP at a higher dose
Table 3. Guidelines in case of NAIDS-induced peptic ulcer
2.4. Zollinger-Ellison Syndrome

ZE syndrome is due to the presence of a gastrinoma, a gastrin-producing tumor, which in turn causes a peptic ulcer.
Tumor size is variable, but sometimes it is so small it cannot be seen
with imaging methods or even surgery. Two thirds of cases are malignant. Prognosis is very poor if the tumor appears in the context of a
syndrome of multiple endocrine neoplasia (MEN).
The most common location of the tumor is the duodenal wall, followed by
the pancreas. As a result of gastrin eects on gastric mucosa, sometimes
small gastric, multicenter, noninvasive carcinoids have been found.
In 20% of patients, the gastrinoma is part of a MEN 1 transmitted as an
autosomal dominant with high penetrance, and whose gene is located
on chromosome 11. In these cases, gastrinomas are smaller, multiple
and tend to be located in the wall of the duodenum more frequently
than in sporadic cases.
Symptoms
It is more common in men and it occurs mainly between 35 and 65
years of age. The most common symptom is abdominal pain from
an ulcer. It is caused by increased secretion of acid and pepsin. Ulcers, which are sometimes multiple, occur mainly in the duodenal
bulb, but they can also be in the postbulbar or jejunum, stomach and
esophagus. A total of 40% to 50% of patients have ulcer complications and they generally respond poorly to conventional therapy.
Diarrhea is also common and may precede ulceration. Diarrhea is
caused by the passage into the intestine of excesive gastric secretion. Occasionally there is steatorrhea secondary to intense acidity
and which inactivates pancreatic lipase; in addition, conjugated bile
acids are precipitated in the duodenum and jejunum. Inactivation of
pancreatic enzymes also accounts for the malabsorption of vitamin
B12. Esophageal involvement is often significant.
Gastrinomas, apart from gastrin, can secrete many other peptides; the
most common among them is ACTH, which may lead to Cushings syndrome, usually constituting a poor prognosis because, when diagnosed,
there are usually liver metastases.
Diagnosis
ZE syndrome should be suspected in patients who have ulcers in unusual locations: ulcers that persist despite medical treatment; ulcer and
diarrhea; abnormally large gastric folds; ulcers and other manifesta-
12
tions of endocrine tumors; family history of ulcer disease and recurrent

ulcers after surgery.
If gastrin level is abnormally high, gastric acid secretion should be measured: if it is too high, the patient will probably have ZE syndrome (as hypochlorhydria or achlorhydria would be excluded as causes of hypergastrinemia). In doubtful cases, with serum gastrin lower than 1,000 ng/L,
the secretin stimulation test is used; secretin intravenous injection in
patients with ZE results in a large increase of gastrin.
For the localization of the tumor, a CAT scan, an MRI and labeled octreotide
scintigraphy should be performed to investigate metastasis. Finally, it is often
necessary to use endoscopic ultrasonography, useful for detecting small tumors, although sometimes it is necessary to perform operative ultrasound.
Treatment
Medical treatment (palliative) comprises administering proton pump inhibitors, which are the symptomatic treatment of choice for patients with
ZE syndrome. Usually the recommended dose is 60 mg, administered
before breakfast. However, in over 50% of patients, the tumor has a malignant behavior and approximately 50% of patients with ZE syndrome in
which the tumor could not be removed, die of tumor invasion.
Surgical treatment the Zollinger-Ellison syndrome is etiologic. The ideal
solution is surgical resection of the original tumor, if possible (either
duodenal or pancreatic). Moreover, it is a tumor (gastrinoma) with a
significant tendency to spread.
Classically, total gastrectomy has been the cornerstone of palliative
treatment until the appearance of medical treatment. The superselective vagotomy has facilitated the control of acid hypersecretion in patients in whom resection of the tumor was not possible and it was not
completely controlled medically. However, for this purpose it continues
to be the most commonly used esophagojejunal total gastrectomy with
anastomosis because of the risk of fulminant ulcers when you cannot
remove the pancreatic injury.
2.5. Gastric Tumors

Gastric Adenocarcinoma
Despite the decrease in the incidence of gastric carcinoma in many industrialized countries, it remains one of the most common causes of
cancer death.
Epidemiology and biology

During the last two decades, the incidence rate tends to decrease. It is
rare before age 40, but later it increases with a peak incidence in the
seventh decade. It is twice as common in men than women.
The reduction in the incidence of gastric cancer has been at the expense
of the distal cancer (corpus and antrum), because the incidence of proximal gastric cancer (cardia and gastroesophageal junction) is increasing
significantly.
Pathologic anatomy
Diagnosis
Gastric adenocarcinomas can be divided into two types:

Intestinal, characterized by cells that form glandular structures,
reminiscent of colon carcinoma. In general, it is a distinct tumor and
its origin is associated with intestinal metaplasia. Intestinal-type lesions ulcerate and locate most often in the distal portion, and they
are more associated with precancerous conditions.
Diuse, without cohesion among its cells, which infiltrates and thickens the gastric wall in any location, without forming a mass, and
sometimes reduces gastric compliance, a type called linitis plastica.
The gold standard for its diagnosis is endoscopy with multiple biopsies.
For the extension study, abdominal CT is the best method. However,
when compared with laparotomy findings, it is observed that the extent
of the disease may be underestimated. In doubtful cases, laparoscopy is
used to evaluate the depth of the wall and the presence of lymph node
metastases.
Precusory lesions
The chronic atrophic gastritis with intestinal metaplasia is the predisposing lesion most clearly related to gastric cancer, primarily with
the intestinal type. Atrophic gastritis usually begins as a multifocal
process in the distal part of the stomach. When these focal points
converge: metaplasia, dysplasia and finally carcinoma progress and
develop.
Pernicious anemia produces a two to three times higher risk of gastric cancer in people having this disease than in general population.
They may also present gastric carcinoid by neuroendocrine hyperplasia.
Distal gastrectomy increases the risk of gastric cancer after 20 years
of resection.
There is an increased risk in Menetrier disease or in gastric adenomatous polyps larger than 2 cm.
Hiccup and achlorhydria. All precursory lesions previously reported
correspond to distal gastric cancer. However, the increased incidence
of proximal gastric and distal esophagus seems to be clearly related to
the increased incidence of Barretts esophagus.
Symptoms
When superficial and removed by surgery, it is usually asymptomatic.
When it shows symptoms, it is usually regarded as an advanced and
incurable disease. The most common presenting symptoms are epigastric pain and weight loss. In distal gastric cancer, vomiting is frequent as
a consequence of the pylorus being aected, and in proximal, gastric
cancer, dysphagia is a common symptom. Acute gastrointestinal bleeding is not frequent.
The disease spreads by direct extension to perigastric organs, especially the liver and pancreatic tail. It is also spread via the lymphatic
system to intraabdominal and supraclavicular (Virchows node) nodes.
If it spreads throughout the peritoneal surface, it may cause periumbilical lymphadenopathy (Sister Maria Jose nodule), ovarian involvement (Krukenberg tumor), a mass in the pouch (Blumer shield) or a
peritoneal carcinomatosis with malignant ascitis. The liver is the most
frequent organ of hematogenous spread, although lungs can also be
aected. Regarding laboratory data, anemia was observed in 42%, fecal
occult blood in 40%, liver abnormalities and hypoproteinemia in 26%.
Rarely it may present as a paraneoplastic episode. The most common
symptoms are microangiopathic hemolytic anemia, membranous nephropathy, sudden appearance of seborrheic keratoses (sign of LeserTrlat), appearance of filiform and papular pigmented lesions in cutaneous and mucosal folds (acanthosis nigricans), chronic intravascular
clotting, which can lead to arterial and venous thrombosis (Trousseau
syndrome), and in rarer cases, dermatomyositis.
In early gastric cancer (which invades no more deeply than the submucosa, irrespective of lymph node metastasis), diagnosis with endoscopy
can be improved with methylene blue-congo red staining, although radiologic study can also be eective with thin-film techniques and double contrast.
Tumor markers. None of them are clearly eective. CEA is elevated in 40%
to 50% of cases with metastases, not being useful in diagnosis, but it may
be useful in postoperative follow-up.
Screening. Currently it is not justified in our setting, but it may in areas
where the disease prevalence is high, as in Japan, where endoscopy
screening for cancer has enabled 40% to 60% of cases to be diagnosed at
an early stage.
Pathology
Chapter 03
of the Small
and Large Intestine
3.1. Diarrhea
Diarrhea is defined as the increase in daily stool weight above 200 g. It is
usually accompanied by an increased number of stools, and a reduction
in consistency. The normal number of stools varies from three a day to
three a week.
Pseudodiarrhea is defined as increased bowel movements without increased stool weight. Within two or three weeks, it is considered acute
diarrhea, and when it lasts longer, chronic diarrhea.
Acute Infectious Diarrhea

A patient is considered to have diarrhea when there is a significant variation in the characteristics of stools regarding number, frequency and
consistency.
According to WHO, diarrhea is the passage of three or more loose or
liquid stools per day (or more frequent passage than is normal for the
individual), and a diarrheal episode is an event that complies with the
abovementioned criteria and that ends when the last day with diarrhea
is followed by at least 48 hours of normal stool.
13
Infections are the

most frequent cause
of diarrhea. This disease may also be
caused by drugs, toxins, resumption of
eating after fasting,
faecaloma (overflow
of liquid stools), being a marathon runner, etc.
Acute diarrhea lasts
less than four weeks,
whereas chronic diarrhea lasts longer.
3.2. Acute
MICRO-ORGANISM
COMMON VEHICLES
MEDIAN
INCUBATION
CLINICAL
PERIOD :
CHARACTERISTICS*
HOURS (LIMITS)
MEDIAN
DURATION
(DAYS)
Bacillus cereus
Fried rice, vanilla sauce, cream,

meat balls, boiled beef and roast
chicken
2 (1-16)
V, C, D
0.4 (0.2-0.5)
Clostridium perfringens
beef, turkey and chicken
12 (8-22)
D, C (N, V, F rara)
1 (0.3-3)
Vibrio parahaemolyticus Seafood, rarelly salted water or

vegetables
12 (2-48)
D, C, N, V, H , F
3 (2-10)
Staphylococcus aureus
Seafood and sea fish, rarely salted

water or salted vegetables
3 (1-6)
V, N, C, D, F
1 (0.3-1.5)
Escherichia coli
Ham, pork, canned beef and pies

stuffed with cream
48 (24-240)
D, F, C, B, H, M
7 (2-30)
Salmonella
Eggs, red meat and poultry
96 (24-120)
F, M, D, C
3 (1-4)
Shigella
Milk and salads
24 (7-168)
C, F, D, B, H, N , V
3 (0.5-14)
* B: sanguineous diarrhea, C: abdominal pain (colic), D: diarrhea, F: fever, H: headaches, N: nausea and V: vomiting
Infectious
Diarrhea
Table 4. Toxigenic bacterial diarrheas
Etiology and Epidemiology

Infectious diarrhea is a syndrome caused by a virus, protozoans, bacteria and helminths. Most infectious diarrhea occurs by fecal-oral route
transmission. Person-to-person transmission may also occur by aerosolization (Nowalk agent, rotavirus), by contaminated hands and surfaces,
or by sexual activity.
The main risk factors associated with an acute diarrheal episode are the
following:
Insucient personal hygiene (washing hands)
Malnutrition
Recent travel to endemic zones
Feces-contaminated water and food
Self-medication
Ingestion of seafood from polluted water
Undercooked meat
Prior intake of antibiotics
Residence in psychiatric and geriatric institutions, hospitals.
Types
Colonization of the proximal portion of the intestine occurs and an enterotoxin is created (producing hypersecretion at the intestinal level).
The mucosal architecture remains intact (with no evidence of cellular
destruction), whereby bacteremia does not occur. The fecal euent is
watery and often voluminous, so that diarrhea can result in clinical dehydration.
These bacteria are also responsible for food poisoning caused by
consumption of food contaminated by bacteria or bacterial toxins.
Symptoms and signs manifested in case of food poisoning depend
on the number and quality of the toxic substances ingested. Generally, symptoms appear a few hours (four or less) after consumption
and may disappear within the following three days. One or more of
the following symptoms may appear according to the agent involved:
nausea, abdominal pain, vomiting, diarrhea, fever, headache and fatigue.
Invasive Bacterial Diarrhea (inflammatory diarrhea)

Invading prototype micro-organisms in this group are enteroinvasive
E. coli, Salmonella, Shigella, Campylobacter and Yersinia.
Invading micro-organisms impact mainly invading the intestinal epithelium, and primarily aect the distal intestine, mainly the ileum and distal colon. Mucosal ulceration with acute inflammatory reaction in the
lamina propria is the main histologic finding.
Bacterial diarrhea
Acute bacterial diarrhea may be classified into the following types:
Toxigenic (mediated by enterotoxins)
Invasive (first, the micro-organism enters the mucosal surface).
Invasive bacterial diarrhea is characterized by a dysenteric syndrome:

bloody mucoid diarrhea, urgency, fever, intestinal colic, and multiple
polymorphonuclear leukocytes in feces.
Travelers Diarrhea
Toxigenic Bacterial Diarrhea (noninflammatory diarrhea) (Table 4)
LPrototype micro-organisms in this group are Clostridium perfringens,
Staphylococcus aureus, Vibrio (V. cholerae and V. parahaemolyticus),
Bacillus cereus, Salmonella, Clostridium botulinum, Shigella and enterotoxigenic Escherichia coli.
14
Travelers diarrhea is the most common illness aecting travelers. It is

not caused by a specific organism, but Escherichia coli is the most common enterotoxigenic agent. Shigella species cause approximately 10%
of cases.
Diarrhea caused by Shigella is sometimes more severe than usual. Campylobacter strain appears in 41% of cases.
It is acquired by ingestion of feces-contaminated water or food. Food
constituting special risk includes undercooked vegetables, meat and
seafood, as well as water, ice, unpasteurized milk and dairy products,
and unpeeled fruits.
tries, and become diseased during the visit to that country or soon after
having returned), pseudomembranous colitis and cholera.
Remember
Post diarrheal episodes may be because of a transient lactase deficiency
Clinically, this diarrhea starts the second or third day after it is acquired.
Average duration in nontreated subjects is three to five days. Watery
diarrhea and abdominal cramps are the most frequent symptoms.
Diagnosis
Given the limited progression of this illness, a diagnostic study is required only in patients with very high temperature, severe signs or
sanguineous diarrhea patients who traveled abroad recently, immunosuppressed patients or in case of food poisoning. This study consists in evaluating the presence of fecal leukocytes, stool cultures,
and sometimes, of blood cultures. If diarrhea persists over 10 days
and invasive diarrhea is suspected, a rectosigmoidoscopy may be conducted.
Remember
Diagnostic-therapeutic gestures are regarded as necessary in severe clinical
pictures (as sanguineous diarrhea or severe dehydration) which pose a vital
threat.
The following patients must also be treated with antibiotics, regardless

of the cause of infectious diarrhea: patients severely clinically aected,
immunocompromised patients, patients with tumors, with a prosthetic
cardiac valve or any type of intravascular prosthesis, patients with hemolytic anemia and the elderly.
Antidiarrheal drugs (loperamide and codeine are the most used) must
be avoided upon suspicion of an enteroinvasive agent or severe ulcerous colitis. Bismuth subsalicylate may prevent infection by enterotoxigenic E. coli, and furthermore, produces symptomatic relief in patients
with infectious watery diarrhea, irrespective of whether the cause is
bacterial or viral.
Remember
Antidiarrheics should be restricted in the context of a possible infectious
diarrhea.
Viral Diarrhea
Differential diagnosis
Virtually any drug may produce diarrhea. Toxins such as organphosphate
insecticides, caeine among others, may cause diarrhea. Acute diverticulitis seldom appears with diarrhea, fever and abdominal cramping.
In case of bloody diarrhea, intestinal vascular problems, drug-induced
colitis and intestinal chronic inflammatory disease must be considered
(among the most frequent episodes).
The main pathogens of humans may be grouped into five categories: rotavirus, enteric adenovirus, calicivirus (Norwalk virus included), astrovirus
and torovirus (Table 5). In most cases, viral diarrhea is self-limiting and
only requires symptomatic treatment.
Diarrhea because of intestinal protozoa

Entamoeba Histolytica (Figure 16)
Treatment
Treatment includes rest and hydration. Replacement of lost fluids may
be orally or intravenously, depending on the clinical situation.
It must be taken into account that preparations may vary according to
their composition. The recommended preparation by WHO for oral rehydration contains the following (expressed in millimole/liter): 111 glucose, 60 sodium chloride, 20 potassium chloride and 30 sodium bicarbonate, osmolality being 331mOsm/kg.
The use of fluids and electrolytes is appropriate for acute diarrhea produced by enterotoxigenic bacteria. In cases of moderate diarrhea, ingestion may not be interrupted and an adequate caloric intake, if tolerated, must be assured. Ingestion of lactose food must be temporarily
suspended in case a transient lactase deficiency occurs.
Administration of antibiotics is controversial, and generally not necessary. However, antibiotics must be considered for Shigella diarrhea,
travelers diarrhea (acute diarrhea in people who travel to other coun-
It is an anaerobic parasitic protozoan with amoeboid shape as its names

indicates- part of the genus Entamoeba. It is pathogenic for humans
and canines causing amebiasis and amebic liver abscess. As most infections, it is frequent in developing countries due to their socio-economic
conditions. The life cycle of this protozoan is simple and involves two
stages: infectious cysts and trophozoites. Cysts are relatively resistant to
chlorine disinfection and to desiccation, and survive under wet conditions for many weeks. Infection is caused by swallowing cysts deriving
from food or contaminated water. Around 90% of infected individuals
become asymptomatic carriers of the cyst. In the remaining 10%, trophozoites invade colonic epithelium in the gut lumen and cause colitis.
Trophozoites gaining access to the bloodstream may disseminate to create an infection in distant locations (most frequently liver abscess).
Clinically, the infection may progress in three ways:
90% of individuals remain asymptomatic.
10% shows invasive amebiasis characterized by dysentery (amebic
colitis: gradual-onset diarrhea with abdominal cramps, urgency,
weight loss and fever).
15
VIRUS
EPIDEMIOLOGY
CLINICAL PRESENTATION
DIAGNOSIS
Rotavirus
Severe diarrhea in infants and small children
Dehydrating diarrhea for five to seven days.

Very common vomiting and fever
Immunoassay and electron

microscopy
Calicivirus
Pediatric diarrhea associated with fish and

seafood and other food in adults
Similar to rotavirus

microscopy
Enteric
adenovirus
Endemic diarrhea in infants and small

children
Prolonged diarrhea for 5-12 days,

vomiting and fever

microscopy
Astrovirus
Pediatric diarrhea and diarrhea in the

elderly
Aqueous diarrhea with a duration

of two to three days

microscopy
Torovirus
Acute and persistent pediatric diarrhea.

