Esophagus
ď Ž
Normal esophageal mucosa appears white to tan www.indiandentalacademy.com
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ď Ž ď Ž
Esophageal mucosa is lined by non-keratinized stratified squamous epithelium www.indiandentalacademy.com Gastric mucosa is lined by columnar glandular epithelium
Selected disorders of the esophagus
Motor disorders: Achalasia Mechanical injury: Lacerations (Mallory-Weiss syndrome) Varices Esophagitis: Reflux, infections, drugs, irradiation Barrett’s esophagus Malignant neoplasms www.indiandentalacademy.com
Achalasia (failure to relax)
Incomplete relaxation of lower sphincter during swallowing leading to functional obstruction and proximal dilatation Aperistalsis, incomplete relaxation, increased resting tone Ganglion cells of the myenteric plexus are diminished or absent Loss of inhibitory innervation to the sphincter Clinical picture: dysphagia, regurgitation and aspiration Histology: Inflammation in the area of M. plexus Hypotheses: autoimmune, viral infections May occur secondary to Trypanosoma cruzi infection (Chagas disease) 5% develop squamous cell carcinoma, at younger age www.indiandentalacademy.com
Esophageal lacerations (MalloryWeiss syndrome)
Longitudinal tears at the gastroesophageal junction Clinical setting: chronic alcoholics after a bout of severe vomiting Tear may be superficial or deep affecting all layers Clinical picture: Pain, bleeding, superimposed infection Hiatal hernia is found in 75% of patients Most often bleeding stops w/o intervention, but lifethreatening hematemesis may occur. Supportive therapy and balloon tamponade. Healing is prompt with minimal or no residue www.indiandentalacademy.com
Hiatal hernia Dilatation of the space between the diaphragmatic muscles which permits a dilated segment of the stomach to protrude above the diaphragm. 95%
5%
1-20% of adult subjects; only 9% of those affected suffer from heartburn www.indiandentalacademy.com and reflux esophagitis; complications may include ulceration and bleeding
Esophagitis
Reflux esophagitis Infections Crohn disease, acute graft versus host disease Prolonged gastric intubation Ingestion of irritant substance Chemotherapy and irradiation www.indiandentalacademy.com
Reflux esophagitis
Reflux of gastric contents into esophagus Possible etiologies: inadequate function of lower sphincter; sliding hiatal hernia CP: “heart burn” Complications: ulceration, bleeding, stricture, Barrett esophagus www.indiandentalacademy.com
Infection-induced esophagitis
More common in patients with impaired immunity Fungal : Candida Viruses: Herpes and Cytomegalovirus www.indiandentalacademy.com
Barrett esophagus
A complication of long standing reflux esophagitis Replacement of squamous epithelium by columnar epithelium with goblet cells 30- to 40-fold greater risk to develop adenocarcinoma www.indiandentalacademy.com
Esophageal varices
ď Ž
Tortuous dilated veins in the submucosa of distal esophagus www.indiandentalacademy.com
Esophageal varices
Etiology: portal hypertension secondary to liver cirrhosis Asymptomatic until they rupture leading to massive hemorrhage 50% subsides spontaneously 20-30% die during the first episode Rebleeding occurs in 70% of cases within one year www.indiandentalacademy.com
Esophageal carcinoma
Squamous cell carcinoma
More prevalent worldwide Risk factors: long-standing esophagitis, achalasia, smoking, alcohol, diet (low vitamins and zinc), genetics 50% in middle 1/3
Adenocarcinoma
More common in USA Occurs on top of Barrett esophagus More in distal 1/3
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Stomach 2 1 3
1) Cardia 2) Body: Parietal and Chief cells 3) Antrum: Mucin secretion and Gcells that secrete gastrin www.indiandentalacademy.com
Selected disorders of the stomach
Gastritis Peptic ulcers Gastric cancer
