Digestive System Disease

Chapter

eight

Digestive System Disease

histology • Lamina mucosa: epithelium, lamina propria, muscular mucosa • Submucosa: loose connective tissue • Muscular propria • Lamina serosa

Section 1 gastritis • Chronic gastritis and acute gastritis • Chronic gastritis is defined as the presence of chronic mucosal inflammatory changes leading eventually to mucosal atrophy and epithelial metaplasia. • Etiology and pathogenesis: Infectious agents: helicobacter pylori: bacterial enzyme, toxin, neutrophils. Chemicals: nonsteroidal anti-inflammatory drugs Autoimmune factor: antibody to parietal cells.

morphology • Inflammatory cells infiltration: usually lymphocytes and plasma cells, in active disease neutrophils infiltrate within the mucosa. • Epithelial degeneration necrosis: • Gland loss and mucosal atrophy: metaplasia • Dysplasia-------carcinoma • Lymphoid tissue proliferation------lymphoma

classification • Chronic superficial gastritis: the lesion within the upper 1/3 of the lamina mucosa Endoscopically, mucosal hyperemia and edema Microscopically, mucosal hyperemia and edema, epithelial necrosis, lamina propria inflammatory infiltration • Chronic atrophic gastritis: Endoscopically, the lamina mucosa turned thinner and pale, the mucosal ruga disappeared, the submucosal vessels appeared. Microscopically, besides the inflammatory infiltration, the glands lost with mucosal fibrosis and intestinal metaplasia, dysplasia

Clinical pathological relation • Symptom Stomach ache Dyspepsia pernicious anemia: lack of intrinsic factor, vitamin B12 shortage, • Treatment: antibiotics to H.pylori

Section 2 Peptic ulcer disease Peptic ulcers are chronic, most often solitary, lesions that occur in any portion of the gastrointestinal tract exposed to the aggressive action of acid-peptic juices. Morphologically, it is a breach in the mucosa that extends through the muscularis mucosa into the submucosa or deeper. Most peptic ulcers are either in the first portion of the duodenum or in the stomach.

Epidemiology Remitting, relapsing lesion are most often diagnosed in middle-aged to older adults, but may appear in young adult life. Common in industrialized nations; prevalence 10% ( American) Male: female ratio 2.5:1.5 (American)

Pathogenesis Still poorly understood. There are two key facts: first, the fundamental requisite for peptic ulceration is mucosal exposure to gastric acid and pepsin. Second, there is a very strong causal association with H.pylori infection.

Aetiology and pathogenesis

Major influences for duodenal ulcers (1) Increased parietal cell mass in the stomach and hence a tendency to secrete more acid and pepsin. Higher basal acid output and increased responsiveness to stimuli of acid secretion. (2) Abnormally rapid gastric emptying , exposing the duodenum to a greater acid load. (3) Personality: stress, anxiety, and fatigue are associated, especially with relapse, but the role of a “type A” personality is not proved. (4) Other possible influence: Helicobacter pyloris, alcohol, tobacco use, unbuffered aspirin, corticosteroids. Most patients with duodenal ulcers secrete a greater than normal amount of gastric acid and have a greater than normal number of parietal cells in the stomach.

Major influences for gastric ulcers (1) Tendency toward low-to-normal levels of gastric acid, but no true achlorhydria. (2)  Most likely a primary defect in gastric mucosal resistance to acid with a tendency toward increased backdiffusion of acid. (3)  Frequent association of chronic antral gastritis with the ulcer; this may have a causal role because gastritis persists after healing of the ulcer. (4) May involve decreased pyloric sphincter tone, and reflux of bile acids and lysolecithin.

Major influences for gastric ulcers (5) Exogenous agents that damage the mucosa are more likely to cause gastric ulcers than duodenal ulcers, e.g., unbuffered aspirin, alcohol, nonsteroidal antiinflammatory agents and other drugs. (6) Possible defect in gastric mucus with the presence of Helicobacter. (7) Predilection for the antral mucosal region in the area crossed by a band of muscle may be related to muscle tension–induced decrease in mucosal blood flow. The patients with gastric ulcer are associated with a normal or low amount of gastric secretion with no increase in the number of parietal cells

Morphology 80% are solitary lesions, with coexistence of gastric and duodenal ulcers in 10 to 20%.

