Barrett's esophagus

Barrett's esophagus is a condition in which abnormal cells develop on the inner lining of the lower part of the gullet (esophagus). The esophagus is the muscular tube that carries food from the mouth to the stomach.

Barrett's esophagus is not in itself a cancerous condition, but over a period of time it can occasionally lead to cancer developing in the lower part of the esophagus. A cancer happens when cells in the affected area continue to grow and reproduce and become increasingly abnormal.

Diagram of comparison between normal esophagus and Barrett's esophagus

Normal

Barrett's esophagus

  Images taken from www.barrettsinfo.com/

Development of Barret's esophagus

 

Barrett’s oesophagus occurs when the acidic stomach contents are continuously refluxed onto the lining of the oesophagus, causing changes to the structure of the tissue. Over time, your body replaces the normal cells lining the oesophagus with cells of a different type. This new type of cell secretes mucus which makes it more resistant to the acid coming up from the stomach. The presence of these cells in the oesophagus is known as Barrett’s oesophagus or Barrett’s metaplasia.

Sign and symtoms

Barrett's esophagus itself does not cause symptoms. The acid reflux that causes Barrett's esophagus results in symptoms of heartburn. Rarely, Barrett's esophagus can progress to cancer of the esophagus, the symptoms of which may be difficulty swallowing or weight loss

 

 

Diagnosis

Diagnosis of the condition usually requires taking a sample of tissue by endoscopy. Doctors insert a lighted, flexible tube (endoscope) with a camera on its tip through the mouth and into the esophagus. Patients are given a local anesthetic or sedated for the procedure. During endoscopy, doctors may remove tissue samples (biopsies) of potentially abnormal areas for examination under a microscope.

Barrett's esophagus without dysplasia (cancerous changes) — If, at the first endoscopy all biopsies are without dysplasia, a second examination is recommended in one year. This is done to make sure that a very small cancer (also known as a prevalent cancer) was not missed at the first endoscopy. For those without dysplasia at the second examination, follow-up endoscopy is recommended in three to five years.

Barrett's esophagus with low-grade dysplasia — follow-up endoscopy is recommended every six months for a year, than every 12 months. Low grade dysplasia, by itself, is usually not lethal. Follow up is to make sure a serious finding is not missed.

Barrett's esophagus with high-grade dysplasia — If two pathologists agree that biopsies show high grade dysplasia, then intervention is usually suggested. The standard of care treatment is esophagus resection surgery or minimally invasive treatment such asphotodynamic therapy. In cases where the high grade dysplasia is only found in one small bump, an experimental option, endoscopic mucosal resection, may be possible. If a patient is not a good candidate for surgery, the doctor may opt to increase acid suppression medications and repeat an endoscopic examination in three months

 

Treatment

Barrett's esophagus usually is treated with medicines called proton pump inhibitors (one brand name: Nexium). These medicines reduce the amount of acid in your stomach. In some cases, surgery is used to keep stomach acid out of the esophagus. Your doctor may recommend that you make some lifestyle changes, such as quitting smoking if you smoke, exercising, losing weight, and avoiding foods that make your heartburn worse.

Heart Defect - Comparison by Diagrame

Atrial Septal Defect

Image taken from http://www.web-books.com/

Pulmonary Stenosis

Venticular Septal Defect

Image taken from ttp://www.web-books.com/

Coarctation of Aorta

Patent Ductus Arterosus

diagramme taken from http://www.maxshouse.com/Cardiology/myocardial_diseases_of_the_

cat.htm

Tetralogy of Fallot

Tetralogy of Fallot involves four defects:



1. A large ventricular septal defect (VSD)

2. Pulmonary stenosis

3. Right ventricular hypertrophy

4. An overriding aorta   





Ventricular Septal Defect 



The heart has a wall that separates the chambers on its left side from those on its right side. This wall is called a septum. The septum prevents blood from mixing between the two sides of the heart.



A VSD is a hole in the part of the septum that separates the ventricles—the lower chambers of the heart. The hole allows oxygen‑rich blood to flow from the left ventricle into the right ventricle instead of flowing into the aorta, the main artery leading out to the body.

Pulmonary Stenosis  

This is a narrowing of the pulmonary valve and the passageway through which blood flows from the right ventricle to the pulmonary arteries. Normally, oxygen-poor blood from the right ventricle flows through the pulmonary valve into the pulmonary arteries and out to the lungs to pick up oxygen. In pulmonary stenosis, the heart has to work harder than normal to pump blood, and not enough blood can get to the lungs.

Right Ventricular Hypertrophy

This is when the right ventricle thickens because the heart has to pump harder than it should to move blood through the narrowed pulmonary valve. 

Overriding Aorta 

This is a defect in the location of the aorta. In a healthy heart, the aorta is attached to the left ventricle, allowing only oxygen-rich blood to go to the body. In tetralogy of Fallot, the aorta is between the left and right ventricles, directly over the VSD. As a result, oxygen‑poor blood from the right ventricle can flow directly into the aorta instead of into the pulmonary artery to the lungs.

Fetal Circulation

• During pregnancy, the fetal circulatory system works differently than after birth:

• The fetus is connected by the umbilical cord to the placenta, the organ that develops and implants in the mother's uterus during pregnancy.


• Through the blood vessels in the umbilical cord, the fetus receives all the necessary nutrition, oxygen, and life support from the mother through the placenta.


• Waste products and carbon dioxide from the fetus are sent back through the umbilical cord and placenta to the mother's circulation to be eliminated

• Blood from the mother enters the fetus through the vein in the umbilical cord. It goes to the liver and splits into three branches. The blood then reaches the inferior vena cava, a major vein connected to the heart.

Inside the fetal heart

• Blood enters the right atrium, the chamber on the upper right side of the heart. Most of the blood flows to the left side through a special fetal opening between the left and right atria, called the foramen ovale.


• Blood then passes into the left ventricle (lower chamber of the heart) and then to the aorta, (the large artery coming from the heart).


• From the aorta, blood is sent to the head and upper extremities. After circulating there, the blood returns to the right atrium of the heart through the superior vena cava.


• About one-third of the blood entering the right atrium does not flow through the foramen ovale, but, instead, stays in the right side of the heart, eventually flowing into the pulmonary artery.  


• Because the placenta does the work of exchanging oxygen (O₂) and carbon dioxide (CO₂) through the mother's circulation, the fetal lungs are not used for breathing. 