It occurs in communities and hospital
environment
Aqueous dehydrating diarrhea, on some

occasions, sanguineous with vomiting
and abdominal pain. Duration 5-7 days

microscopy
Table 5. Epidemiologic characteristics, clinical presentations and diagnosis of the main pathogens in the human being
Giardia lamblia (Figure 17)
Ingests contaminated food and water

with tetranucleotide cysts
Man with poor
hygiene habits
Once food is ingested, cysts membrane softens because of

gastric juices and trophozoites being formed
They contaminate
water and food
in the environment
Trophozoites invade
large intestinal mucosa
where they multiply
Trophozoites
are destroyed
in the environment
while cysts are resistant
Causing dysenteric
diarrhea
Cysts and trophozoites

are excreted through
the host's feces
Some trophozoites
transform in cysts
and can cause

extraintestinal
invasions
Liver
Lung
Brain
It is a flagellated protozoan parasite

causing diarrhea by malabsorption.
This parasite attaches to the epithelium of the proximal small intestine
(with no evidence of mucosal invasion). In a biopsy, anatomopathologic
changes vary from a normal aspect
(except for adherent trophozoics) to
intense atrophy of intestinal villi. The
severity of diarrhea appears to correlate with the intensity of histologic
changes. Immunologic response of the
subject is crucial to limit the severity of
giardiasis.
Figure 16. Entamoeba histolytica cycle
In the minority of cases, extraintestinal illness is present (the most

frequent is amebic liver abscess).
Diagnosis with microscopic examination of stool samples reveals low sensitivity (30% to 60%). Serum antibodies are detected in 92% to 97% of
patients. The first-choice diagnosis is colonoscopy with biopsies.
The treatment is classified into:
Luminal amebicides: paromomycin, iodoquinol, diloxanide furoate.
Tissue therapy: metronidazole, tinidazole, eritromicine and chloroquine. Metronidazole has the greatest healing rate (> 90%).
Since almost 10% of asymptomatic patients will develop invasive illness,
they must receive treatment. In case of noninvasive illness, treatment
with only one luminal agent is appropriate. Patients having amebic
colitis must be treated orally with metronidazole (such as paromomycin) followed by a luminal agent in order to prevent recurrent infection
(Table 6).
16
Cysts ingested by
susceptible host
in contaminated food
Excystation and colonization

of trophozoites in duodenum
Excreted cysts
into the environment
through feces
Reservoir hosts
(Beaver, monkey, otter,
cat and dog are often
involved as potential reservoirs.
Figure 17. Life cycle of Giardia lamblia
AMEBICIDE
AGENT
ADVANTAGES
DESADVANTAGES
in most patients. There are three well dierentiated types of ascariasis:

pulmonary, intestinal and hepatobiliary.
Luminal amebicides
Paromomycin
Cycle of seven
days treatment
It may be useful
during pregnancy
Frequent GI disorders
Ototoxicity (rare)
Iodoquinol
Economic
and effective
Cycle of 20 days
treatment
It contains iodine
Neuritis (rare)
Optical atrophy
with prolonged use
Diloxanide
furoate
Only for massive intestinal disease
Tetracyclines
and
erythromycin
Inactive in liver
abscesses
Frequent GI disorders.
Tetracyclines must
not be administered
to children or pregnant
women
Only for massive intestinal and extraintestinal diseases

Metronidazole
Drug of choice
for amebic colitis
and liver abscess
Anorexias, nausea, vomiting

and metallic taste in almost
one third of patients at used
doses
Similar reaction to that of
disulfiram with alcohol
Convulsion (rare)
Chloroquine
Only useful
for amebic
liver abscess
Occasionally, headaches,
pruritus, nausea, alopecia
and myalgias
Rarely, cardiac block and
irreversible lesion in the
retina
Table 6. Amebic agents: advantages and disadvantages

Clinically, it ranges from asymptomatic infection to severe chronic diarrhea with malabsorption.
In diagnostic made with samples directly taken from duodenal contents, sensitivity to 80%.
Metronidazole is the first-choice treatment (250 mg, oral administration, three times a day, for five days) and it is eective to eradicate Giardia in 80% to 95% of the cases.
Intestinal Helminth Infections

These infections are divided into nematodes, cestodes -or tapewormsand trematodes -or staves.
Pulmonary ascariasis develops 4-16 days after ingestion. An alveolar inflammatory response occurs and causes pneumonia. A large number of
parasites may produce severe intestinal symptoms, such as intestinal
obstruction. Diarrhea may occur, although it is not common. If worms
migrate from the intestine through the papilla, they may cause biliary
symptoms (colics, jaundice, cholangitis, and pancreatitis). It is diagnosed by visualization of the eggs directly extended over feces. Treatment consists in administration of albendazole (400 mg, single dose,
orally).
Strongyloides stercolaris penetrates intact human skin. As a parasite,
it lives in the intestine where it deposits eggs which mature as long as
they remain in the intestine. Larvae develop inside the intestine, and
migrate and mature to increase the number of adult parasites. Most
patients do not present intestinal symptoms; rather, they may have a
serpiginous urticarial rash caused by fast dermal tissue migration. At
times, patients have nausea, abdominal cramps or fecal occult blood.
This parasite is diagnosed by determination of IgG antibody against S.
stercoralis by ELISA. Ivermectin (200 g/kg oral single dose) is the drug
of choice for treatment.
Trichuris trichiura, also frequently called whipworm, is a global worm.
Human beings acquire it by ingestion of embryonated eggs. Most individuals do not present symptoms, even though infection with a large
number of parasites is associated with a syndrome similar to dysentery.
The diagnosis method involves identifying whipworm eggs in a stool
sample. Mebendazole (100 mg, twice a day for three days) is the drug
of choice for treatment.
Species of Trichinella. Trichinosis is a systemic disease caused by any of
the five species related to Trichinella. The parasite is acquired by ingestion of larvae in raw or undercooked meat from animals. Both the intestinal phase and the systemic phase are characterized by nausea, diarrhea, fever, myalgia and periorbital edema. Trichinosis may cause death
because of intense symptoms such as myositis, neuritis and thrombosis.
It is diagnosed by stool examination or by intestinal biopsy. Treatment
may consist of administration of albendazole (400 mg per day, for 3
days) or mebendazole (200 mg per day, for five days) and glucocorticoids (which reduce inflammation and systemic symptoms).
Cestodes or Tapeworms
Taenia saginata and Taenia solium. Colonization occurs as a result of
ingestion of raw or undercooked meat infected with cysts. Most colonized individuals remain asymptomatic. Cysticercosis is the most severe T. solium infection. Eggs penetrate the intestine wall, disseminate
through the body and cause cysticercosis, which may result in localized inflammation in the brain, spinal cord, eyes and heart. Diagnosis
involves identification of the eggs in stool samples, and treatment requires praziquantel (10 mg/kg oral single dose). Patients having cysticercosis must be treated with albendazole (5 mg/kg every eight hours
for one to four weeks).
Nematodes
Trematodes
Ascaris lumbricoides is the largest worm colonizing human beings. It is
ingested by eggs laid into contaminated soil or by raw vegetables irrigated with contaminated water. This worm does not produce symptoms
Most intestinal trematodes aect a wide spectrum of subjects and include more than 50 dierent species able to colonize humans. Patients
17
having these worms are asymptomatic. Diagnosis requires finding eggs

in stool. The patient is treated with praziquantel (25 mg/kg oral administration every eight hours for one day).
PATHOGEN
Table 7 and Table 8 summarize the pharmacologic treatment and

clinical and epidemiologic characteristics of the dierent pathogens.
RECOMMENDATIONS FOR ADULTS
Shigella spp
Ciprofloxacin, 500 mg, twice a day. Treatment one to three days

Alternative: trimethroprim/sulphamethoxazole 800/160 mg twice a day
Salmonella spp
Trimetroprim/sulphamethoxazole 800/160 mg; ciprofloxacin 500 mg, twice a day, for five to seven days
species no typhi
E. coli
Ciprofloxacin, 500 mg, twice a day. Treatment 1-3 days

Alternative: trimethroprim/sulphamethoxazole 800/160 mg for seven days
Yersinia spp
Doxycycline, 300 mg and aminoglycosides

Alternative: trimetroprim/sulphamethoxazole
Vibrio cholera
Single doses of doxycycline, 300 mg. Tetracyclines, 500 mg, four times a day for three days
Alternative: ciprofloxacin, single dose
C. difficile
Metronidazole, 250 mg, four times a day (up to 500 mg), three times a day for 10 days
Giardia spp
Metronidazole, 250 to 500 mg, three times a day for 7-10 days
E. hystolytica
Metronidazole, 500 mg, three times a day for 5-10 days plus Iodoquinol, 650 mg three times a day for 10 days
Salmonella thypi
Ciprofloxacin, 500 mg, twice a day for 5-10 days, ceftriaxone 1-2 g/day for 10 days
Bismuth subsalicylate in suspension is suggested in noncomplicated, mild-moderate acute diarrheas: 10 mL orally,
every four hours and an additional 10 mL after each evacuation
Loperamide, a 2 mg-tablet every eight hours
Table 7. Pharmacologic treatment of dierent pathogens
PATHOGEN
EPIDEMIOLOGICAL
CLINICAL FINDINGS
FEVER
ABDOMINAL
PAIN
BLOOD
IN
EVACUATIONS
NAUSEA
AND
VOMITING
LEUKOCYTES
IN FECES
Salmonella sp.
Fecal-oral transmission,
community acquired
Present
Present
Present
May occur
Present
Variable
Campylobacter sp.
Badly cooked chicken

consumption,
community-acquired
Present
Present
Present
May occur
Present
Variable
Shigella sp.
Person to person,
community- acquired
Present
Present
Present
Present
Present
Variable
C. difficile
Nosocomial infection
May
occur
May occur
Present
NC
Present
May occur
Vibrio sp.
Seafood intake
Variable
Variable
Variable
Variable
Variable
Variable
E. histolytica
Trips to tropical
regions
May
occur
May occur
Variable
Variable
Variable
Present
Crytosporidium sp.
Transmission
through water and
immunocompromised
people
Variable
Variable
Not present
May occur
NC
NC
Giardia sp.
Day care facilities,

asylums and IgA
deficiency
NC
Present
NC
May occur
NC
NC
Norovius
Sprouts during winter.

Day care and asylums
Variable
Present
NC
Present
NC
NC
Table 8. Clinical and epidemiologic characteristics of dierent pathogens
18
HYDROELECTROLYTIC
IMBALANCE
Chronic diarrhea
It is diarrhea that persists for weeks or months, either continuously or
intermittently. Pathophysiologically, it can be divided into osmotic diarrhea, secretory diarrhea, inflammatory diarrhea, diarrhea by altered
intestinal motility and factitious diarrhea.
Osmotic diarrhea. It is caused by the accumulation of nonabsorbable solutes in the intestinal lumen. Osmotic diarrhea stops when
the patient fasts and solute gap of fecal fluid increases [solute fecal
osmolality gap = -2 (Na++K+)]. An exception is congenital chloridorrhea, wherein the chlorine concentration in feces exceeds the sum
of the concentration of sodium and potassium. Causes of osmotic
diarrhea can be grouped into:
Ingestion of substances that are poorly absorbed, such as mannitol, sorbitol, magnesium laxatives, lactulose, etc.
Lactase deficiency and glucose-galactose malabsorption.
Steatorrheic diarrhea. It occurs because of intraluminal maldigestion (pancreatic and bacterial overgrowth), malabsorption of intestinal mucosa (celiac, Whipple, ischemia) or lymphangiectasia.
Secretory diarrhea. Secretory diarrhea is clinically characterized by
large volume stool and watery stool (over a liter a day) and diarrhea
that persists despite fasting. The osmolality of stool is normal. Examples of secretory diarrhea are the following:
Diarrhea induced by enterotoxin, as in cholera infection or E. coli
enterotoxigenic infection.
Tumors secreting hormones such as serotonin, histamine, catecholamines, prostaglandins and kinins in carcinoid syndrome, gastrin in
Zollinger-Ellison syndrome (because the eect of the large volume
of acid secretion prevails despite the fact that steatorrhea is present); VIP, PP, secretin and others in pancreatic endocrine tumors;
calcitonin in medullary thyroid carcinoma; histamine in systemic
mastocytosis. The somatostatinoma produces pancreatic synthesis
inhibition, steatorrhea and, therefore, osmolar diarrhea.
Diarrhea caused by bile acids not reabsorbed and that, when passing through the colon, act by increasing the secretion of the colonic
mucosa. This occurs in the case of a disease by ileal resection, in the
case of a selective defect of ileal transport or in bile acid malabsorption seen in postcholecystectomy or postvagotomy.
The diarrhea as a result of rectal villous adenoma or large size
sigma.
Diarrhea by altering gut motility. There are, among others: irritable bowel syndrome, diarrhea postvagotomy syndrome, diarrhea
of diabetic neuropathy, hyperthyroidism and diarrhea dumping
postgastrectomy syndrome dumping and diarrhea. Regarding motility disorders, bacterial overgrowth may develop.
Inflammatory diarrhea. Typical of ulcerative colitis, Crohns disease,
radiation colitis, eosinophilic gastroenteritis or associated with AIDS.
Diarrhea factitious. It is a self-induced diarrhea, more common in
women. Usually watery, hypokalemia, weakness and edema. Laxative abuse is the most common cause. Patients mostly deny having
taken laxatives, and sometimes, the only data giving account of the
episode is the presence of psychiatric illness or melanosis coli in
lower endoscopy.
Diagnosis
In general, diarrheas by alteration at the level of the small bowel or
right colon are large in volume, while those from the left colon are
small in volume and require urgency. Bloody diarrhea suggests inflammation. Diarrhea with mucus without blood suggests irritable colon,
as well as a history of small volume diarrhea alternating with constipation.
Certain criteria suggest an organic and nonfunctional disorder, such as:
diarrhea of short duration (generally within three months), predominantly nocturnal diarrhea, continuous rather than intermittent, sudden
onset, loss of more than 5 kilos, elevated sedimentation rate, low hemoglobin, low albumin level, or daily weight of stool over 400 grams.
Often chronic diarrhea is accompanied by incontinence. Furthermore,
some patients are studied in depth as a result of suspected chronic
diarrhea, and incontinence is only diagnosed. Diarrhea in a patient assumed to suer from anorexia nervosa suggests laxative abuse
Treatment
It is specific depending on each etiology.
3.3. Malabsorption
Clinical Findings
Symptoms usually include diarrhea, weight loss and malnutrition.
These, along with variable abdominal discomfort and bloating, are the
most common symptoms. In addition, there are symptoms and signs
arising from the lack of certain specific nutrients, depending on the type
of disease and the aected segment. The same applies to laboratory
data, although the presence of hypoalbuminemia and hypocholesterolemia and electrolyte disturbances of sodium, potassium, magnesium,
chlorine, acid - base, a decreased in calcium, phosphorus and zinc is
quite common.
Causes of Malabsorption
Maldigestion: exocrine pancreatic insuciency, gastric surgery, gastrinoma.
Decreased concentration of bile salts: liver disease, bacterial overgrowth, ileal disease or resection.
Abnormalities of the intestinal mucosa: disaccharidase deficiency,
impaired transport of monosaccharides, folate or cobalamin deficiency, nontropical sprue, nongranulomatous jejunoileitis, amyloidosis, Crohns disease, eosinophilic enteritis, radiation enteritis,
abetalipoproteinemia, cystinuria and Hartnup disease.
Decrease in the absorbing surface: short bowel syndrome and jejunal ileal bypass.
Infection: tropical sprue, Whipples disease, acute infectious enteritis and parasitic infections.
Lymphatic obstruction: lymphoma, tuberculosis and lymphangiectasia.
Cardiovascular disorders: congestive heart failure, constrictive pericarditis, mesenteric vascular insuciency.
Induced by drugs: cholestyramine, neomycin, colchicine, phenindione and laxatives.
Unexplained: carcinoid syndrome, diabetes mellitus, adrenal insufficiency, hyper and hypothyroidism, systemic mastocytosis and hypogammaglobulinemia.
19
Diagnosis of Malabsorption
Test of fat malabsorption. Although there may be malabsorption
of specific nutrients, most patients with clinically significant malabsorption have steatorrhea, and therefore, a quantitative test
is fundamental. The best screening test for malabsorption is the
quantification of fecal fat in 24 hours. A total of 7 g or more fecal
fat per 24 h is considered pathologic. A qualitative study of fecal fat
(Sudan staining) may be performed as it is easy and inexpensive,
but it can give false negatives when steatorrhea is mild.
Test D-Xylose. Xylose administration after patient fasted, six-hour
urine collection and serum sample at the time of xylose administration. This type of sugar is absorbed passively provided the bowel
wall is intact and undamaged: mostly proximal jejunum and ileum.
It does not detect small changes.
D-xylose is absorbed in the jejunum by passive diusion. It is not
normal when the jejunum is aected. Its use is declining because of
a high false negative rate, especially if bowel injury is not extensive.
False positives in bacterial overgrowth, in renal failure, in the elderly
and in patients with ascitis may result.
Determination of fecal alpha-1-antitrypsin. It is useful upon suspicion of a protein losing enteropathy, although iv injection of albumin labeled with chromium remains referential.
Test of urinary excretion of bentiromide. Bentiromide is a synthetic peptide bound to the PABA. That bond is easily split by chymotrypsin. Bentiromide is administered orally, PABA is absorbed in the proximal intestine,
partially conjugated in the liver and excreted by urine as arylamines. Excretion as arylamines in a 6-hour urine test of less than 50% of that ingested as bentiromide is virtually a diagnosis of pancreatic insuciency.
If this is normal, exclude pancreatic insuciency. This is not assessable
if creatinine is greater than 2 mg/dL. With apparent basis, but with another molecule, the pancreolauryl test is performed.
Test of secretin-cholecystokinin. Although they are dicult to perform, they are the most sensitive and specific tests of exocrine pancreatic insuciency. The extreme of a fluorosopically guided tube
is placed on the second portion of the duodenum towards Wirsung
exit. A hormone is administered intravenously and the component of
pancreatic secretion is measured (bicarbonate after secretin; trypsin,
amylase and lipase after cholecystokinin). It is the test for earliest detection of incipient chronic pancreatitis, since it identifies alterations
in cellular synthesis long before the pancreatic ducts fibrosis occurs.
Cobalamin absorption test. It is the Schilling test, there are several steps
in order to correctly detect whether the alteration of absorption is because of a pancreatic or gastric problem, bacterial overgrowth or ileal
disease.
Breathing tests. Respiratory tests are based on the ability of bacteria
to ferment a substrate: lactulose, glucose or xylose. If there are several bacteria, it ferments more. More hydrogen is produced, which
is exhaled in larger amounts than in breath.
Respiratory test of lactose-H2: It is basically used for the diagnosis of lactase deficiency.
Respiratory test of xylose marked with C14: It is very useful for
the diagnosis of bacterial overgrowth.
Respiratory test of lactulose-H2: it can also be used for diagnosing
bacterial overgrowth. There is also a test of oral glucose in breath.
Respiratory test of bile acids labeled with carbon 14 (14C-Coliglicine): it is also used for the diagnosis of bacterial overgrowth
and to diagnose malabsorption of bile acids. For the latter diagnosis the test of abdominal retention of 75 selenium-homotaurocolato (SeHCAT) may also be used.
20
Respiratory Test of triolein labeled with carbon 14: It is a test

that correlates well with the degree of steatorrhea.
Culture of intestinal aspiration. The proximal intestine of normal
subjects have fewer than 105 organisms per milliliter of jejunal fluid,
which are usually streptococci and staphylococci, and occasionally
coliforms or bacteroides.
The ileocecal area is a transitional area with qualitative and quantitative
changes to the pattern of the colon. In the colon, there is an increase in
aerobic and anaerobic bacteria, predominantly anaerobes and coliforms.
In bacterial overgrowth of the small intestine, this adopts a flora
similar to the colons. Cultures should be suspected if there are more
than 103 organisms per milliliter, being clearly abnormal if more
than 105 is clearly anbormal, and even more if there are anaerobes.
Radiology. All patients with malabsorption should have a radiographic study of the small intestine. Traditional radiologic findings
suggesting malabsorption include barium flocculation and fragmentation and segmentation of the barium column. However, these patterns are more dicult to demonstrate today because of the use of
barium products containing nonflocculating suspension. Since the
radiographic findings are often nonspecific, the most important current value of radiologic study is the location of the injury. In this
regard, the study by enteroclysis increases eciency.
Intestinal biopsy. Today, most intestinal biopsies are obtained by
endoscopic procedures. Situations in which biopsy is always diagnostic are abetalipoproteinemia, hypogammaglobulinemia and
Whipples disease.
3.4. Disaccharidase Deficiency

Lactase deficiency is the most common disorder of nutrient assimilation.
Furthermore, any disease that impairs enterocyte can result in a secondary deficiency. These patients are intolerant to milk or dairy products, experiencing bloating, abdominal pain and osmotic diarrhea. Diagnosis is by
clinical history and the breath test lactose -H2. Lactase activity in the biopsy may also be measured by immunohistochemical methods, considering
that the microscopic appearance is normal. Treatment is lactase (derived
from Aspergillus oryzae), which is commercially available. There are other
much rarer deficits of disaccharidases such as sucrase-alpha-dextrinase
deficiency and glucose-galactose malabsorption.
3.5. Carcinoid Syndrome

Carcinoid tumors are most often located in the ileum and appendix and
they produce serotonin.
Clinically, these tumors cause skin redness, diarrhea, abdominal pain
and involvement of the right heart valves.
It is diagnosed with urinary levels of 5-hydroxyindoleacetic (which are
high). This confirms the tumor existence and it requires the performance of octreoscan to locate it.
Treatment includes the use of octreotide and surgery.
3.6. Irritable Bowel Syndrome

