¹ 6. Stomach. Gastrointestinal
Diseases (Gastritis. Ulcers.).
In anatomy, the stomach (in
ancient Greek στόμαχος) is an organ of
the gastrointestinal tract involved in the second phase of digestion, following
mastication. The terms gastro- and gastric (meaning related to the stomach) are
derived from the Latin words Ventriculus] and Gaster (Greek
γαστήρ).
Functions
The stomach is usually a highly
acidic environment due to gastric acid production and secretion which produces
a luminal pH range usually between 1 and 4 depending on food intake and other
factors. Such an environment is able to break down large molecules (such as
from food) to smaller ones so that they can eventually be absorbed from the
small intestine. The stomach can produce and secrete about 2 to 3 liters of gastric acid
per day.
Pepsinogen is secreted by chief
cells and turns into pepsin under low pH conditions and is a necessity in
protein digestion.
Absorption of vitamin B12 from
the small intestine is dependant on conjugation to a glycoprotein called
intrinsic factor which is produced by parietal cells of the stomach.
Other functions include absorbing
water, some ions, and some lipid soluble compounds such as alcohol, aspirin,
and caffeine.
Anatomy
of the human stomach
The stomach lies between the
esophagus and the duodenum (the first part of the small intestine). It is on
the left side of the abdominal cavity. The top of the stomach lies against the
diaphragm. Lying beneath the stomach is the pancreas, and the greater omentum
which hangs from the greater curvature.
Two smooth muscle valves, or
sphincters, keep the contents of the stomach contained. They are the Cardiac or
esophageal sphincter dividing the tract above, and the Pyloric sphincter
dividing the stomach from the small intestine.
In humans, the stomach has a
volume of about 50 mL when empty. After a meal, it generally expands to hold
about 1 litre
of food, but it can actually expand to hold as much as 4 litres . When drinking
milk it can expand to just under 6 pints , or 3.4 litres .
Sections
The stomach is divided into four
sections, each of which has different cells and functions. The sections are:
|
Cardia |
where the
contents of the esophagus empty into the stomach. |
|
Fundus |
formed by the
upper curvature of the organ. |
|
Body |
the main, central region. |
|
Pylorus or antrum |
the lower section of the organ
that facilitates emptying the contents into the small intestine. |
Vessels and
nerves
• Arteries:
The arteries supplying the
stomach are branches of the celiac trunk. They are the left gastric, the right
gastric, left gastroepiploic, right gastroepiploic and short gastric arteries.
They supply the muscular coat, ramify in the submucous coat, and are finally
distributed to the mucous membrane.
• Capillaries: The arteries break up at the
base of the gastric tubules into a plexus of fine capillaries, which run upward
between the tubules, join with each other, and end in a plexus of larger capillaries,
which surround the mouths of the tubes, and also form hexagonal meshes around
the ducts.
• Veins: From these the veins arise, and
pursue a straight course downward, between the tubules, to the submucous
tissue; They end either in the splenic and superior
mesenteric veins, or directly in the portal vein.
• Lymphatics: The lymphatics are numerous:
They consist of a superficial and a deep set, and pass to the lymph glands
found along the two curvatures of the organ.
• Nerves: The nerves are the terminal
branches of the right and left and other parts, the former being distributed
upon the back, and the latter upon the front part of the organ. A great number
of branches from the celiac plexus of the sympathetic are also distributed to
it. Nerve plexuses are found in the submucous coat and between the layers of
the muscular coat as in the intestine. From these plexuses fibrils are
distributed to the muscular tissue and the mucous membrane. Contrary to popular
belief, you have more nerve endings in your stomach than in your head.
Histology
of the human stomach
Layers
Like the other parts of the
gastrointestinal tract, the stomach walls are made of the following layers,
from inside to outside:
|
The
first main layer is the "mucosa". This consists of an epithelium,
the lamina propria underneath, and a thin bit of smooth muscle called the muscularis
mucosae. |
|
|
submucosa |
The
"submucosa" lies under this and consists of fibrous connective
tissue, separating the mucosa from the next layer. The Meissner's
plexus is in this layer. |
|
muscularis externa |
The
"muscularis externa" in the stomach differs from that of other GI
organs in that it has three layers of smooth muscle
instead of two.
|
|
serosa |
Under these muscle layers is the "serosa",
layers of connective tissue continuous with the omenta. |
Cross section of
stomach wall.
Microscopic
cross section of the pyloric part of the stomach wall.
Glands
The epithelium
of the stomach forms deep pits. The glands at these locations are named for the
corresponding part of the stomach:
|
Cardiac glands |
Pyloric glands |
Fundic glands |
|
|
|
|
Different
types of cells are found at the different layers of these glands:
|
Layer of stomach |
Name |
Secretion |
Region of stomach |
Staining |
|
Isthmus of gland |
goblet cells |
mucus gel layer |
Fundic, cardiac, pyloric |
Clear |
|
Neck of gland |
parietal (oxyntic) cells |
gastric
acid and intrinsic factor |
Fundic, cardiac, pyloric |
Acidophilic |
|
Base of gland |
chief (zymogenic) cells |
pepsinogen, rennin |
Fundic only |
Basophilic |
|
Base of gland |
enteroendocrine (APUD) cells |
hormones |
Fundic, cardiac, pyloric |
- |
Control
of secretion and motility
The
movement and the flow of chemicals into the stomach are controlled by both the autonomic
nervous system and by the various digestive system hormones:
|
Gastrin |
The
hormone gastrin causes an increase in the secretion of HCl, pepsinogen
and intrinsic factor from parietal cells in the stomach. It also causes
increased motility in the stomach. Gastrin is released by G-cells in the
stomach to distenstion of the antrum, and digestive products. It is inhibited
by a pH normally less than 4 (high acid), as well as the hormone somatostatin. |
|
Cholecystokinin |
Cholecystokinin
(CCK) has most effect on the gall bladder, but it also decreases gastric
emptying. |
|
Secretin |
In
a different and rare manner, secretin, produced in the small
intestine, has most effects on the pancreas, but will also diminish acid
secretion in the stomach. |
|
Gastric inhibitory peptide |
Gastric
inhibitory peptide (GIP) decreases both gastric acid
and motility. |
|
Enteroglucagon |
enteroglucagon
decreases both gastric acid and motility. |
Other
than gastrin, these hormones all act to turn off the stomach action. This is in
response to food products in the liver and gall bladder, which have not yet
been absorbed. The stomach needs only to push food into the small intestine
when the intestine is not busy. While the intestine is full and still digesting
food, the stomach acts as storage for food.
Ruminants
In ruminants,
such as bovines, the stomach is a large multichamber organ which hosts symbiotic
bacteria
that produce enzymes required for the digestion of cellulose from plant matter.
The partially digested plant matter passes through each of the intestine
chambers in sequence, being regurgitated and rechewed at least once in the
process.
Diseases of the
stomach
• Dyspepsia
• Stomach
ache
• Peptic
ulcer
• Achlorhydria
• Hypochlorhydria
• Linitis
plastica
• Zollinger-Ellison
syndrome
• Gastroparesis
• GERD
• Borborygmus
Historically,
it was widely believed that the highly acidic environment of the stomach would
keep the stomach immune from infection. However, a large number of studies have
indicated that most cases of stomach ulcers, gastritis and stomach cancer are
caused by Helicobacter pylori infection. One of the ways it's able to survive
in the stomach has to do with its urease enzyme which metabolizes urea to
ammonia and bicarbonate which neutralizes gastric acid and thus prevents its
digestion. It is thought by some that excess gastric acid can cause stomach
ulcers in the presence of holes in the mucus gel layer.
Ulcer
Endoscopic images of a duodenal ulcer.
An ulcer
(from Latin ulcus) is an open sore of the skin, eyes or mucous membrane,
often caused, but not exclusively, by an initial abrasion and generally
maintained by an inflammation, an infection, and/or medical conditions which
impede healing. Or in other words, it is a macroscopic discontinuity of the
normal epithelium (microscopic discontinuity of epithelium is called erosion).
Other causes of skin ulcerations include pressure from various sources and
venous insufficiency.
Peptic ulcer
Classification
and external resources
Deep gastric ulcer
ICD-10 K25–K27
ICD-9 531–534
DiseasesDB 9819
MedlinePlus 000206
eMedicine med/1776 ped/2341
MeSH D010437
Classification
By
Region/Location
·
Duodenum (called duodenal ulcer)
he
duodenum /ˌduːəˈdinəm/ is the first section of the small
intestine in most higher vertebrates, including mammals, reptiles, and birds.
In fish, the divisions of the small intestine are not as clear, and the terms
anterior intestine or proximal intestine may be used instead of duodenum. In
mammals the duodenum may be the principal site for iron absorption.
The
duodenum precedes the jejunum and ileum and is the shortest part of the small
intestine, where most chemical digestion takes place The name duodenum is from
the Latin duodenum digitorum, or "twelve fingers' breadth".
In
humans, the duodenum is a hollow jointed tube about 25-38cm (10-
Schematic
diagram of the gastrointestinal tract, highlighting the duodenum.
Function
The
duodenum is largely responsible for the breakdown of food in the small
intestine, using enzymes. Brunner's glands, which secrete mucus, are found in
the duodenum. The duodenum wall is composed of a very thin layer of cells that
form the muscularis mucosae. The duodenum is almost entirely retroperitoneal.
The
duodenum also regulates the rate of emptying of the stomach via hormonal
pathways. Secretin and cholecystokinin are released from cells in the duodenal
epithelium in response to acidic and fatty stimuli present there when the
pylorus opens and releases gastric chyme into the duodenum for further
digestion. These cause the liver and gall bladder to release bile, and the
pancreas to release bicarbonate and digestive enzymes such as trypsin, lipase
and amylase into the duodenum as they are needed.
Sections
The
duodenum is divided into four sections for the purposes of description. The
first three sections curve in a "C"-loop concavity in which the head
of the pancreas lies. Only the first
First
part
The
first (superior) part begins as a continuation of the duodenal end of the
pylorus. From here it passes laterally (right), superiorly and posteriorly, for
approximately
·
Anterior
·
Gallbladder
·
Quadrate lobe of liver
·
Posterior
·
Bile duct
·
Gastroduodenal artery
·
Portal vein
·
Inferior vena cava
·
Head of pancreas
·
·
Neck of gallbladder
·
Hepatoduodenal ligament (lesser
omentum)
·
Inferior
·
Neck of pancreas
·
Greater omentum
·
Head of pancreas
Second
part
The
second (descending) part of the duodenum begins at the superior duodenal
flexure. It passes inferiorly to the lower border of vertebral body L3, before
making a sharp turn medially into the inferior duodenal flexure (the end of the
descending part).
The
pancreatic duct and common bile duct enter the descending duodenum, commonly
known together as the hepatopancreatic duct (or pancreatic duct in the
Third
part
The
third (inferior/horizontal) part of the duodenum begins at the inferior
duodenal flexure and passes transversely to the left, crossing the right
ureter, right testicular/ovarian vessels, inferior vena cava, abdominal aorta,
superior mesenteric artery and the vertebral column.
Fourth
part
The
fourth (ascending) part passes superiorly, either anterior to, or to the left
of, the aorta, until it reaches the inferior border of the body of the
pancreas. Then, it curves anteriorly and terminates at the duodenojejunal
flexure where it joins the jejunum. The duodenojejunal flexure is surrounded by
a peritoneal fold containing muscle fibres: the ligament of Treitz.
Blood
supply
The
duodenum receives arterial blood from two different sources. The transition
between these sources is important as it demarcates the foregut from the
midgut. Proximal to the 2nd part of the duodenum (approximately at the major
duodenal papilla – where the bile duct enters) the arterial supply is from the
gastroduodenal artery and its branch the superior pancreaticoduodenal artery.
Distal to this point (the midgut) the arterial supply is from the superior
mesenteric artery (SMA), and its branch the inferior pancreaticoduodenal artery
supplies the 3rd and 4th sections. The superior and inferior
pancreaticoduodenal arteries (from the gastroduodenal artery and SMA
respectively) form an anastomotic loop between the celiac trunk and the SMA; so
there is potential for collateral circulation here.
The
venous drainage of the duodenum follows the arteries. Ultimately these veins
drain into the portal system, either directly or indirectly through the splenic
or superior mesenteric vein.
Lymphatic
drainage
The
lymphatic vessels follow the arteries in a retrograde fashion. The anterior
lymphatic vessels drain into the pancreatoduodenal lymph nodes located along
the superior and inferior pancreatoduodenal arteries and then into the pyloric
lymph nodes (along the gastroduodenal artery). The posterior lymphatic vessels
pass posterior to the head of the pancreas and drain into the superior
mesenteric lymph nodes. Efferent lymphatic vessels from the duodenal lymph
nodes ultimately pass into the celiac lymph nodes.
·
Esophagus (called esophageal ulcer)
·
Stomach (called gastric ulcer)
he
stomach is a muscular, hollow, dilated part of the digestion system which
functions as an important organ of the digestive tract in some animals,
including vertebrates, echinoderms, insects (mid-gut), and molluscs. It is
involved in the second phase of digestion, following mastication (chewing).
The
stomach is located between the esophagus and the small intestine. It secretes
protein-digesting enzymes called protease and strong acids to aid in food
digestion, (sent to it via oesophageal peristalsis) through smooth muscular
contortions (called segmentation) before sending partially digested food
(chyme) to the small intestines.
The
word stomach is derived from the Latin stomachus which is derived from the
Greek word stomachos, ultimately from stoma (στόμα),
"mouth". The words gastro- and gastric (meaning related to the
stomach) are both derived from the Greek word gaster (γαστήρ).
Diagram from cancer.gov:
*
1. Body of stomach
* 2. Fundus
* 3. Anterior wall
* 4. Greater curvature
* 5. Lesser curvature
* 6. Cardia
* 9. Pyloric sphincter
* 10. Pyloric antrum
* 11. Pyloric canal
* 12. Angular notch
* 13. Gastric canal
* 14. Rugal folds
Anatomy
of the stomach
The stomach lies between the
esophagus and the duodenum (the first part of the small intestine). It is on
the left upper part of the abdominal cavity. The top of the stomach lies
against the diaphragm. Lying behind the stomach is the pancreas. The greater
omentum hangs down from the greater curvature.
Greater omentum and stomach
Two
sphincters keep the contents of the stomach contained. They are the esophageal
sphincter (found in the cardiac region, not an anatomical sphincter) dividing
the tract above, and the Pyloric sphincter dividing the stomach from the small
intestine.
Stomach
The
stomach is surrounded by parasympathetic (stimulant) and orthosympathetic
(inhibitor) plexuses (networks of blood vessels and nerves in the anterior
gastric, posterior, superior and inferior, celiac and myenteric), which
regulate both the secretions activity and the motor (motion) activity of its
muscles.
In adult humans, the stomach
has a relaxed, near empty volume of about 45 to 75 ml[4]. Because it is a
distensible organ, it normally expands to hold about one litre of food,[5] but
can hold as much as two to three litres. The stomach of a newborn human baby
will only be able to retain about 30 ml.
·
Meckel's diverticulum (called
Meckel's diverticulum ulcer; is very tender with palpation)
A
Meckel's diverticulum, a true congenital diverticulum, is a small bulge in the
small intestine present at birth. It is a vestigial remnant of the
omphalomesenteric duct (also called the vitelline duct or yolk stalk), and is
the most frequent malformation of the gastrointestinal tract. It is present in
approximately 2% of the population, with males more frequently experiencing
symptoms.
It
was first described by Fabricius Hildanus in the sixteenth century and later named
after Johann Friedrich Meckel, who described the embryological origin of this
type of diverticulum in 1809.
Schematic
drawing of a Meckel's diverticulum with a part of the small intestine.
Meckel's
diverticulum is located in the distal ileum, usually within about 60–100 cm (
As
the vitelline duct consists of pluripotent cell lining, Mekel’s diverticulum
may harbor abnormal tissues, containing embryonic remnants of other tissue
types. Jejunal, duodenal mucosa or Brunner tissue were each found in 2% of
ectopic cases. Heterotopic rests of gastric mucosa and pancreatic tissue are
seen in 60% and 6% of cases respectively. Heterotopic means the displacement of
an organ from its normal anatomic location.
A
memory aid is the rule of 2s: 2% (of the population).
However,
the exact value for the above criteria range from 0.2-5 (for example,
prevalence is probably 0.2-4%).
It
can also be present as an indirect hernia, typically on the right side, where
it is known as a "Hernia of Littré". A case report of
strangulated umbilical hernia with Meckel's diverticulum has also been
published in the literature. Furthermore, it can be attached to the umbilical
region by the vitelline ligament, with the possibility of vitelline cysts, or
even a patent vitelline canal forming a vitelline fistula when the umbilical
cord is cut. Torsions of intestine around the intestinal stalk may also occur,
leading to obstruction, ischemia, and necrosis.
Symptoms
The
majority of people afflicted with Meckel's diverticulum are asymptomatic. If
symptoms do occur, they typically appear before the age of two.
The
most common presenting symptom is painless rectal bleeding such as melaena-like
black offensive stools, followed by intestinal obstruction, volvulus and
intussusception. Occasionally, Meckel's diverticulitis may present with all the
features of acute appendicitis. Also, severe pain in the epigastric region is
experienced by the patient along with bloating in the epigastric and umbilical
regions. At times, the symptoms are so painful such that they may cause
sleepless nights with acute pain felt in the foregut region, specifically in the
epigastric and umbilical regions.
Most
of the time, bleeding occurs without warning and stops spontaneously. The
symptoms can be extremely painful, often mistaken as just stomach pain
resulting from not eating or constipation.
