pathology

72

Diseases of the esophagus 1

4-11-2009

إسماعيل . دخليل & مطالقة صالح بني الله عبد

قرارعة

The Esophagus

As you know the digestive system or GIT includes: the oral cavity with salivary glands, esophagus, the stomach, small intestine, colon, appendix, liver, biliary tract, and pancreas.

In the next 15 lectures, we will cover all the pathological aspects and diseases and cancers of all these organs.

Today we are going to continue with another organ of the alimentary tract, which is the esophagus.

The esophagus is tube that connects the oral cavity with the stomach.

Of course we are not going to talk about the anatomy or the histology of GIT, although in sometime in some specific organ we will touch a little bit some histological and physiological aspects which are important to understand the mechanism of the disease itself or the tumors.

For esophagus, it is straight forward anatomy and histology, it is lined by the stratified squamous epithelium, and at the lower end of the esophagus there is junctional mucosa, it is zigzag junctional mucosa, in which small amount of glandular gastric mucosa will protrude into the esophagus, in the gastro-esophageal junction.

From anatomical point of view, again we have anatomical gastro-esophageal junction, and histological gastro-esophageal junction:

The anatomical one: it is where the esophagus meets to the stomach, 1 cm below the diaphragm, is that important or have clinical significant? Yes

Because this junction act as valve, with swallowing process, you swallow food for example and get into the stomach, where there is increased in intra abdominal pressure and this increase will close this junction and will prevent the reflux of the food and gastric juices into the esophagus, if any defect or abnormality happens at that junction, what we are going to have is reflux, and it can be in the form gastric juices reflux or food reflux.

The histological junction: it is where the glandular or the columnar lined mucosa of the stomach meets the stratified squamous epithelium of the esophagus. It is very important because if the squamous epithelium of the esophagus replace by glandular epithelium, this is pathological process that we call Barrett’s esophagus.

So what kinds of diseases associate with the esophagus?

The main groups or categories of disease that affect the esophagus are:

1. Congenital anatomic disorders include:Agenesis, atresia, fistula, stenosis.

2. Acquired anatomic/motor disorders:Stenosis, webs & rings, hiatus hernia, achalasia.

3. Inflammations:Reflux esophagitis

4. Barrett’s esophagus.5. Vascular diseases.6. Tumors.

So what are the clinical features of the diseases of the esophagus?

There are some symptoms and signs which more or less are shared by most of the diseases of the esophagus, so there are different esophageal diseases will have limited number of symptoms and signs, and these symptoms include;

Dysphagia ( dys: mean abnormal, phagia: mean swallowing): difficulty in swallowing and this is might be caused by either functional or mechanical process:

If there is deranged esophageal motor function, then this is functional cause of Dysphagia.

And if there is narrowing or obstruction of the lumen, then this is mechanical cause of Dysphagia.

Heartburn: it is retrosternal burning pain or sensation, caused mainly by regurgitation of the gastric contents, so any regurgitation will lead to some sort of burning sensation or burning pain.

Hematemesis: it is blood vomiting and the sources of this blood can be from: esophagus itself, or stomach, or first part of duodenum.

Melena: it is blood in stools, or blackish tarry stools, because of presence of altered blood in the stools, because blood that passes through stools in the small intestine and colon get altered by the different juices and the different foods and acids within small intestine and colon and become like what we call Melena.

What is the cause of bleeding?

We have many causes of bleeding in the GIT either it is upper or lower GIT bleeding; it might be severe inflammation, ulceration, or laceration in the esophagus, or ulcerative tumor, etc.

Respiratory symptoms: like dyspnea and cough, it is mainly caused by aspiration, if we have reflux of food or acid or gastric juices, there will be reflux back to the mouth then to the trachea leading to aspiration (presence of food or fluid in the trachea and lungs).

In some cases of aspiration, aspiration pneumonia could develop.

Congenital disease of the esophagus:

Some of these present at birth with severs vomiting might be related to destruction of esophagus, or aspiration (pneumonia, asphyxia), or gastric distention if we have distal obstruction.

Agenesis : complete absence of esophagus which is extremely rare, and not compatible with life.

Atresia : failure of development of a segment of esophagus, which is replaced by a thin noncanalized cord or tube which means absence of lumen. with formation of upper & lower pouches; associated with tracheoesophageal fistula

Stenosis : developmental defect resulting in partial obstruction or narrowing of the esophageal lumen

In cases of these congenital anomalies we do urgent medical & surgical intervention, one of the routine examination of newborn is insert tube from his nose into esophagus and into the stomach and see if he is patent or not.

Also we can see if there is some sort of difficulty in breast feeding, by trying to feed baby in first hour, if he is not feeding well then there is some abnormalities.