De inition
It is the most common gastrointestinal disease. It is characterized by
alterations in bowel habits, constipation or diarrhea, and abdominal
pain in the absence of detectable structural abnormalities. Although it
was initially thought that the condition was limited to the colon, it is
now known that there may be similar disturbances at other levels of
the digestive tract.
Physiopathology
Biochemical, microbiologic and histologic alterations have not been
proven. These patients may have abnormalities in motor and myoelectric
activity of the intestine, although its exact role is unknown, since they
do not appear in all patients nor they justify the entire clinical spectrum.
A decrease in the threshold for induction of spastic contractions is also
detected after rectal distention. The most common finding is abnormal
perception of physiologic intestinal motor activity (visceral hyperalgesia)
clinically translated as pain, meteorism or other sensations.
Symptoms
Abdominal pain, with constipation, diarrhea or both, in alternating periods. Symptoms begin in adults. The most common clinical finding is a
change in bowel function. Usually constipation alternating with diarrhea,
one of the two predominating symptoms over time. Constipation may
become intractable. Patients usually have hard stools, of small size and a
feeling of incomplete evacuation Low-volume diarrhea is (< 200 mL), it is
aggravated by emotional distress or food. It does not occur at night and it
may be accompanied by large amounts of mucus. There is no malabsorption, weight loss and blood, unless there is an accompanying process such
as hemorrhoids. Abdominal pain is variable in intensity and localization.
It is usually occasional and does not alter sleep. It is often exacerbated by
emotional distress or meals and is relieved with defecation or by eliminating gas. Patients with irritable bowel syndrome often complain of flatulence, bloating, and a significant percentage report upper gastrointestinal
symptoms such as nausea, vomiting, indigestion or heartburn. Physical
examination should be normal. Patients usually present anxiety or depression disorders.
Diagnosis
The absence of pathognomonic features would lead to a diagnosis
of exclusion. To facilitate diagnosis and to reduce the need for costly
multiple scans, a panel of diagnostic criteria that define IBS has been
developed (Table 9). Despite these criteria constituting a reliable-oriented diagnosis, the similarity of some of the symptoms with those of
organic disease must be considered (Table 10). The appearance in an
elderly patient, progression of the symptoms, persistent diarrhea after
48 hours of fasting, and the presence of nocturnal diarrhea or steatorrhea would be against the diagnosis of irritable bowel syndrome. It is
recommended that all patients have a complete blood count and full
biochemical study for all patients as well as thyroid function tests, stool
culture and search for parasites in feces. In patients over 40 years of
age and in all patients with predominant diarrhea, sigmoidoscopy, and
sometimes barium enema should be performed. If diarrhea is predomi-
nant, lactase deficiency should be investigated. In patients with dyspepsia, radiologic EGD or upper tract study is recommended. In patients
with postprandial pain in the right upper quadrant, an ultrasound of
the gallbladder is recommended. Some laboratory data that would go
against the diagnosis of irritable bowel may be: anemia, leukocytosis,
elevated sedimentation rate, blood in stool or volume of stool above
200-300 mL/day.
ROME III DIAGNOSTIC CRITERIA FOR IBS

During the last three months, the patient must present continuous
or recurrent abdominal pain or discomfort, for a minimum of three
days, associated with two or more of the following symptoms:
It improves with defecation
It is associated with a change in the frequency of depositions
It is associated with a change in the feces consistency
Table 9. Rome III Diagnostic criteria

for irritable bowel syndrome
ALARM DATA IN IBS
Weight loss, anemia, rectorraghias, positive hidden blood in feces

Increase in ESR
Fever
Record of stays in countries where there are endemic parasite
diseases
Nocturnal symptoms presentation
Symptomatology onset at age > 50
Family record of colon cancer
Family record of inflammatory intestinal disease
Family record of celiac disease
Presence of dermatitis or arthritis during physical exploration
Table 10. Clinical alarm data in irritable bowel syndrome
Treatment
A good doctor-patient relationship is vital. The patient should be reassured
and the doctor should explain the disease: symptoms are longstanding,
but not life threatening; rather, they are paroxysmal and generally they
improve over time. If symptoms are exacerbated by any food, it wil be
recommended to remove it from the diet. For constipation, diets rich in
fiber and laxatives increasing stool volume are useful. In patients with abdominal cramping, anticholinergic may be useful used before meals and
amitriptyline antidepressants or anxiolytics during exacerbations. In periods of diarrhea antidiarrheal loperamide or diphenoxylate will be used
temporarily. In severe cases, alosetron (receptor antagonist of serotonin)
and fedotozine (kappa opioid analogue) are being used as analgesics.
3.7. Inflammatory Disease

Symptoms and Diagnosis
In ulcerative colitis, symptoms depend on the extent and severity of the
inflammation. The fragility of the mucosa causes bleeding easily, which
explains why rectal bleeding usually occurs. Patients with proctitis have
rectal bleeding, urgency and passage of mucus and pus. The stool con-
21
sistency is variable, and patients may even be constipated. The longer

the involvement, the more likely diarrhea will be usually bloody.
Upon increased severity of inflammation, the more likely the occurrence of systemic symptoms such as fever, malaise, nausea and vomiting. Abdominal pain, which is usually mild, colic and relieved by defecation is not a frequent finding. In periods of remission, the patient
generally continues eliminating mucus in the stool. Genrally, the most
common sign or symptom is bloody diarrhea. Laboratory data reflects
its severity, with a possible increase in acute phase reactants, iron deficiency anemia and hypoalbuminemia.
The diagnosis is set when is demonstrated, in a patient with suspicious
symptoms, endoscopic signs typical of the disease and compatible histologic data are aproved, in turn rejecting other episodes of specific
etiology. Flexible sigmoidoscopy is the method of choice, but a subsequent complete colonoscopy is required to evaluate the extent and,
in some cases, to make it easy to dierentiate it from Crohns disease.
In Crohns disease, the symptomatology depends on the organ aected. In
this case of gastroduodenal involvement, the symptoms may be similar to
that of a peptic ulcer. With small bowel involvement, abdominal pain and
diarrhea appears. If the colon is aected, there may be abdominal pain and
bloody diarrhea. Transmural inflammation leads to fibrosis, which may lead
to intestinal obstruction. Weight loss, by diarrhea or by malabsorption, is
more common in Crohns disease than in ulcerative colitis. Sometimes when
there is ileal involvement this is presented as pain in the right iliac fossa with
a mass. The presence of masses or plastrons is typical of this disease, reflecting the transmural inflammation, which can eventually produce abscess.
Figure 18. Ileal Crohns disease
The presence of fistulas, which can be enteroenteric, in the bladder, vagina, urethra, prostate, skin and often perianal is
also frequent. Fistulas may also lead to abscesses.
ULCEROUS COLITIS
CROHNS DISEASE
Most cases are associated with intestinal inflamLocalization
It starts in the rectum
50% does not affect the rectum. Any
mation, so treatment must be accompanied by
and extends proximally
other section of GIT, especially the
control of the inflammatory activity. Perianal disterminal ileum and right colon
ease is specifically characterized by the presence
Macroscopy
Continuous
Segmentary
of simple or complex fistulas that require specific
Thinned
wall
Thickened wall
medical-surgical, treatment will be discussed later.
Diagnosis is based on endoscopic findings: erythematous mucosa and aphthoid transverse and
longitudinal ulcers with cobblestone appearance
of inflammatory polyps. The barium study reveals edema, separation of loops, ulcers, fibrosis
and fistulas. CT is very useful to demonstrate the
existance of abscesses. Scan with leukocytes labeled with indium-111 is useful in assessing the
extent and the degree of activity. Acute phase
reactants have been used to monitor the activity of Crohn, including C-reactive protein, whose
levels are in good correlation with the activity
(whereas in ulcerative colitis, there is no good
correlation with the activity).
Final diagnosis is histologic in both diseases, although sometimes the findings can be misleading. Dierential diagnosis includes several infectious diseases, such as Mycobacterium avium, C.
dicile, C. jejuni or amebiasis.
22
Microscopic
Granular-like mucosa with ulcers

and pseudopolyps
Mucosa with cobblestone appearance
Superficial ulcers
Deep ulcers with fistulas and fissures
Only mucosa
Transmural
Nonspecific inflammatory infiltrate
Noncaseating granulomas (50%)
No
Lymphoid aggregates
Cryptic abscesses PMN
Rare
Clinical
presentation
Tenesmus
Sanguineous
Fever + diarrhea + abdominal pain

Palpable mass
Tobacco
Complications
Toxic megacolon
Perforation
Malignancy risk
Obstruction
Fistulas (perianal)
Associations
Gangrenous Pyoderma
Sclerosing cholangitis
Erythema nodosum
Sores
Oxalate calculus
Curative colectomy
Post surgery relapse
Lead pipe appearance
Garden hose appearance
X-ray
Table 11. Clinical-pathologic dierential diagnosis between ulcerous colitis and Crohns disease
Treatment
It is performed in both conditions with topical or oral 5-ASA, with corticosteroids, immunomodulators and biological therapies.
For refractory intestinal bowel disease treatment involves surgery.
Complications Associated with

In lammatory Bowel Disease
Intestinal Complications
Furthermore, biopsies of abnormal locations are suggested. New endoscopic techniques (such as chromoendoscopy combined with magnification endoscopy) benefit early detention of intra-epithelial neoplasia and dysplasia because of targeted biopsy. In case of pancolonic
involvement, screening must be initiated 8-10 years after the onset of
the disease; in the case of left colitis, it must be initiated 15 years after
onset.
Proctitis does not require follow-up because the risk of carcinoma is not
increased. Colonoscopy must be repeated every two years until reaching 20 years of progression of the disease, and every year thereafter.
Additionally, there seems to be a protective eect of sulphasalazine and
other 5ASA.
Rectal Bleeding
Control is attempted with an endoscopy or embolization by arteriogram. If these procedures fail, colectomy is the indicated alternative.
Toxic Megacolon
This complication may appear in any inflammatory disease aecting the
colon, more frequent in ulcerative colitis. It appears in 5% of patients. This
complication is quite severe and causes colon dilation associated with
increased abdominal pain, distension -with or without peritonitis symptoms- fever, tachycardia, dehydration and a decrease in intestinal murmur.
Even in the absence of significant colon dilation, similar symptoms serve to
diagnose severe colitis with an identical risk of rupture. Precipitating circumstances include severe colitis, barium or endoscopic studies in severe
colitis, potassium depletion or the use of anticholinergic drugs or opiates.
Toxic megacolon must be suspected in patients with severe colitis, which
is diagnosed by dilatation of more than 6 cm in transverse colon (simple
abdominal x-ray). These patients require close monitoring with physical,
radiologic examination and repeated laboratory studies. If there is no improvement upon intense treatment with intravenous fluids, corticosteroids
and antibiotics covering anaerobics, treatment with infliximab may be conducted. If, however, no improvement is attained within 12 or 24 hours after administration, total colectomy must be conducted since morbility and
mortality in a perforation may exceed 20% of cases.
Perforation (rupture)
It occurs in approximately 5% of Crohns disease and may appear in
toxic megacolon.
Tumor Risk
There is an increased risk of collateral cancer in patients with EII with
colonic involvement. Risk factors include a prolonged duration of the
disease, extensive inflammatory involvement (especially in pancolitis), primary sclerosing cholangitis, and family background of collateral cancer. However, a correlation between the development of the
disease and the risk of neoplasia has not been demonstrated, but
the fact that most colectomies are performed in patients with active
disease constitutes a fundamental bias in this assessment.
Conventional endoscopy screening is recommended in clinical practice because it may early detect dysplasia and/or colorectalcarcinoma (CRC). A biopsy in the four quadrants of the colon every 10 cm is
also recommended, thus obtaining 30-40 biopsies.
High-dose aminosalicylates are used as first-line treatment in the induction and maintenance of remission due to their anti-inflammatory
eects. Their structure is similar to that of AAS: both have anti-inflammatory and anticarcinogenic properties with no relevant side eects,
whereby they are considered a good option for the prevention of CRC.
They also produce a delayed eect in the progression of dysplasia to
carcinoma. Patients with ulcerative colitis associated with primary sclerosing cholangitis have a high risk of cholangiocarcinoma and CRC. That
is why the first colonoscopy screening is performed by the time both pathologies are diagnosed, and it needs to be repeated annually. Ursodeoxycholic acid is a synthetic bile acid with low-toxicity for humans proven to be beneficial for the prevention of cholangiocarcinoma in primary
sclerosing cholangitis and for CRCassociated with cholangitis. Likewise,
folic acid deficiency is associated with carcinogenesis of many tumors,
including CRC, for which supplementary folic acid must be taken. There
is nearly a 50% probability of synchronic CRC in patients with a highgrade dysplasia. If that is the case, a case colectomy must be performed.
Whenever dysplasia is detected by a screening colonoscopy, biopsies
must be evaluated by a second phathologist to confirm diagnosis.
In patients with low-grade dysplasia, a meticulous endoscopic follow-up
must be performed every three to six months: If high-grade dysplasia
is detected in subsequent physical examinations, a colonoscopy will be
required. The observation of high-grade lesions morphologically similar to that of an adenoma leads to polypectomy and strict endoscopic
follow-up may be considered as treatment. For this purpose, it is necessary to assure complete resection and to prove absence of dysplasia
around the margins of resection. If some of these criteria are not met,
proctocolectomy is recommended (Figure 19).
In Crohn disease, there is an increase in colorectal adenomas and the
risk of adenocarcinoma of the small intestine, mainly in isolated segments, due to surgery or to the disease itself, through enteroenteric
fistulas.
Remember
The risk of colonic neoplasias in ulcerous cholitis is related to time

(maximum risk starts at 10 years course) and with lesions extension,
whereas in Crohn, although colonic carcinoma may be present,
neoplasias because of partial respective surgery or fistulas may occur.
Ileal affectation in Chrons disease can result in oxalate urolithiasis
secondary to calcium sequestration (saponification process) as a result
of unabsorbed fats.
23
Probiotics have demonstrated to be ecient in the maintenance of remission obtained with antibiotics and in the prevention of pouchitis.
Pancolitis with a duration of eight years or more

Left colitis with a duration of more than 15 years
Colonoscopy every one to two years, with three to four biopsies each 20 cm from
the cecum to the rectum. Biopsies of any suspicious lesion or mass (not adenoma)
Skin Manifestations
Without dysplasia
Low-grade
dysplasia
High-grade
dysplasia
Carcinoma
Every two years until

20 years course
Annual after 20 years
Monitor every three months
Confirm
2.nd pathologist
Colectomy
Figure 19. Prevention of colorectal cancer in IBD
Erythema nodosum. It is the cutaneous disorder most frequently seen and

it correlates with the activity of the disease. Erythemas appear as red nodules
located on the extensor surfaces of the
extremities. They respond to the treatment of the underlying disease or to
topic steroids. Erythemas appear more
frequently in Crohns than in ulcerative
colitis (Figure 20).
Pouchitis
Total proctocolectomy with ileal pouch-to-anal anastomosis and Jpouches procedure constitute the surgical treatment of choice for
ulcerative colitis. After the surgery, within a variable time frame, the
pouch undergoes a functional and morphologic adaptation process
(colonic metaplasia) by which a similar inflammatory process to that
of the original disease develops (pouchitis). The risk of developing
pouchitis 1, 5 and 10 years after surgery is 15%, 30% and 46%, respectively. The etiology of pouchitis is not clear, but it has been considered as an ulcerative colitis of the pouch in which bacteria development will play a significant role.
The most frequent symptoms include: an increase in the number
of water liquid stool, urgent bowel movements, abdominal cramps,
and pelvic discomfort. Endoscopy reveals edema, granularity, friability, loss of vascular pattern, mucosal swab and ulcerations. Biopsy
samples reveal acute inflammatory infiltrate (polymorphonuclear infiltrate, crypt abscess, ulcers and mucin depletion) or chronic inflammatory infiltrate (subtotal/total villous atrophy, crypt hyperplasia and
colic metaplasia).
Diagnosis requires the presence of symptoms as well as endoscopic
and histologic alterations typical of the disease.
The treatment can be:
Acute pouchitis (acute inflammation of the pouch with good response to conventional treatment with antibiotics):
Ciprofloxacin and metronidazole.
Budesonide.
Probiotics.
Figure 20. Erythema nodosum

Pyoderma gangrenosum. It is a severe necrotic ulcerative lesion
independent from the activity of the disease. It is more frequent
in ulcerative colitis Treatment consists of immunosuppressants.
Antibiotics and topic steroids are useful for treatment; intravenous
steroids and infliximab (IFX) may be needed Good respond is also
seen with sulfone (oral). Sometimes, resection of the aected intestinal segment is required. It must not be confused with ecthyma
gangrenosum (it is a good opportunity to review this lesion caused
by Pseudomonas).
Stomatosis and canker sores. Its presence is especially associated
with Crohns disease.
Ocular Manifestation
Chronic pouchitis (acute pouchitis with good response to conventional treatment with antibiotics, but with precocious relapse in less
than three months, whether the episode lasts more than four weeks
or two episodes of acute pouchitis occur per year):
Metronidazole and ciprofloxacin.
As an alternative:
Oral budesonide.
In refractory cases:
Infliximab.
24
Conjunctivitis, episcleritis, uveitis and iritis are generally associated with

the activity of the disease. Occasionally, uveitis associated with HLA-B27
may progress independently from the disease.
Hepatobiliary Complications
Cholestasis by cholesterol stones caused secondary to a reduction of
biliary salts in Crohns due to an impairment of the absorption of the
terminal ileum; steatosis by malnutrition; pericholangitis; sclerosing
cholangitis mainly associated with ulcerative colitis, but no association

with the activity of the disease.
Renal Complications
Renal urolithiasis because of dehydration or by oxalate, especially, in
Crohns disease, and in Crohns disease.
Osteoporosis and osteomalacia as a consequence of corticosteroid treatment and by a decrease in vitamin D and calcium absorption.
Peripheral arthritis in large joints, such as knees, elbows, ankles,
usually parallel to intestinal inflammation. It is an asymmetric arthritis, nondeforming and seronegative, which responds to the treatment of inflammation.
Axial arthropathy associated with HLA-B27 that progresses independently from the disease.
Hematologic Manifestations
Anemia is the most common manifestation. Most frequent types of anemia in ulcerative colitis are: iron deficiency anemia, anemia of chronic
disease, and multifactorial anemia.
Other manifestations include Coombs positive hemolytic anemia or deficiency of iron, folate or B12 vitamin in Crohns in both leukocytosis and
thrombocytosis.
Fertility, Pregnancy and Breastfeeding

There is no evidence of ulcerative colitis or inactive Crohns aecting
fertility. However, active Crohns disease may reduce fertility; this is
why remission improves the chances of conception. So, pregnancy in
patients with EII must be planned considering the remission periods of
the disease.
Reduction of Fertility. Causes:
Pelvic surgery in males may cause ejaculation problems or impotency.
Surgery (whether abdominal or pelvic) in females reduce fertility.
Sperm quality may be aected by sulphasalazine, methotrexate and
inflimax.
Drugs and Teratogenicity:
Methotrexate must be suspended six months before pregnancy.
Ciprofloxacin and metronidazole must be suspended three to six month
before pregnancy.
5-ASAs, corticosteroids, thiopurines and biological drugs may be administered during pregnancy.
There are some extra-intestinal manifestations of EII related to the
activity of the disease shown in Table 12.
RELATED TO
UNRELATED TO
DISEASE ACTIVITY
DISEASE ACTIVITY
Erythema nodosum
Ocular [except for HLA-B27(+)associated uveitis]
Ankylosing spondylitis
Gangrenous Pyoderma
Primary sclerosing cholangitis
Table 12. Extra-intestinal manifestations of IBD and its relation with

disease activity
Remember
Independent complications of EII:
Gangrenous Pyoderma (UC mainly).
Ankylosing spondylitis* (Crohn mainly).
Uveitis*.
Primary sclerosing cholangitis.
*Related to HLA-B27 haplotype (-)/(+)
3.8. Diverticular Disease