Diagnosis
A
technetium-99m (99mTc) pertechnetate scan, also called Meckel scan, is the
investigation of choice to diagnose Meckel's diverticula. This scan detects
gastric mucosa; since approximately 50% of symptomatic Meckel's diverticula
have ectopic gastric or pancreatic cells contained within them, this is
displayed as a spot on the scan distant from the stomach itself. This scan is
highly accurate and noninvasive, with 95% specificity and 85% sensitivity.
Patients
with these misplaced gastric cells may experience peptic ulcers as a
consequence. Therefore, other tests such as colonoscopy and screenings for
bleeding disorders should be performed, and angiography can assist in
determining the location and severity of bleeding. Colonoscopy might be helpful
to rule out other sources of bleeding but it is not used as an identification
tool. Angiography might identify briskly bleeding in patients with Meckel's
diverticulum..
Ultrasonography
could demonstrate omphaloenteric duct remnants or cysts. Computed tomography
(CT scan) might be a useful tool to demonstrate a blind ended and inflamed
structure in the mid-abdominal cavity, which is not an appendix.
In
asymptomatic patients, Meckel's diverticulum is often diagnosed as an
incidental finding during laparoscopy or laparotom
Treatment
Meckel's
diverticulum surgical specimen.
Treatment
is surgical, potentially with laparoscopic resection. In patients with
bleeding, strangulation of bowel, bowel perforation or bowel obstruction,
treatment involves surgical resection of both the Meckel's diverticulum itself
along with the adjacent bowel segment, and this procedure is called a small
bowel resection. In patients without any of the aforementioned complications,
treatment involves surgical resection of the Meckel's diverticulum only, and this
procedure is called a simple diverticulectomy.
With
regards to asymptomatic Meckel's diverticulum, some recommend that a search for
Meckel's diverticulum in every case of appendicectomy/ laparotomy done for
acute abdomen should be conducted, and if found, Meckel's diverticulectomy or
resection should be performed to avoid secondary complications arising from it
Epidemiology
Meckel's
Diverticulum occurs in about 2% of the population. Prevalence in males is 3-5
times higher than in females. Only 2% of cases is symptomatic, which usually
presents among children at the age of 2.
Most
cases of Meckel's diverticulum are diagnosed when complications manifest or
incidentally in unrelated conditions such as laparotomy, laparoscopy or
contrast study of the small intestine. Classic presentation in adults includes
intestinal obstruction and inflammation of the diverticulum (diverticulitis).
Painless rectal bleeding most commonly occurs in toddler.
Inflammation
in the ileal diverticulum has symptoms that mimic appendicitis, therefore its
diagnosis is of clinical importance. Detailed knowledge of the
pathophysiological properties is essential in dealing with the life threatening
complications of Meckel's diverticulum.
Developmental
background
The
omphalomesenteric duct (omphaloenteric duct, vitelline duct or yolk stalk)
normally connects the embryonic midgut to the yolk sac ventrally, providing
nutrients to the midgut during embryonic development. The vitelline duct
narrows progressively and disappears between the 5th and 8th weeks gestation.
In
Meckel’s diverticulum, the proximal part of vitelline duct fails to regress and
involute, which remains as a remnant of variable length and location. The
solitary diverticulum lies on the antimesenteric border of the ileum (opposite
to the mesenteric attachment) and extends into the umbilical cord of the
embryo. The left and right vitelline arteries originate from the primitive
dorsal aorta, and travel with the omphaloenteric duct. The right becomes the
superior mesenteric artery that supplies a terminal branch to the diverticulum,
while the left involutes. Having its own blood supply, Meckel’s diverticulum is
susceptible to obstruction or infection.
Other
possible types of omphaloenteric duct anomalies
1.
An omphalomesentric ligament/ fibrous band connecting the diverticulum to the
umbilicus.
Omphalomesentric
ligament/ fibrous band
2.
An open omphalomesenteric fistula developing from the persisting
intra-abdominal part of the ophaloenteric duct.
Omphalomesenteric
fistula
3.
An omphalomesentric cyst/ enterocyst connecting the umbilicus with the
abdominal wall due to part of the vaitelline duct persists within the abdominal
wall.
Omphaloenteric
cyst within the umbilicus and the fibrous remnant of the omphaloenteric duct
Vitelline
artery extends along the fibrous remnant of the omphaloenteric duct
5.
Formation of a twisted (volvulus) ileal diverticulum and an umbilical sinus
from the persistence of the omphaloenteric duct in the umbilicus
Pathophysiology
of Complications
Haemorrhage
Bleeding
of the diverticulum is most common in young children, especially in males who
are less than 2 years of age. Symptoms may include bright red blood in
stools(hematochezia), weakness, abdominal tenderness or pain, and even anaemia
in some cases.
Haemorrhage
may be caused by:
Ectopic
gastric or pancreatic mucosa
Where
diverticulum contains embryonic remnants of mucosa of other tissue types.
Secretion
of gastric acid or alkaline pancreatic fluid from the ectopic mucosa leads to
ulceration in the adjacent ileal mucosa i.e. peptic or pancreatic ulcer (Figure
1.9).
Pain,
bleeding or perforation of the bowel at the diverticulum may result.
Mechanical
stimulation may also cause erosion and ulceration.
Gastrointestinal
bleeding may be self-limiting but chronic bleeding may lead to iron deficiency
anaemia.
The
appearance of stools may indicate the nature of haemorrhage:
Tarry
stools: Alteration of blood produced by slow bowel transit due to minor
bleeding in upper gastrointestinal tract
Bright
red blood stools: Brisk haemorrhage
Stools
with blood streak: Anal fissure
Currant
jelly stools: Ischaemia of the intestine leads to copiod mucus production, may
indicate that one part of the bowel invaginates into another (intussusception)
Diverticulitis
Inflammation
of the diverticulum can mimic symptoms of appendicitis i.e. periumbilical tenderness
and intermittent crampy abdominal pain. Perforation of the inflamed
diverticulum can result in peritonitis. Diverticulitis can also cause
adhesions, leading to intestinal obstruction.
Diverticulitis
may result from:
Association
with the mesodiverticular band attaching to the diverticulum tip where torsion
has occurred, causing inflammation and ischaemia.
Peptic
ulceration resulting from ectopic gastric mucosa of the diverticulum
Following
perforation by trauma or ingested foreign material e.g. stalk of vegetable,
seeds or fish/chicken bone that become lodged in Meckel's diverticulum.
Luminal
obstruction due to tumors, enterolith, foreign body, causing stasis or
bacterial infection..
Association
with acute appendicitis
Intestinal
obstruction
Symptoms:
Vomiting, abdominal pain and severe or complete constipation.
The
vitelline vessels remnant that connects the diverticulum to the umbilicus may
form a fibrous or twisting band (volvulus), trapping the small intestine and
causing obstruction (Figure 2.0). Localised periumbilical pain may be
experienced in the right lower quadrant (like appendicitis).
Incarceration:
when a Meckel’s diverticulum is constricted in an inguinal hernia, forming a
Littré hernia that obstructs the intestine.
Chronic
diverticulitis causing stricture
Strangulation
of the diverticulum in the obturator foramen
Tumors
e.g. carcinoma: direct spread of an adenocarcinoma arising in the diverticulum
may lead to obstruction
Lithiasis,
stones that are formed in Meckel's diverticulum can:
Extrude
into the terminal ileum, leading to obstruction
Induce
local inflammation and intussusception.
The
diverticulum itself or tumour within it may cause intussusception (Figure 2.1),
for example, from the ileum to the colon, causing obstruction. Symptoms of this
include currant jelly stools and a palpable lump in the lower abdomen. This
occurs when the diverticulum inverts into the lumen of the ileum, due to
either:
An
active peristaltic mechanism of the diverticulum that attempts to remove
irritating factors
A
passive process such as the transit of food
Umbilical
anomalies
Anomalies
between the diverticulum and umbilicus may include the presence of fibrous
cord, cyst, fistula or sinus, leading to:
Infection
or excoriation of periumbilical skin, resulting in a discharging sinus
Recurrent
infection and healing of sinus
Abscess
formation in the abdominal wall
Fibrous
cord increases the risk of volvulus formation and internal herniation
Neoplasm
Tumors
in Meckel's diverticulum may cause bleeding, acute abdominal pain,
gastrointestinal obstruction, perforation or intussusception.
Benign
tumors:
·
Leiomyoma
·
Lipoma
·
Vascular and neuromuscular hamartoma
Malignant
tumors:
Carcinoids:
most common,44% (Figure 2.2)
Mesenchymal
tumors: Leiomyosarcoma,peripheral nerve sheath and gastrointestinal stromal
tumors (35%)
Adenocarcinoma,
16%
Desmoplastic
small round cell tumor
Other
complications
A
diverticulum inside a Meckel’s diverticulum (Daughter diverticula)
Stones
and phytobezoar (a bezoar of vegetable fibers) in Meckel’s diverticulum
Vesicodiverticular
fistula
A
peptic ulcer, also known as peptic ulcer disease (PUD), is the most common
ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely
painful. It is defined as mucosal erosions equal to or greater than
Four
times as many peptic ulcers arise in the duodenum—the first part of the small
intestine, just after the stomach—as in the stomach itself. About 4% of gastric
ulcers are caused by a malignant tumor, so multiple biopsies are needed to
exclude cancer. Duodenal ulcers are generally benign.
Classification
By
Region/Location
Duodenum
(called duodenal ulcer)
Esophagus
(called esophageal ulcer)
Stomach
(called gastric ulcer)
Meckel's
diverticulum (called Meckel's diverticulum ulcer; is very tender with
palpation)
Modified
Johnson Classification of peptic ulcers:
Type
I: Ulcer along the body of the stomach, most often along the lesser curve at
incisura angularis along the locus minoris resistantiae.
Type
II: Ulcer in the body in combination with duodenal ulcers. Associated with acid
oversecretion.
Type
III: In the pyloric channel within
Type
IV: Proximal gastroesophageal ulcer
Type
V: Can occur throughout the stomach. Associated with chronic NSAID use (such as
aspirin).
Signs
and symptoms
Symptoms
of a peptic ulcer can be
·
abdominal pain, classically
epigastric strongly correlated to mealtimes. In case of duodenal ulcers the
pain appears about three hours after taking a meal;
·
bloating and abdominal fullness;
·
waterbrash (rush of saliva after an
episode of regurgitation to dilute the acid in esophagus - although this is more
associated with gastroesophageal reflux disease);
·
nausea, and copious vomiting;
·
loss of appetite and weight loss;
·
hematemesis (vomiting of blood); this
can occur due to bleeding directly from a gastric ulcer, or from damage to the
esophagus from severe/continuing vomiting.
·
melena (tarry, foul-smelling feces
due to oxidized iron from hemoglobin);
·
rarely, an ulcer can lead to a
gastric or duodenal perforation, which leads to acute peritonitis. This is
extremely painful and requires immediate surgery.
A
history of heartburn, gastroesophageal reflux disease (GERD) and use of certain
forms of medication can raise the suspicion for peptic ulcer. Medicines
associated with peptic ulcer include NSAID (non-steroid anti-inflammatory
drugs) that inhibit cyclooxygenase, and most glucocorticoids (e.g.
dexamethasone and prednisolone).
In
patients over 45 with more than two weeks of the above symptoms, the odds for
peptic ulceration are high enough to warrant rapid investigation by
esophagogastroduodenoscopy.
The
timing of the symptoms in relation to the meal may differentiate between
gastric and duodenal ulcers: A gastric ulcer would give epigastric pain during
the meal, as gastric acid production is increased as food enters the stomach.
Symptoms of duodenal ulcers would initially be relieved by a meal, as the
pyloric sphincter closes to concentrate the stomach contents, therefore acid is
not reaching the duodenum. Duodenal ulcer pain would manifest mostly 2–3 hours
after the meal, when the stomach begins to release digested food and acid into
the duodenum.
Also,
the symptoms of peptic ulcers may vary with the location of the ulcer and the
patient's age. Furthermore, typical ulcers tend to heal and recur and as a
result the pain may occur for few days and weeks and then wane or disappear.
Usually, children and the elderly do not develop any symptoms unless
complications have arisen.
Burning
or gnawing feeling in the stomach area lasting between 30 minutes and 3 hours
commonly accompanies ulcers. This pain can be misinterpreted as hunger,
indigestion or heartburn. Pain is usually caused by the ulcer but it may be
aggravated by the stomach acid when it comes into contact with the ulcerated
area. The pain caused by peptic ulcers can be felt anywhere from the navel up to
the sternum, it may last from few minutes to several hours and it may be worse
when the stomach is empty. Also, sometimes the pain may flare at night and it
can commonly be temporarily relieved by eating foods that buffer stomach acid
or by taking anti-acid medication. However, peptic ulcer disease symptoms may
be different for every sufferer.
Complications
Gastrointestinal
bleeding is the most common complication. Sudden large bleeding can be
life-threatening It occurs when the ulcer erodes one of the blood vessels, such
as the gastroduodenal artery.
Perforation
(a hole in the wall) often leads to catastrophic consequences. Erosion of the
gastro-intestinal wall by the ulcer leads to spillage of stomach or intestinal
content into the abdominal cavity. Perforation at the anterior surface of the
stomach leads to acute peritonitis, initially chemical and later bacterial
peritonitis. The first sign is often sudden intense abdominal pain. Posterior
wall perforation leads to bleeding due to involvement of gastroduodenal artery
that lies posterior to the 1st part of duodenum.
perforation
and Penetration are when the ulcer continues into adjacent organs such as the
liver and pancreas.
Gastric
outlet obstruction is the narrowing of pyloric canal by scarring and swelling
of gastric antrum and doudenum due to peptic ulcers. Patient often presents
with severe vomiting without bile.
Cancer
is included in the differential diagnosis (elucidated by biopsy), Helicobacter
pylori as the etiological factor making it 3 to 6 times more likely to develop
stomach cancer from the ulcer.
Cause
A
major causative factor (60% of gastric and up to 90% of duodenal ulcers) is
chronic inflammation due to Helicobacter pylori that colonizes the antral
mucosa. The immune system is unable to clear the infection, despite the
appearance of antibodies. Thus, the bacterium can cause a chronic active
gastritis (type B gastritis), resulting in a defect in the regulation of
gastrin production by that part of the stomach, and gastrin secretion can either
be increased, or as in most cases, decreased, resulting in hypo- or
achlorhydria. Gastrin stimulates the production of gastric acid by parietal
cells. In H. pylori colonization responses to increased gastrin, the increase
in acid can contribute to the erosion of the mucosa and therefore ulcer
formation. Studies in the varying occurrence of ulcers in third world countries
despite high H. pylori colonization rates suggest dietary factors play a role
in the pathogenesis of the disease.
Another
major cause is the use of NSAIDs. The gastric mucosa protects itself from
gastric acid with a layer of mucus, the secretion of which is stimulated by
certain prostaglandins. NSAIDs block the function of cyclooxygenase 1 (cox-1),
which is essential for the production of these prostaglandins. COX-2 selective
anti-inflammatories (such as celecoxib or the since withdrawn rofecoxib)
preferentially inhibit cox-2, which is less essential in the gastric mucosa,
and roughly halve the risk of NSAID-related gastric ulceration.
The
incidence of duodenal ulcers has dropped significantly during the last 30
years, while the incidence of gastric ulcers has shown a small increase, mainly
caused by the widespread use of NSAIDs. The drop in incidence is considered to
be a cohort-phenomenon independent of the progress in treatment of the disease.
The cohort-phenomenon is probably explained by improved standards of living
which has lowered the incidence of H. pylori infections.
Although
some studies have found correlations between smoking and ulcer formation,
others have been more specific in exploring the risks involved and have found
that smoking by itself may not be much of a risk factor unless associated with
H. pylori infection. Some suggested risk factors such as diet, and spice consumption,
were hypothesized as ulcerogens (helping cause ulcers) until late in the 20th
century, but have been shown to be of relatively minor importance in the
development of peptic ulcers. Caffeine and coffee, also commonly thought to
cause or exacerbate ulcers, have not been found to affect ulcers to any
significant extent. Similarly, while studies have found that alcohol
consumption increases risk when associated with H. pylori infection, it does
not seem to independently increase risk, and even when coupled with H. pylori
infection, the increase is modest in comparison to the primary risk factor.
Gastrinomas
(Zollinger Ellison syndrome), rare gastrin-secreting tumors, also cause
multiple and difficult-to-heal ulcers.
Diagnosis
Endoscopic image
of gastric ulcer, biopsy proven to be gastric cancer.
The
diagnosis is mainly established based on the characteristic symptoms. Stomach
pain is usually the first signal of a peptic ulcer. In some cases, doctors may
treat ulcers without diagnosing them with specific tests and observe whether
the symptoms resolve, thus indicating that their primary diagnosis was
accurate.
Confirmation
of the diagnosis is made with the help of tests such as endoscopies or barium
contrast x-rays. The tests are typically ordered if the symptoms do not resolve
after a few weeks of treatment, or when they first appear in a person who is
over age 45 or who has other symptoms such as weight loss, because stomach
cancer can cause similar symptoms. Also, when severe ulcers resist treatment,
particularly if a person has several ulcers or the ulcers are in unusual
places, a doctor may suspect an underlying condition that causes the stomach to
overproduce acid.
An
esophagogastroduodenoscopy (EGD), a form of endoscopy, also known as a
gastroscopy, is carried out on patients in whom a peptic ulcer is suspected. By
direct visual identification, the location and severity of an ulcer can be
described. Moreover, if no ulcer is present, EGD can often provide an
alternative diagnosis.