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Chronic Gastritis
Infiltration of the mucosa by chronic inflammatory cells (lymphocytes and plasma cells) Causes:
Helicobacter pylori: G-ve bacilli; Noble prize in Medicine 2005, for Barry Marshal & Robin Warren Autoimmune: rare in USA, autoantibodies to parietal cells (decreased acid and intrinsic factor)
Helicobacter pylori is present in 70-90% of patients with gastric and duodenal ulcers, respectively Look for intestinal (goblet cell) metaplasia as a precancerous lesion www.indiandentalacademy.com
Helicobacter pylori and associated disorders
H. pylori
Gastric ulcer
Gastritis (chronic and acute), peptic (gastric and duodenal) ulcers Gastric adenocarcinoma, intestinal type Gastric lymphoma www.indiandentalacademy.com
Mechanisms of H. pylori-induced pathology
Although the organism is not invasive, it induces intense inflammatory and immune response: cytokines and B-cell activation Enhances gastric acid secretion Bacterial products such as urease, lipases and proteases that induce epithelial injury
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Acute gastritis “gastropathy”
Injury to the gastric mucosa (erosions) with no significant participation of inflammatory cells Causes include: Non-steroidal antiinflammatory drugs Alcohol Hypovolemia Shock Stress Uremia Enterogastric reflux
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Peptic ulcer
Location: stomach or first portion of duodenum Life time risk is 10% in the USA More frequent in patients with alcoholic cirrhosis, chronic obstructive pulmonary disease, chronic renal failure and hyperparathyroidism. Causes include: H. pylori and causes of acute gastritis (especially NSAID) Clinical features: Epigastric pain (worse at night and relieved by food), bleeding (30%) and perforation (5%; accounts for 2/3 of deaths). www.indiandentalacademy.com
Gastric cancer
Intestinal-type:
Risk factors: diet (nitrites, smoked food, increased salt), chronic gastritis (H. pylori), altered anatomy after resection On top of intestinal metaplasia Decreasing in incidence Glandular morphology
Diffuse-type: Undefined risk factors ( no known relation to H. pylori) Signet cell morphology
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Macroscopic growth patterns of gastric adenocarcinoma Mass
Ulcer
Lintis plastica
Clinical picture: asymptomatic or abdominal discomfort, weight loss, anemia www.indiandentalacademy.com
Small and large bowel
Developmental: Meckel diverticulum Vascular Diarrheal disease: Infections: viruses, bacteria, protozoa Idiopathic inflammatory bowel disease Malabsorption
Diverticular disease Tumors www.indiandentalacademy.com
Meckel diverticulum Meckel diverticulum
A blind pouch located in distal small bowel The most common congenital anomaly of the small intestine; results from failure of the involution of the omphalomesenteric (vitelline) duct The rule of 2’s:
2% of the population, 2 inches in length, 2 feet proximal to the ileocecal valve, 2 types of heterotopic tissue (pancreas and stomach); 2% are symptomatic.
Symptoms are rare:
Overgrowth of bacteria that depletes vitamin B12 leading to anemia “Peptic” ulcer and bleeding www.indiandentalacademy.com
Types and causes of diarrheal illness
Secretory diarrhea: loss of intestinal fluid that is isotonic with plasma and persists during fasting Viruses: rotavirus: destroy the absorptive surface children 6-24 M of age, 130 million cases per year, fecal oral mode of transmission. Toxin-mediated: Vibrio cholera, E.coli (need time) Preformed toxin: Stapylococcus aureus (immediate effect) Excessive laxatives
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Types and causes of diarrheal illness, continued
Osmotic diarrhea: secondary to intraluminal fluids with high osmolarity; it abates with fasting.