As you can see in the figure, this is esophageal atresia

It will form upper noncanalized segment or pouch and the lower one fistulized with the trachea and this will form tracheoesophageal fistula.

So this is esophageal atresia and usually or most of the time has some degree of fistulization with the trachea.

Acquired anatomic disorder:

1. Stenosis : it can be congenital or acquired disorder, it caused by:

Caustic strictures: if child drinks some chlor or hypex it might be fatal and lead to death, but if it is less severe it might lead to some sort of injury, ulceration which will heal by fibrosis and cause stenosis called caustic strictures.

Post-surgical condition could lead to stenosis, inflammatory condition, tumors , autoimmune diseases such as scleroderma.

2. Webs & Rings: Mucosal webs or mucosal and submucosal concentric ring partially occluding the esophagus.

3. Diverticula: acquired outpouching of the esophageal wall, if this diverticulum in the upper part of esophagus it is called zenker diverticulum,

and if it is in the lower part of esophagus it is called epiphrenic diverticulum.

Hiatus hernia:

It is protrusion of a dilated sac-like segment of stomach above the diaphragm, from anatomical point of view the stomach is located below the diaphragm and there is short segment of esophagus is below the diaphragm when there is sac protrusion of the stomach protrude above the diaphragm we call this hiatus hernia and it is related mainly to separation of diaphragmatic crura.

The incidence: up to 20% of adults and usually increase with age

Mostly asymptomatic, but once it symptomatic, it will lead to many kinds of problems likes:

Heartburn & regurgitation of gastric juices in 9% due to LES (lower esophageal sphincter) incompetence; related to position; symptoms are accentuated by positions favoring reflux, when patient line flat or in supine position this will intensify or augment the reflex, more gastric acid goes to esophagus.

Patients with severe reflux esophagitis usually have Hiatus Hernia; however,

HH & reflux are not the same condition.

Hiatus hernia is separate entity, and separate pathological condition, also reflux is separate one.

In hiatus hernia we have two anatomic patterns:

– Sliding (axial) hernia: most common one 95% of cases; bell-shaped dilation; due to congenital short esophagus,( some pathologists think it is mainly related to short esophagus, since it is short it will try to pull the stomach upward, therefore part of the stomach will protrude through the diaphragm leading to sliding hernia) strictures, spasm or

long-standing fibrous scarring of esophagus, resulting in traction on stomach

– paraesophageal (non-axial or rolling): segement of cardiac stomach dissects alongside esophagus through a defect. May follow traumatic rupture of diaphragm; may strangulate and get infarct

Achalasia

Achalasia: (A: mean absence, chalasia: mean relaxation) one of the functional obestruction

From physiology you know the process of swallowing which start in the mouth by chewing food and subdivided into small fragments and then swallow it passing through the esophagus to the stomach, the esophagus has no digestive effect at all it is just passage, when the intra luminal pressure within the esophagus is increased it will relax the lower esophageal sphincter LES allowing food to enter to the stomach. When the esophagus empty the LES close completely to prevent the reflex gastric juices, while when the esophagus has food in the lumen the LES relax.

Achalasia is failure to relax, i.e. incomplete relaxation of LES in response to swallowing, producing functional obstruction & dilation of more proximal esophagus

Usually it complain of progressive dysphagia to liquids and solid food, nocturnal (during night) regurgitation & aspiration of undigested food, aspiration pneumonia

Manometric studies show three abnormalities: 1. aperistalsis 2. partial relaxation of LES & 3. increased basal tone of LES.

Pathology: there is deranged innervation of LES and absent myenteric ganglia in the body of esophagus

The muscular wall of esophagus are two layers: circular and longitudinal, so this muscular wall might be normal, hypertrophic, or thinning of muscles due to continuous pushing against failing LES it might be thin.

Achalasia also might be associated with mucosal inflammation, ulcer or fibrosis.

There are two main types of achalasia:

1. Primary (sporadic): Commoner. Unknown cause, no clear cause, they think it might be related to autoimmune diseases leading to destruction or abnormal innervations of the LES.

2. Secondary causes:

Chaga’s disease which is caused by Trypanosoma cruzi infection. This is a parasite which also has a specific affinity to affect the myenteric plexus ganglion cells in the GI tract, the ureter, and the duodenum, leading to megaduodenum, megacolon, megaureter and Achalasia, and neurogenic bladder of course.

Diabetes. Among the complications of diabetes is Autonomic neuropathy that leads to vagus nerve injury and achalasia like manifestations or what we call secondary achalasia.