One
of the reasons that blood tests are not reliable for accurate peptic ulcer
diagnosis on their own is their inability to differentiate between past
exposure to the bacteria and current infection. Additionally, a false negative
result is possible with a blood test if the patient has recently been taking
certain drugs, such as antibiotics or proton pump inhibitors.
The
diagnosis of Helicobacter pylori can be made by:
Urea
breath test (noninvasive and does not require EGD);
Direct
culture from an EGD biopsy specimen; this is difficult to do, and can be
expensive. Most labs are not set up to perform H. pylori cultures;
Direct
detection of urease activity in a biopsy specimen by rapid urease test;
Measurement
of antibody levels in blood (does not require EGD). It is still somewhat
controversial whether a positive antibody without EGD is enough to warrant
eradication therapy;
Stool
antigen test;
Histological
examination and staining of an EGD biopsy.
The
breath test uses radioactive carbon atom to detect H. pylori. To perform this
exam the patient will be asked to drink a tasteless liquid which contains the
carbon as part of the substance that the bacteria breaks down. After an hour,
the patient will be asked to blow into a bag that is sealed. If the patient is infected
with H. pylori, the breath sample will contain radioactive carbon dioxide. This
test provides the advantage of being able to monitor the response to treatment
used to kill the bacteria.
The
possibility of other causes of ulcers, notably malignancy (gastric cancer)
needs to be kept in mind. This is especially true in ulcers of the greater
(large) curvature of the stomach; most are also a consequence of chronic H.
pylori infection.
If
a peptic ulcer perforates, air will leak from the inside of the gastrointestinal
tract (which always contains some air) to the peritoneal cavity (which normally
never contains air). This leads to "free gas" within the peritoneal
cavity. If the patient stands erect, as when having a chest X-ray, the gas will
float to a position underneath the diaphragm. Therefore, gas in the peritoneal
cavity, shown on an erect chest X-ray or supine lateral abdominal X-ray, is an
omen of perforated peptic ulcer disease.
Macroscopic
appearance
A benign
gastric ulcer (from the antrum) of a gastrectomy specimen.
Gastric
ulcers are most often localized on the lesser curvature of the stomach. The
ulcer is a round to oval parietal defect ("hole"), 2 to
Microscopic
appearance
A
gastric peptic ulcer is a mucosal defect which penetrates the muscularis
mucosae and lamina propria, produced by acid-pepsin aggression. Ulcer margins
are perpendicular and present chronic gastritis. During the active phase, the
base of the ulcer shows 4 zones: inflammatory exudate, fibrinoid necrosis,
granulation tissue and fibrous tissue. The fibrous base of the ulcer may
contain vessels with thickened wall or with thrombosis.
Differential
diagnosis
·
Gastritis
·
Stomach cancer
·
Gastroesophageal reflux disease
·
Pancreatitis
·
Hepatic congestion
·
Cholecystitis
·
Biliary colic
·
Inferior myocardial infarction
·
Referred pain (pleurisy,
pericarditis)
·
Superior mesenteric artery syndrome
Treatment
Younger
patients with ulcer-like symptoms are often treated with antacids or H2
antagonists before EGD is undertaken. Bismuth compounds may actually reduce or
even clear organisms, though the warning labels of some bismuth subsalicylate
products indicate that the product should not be used by someone with an ulcer.
Patients
who are taking nonsteroidal anti-inflammatories (NSAIDs) may also be prescribed
a prostaglandin analogue (Misoprostol) in order to help prevent peptic ulcers,
which are a side-effect of the NSAIDs.
When
H. pylori infection is present, the most effective treatments are combinations
of 2 antibiotics (e.g. Clarithromycin, Amoxicillin, Tetracycline,
Metronidazole) and 1 proton pump inhibitor (PPI), sometimes together with a
bismuth compound. In complicated, treatment-resistant cases, 3 antibiotics
(e.g. amoxicillin + clarithromycin + metronidazole) may be used together with a
PPI and sometimes with bismuth compound. An effective first-line therapy for
uncomplicated cases would be Amoxicillin + Metronidazole + Pantoprazole (a
PPI). In the absence of H. pylori, long-term higher dose PPIs are often used.
Treatment
of H. pylori usually leads to clearing of infection, relief of symptoms and eventual
healing of ulcers. Recurrence of infection can occur and retreatment may be
required, if necessary with other antibiotics. Since the widespread use of
PPI's in the 1990s, surgical procedures (like "highly selective
vagotomy") for uncomplicated peptic ulcers became obsolete.
Perforated
peptic ulcer is a surgical emergency and requires surgical repair of the
perforation. Most bleeding ulcers require endoscopy urgently to stop bleeding
with cautery, injection, or clipping.
Ranitidine
and famotidine, which are both H2 antagonists, provide relief of peptic ulcers,
heartburn, indigestion and excess stomach acid and prevention of these symptoms
associated with excessive consumption of food and drink. Ranitidine and
famotidine are available over the counter at pharmacies, both as brand-name
drugs and as generics, and work by decreasing the amount of acid the stomach
produces allowing healing of ulcers.
Sucralfate,
(Carafate) has also been a successful treatment of peptic ulcers.
Epidemiology
The
lifetime risk for developing a peptic ulcer is approximately 10%.
In
Western countries the prevalence of Helicobacter pylori infections roughly
matches age (i.e., 20% at age 20, 30% at age 30, 80% at age 80 etc.).
Prevalence is higher in third world countries where it is estimated at about
70% of the population, whereas developed countries show a maximum of 40% ratio.
Overall, H. pylori infections show a worldwide decrease, more so in developed
countries. Transmission is by food, contaminated groundwater, and through human
saliva (such as from kissing or sharing food utensils).
A
minority of cases of H. pylori infection will eventually lead to an ulcer and a
larger proportion of people will get non-specific discomfort, abdominal pain or
gastritis.
Peptic
ulcer disease had a tremendous effect on morbidity and mortality until the last
decades of the 20th century, when epidemiological trends started to point to an
impressive fall in its incidence. The reason that the rates of peptic ulcer
disease decreased is thought to be the development of new effective medication
and acid suppressants and the discovery of the cause of the condition, H.
pylori.
In
the
Diet
as a predisposing Cause
While
working as a general surgeon at
History
John
Lykoudis, a general practitioner in
Helicobacter
pylori was rediscovered in 1982 by two Australian scientists, Robin Warren and
Barry J. Marshall as a causative factor for ulcers. In their original paper,
Warren and Marshall contended that most gastric ulcers and gastritis were
caused by colonization with this bacterium, not by stress or spicy food as had
been assumed before.
The
H. pylori hypothesis was poorly received, so in an act of self-experimentation
In
1997, the Centers for Disease Control and Prevention, with other government
agencies, academic institutions, and industry, launched a national education
campaign to inform health care providers and consumers about the link between
H. pylori and ulcers. This campaign reinforced the news that ulcers are a
curable infection, and that health can be greatly improved and money saved by
disseminating information about H. pylori.
In
2005, the Karolinska Institute in
Some
believed that mastic gum, a tree resin extract, actively eliminates the H.
pylori bacteria. However, multiple subsequent studies have found no effect of
using mastic gum on reducing H. pylori levels.
Stomach
disease
The
stomach is an important organ in the body. It plays a vital role in digestion
of foods, releases various enzymes and also protects the lower intestine from
harmful organisms. The stomach connects to the esophagus above and to the small
intestine below. It is intricately related to the pancreas, spleen and liver.
The stomach does vary in size but its J shape is constant. The stomach lies in
the upper part of the abdomen just below the left rib cage.
Gastropathy
is a general term used for stomach disease. Examples including the name include
Portal hypertensive gastropathy, and Ménétrier's disease, also
known as "hyperplastic hypersecretory gastropathy". However, there
are many other stomach diseases that don't include the word "gastropathy"
such as gastric or peptic ulcer disease, gastroparesis, and dyspepsia.
Many
stomach diseases are associated with infection. Historically, it was widely
believed that the highly acidic environment of the stomach would keep the
stomach immune from infection. However, a large number of studies have
indicated that most cases of stomach ulcers, gastritis, and stomach cancer are
caused by Helicobacter pylori infection. One of the ways it is able to survive
in the stomach involves its urease enzymes which metabolize urea (which is
normally secreted into the stomach) to ammonia and carbon dioxide which
neutralises gastric acid and thus prevents its digestion. In recent years, it
has been discovered that other Helicobacter bacteria are also capable of
colonising the stomach and have been associated with gastritis.
Having
too little or no gastric acid is known as hypochlorhydria or achlorhydria
respectively and are conditions which can have negative health impacts. Having
high levels of gastric acid is called hyperchlorhydria. Many people believe
that hyperchlorhydria can cause stomach ulcers. However, recent research
indicates that the gastric mucosa which secretes gastric acid is
acid-resistant.
Gastritis
and stomach cancer can be caused by Helicobacter pylori infection.
There
are many types of chronic disorders which affect the stomach. However since the
symptoms are localized to this organ, the typical symptoms of stomach problems
include nausea, vomiting, bloating, cramps, diarrhea and pain.
Chronic
disorders
Disorders
of the stomach are very common and induce a significant amount of morbidity and
suffering in the population. Data from hospitals indicate that more than 25% of
the population suffers from some type of chronic stomach disorder including
abdominal pain and indigestion. These symptoms occur for long periods and cause
prolonged suffering, time off work and a poor quality of life. Moreover visits
to doctors, expense of investigations and treatment result in many days lost
from work and a colossal cost to the financial system.
The
stomach is subject to both acute and chronic disorders, but this chapter will
be devoted to the chronic disorders. It might be mentioned here that in acute
conditions almost without exception. Whether in the stomach or any other part
of the body, if the fast is initiated at its onset and all of the other factors
frequently advised in this volume for purifying the blood-stream, aiding in the
re-establishment of normal nerve-tone and adequate elimination through all
channels, there need be no prolonged attack and there need be no complications.
There
are numerous chronic disorders of the stomach that are quite common. As a rule
it may be considered that they are different stages of the same condition. That
condition is an irritation resulting from abuse through wrong selection of food
and from wrong eating habits, and from
such an abnormal condition of chemistry within the body (toxemia and acidosis)
that the cells of the stomach cannot be properly nourished.
Gastric
hyperacidity is a condition in which, the gastric juice is secreted in
excessive amounts. Too much food, highly seasoned, hot and spiced foods,
alcoholic drinks, worry grief and other detrimental emotional conditions,
mental over activity, diseases of the liver, gallbladder and gall-duct, chronic
appendicitis, and inflammation of other abdominal organs, are among the leading
causes of this condition. Sometimes it seems to be due solely to some spinal
lesion, either bony, muscular or ligaments.
The
symptoms are pain below the breastbone an hour or so after eating; gas and sour
eructation’s, headache, dizziness, melancholia,aggravation of the pain by the
intake of sugars and starches, and relief of the pain by protein foods which
utilize the acid.
Dyspepsia
is a term once commonly applied to this condition, although dyspepsia may mean
a variety of digestive disorders. It usually means abnormal stomach digestion
and is in a large measure discarded now in general use.
Chronic
gastritis is usually a chronic gastric catarrh. There usually are loss of
appetite, pain after meals, eructations, loss of weight to an appreciable
extent, constipation, and considerable mental uneasiness until one becomes a
neurasthenic. Often no type of food is found to digest satisfactorily, though
sometimes the simplest foods will agree reasonable well. Combinations of foods may cause trouble,
while a single article of food, even if not of the best type, may agree
perfectly. In this condition there often
is such failure of stomach-gland activity and circulation in the parts
involved, that an ulceration develops.
Ulcer
of the stomach is a comparatively common and more or less serious disease of
the stomach. It often follows prolonged
dyspepsia or hyperacidity. It results
from the same causes mentioned as being responsible for hyperacidity. Some people may have hyperacidity for a long
time and never develop ulcer, as there seems to be some particular requirement
before an ulcer develops, be some particular requirement before an ulcer
develops. This requirement frequently is
considered to be an emotional state of depressing nature. Worry, anxiety, grief for instance, are not
infrequently followed by peptic ulcer.
Hypopepsia- This is a condition in which there is
reduction of the digestive secretions of the stomach. This is the usual condition in a simple
dyspepsia. Most cases follow a more or
less extended period of hyperacidity, the causes of which have been given. Additional causes are a chronic catarrh
condition of the stomach or chronic gastritis; such neurons as neurasthenia and
hysteria; and aprlonged worry, anxiety and suspense; severe anemias and
toxemia’s, such as from certain types of goiter.
Nervous
disease of the stomach usually are considered neuroses. They may involve the nerves or the secretions
or the motor activity of the stomach.
Hypopensia, in fact, usually is a gastric neurosis. The symptoms of these neuroses are slight or
extreme, depending considerably upon the nervousness of the patient. Usually the discoverable causes are
insignificant, even when the symptoms seemingly are pronounced. Any factors which will produce a neurasthenic
or neurotic condition or that will seriously reduce the nerve-tone, combined
with special susceptibility of the stomach or certain dietetic and other habits
which tend to center trouble at this point, lead to the development.
A
peptic ulcer may be either in the stomach or in the duodenum, just beyond the
outlet of the stomach. The causes of
ulcers in these two locations are the same, the symptoms are much the same, and
the treatment will be the same.
Symptoms
preceding a peptic ulcer are dyspepsia, sour eructation’s, heartburn and more
or less severe gnawing stomach pains before meals. The pain is relieved by eating, but in
stomach ulcers it comes on again an hour or so after eating, and in duodenal
ulcer two or three hours after eating in either case when the acidity reaches
its height. Vomiting immediately after
food is taken as the first serious symptom, and when the vomit is tinged with
blood an ulcer may be diagnosed--though tentatively. These symptoms may appear and disappear for
years.
In
some instances it is fund that the enforced rest given to the stomach by the
prompt rejection of all food sometimes is sufficient to bring about a temporary
healing. Continual eidetic errors will
bring the condition on again, and with each recurrence the ulcerated area
extends in size. Not infrequently the
ulcer eats its way through the stomach wall and we have perforation into the
peritoneal cavity resulting in peritonitis, an extremely grave condition
demanding immediate operation.
Cancer
of the stomach is a result of chronic irritation often developing on the site
of an old ulcer. However, it may develop
in stomachs never the seat of ulcer. But
in every instance there have been years of abuse of the stomach and years of a
pronounced systemic toxemia. Often there
is an earlier history of excellent digestion.
Some of those who develop cancer often pride themselves on being “able
to eat nails”. All at once dyspepsia
develops, a severe pain appears in the stomach region, and from then on
digestion is painful and gradually more and more difficult. The signs by which a cancer can be recognized
early are indefinite. One early symptom
is a catarrhal condition that is more or less intractable. Emaciation develops, anemia also, and a
peculiar yellowish tint takes the place of normal color in the skin. Vomiting upon the intake of food is common late
symptom, giving the appearance of coffee-grounds. The stools are tarry, from the presence of
decomposed blood. In some instances a definite tumor mass can be felt upon
palpation over the stomach area.
Dilatation
of the stomach is a serious illness resulting from prolonged dyspepsia,
gastritis or other conditions in which the stomach is overloaded by food and
distended by gas. For its development it
is also necessary for general tone to be reduced, and in many cases there is a
spinal lesion. The chief characteristic
of the disease is the expansion of the walls of the stomach, with such increase
in capacity that the appetite becomes voracious and yet digestion takes place
slowly. Vomiting, often of a severe nature,
is a frequent symptom in severe dilatations, and there may be vomiting of food
taken a day or two before.
Prolapsed
of the stomach is a very common condition, said to exist in at fleets seven out
of ten women and a considerable number of men.
It is due much to the same causes as result in dilatation, but other
causes are rapid loss of weight, weight-lifting or other straining activities,
and , in women, to the frequent bearing of children. There may be no symptoms of this condition or
there may be uneasiness or any degree of dyspepsia dympyomd. All of these are relieved upon reclining.
Treatment
- The stomach is the one organ which can be given a thorough rest, and diseases
of this organ are among the most certain of correctionby natural means with
emphasis upon the fast and later diet.
Even the intestines are used by the body to receive waste material
brought from all parts of the body during a fast. The stomach usually is not called upon in
this manner, hence can receive a complete rest and recover much of its original
healthful functioning.
In
all diseases of the stomach, without exception, the fast is of some value, and
in most of them it is the greatest single factor of treatment. Many patients with gastric disorders have
already become greatly emitted and are unable to take a protracted fast. In most of these cases the fruit juice diet
will be of benefit, though there are some cases of hyperacidity and some of
cancer of the stomach in which fruit juice is not well tolerated. In these case a clear vegetable broth is much
to be preferred. The duration of the
fast or fruit or vegetable broth diet should depend upon the patient’s general
condition and upon the severity of the gastric disorder. Benefit will be derived from even two or
three days of the fast or limited diet, but s a rule it is better to have from
five to thirty days, depending upon effects and needs. Ten to fifteen days probably is a good
average for these cases.
If
the fast is tasdken it should be terminated by a fruit juice or vegetable broth
diet. After this diet or after the same
diet when the fast is not taken, the milk diet should be adopted it possible.
With the possible exception of some cases of cancer, there is no disorder of
the stomach in which the milk diet can not be used satisfactorily and with benefit--except
in some individual cases in which the intolerance of milk cannot be explained.
The
quantity of milk used will vary considerably in the different diseases. In the majority of cases the usual plan may
be followed with benefit. Form one-half
to one glass of milk every two hours the first day (depending upon the length
of the fast or preliminary diet); if one-half glass is required the first day,
a full glass may be used every two hours the second day. Continue using one glass at each feeding,
shortening the interval between the feedings on successive days to one and a
half hours, one hour, three quarters of an hour and one-half hour, then
continue taking one glass of milk every half hour for eleven or twelve hours of
each day of the diet.