Specific therapies: Lactulose therapy: used for constipation and hepatic encephalopathy Gut lavage before endoscopy Antacids
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Types and causes of diarrheal illness, continued
Exudative diarrhea: pruluent bloody stool (inflammation of the mucosa and/or hemorrhage) Infections causing tissue damage: Shigella, Salmonella, Entamoeba histolytica Infections causing both tissue damage and toxins: Clostridium difficile; with antibiotic therapy, leading to pseudomembranous colitis Idiopathic inflammatory bowel disease
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Parasites
Entamoeba histolytica: Invasive, amebic colitis and amebic liver abscesses Giardia lamblia: noninvasive, duodenum and jejunum, diarrhea and malabsorption Cryptosporidium: self-limited diarrhea in immunocompetent individuals; long course in AIDS patients Worms: uncommon in USA www.indiandentalacademy.com
Types and causes of diarrheal illness, continued
Exudative diarrhea: pruluent bloody stool (inflammation of the mucosa and/or hemorrhage) Infections causing tissue damage: Shigella, Salmonella, Entamoeba histolytica Infections causing both tissue damage and toxins: Clostridium difficile; with antibiotic therapy, leading to pseudomembranous colitis Idiopathic inflammatory bowel disease
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Pseudomembranous colitis
ď Ž ď Ž
Membranes made of neutrophils and fibrin Seen in Cl. Difficile infection and in ischemia www.indiandentalacademy.com
Types and causes of diarrheal illness, continued
Exudative diarrhea: pruluent bloody stool (inflammation of the mucosa and/or hemorrhage) Infections causing tissue damage: Shigella, Salmonella, Entamoeba histolytica Infections causing both tissue damage and toxins: Clostridium difficile; with antibiotic therapy, leading to pseudomembranous colitis Idiopathic inflammatory bowel disease
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Idiopathic inflammatory bowel disease Crohn disease
Small bowel and colon (mostly right side) Patchy involvement Transmural inflammation, fistulas, strictures, serositis Non-caseating granulomas Poor response to surgery Increased risk for cancer
Ulcerative colitis
Colon only Continuous involvement Superficial inflammation No granulomas Good response to surgery Increased risk for cancer
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Types and causes of diarrheal illness, continued ď Ž
Malabsorption diarrhea (steatorrhea): voluminous bulky stool with increased osmolarity resulting from unabsorbed nutrients and excess fat; usually abates on fasting. ď Ž
Malabsorption syndromes
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Malabsorption syndromes
Defective intraluminal digestion: pancreatic insufficiency Defective bile secretion Mucosal abnormalities: Disaccharide deficiency (lactose intolerance) Reduced surface area Gluten-sensitive enteropathy (Celiac disease) Surgical resection Infections: Tropical sprue, whipple disease www.indiandentalacademy.com
Selected malabsorption syndromes
Gluten-sensitive enteropathy (celiac disease): 1:300 persons are affected, hypersensitivity to gliadin, a component of gluten (present in wheat flour) leading to blunted villi and increased intraepithelial lymphocytes. Increased risk for lymphoma. Tropical sprue: malabsorption and diarrhea after a visit to the tropics. Infectious etiology, responds to antibiotics. Whipple disease: systemic disease that affects GIT, nervous system and joints. Caused by T. whippelii (gram-positive actinomycete). www.indiandentalacademy.com
Clinical features of malabsorption syndromes
Hematopietic system:
Musculoskeletal system:
Amenorrhea, impotence, infertility
Skin:
Osteopenia: calcium and vitamin D deficiency
Endocrine system:
Anemia: iron, folate and B12 deficiency Bleeding: vitamin K deficiency
Purpura: vitamin K deficiency Dermatitis: vitamin A deficiency
Nervous system:
Peripheral neuropathy: folate and B12 deficiency. www.indiandentalacademy.com
Diverticulosis
Herniation of the mucosa and submucosa through the muscle wall 50% after age 50 Related to low-fiber diet, increased intraluminal pressure and focal defects in muscular layer Mostly in sigmoid colon Asymptomatic unless infected www.indiandentalacademy.com
Tumors of the large bowel
Hyperplastic polyps: not precancerous Adenomatous polyps: precancerous Familial polyposis syndrome: Autosomal dominant; 500-2500 polyps, 100% risk for developing cancer; mutations in APC gene
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Colonic adenocarcinoma:
Almost always arises from adenomatous polyp Risk factors: low fiber, high fat, decreased vit A, C, E, idiopathic inflammatory bowel disease, familial adenomatous polyposis Several hits to different genes: APC, k-ras, p53; or DNA mismatch repair genes Survival depends on stage (depth of invasion and node metastasis) www.indiandentalacademy.com
Colonic adenocarcinoma Exophytic tumor leading to partial obstruction
ď Ž
Clinical picture: Asymptomatic or fatigue, weakness and iron deficiency anemia in tumors of right side. Left sided tumors may produce bleeding, change in bowel habits and crampy pain www.indiandentalacademy.com
Colonic adenocarcinoma ď Ž
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Course: tumor invades bowel wall and lymphatics/blood vessels with metastasis to lymph nodes, liver, lungs, and bones. 25% of patients have metastatic disease at presentation Diagnosis is based on endoscopy and biopsy Prognosis depends on stage (depth of invasion, nodal and distant metastasis), and 5-year survival varies from >90% in stage I, to 4% with distant metastasis. www.indiandentalacademy.com
ď Ž
A 47-year-old man has a history of drinking 1 to 2 liters of whisky per day for the past 20 years. He has had numerous episodes of nausea and vomiting in the past 5 years. He experiences a bout of prolonged vomiting, followed by massive hematemesis. On physical examination in the emergency room, he has vital signs with T 36.8 C, P 110, RR 22, and BP 80/40 mm Hg. His heart has a regular rate and rhythm with no murmurs and his lungs are clear to auscultation. There is no abdominal tenderness or distension and bowel sounds are present. His stool is negative for occult blood. Which of the following is the most likely diagnosis? 1. 2. 3. 4. 5.