• Instead of blood flowing to the lungs to pick up oxygen and then flowing to the rest of the body, the fetal circulation shunts (bypasses) most of the blood away from the lungs. 


• In the fetus, blood is shunted from the pulmonary artery to the aorta through a connecting blood vessel called the ductus arteriosus.

Fetal versus adult hemoglobin

• Fetus has high percentage (75%) of haemoglobin F (HbF). 


• HbF has lower affinity 2,3-diphosphoglycerate (2,3-DPG).


• Fetus has a higher haemoglobin concentration (18g/dl-1) at birth.


• The oxyhaemaglobin dissociation curve for HbF is shifted to the left compared with adult haemoglobin due to a lower affinity for 2,3-DPG. This favours oxygen uptake in the placenta.
  
  

Changes at birth 

• Several cardiopulmonary adaptations occur which result in gas exchange being transferred from placenta to the lungs. 


• The umbilical vessels are obliterated when the cord is clamped externally.


• There is therefore a fall in blood flow through the IVC and the ductus venosus, the latter subsequently closes passively over the next 3-10 days.


• A dramatic fall in the pulmonary vascular resistance (PVR) occurs with lung expansion (opening up the pulmonary vessels).


• A reduction in hypoxic pulmonary vasoconstriction and stimulation of pulmonary stretch receptors contribute to this process.


• The increase in pulmonary blood flow leads to a large rise in pulmonary venous return to the left atrium.


• The left atrial pressure therefore exceeds the right atrial pressure. This reversal of pressure gradient across the atria allows the flap of the foramen ovale to push against the atrial septum and the atrial shunt is effectively closed. 


• Although the initial closure of the foramen ovale occurs within minutes to hours of birth, anatomical closure by tissue proliferation takes several days. As a result, all blood from the right atrium now passes into the right ventricle. 


• The ductus arteriosus constricts due to the high partial pressure of oxygen. The process is usually complete within 2 days after birth.


• Other changes over several weeks include a reduction in the thickness of the walls of right ventricle and the muscle layer of the pulmonary arterioles; and an increase in the left ventricular wall.
  
  

Hemorrhagic Stroke (Pathology of Nervous System)

 Image taken from www.merck.com

A hemorrhagic stroke is damage to brain tissue resulting from bleeding inside the skull.

• There are two main types of hemorrhagic strokes: intracerebral hemorrhage and subarachnoid hemorrhage.
• Intracerebral hemorrhage occur within the brain while subarachnoid hemorrhage occur within a space between pia and arachnoid mater of the tissue covering the brain (meninges).
• Bleeding inside the skull can also result in epidural and subdural hematomas, which are usually caused by a head injury and cause different symptoms.

Intracerebral Hemorrhage  

 

An intracerebral hemorrhage is bleeding within the brain.

•  Intracerebral hemorrhage accounts for about 10% of all strokes but for a much higher  percentage of death due to stroke.
• Among people older than 60, intracerebral hemorrhage is more common than subarachnoid hemorrhage.
• Causes of intracerebral hemorrhage include high blood pressure and in older people, fragile blood vessels.
• Bleeding disorders and use of anticoagulants increase the risk of dying from an intracerebral hemorrhage.

Symptoms and Diagnosis

 Image taken from  uwmedicine.washington.edu

• An intracerebral hemorrhage begin abruptly. In about half of the people, it begins with a severe headache.
• Neurologic symptoms develop and steadily worsen. They include weakness, paralysis, numbness, loss of speech or vision, and confusion.
• Symptoms worsen as the hemorrhage expands. Nausea, vomiting, seizures, and loss of consciousness are common and may occur within seconds to minutes.
• Doctor can often diagnose intracerebral hemorrhages on the basic of symptoms and the results of a physical examination.
• However, CT or MRI scan is usually performed when a stroke is suspected. Both procedures can help doctors distinguish a hemorrhagic stroke from an ischemic stroke. The procedures can also detect how much brain tissue has been damaged and whether pressure is increased in other areas of the brain.
• A lumbar puncture (LP)  is not usually performed. LP cab cause herniation of the brain, a life threatening disorder.

Treatment and Prognosis.

• Treatment of hemorrhagic stroke differs from that of an ischemic stroke.
• Anticoagulants, thrombolytic drugs, and anti-platelet drugs (such as aspirin) are not given, and surgery may save the person's life.
• The goal of surgery is to remove blood that has accumulated in the brain and to relieve the resulting increased pressure.
• Stroke due to intracerebral hemorrhage is more dangerous that ischemic stroke. The stroke is usually large and catastrophic, especially in people who have chronic high blood pressure.
• More than have of the people who have large hemorrhages die within a few days. Those who survive usually recover consciousness and some bran function as the body absorbs the leaked blood.
• Ever after surgery, many people continue to have some neurologic symptoms. The symptoms may include weakness, paralysis, loss of sensation on one side of the body, or difficulty understanding and using language (aphasia).
• However, people with small hemorrhages recover to a remarkable degree.

Subarachnoid Hemorrhage

Image taken from uwmedicine.washington.edu

A subarachnoid hemorrhage is sudden bleeding into the space (subarachnoid space) between the inner layer (pia mater) and middle layer (arachnoid mater) of the meninges.

• Usually, the cause is the sudden rupture of an aneurysm in a cerebral artery or blood vessel (atriovenous) malformation of the arteries or veins in or around the brain.
• An aneurysm  may rupture because of the pressure  of blood inside the artery; hemorrhage and stroke may result.
• An arteriovenous malformation may be present at birth, but it is identified only if symptoms develop, it may cause bleeding, usually during adolescence or young adulthood, and sudden collapse, stroke, and death may result.
• Rarely, atherosclerosis or a bacterial infection damage a blood vessel, causing it to rupture. Ruptures can occur in people of any age of 25 and 50. A subarachnoid hemorrhage can also result from a head injury.
• A subarachnoid hemorrhage is the only one type of stroke more common among women than among men.