Most
cases will benefit by the addition of lemon juice to the milk itself or as
desired during the day. From then to
twenty drops of lemon juice may be added to each glass of milk or to as many as
desired. The total quantity of lemons
may be from one to a dozen daily. If
there is a hypopepsia then more lemon juice will be required than in some other
conditions. In hyperpepsia or
hyperacidity lemon juice is not required.
In this condition it often is better to take a pint of milk every hour,
or a quart every hour, or a quart of milk every two hours during the day. In a case of hyperacidity, the patient
usually can assimilate full cream. In a
hyperacid case part of the cream should be removed.
After
the milk diet has been continued until the results from it and the fast have
been considerable, a very excellent plan is to discontinue taking the milk
every day at two o’clock and then wait until between six and seven o’clock,
when a balanced meal may be taken. This
meal should be a simple combination and formed around a protein or a
starch. That is, any desired protein
that experience knows to be agreeable may be selected; or a desired starch,
such as potatoes, macaroni, baked rice, etc.
The rest of the meal may be cooked and raw greed vegetable.
It
there is any pronounced irritation in the stomach it usually is better to
eliminate the raw vegetable, or at least to be certain to masticate them
thoroughly and then discard from the mouth the fibrous materials that can not
be reduced to a liquid or fine pulp.
Many time it is better to run the vegetables through a sieve. In this manner, it will be practicable to
make a puree of almost any sort of vegetable.
This is particularly important in cases of peptic ulcer and cancer of
the stomach. In these cases animal
proteins usually should be omitted as they increase the amount of acid, which
is undesirable. Al other proteins
increase acid, but not to the extent that animal proteins do.
Other
factors of treatment are of much benefit in these cases and usually will be
required in some measure. When strength
and energy permit, one should secure gradually increasing amounts of exercise,
being always careful to avoid any special strain or fatigue. The tepid or somewhat cool general bath, by
any preferred means, is of value, but extremely cold or hot baths should be
avoided. In some instances a cold
compress over the stomach region will improve circulation and digestion in the
stomach. There must be plenty of rest
and sleep, fresh air, and a serene mental attitude.
As
for individual diseases, some additional points of interest will be given
below.
In
hyperacidity it is better to drink warm or hot water quite abundantly during
the fast, rather than cold water, since the latter increases the amount of acid
secreted in the stomach.
While
cancer usually is a progressively destructive disease numerous cases diagnosed
as cancer of the stomach have been completely cured by natural treatment.
However, prevention of this condition is decidedly preferable, and depends upon
a reasonably strict physical culture program of living. In cancer particularly, the juice of freest
grapes of unsweetened bottled grape juice may be used fairly liberally and
usually with as good results or better than can be secured on other fruit
juices.
In
dilatation and prolapsed of the stomach the milk diet is particularly
helpful. If the abnormality is very
pronounced it would be better for the patients remain in bed for two or three
weeks while taking the diet, to permit the tissue tone to the recovered to a
considerable extent before subjecting the stomach walls and supports to
additional stress.
In
these cases the fast is of especial value, the stomach often returning to
normal size and position of a fast of several days. In both conditions also, the position and
exercise on the inclined table or support are practically essential to definite
correction. The patient should lie head
down and perform those movements that are enumerated in the chapter or
Rupture. Concussion of the fifth dorsal
vertebrae for half a minute and repeating twice after half-minute rests may be
given twice daily with benefit. In these
two conditions also it is of value to have the foot of the bed elevated on
blocks, or the spring of the bed elevated at the foot five to eight inches in
height by means of a board.
In
many of these disorders it is necessary to repeat the fast or other preliminary
diet and the milk diet. There is no treatment that will produce results of a
lasting nature more fully than the treatment outlined, but if there is
considerable abnormally will take time.
In
some cases of gastric ulcer the mild diet or the milk and cream diet as
recommended by Sippy is preferable to a fast.
Small quantities (two ounces) of one-third cream and two-thirds milk, or
in some cases one-half cream and one-half cream and one-half milk given every
two hours for a few days. This will
usually greatly ameliorate pain and frequently will check vomiting. After a few days the diet is modified by
adding white of egg, gelatin and some form of cereal with cream. Later, during the third week, custards, milk
toast, soft boiled egg, and purees of green vegetables may be given.
Gastritis
In
the stomach there is a slight balance between acid and the wall lining which is
protected by mucus. When this mucus lining is disrupted for whatever reason,
signs and symptoms of acidity result. This may result in upper abdominal pain,
indigestion, loss of appetite, nausea, vomiting and heartburn. When the
condition is allowed to progress, the pain may become continuous; blood may
start to leak and be seen in the stools. If the bleeding is rapid and of
adequate volume it may even result in vomiting of bright red blood
(hematemesis). When the acidity is uncontrolled, it can even cause severe blood
loss (anemia) or lead to perforation (hole) in the stomach which is a surgical
emergency. In many individuals, the progressive bleeding from an ulcer mixes
with the feces and presents as black stools. Presence of blood in stools is
often the first sign that there is a problem in the stomach
Gastritis
is an inflammation of the lining of the stomach, and has many possible causes.
The main acute causes are excessive alcohol consumption or prolonged use of
nonsteroidal anti-inflammatory drugs (also known as NSAIDs) such as aspirin or
ibuprofen. Sometimes gastritis develops after major surgery, traumatic injury,
burns, or severe infections. Gastritis may also occur in those who have had
weight loss surgery resulting in the banding or reconstruction of the digestive
tract. Chronic causes are infection with bacteria, primarily Helicobacter
pylori, chronic bile reflux, and stress; certain autoimmune disorders can cause
gastritis as well. The most common symptom is abdominal upset or pain. Other
symptoms are indigestion, abdominal bloating, nausea, and vomiting and
pernicious anemia. Some may have a feeling of fullness or burning in the upper
abdomen. A gastroscopy, blood test, complete blood count test, or a stool test
may be used to diagnose gastritis. Treatment includes taking antacids or other
medicines, such as proton pump inhibitors or antibiotics, and avoiding hot or
spicy foods. For those with pernicious anemia, B12 injections are given.
Micrograph
showing gastritis.
H&E stain
Signs
and symptoms
A peptic ulcer may accompany
gastritis. Endoscopic image.
Many
people with gastritis experience no symptoms at all. However, upper central
abdominal pain is the most common symptom; the pain may be dull, vague,
burning, aching, gnawing, sore, or sharp. Pain is usually located in the upper
central portion of the abdomen, but it may occur anywhere from the upper left
portion of the abdomen around to the back.
Other
signs and symptoms may include:
·
Nausea
·
Vomiting (if present, may be clear,
green or yellow, blood-streaked, or completely bloody, depending on the
severity of the stomach inflammation)
·
Belching (if present, usually does
not relieve the pain much)
·
Bloating
·
Feeling full after only a few bites
of food[6]
·
Loss of appetite
·
Unexplained weight loss
Causes
Acute
Erosive
gastritis is a gastric mucosal erosion caused by damage to mucosal defenses.
Alcohol consumption does not cause chronic gastritis. It does, however, erode
the mucosal lining of the stomach; low doses of alcohol stimulate hydrochloric
acid secretion. High doses of alcohol do not stimulate secretion of acid.
NSAIDs inhibit cyclooxygenase-1, or COX-1, an enzyme responsible for the
biosynthesis of eicosanoids in the stomach, which increases the possibility of
peptic ulcers forming. Also, NSAIDs, such as aspirin, reduce a substance that
protects the stomach called prostaglandin. These drugs used in a short period
are not typically dangerous. However, regular use can lead to gastritis.
Chronic
Chronic
gastritis refers to a wide range of problems of the gastric tissues. The immune
system makes proteins and antibodies that fight infections in the body to
maintain a homeostatic condition. In some disorders the body targets the
stomach as if it were a foreign protein or pathogen; it makes antibodies against,
severely damages, and may even destroy the stomach or its lining. In some cases
bile, normally used to aid digestion in the small intestine, will enter through
the pyloric valve of the stomach if it has been removed during surgery or does
not work properly, also leading to gastritis. Gastritis may also be caused by
other medical conditions, including HIV/AIDS, Crohn's disease, certain
connective tissue disorders, and liver or kidney failure.
Metaplasia
Mucous
gland metaplasia, the reversible replacement of differentiated cells, occurs in
the setting of severe damage of the gastric glands, which then waste away
(atrophic gastritis) and are progressively replaced by mucous glands. Gastric
ulcers may develop; it is unclear if they are the causes or the consequences.
Intestinal metaplasia typically begins in response to chronic mucosal injury in
the antrum, and may extend to the body. Gastric mucosa cells change to resemble
intestinal mucosa and may even assume absorptive characteristics. Intestinal metaplasia
is classified histologically as complete or incomplete. With complete
metaplasia, gastric mucosa is completely transformed into small-bowel mucosa,
both histologically and functionally, with the ability to absorb nutrients and
secrete peptides. In incomplete metaplasia, the epithelium assumes a histologic
appearance closer to that of the large intestine and frequently exhibits
dysplasia.
Helicobacter
pylori
Helicobacter
pylori colonizes the stomach of more than half of the world's population, and the
infection continues to play a key role in the pathogenesis of a number of
gastroduodenal diseases. Colonization of the gastric mucosa with Helicobacter
pylori results in the development of chronic gastritis in infected individuals
and in a subset of patients chronic gastritis progresses to complications (i.e.
ulcer disease, gastric neoplasias, some distinct extra gastric disorders).
However, gastritis has no adverse consequences for most hosts and emerging
evidence suggests that H. pylori prevalence is inversely related to
gastroesophageal reflux disease and allergic disorders. These observations
indicate that eradication may not be appropriate for certain populations due to
the potentially beneficial effects conferred by persistent gastric inflammation.
Diagnosis
Often,
a diagnosis can be made based on the patient's description of his or her
symptoms, but other methods which may be used to verify gastritis include:
1.
Blood tests:
2.
Blood cell count
3.
Presence of H. pylori
4.
Pregnancy
5.
Liver, kidney, gallbladder, or
pancreas functions
6.
Urinalysis
7.
Stool sample, to look for blood in
the stool
8.
X-rays
9.
ECGs
10. Endoscopy,
to check for stomach lining inflammation and mucous erosion
11. Stomach
biopsy, to test for gastritis and other conditions
Treatment
Over-the-counter
antacids in liquid or tablet form are a common treatment for mild gastritis.
Antacids neutralize stomach acid and can provide fast pain relief. When
antacids don't provide enough relief, medications such as cimetidine,
ranitidine, nizatidine or famotidine that help reduce the amount of acid the
stomach produces are often prescribed. An even more effective way to limit
stomach acid production is to shut down the acid "pumps" within
acid-secreting stomach cells. Proton pump inhibitors reduce acid by blocking
the action of these small pumps. This class of medications includes omeprazole,
lansoprazole, rabeprazole, and esomeprazole. Proton pump inhibitors also appear
to inhibit H. pylori activity. Cytoprotective agents are designed to help
protect the tissues that line the stomach and small intestine. They include the
medications sucralfate and misoprostol. If NSAIDs are being taken regularly,
one of these medications to protect the stomach may also be taken. Another
cytoprotective agent is bismuth subsalicylate. Many people also drink milk to
relieve symptoms, however the high calcium levels actually stimulate release of
gastric acid from parietal cells, ultimately worsening symptoms. In addition to
protecting the lining of stomach and intestines, bismuth preparations appear to
inhibit H. pylori activity as well. Several regimens are used to treat H.
pylori infection. Most use a combination of two antibiotics and a proton pump
inhibitor. Sometimes bismuth is also added to the regimen. The antibiotic aids
in destroying the bacteria, and the acid blocker or proton pump inhibitor
relieves pain and nausea, heals inflammation, and may increase the antibiotic's
effectiveness.
Gastroparesis
Another
very common long term problem which is now more appreciated is gastroparesis. Gastroparesis
affects millions of individuals and is often never suspected and most patients
have a delay in diagnosis. Basically in gastroparesis, the stomach motility
disappears and food remains stagnant in the stomach. The most common cause of
gastroparesis is diabetes but it can also occur from a blockage at the distal
end of stomach, a cancer or a stroke. Symptoms of gastroparesis includes
abdominal pain, fullness, bloating, nausea, vomiting after eating food, loss of
appetite and feeling of fullness after eating small amounts of food.
Gastroenteritis
is a medical condition characterized by inflammation ("-itis") of the
gastrointestinal tract that involves both the stomach ("gastro"-) and
the small intestine ("entero"-), resulting in some combination of
diarrhea, vomiting, and abdominal pain and cramping. Gastroenteritis has also
been referred to as gastro, stomach bug, and stomach virus. Although unrelated
to influenza, it has also been called stomach flu and gastric flu.
Globally,
most cases in children are caused by rotavirus. In adults, norovirus and
Campylobacter are more common. Less common causes include other bacteria (or
their toxins) and parasites. Transmission may occur due to consumption of
improperly prepared foods or contaminated water or via close contact with
individuals who are infectious.
The
foundation of management is adequate hydration. For mild or moderate cases,
this can typically be achieved via oral rehydration solution. For more severe
cases, intravenous fluids may be needed. Gastroenteritis primarily affects
children and those in the developing world.
Gastroenteritis viruses: A =
rotavirus, B = adenovirus, C = Norovirus and D = Astrovirus. The virus
particles are shown at the same magnification to allow size comparison.
Symptoms
and signs
Type 7 on the
Gastroenteritis
typically involves both diarrhea and vomiting, or less commonly, presents with
only one or the other. Abdominal cramping may also be present. Signs and
symptoms usually begin 12–72 hours after contracting the infectious agent. If
due to a viral agent, the condition usually resolves within one week. Some
viral causes may also be associated with fever, fatigue, headache, and muscle
pain. If the stool is bloody, the cause is less likely to be viral and more
likely to be bacterial. Some bacterial infections may be associated with severe
abdominal pain and may persist for several weeks.
Children
infected with rotavirus usually make a full recovery within three to eight
days. However, in poor countries treatment for severe infections is often out
of reach and persistent diarrhea is common. Dehydration is a common
complication of diarrhea, and a child with a significant degree of dehydration
may have a prolonged capillary refill, poor skin turgor, and abnormal
breathing. Repeat infections are typically seen in areas with poor sanitation,
and malnutrition, stunted growth, and long-term cognitive delays can result.
Reactive
arthritis occurs in 1% of people following infections with Campylobacter
species, and Guillain-Barre syndrome occurs in 0.1%. Hemolytic uremic syndrome
(HUS) may occur as a result of infection with Shiga toxin-producing Escherichia
coli or Shigella species, resulting in low platelet counts, poor kidney
function, and low red blood cell count (due to their breakdown). Children are
more predisposed to getting HUS than adults. Some viral infections may produce
benign infantile seizures.
Cause
Viruses
(particularly rotavirus) and the bacteria Escherichia coli and Campylobacter
species are the primary causes of gastroenteritis. There are, however, many
other infectious agents that can cause this syndrome. Non-infectious causes are
seen on occasion, but they are less likely than a viral or bacterial etiology.
Risk of infection is higher in children due to their lack of immunity and
relatively poor hygiene.
Viral
Rotavirus,
norovirus, adenovirus, and astrovirus are known to cause viral gastroenteritis.
Rotavirus is the most common cause of gastroenteritis in children, and produces
similar incidence rates in both the developed and developing world.[ Viruses
cause about 70% of episodes of infectious diarrhea in the pediatric age group.
Rotavirus is a less common cause in adults due to acquired immunity.
Norovirus
is the leading cause of gastroenteritis among adults in America, causing
greater than 90% of outbreaks. These localized epidemics typically occur when
groups of people spend time in close physical proximity to each other, such as
on cruise ships, in hospitals, or in restaurants. People may remain infectious
even after their diarrhea has ended. Norovirus is the cause of about 10% of
cases in children.
Bacterial
Salmonella enterica serovar
Typhimurium (ATCC 14028) as seen with a microscope at 1000 fold magnification
and following Gram staining.
In
the developed world Campylobacter jejuni is the primary cause of bacterial
gastroenteritis, with half of these cases associated with exposure to poultry.
In children, bacteria are the cause in about 15% of cases, with the most common
types being Escherichia coli, Salmonella, Shigella, and Campylobacter species.
If food becomes contaminated with bacteria and remains at room temperature for
a period of several hours, the bacteria multiply and increase the risk of
infection in those who consume the food. Some foods commonly associated with
illness include raw or undercooked meat, poultry, seafood, and eggs; raw
sprouts; unpasteurized milk and soft cheeses; and fruit and vegetable juices.
In the developing world, especially sub-Saharan Africa and Asia, cholera is a
common cause of gastroenteritis. This infection is usually transmitted by
contaminated water or food.
Toxigenic
Clostridium difficile is an important cause of diarrhea that occurs more often
in the elderly. Infants can carry these bacteria without developing symptoms.
It is a common cause of diarrhea in those who are hospitalized and is
frequently associated with antibiotic use. Staphylococcus aureus infectious
diarrhea may also occur in those who have used antibiotics. "Traveler's
diarrhea" is usually a type of bacterial gastroenteritis. Acid-suppressing
medication appears to increase the risk of significant infection after exposure
to a number of organisms, including Clostridium difficile, Salmonella, and
Campylobacter species. The risk is greater in those taking proton pump
inhibitors than with H2 antagonists.