Barrett’s esophagus Esophageal stricture Esophageal lacerations (Mallory Weiss syndrome) Esophageal squamous cell carcinoma Achalasia www.indiandentalacademy.com
ď Ž
All these statements about Barrett’s esophagus are true, except: 1.
2. 3. 4.
5.
It is associated with 30- to 40-fold greater risk to develop adenocarcinoma It appears as salmon-pink mucosa on endoscopy It is associated with high risk for esophageal bleeding It represents replacement of the stratified squamous epithelium by columnar epithelium with goblet cells It could be a complication of long-standing reflux esophagitis www.indiandentalacademy.com
ď Ž
All these statement about Helicobacter pylori are correct except: 1. 2.
3. 4.
5.
H. pylori organisms are Gram negative bacilli It is associated with intestinal-type gastric adenocarcinoma It is associated with gastric lymphoma It is associated with diffuse-type gastric adenocarcinoma It is associated with peptic ulcer
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ď Ž
1. 2. 3. 4.
A 20-year-old man has noted cramping abdominal pain for the past week associated with fever and lowvolume diarrhea. On physical examination, there is right lower quadrant tenderness. Bowel sounds are present. His stool is positive for occult blood. A colonoscopy reveals mucosal edema and ulceration in the ascending colon, but the transverse and descending portions of the colon are not affected. Which of the following microscopic findings is most likely to be present in biopsies from his colon Entamoeba histolytica organisms Adenocarcinoma Non-caseating granulomas Diverticulosis www.indiandentalacademy.com
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1. 2. 3. 4. 5.
A 35-year-old woman has a 10 year history of intermittent, bloody diarrhea. She has no other major medical problems. On physical examination there are no lesions palpable on digital rectal examination, but a stool sample is positive for occult blood. Colonoscopy reveals a friable, erythematous mucosa with focal ulceration that extends from the rectum to the mid-transverse colon. Biopsies are taken and all reveal mucosal acute and chronic inflammation with crypt distortion, occasional crypt abscesses, and superficial mucosal ulceration. This patient is at risk for development of which of the following conditions? Diverticulitis Acute pancreatitis Colonic adenocarcinoma Peri-rectal fistula Appendicitis www.indiandentalacademy.com
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1. 2. 3. 4. 5.
A 25-year-old man complains of a low volume but chronic, foul smelling diarrhea for the past year. He has no nausea or vomiting. On physical examination there is no abdominal pain or masses and bowel sounds are present. His stool is negative for occult blood. Laboratory studies include a quantitative stool fat of 10 g/day. Upper GI endoscopy is performed with biopsies of the duodenum. The biopsies reveal the absence of villi, and increased surface intraepithelial lymphocytes. Which of the following therapies is most likely to be useful for this man? Antibiotics Anti-Entamoeba therapy Corticosteroids Gluten-free diet Surgical resection www.indiandentalacademy.com
Diseases of the liver
Sherif Tawfic, MD, Ph.D. Surgical Pathology Fairview University Medical Center, and University of Minnesota tawfi001@umn.edu
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Liver Normal liver has smooth brown surface Weight: 1200-1600 g
Maintaining body metabolic homeostasis:
Lipid and carbohydrate metabolism: production and secretion of glucose Protein synthesis: albumin, coagulation factors Detoxification and drug metabolism Conjugation and excretion of bilirubin Synthesis and excretion of bile salts www.indiandentalacademy.com
Liver anatomy and histology
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Patterns of hepatic injury
Inflammation Steatosis: accumulation of fat droplets within hepatocytes Cell death: those cells closer to the central vein are more susceptible to ischemia, toxins and drugs leading to “centrilobular” necrosis Fibrosis: Irreversible, affect blood flow and hepatocyte function Cirrhosis: End stage liver disease with diffuse fibrosis and regenerating nodules www.indiandentalacademy.com
Steatosis Alcohol Obesity Diabetes Hyperlipidemia
Clinical picture: Silent, or fatigue, malaise, right upper quadrant discomfort www.indiandentalacademy.com
Liver cirrhosis ď Ž
Definition: bridging fibrous septa and parenchymal nodules with disruption of architecture. End stage for many diseases affecting the liver
Mechanism: cell death, regeneration and fibrosis www.indiandentalacademy.com
Clinical consequences of liver disease (life-threatening complications are in yellow)
Hepatic dysfunction:
Decrease synthesis capacity leading to :
Decrease detoxification capacity leading to:
Hypoalbuminemia: edema, ascitis, muscle wasting, weight loss Hypoglycemia: weakness and syncope Coagulation factor deficiency: bleeding Hyperammonemia and increase toxic metabolites: Encephalopathy (altered behavior and disturbances in consciousness that may lead to deep coma and death) Injury to other organs by active toxins
Hepatorenal syndrome:
Renal failure without intrinsic or functional causes of renal failure. ? Altered blood flow to the kidney. www.indiandentalacademy.com
Clinical consequences of liver disease, continued
Jaundice: yellow discoloration of skin and sclera due to accumulation of bilirubin Cholestasis: systemic accumulation of bilirubin in addition to bile salts and cholesterol (usually secondary to obstruction) Portal hypertension in cirrhosis: increased resistance to portal blood flow
Esophageal varices Ascitis Splenomegaly Hemorrhoids
Malignancy on top of cirrhosis www.indiandentalacademy.com
Jaundice
Accumulation of bilirubin in tissue leading to yellow discoloration of skin and sclera (icterus) Normal serum level: 0.3-1.2 mg/dl; jaundice appears with levels above 2.0-2.5 mg/dl Source of bilirubin: the breakdown of senescent red blood cells in the spleen releases heme that changes into bilirubin by specific enzymes.
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Bilirubin
Conjugation is a function of the liver by adding glucuronic acid to bilirubin
ď Ž -
Unconjugated Albumin bound Insoluble in water, toxic
ď Ž -
-
Conjugated Loosely bound to albumin Water soluble, non-toxic, excreted in urine
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Laboratory evaluation of liver disease
Hepatocyte function:
Hepatocyte injury (enzymes normally present inside the hepatocytes and released with injury):
Serum albumin Prothrombin time: measuring coagulation factors (II, V, VII, X); prolonged in liver cirrhosis Serum ammonia
Serum aspartate aminotransferase (AST) Serum alanine aminotransferase (ALT) Serum lactate dehydrogenase
Biliary excretory function:
Serum bilirubin Serum alkaline phosphatase Serum gamma-glutamyl transpeptidase www.indiandentalacademy.com
Laboratory evaluation of liver disease
Searching for etiology: Hepatitis viral antigens and antibodies Autoimmune antibodies: for autoimmune hepatitis Tissue iron and copper: for hemochromatosis and Wilson disease
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Selected disorders of the liver
Viral hepatitis Drug-induced hepatitis Autoimmune hepatitis Alcoholic hepatitis Hemochromatosis Wilson disease Neoplasms of the liver www.indiandentalacademy.com
Hepatitis A virus RNA virus Mode of transmission: fecal-oral (contaminated water and food) Incubation period: 2-6 weeks Virus shedding: 2-3 weeks before and 1 week after appearance of jaundice 50% of population above age 50 are seropositive in USA, no carrier state No increase risk for chronic hepatitis, or carcinoma Because viremia is transient, no need to screen donated blood
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Hepatitis B virus
dsDNA virus Mode of transmission: parenteral (blood products, contaminated needles and IV drug abuse), and body fluids (including saliva) Incubation period: 4-26 weeks Carrier state: yes, 350 million carriers around the world
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Hepatitis B infection: Possible outcomes
Possible outcomes of infection: Subclinical or acute hepatitis with recovery and clearance (85%); 1% of those may develop fulminant hepatitis and death Healthy carriers (10%) Persistent infection (5%): 80% recover and 20% develop chronic hepatitis 20% of chronic hepatitis patients develop cirrhosis and 10% of those develop hepatocellular carcinoma
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Hepatitis C
ssRNA virus Mode of transmission: parenteral, sexual and vertical, 40% unknown source. It is present in the saliva. Incubation period: 2-26 weeks Outcomes of infection:
HCV is the leading cause for chronic liver disease www.indiandentalacademy.com
Hepatitis D
Defective RNA virus that needs Hep B capsule to replicate Mode of transmission: Parenteral Coinfection of B and D: mild disease with recovery in most cases, <5% chronic hepatitis Superinfection by D after B: accelerated more severe hepatitis; 80% chronic hepatitis
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Hepatitis E
ssRNA virus Mode of transmission: waterborne Incubation period: 2-8 weeks Endemic in certain populations; 40% in Indian population Self-limited infection but with higher mortality in pregnant females www.indiandentalacademy.com
The points to remember Hepatitis A Hepatitis B
Hepatitis C
Transmission Oral-fecal Parenteral
Parenteral
Carrier state
None
Present
Present
Chronic hepatitis
None
5-10%
>70%
Fulminant hepatitis
0.1%
0.1-1.0%
Rare
Carcinoma
No
Yes
Yes
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Drug-indued hepatitis