An important thing is that achalasia will increase the risk for Esophageal squamous cell carcinoma, it’s reported to occur in about 5% of patients and typically at an earlier age than in those without achalasia. So there is a slight increase in risk of developing squamous cell carcinoma in people with achalasia, this is probably due to the long standing ulceration in the (histology and anatomy)!, and there is continuous damage, continuous ulceration and continuous mucosal turnover etc.

LACERATIONS

Another name for it is Mallory-Weiss Syndrome. It means Longitudinal tears at the esophagogastric junction, tears mean superficial erosions not deep ulcers ( تشخيط بتشخط .(يعني

What are the causes?

It’s usually encountered in alcoholics “heavy drinkers” after a bout of sever retching1 or vomiting, a continuous sort of retching and vomiting. (alcoholics have a high tendency for vomiting and retching, leading to tears in the esophagogastric junction).

In addition there is inadequate relaxation of the muscles of the lower esophageal sphincter during vomiting, with stretching and tearing of the esophagogastric junction at the moment of expulsion of gastric contents, inappropriate function of such sphincter or muscle during vomiting will potentiate or exacerbate the presence of tears in that part.

However this might occur in patients without a history of vomiting. it can happen there with unknown reasons.

Hiatal hernia is found in 75% of patients with Mallory-Weiss Syndrome, again there is an association or increasing risk of such condition

The tears are linear irregular lacerations, few mm-cm in length and they involve the mucosa mainly or deeply penetrate & perforate the wall in rare cases. They are usually mucosal and superficial.

5-10% of laceration cases will lead to massive hemetemesis, massive GI bleeding, however the majority of them do not cause profuse bleeding and might not be that much life threatening.

1 Gastric and esophageal movements of vomiting without expulsion of vomitus.

This is an example of Mallory-Weiss Syndrome, notice the esophagus and the stomach, you can also see laceration and the bleeding from it.

you’ll see more in the practical.

Again laceration mainly occurs in the mucosa but sometimes if it’s so sever, it might extend down to the wall and lead to perforation but it’s mainly mucosal from inside.

VARICES

Esophageal varices is a vascular lesion of the esophagus “دوالي المريء”.

Usually you’ll here about a common scenario that someone developed liver cirrhosis and after that he suffered from esophageal varices and at some point he developed a massive profuse bleeding from the esophagus, “severe massive upper GI bleeding as a result of the varices”, and eventually died. This is probably the usual scenario of severe form of esophageal varices. This story summarizes the underlying causes, usually but there are other causes, the manifestations and of course the natural history of most cases.

It’s mainly due to portal hypertension, which leads to formation of portal-systemic collateral bypass channels.

There are four sites where the portal and systemic circulation anastomose:

1. Esophagus.2. Hemorrhoids, in the anus. “بواسير” 3. Around the umbilicus, where you can see manifestations of liver cirrhosis, dilated tortuous

blood vessels around the umbilicus called “Caput medusa”. 4. Retroperitoneum .

You should know this from anatomy and physiology to understand the disease pathogenesis.

Again there is portal hypertension creating portal-systemic anastomosis or collateral veins between the stomach and the esophagus. So collateral veins will develop in the region of lower esophagus when portal flow is diverted through the coronary veins of stomach into the plexus of esophageal submucosal veins into the azygous veins.

Of course the most common cause of portal hypertension is liver cirrhosis, portal hypertension causes esophageal varices, that could rupture causing bleeding that might be life threatening and can lead to death.

Rare causes of portal hypertension are portal vein thrombosis, hepatic vein thrombosis (Budd-Chiari syndrome) which we’ll talk about later, pylephlebitis2, tumor compression or invasion into major portal radicals, so all these can cause portal hypertension. In principle, to have esophageal varices you need to have portal hypertension which is caused mainly by liver cirrhosis but can be also caused by other reasons including the above.

** the bleeding will be into the lumen causing hemetemesis, because these collateral veins go to the submucosal esophageal veins to drain in the azygos vein.

This is an open esophagus and stomach.

Notice the tortuous dilated structures, these are the esophageal varices

Varices appear as tortuous dilated veins directly beneath mucosa3 or in periesophageal tissue and that is why they

2 Inflammation of the portal vein or any of its branches.3 From the book: the dilated veins lie primarily within the submucosa of the distal esophagus & proximal stomach.

will bleed into the lumen, they are submucosal veins, so if there is any kind of ulceration to the mucosa for example or if the veins are so much dilated having very high pressure, they will rupture into the lumen throw the mucosa. The overlying mucosa may be normal or eroded and inflamed +/- thrombosis which might occur within these blood vessels.

It may be asymptomatic until they rupture with massive hemetemesis resulting. Rupture may be spontaneous or secondary to vomiting. Hemorrhage rarely subsides spontaneously, 40% die after the first episode, so it has a very high mortality rate, 70% of the survivals that escaped the first episode will have rebleed within one year with still high mortality rate of 40%. It Develops in 2/3 of cirrhotic patients; accounting for 50% of deaths in liver cirrhosis.it’s the main cause of mortality in liver cirrhosis.