Parasitic
A
number of protozoans can cause gastroenteritis – most commonly Giardia lamblia
– but Entamoeba histolytica and Cryptosporidium species have also been
implicated. As a group, these agents comprise about 10% of cases in children.
Giardia occurs more commonly in the developing world, but this etiologic agent causes
this type of illness to some degree nearly everywhere. It occurs more commonly
in persons who have traveled to areas with high prevalence, children who attend
day care, men who have sex with men, and following disasters.
Transmission
Transmission
may occur via consumption of contaminated water, or when people share personal
objects. In places with wet and dry seasons, water quality typically worsens
during the wet season, and this correlates with the time of outbreaks. In areas
of the world with seasons, infections are more common in the winter.
Bottle-feeding of babies with improperly sanitized bottles is a significant
cause on a global scale. Transmission rates are also related to poor hygiene,
especially among children, in crowded households, and in those with
pre-existing poor nutritional status. After developing tolerance, adults may
carry certain organisms without exhibiting signs or symptoms, and thus act as
natural reservoirs of contagion. While some agents (such as Shigella) only
occur in primates, others may occur in a wide variety of animals (such as
Giardia).
Non-infectious
There
are a number of non-infectious causes of inflammation of the gastrointestinal
tract. Some of the more common include medications (like NSAIDs), certain foods
such as lactose (in those who are intolerant), and gluten (in those with celiac
disease). Crohn's disease is also a non-infection source of (often severe)
gastroenteritis. Disease secondary to toxins may also occur. Some food related
conditions associated with nausea, vomiting, and diarrhea include: ciguatera
poisoning due to consumption of contaminated predatory fish, scombroid
associated with the consumption of certain types of spoiled fish, tetrodotoxin
poisoning from the consumption of puffer fish among others, and botulism
typically due to improperly preserved food.
Pathophysiology
Gastroenteritis
is defined as vomiting or diarrhea due to infection of the small or large
bowel. The changes in the small bowel are typically noninflammatory, while the
ones in the large bowel are inflammatory. The number of pathogens required to
cause an infection varies from as few as one (for Cryptosporidium) to as many
as 108 (for Vibrio cholerae).
Diagnosis
Gastroenteritis
is typically diagnosed clinically, based on a person's signs and symptoms.
Determining the exact cause is usually not needed as it does not alter
management of the condition. However, stool cultures should be performed in
those with blood in the stool, those who might have been exposed to food
poisoning, and those who have recently traveled to the developing world.
Diagnostic testing may also be done for surveillance. As hypoglycemia occurs in
approximately 10% of infants and young children, measuring serum glucose in
this population is recommended. Electrolytes and kidney function should also be
checked when there is a concern about severe dehydration.
Dehydration
A
determination of whether or not the person has dehydration is an important part
of the assessment, with dehydration typically divided into mild (3–5%),
moderate (6–9%), and severe (≥10%) cases. In children, the most accurate
signs of moderate or severe dehydration are a prolonged capillary refill, poor
skin turgor, and abnormal breathing. Other useful findings (when used in
combination) include sunken eyes, decreased activity, a lack of tears, and a
dry mouth. A normal urinary output and oral fluid intake is reassuring.
Laboratory testing is of little clinical benefit in determining the degree of
dehydration.
Differential
diagnosis
Other
potential causes of signs and symptoms that mimic those seen in gastroenteritis
that need to be ruled out include appendicitis, volvulus, inflammatory bowel
disease, urinary tract infections, and diabetes mellitus. Pancreatic
insufficiency, short bowel syndrome, Whipple's disease, coeliac disease, and
laxative abuse should also be considered. The differential diagnosis can be
complicated somewhat if the person exhibits only vomiting or diarrhea (rather
than both).
Appendicitis
may present with vomiting, abdominal pain, and a small amount of diarrhea in up
to 33% of cases. This is in contrast to the large amount of diarrhea that is
typical of gastroenteritis. Infections of the lungs or urinary tract in
children may also cause vomiting or diarrhea. Classical diabetic ketoacidosis
(DKA) presents with abdominal pain, nausea, and vomiting, but without diarrhea.
One study found that 17% of children with DKA were initially diagnosed as
having gastroenteritis.
Prevention
Percentage of rotavirus tests with
positive results, by surveillance week,
Lifestyle
A
supply of easily accessible uncontaminated water and good sanitation practices
are important for reducing rates of infection and clinically significant
gastroenteritis. Personal measures (such as hand washing) have been found to
decrease incidence and prevalence rates of gastroenteritis in both the
developing and developed world by as much as 30%. Alcohol-based gels may also
be effective. Breastfeeding is important, especially in places with poor
hygiene, as is improvement of hygiene generally. Breast milk reduces both the
frequency of infections and their duration. Avoiding contaminated food or drink
should also be effective.
Vaccination
Due
to both its effectiveness and safety, in 2009 the World Health Organization
recommended that the rotavirus vaccine be offered to all children globally. Two
commercial rotavirus vaccines exist and several more are in development. In
Africa and Asia these vaccines reduced severe disease among infants and
countries that have put in place national immunization programs have seen a
decline in the rates and severity of disease. This vaccine may also prevent
illness in non-vaccinated children by reducing the number of circulating
infections. Since 2000, the implementation of a rotavirus vaccination program
in the United States has substantially decreased the number of cases of
diarrhea by as much as 80 percent. The first dose of vaccine should be given to
infants between 6 and 15 weeks of age. The oral cholera vaccine has been found
to be 50–60% effective over 2 years.
Management
Gastroenteritis
is usually an acute and self-limiting disease that does not require medication.
The preferred treatment in those with mild to moderate dehydration is oral
rehydration therapy (ORT). Metoclopramide and/or ondansetron, however, may be
helpful in some children, and butylscopolamine is useful in treating abdominal
pain.
Rehydration
The
primary treatment of gastroenteritis in both children and adults is
rehydration. This is preferably achieved by oral rehydration therapy, although
intravenous delivery may be required if a there is a decreased level of
consciousness or if dehydration is severe. Oral replacement therapy products
made with complex carbohydrates (i.e. those made from wheat or rice) may be
superior to those based on simple sugars. Drinks especially high in simple
sugars, such as soft drinks and fruit juices, are not recommended in children
under 5 years of age as they may increase diarrhea. Plain water may be used if
more specific and effective ORT preparations are unavailable or are not
palatable. A nasogastric tube can be used in young children to administer
fluids if warranted.
Dietary
It
is recommended that breast-fed infants continue to be nursed in the usual
fashion, and that formula-fed infants continue their formula immediately after
rehydration with ORT. Lactose-free or lactose-reduced formulas usually are not
necessary. Children should continue their usual diet during episodes of
diarrhea with the exception that foods high in simple sugars should be avoided.
The BRAT diet (bananas, rice, applesauce, toast and tea) is no longer
recommended, as it contains insufficient nutrients and has no benefit over
normal feeding. Some probiotics have been shown to be beneficial in reducing
both the duration of illness and the frequency of stools. They may also be
useful in preventing and treating antibiotic associated diarrhea. Fermented
milk products (such as yogurt) are similarly beneficial. Zinc supplementation
appears to be effective in both treating and preventing diarrhea among children
in the developing world.
Antiemetics
Antiemetic
medications may be helpful for treating vomiting in children. Ondansetron has
some utility, with a single dose being associated with less need for
intravenous fluids, fewer hospitalizations, and decreased vomiting.
Metoclopramide might also be helpful.However, the use of ondansetron might
possibly be linked to an increased rate of return to hospital in children. The
intravenous preparation of ondansetron may be given orally if clinical judgment
warrants. Dimenhydrinate, while reducing vomiting, does not appear to have a
significant clinical benefit.
Antibiotics
Antibiotics
are not usually used for gastroenteritis, although they are sometimes
recommended if symptoms are particularly severe or if a susceptible bacterial
cause is isolated or suspected. If antibiotics are to be employed, a macrolide
(such as azithromycin) is preferred over a fluoroquinolone due to higher rates
of resistance to the latter. Pseudomembranous colitis, usually caused by
antibiotic use, is managed by discontinuing the causative agent and treating it
with either metronidazole or vancomycin. Bacteria and protozoans that are amenable
to treatment include Shigella Salmonella typhi, and Giardia species. In those
with Giardia species or Entamoeba histolytica, tinidazole treatment is
recommended and superior to metronidazole. The World Health Organization (WHO)
recommends the use of antibiotics in young children who have both bloody
diarrhea and fever.
Antimotility
agents
Antimotility
medication has a theoretical risk of causing complications, and although clinical
experience has shown this to be unlikely, these drugs are discouraged in people
with bloody diarrhea or diarrhea that is complicated by fever. Loperamide, an
opioid analogue, is commonly used for the symptomatic treatment of diarrhea.
Loperamide is not recommended in children, however, as it may cross the
immature blood–brain barrier and cause toxicity. Bismuth subsalicylate, an
insoluble complex of trivalent bismuth and salicylate, can be used in mild to
moderate cases, but salicylate toxicity is theoretically possible.
Epidemiology
It
is estimated that three to five billion cases of gastroenteritis occur globally
on an annual basis, primarily affecting children and those in the developing
world. It resulted in about 1.3 million deaths in children less than five as of
2008, with most of these occurring in the world's poorest nations. More than
450,000 of these fatalities are due to rotavirus in children under 5 years of
age. Cholera causes about three to five million cases of disease and kills approximately
100,000 people yearly. In the developing world children less than two years of
age frequently get six or more infections a year that result in clinically
significant gastroenteritis. It is less common in adults, partly due to the
development of acquired immunity.
In
1980, gastroenteritis from all causes caused 4.6 million deaths in children,
with the majority occurring in the developing world. Death rates were reduced
significantly (to approximately 1.5 million deaths annually) by the year 2000, largely
due to the introduction and widespread use of oral rehydration therapy. In the
US, infections causing gastroenteritis are the second most common infection
(after the common cold), and they result in between 200 and 375 million cases
of acute diarrhea and approximately ten thousand deaths annually, with 150 to
300 of these deaths in children less than five years of age.
History
The
first usage of "gastroenteritis" was in 1825. Before this time it was
more specifically known as typhoid fever or "cholera morbus", among
others, or less specifically as "griping of the guts",
"surfeit", "flux", "colic", "bowel
complaint", or any one of a number of other archaic names for acute
diarrhea.
Society
and culture
Gastroenteritis
is associated with many colloquial names, including "Montezuma's
revenge", "Delhi belly", "la turista", and "back
door sprint", among others. It has played a role in many military
campaigns and is believed to be the origin of the term "no guts no
glory".
Gastroenteritis
is the main reason for 3.7 million visits to physicians a year in the United
States and 3 million visits in France. In the United States gastroenteritis as
a whole is believed to result in costs of 23 billion USD per year with that due
to rotavirus alone resulting in estimated costs of 1 billion USD a year.
Research
There
are a number of vaccines against gastroenteritis in development. For example,
vaccines against Shigella and enterotoxigenic Escherichia coli (ETEC), two of
the leading bacterial causes of gastroenteritis worldwide.
Diarrhea
During
digestion, food is stored in the liquid present in the stomach. The food that
is not digested travels to the small intestine and colon in liquid form. These
organs begin to absorb the water turning the food into a more solid form.
Different viruses or bacteria can increase the amount of liquid that is
secreted and moves too quickly through the digestive tract for the water to be
absorbed. Diarrhea can exist in one of two types, acute diarrhea or chronic
diarrhea. The acute diagnosis can last for a few days up to a week of time.
Chronic diarrhea lasts for several days or longer periods of time lasting a few
weeks. The difference in diagnosis will help determine the cause of the
illness.
Diarrhea
(or diarrhoea) (from the Greek διάρροια,
δια dia "through" + ρέω rheo
"flow" meaning "flowing through") is the condition of
having three or more loose or liquid bowel movements per day. It is a common
cause of death in developing countries and the second most common cause of
infant deaths worldwide. The loss of fluids through diarrhea can cause
dehydration and electrolyte disturbances such as potassium deficiency or other
salt imbalances.
In
2009 diarrhea was estimated to have caused 1.1 million deaths in people aged 5
and over and 1.5 million deaths in children under the age of 5. Oral
rehydration solutions (ORS) with modest amounts of salts and zinc tablets are
the treatment of choice and have been estimated to have saved 50 million
children in the past 25 years. In cases where ORS is not available, homemade
solutions are often used.
Definition
Diarrhea
is defined by the World Health Organization as having three or more loose or
liquid stools per day, or as having more stools than is normal for that person.
Secretory
Secretory
diarrhea means that there is an increase in the active secretion, or there is
an inhibition of absorption. There is little to no structural damage. The most
common cause of this type of diarrhea is a cholera toxin that stimulates the
secretion of anions, especially chloride ions. Therefore, to maintain a charge
balance in the lumen, sodium is carried with it, along with water. In this type
of diarrhea intestinal fluid secretion is isotonic with plasma even during
fasting. It continues even when there is no oral food intake.
Osmotic
Osmotic
diarrhea occurs when too much water is drawn into the bowels. If a person
drinks solutions with excessive sugar or excessive salt, these can draw water
from the body into the bowel and cause osmotic diarrhea. Osmotic diarrhea can
also be the result of maldigestion (e.g., pancreatic disease or Coeliac
disease), in which the nutrients are left in the lumen to pull in water. Or it
can be caused by osmotic laxatives (which work to alleviate constipation by
drawing water into the bowels). In healthy individuals, too much magnesium or
vitamin C or undigested lactose can produce osmotic diarrhea and distention of
the bowel. A person who has lactose intolerance can have difficulty absorbing
lactose after an extraordinarily high intake of dairy products. In persons who
have fructose malabsorption, excess fructose intake can also cause diarrhea.
High-fructose foods that also have a high glucose content are more absorbable
and less likely to cause diarrhea. Sugar alcohols such as sorbitol (often found
in sugar-free foods) are difficult for the body to absorb and, in large
amounts, may lead to osmotic diarrhea. In most of these cases, osmotic diarrhea
stops when offending agent (e.g. milk, sorbitol) is stopped.
Exudative
Exudative
diarrhea occurs with the presence of blood and pus in the stool. This occurs
with inflammatory bowel diseases, such as Crohn's disease or ulcerative
colitis, and other severe infections such as E. coli or other forms of food
poisoning.
Motility-related
Motility-related
diarrhea is caused by the rapid movement of food through the intestines
(hypermotility). If the food moves too quickly through the gastrointestinal
tract, there is not enough time for sufficient nutrients and water to be
absorbed. This can be due to a vagotomy or diabetic neuropathy, or a
complication of menstruation. Hyperthyroidism can produce hypermotility and
lead to pseudodiarrhea and occasionally real diarrhea. Diarrhea can be treated
with antimotility agents (such as loperamide). Hypermotility can be observed in
people who have had portions of their bowel removed, allowing less total time
for absorption of nutrients.
Inflammatory
Inflammatory
diarrhea occurs when there is damage to the mucosal lining or brush border,
which leads to a passive loss of protein-rich fluids, and a decreased ability
to absorb these lost fluids. Features of all three of the other types of
diarrhea can be found in this type of diarrhea. It can be caused by bacterial
infections, viral infections, parasitic infections, or autoimmune problems such
as inflammatory bowel diseases. It can also be caused by tuberculosis, colon
cancer, and enteritis.
Dysentery
Generally,
if there is blood visible in the stools, it is not diarrhea, but dysentery. The
blood is trace of an invasion of bowel tissue. Dysentery is a symptom of, among
others, Shigella, Entamoeba histolytica, and Salmonella.
ifferential
diagnosis
Diagram of
the human gastrointestinal tract.
Diarrhea
is most commonly due to viral gastroenteritis with rotavirus, which accounts
for 40% of cases in children under five. (p. 17) In travelers however bacterial
infections predominate. Various toxins such as mushroom poisoning and drugs can
also cause acute diarrhea.
Chronic
diarrhea can be the part of the presentations of a number of chronic medical
conditions affecting the intestine. Common causes include ulcerative colitis,
Crohn's disease, microscopic colitis, celiac disease, irritable bowel syndrome
and bile acid malabsorption.
Infections
There
are many causes of infectious diarrhea, which include viruses, bacteria and
parasites. Norovirus is the most common cause of viral diarrhea in adults, but
rotavirus is the most common cause in children under five years old. Adenovirus
types 40 and 41, and astroviruses cause a significant number of infections.
The
bacterium Campylobacter is a common cause of bacterial diarrhea, but infections
by Salmonellae, Shigellae and some strains of Escherichia coli (E.coli) are
frequent.
In
the elderly, particularly those who have been treated with antibiotics for
unrelated infections, a toxin produced by Clostridium difficile often causes
severe diarrhea.
Parasites
do not often cause diarrhea except for the protozoan Giardia, which can cause
chronic infections if these are not diagnosed and treated with drugs such as
metronidazole, and Entamoeba histolytica.
Other
infectious agents such as parasites and bacterial toxins also occur. In
sanitary living conditions where there is ample food and a supply of clean
water, an otherwise healthy person usually recovers from viral infections in a
few days. However, for ill or malnourished individuals, diarrhea can lead to
severe dehydration and can become life-threatening.
Malabsorption
Malabsorption
is the inability to absorb food fully, mostly from disorders in the small
bowel, but also due to maldigestion from diseases of the pancreas.
Causes
include:
enzyme
deficiencies or mucosal abnormality, as in food allergy and food intolerance,
e.g. celiac disease (gluten intolerance), lactose intolerance (intolerance to
milk sugar, common in non-Europeans), and fructose malabsorption.
pernicious
anemia, or impaired bowel function due to the inability to absorb vitamin B12,
loss
of pancreatic secretions, which may be due to cystic fibrosis or pancreatitis,
structural
defects, like short bowel syndrome (surgically removed bowel) and radiation
fibrosis, such as usually follows cancer treatment and other drugs, including
agents used in chemotherapy; and
certain
drugs, like orlistat, which inhibits the absorption of fat.