Symptoms and Diagnosis

 Image taken from  uwmedicine.washington.edu

• Before rupturing, aneurysms that cause subarachnoid hemorrhages usually produce no symptoms. However, aneurysm sometimes press on a nerve or leak small amounts of blood before a major rupture, thereby producing warning signs, such as headache, facial pain, double vision, or other visual problems.
• The warning signs can occur minutes to weeks before the rupture. People should always report such symptoms to a doctor immediately, because steps may be taken to prevent a massive hemorrhage.
• A rupture usually produces a sudden, severe headache, often followed by a brief loss of consciousness. Some people remain in a coma, but more people wake up, feeling confused and sleepy.
• Blood and cerebrospinal fluid around the brain irritate the layers of tissue covering the brain (meninges), producing dizziness.
• Frequent fluctuations in the heart rate and in the breathing rate often occur, sometimes accompanied by seizures. Within hours or even minutes, people may again become sleepy and confused.
• About 25% of people have neurologic symptoms, usually paralysis on one side of the body.
• A subarachnoid hemorrhage can usually be diagnosed by CT scan, which pinpoints the site of bleeding.
• LP if necessary can detect any blood in the CSF.
• Cerebral angiography is usually performed within 72 hours to confirm the diagnosis and to identify the site of the aneurysm or arteriovenous malformation causing the bleeding, so that surgery can be performed.

An angiogram shows a left-sided aneurysm

Image taken from www.thecni.org

Treatment and Prognosis

• People who may have had a subarachnoid hemorrhage are hospitalized immediately and instructed to avoid exertion.
• Analgesics such as opioids (but not  aspirin or other NSAID)  are given to control the severe headaches.
• Occasionally, a drainage tube may be placed in the brain to relieve pressure.
• Nimodipine, a calcium channel blocker, is usually given to prevent spasm of an artery. This drug  helps prevent late spasm and ischemic stroke.
• For people who have an aneurysm, surgery that isolates, blocks off, or supports the walls of the weak artery reduce the risk of fatal bleeding later. These procedures are difficult, and regardless of which one is used, the risk of death is high, especially for people whoa are in a stupor or coma.
• The best time for surgery is somewhat controversial and must be decided based on the person's situation.
• Most neurosurgeon  recommend operating within 3 days of the start of symptoms, before the brain becomes swollen and inflamed.
• Delaying in operation 10 or more days reduces the risk of surgery, but bleeding is more likely to recur in the longer interim.
• A common procedure is placement of a metal clip across the aneurysm, which prevents blood from entering  the aneurysm and thus eliminates the risk of rupture. People who have clips remains on place permanently. 
• People who had clips placed years ago cannot undergo MRI: newer clips are not affected by the magnetic forces.
• An alternative procedure, called neuroendovascular surgery, involves the insertion of coiled wires into the aneurysm. The coils are placed using a catheter inserted into an artery and threaded to the aneurysm. Thus, this procedure does not require that the skull be opened.  By slowing blood flow, the coils promote clot formation, which seals of the aneurysm.
• About 35% if people who have a subarachnoid hemorrhage due to an aneurysm die during the first episode because of extensive brain damage.
• Another 15% die within  a few weeks because of subsequent bleeding.
• People who survive for 6 months but who do not have surgery for the aneurysm may have a 3% chance of another rupture each year.
• The outlook is better when the cause is an arteriovenous malformation. Occasionally, the hemorrhage is caused by a small defect that is not detected by cerebral angiography becayse it has already sealed itself off. In such cases, the outlook is very good.
• Many people recover most or all mental and physical function after a subarachnoid hemorrhage.
• However, neurologic symptoms, such as weakness, paralysis, loss of sensation on one side of the body, or difficulty in understanding and using language (aphases) sometimes persist.
  

Extra Class for Pathology

For those who are taking pathophysiology subjects, please be inform that we have an additional classes on basic pathology. The detail is as below;

• 31st of July, 1st,  7th and 8th of  August 2008
• 5-7pm
• Theater Hall

Attendance is compulsory.

Histology of Trachea

 Image taken from www.lab.anhb.uwa.edu.au

• After inhaled air has passed through the nose, pharynx, and larynx, it enters the trachea. 
• The trachea is a thick-walled tube, some 12 cm in length, that directs air down toward the pair of primary bronchi that enter the lung. 
• The trachea's inner surface, facing the lumen, is lined by a pseudostratified columnar epithelium  that contains ciliated cells, goblet cells, and Basal Cells. 
• The tracheal epithelium  lies atop a highly elastic lamina propria, which grades into the submucosa. 
• The well-developed submucosa contains conspicuous rings of hyaline cartilage that keep the trachea open when the neck is bent or turned. 
• The cartilage is covered by a tough perichondrium, which, in the outer region of the wall, is covered by the adventitia, a sheath of loose connective tissue that envelops the outer surface of the trachea. 
• This spatial arrangement of component tissues - epithelium, lamina propria, submucosa, and adventitia - is common to many of the body's interior tubular systems. 

  Image taken from www.lab.anhb.uwa.edu.au

• The epithelium and lamina propria are shown in greater detail in above image.
• The goblet cells, as the name suggests, have a goblet-shaped cytoplasm filled with mucus droplets that displace the nucleus and bio synthetic machinery toward the basal pole of the cell. 
• The ciliated cells  appear much darker and have numerous motile cilia projecting from the cell surface. Taken together, these two cell types generate the mucociliary blanket that protects the inner tracheal surface. 
• The goblet cells, along with large submucosal glands, produce and secrete the mucus; the cilia move mucus toward the mouth. In this way, foreign materials that enter the respiratory system are entrapped by the sticky mucus and are rapidly moved toward the throat to be swallowed or expectorated. 
• At the bottom of the epithelium are the basal cells, stem cells that replace worn-out ciliated and goblet cells.

Overview of the Heart

Anatomy

• Size, shape, location and orientation
• Covering of the heart
• Pericardium
• fibrous pericardium
• parietal pericardium
  
• Visceral layer (epicardium)
• *pericardial cavity between parietal & visceral layer
  
• Layers of heart wall.
• Epicardium
• Myocardium
• Endocardium
  
• 4 heart chambers
• Rt ventricle
• Lt ventricle
• Rt atrium
• Lt atrium
  
• Pathway of blood through the heart
• Systemic circulation
• Pulmonary circulation
  
• Coronary circulation
• Coronary arteries
• Coronary veins
• Heart valves
• Mitral (bicuspid)
  
• Tricuspid (tricups)
• Aortic (tricups)
  
• Pulmonary (tricups)
• Surface anatomy
• The valves
• Apex
  
• Point of maximum intensity
  

Physiology

• Properties of cardiac muscle
• Conducting system of the heart
• Intrinsic innervation
• SA node
• 3 Internodal pathyway (anterior, middle, posterior)
• AV node
• Bundle of His
• Purkinje fibers
• Extrinsic innervation
• Para sympathetic (cardioinhibitory center)
  