Predictable or unpredictable (idiosyncrasy) Mechanisms: direct toxicity, conversion of drug to an active toxin, immune-mediated A long list of drugs can cause different forms of injury: hepatitis, fibrosis, granulomas, necrosis, cholestasis, vascular disorders and neoplasia Example: Acetaminophen overdose induces centrilobular necrosis www.indiandentalacademy.com
Autoimmune hepatitis
More in females (70%) The absence of serologic markers for viral hepatitis Elevated serum IgG levels High titers of autoantibodies (antinuclear, anti-smooth muscle, and anti-microsomal) Increased frequency of HLA-B8 and DRw3 Associated with other forms of autoimmune disorders such as rheumatoid arthritis and ulcerative colitis Risk for cirrhosis is 5% Respond to immunosuppressive drugs www.indiandentalacademy.com
Alcoholic liver disease
100,000 death annually related to alcohol; 20,000 are related directly to end-stage liver cirrhosis; the rest is related to car accidents Effects on liver:
80% fatty liver (steatosis) 10% alcoholic hepatitis 10% cirrhosis
Short-term ingestion of 80 g (8 beers) of ethanol per day leads to reversible steatosis Daily ingestion of 160 g for 10-20 years leads to severe injury www.indiandentalacademy.com
Hereditary hemochromatosis
Autosomal recessive disease characterized by increased accumulation of body iron, most of which is deposited in the liver and pancreas. Mostly due to increased iron absorption and accumulation over the years. Normal total body iron is 2-6 g. In hemochromatosis it may reach 50 gm. Due to mutations in the hemochromatosis gene (HFE); a gene that regulates iron absorption. The frequency of being heterozygous is 10% (1 of every ten persons) and that of being homozygous is 0.45% (1 of every 220 persons) www.indiandentalacademy.com
Hereditary hemochromatosis
Excess iron damages DNA, lipids and stimulates collagen formation (fibrosis) Clinical picture: Males are more affected; 50-60 years old Liver cirrhosis, skin pigmentation, diabetes (pancreatic fibrosis), risk for hepatocellular carcinoma. Diagnosis: elevated serum and tissue iron. Early detection and therapy by phlebotomy and iron chelators lead to normal life expectancy
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Wilson disease
Autosomal recessive disorder characterized by accumulation of copper in liver, brain and eyes, among other organs The frequency of being heterozygous is 1:200 (less common than hemochromatosis) The mutated gene (ATP7B) is located on chromosome 13; the mutation leads to failure to excrete copper into bile, and its accumulation in tissue Clinical picture: neuropsychiatric manifestations, acute and chronic liver disease and Kayser-Fleisher rings in the cornea (green to brown deposits) Diagnosis: Clinical picture, increased hepatic and urinary copper, and decreased serum ceruloplasmin (a copper binding protein). www.indiandentalacademy.com
Biliary disease ď Ž
ď Ž
ď Ž
Secondary biliary cirrhosis: secondary to extrahepatic bile obstruction by stones, atresia or tumors Primary biliary cirrhosis: immune-mediated destruction of intrahepatic bile ducts, more in females, presence of anti-mitochondrial antibodies Primary sclerosing cholangitis: chronic fibrosis of intra- and extra-hepatic bile ducts; more in men, association with ulcerative colitis www.indiandentalacademy.com
Tumor of the liver ď Ž
Liver cell adenoma ď Ž
Occurs in women of childbearing age in relation to oral contraceptives; it regresses on discontinuation of hormones
Sheets of hepatocytes with no www.indiandentalacademy.com portal tracts
Well circumscribed mass
Liver cell adenoma
Significance of this benign tumor: It may be mistaken for carcinoma Subcapsular adenomas are at risk for rupture, especially during pregnancy leading to lifethreatening intraabdominal hemorrhage
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Hepatocellular carcinoma (HCC)
Risk factors: Strongly associated with hepatitis B and C infection. The carrier state for hepatitis B carries 200-fold increased risk for HCC Chronic liver disease (e.g. alcohol) Hepatotoxins (aflatoxin present on moldy peanuts and grains)
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Hepatocellular carcinoma
Clinical picture: Often patient already has liver cirrhosis, with rapid increase in liver size, worsening ascites, fever and pain; elevated serum alpha fetoprotein levels (>1000 ng/ml) Median survival is 7 months (death from bleeding, liver failure, or profound cachexia)
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Metastatic carcinoma ď Ž ď Ž ď Ž
The most common malignant tumors in the liver Usually multiple lesions The most common primary sites are colon, lung, breast, pancreas and stomach
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Oral manifestation of liver dysfunction
Hematoma, gingival bleeding Jaundiced mucosa Glossitis (in alcoholic hepatitis) Reduced healing after surgery
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ď Ž
1. 2. 3. 4.