True diverticula (ie, numerous tiny pockets in the wall of the colon) in
the colon are rare; they are usually congenital, solitary, frequently located in the right colon and rarely become inflamed or perforated.
The term diverticulosis describes the presence of pseudodiverticula
(formed by mucosa, submucosa and serosa), which develops as a result of herniation of the mucosa because of overpressure of the weakest wall of the colon areas. This disorder is very common, detected
in up to 50% of people over 50 years of age. It is more frequent in
industrialized countries, probably related to low fiber diets. In 95%
of cases pockets are located in the sigma. They are usually asymptomatic. Sometimes they may present recurrent pain, but mostly, its
charactaristics suggest irritable bowel syndrome. Diagnosis is generally made on barium enema or colonoscopy performed because of
another diagnostic suspicion; if this disease requires research, barium
enema is the test of choice. Patients may be complicated by bleeding or swelling, which will result in diverticula disease of the colon. If
there are no complications, treatment is not required: only a fiber rich
diet is recommended.
Acute Diverticulitis
It is caused by inflammation of a diverticulum, and it frequently worsens,
aecting the peridiverticular contiguous area. It is caused by obstruction
of the lumen of the diverticulum by colonic material known as fecalito.
The obstruction facilitates the proliferation of bacteria and in turn, the
fecalito hinders irrigation, so that the inflamed diverticulum is susceptible
of perforation. In fact, for the existence of diverticulitis to be diagnosed,
microperforation must exist (which should not be confused with free
perforation in the peritoneal cavity, which determines a severe peritonitis). The inflammatory process varies from a small intramural or pericolic
abscess up to a generalized peritonitis. It is more common in males and it
occurs mostly in the sigmoid and descending colon.
Symptoms
Some attacks can be minimally symptomatic and resolve spontaneously. The typical clinical presentation consists of fever, pain in the lower
abdomen or left iliac fossa and signs of peritoneal irritation (Left appendicitis). In the acute phase, constipation and diarrhea are common,
and in 25% of cases there is bleeding, usually microscopic. In analytic
studies, leukocytosis with deviation to the left are seen. Complications
of acute diverticulitis include: free perforation with peritonitis, sepsis
and shock; localized perforation with abscess formation; fistulas to other organs (especially bladder); stenosis with obstruction of the colon.
25
3.9. Ileus
Diagnosis
Diagnosis in the acute phase is clinical. The most useful imaging test
at this stage is CT, which evaluates wall thickening or peridiverticular
abscesses. Once the acute phase is solved, colonoscopy or barium
enema may be conducted to show leak of barium, a stenotic area,
pericolic inflammatory mass or a complicated neoplasia.
Treatment
Treatment consists of bowel rest, intravenous fluids and antibiotics covering gram-negative and anaerobic micro-organisms. If the patient has a
small symptomatic pericolic abscess, the same treatment may be maintained. In abscesses larger greater than 5 cm or when the patient is entirely aected, cytology and drainage of the abscess guided by CT is recommended. Emergency laparotomy is indicated in case of purulent or faecal
peritonitis.
Programmed surgical treatment is indicated if there are repeated outbreaks in the elderly, and after the first outbreak in young patients.
Emergency treatment is reserved for the case of stenosis, uncontrolled
bleeding, perforation by peritonitis and sepsis). Conventionally, surgery is performed in two stages: resection and colostomy (Hartmann
procedure) with subsequent reconstruction of intestinal transit.
Currently, if the peritonitis is localized and the patient tolerates the surgery, there is a tendency to perform a resection and a primary anastomosis with intra-operative antegrade colonic lavage, to avoid colostomy
and the second intervention.
Diverticular Hemorrhage
It is the most common cause of massive lower gastrointestinal hemorrhage.
It occurs mostly in people over 60 years of age. In 70% of cases, bleeding
originates from a diverticulum of the right colon that is not inflamed (the
bleeding may be massive). In most cases, the bleeding stops spontaneously
and is not recurrent, in which case, no further treatment is needed. The use
of vasopressin can help stop the bleeding. It is recurrent in 20% of cases and
patients may need surgery or arterial embolization (Figure 21).
It is the generic name for the detention of the digestive tract, regardless
of the cause (paralytic or obstructive).
It is manifested by abdominal discomfort, nausea and vomiting along
with abdominal distension, and decreased or absence of peristalsis. Abdominal radiography shows dilated loops of small and large intestine
with gas accumulation, and fluids may appear if performed standing.
Types:
1. Paralytic or adynamic. It is caused by an aggression in the abdominal cavity or its borders. The most common cause is abdominal surgery (Postoperative ileus reflection). After surgery, the small intestine is the first to restore mobility after 24 h, followed by the stomach
(24-48 h), while the colon takes three to five days.
Other causes include lesions aecting the retroperitoneum, chest injuries (basal pneumonia, rib fracture), systemic causes (hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, anemia or acute septicemia), drugs (morphine and derivatives, anticoagulants, phenothiazines)
and conditions causing hyperactivity of the sympathetic nervous system.
Treatment involves gastric aspiration by tube, intravenous hydration
or nutrition and correction of electrolyte imbalance. If the subject
does not respond to conservative treatment, diagnosis should be
reconsidered and surgery will be required.
2. Obstructive or mechanical. See topic intestinal obstruction.
3. Spastic. It consists of uncoordinated intestinal hyperactivity heavy metal
poisoning, porphyria and uremia. Systemic disease should be treated.
4. Ileum of vascular occlusion. Uncoordinated mobility of the ischemic bowel.
See Figure 22.
Sigma wall inflammation secondary

to uncomplicated diverticulits
Figure 21. CT scan of uncomplicated diverticulitis (Hinchey I)
26
Figure 22. Hydroaeric levels: small intestine obstruction
3.10. Intestinal Obstruction

De inition
Intestinal obstruction occurs when there is an interference with the
normal progression of intestinal contents. There is a mechanical obstruction when there is a real physical barrier obstructing the lumen.
The most common site is the small intestine. It is said that there is a
closed loop obstruction when there is obstruction of the aerent and
eerent ends of a bowel loop.
Strangulation occurs when a blocked loop also has irrigation occlusion. Colonic obstruction usually occurs less dramatically, with less propensity to
choke, except in the volvulus; massive distension may occur when there is
a competent ileocecal valve; then the obstruction occurs a in closed loop.
Small Bowel Obstruction

Etiology
The most common cause of SB obstruction is adhesions, followed by
hernias (first cause in patients without previous surgery), tumors (intrinsic and extrinsic), intussusception, volvulus, IBD, stenosis and cystic
fibrosis. It has a mortality of 10%.
Symptoms
It is characterized by abdominal pain, vomiting (fecaloid, if distal), abdominal distension (the more distal the blockage, the greater the distension), hyperperistalism with metallic noises. An incarcerated hernia
must be ruled out. In strangulation, fever rises, the pain becomes intense and continuous, and muscle stiness is observed.
As intraluminal pressure increases, mesenteric venous return is hindered, stopping completely when the pressure is equalized to systolic
pressure. First the flow intestinal mucosa is aected, resulting in a wall
edema and transudation of fluid into the intestinal lumen, thus increasing the defect of irrigation and distension. Normal gut secretions are
sequestered in the clogged portion, resulting in dehydration with electrolyte loss, particularly potassium.
The most common site of perforation is the cecum because it has a
larger diameter, and according to the Laplace Principle, it supports an
increased wall tension. The site of primary tumor is perforated by thinning and distortion of the normal bowel layers.
The perfusion defect produces a bacterial translocation to the mesenteric vessels and nodes, which increases the chances of postoperative
septic complications.
When clogging occurs, the colon responds with an initial increase in
peristalsis in the proximal to the stop area, along with a decrease
in the activity of the right colon and terminal ileum, in an attempt to
overcome the obstruction. As the obstruction progresses, this activity
decreases to stop completely. It has a mortality of 20%.
Symptoms
The symptoms of colon obstruction are abdominal pain and distension,
vomiting and constipation, with inability to pass gas or stool. Obstruction because of colorectal cancer is instituted slowly, while that as a
result of a volvulus occurs suddenly.
The colonic distension is greater if produced in a closed loop or if the
ileocecal valve is appropriate, increasing the risk of ischemia and perforation. Perforation occurs more frequently in the cecum and in the
same tumor.
Among the laboratory data there is hemoconcentration, electrolyte

disorders, and serum amylase may be increased. Leukocytosis should
make us suspect strangulation.
It may be accompanied by dehydration, septicemia, abnormal bowel

sounds with metallic noises, palpable abdominal mass and peritonitis.
Air-fluid levels are characteristic on abdominal x-rays standing or dilated

loops when lying. The colon is usually devoid of gas. We must systematically seek air in the bile duct and opaque gallstones.
The appearance of hepatomegaly and ascites in a colorectal cancer patient who has undergone surgery suggests carcinomatosis and, therefore, poor prognosis.
Treatment
In a patient with large bowel obstruction in which fever, tachycardia or

signs of peritoneal irritation appear, we suspect strangulation or perforation, requiring emergency laparotomy.
A total 90% of SB obstructions are resolved with NGA and electrolyte replacement. Surgery is necessary when strangulation is suspected, pain
and fever increase, if not resolved within three to five days. If there are
adhesions and the bowel is viable, enterolysis is sucient.
Gangrenous nonviable intestine should be resected, like tumors, a primary anastomosis is performed except when diuse peritonitis is observed. Foreign bodies should be extracted by enterotomy.
Large Bowel Obstruction

Etiology and Physiopathology
Colonic obstructions are usually caused mainly by colorectal cancer
(more common in the rectum and sigma); also volvulus, diverticulitis,
IBD and actinic or radiation colitis may cause it.
Treatment
If not resolved, or when signs of ischemia or perforation (peritoneal irritation, fever, metabolic acidosis) appear, surgery is indicated. In tumors
of the right and transverse colon (near the splenic flexure), resection
with primary anastomosis is widely accepted.
The exception would be the patient in a very severe condition with generalized peritonitis or perforation, which requires ileostomy with externalization of the distal end that is defunctionalized (mucous fistula). In
tumors of the left colon there are several possible interventions: excision and colostomy (Hartmann), resection and primary anastomosis
after intra-operative antegrade lavage or proximal diversion (colostomy
or cecostomy).
27
Frequency
70%
30%
The venous AMI is caused by thrombosis (MVT) and it is fostered by portal hypertension, sepsis, cirrhosis, hypercoagulable states (such as antithrombin III deficiency, proteins C and S deficiency, dysfibrinogenemia,
abnormal plasminogen, PV, thrombocytosis, sickle cell disease), viscera
perforation, pancreatitis, splenomegaly, cancer, diverticular disease, trauma, and use of oral contraceptives. Venous stasis favors the fluid outlet
into the intestinal lumen, with consequent hypovolemia and hemoconcentration (which also reduces blood flow) and wall edema.
Abdominal
X-ray
No air in colon and

there may be rectal air
Air in colon. Absence

of rectal air
Clinical Presentation
New approaches are emerging, such as tumor ablation of the neoplasia with
laser, endoscopic graft stent or balloon dilation, in order to resolve the obstruction and then prepare the colon for resection and primary anastomosis
(Table 13).
SMALL INTESTINE
COLON
Most frequent Adherences and hernias

etiology
(in nonoperated)
Colorectal tumors
(rectum and sigma)
Other causes Intrinsic and extrinsic tumors,

intussusception, volvulus, IBD,
cystic stenosis and fibrosis
Volvulus, IBD, actinic

colitis and diverticulitis
Most frequent Trapped loop

perforation
site
Caecum (because of
distension)
Treatment
Generally conservative
Generally surgical
Table 13. Dierences between small intestine and colon obstruction
There is often bleeding hidden in feces (positive guaiac test) or blood

Hyphenate blood and stained stained stools. The abdomen does not get
to relax until the late stages.
(AMI)
In the initial stages, when the diagnosis must be made, on physical examination abdominal rigidity is not evidenced, which later appears with
hypersensitivity; bowel sounds, although in the early stages may be increased, decrease rapidly and disappear in the typical abdominal silence.
Intestinal infarction produces feculent breath odor.
It is a serious condition with high mortality, in which diagnosis has to be

established through symptoms, in a patient with predisposing diseases
(heart disease).
Acute mesenteric venous thrombosis (MVT) has the same symptoms,

even more hidden, pain disproportionate to physical data, slow and
steady progression of more than 48 hours, which delays diagnosis and
increases mortality.
3.11. Acute Mesenteric Ischemia
It is a clinical condition characterized by the involvement of the blood

flow of the superior mesenteric artery. An ischemia of the intestinal
mucosa occurs which starts in the microvilli, altering absorption, and it
subsequently aects all layers of the intestine, to finally cause infarction
of the small intestine and/or the right colon.
Diagnosis
It is dicult to arrive at a correct diagnosis, especially in occlusion of
a short segment of the intestine, so we should suspect in cases of abdominal pain in the context referred.
Acute arterial ischemia can be caused by an embolus or thrombus. In

the arterial embolic AMI (the most common), this is caused by valvular disease or heart arrhythmias (from post-infarction thrombus of left
ventricle or atrial fibrillation by mitral stenosis) and it is located 3-10 cm
distal to the origin of the middle colic artery.
Elevated white blood cell count with predominance of immature forms

(left shift) is typical, as well as the elevation of dierent intracellular
enzymes (LDH) and blood amylase. There are elevated hematocrit and
hemoglobin (hemoconcentration). Metabolic acidosis with base deficit
in blood gases is common.
The nonocclusive mesenteric ischemia (NOMI), arterial or venous, is

caused by a low mesenteric flow (the second most common cause), by
low cardiac output or vasospasm in the context of an underlying arteriosclerosis. It should be suspected in elderly patients with risk factors such as acute myocardial infarction, congestive heart failure, dysrhythmias, hypovolemia by burns, sepsis, pancreatitis, hemorrhagic
shock, use of alpha-adrenergics or digitalis (it produces a paradoxic and
sustained contraction of the arterial and venous mesenteric smooth
muscle). They are becoming less frequent due to the widespread use of
vasodilators such as calcium channel blockers and nitrates.
Radiology usually shows dilated small bowel loops and adynamic ileus,
thickening of the bowel wall. In advanced cases, there may be pneumatosis of the bowel wall and gas in the portal vein (ominous sign).
AMI by arterial thrombus (the third most common) originates on the

basis of arteriosclerosis, and therefore, the patient has a history of
chronic mesenteric ischemia with postprandial pain, weight loss, fear
of food and early satiety.
28
The most frequent and significant early clinical feature is the severity
of abdominal pain, disproportionate to the few physical signs, and the
lack of response to narcotic analgesia. The history of bowel movement
at the onset of pain and a history of cardiac disease. Initially, the pain is
colic and localized in the epigastrium or mesogastrium; subsequently, it
is continuous and widespread.
In expert hands, Eco-Doppler can verify decreased flow in proximal lesions of the AMS or the celiac axis.
The mere suspicion of AMS is an indication of mesenteric arteriography,
the definitive diagnostic study, and anteroposterior and lateral projections should be made (to visualize the beginning of the celiac axis and
the SMA). The meniscus sign in the site of occlusion is classical. In the
NOMI, it reveals multiple areas of narrowing and irregularity (string
of sausages sign). For mesenteric venous thrombosis there is reflux of
contrast material into the aorta, and during the venous phase, there is
a defect or lack of filling of the portal vein.
The most appropriate diagnostic test in acute MVT is CT, which shows a
thrombus in the superior mesenteric vein, along with thickening of the
bowel wall, pneumatosis and mesentery in strips.
Treatment
The only definitive treatment is surgical revascularization using bypass

with dacron graft or saphenous vein, or endarterectomy.
Chronic MVT is asymptomatic or produces vague abdominal pain and
bloating. CT is the most sensitive test. In most cases, the collateral circulation is sucient for draining the aected intestine (Figure 23).
Initially, electrolyte replacement, correction of acidosis and administration of antibiotics. The presence of signs of peritonitis requires emergency surgical exploration.
In occlusive mesenteric ischemia, after stabilization of the patient and
administration of heparin, revascularization will be performed by embolectomy or bypass with graft of Dacron or saphenous vein, in the
event of thrombosis. Make sure bowel is viable. If there is evidence of
intestinal infarction, a resection of the nonviable part of the bowel must
be performed.
Inferior
mesenteric
artery
In patients with nonocclusive ischemia (NOMI), surgery is not required. During arteriography intraarterial vasodilators (papaverine) should be injected.
Sodium heparin should not be administered simultaneously because
of its chemical incompatibility with papaverine. Also, try to correct the
precipitating factors. It requires surgery when there are signs of ischemia or necrosis (hypersensitivity and defense), increasing leukocytosis,
gastrointestinal hemorrhage, pneumoperitoneum, or intramural gas on
exploration.
Acute MVT should be treated surgically if there is peritonitis. Intestinal
resection may be necessary, and thrombectomies have been reported
if the thrombus is located in the proximal portion of the superior mesenteric vein. In all cases, treatment should be commenced with heparin
and lifelong anticoagulation.
Superior
mesenteric
artery
Wide network of collateral vessels
Figure 23. Image of an angiography of chronic mesenteric ischemi
3.12. Chronic Mesenteric
Ischemia or Intestinal Angina
3.13. Ischemic Colitis
It is a rare disorder in which early diagnosis is important to prevent

stroke. It is more common in women and in smokers. It is associated
with hypertension, coronary artery disease or cerebral vascular disease.
Arteriosclerosis occurs at least in two of the three main mesenteric arteries. Most of them have aected the celiac and superior mesenteric
artery. It occurs in circumstances of high demand for splanchnic blood
flow, so it is also called intestinal angina.
It is characterized basically by circulatory insuciency of the colon. It may

be occlusive (by emboli or thrombi, by hypercoagulation, portal HT or pancreatitis) or nonocclusive (because of low flow from any source, and energetic vasoconstriction by cocaine, digital, oral contraceptives, nasal decongestants and some NSAIDs). The most often localized region is the splenic
flexure of the colon (Grith point), although the incidence is increasing in
the right colon in cases of low output. It rarely aects the rectum.
Symptoms, Diagnosis and Treatment

It usually aects elderly patients. It is characterized by dull pain, periumbilical or lower abdominal cramping arising 15-30 minutes after
meals and persisting for several hours. Postprandial pain is so typical
that is considered pathognomonic. The most common physical sign is
the significant weight loss by decreased intake (fear of food).
In half of the cases a systolic abdominal bruit is heard. There are usually no biochemical abnormalities, except those typical of malnutrition.
The diagnostic method of choice is arteriography.
In most patients the etiology is not identified. It is more common in

elderly male patients with cardiovascular disorders, diabetes or kidney
failure. It occurs in the absence of mesenteric arterial occlusion.
From the early stages, if the ischemia progresses, it can progress to ulceration and subsequent stenosis of the aected colonic segment. In
some instances, if the ischemia is transmural, it may cause gangrene of
the aected segment.
Ischemic colitis is typical after reconstructive surgery of the abdominal
aorta, which characteristically aects the sigmoid colon and appears in
5% of aneurysm repairs. It should be suspected if in the preoperative ar-
29
teriography there is a retrograde filling of the inferior mesenteric artery

from the superior mesenteric artery.
Symptoms
Moderate colic type pain of sudden onset is typical and may be accompanied by rectal bleeding or bloody diarrhea. Vomiting is rare. It
can manifest in a fulminant form, or more usually in a subacute form.
When progressing to gangrene, pain becomes constant and symptoms
of acute abdomen appear. In severe cases, colon segmental stenosis
may occur, with the risk it involves.
stem or sessile, with broad-based implant. The colon polyps can be

single or multiple, sporadic or form part of an inherited syndrome
(Figure 24). Their presence is significant since they may bleed and
some of them can become malignant. From the histologic point of
view, colon polyps can be classified into neoplastic and nonneoplastic
polyps.
Diagnosis
Definitive diagnosis is made by colonoscopy. Barium enema is rarely
used, which reveals the classic figure of the digital impressions or stenosis in the aected colonic segment. It is contraindicated in patients
with suspected gangrene. Arteriography is not helpful and it does not
demonstrate vascular abnormalities, suggesting that it is a disease of
the microvascularization.
Treatment
In transient ischemic colitis (the most common), symptoms are mild and
well controlled with conservative measures. In stenosing gangrenous
colitis, segmental resection is indicated, with or without anastomosis,
depending on the inflammatory response and the existing peritonitis in
the clinical picture.
Figure 24. Colon polyp (endoscopy)
3.14. Gastrointestinal Bleeding

Upper gastrointestinal bleeding: the one that occurs over the Treitz angle. It presents clinically as hematemesis and/or melaenas. Diagnosis is
made by upper endoscopy.
Treatment is based on hemodynamic stabilization and endoscopic
treatment.
Lower GI bleeding: produced in distal sections. It manifests clinically as
rectal bleeding or hematochezia. It is diagnosed by colonoscopy.
The treatment is based on hemodynamic stabilization and endoscopic
treatment.
3.15. Malignant Tumors
of the Large Intestine