• Sympathetic (cardioacceleratory center)
• ECG
• Cardiac cycle
• Atrial & ventricles dystole (atrial & ventricular filling)
  
• Atrial systole, ventricles dystole (ventricular filling)
• Atrial dystole, ventricles systole (ventricular ejection & atrial filling)
  
• Heart sounds
• Stroke volume, cardiac output and heart beat
• Stroke volume, SV  = EDV - ESV=120ml - 50ml = 70ml per beat
•  Heart Rate, HR = 72~75 beats per min
  
• Cardiac output, CO =  Heart Rate, HR x SV = 75 beats x 70ml = 5.25 L/min
• Regulation of stroke volume
• Preload: degree of stretch  of heart muscle
• Contractility
• Afterload: back pressure exerted by arterial blood
  
• Regulation of heart rate
• ANS
• Parasympathetic
• Sympathetic
  
• Chemical regulation
• Hormones (epinephrine, thyroxine)
  
• Ions
  
• age, gender, exercise, temperature, etc
  

Venous Drainage of the Heart

• About 2/3 of the venous drainage of the heart is achieved by veins whcich accompany the coronary arteries and which open into the right atrium.
• The rest of the blood drains by means of small veins (called as venae cordis minimae) directly into the cardiac cavity.
• By looking at the posterior aspect of the heart, we can see the veins come from  coronary sinus lies in the posterior atrioventricular groove and opens into the right atrium  just to the left of the mouth of the inferior vena cava.

• Then later, it branches into;

1. the great cardiac vein  in the anterior interventricular groove (can be seen at anterior view of the heart)
   
2. the middle cardiac vein the inferior interventricular groove;
3. the small cardiac vein - accompanying the marginal artery along the lower border of the heart,
4. the oblique vein - descends obliquely on the posterior aspect of the left atrium (not labeled in the picture, located just above the circumflex coronary artery)
   

• At the anterior surface of the heart, anterior cardiac veins (up to three or four in number) cross the anterior atrioventricular groove, drain much of the  anterior surface of the heart and open directly into the right atrium.

Click here to read about coronary arteries (in bahasa Malaysia)

All images are taken from http://home.comcast.net/

Esophagus (review of anatomy & physiology)

Anatomy

•  The esophagus develops from the cranial portion of the foregut and is recognizable by the 3rd week of gestation. 
• The normal esophagus is a hollow, highly distensible muscular tube that extends from the epiglottis in the pharynx, at about the level of C6 vertebra, to the gastroesophageal junction at the level of the T11 or T12. 
• Measuring between 10 and 11 cm in the newborn, it grows to a length of about 25 cm in the adult.
• For the endoscopist, the esophagus is recorded as the anatomic distance  between  15 and 40 cm from the incisor teeth, with the gastroesophageal junction located at the 40-cm point.
• Several points of luminal narrowing can be identified along its course-proximally at the cricoid cartilage, midway in its course alongside the aortic arch and at the anterior crossing of the left main bronchus and left atrium, and distally where it pierces the diaphragm.
• Although the pressure in the esophageal lumen is negative compared with the atmosphere, manometric recordings of intraluminal pressures have identified two higher-pressure areas that remain relatively contracted in the resting phase.
• A 3-cm segment in the proximal esophagus at the level of the cricopharyngeus muscle is referred to as the upper esophageal sphincter (UES).
• The 2- to 4-cm segment just proximal to the anatomic gastroesophageal junction, at the level of the diaphragm, is referred to as the lower esophageal sphincter (LES). Both 'sphincters' are physiologic, in that there are no anatomic landmarks that delineate these higher-pressure regions from the intervening esophageal musculature.

Wall of esophagus

Taken from www.mc.vanderbilt.edu

• The wall of the esophagus consists of a mucosa, submucosa, muscularis propria/externa, and adventitia, reflecting the general structural organization of the gastrointestinal tract.
• The mucosa has a smooth, glistening , and pink-tan surface. It has three components;
1. a non-keratinizing stratified squamous epithelial layer,
2. lamina popria,
3. muscularis mucosa

1. The epithelial layer has mature squamous cells overlying  basal cells. The basal cells, constituting 10% to 15% of the mucosal thickness, are reserve cells with great proliferative potential.
   
   
   
   
   
   
   
   • A small number of specialized cell type, such as melanocytes, endocrine cells, dendritic cells, and lymphocytes, are present in the deeper  portion of the epithelial layer.
2.  The lamina propria is the non-epithelial portion of the epithelial layer, above the muscularis  mucosae.
•  It consists of areolar connective tissue and contain vascular structures and scattered leukocytes.
•  Finger-like extensions of the lamina propria, called papillae, extend into the epithelial layer. 
3. The muscularis mucosa is a delicate layer of longitudinally oriented smooth-muscle bundles.

• The submucosa consists of loose connective tissue containing;
• blood vessels, 
• a rich network of lymphatics, 
• a sprinkling of leukocytes with occasional lymphoid follicles, 
• nerve fibers (including the ganglia of Meissner plexus), and
  
• submucosal glands.
• Submucosal glands connected to the lumen by squamous epithelium-line ducts are scattered along the entire esophagus but are more concentrated in the upper and loweer portions. Their mucin-containing fluid secretions help lubricate the esophagus
• As is true throughout the alimentary tract, the muscularis propria/externa consists of an inner circular and an outer longitudinal coat of smooth muscle with an intervening, well-developed myenteric plexus (Auerbach plexus).
• The muscularis propria striated muscle fibers from the cricopharyngeus muscle.
• Besides creating a unique histologic interplay of smooth muscle and skeletal muscle fibers, this feature explains why skeletal muscle disorder can cause upper esophageal dysfunction.
  