•Gastric ulcers location They are located primarily along the lesser curvature, mainly in the antrum, the posterior wall near the lesser curvature, and are typically small, but size does not help differentiate between cancerous and benign gastric ulcers.

•Duodenal ulcers location They are located primarily in the first portion of the duodenum, within a few centimeters of the pylorus, more often the anterior wall and posterior wall. Classic peptic ulcer is a round-to-oval, sharply punched-out defect with relatively straight walls and essentially flat adjacent mucosa. The surrounding mucosal folds may radiate like wheel spokes.

Pathologic change

•Histologic zones (1)   Superficial layer of necrotic debris, (2)  Zone of active predominating,

inflammation

with

neutrophils

(3)   Active granulation tissue, (4)   A base of scar tissue. Arteritis and arterial occlusion

•Surrounding wall Mixed inflammation of mucosa (including eosinophils), thickened blood vessels, gastric or duodenal arteries may be eroded ,with disastrous results, widely ramifying scar tissue.

     Duodenal ulcers Pain approximately 90 minutes after a meal, relieved by milk, food, antacids, vomiting.

     Gastric ulcers Pain may begin approximately 30 minutes after a meal, and is not relieved by eating.

Complications •Bleeding A erosion of small artery in the base of a gastric ulcer thus causes bleed, which may be massive or occult repeated small hemorrhages results in the vomiting of blood or hematemesis and subsequently in melaena, produce secondary anemia, severe hemorrhages may produce fatal.

•     Perforation The ulcerating process may extend deep into the muscular layer and even right through the wall to perforate into the peritoneal cavity causing shock and peritonitis: slow penetration results in a fibrous reaction.

•

Pyloric obstruction

•     Stenosis from edema or scarring •

Malignancy change

Malignancy dose not occur with duodenal ulcers; in a gastric ulcer it most likely represents ulceration of a preexisting gastric cancer.

Consequence and complications • Healing • Hemorrhage • Perforation • Pyloric stenosis • Malignant transformation

 Clinical features • Chronic, recurring lesions Typically burning /gnawing intermittent, relatively regularly, epigastric pain.

Section 2

Viral hepatitis

Aetiology and pathogenes HAV

HBV HCV HDV HEV HFV

The term viral hepatitis refers to hepatitis caused by hepatotrophic virus,the hepatitis virus ,although a generally mild involvement of the liver is usually seen in some systemic viral infectious such as infections mononucleosis. yellow fever and cytomegalovirus infectious, six hepatitis viruses are identified:

 Etiology and pathogenesis Hepatitis viruses characteristics (table 1)

Pathology All the hepatotropic viruses cause essentially similar clinial and morphologic pattern of hepatitis.

Liver cell degeneration and necrosis (1) Hepatocytes swelling ,”ballooning” because hydropic distention of endoplasmic reticulum and call ballooning degeneration, fat degeneration often appear in hepatitis C ,rare in other types. (2) Eosinophilic change or necrosis. Single cell death appear eosinophilic rounded up cells called acidophilic body or Councillman bodies ,belong to cell apoptosis. (3) Spotty necrosis. Small focal necrosis scattered in lobules, only involvement single or a few hepatocyto with inflammatory infiltration.

(4) Lytic necrosis.that more often driver from balloning degeneration. Fulminant hepatitis often show this appearance. (5) Piecemeal necrosis:inflammatory cells in direct contact with live cells that are undergoing degeneration and fragmentation,lending a “moth-eaten” appearance to the limiting plate(a characteristic feature) (6) Bridging necrosis:confluent necrosis of hepatocytes leading to collapse of the reticulin framework,linking portal-central,portal-portal or/and central-central areas. Progresive fibrosis extending from the portal tracts into the hepatic parenchyma, leading in many cases to a fully developed cirrhosis.

Inflammatory infiltration It includes lymphocytes, mononuclear cells and a few plasma cell and leukocytes.

Stroma reactive proliferations and hepatocytes regeneration. (1) Kuffer’s cell hyperplasia and hypertrophy (2) Menigi and fibroblast proliferations. A number of fibroblast proliferation progressively may result in liver fibrosis and cirrhosis (3) Hepatocytes regeneration:when hepatocytes develop necrosis , nearly normal hepatocytes regeneration and repair by directly or indirectly mitosis. The regeneration cell larger often with bi and tri nucleate hepatocytes, chronic cases appear proliferating ductules:

Clinical pathologic types Two types were divided for general and fulminant types. General type progressively divided into chronic and acute types,with jaundice or not.