Overview
The term polyp has been classically defined as a tumor or circumscribed protrusion which projects into the surface of a mucosa and is
macroscopically visible in the intestinal lumen. According to the attachment surface, polyps may be pedunculated, i.e. having an implant
30
Neoplastic Polyps
Adenomas are potentially malignant mucosal neoplasms. Their prevalence is high and WHO classifies them into tubular adenomas, tubulovillous adenomas and villous adenomas. All adenomas have some
degree of dysplasia, which is a premalignant microscopic lesion of the
epithelium covering the glands. The dysplasia can be low or high. The
in situ carcinoma corresponds to high-grade dysplasia, in which the carcinoma cells are confined to the basal membrane (intraepithelial carcinoma) or lamina propria (intramucosal carcinoma), without exceeding
the muscularis mucosae and therefore with a nonexistent spread capacity. Instead, malignant polyps, also known as invasive carcinomas,
are those extending to the submucosal layer and have the ability to
spread. Factors influencing the malignant potential are as follows:
Size: with a direct connection. Tumors greater than 1 cm, have a risk
of almost 50% of becoming malignant.
Histologic type: villous adenomas bear more risk; tubular adenomas
bear less risk and tubulovillous adenomas bear intermediate risk.
Degree of dysplasia: also generally correlated to size and histologic
type.
Presence of certain cytogenetic alterations.
Multiplicity of adenomas (X > 3).
There are other factors, albeit less typical, also associated with an increased risk of developing colorectal cancer, which are unrelated to the
polyp. Examples of these factors are advanced age, male gender, family history of colorectal cancer and personal or family adenomas background.
From the clinical point of view, most are asymptomatic, and when they
are clinically diagnosed, they usually cause bleeding. Villous adenomas
sometimes cause aqueous diarrhea and hypokalemia.
Colonoscopy is the procedure of choice for the diagnosis and treatment
of polyps, since this enables polyp identification and performance of a
polypectomy during the colonoscopy procedure. Monitoring after polypectomy aims to reduce the risk of colorectal cancer to the maximum
degree possible by removing both lost synchronous polyps (which appear
simultaneously) and metachronous polyps (those that appear some time
after lost synchronous polyps were diagnosed). The tracking criterion
must be established from the findings of the first colonoscopy, so it is
imperative this first examination meet quality criteria (proper colon preparation that facilitates proper inspection of colonic walls, complete colonoscopy to the caecum and time to remove the endoscope not shorter
than six minutes). In case of patients diagnosed with colon adenoma, it is
essential to recommend a planned follow-up (Table 14).
The endoscope follow-up must be suspended in case of serious comorbidity or in case the patient has a life expectancy lower than 10 years.
As for adenoma management, it is recommended to perform an endoscopic polypectomy and in the event such procedure is not possible since
the adenoma is very large, there are many adenomas or an infiltration
is present after the polypectomy, a resection of the aected colon or a
colectomy should be performed.
Perforation and bleeding are two complications reported following an endoscopic polypectomy.
If during the anatopathologic study, a completely removed in situ carcinoma (does not go through the basal membrane) is found, no further
treatment is necessary (but a close follow-up). If it turns out to be an infiltrating carcinoma of the pecule of the polyp, it must be treated as cancer
(although it may be sucient to perform a colectomy more conservative
than conventional colestomies) (Table 15).
PLANNED FOLLOWUP
Nonneoplastic Polyps
Hyperplastic polyps. They are small (2-3 mm), single or multiple,
and asymptomatic. They are distributed predominantly in the rectosigmoid, but can manifest throughout the whole extension of the
colon. There is a rare situation called hyperplastic polyposis syndrome characterized by the presence of multiple hyperplastic polyps scattered throughout the colon; they are large and lie especially
in the ascending colon. In this situation, the polyps may present different degrees of dysplasia and evolve to colorectal cancer.
For patients with excised rectosigmoid hyperplastic small polyps (X
< 1 cm), follow-up is recommended every 10 years.
Inflammatory polyps. They can be found in several colonic diseases
which take place with inflammatory processes of the mucosa, such
as inflammatory bowel disease, chronic schistosomiasis, amoebic
colitis and bacillary dysentery. They stem from the regenerative
process of an inflammatory focus. They do not have malignant potential.
Hamartomatous polyps. They represent the proliferation of mature
cells of the mucosa. If they are alone, they should not be considered
premalignant. Those associated with polyposis, juvenile polyposis
and Peutz-Jeghers syndrome do have malignant potential.
Mixed polyps. Recently reported. They may be mixed hyperplasticadenomatous polyps and serrated adenomas. They have malignant
potential, k-ras mutations are identified; they contain dysplasia and
may present adenocarcinoma focuses.
Colorectal Cancer
Cancer of the large intesne (colorectal adenocarcinoma) is the most
common of the intesnal tract, and the third most common in the general populaon. Other cancers include squamous cell carcinoma, lymphoma, leiomyosarcoma, malignant carcinoid or Kaposis sarcoma.
Here we will exclusively report colorectal adenocarcinoma.
RISK FACTOR
Population with intermediate

risk
Two or more first-grade

relatives of any age or a firstgrade relative < 60 years
of age with CRC or advanced
adenoma
Colonoscopy every 5 years, starting

at the age of 40 or 10 years before
the affected youngest relative
A first-degree relative of age

> 60 with CRC or advanced
adenoma with, or two secondgrade affected with CRC
Colonoscopy every 10 years

starting at the age of 40
Relatives of second or third

degree with CRC
The same as for intermediate risk

population
Revision in 10 years
Initial colonoscopy with no findings
Rectal hyperplastic polyps < 10 mm
Revision in 5-10 years
1-2 tubular adenomas < 10 mm
Revision in 3 years
3-10 adenomas
1 o more tubular adenomas > 10 mm
1 or more hairy component
1 or more adenoma with HGD
Revision in less than 3 years
More than 10 adenomas

Revision in less than 3 months
(Suspicion of ) Incomplete resection
Table 14. Follow up protocol of a patient with colon adenoma
SCREENING RECOMMENDATION
Colonoscopy every 10 years
Sigmoidoscopy every 5 years
Annual or biannual FOBT starting
at the age of 50
Table 15. Population screening strategies in CRC
Epidemiology
There is a wide geographic variation in the incidence and prevalence
of colorectal adenocarcinoma. However, it is one of the most common
malignancies in the Western world. It is more common in men and it
occurs mainly after the age of 50.
31
Etiology
1. Environmental factors: it seems that a diet rich in saturated fats favors
their occurrence and that high caloric intake and obesity increase the
risk. Calcium supplements and aspirin can reduce the risk of colon
cancer. The fiber, however, has not demonstrated any protection.
2. Age: the risk begins to increase from 40 years and peaks at 75.
3. Associated diseases (lower-case): ulcerative colitis, Crohns disease,
Streptococcus bovis bacteremia (associated, it is not a cause) ureterosigmoidostomy.
4. Personal history: colorectal cancer, colorectal adenomas, breast and
genital tract cancer.
5. Family history: familial polyposis syndromes, hereditary colorectal
cancer not associated with polyposis.
Sporadic colon cancers account for 90%. Adenomatous polyposis syndromes account for 1% and hereditary colon carcinoma not associated
with polyposis accounts for 5% to 10%.
Location
A total of 75% of colorectal cancers appear in the descending colon, sigmoid colon and rectum. However, in recent decades a decrease in the
number of rectal cancers has been detected increasing the proportion
of tumors in the proximal descending colon. It is assumed that approximately 50% of colorectal cancers are within reach of the sigmoidoscope.
Other prognostic factors for colorectal cancer include the poorly dierentiated histology, the existence of perforation, the presence of venous
invasion, preoperative CEA increase above 5 ng/mL, and aneuploidy or
chromosomal deletions in certain tumor cells.
Treatment
Surgery is the first line treatment. If adenopathies are positive, adjuvant
chemotherapy is recommended.
Periodic control with CEA values, colonoscopy and thoracic-abdominal
CT to detect recurrence and/or metastases.
3.16. Inguinal Hernias

Hernias are among the most common surgical pathologies. The term
hernia can be defined as a protrusion through a weakness or abnormal
opening in a covering layer (in this case, the abdominal wall).
Inguinal Hernias
The inguinal region is that area of the anterior abdominal wall extending below the iliac spines. Given the complexity of this area, an anatomic review is recommended for a better understanding of the surgical
treatment.
Symptoms
Clinical symptoms will depend in part on the location and size of the
tumor. Tumors of the cecum and ascending colon occur more often as
symptoms resulting from bleeding (microcytic hypochromic anemia)
and it is rarer that they provoke obstructive symptoms. In the transverse colon it is more usual that they provoke obstructive symptoms,
including perforation, whereas in tumors of the rectosigmoid junction,
we find hematochezia or tenesmus more often.
As a brief summary, it must be pointed out that the spermatic cord follows a downward slant path through the inguinal canal from the deep
inguinal ring (hole at the level of the transversalis fascia).
The medial edge of this inner ring is defined by the inferior epigastric
artery (adjacent to the ligament of Hesselbach), which branches from
the external iliac artery. The cord is above the inguinal ligament and
anterior to the transversalis fascia. It exits through the superficial or
external inguinal ring (hole in the aponeurosis of the external oblique).
Diagnosis
The fecal occult blood test is used as a screening method for colon cancer in
patients over 50 years with no other risk factors, as well as the detection of
malignant cells in stool. Their positivity leads to performing full colonoscopy.
Colonoscopy is the most sensitive method of diagnosis and should always
be performed for suspected colon cancer. If colon cancer is detected by
sigmoidoscopy, it is always required to performing a complete colonoscopy, and if you cannot do it before the surgery, it should be done later.
Types
Prognosis
The crural or femoral hernia depends for its development on an insufficiency in the transversalis fascia. It is a hernia of the inguinal region,
but it has no relation to the inguinal canal. In this type of hernia there is
a peritoneal sac passing under the inguinal ligament to the femoral region (accompanying femoral vein). Because of the narrow neck of these
hernias, the risk of incarceration and strangulation is higher than in any
other hernia. They are more frequent in women than in men.
The prognosis of colorectal cancer is correlated with the extent of tumor in the colon wall, the involvement of regional lymph nodes and the
presence of metastases. The staging of the disease according to Dukes
classification, the Modified Astler-Coller classification or the TNM system, is useful in determining the prognosis of the disease, not to decide
the extent of resection.
The indirect inguinal hernia goes out of the abdominal cavity through
the deep ring. Therefore, it goes out laterally to the epigastric artery
and the Hesselbach ligament (that is why it is also referred to as external oblique). It accompanies the inguinal cord structures through the
fibers of the cremaster muscle, it may leave through the external opening into the scrotum.
Other diagnostic methods include endoscopic ultrasonography and

barium enema. The level of carcinoembryonic antigen (CEA) has more
prognostic than diagnostic interest.
32
The femoral canal is delimited on the superior side by the inguinal ligament, by the lacunar or Gimbernat ligament medially; by the Cooper or
pectinate ligament on the posterior side and laterally, by a fascial septum extending between the anterior and posterior wall of the femoral
sheath, supported by the femoral vein.
The direct hernia protrudes through the floor of the inguinal canal at
the Hesselbach triangle, which is formed by the transversalis fascia reinforced by aponeurotic fibers of the transversus abdominis.
Thus, these hernias do not pass through the deep hole and are not located inside the fibers of the cremaster, but behind.
They may rarely enter in the scrotum through the superficial ring and
behing the spermatic cord. Since these hernias arise from a diuse
weakness of the transversalis fascia, in the absence of a narrow hernia
neck, incarceration risk is low.
We can try to reduce a hernia incarcerated under mild sedation, but

never a strangulated hernia, because of the risk involved in reintroducing an intestinal segment with vascular compromise.
Surgical Treatment
The repair of inguinal hernias is based on the restoration of the continuity
of the deep musculoaponeurotic layer of the groin (transverse muscletransversalis fascia). To this end, various techniques have been devised
(Figures 25 and 26 and Table 16).
Inguinal hernias are more common in men, except the crural, which is
more common in women. However, the most common inguinal hernia
in women, as in men, is the indirect inguinal. Direct hernias are more
common in elderly patients.
Diagnosis
Physical examination is the most important aspect of diagnosis. A hernia may be an asymptomatic insuficiency that is discovered incidentally.
They usually manifest initially by localized pain that worsens with position changes and physical eort. A hernia that was not initially identified will be demonstrated by having the patient push. It is important
to dierentiate a crural hernia, as in these cases the approach will be
dierent. Incarcerated hernias are accompanied by pain and inability to
reduce them. Hernias with strangulation usually present signs of intestinal obstruction if they contain digestive viscera.
Incarcerated hernia
Strangulated hernia
Figure 26. Hernia complications
INDIRECT INGUINAL HERNIA
DIRECT INGUINAL HERNIA
Access to groin canal
Deep inguinal ring
Posterior wall of the canal
Exit of groin canal
Superficial inguinal ring
Superficial inguinal ring
Approach to the scrotum
Easily
Rare
Strangulation
More frequent
Rare
Situation with respect to epigastric vessels
Lateral (external oblique)
Medial
Pathogeny
Generally congenital
Weakness in muscle wall-fascia transversalis
Table 16. Comparison between direct and indirect inguinal hernia
Epigastric vessels
Internal abdominal
oblique muscle
Fascia of the external

abdominal oblique
Indirect hernias
Epigastric vessels
Direct hernias
Direct
hernia
Connective
tendon
Indirect hernia
Femoral vessels
Inguinal ligament
Figure 25. Direct and indirect inguinal hernia
33
Liver Pathology
Chapter 04
4.1. Study of Patients with
Hepatobiliary Disease
Liver function tests
Transaminases. GOT and GPT or AST or ALT are the most commonly
used. Generally, they are markers of cytolysis, although there is no
absolute correlation to the enzyme activity and the degree of histologic injury. The GOT is less specific for liver disease as it can also
be seen when there is damage to other tissues such as heart, skeletal muscle, kidney or brain. In normal individuals, the levels of GOT
and GPT are similar, whereas in the majority of liver diseases, the
GOT/GPT ratio is less than 1. An exception is alcoholic liver disease,
where the GOT is usually twice the GPT. You may also see a greater
increase in GOT over GPT on the fatty liver of pregnancy, and sometimes, in hepatocellular carcinoma.
Serum proteins. A decrease in serum albumin is a good marker of the
severity of chronic liver disease. In most chronic liver diseases, and
many acute, a polyclonal increase in gamma globulins is observed;
yet, it does not have diagnostic value. The liver synthesizes six coagulation factors, the I, II, the V, VII, IX and X. All are dependent on
vitamin K, except factor V. The elongation of prothrombin time is a
good marker of liver disease in patients unresponsive to parenteral
administration of vitamin K. Furthermore, in both acute and chronic
liver disease, it is a marker of poor prognosis.
Blood ammonia level. The blood ammonia level in blood is elevated
in many patients with acute and chronic liver diseases, especially
when there is a massive hepatic necrosis accompanied by hepatic encephalopathy. However, there is no direct correlation between the
levels of blood ammonia level and the degree of encephalopathy.
Alterations in carbohydrate metabolism. Both hyper and hypoglycemia may occur. The latter is particularly dangerous, especially in
situations of acute liver failure. Hypoglycemia may be because of
decreasing gluconeogenesis, decreased hepatic glycogen synthesis,
hepatic glucagon resistance, poor oral intake and hyperinsulinemia
secondary to the presence of portosystemic shunts.
Bilirubin. Most of the bilirubin in blood comes from the metabolism of the heme group of the aged erythrocytes. Bilirubin found in
blood is a mixture of indirect (or unconjugated) bilirubin and direct
bilirubin (or conjugated). The increase of indirect bilirubin is due either to a disorder or condition of the conjugation or to an increased
production of bilirubin. Increased direct bilirubin (over 50% of the
total) is due to an impaired secretion of the liver cell or to some level
of bile ducts. Direct bilirubin is water soluble, and thus is the only
fraction that appears in urine.
Study of Patients with Cholestasis

Cholestasis is defined by the presence of bile flow blockage that
does not enable, totally or partially, the arrival of bile into the duo-
34
denum. It manifests clinically with the presence of jaundice, dark

urine, acholia and itching. In biochemistry, mainly with the cholestatic enzymes, bile salts and conjugated bilirubin rise. If the obstruction is in the liver parenchyma, it is an intrahepatic cholestasis,
while if it is in the path of extrahepatic bile duct, it is extrahepatic
cholestasis.
Cholestasis enzymes. Alkaline phosphatase, 5-nucleotidase and
gamma glutamyl are the enzymes mainly used. The most commonly used is alkaline phosphatase, which is essentially a marker of intra and extrahepatic cholestasis, although it increases in
many types of liver disease. Keep in mind that it can increase in
situations other than liver diseases; 5-nucleotidase is only used
to confirm that a high level of alkaline phosphatase is of hepatic
origin, but it may occasionally be normal with hepatic impairment and increased alkaline phosphatase. Gamma-glutamyl
transpeptidase is a very sensitive marker of biliary disease, but
it is not very specific, it enables determining the hepatic origin
of elevated alkaline phosphatase. Moreover, it is an enzyme capable of being induced, which is often high in patients with alcoholism or taking certain drugs that induce hepatic microsomal
systems.
Hepatobiliary ultrasound. It is the first examination to be performed in a patient with cholestasis. It facilitates assessing with
high reliability the existence of dilatation of the biliary tree or cholelithiasis. The biliary dilatation suggests extrahepatic cholestasis
and the absence of intrahepatic dilatation. In the liver, it enables
detecting focal or multiple liver injuries and to guide a biopsy toward those injuries.
Computed tomography (CT). In general, it can better define the
anatomy of the structures and it has a similar sensitivity to ultrasound to detect bile duct dilatation, but is more expensive. Certain
injuries may appear as an image typical enough as to be able to
make the diagnosis with this method. It is more useful in the liver
than in the bile duct.
Cholangiography. It can be performed by two techniques. Transhepatic cholangiography consists of the percutaneous injection of a
contrast in the biliary tree. It is useful especially when there is dilatation of the intrahepatic bile ducts and enables defining the anatomy
and to study the cause of proximal biliary obstruction and establish
an external biliary diversion. It is seldom used for diagnosis and
treatment is used more as stenosis or fistula treatment or to place
a drainage catheter. The other technique is endoscopic retrograde
cholangiopancreatography.
It consists of cannulating the ampulla of Vater and injecting a contrast to visualize the biliary and pancreatic ducts. This technique is
recommended when an ampullary, pancreatic or distal common bile
duct injury is suspected. Also, it enables performing a sphincterotomy and extraction of common bile duct stones, taking biopsies of
the ampullary region and samples for the cytologic study of the bile
and pancreatic fluids. It can also cause dilatation of stenotic lesions
and placement of prothesis to solve obstructive problems in the bile
duct. As a side eect, it can cause a transient increase in amylase
(pancreatitis, usually mild).
Colangio-MRI. It has a sensitivity and specificity for pathology similar to ERCP biliary without blood. On the contrary, it does not enable therapeutic maneuvers. Endoscopic ultrasound is a technique
of high profitability in the distal parts of the bile duct.
Liver biopsy. Indicated when intrahepatic cholestasis and diuse
liver diseases are suspected. It is contraindicated if there is dilatation of the bile duct (Figure 27).
terms of clinical manifestations that they result in, histologic findings and treatment, which will be reviewed together. The characteristics of the infection caused by each virus will be subsequently
reviewed.
Figure 27. Management of cholestasis
4.2. Hyperbilirubinemia
The typical clinical picture (which is not the most common) is similar
for all viruses, occurring after a variable incubation period for each
of them. It begins with a prodromal phase, lasting one or two weeks,
consisting of a picture with constitutional symptoms, anorexia, nausea, vomiting, fatigue, arthralgia, myalgia, headache, and alterations
in smell and taste. There may also be varying fever. Subsequently
the state phase appears, whic lasts between two and six weeks, and
where evident jaundice accompanied by hepatomegaly may occur,
and in 10% to 25% of cases, splenomegaly and cervical lymphadenopathy. The symptoms of the prodromal phase usually improve during
the state phase. It is then followed by a recovery phase in which all
symptoms and signs disappear gradually, usually longer in hepatitis B
and C, and less on the A and E, although, in general, in two to twelve
weeks all cases progressing to healing have been resolved. Regarding
the biochemical features, it is characterized by a variable increase in
transaminases that does not correlate to the degree of liver damage
and a variable increase of bilirubin at the expense of the two fractions. Since we are dealing with symptoms of hepatitis, elevated transaminases will prevail on the parameters of cholestasis. Neutropenia,
lymphopenia or lymphocytosis even with atypical lymphocytes can be
observed.
See Table 17.
4.3. Viral Hepatitis

General Aspects of Acute Viral Hepatitis
Acute viral hepatitis is a systemic disease that preferentially affects
the liver and is caused by several viruses that have special hepatic
tropism. Infection with these viruses has many common features in
However, anicteric hepatitis is more common. Sometimes hepatitis has

a predominance of cholestasis; this is more common in hepatitis A in
evolution. Other times it follows a longer clinical course or recurs after
initial improvement; It is also more common in A and sometimes in C.
Finally, there are serious forms that occur with complications and fulminant forms (encephalopathy and decreased prothrombin time below
40% in a previously healthy liver) more frequent with hepatitis B (especially superinfection D and infection B precore mutants) and with E in
pregnant women.
Treatment is symptomatic, in the case of acute hepatitis.
INDIRECT
MIXED
Gilbert
Crigler-Najjar
Dubin-Johnson
Rotor
Type I
Type II
Inheritance
AD
AR
AD
AR
AR
Incidence
The most frequent

(5% to 7% of population)
Very rare
Infrequent
Infrequent
Rare
Defect
Alt. Conjugation
Impaired uptake
Hidden hemolysis
*UDPGT
*UDPGT
Alt. in excretion
Alt. in storage
Bilirubin (mg/dL)
< 5 mg/dL
> 20
6 to 20
3 to 10
<7
Type of predominant
bilirubin
Indirect
Indirect
Indirect
Direct + Indirect
Direct + Indirect
Oral cholecystography
Biliary pathway is not observed
Liver biopsy
Black pigment
Prognosis
Early death
*UDPGT: UDP-glucuronosyltransferase
Table 17. Types of hereditary jaundice (N: normal)
35
HAV Infection
contact or sexual transmission; it is probably the transmission mechanism in male homosexuals, prostitutes and spouses of HBY-infected
patients.
Epidemiology
The epidemiology of hepatitis A is conditioned by two facts: transmission
almost exclusively via the fecal-oral route and development of permanent
immunity after cure of the disease. Hepatitis A is prevalent worldwide,
but the degree of endemicity that can be recognized by the prevalence of
total anti-HAV antibodies which varies substantially with socio-economic
status.
Diagnosis
The diagnosis of acute HAV infection is made by detection of IgM antiHAV in serum. Detection of anti-HAV IgG indicates a past infection and
permanent immunity. The detection of HAV-Ag and RNA-HAV are not
used in clinical practice (Figure 28).
The third mechanism is perinatal transmission from infected mother to

child. This risk occurs in women who suer from hepatitis B in the last trimester or postpartum and children of women with chronic HBV infection.
The risk of transmission is directly proportional to the presence of HBeAg,
being 90% if the mother is HBeAg positive, whereas if the mother is positive anti-HBe, the risk is only 10% to 15%. This transmission mechanism is
very important since the risk of chronicity of infection when acquired in
this neonatal period is very high (90%). Transmission occurs primarily during childbirth (Figures 29 and 30).
800
700
HBsAg
600
HBsAg
Total anti-A
anti-A-IgG
anti-A-IgM
HBsAg
500
DNA-HBV
400
Hepatitis
300
Infection
200
Fecal
excretion of
the virus
100
0
12
26
36
48
Months
Figure 29. Natural course of HBV
Symptoms
26
52
weeks
SGPT
Anti-HBc
Figure 28. Natural course of hepatitis A

IgM
Anti-HBc
HBV Infection
Anti-HBs
HBsAg
Epidemiology
HBeAg
DNAp
The main reservoir of the infection is constituted by HBV infected patients.