Inflammatory
bowel disease
The
two overlapping types here are of unknown origin:
1.
Ulcerative colitis is marked by
chronic bloody diarrhea and inflammation mostly affects the distal colon near
the rectum.
2.
Crohn's disease typically affects
fairly well demarcated segments of bowel in the colon and often affects the end
of the small bowel.
Irritable
bowel syndrome
Another
possible cause of diarrhea is irritable bowel syndrome (IBS) which usually presents
with abdominal discomfort relieved by defecation and unusual stool (diarrhea or
constipation) for at least 3 days a week over the previous 3 months. Symptoms
of diarrhea-predominant IBS can be managed through a combination of dietary
changes, soluble fiber supplements, and/or medications such as loperamide or
codeine. About 30% of patients with diarrhea-predominant IBS have bile acid
malabsorption diagnosed with an abnormal SeHCAT test.
Other
causes
Diarrhea
can be caused by chronic ethanol ingestion.
Ischemic
bowel disease. This usually affects older people and can be due to blocked
arteries.
Microscopic
colitis, a type of inflammatory bowel disease where changes are only seen on
histological examination of colonic biopsies.
Bile
salt malabsorption (primary bile acid diarrhea) where excessive bile acids in
the colon produce a secretory diarrhea.
Hormone-secreting
tumors: some hormones (e.g., serotonin) can cause diarrhea if excreted in
excess (usually from a tumor).
Chronic
mild diarrhea in infants and toddlers may occur with no obvious cause and with
no other ill effects; this condition is called toddler's diarrhea.
Pathophysiology
Evolution
According
to two researchers, Nesse and Williams, diarrhea may function as an evolved
expulsion defense mechanism. As a result, if it is stopped, there might be a
delay in recovery. They cite in support of this argument research published in
1973 which found that treating Shigella with the anti-diarrhea drug
(Co-phenotrope, Lomotil) caused people to stay feverish twice as long as those
not so treated. The researchers indeed themselves observed that: "Lomotil
may be contraindicated in shigellosis. Diarrhea may represent a defense
mechanism".
Diagnostic
approach
The
following types of diarrhea may indicate further investigation is needed:
In
infants
Moderate
or severe diarrhea in young children
Associated
with blood
Continues
for more than two days
Associated
non-cramping abdominal pain, fever, weight loss, etc.
In
travelers
In
food handlers, because of the potential to infect others;
In
institutions such as hospitals, child care centers, or geriatric and
convalescent homes.
A
severity score is used to aid diagnosis in children.
Prevention
A rotavirus
vaccine decrease the rates of diarrhea in a population. New vaccines against
rotavirus, Shigella, ETEC, and cholera are under development, as well as other
causes of infectious diarrhea.
Probiotics
decrease the risk of diarrhea in those taking antibiotics. In institutions and
in communities, interventions that promote hand washing lead to significant
reductions in the incidence of diarrhea.
Management
In
many cases of diarrhea, replacing lost fluid and salts is the only treatment
needed. This is usually by mouth – oral rehydration therapy – or, in severe
cases, intravenously. Diet restrictions such as the BRAT diet are no longer
recommended. Research does not support the limiting of milk to children as
doing so has no effect on duration of diarrhea. To the contrary, WHO recommends
that children with diarrhea continue to eat as sufficient nutrients are usually
still absorbed to support continued growth and weight gain and that continuing
to eat speeds also recovery of normal intestinal functioning. CDC recommends
that children and adults with cholera also continue to eat.
Medications
such as loperamide (Imodium) and bismuth subsalicylate may be beneficial;
however they may be contraindicated in certain situations.
Fluids
and preventing dehydration
To
prevent dehydration and salt loss, it is widely recommended a person begin
drinking Oral Rehydration Solution (ORS) as soon as possible. This strategy
adds modest amounts of sugar and salt to water. There are prepackaged ORS
products available. A person can also use home products such as lightly salted
soup and/or lightly salted water from the cooking of rice. Supplemental zinc
and potassium are also helpful, but ORS should not be delayed in the case that
these are not immediately available.
Oral
Rehydration Solution (ORS) can be used to prevent dehydration and in many cases
is quite literally a life saver. Standard home solutions such as salted rice
water, salted yogurt drinks, vegetable and chicken soups with salt can be
given. Home solutions such as water in which cereal has been cooked, unsalted
soup, green coconut water, weak tea (unsweetened), and unsweetened fresh fruit
juices can have from half a teaspoon to full teaspoon of salt (from
one-and-a-half to three grams) added per liter. Clean plain water can also be
one of several fluids given. There are commercial solutions such as Pedialyte,
and relief agencies such as UNICEF widely distribute packets of salts and
sugar. A WHO publication for physicians recommends a homemade ORS consisting of
one liter water with one teaspoon salt (
Appropriate
amounts of supplemental zinc and potassium should be added if available. But
the availability of these should not delay rehydration. As WHO points out, the
most important thing is to begin preventing dehydration as early as possible.
In another example of prompt ORS hopefully preventing dehydration, CDC
recommends for the treatment of cholera continuing to give Oral Rehydration
Solution during travel to medical treatment.
Vomiting
often occurs during the first hour or two of treatment with ORS, especially if
a child drinks the solution too quickly, but this seldom prevents successful
rehydration since most of the fluid is still absorbed. WHO recommends that if a
child vomits, to wait five or ten minutes and then start to give the solution
again more slowly.
Drinks
especially high in simple sugars, such as soft drinks and fruit juices, are not
recommended in children under 5 years of age as they may increase dehydration.
A too rich solution in the gut draws water from the rest of the body, just as
if the person were to drink sea water Plain water may be used if more specific
and effective ORT preparations are unavailable or are not palatable.
Additionally, a mix of both plain water and drinks perhaps too rich in sugar
and salt can alternatively be given to the same person, which the goal of
providing a medium amount of sodium overall. A nasogastric tube can be used in
young children to administer fluids if warranted.
Continuing
to eat is recommended
WHO
recommends a child with diarrhea continue to be fed. Continued feeding speeds
the recovery of normal intestinal function. In contrast, children whose food is
restricted, have diarrhea of longer duration and recover intestinal function
more slowly. A child should also continue to be breastfed. A 2005 WHO manual
for physicians and other senior health workers is quite emphatic regarding this
point: "Food should never be withheld and the child's usual foods should
not be diluted. Breastfeeding should always be continued." And in the
specific example of cholera, CDC also makes the same recommendation.
Antibiotics
While
antibiotics are beneficial in certain types of acute diarrhea, they are usually
not used except in specific situations. There are concerns that antibiotics may
increase the risk of hemolytic uremic syndrome in people infected with
Escherichia coli O157:H7. In resource poor countries, treatment with antibiotics
may be beneficial. However, some bacteria are developing antibiotic resistance,
particularly Shigella.
Antibiotics
can also cause diarrhea, and antibiotic-associated diarrhea is the most common adverse
effect of treatment with general antibiotics.
Bismuth
compounds
While
bismuth compounds (Pepto-Bismol) decreased the number of bowel movements in
those with travelers' diarrhea, they do not decrease the length of illness.
These agents should only be used if bloody diarrhea is not present.
Anti
motility agents
Anti
motility agents like loperamide are effective at reducing the duration of
diarrhea.
Codeine
is used in the treatment of diarrhea to slow down peristalsis and the passage
of fecal material through the bowels - this means that more time is given for
water to reabsorb back into the body, which gives a firmer stool, and also
means that feces is passed less frequently.
Bile
acid sequestrants
Bile
acid sequestrants such as cholestyramine, colestipol and colesevelam can be
effective in chronic diarrhea due to bile acid malabsorption. Therapeutic
trials of these drugs are indicated in chronic diarrhea if bile acid
malabsorption cannot be diagnosed with a specific test, such as SeHCAT
retention.
Alternative
therapies
Zinc
supplementation benefits children suffering from diarrhea in developing
countries, but only in infants over six months old. This supports the World
Health Organisation guidelines for zinc, but not in the very young.
Probiotics
reduce the duration of symptoms by one day and reduced the chances of symptoms
lasting longer than four days by 60%. The probiotic lactobacillus can help
prevent antibiotic associated diarrhea in adults but possibly not children. For
those who with lactose intolerance, taking digestive enzymes containing lactase
when consuming dairy products is recommended.
Epidemiology
World
wide in 2004 approximately 2.5 billion cases of diarrhea occurred which results
in 1.5 million deaths among children under the age of five. Greater than half
of these were in Africa and South Asia. This is down from a death rate of 5
million per year two decades ago. Diarrhea remains the second leading cause of
infant mortality (16%) after pneumonia (17%) in this age group.
Crohn's disease
Crohn's
disease is an inflammatory bowel disease that can affect any part of the
digestive tract, even the stomach, although it's a rare presentation. Its main
feature is inflammatory ulcers that can affect the total thickness of the
stomach wall and can bleed but rarely perforate. Symptoms include abdominal
pain, loss of appetite, and weight loss. Diarrhea is also a symptom that can
develop, so checking stools for the appearance of blood is important. It is
possible for symptoms of Crohn's Disease to remain with a person for weeks or
go away on their own. Reporting the symptoms to a doctor is recommended to
prevent further complications.
Crohn's
disease, also known as Crohn syndrome and regional enteritis, is a type of
inflammatory bowel disease that may affect any part of the gastrointestinal
tract from mouth to anus, causing a wide variety of symptoms. It primarily
causes abdominal pain, diarrhea (which may be bloody if inflammation is at its
worst), vomiting (can be continuous), or weight loss, but may also cause
complications outside the gastrointestinal tract such as skin rashes,
arthritis, inflammation of the eye, tiredness, and lack of concentration.
Crohn's disease is caused by interactions between environmental, immunological
and bacterial factors in genetically susceptible individuals. This results in a
chronic inflammatory disorder, in which the body's immune system attacks the
gastrointestinal tract possibly directed at microbial antigens. Crohn's disease
has wrongly been described as an autoimmune disease in the past; recent
investigators have described it as an immune deficiency state.
There
is a genetic association with Crohn's disease, primarily with variations of the
NOD2 gene and its protein, which senses bacterial cell walls. Siblings of
affected individuals are at higher risk. Males and females are equally
affected. Smokers are two times more likely to develop Crohn's disease than
nonsmokers. Crohn's disease affects between 400,000 and 600,000 people in North
America. Prevalence estimates for Northern Europe have ranged from 27–48 per
100,000. Crohn's disease tends to present initially in the teens and twenties,
with another peak incidence in the fifties to seventies, although the disease
can occur at any age. There is no known pharmaceutical or surgical cure for
Crohn's disease. Treatment options are restricted to controlling symptoms,
maintaining remission, and preventing relapse. The disease was named after
gastroenterologist Burrill Bernard Crohn, who, in 1932, together with two other
colleagues at Mount Sinai Hospital in New York, described a series of patients
with inflammation of the terminal ileum, the area most commonly affected by the
illness.
The three most common sites of
intestinal involvement in Crohn's disease are
ileal, ileocolic and colonic.
Classification
Distribution
of gastrointestinal Crohn's disease. Based on data from American Gastroenterological
Association.
Signs
and symptoms
Symptoms
in Crohn's disease vs. ulcerative colitis (v · d · e)
|
|
Crohn's
disease |
Ulcerative
colitis |
|
Defecation |
Often
porridge-like, sometimes steatorrhea |
Often mucus-like and with blood |
|
Tenesmus |
Less
common |
More common |
|
Fever |
Common |
Indicates severe disease |
|
Fistulae |
Common[ |
Seldom |
|
Weight
loss |
Often |
More seldom |
Gastrointestinal
Endoscopy
image of colon showing serpiginous ulcer, a classic finding in Crohn's disease.
Many
people with Crohn's disease have symptoms for years prior to the diagnosis.]The
usual onset is between 15 and 30 years of age, but can occur at any age.
Because of the 'patchy' nature of the gastrointestinal disease and the depth of
tissue involvement, initial symptoms can be more subtle than those of
ulcerative colitis. People with Crohn's disease experience chronic recurring
periods of flare-ups and remission.
Abdominal
pain may be the initial symptom of Crohn's disease. It is often accompanied by
diarrhea, especially in those who have had surgery. The diarrhea may or may not
be bloody. The nature of the diarrhea in Crohn's disease depends on the part of
the small intestine or colon involved. Ileitis typically results in
large-volume, watery feces. Colitis may result in a smaller volume of feces of
higher frequency. Fecal consistency may range from solid to watery. In severe
cases, an individual may have more than 20 bowel movements per day and may need
to awaken at night to defecate. Visible bleeding in the feces is less common in
Crohn's disease than in ulcerative colitis, but may be seen in the setting of
Crohn's colitis. Bloody bowel movements are typically intermittent, and may be
bright or dark red in color. In the setting of severe Crohn's colitis, bleeding
may be copious.[ Flatulence and bloating may also add to the intestinal discomfort.
Symptoms
caused by intestinal stenosis are also common in Crohn's disease. Abdominal
pain is often most severe in areas of the bowel with stenoses. In the setting
of severe stenosis, vomiting and nausea may indicate the beginnings of small bowel
obstruction. Although the association is greater in the context of ulcerative
colitis, Crohn's disease may also be associated with primary sclerosing
cholangitis, a type of inflammation of the bile ducts.
Perianal
discomfort may also be prominent in Crohn's disease. Itchiness or pain around
the anus may be suggestive of inflammation, fistulization or abscess around the
anal area or anal fissure. Perianal skin tags are also common in Crohn's
disease. Fecal incontinence may accompany perianal Crohn's disease. At the
opposite end of the gastrointestinal tract, the mouth may be affected by
non-healing sores (aphthous ulcers). Rarely, the esophagus, and stomach may be
involved in Crohn's disease. These can cause symptoms including difficulty
swallowing (dysphagia), upper abdominal pain, and vomiting.
Systemic
Crohn's
disease, like many other chronic, inflammatory diseases, can cause a variety of
systemic symptoms. Among children, growth failure is common. Many children are
first diagnosed with Crohn's disease based on inability to maintain growth. As
it may manifest at the time of the growth spurt in puberty, up to 30% of
children with Crohn's disease may have retardation of growth. Fever may also be
present, though fevers greater than 38.5 ˚C (101.3 ˚F) are uncommon
unless there is a complication such as an abscess. Among older individuals,
Crohn's disease may manifest as weight loss, usually related to decreased food
intake, since individuals with intestinal symptoms from Crohn's disease often
feel better when they do not eat and might lose their appetite. People with
extensive small intestine disease may also have malabsorption of carbohydrates
or lipids, which can further exacerbate weight loss.
Extraintestinal
Erythema
nodosum on the back of a person with Crohn's disease.
In
addition to systemic and gastrointestinal involvement, Crohn's disease can
affect many other organ systems. Inflammation of the interior portion of the
eye, known as uveitis, can cause eye pain, especially when exposed to light (photophobia).
Inflammation may also involve the white part of the eye (sclera), a condition
called episcleritis. Both episcleritis and uveitis can lead to loss of vision
if untreated.
Crohn's
disease is associated with a type of rheumatologic disease known as
seronegative spondyloarthropathy. This group of diseases is characterized by
inflammation of one or more joints (arthritis) or muscle insertions
(enthesitis). The arthritis can affect larger joints, such as the knee or
shoulder, or may exclusively involve the small joints of the hands and feet.
The arthritis may also involve the spine, leading to ankylosing spondylitis if
the entire spine is involved or simply sacroiliitis if only the lower spine is
involved. The symptoms of arthritis include painful, warm, swollen, stiff
joints and loss of joint mobility or function.
Pyoderma
gangrenosum on the leg of a person with Crohn's disease.
Crohn's
disease may also involve the skin, blood, and endocrine system. One type of
skin manifestation, erythema nodosum, presents as red nodules usually appearing
on the shins. Erythema nodosum is due to inflammation of the underlying
subcutaneous tissue, and is characterized by septal panniculitis. Another skin
lesion, pyoderma gangrenosum, is typically a painful ulcerating nodule. Crohn's
disease also increases the risk of blood clots; painful swelling of the lower
legs can be a sign of deep venous thrombosis, while difficulty breathing may be
a result of pulmonary embolism. Autoimmune hemolytic anemia, a condition in which
the immune system attacks the red blood cells, is also more common in Crohn's
disease and may cause fatigue, pallor, and other symptoms common in anemia.
Clubbing, a deformity of the ends of the fingers, may also be a result of
Crohn's disease. Finally, Crohn's disease may cause osteoporosis, or thinning
of the bones. Individuals with osteoporosis are at increased risk of bone
fractures.
Crohn's
disease seems to be caused by a combination of environmental factors and
genetic predisposition. Crohn's is the first genetically complex disease in
which the relationship between genetic risk factors and the immune system is
understood in considerable detail. Each individual risk mutation makes a small
contribution to the overall risk of Crohn's (approximately 1:200). The genetic
data, and direct assessment of patient immunity, indicates a malfunction in the
innate immune system. In this view, the chronic inflammation of Crohn's is
caused when the adaptive immune system tries to compensate for a deficient
innate immune system.
Genetics
Schematic
of NOD2 CARD15 gene, which is associated with certain disease patterns in
Crohn's disease.
Crohn's
has a genetic component. The disease runs in families, and siblings are 30
times more likely to develop Crohn's than the general population.