• In sharp contrast to the rest of the gastrointestinal tract, the esophagus is mostly devoid of a serosal coat. Only small segments of the intra-abdominal esophagus are covered by serosa; the thoracic esophagus is surrounded by fascia that condenses around the esophagus to form a sheath like structure.
• In the upper mediasternum, the esophagus is supported by this fascial tissue, which forms a similar sheath around adjacent structures, the great vessels and the tracheobronchial tree. This intimate anatomic proximity to important throracic viscera is of significance in permitting the ready and widespread dissemination of infections and tumors of the esophagus into the posterior mediasternum. The rich network of mucosal and submucosal lymphatics that runs longitudinally along the esophagus further facilitates spread.
• As a summary, wall of esophagus composed of;
1. Mucosa
1. epithelial cells (non-keratinized stratified columnar epithelium)
2. lamina popria
3. muscularis mucosa (longitudinal smooth muscle)
2. Submucosa
1. submucosal plexus (Myentric's)
3. Muscularis externa/popria
1. inner circular smooth muscle
1. Meissner plexus (Auerbach's)
2. outer longitudinal muscle
   
4. Adventitia
   

Physiology of esophagus

• The main functions of the esophagus are;
1. to conduct food and fluids from the pharynx to the stomach, 
2. to prevent passive diffusion from the  pharynx to the stomach, 
3. to prevent passive diffusion of substances from the food into the blood, and 
4. to prevent reflux of gastric contents into the esophagus.
• These functions require motor activity  coordinated with swallowing, namely a wave of peristaltic contraction, relaxation of the LES in anticipation of the peristaltic wave, and closure of the LES after the swallowing reflex. The mechanisms governing this motor function are complex, involving both extrinsic and intrinsic innervation, humoral regulation and properties of the muscle wall itself.
• The control of the lower esophageal sphincter (LES) is critical to esophageal function. Maintenance of sphincter tone is necessary to prevent reflux of gastric contents, which are under positive pressure relative to the esophagus.
• During deglutition, both active inhibition of the muscularis propria muscle fibers by inhibitory nonadrenergic/noncholinergic neurons and cessation of tonix excitation by cholinergeic neurons enable the LES to relax. 
• Many chemical agents (eg gastrin, acetylcholine, serotonin, prostaglandin F20, motilin, substance P, histamine and pancreatic polypeptide)l decrease the tone. However, their precise roles in normal esophageal function remain unclear.
  

Hydrocephalus (Pathophysiology of NS)

Image taken from www.lucinafoundation.org/. 

Copyright of Lucina Foundation. All right reserved 

• The fluid surrounding the brain (cerebrospinal fluid, CSF) is produced in spaces within the brain called ventricles. The fluid must be drain to a different area, where it is absorbed into the blood. When the fluid cannot drain, hydrocephalus (water in the brain) develops.
• Hydrocephalus often increases the pressure in the ventricles, which compresses the brain. 
• Many conditions, such as a birth defect, bleeding within the brain, or brain tumours can block drainage and cause hydrocephalus.
• An abnormally large head my be a symptom of hydrocephalus. The infant usually fails to develop normally.
• CT scan, ultrasound, or MRI scan of the head reveals the diagnosis as well as the degree of brain compression.
• The goal of treatment is to keep pressure normal within the brain. A permanent alternate drainage path (shunt) for CSF decrease the pressure and volume of the fluid inside the brain.
• A doctor places the shunt in the ventricles in the brain and runs it under the skin from the head to another site, usually the abdomen (ventriculoperitoneal shunt). The shunt contains a valve that allows fluid to leave the brain if the pressure  becomes too high.
• Although a few children can eventually do without the shunt as they get older, shunts are rarely removed.
• If needed, pressure within the brain can often be temporarily reduced with drugs (such as acetazolamide or furosemide) or repeated lumbar puncture until a shunt is placed.
• Some children with hydrocephalus develop normal intelligence. Others are mentally retarded or have learning disabilities.

Assignment - Gastrointestinal System

For those who are taking Gastrointestinal System by Assoc Prof Dr Karim, please be informed that you have an assignment on;

• Anatomy & histology covering from mouth to stomach (for senior group)
  
• Anatomy & histology covering from  small intestine to anus (for junior group)

The assignments must be submitted before final exam.

Heart Defects (Pathophysiology of CVS)

• One of 120 babies is born with a heart defect. Some are severe, but many are not. Defects may involve abnormal formation of the heart's walls or valves or of the blood vessels that enter or leave the heart.
• Before birth, a fetus uses oxygen obtained from the mother's blood through the placenta. The fetus does not breathe. Also, the path by which blood circulates through the heart and lungs is  different in fetus. After birth, a newborn must obtain oxygen using his own lungs.Therefore, many changes occur in the heart and blood vessels soon after birth.
• Before birth, blood that has not yet traveled to the lungs (venous blood) mixes with blood that has already traveled to the lungs (arterial blood). Such mixing occurs in the foramen ovale, a hole between the right and left atria and ductus arteriosus, a blood vessel connecting the pulmonary artery and the aorta. In the fetus, both venous and arterial blood contain oxygen, so mixing arterial and venous blood does not affect how much oxygen gets pumped to the body. After birth, arterial blood and venous blood do not normally mix. The foramen ovale and ductus arteriosus normally close within days to a couple of weeks after birth.
• Two general processes account for most of the symptoms resulting from heart defects. One is that blood flow gets altered or rerouted(shunting). Another is that not enough gets pumped to the body, usually because of a blockage.
• Shunting can cause oxygen-poor blood to mix with oxygen-rich blood that is pumped to the body tissues (right to left shunt). The more oxygen-poor blood that flows to the body, the more blue the body appears, particularly the skin and lips. Many heart defects are characterized by a bluish discoloration of the skin (cyanosis); cyanosis indicates that not enough oxygen-rich blood is reaching the tissues where it is needed.
• In heart failure, blood also backs up, often in the lungs. Heart failure can also develop when the heart pumps too weakly or when blood is blocked from flowing to the baby's body.
• Blockages may develop in the valves of the heart or in the blood vessels leading away from the heart. Blood may be impeded from flowing to the lungs because of narrowing of the pulmonary valve (pulmonary valves stenosis) or narrowing within the pulmonary artery itself (pulmonary valve stenosis). Blood may be impeded from flowing through the aorta to the body because of narrowing of the aortic valve (aortic valve stenosis) or blockage within the aorta itself (coarctation of the aorta).