The transmission mechanisms are basically three. Percutaneous or parenteral transmission, which can occur through blood transfusions, blood
products or contact with contaminated material. However, today, most of
percutaneous transmissions of HBV are unapparent or occur unnoticed.
Anti-HBe
DNA
12
Exposicin
24
Months
Figure 30. Serologic course of HBV
The second major mechanism of transmission is through intimate

AcHBc IgM
AcHBc IgG
AgHBs
AcHBs
AgHBe
AcHBe
DNA
ACUTE HEPATITIS
ACUTE HEPATITIS IN WINDOW PERIOD
REPLICATIVE CHRONIC HEPATITIS B
PRECORE MUTANT
INACTIVE CARRIER OF HEPATITIS B
CURED HEPATITIS B
VACCINATION
Table 18. Serologic markers of HBV
36
Diagnosis of HBV Infection (Table 18)

Diagnosis is based on studying serologic markers. The existence of antiHBc IgM is essential to diagnose acute HBV infection. Quantitative HBV
detection tests still have significant limitations in terms of standardization that make interpretation dicult (Table 18).
Treatment
See Table 19.
AgHBe
+
+
DNA-HBV
> 2.000 UI/mL
> 2.000 UI/mL
ALT
2 x LSN
> 2 x LSN
the best diagnostic method. With this new tests can be detected Ac six
to eight weeks after exposure and HCV RNA can be detected after one
to two weeks exposure (qualitative determination: amplified genomic).
In the case of acute hepatitis C, we will find a positive PCR with negative anti-HCV, the confirmation being the appearance of seroconversion after time. With PCR, we also quantify HCV RNA, whose levels can
fluctuate within the same person, sometimes being undetectable when
viral replication is very low. It is not indicated to routinely perform HCVRNA. It is indicated when: 1) confirmation tests are indeterminate and
2) to monitor perinatal transmission or response to antiviral therapy.
The anti-HCV antibodies are not protective and their presence usually
indicates disease (Table 20).
TREATMENT
Observation. Low efficacy
of current treatments
2 options:
1. peg-IFN 48 weeks
2. Tenofovir or entecavir
until seroconversion. If
seroconversion occurs:
12 more months of
consolidation treatment
> 2.000 UI/mL
> 2 x LSN
Tenofovir or entecavir
indefinitely
< 2.000 UI/mL
Normal
No treatment is needed
HCVAc
HCV-RNA
Acute or chronic HCV infection

(it will depend on the clinical context)
Resolution of false positive of screening

test
Acute infection very precocious

(it did not give enough time
for antibodies synthesis)
Absence of infection
Table 20. Hepatitis C diagnosis
Table 19. Indications for chronic hepatitis B treatment
HCV Infection
The hepatitis C virus (HCV) is responsible for most cases of what was
known as nonA nonB hepatitis some years ago. It is also responsible
for most of the cases thought to be cryptogenic cirrhosis.
Nonstructural proteins involved in viral replication.
INTERPRETATION
Treatment
It is based on the combination of peg-IFN with ribavirin for 24 or 48
weeks.
4.4. Cirrhosis
Epidemiology of HCV infection

HCV transmission is essentially parenteral. Hepatitis C accounts for 90%
of post-transfusion hepatitis. However, the transfusion history explains
only a small percentage of HCV infections. Other risk groups include
people with occupational exposure to blood or derivatives, hemodialysis patients and intravenous drug users. The latter represent the largest
percentage of people at known risk. Sexual transmission is rare but it
probably exists. This transmission mechanism seems more important
in HIV positive people. Infections in household contacts are also rare.
Perinatal transmission is rare, but it exists and occurs especially if the
mother is HIV positive or has high viremia. However, the most important group of HCV-infected patients has no known risk factors and the
mechanism of transmission is unknown.
Diagnosis
The first tests for anti-HCV Ab were insensitive, especially to diagnose
infection early (it could take six months to become positive). They were
not very specific either with false positives in patients with alcoholic
liver disease, autoimmune disorders, and hypergammaglobulinemia.
Currently, second and third generation ELISAs and radioimmunoassay
are available to confirm, with a sensitivity and specificity of 95%, when
compared with the detection of HCV RNA by PCR, which is considered
Cirrhosis is a diuse process characterized by fibrosis and a conversion

of normal architecture of the liver into structurally abnormal nodules.
Cirrhosis is the morphologic consequence and final common pathway
of dierent disorders.
Etiology
See Table 21.
CAUSES FOR CIRRHOSIS
Alcoholism
Post viral hepatitis: B, C and D hepatitis
Drugs (methotrexate)
Congenital and metabolic diseases, for example,
hemochromatosis
Biliary cirrhosis primary and secondary to cardiac failure
Cardiac failure or vein obstruction: congestive cardiac failure, chronic
pericarditis, chronic obstruction of hepatic veins
Others: sarcoidosis, autoimmune chronic hepatitis, diabetes mellitus,
jejunoileal bypass
Table 21. Cirrhosis etiology
37
Pathogenesis of Portal Hypertension

The pressure in the portal system is the result of flow resistance. In liver
cirrhosis (the most common cause of portal hypertension [PAH]) portal
pressure increases along with both components.
The increase in portal blood flow is influenced by a strong systemic
and splanchnic vasodilation because of the presence of vasodilator
substances such as prostaglandins, glucagon, nitric oxide and, possibly,
tumor necrosis factor. These vasodilators are produced in the splanchnic bed and accumulate in the systemic circulation due to an increase
in production or a decrease in metabolism by a sick liver. When the
collateral circulation occurs, the level of vasodilator substances in the
systemic circulation increases.
level of the small intestine, cecum and ostomy sites (ectopic varicose
veins). Those with most clinical relevance are the esophageal.
The risk of bleeding of varicose veins is minimal when the gradient of
portosystemic pressure is less than 12 mmHg.
Esophageal veins
Superior mesenteric vein
Short vessels
Splenic vein
In liver cirrhosis, portal flow resistance occurs mainly at sinusoidal and

presinusoidal level (it can be found listed as both).
Flow resistance has a fixed component conditioned by the distortion of
the vessels because of the cirrhotic nodules and fibrosis, and a variable
component as a result of the action of vasoactive substances, in particular endothelin-1 (Figure 31).
Retroperitoneal
vein plexus
Inferior
mesenteric vein
Cirrhosis
Portal flow
resistance
Vena hemorroidal
superior
Arteriolar
resistance
Umbilical vein
recanalization
Media and inferior

hemorrhoidal vein
Hemorrhoidal plexus
Sinusoidal
pressure
Portal pressure
gradient
Ascites
Collateral
(varices)
Portal flow
Effective
arterial volume
Neurohormonal
systems activation
Sodium and water

retention
Figure 31. Pathophysiology of portal hypertension (PHT)

and main complications (varices and ascites)
Consequences of Portal Hypertension

Depending on the place of obstruction, the PHT is classified as prehepatic or presinusoidal (portal vein thrombosis, schistosomiasis), posthepatic or postsinusoidal (Budd-Chiari Syndrome) or liver (cirrhosis).
Portosystemic collaterals have a high resistance, so usually all the
splanchnic flow goes through the portal (Figure 32).
By increasing the portal blood flow and the resistance to its passage,
the flow increases through the collaterals, which manifest as varicosities in dierent places, such as the lower esophagus, rectum, periumbilical region and around the ovary. Occasionally they may form at the
38
Figure 32. Portosystemic communications in PHT
Symptoms
The symptoms of patients with cirrhosis depend on whether it is
compensated or decompensated, and the cause of cirrhosis. Patients
with compensated cirrhosis may be completely asymptomatic and
not present any analytic abnormality. Patients with decompensated
cirrhosis may present some of the major complications such as bleeding upper gastrointestinal varices, jaundice, ascites, encephalopathy,
spontaneous bacterial peritonitis, sepsis or hepatocarcinoma. As for
the physical examination, they may present a jaundiced tint, vascular spiders, palmar erythema; in alcoholics, it is common to find Dupuytren contracture, parotid gland enlargement, gynecomastia and
feminoid hair distribution. It is common to find hepatomegaly and
splenomegaly may occur.
Regarding laboratory data, they naturally depend on how advanced
the disease is, but we can find abnormal liver biochemistry such as
increases in transaminases, which are usually not very high and with
a GOT higher than GPT; cholestasis enzymes are often high in biliary
cirrhosis. In advanced stages of proteinogram, a decrease in albumin
is often seen with the polyclonal gammaglobulin increase. Coagulation
disorders lead to decreased synthesis because of a decrease in hepatic
factors. Increased fibrinolytic activity. Evidence of hypersplenism such
as thrombocytopenia or leukopenia. Hypocholesterolemia in nonbiliary

cirrhosis and hypercholesterolemia in biliary cirrhosis. And laboratory
abnormalities dependent on the specific etiology.
HEPATORENAL
SYNDROME
Diagnosis
of exclusion.
Prerenal failure as
a result of portal
hypertension
Albumin, terlipressin,
dialysis.
HEPATIC
ENCEPHALOPATHY
Asterixis,
decreased level of
consciousness and
disorientation
Low-protein diet,
laxatives
and nonabsorbable
antibiotics (rifaximin)
Risk of rupture
with larger size
or worse liver
function
Prophylaxis with beta

blockers
Treatment acute
hemorrhage with
somatostatin and
endoscopic treatment
(ligation or sclerosis)
Diagnosis
Diagnosis is made based on the study of a liver biopsy. The etiologic
diagnosis is often made based on serologic studies or clinical history, as
in the case of alcoholism.
Prognosis
In compensated cirrhosis, survival at five years is 90%, while in decompensated, survival is 10%, (Table 22).
PARAMETER
1 POINT
2 POINTS
3 POINTS
Encephalopathy
It does not exist
Grade I-II
Grade III-IV
Ascites
Absent
Mild
To tension
Bilirubin (mg/dL) 1 to 2
2 to 3
>3
Albumin (g/f )
> 3.5
2.8 to 3.5
< 2.8
Prothrombin
> 50%
30% to 50%
< 30%
Table 22. Functional assessment of cirrhosis (Childs classication)
Treatment
ESOPHAGEAL
VARICES
Table 23. Hepatocellular carcinoma and its variants (continued)
4.5. Hepatocarcinoma
Malignant Tumors
of the Liver and Bile Ducts
There is no treatment clearly modifying the natural history of cirrhosis. The

treatment focuses on its complications. In general, patients with uncomplicated cirrhosis do not require any treatment, except in those cases where
cirrhosis results from a disease that requires special treatment, e.g., Wilsons disease. Today, in all cases and in a terminal condition, liver transplantation is possible if there is no contraindication.
Hepatocellular Carcinoma
The three major complications of liver cirrhosis (bleeding varices, ascites and encephalopathy) are associated with portal hypertension, defined as a gradient of hepatic venous pressure higher than 6 mmHg. In
cirrhosis, portal pressure rise is due to an increased resistance to portal
venous flow at presinusoidal, postsinusoidal and sinusoidal levels.
Etiology
Complications of Cirrhosis
See Table 23.
Increased waist
circumference
Low sodium diet.

Diuretics (spironolactone
and furosemide
combination). In
refractory cases
paracentesis
Abdominal pain
+ fever
Count > 250
PMN in ascitic
fluid
Third generation
cephalosporins
intravenously.
Prophylaxis with oral
quinolones
ASCITES
SPONTANEOUS
BACTERIAL
PERITONITIS
Table 23. Hepatocellular carcinoma and its variants (continued)
Liver transplantation
Hepatocellular carcinoma (HCC) is the sixth most frequent neoplasia,

and the third cause of death in our area. It is more common in men, and
the highest incidence rate occurs between the fifth and sixth decades
of life.
Cirrhosis. It underlies most cases of HCC. The etiologies responsible

for causing cirrhosis more frequently associated with HCC are infection with HCV, with HBV, steatohepatitis, hemochromatosis and
alcohol. Cirrhosis after PBC, Wilsons disease or autoimmune hepatitis is rarely related to HCC. Therefore, although there is a clear association between cirrhosis and HCC, other co-factors related to its
etiology are involved in its development.
Chronic HBV infection. It is related to HBV-DNA integration into
the host cell DNA and to transactivation of the hosts oncogenes,
mechanism mediated by HBx protein or by a protein derived from
the pre-S2/S region. It is the most common cause of HCC in the East.
Chronic HCV infection. In Spain, this underlying factor is considered
to be most frequently detected in patients with HCC on cirrhotic
livers. Co-infection with HBV and alcohol consumption increase the
risk of HCC associated with HCV. It is the most common cause of
HCC in the West.
Hemochromatosis. The relative risk of HCC in cirrhotic livers of patients with hemochromatosis is greater than 200. It usually appears
on cirrhotic livers and rarely in precirrhotic stages. It seems to occur
more often in hepatic iron-free loci.
Other metabolic disorders. Glycogenesis type Y, tyrosinemia, porphyria, mainly late hepatocutaneous porphyria, 1- antitrypsin deficiency and Wilsons disease (rare).
39
Alcohol. It is a risk factor for HCC, as it is an etiologic factor of liver cirrhosis, but epidemiologic studies have not confirmed an increased risk compared to other liver diseases.
Other factors. Aflatoxin B1 is a mycotoxin that appears to cause a mutation in the tumor suppressor p53. Some drugs, vinyl chloride and others.
Nodule < 1 cm. Since the probability that an infracentimetric nodule

indicating HCC is very low and the characterization of these nodules is
very complex, it is recommended to monitor closely every three to four
months to detect any early growth that would indicate its malignancy.
Prognosis and Treatment

Clinical Examination and Diagnosis
The first symptoms vary, but the most frequent are abdominal pain or
palpable abdominal mass. In 20% of cases, there is chronic diarrhea of
unclear mechanism. It may result in multiple paraneoplastic complications such as erythrocytosis, hypercalcemia, hypoglycemia, hyperlipidemia, hepatocutaneous porphyria, dysfibrinogenemia, cryoglobulinemia
or gynecomastia. Elevated -fetoprotein was observed in 80% of cases,
but it is a less used method than ultrasound screening. Other proposed
markers have not yet oered advantages as regards -fetoprotein.
On ultrasound imaging, it appears as a hypoechoic nodule in nonnodular
cirrhotic livers. In nodular livers it loses much of its specificity. The CHC
has an almost exclusively arterial vasculature, unlike the rest of the liver
parenchyma, which has a mixed vasculature, both arterial and portal.
This generates a specific vascular pattern on dynamic tests (CT or MRI
with contrast) consisting of intense contrast enhancement in the arterial phase, followed by washing out in the portal and late phases, which
permits a definitive diagnosis of HCC in patients suering from liver cirrhosis, without the need histologic confirmation. The sensitivity of CT is
56%, since small tumors are isodense with the surrounding parenchyma.
Spiral CT images taken with intraarterial contrast showed an improved
sensitivity of 87%, even for tumors of less than 1 cm.
Contrast-enhanced MRI is considered to be more sensitive than CT, and
it is especially useful to distinguish tumors from adenomatous hyperplasia and cavernous hemangioma.
Diagnostic algorithm in case of detection of a liver nodule by ultrasound
of a noncirrhotic liver:
Histologic confirmation is required (ultrasound or CT-guided FNA).
Diagnostic algorithm in case of detection of a liver nodule by ultrasound
of a cirrhotic liver (Figure 33):
Despite major advances in diagnosis and treatment, HCC is one of the

malignancies with lower survival rates, so that the mortality rate almost
equals its incidence rate. In most cases, this cancer appears associated
with liver cirrhosis and the only possibility of treatment with curative intent is to diagnose the disease in its early stages, so all cirrhotic patients
should have an abdominal ultrasound screening every six months. Once
the diagnosis of HCC is made, it is essential to make a correct staging
of the disease, assessing the number and size of the foci, portal vein
invasion and/or extrahepatic disease. Also, considering that most treatments can decompensate the underlying liver disease, it is essential to
accurately assess the hepatic functional reserve. In this regard, dierent staging systems have been developed recently. The staging system
more frequently used in our area is the BCLC (Barcelona Clinic Liver
Cancer), which takes into account tumor extension (size and number of
nodules, portal vein invasion and extrahepatic disease), liver function
(Child-Pugh), general condition of the patient, and relates the stage of
the disease to the possible treatment options (Figure 34).
Very early stage (stage 0). Child A patients with a single nodule of less
than 2 cm. If the patient has compensated cirrhosis without significant
portal hypertension, they will be a candidate for surgery. Otherwise, if
there are no contraindications, the curative treatment of choice is transplantation.
Early stage (stage A). Patients with preserved liver function who have
a limited tumor (single nodule less than 5 cm or up to three nodules of
no more than 3 cm) are candidates for treatment with curative intent:
Surgical resection: noncirrhotic patients or Child A patients without
PHT.
THO: Child B and C patients. HCC and cirrhosis can be cured.
Percutaneous ablation: it is indicated for patients who cannot undergo surgery and when THO is contraindicated due to comorbidity, or as treatment during the waiting period. It can be performed by instilling chemicals, mainly ethanol and acetic acid, or
by modifying the intratumoral temperature, as in the case of radio
frequency.
Hepatic node
in ultrasound screening
< 1 cm
> 1 cm
Followup
every three to four
months
Specific Vascular
pattern CT/MRI
HCC diagnosis
Figure 33. Diagnostic algorithm of hepatocellular carcinoma

Nodule > 1 cm. The diagnosis of HCC can be made without the need
for biopsy/cytology if the specific vascular pattern (arterial uptake
with wash out) is detected by a dynamic imaging technique (contrast enhanced ultrasound, CT or MRI). Otherwise, histologic confirmation is required.
40
Intermediate Stage (stage B). Patients with multi-nodular tumors that

exceed the criteria reported above, without vascular or extrahepatic
invasion, with liver function and overall condition preserved. The only
eective treatment is transarterial chemoembolization (TACE).
Advanced stage (stage C). Patients with preserved liver function with
HCC with vascular invasion and/or extrahepatic or mild deterioration of
the general condition. Chemotherapy with sorafenib, which has been
shown to improve survival and disease progression time compared to
placebo.
Terminal Stage (stage D). Extensive tumor on decompensated cirrhosis
with highly deteriorated liver function and overall condition. Survival is
less than three months and patients can only be oered symptomatic
treatment.
Fibrolamellar Hepatocarcinoma
It is a morphologic variant of hepatocellular carcinoma, although some
studies claim this variant does not exist and that it is simply a hepatocar-
Figure 34. Algorithm of hepatocellular carcinoma treatment

cinoma with better prognostic factors. It makes up a 10% of hepatocarcinomas and up to 40% of those appearing before the age of 45.
It appears between the second and third decade (95% before the age
of 25). No associated etiologic factor is known. The symptoms are abdominal pain, palpable hepatomegaly and constitutional syndrome. In
only 10% of cases there is an increase in -fetoprotein. The diagnosis
is made using ultrasound screening, CT and liver biopsy. They usually
show a single lesion, unencapsulated but well dierentiated from the
rest of the parenchyma. The prognosis is better than in HCC. Nearly 75%
of tumors are resectable and the rate of five-year survival is over 80%.
They do not present metastases during the diagnosis. When the tumor
is unresectable, a liver transplant should be considered.
Remember
The fibrolamellar hepatocarcinoma has a better prognosis because it
appears in healthy young subjects.
Hepatoblastoma
It is a tumor that appears mainly in children under four years old, with
a predominance in men, and unknown associated risk factor. It usually
presents itself like a hepatomegaly and may have systemic manifestations such as precocious puberty, hemihypertrophy or cystathioninuria.
Usually, -fetoprotein levels are very high. They are usually solitary tumors resectable at diagnosis, and have a rate of five-year survival greater than 50% (Table 24).
Cholangiocarcinomas
They originate from epithelial cells of the intrahepatic bile ducts (intrahepatic cholangiocarcinoma) or extrahepatic (extrahepatic cholangiocarcinoma). They are sclerosing (infiltrative pattern), well-dierentiated tumors.
Intrahepatic Cholangiocarcinoma
This is a rare tumor that aects older men mostly. It is related to diseases associated with chronic cholestasis.
Congenital duct anomalies, such as Caroli disease and choledochal
cyst.
Biliary atresia. The Kasai procedure (hepatoportoenterostomy) does
not reduce the risks.
Primary sclerosing cholangitis and ulcerative colitis.
Clonorchis sinensis infestation.
Cholelithiasis and hepatolithiasis.
It does not seem to be related to the hepatitis B virus, or to cirrhosis.
The most common clinical manifestations are constitutional symptoms
and jaundice. The levels of -fetoprotein do not rise during the course of
the disease. The best diagnostic techniques are cholangiography and CT.
The staging of cholangiocarcinoma is determined according to the TNM
(AJCC/UICC) classification.
The preferred treatment for intrahepatic cholangiocarcinoma is liver
resection, although it is rarely possible. This is not a frequent tumor,
it accounts for only 5% to 10% of primitive liver cancers. It appears in
patients of about 65 years of age. The prognosis is very poor. In 75% of
the cases, at the time of the diagnosis there are signs of metastasis. The
diagnosis follows the same procedures as the diagnosis for hepatocarcinoma. Since this cancer recurs in almost all of the patients, transplant is
not recommended. Biliary stents are currently used as palliative treatment.
Remember
Unresectable cholangiocarcinomas, both intrahepatic and extrahepatic, can
be treated with palliative stents.
41
HEPATOCELLULAR
Age
Etiology
fetoprotein
DG
Prognosis and Treatment
50-60
Cirrhosis, HBV,
HCV and others
Positive in 80%
Echo, CT scan
and biopsy
MRI
Very poor. Surgery, transplantation,

alcoholization in small tumors
20-30
Positive in 20%
Echo, CT scan
and biopsy
75% resectable carcinomas. No metastasis.