 Acute hepatitis (1) Morphology Gross: The liver is slightly enlarged and more or less green, dependingon the degree of hepatocellular damage and jaundice. Microscopy: Necrosis of scattered hepatocytes. clumps, or an entire lobule. Isolated necrotic hepatocytes appear as eosinophilic rounded- up cells and lymphocytes may be nearby. Degenerated hepatocytes may also appear ballooned. Inflammatory infiltration in portal spaces. Macrophages engulf necrotic hepatocytes. Clumps of macrophages persist for some time and are indicative of previous hepatocyte necrosis. Disruption of lobular architecture by necrosis is called lobular disarray.Ancillary features include hypertrophy and probably hyperplasia of Kunffer cells and sinusoidal lining cells, and infiltration of portal tracts with inflammatory cells

① Cholestasis is an inconstant feature. ② During the recovery phase, bi- and trinucleate hepatocyles and mitotic figures attest to hepacocyte regeneration. ③ Prognosis: More severe necrosis may result in confluent areas of necrosis linking central and portal areas (termed bridging necrosis). a feature some believe to be a harbinger of progression to chronic disease . About 5-10% HBV 50%HCV infection hepatitis develop into chronic hepatitis. About l% or less of cases of acute hepatitis run a fulminant course with submassive or massive liver necrosis and a high mortality rate.

Chronic hepatities Defined as biochemical or serologic evidence of continuing inflammatory hepatic disaese for more than 6 months, with symptoms and without steady improvement. Follow 5-10% of acute hepatitis,30-40% of acute C type hepatitis. (1) Mild degree:there are spotty necrosis occasionally with light piecemeal necrosis, periportal fibrosis,and lobules structures appear normal . (2) Moderation degree: appearance of necrosis, moderationpiecemeal and bridging necrosis, fibronic space formation and lobules structures keep more complete.

(3) Severe degree widely hepatocytes necrosis, Severe degree piecemeal hepatocytes necrosis and large areas bridging necrosis. Hepatocytes happen irregularly regeneration in necrotic areas. Fibronic bands link lobules structures. Late stage it may convert into cirrhosis, ground –glass hepatocytes may be present in HBV infection. That cell appear eosinophilic granules in cytoplasm and elecmicroscopily line or tubular structure in endoplasmic reticulum. and immunohistochemically HBsAg positive reaction.

 Massive Necrosis (Fulminant Hepatitis) Defined as hepatic insufficiency progressing from onset to death (or hepatic transplantation) within 2 to 3 weeks. A less rapid course extending up to 3 months is termed submassive necrosis. (1) Etiology Viral hepatitis accounts for 50 to 65% of cases. But it may also result from drugs. poisoning (e.g., ,Amanita phalloides). Ischemia and vascular catastrophe, hyperthermia (heat stroke). massive malignant infiltration of the liver, Wilson's disease, microvesicular steatosis (in Reye's syndrome, in acute fatty liver of pregnancy, or drug related), autoimmune hepatitis, and reactivation of chronic HBV with or without HDV.

 Morphology The entire liver may be involved or only portions. with massive involvement. the liver shrinks to as little as 500 to 700 gm and becomes a red limp organ covered by a wrinkled, too large capsule. Blotchy bile staining may be present and the cut surface has a muddy red. mushy appearance with patchy blue staining. Entire lobules or portions thereof may be necrotic.with Liquefaction of hepatocytes and collapse of the reticulin framework. There may be surprisingly little inflammatory reaction.

Clinical feature Hepatic failure may result in hepatorenal syndrome and jaudice ,bleeding, DIC and etc.

Pathologic change 1. Degeneration and necrosis of hepatocytes (1) Rarefaction and ballooning degeneration (2) Acidophilic degeneration and acidophilic necrosis

(3) Spotty necrosis

(4) Lytic necrosis

(5) Piecemeal necrosis

(6) Bridging necrosis

2. Inflammatory infiltration 3. Stromal reactive hyperplasia and regeneration of hepatocytes (1) Proliferation of Kuppfer cells (2) Proliferation of mesenchymal cells and fibroblasts (3) Regeneration of hepatocytes

Clinic-pathologic correlation acute ordinary

non-jaundiced jaundiced slight

Hepatitis

chronic

middling severe

fulminant

acute subacute