ESOPHAGITIS

Inflammation of the esophagus that may be caused by multiple factors:

Reflux of gastric content that is called Reflux esophagitis which is the most common and probably most important cause of esophagitis. VERY IMPORTANT

Ingestion of Irritants like Alcohol, corrosive acids in suicidal attempts, alkali, excessive hot fluids like Tea, heavy smoking, actually there are many factors that cause mechanical irritation of the esophagus.

Bacteremia & Viremia. Caused by sepsis and spread of bacteria in the blood and viremia is the same. They cause direct infection of esophageal wall or contiguous structures. Most common causes of viral esophagitis are HSV and CMV especially in immunocompromised people like diabetics or having steroid or chemotherapy, stress, etc…

a student asked about the treatment. The Dr answered that there are different modalities that we are not going to discuss but sometimes they can do it endoscopically, sometimes they do sclerosing by injecting some material in the blood vessels to get them thrombosed. Other modalities are banding, ballooning (introducing a balloon in the blood vessel then inflating it to stop the bleeding) so there are different modalities therapeutic and prophylactic.

Fungal infections in immunocompromised patients (Candidasis, mucormycosis, aspergillosis) can lead to inflamtion.

Systemic desquamative skin diseases, the lining epithelium of the esophagus is squamous resembling that of the skin so any systemic disease of the skin will lead to the same manifestation in the esophagus. Systemic diseases include pemphigoid.

Graft-versus-host disease, commonly encountered in bone marrow transplant, the graft contains lymphocytes of the donor that will attack the host.

Radiation; cytotoxic therapy; uremia.

But overall the Reflux esophagitis is the most common and important.

REFLUX ESOPHAGITIS

Gastroesophageal Reflux Disease ( GORD ) means reflux of the gastric content in to the esophagus which is the commonest cause of esophagitis.

Pathogenesis, there are many hypotheses about this:

Frequent & protracted reflux due to incompetence of LES and decreased efficacy of the other antireflux mechanisms that include the Diaphragm itself, Cadrioesophageal angle, pressure on intraabdominal esophagus pressure on the short segment of the esophagus below the diaphragm optimizes the closure of the lower esophageal sphincter.

Disordered esophageal motility is another possible mechanism with the gastric contents remains longer in contact with mucosa.

Elevated acid peptic levels of regurgitated fluid and duodenal bile acids & lysolecithin.

Actually there is another theory about reflux esophagitis and a very much related condition called Barrett esophagus, that the content which induces injury and ulceration or irritation is actually the bile acids or the deuodenal content rather than the gastric content, although it’s acidic, but the bile acids and the duodenal secretion are more harmful. This is again part of the theory that you get a plastic

process occurring at the lower part of the esophagus leading to what so called Barrett esophagus is due to the duodenal bile acids mainly.

** Normally bile doesn’t pass throw the pylorus “ البواب but ”فتحة in case of incompetence or abnormality bile can regurgitate to the stomach then the esophagus, but normally it shouldn’t, but some people think that even normally minimum amounts of bile regurgitate to the stomach.

** the other mechanism is that continuous injury, irritation and inflammation with impaired reparative capacity of the esophageal mucosa. When do we have impired regenerative ability of any mucosa? If there are other insults e.g. the patient is a smoker, another example is ischemia or decreased blood flow to the esophagus, etc… Any kind of impairment will lead to ulceration and Reflux esophagitis.

Predisposing factors

They are mainly the factors which lead to some kind of incompetence in the lower esophageal sphincter and other antireflux factors, they include:

Fat, people who eat fatty food like chocolate will experience heartburn, this is normal why? Because it seems that fat and chocolate etc.. affect the function of the LES in an unknown mechanism.

Hiatal hernia, where gastric juice can easily pass to the esophagus because they are already above the diaphragm.

Pregnancy because of intrabdominal pressure. Drugs, some drugs affect the function of the esophagus or the nerve supply,

some other drugs can cause damage to the mucosa itself.

Consequences of reflux

If it is occasional there are no significant consequences.

If it is recurrent and persistent, it will lead to the usual manifestations of Reflux esophagitis in the term of inflammation, ulceration and subsequent bleeding, reparative activity may cause fibrosis and this may lead to stricture.

If the patient developed pathological changes in the form Intestinal Metaplasia or glandular metaplasia this will lead to what we call Barrett esophagus which has a high risk to develop Dysplasia and subsequent Carcinoma.

The End

Done by: Khaleel Qarar3ha & Abdullah B.Saleh

Best wishes…