Surgery or transplantation
Children < 4
years of age
Very high
Echo, CT scan
and biopsy
Good, lonely resectable tumors on

diagnosis
CARCINOMA
FIBROLAMELAR
HEPATOCARCINOMA
HEPATOBLASTOMA
Table 24. Hepatocellular carcinoma and its variants
Hilar Cholangiocarcinoma or Klatskin Tumor

This is a cholangiocarcinoma of the common hepatic tissue, close to the junction. Clinical symptoms appear early, so a prompt diagnosis can be made. In
spite of this, the prognosis is worse than that of extrahepatic cholangiocarcinomas. It appears more frequently associated with ulcerative colitis.
Treatment consists of resection of the tumor and biliary enteric reconstruction (hepaticojejunostomy Y Roux). Postoperative radiation
therapy may extend survival. In case of unresectable tumors, palliative
stents can be placed percutaneously or endoscopically. Tumors of the
distal third will be discussed in the section corresponding to Periampullary tumors. The prognosis is poorer in case of tumors of the proximal
third, and better in tumors of the distal third.
Extrahepatic Cholangiocarcinoma
This is less common than intrahepatic cholangiocarcinoma. It is also related to diseases associated with chronic cholestasis (Figure 35).
Clinical manifestations and diagnostic procedures are similar to those
of intrahepatic cholangiocarcinoma, except when it is so distal that it
acts as a periampullary tumor. The staging is determined according to
the TNM (AJCC/UICC) classification.
Remember
The prognosis of cholangiocarcinoma is poorer in the proximal bile duct.
Angiosarcoma
It is a very rare malignant tumor originating in the liver sinusoidal endothelial cells. In more than 50% of the cases, it is associated with thorium
dioxide (thorotrast) emissions. It has a latency stage of 20 years. It is
also related to arsenic, vinyl chloride, anabolic steroids and hemochromatosis.
Typical clinical signs are constitutional syndrome, liver mass, microangiopathic anemia and thrombocytopenia. It is virtually untreatable.
Complete resection is the best treatment, although in most cases they
are unresectable, and it has a two-year survival rate of 3%.
Periampullary Tumors
They include, in order of frequency, tumor in the head of the pancreas
(this will be discussed separately), ampulloma of the distal common bile
duct and periampullary duodenum. They are more common in patients
of approximately 70 years of age. In younger patients, they are associated with familial adenomatous polyposis.
It causes progressive obstructive jaundice that is initially painless. In
case of duodenal carcinoma, the most common symptom is weight loss
and upper gastrointestinal bleeding, but it may also cause duodenal obstruction similar to pyloric stenosis. Jaundice is rare in these cases.
It is usual to find hidden blood in the stool, and jaundice is more prominent than weight loss.
Remember
The best diagnostic method is ERCP.
Figure 35. Cholangiocarcinoma in the middle third of the bile duct
42
Cephalic pancreaticoduodenectomy or Whipple procedure is the preferred curative treatment for these tumors, but few patients can benefit
from it, depending on the progression of the disease. The prognosis is
better if the origin is not pancreatic.
Remember
The Whipple procedure is the preferred treatment for unresectable tumors
of the head of pancreas.
Physical examination findings depend on the stage of the disease. In the

initial stages, it is normal, and as the disease progresses, hepatomegaly
(70%), splenomegaly (35%) and scratch marks appear. In later stages,
jaundice, xanthomas or evidence of liver decompensation appear. The
presence of Kayser-Fleischer ring is quite rare.
Laboratory Tests
There is elevated alkaline phosphatase in all patients. Other enzymes
of cholestasis also increase. Transaminases are normal or slightly increased. Bilirubin rises as the disease progresses and its level correlates
with the prognosis of the disease.
Metastatic Tumors
They are the most frequent malignant liver tumors (20 times more common than primitive malignant tumors). Any tumor is capable of metastasizing, but adenocarcinomas and undierentiated carcinomas metastasize more frequently than squamous cells carcinomas.
Metastatic tumors occur more frequently in the digestive system, fundamentally in colorectal cancer, followed by lung cancer, breast cancer, melanoma and lymph involvement. Metastases are rare in the thyroid and
prostate glands. Pain in the right hypochondrium is the most frequent
clinical manifestation. In the laboratory, the most common identifying
pattern is dissociated cholestasis, especially with an increase in alkaline
phosphatase levels. The diagnosis is made by imaging and percutaneous
biopsy. Treatment is usually only palliative, although colorectal cancer can
be treated with curative intent in some cases.
There may be a very significant increase of lipids in nearly 85% of patients, often with cholesterol of more than 1000 mg/dL, and the X lipoprotein appears in serum seen in chronic cholestasis. In 70% to 80%
of cases, increased IgM is observed, and in 95% presence of AMA-M2
(specificity of 97%). AMA title does not correlate with the severity or
disease progression. ANA and antismooth muscle antibodies may appear in 35% and 66%, respectively.
Diagnosis
Diagnostic suspicion is based on clinical and laboratory data. If alkaline
phosphatase and IgM are elevated, along with the positivity of AMA, diagnosis is possible and it should be confirmed with a liver biopsy which
also enables us to set the stage. We suggest ruling out extrahepatic biliary
obstruction, given the high frequency of associated cholelithiasis.
Treatment
4.6. Chronic Cholestasis
It has two aspects: symptomatic and disease specific.
Primary Biliary Cirrhosis
Symptomatic treatment includes the use of chelating bile salts for itching,
administration of liposoluble vitamins, if they are deficient, and management of complications of any terminal liver disease.
Primary biliary cirrhosis (PBC) is a chronic and progressive cholestatic

liver disease of unknown cause that usually aects middle-aged women
between 40-60 years. The female-male ratio is 10 to 1. It seems that
genetic factors play an important role in the development of the disease
and familial cases exist. The risk of autoimmune diseases in relatives of
these patients is doubled, compared to the general population. There is
a weak association between CBP and the haplotype HLA-DR8. In 85% of
cases at least another autoimmune disease is associated.
Pathogenesis
Abnormalities of humoral and cellular immunity are common. There is
a decrease in the number of circulating T lymphocytes, probably by sequestration within the portal tracts.
Symptoms
Fatigue and pruritus are the most common symptoms at diagnosis. Between 48% and 60% of patients may be asymptomatic at the time of
diagnosis, and the disease is suspected when analytic alterations are
observed, such as increased alkaline phosphatase, detected in analytic
studies for another reasons. Occasionally, the PBC is manifested by any
of the complications of advanced liver disease.
In the specific treatment of the disease, several drugs have been tested such
as: ursodiol (ursodeoxycholic acid), colchicine, methotrexate, azathioprine
or cyclosporine. Corticosteroids and D-penicillamine are not eective.
Ursodiol has proven to be the most eective drug, postponing the time
when liver transplantation becomes necessary. It should be administered from early stages of the disease, even in asymptomatic patients.
Colchicine and methotrexate have also shown some utility. In a terminal
stage or in a situation of severe complications without treatment option, liver transplantation is necessary. The PBC can recur after transplantation.
Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease of
unknown etiology, characterized by progressive inflammation, destruction and fibrosis of the intrahepatic and extrahepatic bile ducts.
A total of 70% of patients with PSC are male, and the average age at diagnosis
is 39 years of age. A total of 75% of cases is associated with inflammatory
bowel disease, among these, in 87% of patients with ulcerative colitis and in
13% with Crohn disease. But it can occur in association with other diseases
43
such as retroperitoneal or mediastinal fibrosis, orbital pseudotumor, Riedels

thyroiditis, Sjogrens syndrome, and also in isolation and not associated with
any other disease.
4.7. Metabolic Liver Diseases
Diagnosis
Primary Hemochromatosis
It is mandatory to rule out causes of secondary sclerosing cholangitis,

such as: chronic bacterial cholangitis in patients with bile duct stenosis or choledocholithiasis, ischemic lesions in the bile ducts because of
treatment with floxuridine, HIV-associated cholangiopathy, previous
biliary surgery, congenital anomalies of the biliary tree and bile duct
tumors.
This is an autosomal recessive disorder that results in progressive accumulation of iron in the body, especially in some organs. If left untreated,
it leads to liver cirrhosis and other systemic disorders. The cause of iron
overload is not known, but it is clear that there is a genetic defect that
causes an increase in intestinal iron absorption, although there is no genetic form of hemochromatosis. The altered gene is located in chromosome 6. There is a strong association with certain HLA, especially HLA
A3 and HLA B14 and B7. A total of 80% of patients are homozygous for
the C282Y mutation in the HFE gene, located in chromosome 6.
The diagnostic method of choice is ERCP. It is characterized by multifocal narrowing and expansion, generally aecting both extrahepatic and
intrahepatic bile ducts (87% of cases); it only aects intrahepatic bile
ducts in 11% of cases and extrahepatic bile ducts in 2% of cases. The
gallbladder and cystic are aected in 15% of patients.
Biopsy leads to diagnosis in only 30% of cases. Its main role is to define
monitoring of the disease and to help determine the prognosis. The
pathognomonic sign of CEP (the onion skin lesion) is rarely seen on percutaneous liver biopsy. It is more common to find a lack of normal bile
duct with nonspecific fibrosis and inflammation in the portal tracts.
Therefore, diagnosis is usually based on cholangiography. Histologic examination is used to confirm and establish the stage of the disease.
Symptoms
Symptoms usually appear in men over 50 years of age and in women,
somewhat later, at about 60, probably given that menstruation and
pregnancy partially protect them. There are cases, however, where the
disease appears at an earlier age.
Clinical involvement is summarized in the table below. In the clinical picture skin pigmentation, diabetes, liver disease, sexual dysfunction and
restrictive cardiomyopathy usually prevail (Table 25).
Symptoms
Most patients are initially asymptomatic, and the disease is suspected
by biochemical changes, especially by alteration of the enzymes of cholestasis. Symptoms such as itching, fatigue, jaundice and weight loss
generally indicate that the disease is advanced.
Sometimes these patients have episodes similar to bacterial cholangitis
with transient worsening of liver function; it usually lasts from hours to
days, and it resolves without specific treatment.
CLINICAL PRESENTATION OF HEMOCHROMATOSIS

Liver
Deaf pain in right hypochondriac or epigastric

regions (with or without hepatomegaly).
Cirrhosis. Hepatocarcinoma
Skin
Tanned pigmentation (80%), especially in areas

exposed to the sun
Pancreas
Diabetes mellitus (65%)
Joints
Arthropathy (25% to 50%)
Heart
(Restrictive) Hemochromatosis cardiomyopathy.

Frequent and poor prognosis
Hypothalamushypophysis
Lethargy, a decrease in concentration levels and

hypothyroidism
Others
Lethargy, a decrease in concentration level and

hypothyroidism
Treatment
The management of symptoms and complication includes treatment
of pruritus with cholestyramine, colestipol or other drugs. Monitor the
levels of liposoluble vitamins and its treatment, if there are deficiencies.
Antibiotics in infectious episodes of cholangitis. Endoscopic dilation or
surgery of dominant stenosis of the extrahepatic bile ducts, although
it is desirable to avoid surgery in patients who are potential transplant
candidates.
Another problem is the increasing incidence of cholangiocarcinoma in
these patients (9% to 15%). Patients with ulcerative colitis and PSC have
a higher risk of colon cancer than those without PSC.
44
NOTE: clinical presentations depend on functional deterioration because of

iron accumulation in multiple organs and tissues
Table 25. Clinical manifestations of hemochromatosis
Diagnosis
As for the treatment of the disease, many drugs have been tried but
none has shown a clear ecacy: penicillamine, colchicine, azathioprine,
cyclosporin, etc., have not been eective. Drugs currently considered
most useful are ursodeoxycholic acid and methotrexate.
Clinical suspicion is established by measuring the parameters that inform us about iron overload, such as the rate of transferrin saturation,
or serum ferritin, which will all be greatly increased. The desferrioxamine test, which is not in use, is the intramuscular administration of
desferrioxamine, with a large increase in iron excretion in urine in patients with hemochromatosis.
In patients with advanced disease, the treatment of choice is liver transplantation.
When hemochromatosis is suspected, the presence of homozygosity

for C282Y or heterozygosity for C282Y/H63D enables diagnosis of the
disease. In suspected cases, but without mutations in the HFE genotype, liver biopsy is required to quantify iron for diagnosis. However, if
the diagnosis of hemochromatosis was established by elevated ferritin
and compatible genetic alterations, a liver biopsy may be necessary if
there are alterations in transaminases, to assess the presence of liver
cirrhosis. A family genetic study should be performed (Figure 36).
First-degree adult relative of HH
Saturation of transferrin
and serum ferritin on an empty stomach
ST < 45% and normal ferritin
ST 45% and normal ferritin
No subsequent
iron assessment
Genotype
is very characteristic and can be constant, paroxysmal or specific of

certain motor situations.
2. A psychiatric presentation. They may be early signs, profound alterations in school development, personality and behavior, with paranoid
and schizophreniform symptoms having been reported. Psychiatric
symptoms can occur in 20% of cases at disease onset and in more
than 50% of patients with neurologic involvement. If treatment for
WD is not set, there may be a progression to dementia, either because of brain pathologic changes or secondary to liver failure.
3. Presentation as liver disease, which is the most common form in
childhood. It may present as an episode of self-limited acute hepatitis or an acute hepatitis that progresses to severe liver failure in
weeks, and wich can be accompanied by Coombs negative hemolytic anemia. Sometimes the clinical picture is presented as chronic
active hepatitis or cirrhosis, or a complication of the latter. In any
event, it has not been associated with hepatocarcinoma.
4. Other rare forms of presentation are hemolytic anemia or hypersplenism, kidney disease, skeletal abnormalities or as unexplained
recurrent abortions or amenorrhea.
Diagnosis (Table 26)

C282Y/H63D
Compound
Heterozygote
C282Y or no C282Y
C282Y/C282Y
HH
Rule out other liver

or hematologic diseases
liver biopsy
Figure 36. Hematochromatosis in risk groups
Treatment
Repeated phlebotomy, extracting 500 mL once or twice a week. In patients who cannot tolerate bleeding, desferrioxamine can be used parenterally, although it is much less eective. In cases of terminal liver
disease, liver transplantation is in place. Recurrence after transplantation is possible.
Wilson Disease
It is a disease characterized by an inherited disorder in the metabolism
of copper consisting of a decrease in the incorporation of such metal in
ceruloplasmin in the liver and consequent decrease in its biliary excretion. This leads to a progressive accumulation of copper in various organs.
Symptoms
Symptoms appear between 5 and 50 years, and they can do so in three
main ways:
1. Presentation as neurologic abnormalities, whose onset is then
from age 20, as a rigid akinetic syndrome or abnormal involuntary
movements (by basal ganglia injury: lenticular nucleus and, less extensively, caudate). Tremor, rigidity, dystonia, dysarthria, dysphagia,
parkinsonism and gait instability with ataxia appear. Dysarthria and
clumsiness of the hands are the most common early signs. Tremor
Can be used various methods:

1. Kayser-Fleischer ring. It is an accumulation of copper in the Descemets
membrane of the cornea. Overall, all Wilson patients with cerebral
aectation have it and it is not present in all Wilson patients with hepatic involvement. It disappears with chelation therapy. There are KayserFleischer rings in other diseases (primary biliary cirrhosis, chronic active
hepatitis). It may be associated with cataracts (sunflower) caused by
copper deposition in the lens.
2. Concentration of serum ceruloplasmin, which is decreased in
95% of Wilsons cases. Their levels can be distorted with oral contraceptives and inflammatory diseases (it behaves as an acute
phase reactant).
3. Total concentration of serum copper. The total serum copper is decreased, but the free copper is increased.
4. Excretion of urine copper in 24 hours, which is magnified.
5. Liver biopsy with measurement of hepatic copper concentration,
which is what determines the definitive diagnosis. It also helps to
establish a histologic diagnosis of the degree of liver injury.
6. Studies with radioactive copper.
7. The combination of Alzheimer type II glial cells and Opalski has
been regarded as the pathognomonic diagnosis of WD.
CAUSES OF CIRRHOSIS
Kayser- Fleischer ring

Seric ceruloplasmin
Serum copper
Urinary copper
Liver biopsy with copper quantification
DNA tests for mutation analysis
Table 26. Diagnosis for Wilsons disease
Neuroimaging
CT. Most patients are neurologically asymptomatic with normal CT.

The most characteristic findings are: atrophy (in the cortex, caudate
nucleus, brainstem and cerebellum) and hypodensity of the lenticular
nucleus.
45
MRI. In the findings of atrophy seen

on CT, MRI can prove hyperintense lesions in the thalamus, putamen, dentate
nucleus and brainstem in T2W images.
Hypointense lesions rarely appear in the
caudate and putamen. All of this can give
the impresion of a panda bear face at a
mesencephalic level.
TREATMENT
INITIAL THERAPY/
MAINTENANCE
Peniciliamin
Yes/Yes
Increases copper
execration in urine
Trientine
Yes/Yes
Increases copper execration Sideroblastic anemia

in urine and prevents
Ferropenic anemia
intestinal absorption
Zinc
No/Yes
Increases intestinal copper

absorption and links
copper in a nontoxic way
at hepatic level
Treatment (Table 27)

Its goal is to stop disease progression and,
in many cases, to improve developed symptoms. Treatment is for life.
Penicilamine is the first-choice drug. It increases copper urine excretion. Secondary eects can cause hypersensitivity reactions (fever,
skin rash and others) and neurologic symptoms (if this is the case,
substitute with trientine, zinc or tetrathiomolybdate). Penicilamine
needs to be associated with pyridoxine.
Trientine has been the classical second-line treatment. In the last few
years, there has been an increase in the use of first-line drugs (instead
of penicilamine for hepatic and neurologic aectation). Trientine increases copper urine excretion and prevents intestinal absorption. Sideroblastic anemia and ferropenic anemia can appear as side eects.
Zinc is used in asymptomatic patients as a maintenance treatment
after detoxification. Zinc decreases intestinal absorption of copper
and, at hepatic level, binds nontoxic copper. Gastritis and elevation
of amylase and lipase are associated side eects.
Tetrathiomolybdate is the most potent chelate. It forms a nontoxic
complex with copper, preventing its tissue fixation. It is less eective and more toxic than the combination of trientine + zinc. Tetrathiomolybdate is utilized if neurologic toxicity appears with penicilamine.
In the event of terminal liver disease, hepatic transplantation will cure
the live disease in question and the metabolic disorder.
This kind of patient may develop a hepatocarcinoma in the context of
secondary cirrhosis to this process.
MECHANISM
OF ACTION
SIDE
EFFECTS
SH reactions
Neurologic clinic presentation
Gastritis
Increase in amylase and lipase
Table 27. Treatment for Wilsons disease

Gallbladder
Left hepatic duct
Right hepatic duct
Celiac trunk
Cystic duct
Bile duct
Portal vein
Cava vein
Figure 37. Anatomy of bile ducts

