Download Gastrointestinal tract

Pathology lec. 8
Gastrointestinal tract
Esophagus
We'll start talking about GIT , and first we'll start with the
esophagus .
Esophageal diseases are categorized into obstructive disease ,
including mechanical and functional obstruction , esophagitis
which is a very common disorder , specially gastroesophageal
reflux disease , and tumors of the esophagus ,
First we'll talk about obstructive and vascular diseases of the
esophagus.
Mechanical obstruction could be congenital or acquired disease.
The congenital one is usually discovered shortly after birth
because any obstruction of the esophagus will cause regurgitation
of the food and fluid or milk and aspiration to the lung instead of
going to the stomach.
Causes of mechanical obstruction:
-Absence or agenesis , a rare condition in which the esophagus is
not present .
-Atresia which is more common. you know that the esophagus is a
hollow organ there is a lumen in the center . in atresia this lumen is
lost and replaced by a fibrous segment leading to obstruction , so
it's a thin noncanalized cord replaces a segment of the esophagus
. most of the time it's associated with a fistula connecting the
esophagus to the bronchus or the trachea.
Complications of atresia : regurgitation of the food or drink to the
air ways which could lead to pneumonia ( infection of the lung ) ,
suffocation , aspiration .
Aspiration is when the material like food particles enter the lungs (
foreign body aspiration ) and initiates inflammatory reaction.
Third cause of mechanical obstruction is stenosis , it's narrowing of
the esophagus due to fibrosis of the submucosa.
( layers of the wall of the esophagus : mucosa , submucosa ,
muscularis , serosa )
When fibrosis happens in the wall of the esophagus , there will be
narrowing which impedes the flow of food and fluid through it . this
fibrosis is often due to inflammation and scarring , which may be
caused by chronic GERD ( gastroesophageal reflux disease ) ,
which is when the gastric contents goes back to the lower
esophagus , irradiation is another cause of inflammation , and
caustic injury . caustics are chemical substances that causes
burning like acids.
Symptoms of stenosis : dysphagia ( difficulty in swallowing ) is the
main symptom. it's progressive , it starts with difficulty swallowing
solid food , with time it progresses to include liquids .
Tumors can also cause mechanical obstruction .
Functional obstruction: there is abnormality in the muscles or the
innervation , there is no lesion . Normally when we swallow food
peristaltic movement and gravity aid moving food to the stomach ,
gravity alone doesn't work , there should be peristaltic movement .
When food gets to lower esophageal sphincter ( LES ) it should
dilate to let the food get to the stomach then it should close. Any
problem with the LES whether it dilates too much or it's contracted
too much , will lead to abnormality.
In functional obstruction there is increased tone of the LES which
can result from impaired smooth muscle relaxation with
consequent obstruction.
The disorder of functional obstruction is achalasia , it's abnormality
of the LES which is characterized by the triad of : incomplete LES
relaxation , increased LES tone ( LES is contracted all the time ) ,
and esophageal aperistalsis ( with time due to the contracted
sphincter , food will accumulate in the esophagus and it will dilate ,
so peristalsis movement will be lost ).
The end result of this disorder is distention of the esophagus.
Constant contact between food and the mucosa could be
carcinogenic with time.
Achalasia could be primary or secondary .
Primary means idiopathic , no underlying cause , it's failure of the
distal esophageal inhibitory neurons which normally inhibit the
contraction.
Secondary achalasia is due to infection or chagas disease , it's
infection by trypanosome cruzi that causes destruction of the
myenteric plexus between the muscle fibers in the wall of the
esophagus , and failure of the LES relaxation , and esophageal
dilatation.
Achalasia is characterized by progressive dysphagia , nocturnal
regurgitation ( at night ) , and aspiration of undigested food to the
airways.
The most serious problem is development of squamous cell
carcinoma in about 5% of patients at an earlier age than in those
without achalasia.
Third disorder of the esophagus is ectopia.
Ectopia means normal tissue in abnormal place.
Normal lining of the esophagus is squamous . when there's gastric
mucosa in the esophagus this is ectopic gastric mucosa . most
frequently seen in the upper third of the esophagus. This gastric
mucosa secretes acids , leading to irritation and inflammation and
esophagitis , with time esophagitis could lead to barrett esophagus
and adenocarcinoma. The main symptom in ectopia if it caused
inflammation is dysphagia.
Fourth disease is esophageal varices.
Normally blood that goes out of the GIT goes to the liver through
the portal vein to be filtered . circulation in the liver is called
splanchnic circulation where veins of the GIT collect together then
to the portal vein and the liver.
Any impedance of the blood flow to the liver through the portal vein
results in portal hypertension. Then blood won't be able to go to
the liver, so it will go to the places where there's
anastomosis(communication) between this splanchnic circulation
and systemic venous circulation. The lower esophagus is one of
the places where these circulations communicate.
Diseases that impede blood flow to the liver , make portal
hypertension and this induces development of collateral channels
in the lower esophagus.
When blood flows through collateral veins they will dilate ( just like
varices of the lower limb) , in the mucosa and submucosa of the
esophagus with a risk of rupture and bleeding.
Varices develop in 90% of cirrhotic patients. Cirrhosis could be
alcoholic or viral( hepatitis )
The second most common cause of varices is hepatic
schistosomiasis , which is bilharzias when it involves the liver , it
impedes blood flow to the liver and causes portal hypertension.
Often these varices are asymptomatic except when they're
distended very much , and discovered usually by endoscopy or
angiography.
Their rupture can lead to massive bleeding, hypovolemic shock
and even death.
Varices rupture is a medical emergency and despite intervention ,
as many as half of the patients die from the first bleeding episode.
So as a result , greater then half the deaths associated with liver
cirrhosis is because of varices rupture.
