Case 1

Southwestern University-Matias H. Aznar Memorial, Inc.College of Medicine

Case 1

Submitted by:II-A Group 1Abdulatiffh, Sittie AliaAbecia, EvalaineAboy, Jose LorenzAcabo, Gideon ReyAlarcon, Maelisa GraceAlawi, JuharaArellano, Jemer GraceArendain, Gerald IanArdosa, RondyAtuel, Kristhy

6/25/2014

Case 1

A 50-year old security guard presents with a long-standing history of retrosternal burning and belching which he commonly gets after meals. He has been smoking since the age of 13 and he consumes five bottles of beer every night. A month ago he was treated for gastroesophageal reflux dyspepsia. Upper gastrointestinal endoscopy reveals streaks of red to velvety mucosa at the gastroesophageal junction. Biopsy from this site shows the presence of gastric and intestinal-type columnar cells.

1. Review the anatomy and histology of the organ involved.

Esophagus: Anatomy Muscular tube (25cm long) -average diameter of 2cm Extends from the pharynx to the stomach Function: to convey food from the pharynx to the stomach Passes through the esophageal hiatus in the muscular right crus of the diaphragm just to the left of the median plane at the level of T10 vertebra. Terminates by enetering the stomach at the cardial orifice of the stomach to the left of the midline at the level of the 7th left costal cartilage and T11 vertebra. Esophagogastric junction: lies to the left of T11 vertebra; where the mucosa abruptly changes from esophageal to gastric mucosa Histology Mucosa Composed of 3 layers: epithelium, lamina propria, and muscularis externa Lumen is lined by 0.5 mm thick stratified squamous non-keratinized epithelium Lamina propria houses the esophageal cardiac glands and occasionally lymphoid nodules Muscularis externa consists of single layer of longitudinal smooth muscle fibers Submucosa Denses, fibroelastic connective tissue that houses the mucous glands known as esophageal glands proper Muscularis externa Composed of 2 layers: inner circular and outer longitudinal Upper 1/3 of esophagus has mostly skeletal muscle Middle 1/3 contains both skeletal and smooth muscles Lower 1/3 contains only smooth muscles Has 2 physiologic sphincters: the pharyngoesophageal sphincter and the gastroesophageal sphincter which prevent reflux into the pharynx from the esophagus and into the esophagus from the stomach

2. Given the endoscopy and biopsy findings, what is the type of cell adaptation involved in this case? And discuss its mechanism of cellular adaptation.

METAPLASIA - Barrett's esophagus (sometimes called Barrett esophagus, or columnar epithelium lined lower oesophagus (CELLO), Barrett syndrome) refers to an abnormal change (metaplasia) in the cells of the lower portion of the esophagus. It is characterized by the replacement of the normal stratified squamous epithelium lining of the esophagus by simple columnar epithelium with goblet cells (which are usually found lower in the gastrointestinal tract) due to cell adaptation.

The concept of Barret's esophagus is simple. The normal squamous mucosa of the esophagus is replaced by glandular mucosa as an adaptive process usually because there is a reflux of the gastric (highly acidic) materials from the stomach into the esophagus and therefore, the esophagus responds by becoming more gastric-like and less squamous-like since gastric mucosa (simple columnar) has tall columnar epithelial cells which secretes a layer of thick mucus that protects from gastric materials which the former squamous cells do not have.Columnar metaplasia of the distal esophagus represents a squamous to columnar metaplastic reaction that develops from an esophageal stem cell and may pass through an intermediate phase characterized by the presence of a type of epithelium that possesses a mixture of squamous and columnar features, termed multilayered epithelium.

3. What is the most likely cause?We need to take special considerations on such morphological change in the patients epithelial lining. Basing on the case, the patient has been smoking since 13 years of age and has been consuming 5 bottles of beer every night.Smoking weakens the lower esophageal sphincter, the muscle between the esophagus and stomach that keeps contents from flowing back into the esophagus. The stomach is naturally protected from the acids it makes to help break down food. However, the esophagus is not protected from the acids. When the LES weakens, stomach contents may reflux into the esophagus possibly damaging the lining of the esophagus. Furthermore tobacco smoke has chemical that may cause mucosal irritation to cells.Alcohols effect on the body on the other hand is that it may cause direct damage to esophageal and gastric mucosae. In addition, toxic acetaldehyde metalize from alcohol could affect the function of the esophagus and stomach. It is also a depressant and relaxant which may contribute to its effect on the LES thereby initiating reflux of the gastric acids into the esophagus thereby eliciting changes in cell structure just like tobacco. In addition alcohol potentiates the depressant effect of nicotine in the CNS thereby affecting the muscle tone of the LES.Alcohol and tobacco paves the way for acid reflux into the esophagus through its effect on the LES. Presence of acid in the esophagus initiates compensatory mechanisms in the cells to adapt to this new environment hence the metaplasia observed in the esophageal lining.4. Is this physiologic or pathologic? Reversible or irreversible?

This is a pathologic form of metaplasia, since the change is caused by chronic irritation of the lower esophagus by the reflux of hydrochloric acid from the stomach and carries with it undesirable effects such as the ones experience by the patient. However, the change in the epithelium is reversible if the patient undergoes a combination of anti-reflux therapy and endoscopic thermal injury.