Stones are classified by their chemical composition and they usually
contain a variable amount of cholesterol, bilirubin, calcium and protein.
In our environment, the most common gallstones are mixed predominantly with cholesterol, which account for over 75% of cases. Pigmented stones calcify more frequently. Overall, between 25% and 35% of
stones are calcified.
Symptoms
Biliary Pathology:
Chapter 05
Diseases
of the Gallbladder
and Bile Ducts (Figure 37)
5.1. Gallstones
Gallstones usually form in the gallbladder, but they may do so at any
level of the biliary tract.
46
The majority (50%) have no symptoms. When they manifest, they are
due to complications: biliary colic (which has a peak at midnight and
corresponds pathologically to chronic cholecystitis), acute cholecystitis,
choledocholithiasis, cholangitis and acute pancreatitis.
Diagnosis of Gallstones
Ultrasound is the most widely used method. On plain abdominal x-rays
only calcified gallstones will be seen.
Treatment
In general, asymptomatic patients should not be treated. However, cholecystectomy has been recommended in some special situations (some
controversial), even if they are asymptomatic:
1. Stones greater than 2.5 cm (associated more often with acute cholecystitis than small stones).
2. Congenital anomalies with stone.
3. Diabetic patients have higher mortality rates, caused by cholecystitis (up to 20%), but most authors do not recommend prophylactic
cholecystectomy in diabetics.
4. Concomitant with obesity surgery, although this is under discussion.
5. Sickle Cell Anemia: cholecystitis may precipitate severe hemolytic crisis.
6. Vesicular calcification (porcelain gallbladder) because of its common association with bladder cancer, but the link is now in question.
Liver
Hepatic ducts
Cystic duct
Impacted lithiasis
Types of Treatment
Biliary vesicle
Duodenum
Surgery. Today, the procedure of choice is laparoscopic cholecystectomy. It has almost no mortality and minimal morbidity when performed
electively, and works better than any other treatment.
Wirsungs duct
Papilla
5.2. Acute Cholecystitis
Pancreas
(Figure 38)
Figure 38. Acute cholecystitis
Etiology
A total of 90% of cases of cholecystitis are lithiasic. The incidence is
higher in women and the most frequently implicated organism is E. coli.
However, there are cases of Acute acalculous cholecystitis (10%),
more common in males, seen in critically ill patients, traumatized patients, in severe burns, after biliary surgery, in patients with prolonged
parenteral nutrition, after cardiopulmonary bypass, in AIDS (CMV, Salmonella, Cryptosporidium), Diabetes Mellitus, systemic atherosclerosis, and in children with biliary tract abnormalities or certain systemic
diseases. The most commonly isolated organisms are Gram negative
such as E. coli, Klebsiella and group D streptococci, staphylococci, and
Clostridium. It is a very severe disease. Emphysematous cholecystitis
is a rare form of cholecystitis (1%) more frequent in males and diabetics. About 30% to 50% are acalculous. It is characterized by the presence of gas in the lumen and gallbladder wall, usually produced by
Clostridium perfringens. It evolves as a rapidly progressive sepsis, with
high mortality.
trasound is the most commonly used technique (it gives indirect signs);
however, the most specific technique is a HIDA scintigraphy (direct
signs), unless there is an associated cholestasis.
Treatment
Treatment consists of intravenous fluid intake, analgesics and antibiotics adjusted to antibiogram.
The definitive treatment of acute cholecystitis is surgery, since there is
a high risk of recurrence.
There is controversy about the most appropriate time for cholecystectomy. One of the most welcomed approaches is conservative treatment
(which is usually eective in 75% of cases), cooling the cholecystitis and
performing delayed surgery (after 4-6 weeks). After 48 hours of conservative treatment, the patient is reassessed and if progress is unsatisfactory,
early surgery is indicated.
Symptoms
Another option to avoid complications is early intervention (no more

than 72h).
The symptoms are usually triggered after significant food intake. In

most cases, it results from the impaction of a stone in the cystic duct.
The patient complains about pain in the right upper quadrant (first and
most common symptom), often radiating to the scapula, nausea, vomiting and fever. Fever may be absent, especially in ederly patients.
5.3. Gallstone Ileus
On examination, it is common to see hypersensitivity in the right upper

quadrant with pain preventing deep inspiration (positive Murphy sign).
Jaundice is unusual, or only when a cholecystopancreatitis or Mirizzi
syndrome (extrinsic compression of the common bile duct by severely
inflamed gallbladder) occurs. If the pain suddenly intensifies, and peritoneal reaction increases with fever higher than 39C and leukocytosis,
gallbladder perforation should be suspected.
Diagnosis
Diagnosis is derived from the symptoms. Analysis often reveals leukocytosis. In less than 20% of x-rays, a radiopaque stone is displayed. Ul-
(Figures 39 and 40)
Table of mechanical intestinal obstruction caused by a large gallstone

impacted in the terminal ileum, which has migrated from the biliary
tract, usually through a biliary-enteric fistula (usually duodenum).
Stones increase in size by deposition of intestinal contents therein.
However, only 15% to 20% of migrated stones will occur with intestinal
obstruction.
It occurs most often in women aged 65-75 years. At total of 50% to 75%
reports a history of biliary disease. Mortality is high due to late diagnosis and advanced age.
The radiographic study serves as diagnosis when it reveals the presence
of air in the biliary tract (aerobilia). Dilated small bowel with air-fluid
levels is also observed and in less than 20% the stone is displayed.
47
Biliary duct
Pneumobilia
Biliary vesicle
docyst, duodenal diverticulum, congenital choledochal cysts or infection caused by parasites.
Formed fistula
Biliary duct dilation

Retained bile
Infection
Duodenum
Impacted lithiasis
Caecum
Impacted calculus in distal ileum
Figure 39. Ileal and biliary pathogenesis
Figure 41. Acute cholangitis
With the onset of AIDS, there have been cases of cholangitis caused by
CMV or Cryptosporidium.
The most common route of entry of the infection is via portal. There
may also be ascending infection from the duodenum (more common
in patients that have undergone a sphincterotomy or after biliary
enteric bypass), via lymphatic or systemically through the hepatic
artery.
It is clinically characterized by the triad of Charcot: jaundice, right upper
quadrant pain and intermittent fever. They manifest with leukocytosis
and generally positive blood cultures, with E. coli as the micro-organism
most frequently isolated.
Figure 40. Ileal biliary. Calculus in ileum

The treatment of choice is enterolithotomy (location of the stone and
extraction). The recurrence rate attains almost 20%. Concomitant cholecystectomy is determined by the patients general condition and the
diculty of surgery, but many authors advise against that.
A more severe form, albeit less frequent, is acute suppurative cholangitis or acute toxic cholangitis, which occurs almost exclusively in people
over 70, and is characterized by the Reynolds pentad: triad of Charcot
plus shock and lethargy. The treatment is urgent endoscopic or surgical
decompression plus antibiotics.
5.4. Cholangitis
In the East recurrent pyogenic cholangitis, is common from bacterial

causes, presenng as intermient aacks of cholangis without biliary
calculi or stenosis.
(Figure 41)
Infection of the biliary tract, usually secondary to choledocholithiasis,

benign postoperative stenosis and tumors of the biliary and periampullary tracts. Other causes include chronic pancreatitis, pancreatic pseu-
48
The anaerobe most frequently found is Bacteroides fragilis. In most patients a good control is achieved with antibiotics and treatment of the
obstructive cause (usually ERCP). Otherwise, a surgical decompression
is needed without delay.
Other Eastern cholangitis are caused by infection with Clonorchis sinensis or by Ascaris lumbricoides. The first is treated with praziquantel and
the second with pyrantel pamoate.
Pancreatic
Chapter 06
Pathology
6.1. Acute pancreatitis

Etiopathogenesis
The most common cause of acute pancreatitis in our area is gallstones
and, second, alcohol. A total of 80% of suspected idiopathic pancreatitis
is caused by microlithiasis.
Symptoms
It usually presents as severe abdominal pain at epigastrium level and
left upper quadrant with nausea and vomiting. Pain peaks in minutes
and lasts several days.
Diagnosis
Serum amylase values three times or more above the upper limit
of normal, in a patient with abdominal pain, are diagnostic, except
in cases of perforation, intestinal infarction or involvement of the
salivary glands. There is no relationship between pollution levels and
severity.
Treatment
In the event of mild pancreatitis: absolute diet without nasogastric tube
is necesary, except in the presence of vomiting with ileus, intravenous
fluid intake and analgesia. The pain goes away in 2-4 days, and then the
food intake is reset. The use of antibiotics is not justified if there is no
evidence of infection.
In severe acute lithiasic pancreatitis (with choledocholithiasis or dilated bile duct) the course and outcome improve if an endoscopic
papillotomy is performed within 72 hours; it is an absolute indication when there is associated jaundice. Antibiotic prophylaxis is accepted in severe cases with necrosis (due to high risk of infection).
In approximately 50% of cases of necrosis, it can become infected diffusely in the first two weeks (abscess), contributing to a more severe
clinical picture. The diagnosis of infection is made with cytology directed by CT and performing Gram stain and culture of the sample. If confirmed, the solution is surgical necrosectomy.
In 4% of patients with acute pancreatitis, an infection with pus
fluid accumulation occurs at 4-6 weeks (abscess), visible on CT.
Risk factors for development of an abscess are: severe pancreatitis, postoperative pancreatitis, early oral feeding, early laparotomy
and misuse of antibiotics. It can also be formed by infection of a
pseudocyst.
The symptoms consist of fever, leukocytosis, ileus, and deterioration of
the patient. Treatment consists of surgical drainage, although in 50%
nonsurgical drainage under CT control can be useful (Figure 42).
Prognosis
Epigastric pain in belt
Nausea/vomiting
PA: lithiasis and/or alcoholism
Mortality ranges between 3% and 12%. The early identification of patients with poor prognosis is very important. There are several scales
to assess the prognosis of acute pancreatitis. The most commonly used
today are Ranson and APACHE II.
In regard to the Ranson scale, if the patient has three or more risk factors, morbidity and mortality are undoubtedly higher. Obesity must
also be regarded as a poor prognostic factor. The determinations of Creactive protein, granulocytic elastase and activation peptide of urinary
trypsinogen appear to be prognostic biochemical markers.
Amylase/lipase
Abdominal CT
High
Edema
Diagnosis of acute pancreatitis
Ransons criteria
AGE > 55
Leukocytosis > 16,000/mm3
AT THE TIME
OF ADMISSION
Hyperglycemia > 299 mg/dL

GOT > 250 UI/L
OHT > 250 UI/L
Fluid deficiency > 4L
AFTER 48 h
Severe
Mild/moderate
LDH > 400 UI/L
Calcium < 8 mg/dL

PO2 < mg/dL
of BUN > 5 mg/dL
Analgesia
Absolute diet
3-5 days
If lithiasis:
assess
cholecystectomy
If cholangitis
Enteral
or biliary duct
nutrition
obstruction
with
NGP vs TPN
ERCP
If infected
necrosis
Antibiotics +
necrosectomy
If pseudocyst
Follow up
Albumin < 3.2 g/dL
Figure 42. Diagnostic-theurapeutic diagram of acute pancreatitis

Table 28. Ransons criteria
49
Complications
Most patients have mild pancreatitis, requiring less than a week of hospitalization. However, multiple complications may occur early and late
in acute pancreatitis, which cause the mortality rate to reach 10%.
Pseudocyst. It is the most common complication of acute pancreatitis, although the most common cause is chronic pancreatitis. Fluid collections
are displayed in 15% of patients with acute pancreatitis between one and
four weeks after onset of the disease. They have no capsule. A total of 90%
are by pancreatitis and 10% by traumas; 85% are located in the body and
tail of the pancreas and 15% in the head. The usual presentation is abdominal pain. Abdominal mass is palpable. Hyperamylasaemia appears in 75%
of cases. CT is required for diagnosis and ultrasound is used for tracking.
A total of 25% to 40% of the pseudocysts resolve spontaneously. Asymptomatic pseudocysts gradually decrease in size on successive scans
should be monitored without treatment. A pseudocyst of more than 6
cm that persists more than six weeks is unlikely to resolve spontaneously, so it should be operated. This occurs most often in chronic pancreatitis. consists of conducting an internal drainage, variable depending on
the location: cystogastrostomy, cystoduodenostomy or cistoyeyunostomy in Y-Roux (this option is the most desirable). Surgical excision is reserved for a minority of pseudocysts located in the tail of the pancreas.
Complications of pseudocysts include: compression because of the
mass, pain, rupture, hemorrhage, and abscess. The rupture of a pseudocyst has a mortality of 14%, if there is no bleeding, and 60% if bleeding
is observed; rupture and bleeding are two leading causes of death in the
pancreatic pseudocyst.
Some pseudocysts that rapidly increase in size or become infected during
the observation can be treated with percutaneous external drainage. This
technique has a high rate of pancreatic fistula, so it is recommended only in
cases of general malaise. The placement of a transpapillary prosthesis using
endoscopy can be useful in small size pseudocysts with a single cavity, communicated with the pancreatic duct. It appears that the treatment of these
fistulas with somatostatin can reduce the deficit and accelerate healing.
6.2. Chronic Pancreatitis

It may appear after repeated outbreaks of acute pancreatitis or as
a result of chronic damage. The pathophysiology of the disorder is
not known with certainty. It is thought to be due to precipitation of
proteins in the ducts or direct damage of alcohol in the pancreas.
Etiology
The most common cause is chronic alcoholism; less common are hereditary, tropical, obstructive, or hyperparathyroidism. A total of 25%
are idiopathic.
Symptoms
Patients with recurrent chronic pancreatitis have identical symptoms to
acute pancreatitis. Pain is the main symptom, with localization similar
to that of acute pancreatitis.
50
The pain can be triggered by food, and may become constant or so severe that frequent use of narcotics may be required. The pain diminishes as the disease progresses. A loss of more than 90% of the exocrine
function of the pancreas is needed for events of maldigestion, to develop which can lead, among other manifestations, to a significant steatorrhea and B12 deficit (40% in alcoholics). When pancreatic islets are
aected, over the years glucose intolerance and diabetes mellitus may
develop over the years, which has less risk of ketoacidosis but more of
hypoglycemia. The typical triad of pancreatic calcifications, steatorrhea
and diabetes appears in only 30% of patients.
Diagnosis
Amylase and lipase levels are usually normal. There may be increased
alkaline phosphatase and bilirubin caused by secondary cholestasis
with respect to chronic inflammation around the bile duct.
Pancreatic calcifications are very common. Diagnosis is mainly through
imaging. The visualization of calcification is diagnostic: it may be sufficient to objectify on abdominal Rx plain (30%), and if not, use ultrasound, or even better, because of its high sensitivity, abdominal CT.
Complications
The main complications of chronic pancreatitis are:
1. Obstruction of the common bile. There is a transient partial bile
duct obstruction during acute pancreatitis due to pancreatic inflammation and edema, which manifests itself in elevated blood
bilirubin, which resolves when pancreatitis heals.
The common bile duct stenosis secondary to chronic pancreatitis is
the result of repeated inflammation and fibrosis. They are smooth
and long strictures aecting the intrapancreatic bile duct. Elevated
alkaline phosphatase is the most common analysis which is altered.
The patient may have abdominal pain and jaundice. It may be complicated by cholangitis, and even lead to secondary biliary cirrhosis.
It can be easily mistaken with malignant strictures. CT is the best
method for studying the pancreas and cholangiography is the ultimate test to delineate the biliary tree. Surgery is indicated in symptomatic patients with biliary diversion of choice.
2. Duodenal obstruction. The most common duodenal obstruction is
due to pancreatic head cancer and it is uncommon in chronic pancreatitis. Pyloric obstruction is almost universal in situations of pancreatic inflammation by phlegmon or abscess, and it is transient.
Pancreatic pseudocysts also produce extrinsic compression, primarily of the stomach. The duodenal obstruction of chronic pancreatitis typically provokes vomiting, upper abdominal pain and weight
loss. It is diagnosed by gastroduodenal transit, and treatment is abdominal rest, NGT and TPN. If the obstruction persists, it is necessary to perform a gastrojejunostomy.
3. Pancreatic pseudocyst. See previous chapter.
4. Pancreatic fistulas. They may form in the mediastinum or in the
abdominal cavity, producing ascites and/or pancreatic pleural eusion. Pathogenesis is due to disruption of the main pancreatic duct
during the pancreatitis attack. If the disruption is in the front of the
pancreas, pancreatic ascites, without peritonitis, occurs because
pancreatic enzymes are not activated. Ascites are painless. It manifests itself as painless progressive abdominal enlargement. Massive
ascites are common, refractory to diuretic therapy. It is usually a
clear, amber fluid. It is diagnosed when amylase is elevated in ascites fluid. Bilirubin can also be elevated.
If the disruption occurs in the backside, the secretions are directed

by the retroperitoneum to the mediastinum, producing pancreatic
pleural eusion, which should not be confused with the small left
pleural eusion, which frequently occurs in acute pancreatitis and
does not need treatment.
Figures in the pleural fluid amylase are also elevated.
Initial treatment is medical, thoracentesis and paracentesis are sometimes required. Analogs of somatostatin, such as octreotide, are
useful. If medical treatment fails, surgery is indicated to locate the
fistula and perform a Roux-Y.
There are also fistulas to hollow viscera, the most frequent being
the transverse colon and splenic flexure of the colon, stomach, duodenum and bile duct. Bleeding is the most common symptom. It is
usually associated with an abscess. Treatment is surgical.
5. Any benign or malignant condition that aects the pancreas can
produce a splenic vein thrombosis by venous intimal involvement
or extrinsic compression, causing blood stasis and thrombosis. The
most common cause is pancreatic cancer, followed by chronic pancreatitis. It is often asymptomatic. The result is a left portal hypertension with gastric and esophageal varices.
The most common complication is gastrointestinal bleeding. Splenomegaly and intermittent abdominal pain are shown in 36% and 26% of patients, respectively. The best diagnostic method is arterial angiography
in venous phase. A CT is necessary to rule out neoplasia, and endoscopy
is useful for diagnosing and treating bleeding varices. Treatment is splenectomy, in patients with symptomatic thrombosis of the splenic vein.
6. Other. Pseudoaneurysms, subcutaneous fat necrosis, bone pain, arthritis, and increased risk of pancreatic cancer.
Treatment
Analgesics are needed if in pain, although for intractable pain surgery
may be needed for intractable pain. Administration of pancreatic enzyme
preparations is useful, if there is steatorrhea. The new enzyme capsules
have a cover for protection against acid. They can also be used as analgesia, as they relieve pain by indirectly reducing pancreatic secretion.
Antacids with calcium and magnesium must be avoided because they
bind to fats and hinder their uptake. Pseudocysts appearing in exacerbations of chronic pancreatitis require surgery much more often because of the risk of complications.
Surgical Treatment
Treatment of chronic pancreatitis is basically medical. The main indications for surgical treatment are:
Persistent, uncontrolled pain with morphics, often related to poor
drainage of Wirsung (obstruction or stenosis). It is the most common indication.
Obstructive jaundice.
Inability to rule out an underlying malignancy.
Complications.
51

Usmle 01 1415 Manual DG

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Usmle 01 1415 Manual DG

Uploaded by

Copyright:

Available Formats

Gastroenterology

Beatriz Merino Rodrguez

A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

02. Gastric Pathology ................................................................................... 7

03. Pathology of the Small

04. Liver Pathology ...................................................................................... 34

Study of Patients with Hepatobiliary Disease ......................... 34

05. Biliary Pathology: Diseases

06. Pancreatic Pathology ..................................................................... 49

G astro e nte ro l ogy

Chronic Pyrosis Age > 50

Figure 1. Dierential diagnosis of dysphagia

Treatment, in general, for the disease aecting this symptom.

In the primary achalasia, there is an alteration in the esophageal

A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

prior myotomy, children, the existence of an epiphrenic diverticulum

Low surgical risk

High surgical risk

According to patients preference

Figure 2. Achalasia: esophageal dilation

Figure 3. Therapeutic algorithm of achalasia

G astro e nte ro l ogy

Diffuse Esophageal Spasm

If all of the above fails, it may be useful a longitudinal myotomy of the

1.2. Gastroesophageal Re lux Disease

It is shown that there is a localized patchy degeneration in the nerve,

Incomplete LES relaxation

Table 1. Dierential diagnosis of esophagus motor disorders

A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

extraesophageal, and also to assess the ecacy of drug treatment if

Figure 4. Esophagitis (endoscopy)

Figure 5. Barretts esophagus

Surgical Treatment of GERD

Figure 6. Erosions in Barretts esophagus

G astro e nte ro l ogy

1.3. Infectious Esophagitis

diagnosis is the observation of the fungus in properly dyed brushing

1.4. Esophageal Diverticula

Figure 7. Digestive endoscopy revealing CMV pathology

Figure 8. Zenkers diverticulum

A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

1.5. Hiatal Hernia

Sliding Hernia or Type I (90%)

The most common complication is recurrent, chronic, asymptomatic

1.6. Squamous Cell Carcinoma

The esophagogastric junction is displaced through the hiatus. There is no

It is the most common type of neoplasia worldwide.

Paraesophageal Hernia or Type II (10%)

Incidence and etiology

Figure 9. Types of Paraesophageal hiatal hernies

Symptoms and diagnosis

G astro e nte ro l ogy

Histologically, there is loss of gastric mucosa with erosions and diused

The most frequent clinical case is upper gastrointestinal bleeding with

Resection (esophagectomy) and chemotherapy are performed whenever possible.

Treatment consists of improving the underlying illness, steps adopted

In the frequent cases of unresectable disease, mitigation techniques are

A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

The disease is more common in northern Europe and it predominates

Alcohol. Following ingestion, subepithelial bleeding is frequently

Atrophic gastritis without pernicious anemia is more common than the

Acute Gastritis Because of H. Pylori

H. Pylori-Associated Gastritis. Type B Gastritis