Symptoms and Diagnosis

•  Often, heart defects produce few or no symptoms and are  not detectable even during a physical examination of the child. Some mild defects produce symptoms only later in life. 
• However, many heart defect do result in symptoms during childhood. 
• Because oxygen-rich blood is necessary for normal growth, development, and activity, infants and children with heart defects may fail to grow or gain weight normally. They may not be able to exercise fully.
• In more severe cases, cyanosis may develop, and breathing or eating may be difficult.
• Abnormal blood flow through the heart usually produce murmur sound that can be heard using a stethoscope; however, the vast majority of heart murmurs that occur during childhood are not caused by heart defects and are not indicative of any heart problems.
• Heart failure makes the heart beat rapidly and often causes fluid to collect in the lungs or liver.
• Many heart defects can be diagnosed before birth using ultrasound. After birth, heart defects are suspected when symptoms develop or when particular heart murmurs are heard.
• Diagnosing heart defects in children involves the same techniques used for diagnosing heart problems in adults. A doctor may be able to diagnose the defect after asking the family specific questions and performing a physical examination, ECG, and a chest x-ray. Ultrasound (echochardiography) is used to diagnose almost all of the specific defects. Cardiac catheterization often can show small abnormalities that are not detected with echocardiography or can further illuminate the details of the abnormality.

Treatment

      

Comparison of angioplasty and valvuloplasty

Images taken from http://www.know-heart-diseases.com and http://www.cardiosmart.org/

• Many significant heart defects are effectively corrected using open-heart surgery. When to perform the operation depends on the specific, its defect, its symptoms, and severity. For example, it may be better to postpone surgery until the child is a little older. However, severe symptoms resulting from a heart defects are most effectively relieved with immediate surgery.
• A narrowing can sometimes be relieved by passing a thin tube (catheter) through a blood vessel in the arm or leg into the narrowed area. A balloon attached to the catheter is inflated and widens the narrowing, usually in a valve (a procedure called balloon valvuloplasty) or blood vessel (a procedure known as balloon angioplasty). These balloon procedures spare the child from general anesthesia and open heart surgery. However, a balloon procedures are not usually as effective as surgery.
• If the aorta or pulmonary artery is severely blocked, a temporary shunt can sometime be created to keep an adequate amount of blood  flowing. A shunt can be created with a catheter balloon (for example, between the right and left atria - balloon septostomy).
• Drug prostaglandin E1 (alprostadil) can be given to keep the ductus arteriosus open, shunting blood between the aorta and pulmonary artery. 
• In rarer cases, when no other treatment helps, a heart transplant is performed, but the lack of donor hearts limits the availability of this procedue.
•  Most children who have significant heart defects are at increased risk for developing life-threatening bacterial infections of the heart and its valves (endocarditis). They need to take antibiotics before certain treatments and procedures.

Patent Ductus Arteriosus 

 Fetal echocardiogram of the ductus arteriosus (Courtesy of Drs. J. Moodley and Y. Shah)

Image taken from www.sahha.gov.mt/

•  In patent ductus arteriosus, the blood vessel connecting the pulmonary artery and the aorta (ductus arteriosus) fails to close as it usually does within the the first 2 weeks after birth.
• A left-to-right shunt causes extra blood flow, and pressure in the lungs may damage the lung tissue.
• Premature newborns are especially susceptible to patent ductus arteriosus and lung damage.
• Most often, the defect causes no symptoms. When symptoms do occur, they are usually difficulty breathing or cyanosis, which may be present at birth or not for several weeks after birth.
• When the infant has no symptoms, doctors most often suspect the defect when they hear a heart murmur.
• Use of indomethacin, a drug that inhibits the production of prostaglandins, closes the defect in 80% of infants. Indomethacin is most effective if given in the first 10 days after birth and is more effective in premature newborns that in full-term newborns. 
•  If the defect does not close after several doses of indomethacin, it is closed surgically.

Atrial and Ventricular Septal Defects

 

Image taken from www.nmtmedical.com/

• Atrial and ventricular septal defects are holes in the septum that separate the heart into left and right sides.
• Atrial septal defects are located between the atria while ventricular septal defects are located between the ventricles.
• These holes typically cause left-to-right shunting of blood. 
• Many atrial septal defects close by themselves, especially in the first year of life; many ventricular septal defects close within the first 2 years.
• Infants and most older children with atrial septal defects have no symptoms.
• In more severe case, children may develop heart murmurs, fatigue, and difficulty in breathing.
• The symptoms caused by atrial septal defects increase as the person ages. For example, heart failure may develop during middle age.
• Ventricular septal defects can vary from  small holes, which may cause a heart mumur but no symptoms and usually close by themselves, to larger holes that cause symptoms in infants.
• Significant ventricular septal defects usually cause more severe symptoms that atrial septal defects, because there is more shunting of blood.
• Because of the way lungs develop, shunting increases during the first 6 weeks after birth. Usually the murmur becomes louder, and symptoms, typically rapid breathing, sweating, and difficulty feeding, worsen.
• Mild symptoms of ventricular septal defect may be treated with diuretics (such as furosemide) or drugs that decrease resistance to the flow of blood to the body (such as captopril).
• If atrial and ventricular septal defects are large or cause symptoms, they are closed by surgery.

Rhinitis (Pathology of Respiratory System)

 

Rhinitis is inflammation and swelling of the mucous membrane of the nose, characterised by a runny nose and stuffiness and usually caused by the common cold or and an allergy.

The nose is the most commonly infected part of the upper airways. Rhinitis may be acute or chronic. Acute rhinitis commonly results from viral infections but may also be a result of allergies or other causes. Chronic rhinitis usually occurs with chronic sinusitis (chronic rhinosinusitis).

Viral Rhinitis

• Acute viral rhinitis (the common cold) can be caused by a variety of viruses
• Symptoms consists of runny nose, congestion, post nasal drip, cough, and a  low-grade fever.
• Stuffiness can be relieved by taking phenylephrine as a nasal spray or pseudphedrine by mouth. These drugs, available by over the counter, cause the blood vessels of the nasal mucous membrane to constrict. Nasal spray should only be used for only 3 or 4 days because  after that period of time, when the effects of the drugs wear off, the mucous membrane often swells even more that before. This phenomena is called as rebound congestion.
• Antihistamines help  control runny nose but cause drowsiness and other problems, especially in older people.
• Antibiotics are not effective for acute viral rhinitis.