5. What other types of cellular adaptation? Discuss and differentiate each type as to its causes, mechanism, microscopic findings, and give examples.Cellular AdaptationCausesMechanism

Hypertrophy Increased functional demand Stimulation by hormones and growth factorsMechanical stretch/agonists/growth factors|Signal transduction pathways|Transcription factors|Increased synthesis of contractile proteinsIncreased induction of embryonic/fetal genesIncreased production of growth factors

HyperplasiaPhysiologic Hormonal CompensatoryPathologic Excess hormones or growth factors acting on target cells Growth factor-driven proliferation of mature cells Increased output of new cells from tissue stem cells

AtrophyPhysiologic Normal developmentPathologic Decreased workload (atrophy of disuse) Loss of innervation (denervation atrophy) Diminished blood supply Inadequate nutrition Loss of endocrine stimulation Pressure Decreased protein synthesis Increased protein degradation in cells Increased autophagy

Cellular AdaptationMicroscopic FindingsExamples

Hypertrophy Increase in the size of the cells, resulting to increase size of the organ No new cells, just larger cells

The most common stimulus for hypertrophy of muscle is increase workload for example, the bulging muscles of bodybuilders engaged in pumping iron result from an increase in size of the individual muscle fibers in response to increased demand.

In the heart, the stimulus for hypertrophy is usually chronic hemodynamic overload, results from either hypertension or faulty vales

Physiologic hypertrophy of the uterus during pregnancy. A, Gross appearance of a normal uterus (right) and a gravid uterus (removed for postpartum bleeding) (left). B, Small spindle-shaped uterine smooth muscle cells from a normal uterus, compared with C, large plump cells from the gravid uterus, at the same magnification.

Hyperplasia Increase in the number of cells in an organ or tissue Takes place if the cell population is capable of dividingHormonal hyperplasia is well illustrated by the proliferation of the glandular epithelium of the female breast at puberty and during pregnancy. Usually accompanied by enlargement (hypertrophy) of the glandular epithelial cells.

(a) Macroscopic aspect of a normally regenerating liver. (b) Pale liver with hemorrhage resulting from stenosis of the suprahepetic vena cava. (c) H&E staining of a normally regenerating liver section (400 original magnification). Note the number of mitotic figures present in the section (black arrows). (d) H&E staining of the liver shown in panel (b) (200 original magnification). Note the presence of necrotic areas (asterisk).

Atrophy Reduced in size of an organ or tissue resulting from a decrease in cell size and numberCarpal Tunnel Induced Atrophy: Chronic, severe compression of the median nerve within the carpal tunnel has led to atrophy of the Thenar muscles (hand on right). A normal appearing Thenar Eminence is demonstrated on left.

Normal brain of a young adult. B. atrophy of the brain in an 82 years old male with atherosclerotic cerebrovascular disease, resulting in reduce blood supply. Note that loss of brain substance narrows the gyri and widens the sulci. The meninges have been stripped from the right half of each specimen to reveal the suface of the brain

6. Discuss the clinico-pathologic correlations of cell adaptation in this case.

Barrett esophagus is a complication of chronic GERD that is characterized by intestinal metaplasia within the esophageal squamous mucosa. Barrett esohagus most common in males and it typically presents between 40 and 60 years of age.Prolonged exposure of the esophagus to the refluxate can erode the esophageal mucosa, promote inflammatory infiltrate, and ultimate epithelial necrosis. This chronic damage is believed to promote the replacement of healthy esophageal epithelium with the metaplastic columnar cells of the Barrett esophagus, the cellular origin of which remains unknown. This likely is an adaptive response of the esophagus, which, if not for the increased rate of cancer, would have been beneficial.Smoking prevents production of bicarbonate ions by reducing synthesis of prostaglandins, which controls bicarbonate secretion. It also causes alterations in the epithelial barrier leading to changes in the composition of the underlying immune cell population. One of the components of tobacco is nicotine, which increases acid and pepsin secretion, as well as,gastric motility.Alcohol impairs the ability of the lower esophageal sphincter (LES) to contract. Prolonged use damages the protective mucosa in the esophagus and leads to changes in cells that causes overproduction of gastric acid.Barrett esophagus can be recognized as one or several tongues or patches of red, velvety mucosa extending upward from the gastroesophageal junction. This metaplastic mucosa alternates with residual smooth, pale squamous (esophageal) mucosa and interfaces with light-brown columnar (gastric mucosa distally). The secretory columnar epithelium can resist the erosive action of the gastric secretions, suggesting that they may be an adaptation to the chronic acid exposure. Columnar epithelium has a reddish color and velvet-like texture from the pale, glossy appearance of squamous epithelium.Goblet cells normally line the intestines, not the esophagus. When goblet cells develop in a place where they are not supposed to be, like the lining of the esophagus, it is called intestinal metaplasia. Intestinal metaplasia can develop any place where squamous mucosa is normally found. When intestinal metaplasia occurs in the squamous mucosa it is called Barrett esophagus.Diagnosis of Barrett esophagus requires both endoscopic evidence of abnormal mucosa above the gastroesophageal junction and histologically documented intestinal metaplasia. Goblet cells, which have distinct mucous vacuoles that stain pale blue by H & E and impart the shape of a wine goblet to the remaining cytoplasm define intestinal metaplasia and are necessary for diagnosis of Barrett esophagus.ModifiableNon-modifiableSmoking at the age of 13Age- 50 years oldConsumes 5 bottles of beer/nightsex-maleHistory of burning and belching after meals

Smoking Chronic GERD Alcohol

Prevents HCO3 productiondec. LES tonedirect damage to LESdirect cell injury

Inc. gastric acid productioninc. reflux of gastric juices

Alteration in the epithelial barrierCellular injury

Cellular adaptationMETAPLASIAcellular adaptation

Change of squamous epithelium To columnar type

Red, velvety mucosa on gastroesophageal Junction upon endoscopy