The
first mutation found to be associated with Crohn's was a frameshift in the NOD2
gene (also known as the CARD15 gene), followed by the discovery of point
mutations. By now, over thirty genes have been associated. A biological function
is known for most of them. For example, one association is with mutations in
the XBP1 gene, which is involved in the unfolded protein response pathway of
the endoplasmatic reticulum. There is considerable overlap between
susceptibility loci for IBD and mycobacterial infections.
Immune
system
The
prevailing view was that Crohn's disease is a primary T cell autoimmune
disorder. A newer view is that Crohn's results from an impaired innate
immunity. In the newer view, impaired cytokine secretion by macrophages
contributes to impaired innate immunity, and leads to a sustained
microbial-induced inflammatory response in the colon, where the bacterial load
is high. One theory is that the inflammation of Crohn's was caused by an
overactive Th1 cytokine response. More recent studies argue that Th17 is more
important.
The
most recent (2007) gene to be implicated in Crohn's disease is ATG16L1, which
may induce autophagy and hinder the body's ability to attack invasive bacteria.
Another recent study has theorized that the human immune system traditionally
evolved with the presence of parasites inside the body, and that the lack
thereof due to modern hygiene standards has weakened the immune system. Test
subjects were reintroduced to harmless parasites, with positive response.
Microbes
Current
thinking is that microorganisms are taking advantage of their host's weakened
mucosal layer and inability to clear bacteria from the intestinal walls, which
are both symptoms of Crohn's. Different strains found in tissue and different
outcomes to antibiotics therapy and resistance suggest Crohn's Disease is not
one disease, but an umbrella of diseases related to different pathogens.
Some
studies have suggested a role for Mycobacterium avium subspecies
paratuberculosis (MAP), which causes a similar disease, Johne's disease, in
cattle.[66] NOD2, a gene involved in Crohn’s genetic susceptibility, is
associated with diminished killing of MAP by macrophages, reduced innate and
adaptive immunity in the host and impaired immune responses required for
control of intracellular mycobacterial infection. Macrophages infected with
viable MAP are associated with high production of TNF-α.
Other
studies have linked specific strains of enteroadherent E. coli to the disease.
Adherent-invasive Escherichia coli (AIEC), are much more prevalent in CD
patients than in controls, have the ability to make strong biofilms compared to
non-AIEC strains correlating with high adhesion and invasion indices of
neutrophils and the ability to block autophagy at the autolysosomal step, which
allows for intracellular survival of the bacteria and induction of
inflammation. Inflammation drives the proliferation of AIEC and dysbiosis in
the ileum, irrespective of genotype,. AIEC strains replicate extensively into macrophages
inducing the secretion of very large amounts of TNF-α. Monocytes from
Crohn's disease patients produced markedly higher levels of pro-inflammatory
TNF-α (and IL-6) in response to AIEC strain "LF82" than
monocytes from normal subjects (p <.001).
Bacterial
strains, EC15 and EC10, were found to adhere and invade the Caco2 cell line in
pediatric crohn's disease patients, similar to the well-known AIEC strain LF82
(positive control): they upregulated CEACAM6, TNF-α, and IL-8 gene/protein
expression, in vitro and in cultured intestinal mucosa; they could also survive
inside macrophages and damage the epithelial barrier integrity. Lesions in the
inflamed tissues were associated with bacterial infection.
The
mannose-bearing antigens (mannins) from yeast may also cause an antibody
response.
Mouse
studies have suggested some symptoms of Crohn's disease, ulcerative colitis and
irritable bowel syndrome have the same underlying cause. Biopsy samples taken
from the colons of all three patient groups were found to produce elevated
levels of a serine protease. Experimental introduction of the serine protease
into mice has been found to produce widespread pain associated with irritable
bowel syndrome, as well as colitis, which is associated with all three diseases.
Regional and temporal variations in those illnesses follow those associated
with infection with the protozoan Blastocystis.
The
"cold-chain" hypothesis is that psychrotrophic bacteria such as
Yersinia and Listeria species contribute to the disease. A statistical
correlation was found between the advent of the use of refrigeration in the
United States and various parts of Europe and the rise of the disease.
There
is an apparent connection between Crohn's disease, Mycobacterium, other
pathogenic bacteria, and genetic markers. In many individuals, genetic factors
predispose individuals to Mycobacterium avium subsp. paratuberculosis
infection. This bacterium then produces mannins, which protect both itself and
various bacteria from phagocytosis, which causes a variety of secondary
infections.
Still,
this relationship between specific types of bacteria and Crohn's disease
remains unclear.
Environmental
factors
The
increased incidence of Crohn's in the industrialized world indicates an
environmental component. Crohn's is associated with an increased intake of
animal protein, milk protein and an increased ratio of omega-6 to omega-3
polyunsaturated fatty acids. Those who consume vegetable proteins appear to
have a lower incidence of Crohn's disease. Consumption of fish protein has no
association. Smoking increases the risk of the return of active disease
(flares).The introduction of hormonal contraception in the United States in the
1960s is associated with a dramatic increase in incidence, and one hypothesis is
that these drugs work on the digestive system in ways similar to smoking.
Isotretinoin is associated with Crohn's. Stress is sometimes claimed to
exacerbate Crohn's disease.
Section of colectomy showing
transmural inflammation
During
a colonoscopy, biopsies of the colon are often taken to confirm the diagnosis.
Certain characteristic features of the pathology seen point toward Crohn's
disease; it shows a transmural pattern of inflammation, meaning the
inflammation may span the entire depth of the intestinal wall. Ulceration is an
outcome seen in highly active disease. There is usually an abrupt transition
between unaffected tissue and the ulcer - a characteristic sign known as skip
lesions. Under a microscope, biopsies of the affected colon may show mucosal
inflammation, characterized by focal infiltration of neutrophils, a type of
inflammatory cell, into the epithelium. This typically occurs in the area
overlying lymphoid aggregates. These neutrophils, along with mononuclear cells,
may infiltrate the crypts, leading to inflammation (crypititis) or abscess
(crypt abscess). Granulomas, aggregates of macrophage derivatives known as
giant cells, are found in 50% of cases and are most specific for Crohn's
disease. The granulomas of Crohn's disease do not show "caseation", a
cheese-like appearance on microscopic examination characteristic of granulomas
associated with infections, such as tuberculosis. Biopsies may also show
chronic mucosal damage, as evidenced by blunting of the intestinal villi,
atypical branching of the crypts, and a change in the tissue type (metaplasia).
One example of such metaplasia, Paneth cell metaplasia, involves development of
Paneth cells (typically found in the small intestine) in other parts of the
gastrointestinal system.
Diagnosis
Endoscopic
image of Crohn's colitis showing deep ulceration
CT scan
showing Crohn's disease in the fundus of the stomach.
Crohn's disease can mimic ulcerative
colitis on endoscopy. This endoscopic image is of Crohn's colitis showing diffuse
loss of mucosal architecture, friability of mucosa in sigmoid colon and exudate
on wall, all of which can be found with ulcerative colitis.
Endoscopic
biopsy showing granulomatous inflammation of the colon in a case of Crohn's
disease.
H&E stain.
The
diagnosis of Crohn's disease can sometimes be challenging, and a number of
tests are often required to assist the physician in making the diagnosis. Even
with a full battery of tests, it may not be possible to diagnose Crohn's with
complete certainty; a colonoscopy is approximately 70% effective in diagnosing
the disease, with further tests being less effective. Disease in the small
bowel is particularly difficult to diagnose, as a traditional colonoscopy
allows access to only the colon and lower portions of the small intestines;
introduction of the capsule endoscopy aids in endoscopic diagnosis.
Multinucleated giant cells, a common finding in the lesions of Crohn's disease,
are less common in the lesions of lichen nitidus.
Management
There
is no cure for Crohn's disease and remission may not be possible or prolonged
if achieved. In cases where remission is possible, relapse can be prevented and
symptoms controlled with medication, lifestyle and dietary changes, changes to
eating habits (eating smaller amounts more often), reduction of stress,
moderate activity and exercise. Surgery is generally counter-indicated and has
not been shown to prevent remission. Adequately controlled, Crohn's disease may
not significantly restrict daily living. Treatment for Crohn's disease is only
when symptoms are active and involve first treating the acute problem, then
maintaining remission.
Lifestyle
changes
Certain
lifestyle changes can reduce symptoms, including dietary adjustments, elemental
diet, proper hydration, and smoking cessation. Smoking may increase Crohn's
disease; stopping is recommended. Eating small meals frequently instead of big
meals may also help with a low appetite. To manage symptoms have a balanced
diet with proper portion control. Fatigue can be helped with regular exercise,
a healthy diet, and enough sleep. A food diary may help with identifying foods
that trigger symptoms. Some people should follow a low dietary fiber diet to
control symptoms especially if fibrous foods cause symptoms. Some find relief
in eliminating casein (protein found in cow's milk) and gluten (protein found
in wheat, rye and barley) from their diets. They may suffer from specific
dietary intolerances (not allergies).
Medication
Acute
treatment uses medications to treat any infection (normally antibiotics) and to
reduce inflammation (normally aminosalicylate anti-inflammatory drugs and
corticosteroids). When symptoms are in remission, treatment enters maintenance,
with a goal of avoiding the recurrence of symptoms. Prolonged use of
corticosteroids has significant side-effects; as a result, they are, in
general, not used for long-term treatment. Alternatives include
aminosalicylates alone, though only a minority are able to maintain the
treatment, and many require immunosuppressive drugs. It has been also suggested
that antibiotics change the enteric flora, and their continuous use may pose
the risk of overgrowth with pathogens such as Clostridium difficile.
Medications
used to treat the symptoms of Crohn's disease include 5-aminosalicylic acid
(5-ASA) formulations, prednisone, immunomodulators such as azathioprine (given
as the prodrug for 6-mercaptopurine), methotrexate, infliximab, adalimumab,
certolizumab and natalizumab. Hydrocortisone should be used in severe attacks
of Crohn's disease.
The
gradual loss of blood from the gastrointestinal tract, as well as chronic
inflammation, often leads to anemia, and professional guidelines suggest
routinely monitoring for this. Adequate disease control usually improves anemia
of chronic disease, but iron deficiency may require treatment with oral iron
supplements. Occasionally, parenteral iron is required.
Surgery
Crohn's
cannot be cured by surgery, though it is used when partial or a full blockage
of the intestine occurs. Surgery may also be required for complications such as
obstructions, fistulas and/or abscesses, or if the disease does not respond to
drugs. After the first surgery, Crohn's usually shows up at the site of the
resection, however it can appear in other locations. After a resection, scar
tissue builds up, which can cause strictures, which form when the intestines
become too small to allow excrement to pass through easily, which can lead to a
blockage. After the first resection, another resection may be necessary within
five years. For patients with an obstruction due to a stricture, two options
for treatment are strictureplasty and resection of that portion of bowel. There
is no statistical significance between strictureplasty alone versus
strictureplasty and resection in cases of duodenal involvement. In these cases,
re-operation rates were 31% and 27%, respectively, indicating that
strictureplasty is a safe and effective treatment for selected patients with
duodenal involvement.
Short
bowel syndrome (SBS, also short gut syndrome or simply short gut) can be caused
by the surgical removal of the small intestines. It usually develops in those
having had half or more of their small intestines removed. Diarrhea is the main
symptom of short bowel syndrome, however other symptoms may include cramping,
bloating, and heartburn. Short bowel syndrome is treated with changes in diet,
intravenous feeding, vitamin and mineral supplements, and treatment with
medications. Another complication following surgery for Crohn's disease in
which the terminal ileum has been removed is the development of excessive
watery diarrhea. This is due to an inability of the ileum to reabsorb bile
acids after resection of the terminal ileum.
In
some cases of SBS, intestinal transplant surgery may be considered; though the
number of transplant centres offering this procedure is quite small and it
comes with a high risk due to the chance of infection and rejection of the
transplanted intestine.
Alternative
medicine
More
than half of people with Crohn's disease have tried complementary or
alternative therapy. These include diets, probiotics, fish oil and other herbal
and nutritional supplements. Some scientists have suggested more research into
these is needed to discriminate between effective therapies and
"pseudo" therapies that can be ineffective.
Anatabine
is an over-the-counter anti-inflammatory marketed under the brand name
Anatabloc. There are no peer-reviewed studies suggesting its efficacy in IBD,
but anecdotal evidence suggests some patients find it helpful.
Acupuncture
is used to treat inflammatory bowel disease in China, and is being used more
frequently in Western society. There is insufficient evidence to recommend the
use of acupuncture, though further studies are warranted.
Homeopathy
is frequently used in Germany as a treatment for Crohn's disease, though no
clinical trials exist that demonstrate homeopathy is effective.
Prognosis
Crohn's
disease is a chronic condition for which there is no cure. It is characterised
by periods of improvement followed by episodes when symptoms flare up. With
treatment, most people achieve a healthy weight, and the mortality rate for the
disease is relatively low. However, Crohn's disease is associated with an
increased risk of small bowel and colorectal carcinoma, including bowel cancer.
It can vary from being benign to very severe and patients could experience just
one episode or have continuous symptoms. It usually reoccurs, although some
patients can remain disease free for years or decades. Most sufferers live a
normal lifespan.
Epidemiology
The
incidence of Crohn's disease has been ascertained from population studies in
Norway and the United States and is similar at 6 to 7.1:100,000. The Crohn's
and Colitis Foundation of America cites this number as approx 149:100,000; NIH
cites 28 to 199 per 100,000. Crohn's disease is more common in northern
countries, and shows a higher preponderance in northern areas of the same
country. The incidence of Crohn's disease is thought to be similar in Europe
but lower in Asia and Africa. It also has a higher incidence in Ashkenazi Jews[
and smokers.
Crohn's
disease has a bimodal distribution in incidence as a function of age: the
disease tends to strike people in their teens and 20s, and people in their 50s
through to their 70s, and ages in between due to not being diagnosed with
Crohn's and being diagnosed instead with irritable bowel syndrome (IBS). It is
rarely diagnosed in early childhood. It usually strikes females who are
pediatric patients more severely than males. However, only slightly more women
than men have Crohn's disease. Parents, siblings or children of people with
Crohn's disease are 3 to 20 times more likely to develop the disease. Twin
studies show a concordance of greater than 55% for Crohn's disease.
Ileitis
terminalis was first described by Polish surgeon Antoni Leśniowski in
1904, however, due to the precedence of Crohn's name in the alphabet, it became
later to be known in the worldwide literature as Crohn's disease.[citation
needed] Only in Poland it continues to be named Leśniowski-Crohn's
disease. Burrill Bernard Crohn, an American gastroenterologist at New York
City's Mount Sinai Hospital, described fourteen cases in 1932, and submitted
them to the American Medical Association under the rubric of "Terminal
ileitis: A new clinical entity". Later that year, he, along with
colleagues Leon Ginzburg and Gordon Oppenheimer published the case series as
"Regional ileitis: a pathologic and clinical entity".
Research
The
Crohn's Allogeneic Transplant Study's investigation team of Seattle is
currently undergoing a Phase 2 clinical trial to cure Crohn's disease,
involving bone marrow transplant, noting that cases in which bone marrow
transplant had been done for a secondary purpose effectively cured the patient
of Crohn's.
Researchers
at University College London have questioned the wisdom of suppressing the
immune system in Crohn's, as the problem may be an underactive rather than an
overactive immune system: Their study found that Crohn's patients showed an
abnormally low response to an introduced infection, marked by a poor flow of
blood to the wound, and the response improved when the patients were given
sildenafil citrate.
Recent
studies using helminthic therapy or hookworms to treat Crohn's Disease and
other (non-viral) auto-immune diseases seem to yield promising results.
Numerous
preclinical studies demonstrate that activation of the CB1 and CB2 cannabinoid
receptors exert biological functions on the gastrointestinal tract. Activation
of CB1 and CB2 receptors in animals has shown a strong anti-inflammatory effect
Cannabinoids and/or modulation of the endocannabinoid system is a novel
therapeutic means for the treatment of numerous GI disorders, including
inflammatory bowel diseases like Crohn's disease.
Methotrexate
is a folate anti-metabolite drug that is also used for chemotherapy. It is
useful in maintenance of remission for those no longer taking corticosteroids.
Metronidazole
and ciprofloxacin are antibiotics used to treat Crohn's that have colonic or
perianal involvement, although, in the United States, this use has not been
approved by the Food and Drug Administration (FDA). They are also used for
treatment of complications, including abscesses and other infections
accompanying Crohn's disease.
Thalidomide
has shown response in reversing endoscopic evidence of disease.
Crohn's
disease can also cause neurological complications (reportedly in up to 15% of
patients). The most common of these are seizures, stroke, myopathy, peripheral
neuropathy, headache and depression.
Crohn's
patients often also have issues with small bowel bacterial overgrowth syndrome,
which has similar symptoms.
In
the oral cavity crohn's patients may suffer from cheilitis granulomatosa and
other forms of orofacial granulomatosis, pyostomatitis vegetans, recurrent
aphthous stomatitis, geographic tongue and migratory stomatitis in higher
prevalence than the general population.
Crohn's
disease is one type of inflammatory bowel disease (IBD). It typically manifests
in the gastrointestinal tract and can be categorized by the specific tract
region affected. A disease of both the ileum (the last part of the small
intestine that connects to the large intestine), and the large intestine,
Ileocolic Crohn's accounts for fifty percent of cases. Crohn's ileitis,
manifest in the ileum only, accounts for thirty percent of cases, while Crohn's
colitis, of the large intestine, accounts for the remaining twenty percent of cases
and may be particularly difficult to distinguish from ulcerative colitis.