Allergic Rhinitis

• Allergic rhinitis is caused by a reaction of the body's immune system to an enviromental trigger. The most common environmental triggers include dust, molds, pollens, grasses, trees, and animals.
• Symptoms include sneezing, runny nose, stuffiness, and itchy, watery eyes.
• A doctor may diagnose  allergic rhinitis based on a person's history of symptoms. Often, the person has a family history of allergies.More detailed information may be obtained using blood tests or skin testing.
• Avoiding the substance that triggers the allergy prevents symptoms but is often not possible.
• Nasal corticosteroid sprays decrease nasal inflammation caused by many sources and are relatively safe for long-term use.
• Antihistamine help prevent the allergy reaction and thus symptoms.
• Antihistamines dry the mucous membrane of the nose but many of them also cause sleepiness and other problems, especially in older  people.
• Never ones require a prescription but do not have these side effects.
• Allergy shots (desensitization) help to build long therm tolerance to specific  environmental triggers, but they may take months  or years to become fully effective.
• Antibiotic do not relieve the symptoms of allergic rhinitis.

Atrophic Rhinitis

• Atrophic rhinitis is a form of chronic rhinitis in which  the mucous membrane thins (atropies) and hardens, causing the nasal passages to widen and dry out.
• The cells normally found in the mucous membrane of the nose - cells that secrete mucus and have hairlike projections to move dirt particles out - are replaced by cells like those normally found in the skin.
• The disorder can develop in someone who had sinus surgery in which a significant amount of intranasal structures and mucous membranes were removed. 
• A prolong bacterial infection of the lining of the nose is also a factor.
• Crust form inside  the nose, and an offensive odour develops.
• A person may have recurring severe nosebleeds and can lose his sense of smell (anosmia).
• Treatment is aimed at reducing the crusting, elimination the odour, and reducing infections. 
• Topical antibiotics, such as bacitracin applied  inside the nose, kill bacteria.
• Estrogens and vitamins A and D sprayed into the nose or taken by mouth may reduce crusting by promoting mucosal secretions.
• Other antibiotics, given by mouth or intravenously, may also be helpful.
• Surgery to narrow the nasal passages may reduce crusting became the decreased airflow prevents drying if the thinned mucous membrane

Vasomotor Rhinitis

• Vasomotor rhinitis is a form of chronic rhinitis.
• Nasal stuffiness, sneezing, and a runny nose - common allergic symptoms - occur when allergies do not appear to be present.
• In some people, the nose reacts strongly to irritants, perfumes, and pollution.
• The disorder comes and goes but is worsened by dry air.
• The swollen mucous membrane varies fro bright red to purple.
• Sometimes, people also have slight inflammation of the sinuses.
• When persistent, endoscopy of the nose or CT scan of the sinus is not significant.
• Treatment is aimed at relieving symptoms.
• Avoiding smoke and irritants and using a humidified central heating system or vaporizer to increase humidity may be beneficial.
  

Related article :

1. Sinusitis
   

Headaches (Patophysiology of NS)

Headache is defined as pain or discomfort in the head that is located above the eyes or the ears, behind the head (occipital), or in the back of the upper neck.

Headaches are a very common medical problem and a common cause of disability among men and women. Headaches interfere with the ability to work and to perform daily tasks. Some people have frequent headaches; other people hardly ever have them.

Classification of headache are;

• Primary (idiopathic) headache, includes;
  

1. Tension-type of headache
   
2. Migraine (with or without aura)
   
3. Combination of headache
4. Cluster headache
   

• Secondary headache caused by underlying disease

Causes

• Although headaches can be painful and distressing, they rarely indicate a serious condition. Most headaches - tension type, migraine, and cluster headaches - are not caused by another identifiable disorder. Tension type headaches are the most common.
• Less commonly, headaches result from another disorder. Usually, the disorder is not serious. Disorders that cause headaches are often minor or temporary ones that affect the eyes, nose, throat, sinuses, teeth, jaws, ears, or neck.
• Rarely, headaches are caused by a serious disorder. Such disorder include a head injury, stroke, bulge in the wall of an artery supplying the brain (cerebral aneurysm), brain infection (brain abscess, meningitis, and encephalitis), and blood vessel (arteriovenous)malformation near the brain. Infections such as tuberculosis may affect the brain and cause headaches. Disorders that increase pressure within the skull can cause headaches by putting pressure on the brain. Examples area brain tumor, bleeding (hemorrhage), an accumulation of blood (hematoma), and pseudotumor cerebri, in which pressure within the skull increases but ni cause can be identified.
• Other serious diseases that may cause headache include very high blood pressure, which may produce a throbbing sensation in the head. (However, high BP does not usually cause headache.) Lung disorders (such as emphysema) that reduce the oxygen supply to the brain may cause headaches, as may sleep apnea, which temporarily increases levels of carbon dioxide in the blood. Inflammation of large arteries (temporal arteritis), usually in the neck and head, may cause headaches. Temporal arteritis affects older people primarily. Severe cases of influenza and high fever may cause headaches. Lyme disease in its early stages commonly causes headaches.
• Headaches commonly result from withdrawal of caffeine, withdrawal of analgesics after long-term use, and use of certain drugs that widen blood vessels (such as nitroglycerin).

Diagnosis

• Usually, doctors can determine the type or cause of headaches on the basis of the person's medical history, the characteristics of the headache, and results of a physical examinations.
• Characteristics of the headache include its frequency, duration, location, severity, and associated symptoms.
• The following characteristics may indicate that a serious disorder is the cause of headaches, and prompt medical attention is required.

1. Frequent headaches in a person who rarely has headaches,
2. Mild headaches that become severe,
3. headaches that awaken a person from sleep,
4. Any change in the pattern or nature of headaches,
5. Headaches associated with symptoms such as a fever and a stiff neck, changes in sensation, or vision, weakness, loss of coordination, or fainting.
   

• For example, a severe headache with a fever and a stiff neck suggests meningitis - a life threatening infection of the layers of tissue covering the brain and spinal cord (meninges). A headache that occurs suddenly and that is more severe that any others the person has experienced suggests a subarachnoid hemorrhage - often due to ruptured aneurysm.
• When doctors suspect a serious disorder, additional diagnostic procedures are usually performed. If meningitis is suspected, a spinal tap (lumbar puncture) is performed immediately. A spinal tap may also be performed if doctors suspect a ruptured aneurysm. Occasionally, blood tests are performed to check for a disorder such as Lyme disease. The erythrocyte sedimentation rate (ESR - the rate at which RBC settle down to the bottom of a test tube containing blood) may be determined to check for temporal arteritis. A high ESR suggests inflammation.
  
• If doctors suspect a tumor, stroke, hemorrhage, or another structural brain disorder, CT or MRI scan of the head is performed.
  