- Esophagitis ( inflammation of the esophagus )
The first cause of esophagitis is lacerations, the most common
laceration is called Mallory weiss tears. These tears are often
associated with sever vomiting and may occur with acute alcohol
intoxication.
This tear happens because of the sudden opening of the sphincter
during vomiting and the passage of food which lacerates the
esophagus.
These lacerations are usually at the gastroesophageal junction , at
the place of the sphincter. They're superficial and usually don't go
deep to the muscles and don't penetrate the esophagus. They heal
spontaneously without intervention.
The most common symptom is hematemesis , which is vomiting of
blood.
The second one is chemical esophagitis , caused by alcohol ,
corrosive acids or alkalis , hot fluids and heavy smoking.
Medical pills may lodge and dissolve in the esophagus , if it was
swallowed without water , rather than passing into the stomach ,
this is called pill induced esophagitis.
Symptoms: self limited pain , particularly odynophagia ( pain when
swallowing).
Complications : hemorrhage , with time healing with fibrosis could
lead to stenosis or stricture . if there's very severe inflammation it
could lead to perforation.
Sometimes chemical esophagitis could be iatrogenic because of
chemotherapy or radiation therapy (complication of treatment ).
Infectious esophagitis is not very common , it could be viral or
fungal.
Among viruses, herpes simplex virus and cytomegalovirus (CMV)
are the common.
Among fungi, Candida is the most common pathogen, although
mucormycosis and aspergillosis may also cause it.
Infectious esophagitis occurs usually in those who are
immunosuppressed or debilitated.
Morphology in candidiasis: there's a whitish membrane that is
adherent to the esophagus composed of inflammatory cells and
debris and densely matted fungal hyphae.
Herpes virus usually infects epithelial cells , it makes multi
nucleation , abnormality in the chromatin, and nuclear inclusions
and ulcers .
CMV makes cells larger , causes shallower ulcerations and
characteristic nuclear and cytoplasmic inclusions within capillary
endothelium and stromal cells.
- The fourth type of esophagitis is reflux esophagitis , it's very
common , it's caused by the reflux of the gastric contents which
are acidic into the lower esophagus through the partially relaxed
sphincter.
The clinical condition is called gastroesophageal reflux disease (
GERD)
Conditions that decrease LES tone or increase abdominal
pressure contribute to GERD. These conditions include alcohol
and tobacco use ( decrease LES tone ), obesity and pregnancy (
increase abdominal pressure ), CNS depressants which make
muscle relaxation, hiatal hernia is another cause.
In many cases , no definitive cause is identified.
This disease is more common in adults , but it can occur in infants
and children.
Main symptoms are heartburn and dysphagia.
Less often, noticeable regurgitation of sour-tasting gastric
contents.
Rarely in chronic GERD could be attacks of severe chest pain that
may be mistaken for heart disease.
Complications include ulceration , hematemesis, melena ( blackish
stool due to upper GIT bleeding ) , stricture , barrett esophagus.
Treatment is by proton pump inhibitors that reduce gastric acidity
and provide symptomatic relief.
Hiatal hernia is one of the causes of GERD. It's separation of the
diaphragmatic crura and protrusion of the stomach into the thorax
through the resulting gap. The pressure in the thorax is less than in
the abdomen, so there will be symptoms of GERD, but it's
asymptomatic in 90 % of adult cases.
( the crura of the diaphragm are tendinous structures extend
inferiorly from the diaphragm to attach to the vertebral column ).
Barrett esophagus is a complication of GERD, it's gastric or
intestinal metaplasia(columnar epithelium , more resistant to acids
), within the esophageal squamous mucosa.
It occurs in 10 % of people with symptomatic GERD, it increases
the risk of esophageal adenocarcinoma.
Metaplasia could lead to dysplasia which could be low grade or
high grade on the basis of its morphology. It's a preinvasive
condition, develops in 0.2 % to 1% of persons with barrett
esophagus each year.
( the squamous mucosa of the esophagus is normally pinkish, the
mucosa of the stomach is reddish )
-Esophageal tumors are mainly two. Squamous cell carcinoma is
more common, but in the US and western countries
adenocarcinoma is on the rise.
-Adenocarcinoma typically arises in a background of barrett
esophagus and long standing GERD.
It usually occurs in the distal third of the esophagus and may
invade the gastric cardia(below the sphincter ).
Other causes of adenocarcinoma: tobacco use, obesity, radiation
therapy.
Male to female ratio7:1
The main mutation that happens here is TP53 mutation (TP53
is a tumor suppressor gene).
Clinical features: pain or difficulty swallowing, weight loss, chest
pain, vomiting.
By the time symptoms appear, the tumor usually has spread to the
submucosal lymphatic vessels.
In cases that are just limited to mucosa and submucosa there's
80% chance of 5 years of survival , which is not always the case.
-Squamous cell carcinoma affects adults older than 45 years of
age , and affects males 4 times higher than females.
Risk factors include: alcohol, tobacco use, poverty, caustic injury,
achalasia, consumption of hot beverages, radiation, nitrosamines
that are usually in the soil, mutagenic compounds such as those
found in fungus contaminated food , polycyclic hydrocarbons.
Half of it occur in the middle third of the esophagus.
It begins as dysplasia( carcinoma in situ) then squamous cell
carcinoma.
The rich submucosal lymphatic network promotes circumferential(
could cause mechanical obstruction) and longitudinal spread.
Intramural tumor nodules may be present several cms away from
the principal mass.
Clinical features: dysphagia, odynophagia , obstruction , weight
loss, hemorrhage, sepsis, lymph node metastases.
The 5 year survival chance is 75% if it's still in situ or is just in the
mucosa.
The stage of the disease is the most important determinant of
prognosis.