Gastroduodenal Crohn's disease causes inflammation in the stomach and first
part of the small intestine, called the duodenum. Jejunoileitis causes spotty
patches of inflammation in the top half of the small intestine, called the
jejunum (MedlinePlus 2010). The disease can attack any part of the digestive
tract, from mouth to anus. However, individuals affected by the disease rarely
fall outside these three classifications, with presentations in other areas.
Crohn's
disease may also be categorized by the behavior of disease as it progresses.
These categorizations formalized in the Vienna classification of the disease.
There are three categories of disease presentation in Crohn's disease:
stricturing, penetrating, and inflammatory. Stricturing disease causes
narrowing of the bowel that may lead to bowel obstruction or changes in the
caliber of the feces. Penetrating disease creates abnormal passageways
(fistulae) between the bowel and other structures, such as the skin.
Inflammatory disease (or nonstricturing, nonpenetrating disease) causes
inflammation without causing strictures or fistulae.
Cancers
Cancers
of the stomach are rare and the incidence has been declining worldwide. Stomach
cancers usually occur due to fluctuations in acidity level and may present with
vague symptoms of abdominal fullness, weight loss and pain. The actual cause of
stomach cancer is not known but has been linked to infection with H.pylori,
pernicious anemia, Menetriere's disease, and nitrogenous preservatives in food.
Stomach
cancer, or gastric cancer, refers to cancer arising from any part of the
stomach. Stomach cancer causes about 800,000 deaths worldwide per year.
A suspicious
stomach ulcer that was ultimately diagnosed as cancer on biopsy and resected. The surgical specimen was
subsequently kept for educational purposes.
Signs
and symptoms
Endoscopic
image of linitis plastica, a type of stomach cancer where the entire stomach is
invaded, leading to a leather bottle-like appearance with blood coming out of
it.
Endoscopic
image of early stage of the stomach cancer. Its histology was poorly
differentiated adenocarcinoma with signet ring cells.Left above=
Stomach
cancer is often either asymptomatic (producing no noticeable symptoms) or it
may cause only nonspecific symptoms (symptoms which are not specific to just
stomach cancer, but also to other related or unrelated disorders) in its early
stages. By the time symptoms occur, the cancer has often reached an advanced
stage (see below) and may have also metastasized (spread to other, perhaps
distant, parts of the body), which is one of the main reasons for its
relatively poor prognosis. Stomach cancer can cause the following signs and
symptoms:
Stage
1 (Early)
Indigestion
or a burning sensation (heartburn)
Loss
of appetite, especially for meat
Abdominal
discomfort or irritation
Stage
2 (Middle)
Weakness
and fatigue
Bloating
of the stomach, usually after meals
Stage
3 (Late)
Abdominal
pain in the upper abdomen
Nausea
and occasional vomiting
Diarrhea
or constipation
Weight
loss
Bleeding
(vomiting blood or having blood in the stool) which will appear as black. This
can lead to anemia.
Dysphagia;
this feature suggests a tumor in the cardia or extension of the gastric tumor
in to the esophagus.
Causes
Infection
by Helicobacter pylori is believed to be the cause of most stomach cancer while
autoimmune atrophic gastritis, intestinal metaplasia and various genetic
factors are associated with increased risk levels. The Merck Manual states that
diet plays no role in the genesis of stomach cancer. However, the American
Cancer Society lists the following dietary risks, and protective factors, for
stomach cancer: "smoked foods, salted fish and meat, and pickled
vegetables (appear to increase the risk of stomach cancer.) Nitrates and
nitrites are substances commonly found in cured meats. They can be converted by
certain bacteria, such as H. pylori, into compounds that have been found to
cause stomach cancer in animals. On the other hand, eating fresh fruits and
vegetables that contain antioxidant vitamins (such as A and C) appears to lower
the risk of stomach cancer." A December 2009 article in American Journal
of Clinical Nutrition found a statistically significant inverse correlation
between higher adherence to a Mediterranean Dietary Pattern and stomach cancer.
In
more detail, H. pylori is the main risk factor in 65–80% of gastric cancers,
but in only 2% of such infections. The mechanism by which H. pylori induces
stomach cancer potentially involves chronic inflammation, or the action of H.
pylori virulence factors such as CagA. Approximately ten percent of cases show
a genetic component. Some studies indicate that bracken consumption and spores
are correlated with incidence of stomach cancer, though causality has yet to be
established.
A very
important but preventable cause of gastric cancer is tobacco smoking. Smoking
considerably increases the risk of developing gastric cancer considerably: from
40% increased risk for current smokers to 82% increase for heavy smokers.
Gastric cancers due to smoking mostly occur in the upper part of the stomach
near the esophagus Studies are variable with respect to stomach cancer and
alcohol consumption. For example, one recent Japanese study has shown a
positive correlation and another, insufficient evidence to render a conclusion.
There does seem to be a stronger correlation, however, with combined use of
alcohol and tobacco.
Gastric
cancer shows a male predominance in its incidence as up to three males are
affected for every female. Estrogen may protect women against the development
of this cancer form. A very small percentage of diffuse-type gastric cancers
(see Histopathology below) are thought to be genetic. Hereditary Diffuse
Gastric Cancer (HDGC) has recently been identified and research is ongoing.
However, genetic testing and treatment options are already available for
families at risk.
The
International Cancer Genome Consortium is leading efforts to map stomach
cancer's complete genome.
Diagnosis
To
find the cause of symptoms, the doctor asks about the patient's medical
history, does a physical exam, and may order laboratory studies. The patient
may also have one or all of the following exams:
Gastroscopic
exam is the diagnostic method of choice. This involves insertion of a fiber
optic camera into the stomach to visualize it.
Upper
GI series (may be called barium roentgenogram)
Computed
tomography or CT scanning of the abdomen may reveal gastric cancer, but is more
useful to determine invasion into adjacent tissues, or the presence of spread
to local lymph nodes.
Abnormal
tissue seen in a gastroscope examination will be biopsied by the surgeon or
gastroenterologist. This tissue is then sent to a pathologist for histological
examination under a microscope to check for the presence of cancerous cells. A
biopsy, with subsequent histological analysis, is the only sure way to confirm
the presence of cancer cells.
Various
gastroscopic modalities have been developed to increase yield of detected
mucosa with a dye that accentuates the cell structure and can identify areas of
dysplasia. Endocytoscopy involves ultra-high magnification to visualize
cellular structure to better determine areas of dysplasia. Other gastroscopic
modalities such as optical coherence tomography are also being tested
investigationally for similar applications.
A
number of cutaneous conditions are associated with gastric cancer. A condition
of darkened hyperplasia of the skin, frequently of the axilla and groin, known
as acanthosis nigricans, is associated with intra-abdominal cancers such as
gastric cancer. Other cutaneous manifestations of gastric cancer include tripe
palms (a similar darkening hyperplasia of the skin of the palms) and the
Leser-Trelat sign, which is the rapid development of skin lesions known as
seborrheic keratoses.
Various
blood tests may be done, including: Complete Blood Count (CBC) to check for
anemia. Also, a stool test may be performed to check for blood in the stool.
Histopathology
Poor
to moderately differentiated adenocarcinoma of the stomach. H&E stain.
Gastric
signet ring cell carcinoma. H&E stain.
Adenocarcinoma
of the stomach and intestinal metaplasia. H&E stain.
Gastric
adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium
of the gastric mucosa. Stomach cancers are overwhelmingly adenocarcinomas
(90%). Histologically, there are two major types of gastric adenocarcinoma
(Lauren classification): intestinal type or diffuse type. Adenocarcinomas tend
to aggressively invade the gastric wall, infiltrating the muscularis mucosae,
the submucosa, and thence the muscularis propria. Intestinal type
adenocarcinoma tumor cells describe irregular tubular structures, harboring
pluristratification, multiple lumens, reduced stroma ("back to back"
aspect). Often, it associates intestinal metaplasia in neighboring mucosa.
Depending on glandular architecture, cellular pleomorphism and mucosecretion,
adenocarcinoma may present 3 degrees of differentiation: well, moderate and
poorly differentiated. Diffuse type adenocarcinoma (mucinous, colloid, linitis
plastica, leather-bottle stomach) Tumor cells are discohesive and secrete mucus
which is delivered in the interstitium, producing large pools of mucus/colloid
(optically "empty" spaces). It is poorly differentiated. If the mucus
remains inside the tumor cell, it pushes the nucleus to the periphery:
"signet-ring cell".
Around
5% of gastric malignancies are lymphomas (MALTomas, or MALT lymphoma).
Carcinoid
and stromal tumors may also occur.
Staging
If
cancer cells are found in the tissue sample, the next step is to stage, or find
out the extent of the disease. Various tests determine whether the cancer has
spread and, if so, what parts of the body are affected. Because stomach cancer
can spread to the liver, the pancreas, and other organs near the stomach as
well as to the lungs, the doctor may order a CT scan, a PET scan, an endoscopic
ultrasound exam, or other tests to check these areas. Blood tests for tumor
markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)
may be ordered, as their levels correlate to extent of metastasis, especially
to the liver, and the cure rate.
Staging
may not be complete until after surgery. The surgeon removes nearby lymph nodes
and possibly samples of tissue from other areas in the abdomen for examination
by a pathologist.
The
clinical stages of stomach cancer are:
Stage
0. Limited to the inner lining of the stomach. Treatable by endoscopic mucosal
resection when found very early (in routine screenings); otherwise by
gastrectomy and lymphadenectomy without need for chemotherapy or radiation.
Stage
I. Penetration to the second or third layers of the stomach (Stage 1A) or to
the second layer and nearby lymph nodes (Stage 1B). Stage 1A is treated by
surgery, including removal of the omentum. Stage 1B may be treated with
chemotherapy (5-fluorouracil) and radiation therapy.
Stage
II. Penetration to the second layer and more distant lymph nodes, or the third
layer and only nearby lymph nodes, or all four layers but not the lymph nodes.
Treated as for Stage I, sometimes with additional neoadjuvant chemotherapy.
Stage
III. Penetration to the third layer and more distant lymph nodes, or
penetration to the fourth layer and either nearby tissues or nearby or more
distant lymph nodes. Treated as for Stage II; a cure is still possible in some
cases.
Stage
IV. Cancer has spread to nearby tissues and more distant lymph nodes, or has
metastatized to other organs. A cure is very rarely possible at this stage.
Some other techniques to prolong life or improve symptoms are used, including
laser treatment, surgery, and/or stents to keep the digestive tract open, and
chemotherapy by drugs such as 5-fluorouracil, cisplatin, epirubicin, etoposide,
docetaxel, oxaliplatin, capecitabine, or irinotecan.
The
TNM staging system is also used.
In
a study of open-access endoscopy in Scotland, patients were diagnosed 7% in
Stage I 17% in Stage II, and 28% in Stage III. A Minnesota population was
diagnosed 10% in Stage I, 13% in Stage II, and 18% in Stage III However in a
high-risk population in the Valdivia Province of southern Chile, only 5% of
patients were diagnosed in the first two stages and 10% in stage III.
Management
As
with any cancer, treatment is adapted to fit each person's individual needs and
depends on the size, location, and extent of the tumor, the stage of the
disease, and general health. Cancer of the stomach is difficult to cure unless
it is found in an early stage (before it has begun to spread). Unfortunately,
because early stomach cancer causes few symptoms, the disease is usually
advanced when the diagnosis is made. Treatment for stomach cancer may include
surgery, chemotherapy, and/or radiation therapy. New treatment approaches such
as biological therapy and improved ways of using current methods are being
studied in clinical trials. An antibody-drug conjugate IMGN242 is in phase II
clinical trials.
Surgery
Surgery
is the most common treatment. The surgeon removes part or all of the stomach,
as well as the surrounding lymph nodes, with the basic goal of removing all
cancer and a margin of normal tissue. Depending on the extent of invasion and
the location of the tumor, surgery may also include removal of part of the
intestine or pancreas. Tumors in the lower part of the stomach may call for a
Billroth I or Billroth II procedure.
Endoscopic
mucosal resection (EMR) is a treatment for early gastric cancer (tumor only
involves the mucosa) that has been pioneered in Japan, but is also available in
the United States at some centers. In this procedure, the tumor, together with
the inner lining of stomach (mucosa), is removed from the wall of the stomach
using an electrical wire loop through the endoscope. The advantage is that it
is a much smaller operation than removing the stomach. Endoscopic submucosal
dissection (ESD) is a similar technique pioneered in Japan, used to resect a
large area of mucosa in one piece. If the pathologic examination of the
resected specimen shows incomplete resection or deep invasion by tumor, the
patient would need a formal stomach resection.
Surgical
interventions are currently curative in less than 40% of cases, and, in cases
of metastasis, may only be palliative.
Chemotherapy
The
use of chemotherapy to treat stomach cancer has no firmly established standard
of care. Unfortunately, stomach cancer has not been particularly sensitive to
these drugs, and chemotherapy, if used, has usually served to palliatively
reduce the size of the tumor, relieve symptoms of the disease and increase
survival time. Some drugs used in stomach cancer treatment have included: 5-FU
(fluorouracil) or its analog capecitabine, BCNU (carmustine), methyl-CCNU
(Semustine), and doxorubicin (Adriamycin), as well as Mitomycin C, and more
recently cisplatin and taxotere, often using drugs in various combinations. The
relative benefits of these different drugs, alone and in combination, are
unclear. Clinical researchers have explored the benefits of giving chemotherapy
before surgery to shrink the tumor, or as adjuvant therapy after surgery to
destroy remaining cancer cells. Combination treatment with chemotherapy and
radiation therapy has some activity in selected post surgical settings. For
patients who have HER2 overexpressing metastatic gastric or gastroesophageal
(GE) junction adenocarcinoma, who have not received prior treatment for their
metastatic disease, the US Food and Drug Administration granted approval (2010
October) for trastuzumab (Herceptin, Genentech, Inc.) in combination with
cisplatin and a fluoropyrimidine (capecitabine or 5-fluorouracil). This was
based on an improvement of the median overall survival (OS) of 2.5 months with
trastuzumab plus chemotherapy treatment compared to chemotherapy alone (BO18255
ToGA trial). The combination of Herceptin with chemotherapy for treating
metastatic gastric cancer was also sanctioned by the European regulatory
authorities (2010 January). Doctors have also tested putting the anticancer
drugs directly into the abdomen, often with warmed solutions of the medication
(intraperitoneal hyperthermic chemoperfusion).
Radiation
Radiation
therapy (also called radiotherapy) is the use of high-energy rays to damage
cancer cells and stop them from growing. When used, it is generally in
combination with surgery and chemotherapy, or used only with chemotherapy in
cases where the individual is unable to undergo surgery. Radiation therapy may
be used to relieve pain or blockage by shrinking the tumor for palliation of
incurable disease.
Multimodality
therapy
While
previous studies of multimodality therapy (combinations of surgery,
chemotherapy and radiation therapy) gave mixed results, the Intergroup 0116
(SWOG 9008) study showed a survival benefit to the combination of chemotherapy
and radiation therapy in patients with nonmetastatic, completely resected
gastric cancer. Patients were randomized after surgery to the standard group of
observation alone, or the study arm of combination chemotherapy and radiation
therapy. Those in the study arm receiving chemotherapy and radiation therapy
survived on average 36 months; compared to 27 months with observation.
Epidemiology
Stomach
cancer is the fourth most common cancer worldwide with 930,000 cases diagnosed
in 2002. It is a disease with a high death rate (~800,000 per year) making it
the second most common cause of cancer death worldwide after lung cancer. It is
more common in men and in developing countries.
It
represents roughly 2% (25,500 cases) of all new cancer cases yearly in the United
States, but it is more common in other countries. It is the leading cancer type
in Korea, with 20.8% of malignant neoplasms.
Metastasis
occurs in 80-90% of individuals with stomach cancer, with a six month survival
rate of 65% in those diagnosed in early stages and less than 15% of those
diagnosed in late stages.
Less
than
Causes
and Treatment
Smoking
has been linked to a variety of disorders of the stomach. Tobacco is known to
stimulate acid production and impairs production of the protective mucus. This
leads to development of ulcers in the majority of smokers. Chronic stomach
problems have also been linked to excess intake of alcohol. It has been shown
that alcohol intake can cause stomach ulcer, gastritis and even stomach cancer.
Thus, avoidance of smoking and excess alcohol consumption can help prevent the
majority of chronic stomach disorders.
One
of the most causes of chronic stomach problems is use of medications. Use of
aspirin and other non steroidal ant inflammatory drugs to treat various pain
disorders can damage lining of the stomach and cause ulcers. Other medications
like narcotics can interfere with stomach emptying and cause bloating, nausea,
or vomiting.
The
majority of chronic stomach problems are treated medically. However, there is
evidence that a change in life style may help. Even though there is no specific
food responsible for causing chronic stomach problems, experts recommend eating
a healthy diet which consists of fruits and vegetables. Lean meat should be
limited. Moreover people should keep a diary of foods that cause problems and
avoid them.
Endoscopy
There
are many tools for investigating stomach problems. The most common is
endoscopy. This procedure is performed as an outpatient and utilizes a small
flexible camera. The procedure does require intravenous sedation and takes
about 30–45 minutes; the endoscope is inserted via the mouth and can visualize
the entire swallowing tube, stomach and duodenum. The procedure also allows the
physician to obtain biopsy samples. In many cases of bleeding, the surgeon can
use the endoscope to treat the source of bleeding with laser, clips or other
injectable drugs.
X
rays
Other
radiological studies frequently used to asses patients with chronic stomach
problems include a barium swallow, where a dye is consumed and pictures of the
esophagus and stomach are obtained every few minutes. Other tests include a 24
hour pH study, CT scans or MRI.
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