Tension-Type Headaches
Tension type headache is usually mild to moderate, band-like pain that affects the whole head.

The cause of tension-type headaches is not well understood but may be related to a lower-than normal threshold for pain. Stress clearly understood, and it is not the only explanation for the symptoms.

There are two classification of tension type headache;

1. Episodic type headache - tension type headache that occur fewer than 15 days per month.
2. Chronic type headache - occurs more than 15 days per month for at least 6 months.
   

Symptoms and Diagnosis

• The pain is usually mild to moderate, although it may be severe.
  
• It feels like tightening of a band around the head, making whole head ache. The pain may last 30 minutes to 1 week.
  
• Unlike a migraine headache, a tension-type headache is not associated with nausea and vomiting and is not made worse by physical activity, light, sounds, or smells.
  
• Tension-type headaches typically start several hours after waking and rarely awaken a person from sleep.
• The diagnosis is based on the person's description of the headache and the results of a physical examination.
• No specific procedures can confirm the diagnosis.
• Rarely, CT or MRI scan of the head is performed to rule out other disorders that may be causing the headache, particularly if headaches have developed recently.

Treatment

• For most mild to moderate tension-type headaches, almost any over-the counter analgesic, such as aspirin, acetaminophen, or ibuprofen can provide fast, temporarily relief.
• Massaging the affected area may help relieve the pain.
• Severe headaches may require stronger, prescription analgesics, some of which contains opioid (narcotics), such as codeine or oxycodone.
• For some people, caffeine, an ingredient of some headache preparations, enhances the effect of analgesics.
• However, overuse of analgesics or caffeine can lead to chronic daily headaches. Such headaches. called rebound headaches, occur when a dose of an analgesic is missed or late or when caffeine intake is reduced or stopped.

Migraine Headaches

A migraine headache is throbbing, moderate to severe pain, usually on one side of the head that is worsened by physical activity, light sounds, or smells and that is associated with nausea and vomiting.

• Although migraines can start at any age, they usually begin between the ages of 10 and 40.
• In most people, migraines recur periodically, but they usually become significantly less severe or resolve entirely after age 50 or 60.
• Migraines are 3 times more common among women that among men.
• Migraines tend to run in families; more than half of the people who have migraines have close relatives who also have them.
• The cause of migraines is not well understood. According to one theory, migraines occur when arteries to the brain become constrict and then dilate; dilation is thought to activate nearby pain receptors.
• However this theory is too simple to explain the complex changes in blood flow that occur in the brain during a migraine. Furthermore, a series of changes in the nerve cells of the brain occur before the changes in the blood flow.
• A rare subtype of migraine called familial hemiplegic migraine is associated with a genetic defect on chromosomes 1 and 19. The role of genes in the more common forms of migraine is under study.
• Estrogen, the main female hormone, appears to trigger migraines, a possibly explaining why migraines are more common among women.
• During puberty, migraines become much more commons among girls than among boys.
• Some women have migraines just before, during, or just after menstrual periods.
• As menopause approaches (when estrogen level fluctuating), migraines become particularly difficult to control. Oral contraceptives (which control estrogen) and estrogen replacement therapy often make migraines worse.
• Insomnia, changes in barometric pressure, and hunger may also trigger migraines.
• There are two types of migraine;

1. Migraine with aura (classic)
   
2. Migraine without aura (common)
   

Symptoms and Diagnosis

• In a migraine, throbbing pain is typically felt on one side of the head. The pain may be moderate but is often severe and incapacitating.
• Physical activity, light, sounds, or smells may make the headache worse.
• Headache is often accompanied by nausea, sometimes with vomiting.
• A migraine attack often involves more than a headache. It may include a prodrome, an aura, an a postdrome.
• The prodrome is a change in mood or behavior, which can precede the rest of the migraine by 24 hours.
• People may become depressed, elated, irritable, or restlessness.
• Nausea or loss of appetite may also occur.
• About 25% of people experience an aura. The aura involves temporary, reversible disturbances in vision, sensation, balance, movement, or speech.
• Commonly, people see jagged, shimmering, or flashing flashing lights.
• Less commonly, people experience tingling sensations, loss of balance, weakness in an arm or a leg, or difficulty talking.
• The aura occurs within the hour before the migraine and ends as the migraine begins.
• About 25% of people experience a postdrome, which involves changes in mood and behavior after the migraine.
• Migraines attacks may occur frequently for a long period of time but then may disappear for many weeks, month, or even years.
• Migraines are diagnosed on the basics of symptoms. No procedure can confirm the diagnosis.
  
• If headaches have developed recently or if the pattern of symptoms has changed, CT or MRI scan of the head is performed to exclude other disorder.

Prevention &  Treatment

 

• Treatment of migraine headaches involves three types of drugs; drugs to prevent migraines, drug to stop (abort) a migraine as it beginning, and drugs to relive pain.
• People who have more than one migraine a week often benefit from taking drugs every day to prevent migraine attacks.
• Beta blockers, such as propanolol, are often given first.
• Calcium channel blockers, antidepressants, and some anticonvulsants, particularly divalproex, are also effective.
• The choice of a preventive drug is based on the side effects of the drug and another disorders present. For example, if weight gain could cause problems, divalproex is usually not prescribed. If the person is has depression, a tricyclic antidepressant such as nortriptyline may be prescribed.
• To abort a migraine as it is beginning, most doctors prefer a relatively new group of drugs called triptans (5-hydroxytryptophan [5-HT] agonist). Triptans specifically target the receptors that stimulate the nerves supplying the the cerebral blood vessels. Thus, triptans may reverse the dilatation of these blood vessels which contributes to a migraine.
• As soon as people sense a migraine attack is beginning, they take one of these drigs to stop the attack from the processing.
  
• Other drugs used to abort migraines, such as ergotamine, are sometimes used, but they are not as safe or as effective as triptans. Because triptans and ergotamine cause blood vessels to constrict, they are not recommended for people who have angina or other heart disease or for people who have prodromal symptoms that resemble those of stroke (because constriction of arteries may trigger a stroke).
• For less severe migraines, analgesics alone or analgesics that contain caffeine can be useful. They can be taken as needed during a migraine, with or instead of a triptan.
• As for tension-type headaches, overuse of analgesics or caffeine can make the migraine worse.
  
• For more severe migraines, opioids may be needed.
  

Better Migraine Treatment