A 48-year-old man has a long history of chronic alcohol abuse. On physical examination his liver is firm on palpation of the abdomen, but does not appear to be enlarged. An abdominal CT scan reveals that the liver has cirrhosis. He joins a support group for persons with chronic alcohol abuse and he stops drinking. Despite his continued abstinence from alcohol, he most likely remains at risk for development of which of the following diseases? Liver cell adenoma Hepatocellular carcinoma Gallbladder stones Lymphoma www.indiandentalacademy.com
ď Ž
1. 2. 3. 4. 5.
A 28-year-old woman with recent onset of depression ingests an entire bottle (100 capsules, 500 mg each) of a medication containing acetaminophen. She becomes progressively obtunded. Which of the following microscopic findings is most likely to be present in her liver 3 days following this ingestion? Normal histology Steatosis Centrilobular necrosis Cirrhosis Chronic inflammation www.indiandentalacademy.com
ď Ž
1. 2.
3. 4.
Hepatitis C infection is characterized by which one of the following: Absence of carrier status Highest incidence of chronic hepatitis among other viral hepatitis No increase risk for hepatocellular carcinoma It can be transmitted by eating contaminated food
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50 year-old male presented with jaundice and pruritus. Lab studies show elevated serum conjugated bilirubin and alkaline phosphatase. ALT and AST levels were only slightly elevated. The most likely diagnosis is: Hepatitis B Steatosis Hepatitis C Extrahepatic bile duct obstruction Autoimmune hepatitis www.indiandentalacademy.com
The Pancreas
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The Pancreas 85% exocrine: enzymes for digestion Acute and chronic pancreatitis Cystic fibrosis Tumors
15% endocrine: insulin, glucagon and others Diabetes Tumors
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Pancreatic exocrine enzymes
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Acute pancreatitis
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Acute pancreatitis
Clinical presentation: abdominal pain radiating to the back, elevated serum amylase and lipase, hypocalcemia Rise in serum lipase is more specific for pancreatitis. Complications: infections, abscess, pseudocyst Mortality is high: 20-40%, from shock, sepsis or acute respiratory failure, acute renal failure, disseminated intravascular coagulation www.indiandentalacademy.com
Chronic pancreatitis
Progressive destruction of pancreatic parenchyma and its replacement by fibrosis Predisposing factors: alcohol, hypercalcemia or idiopathic 30% of idiopathic cases have been found to have mutation in CFTR gene Complications: Pseudocyst, malabsorption, 2ry diabetes Diagnosis: abdominal pain, malabsorption, calcifications on X-ray www.indiandentalacademy.com
Pancreatic adenocarcinoma
The 5th most frequent cause of death from cancer Risk factors: smoking CP: symptoms are late; pain and jaundice Prognosis is poor: 5% survive for 5 years
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Islet cell tumors
Rare compared to adenocarcinoma Insulinomas: secrete insulin ⇒ hypoglycemia ⇒ behavioral changes, confusion and coma. Over 90% are benign Gastrinomas: secrete gastrin ⇒ increase acid production ⇒ duodenal and gastric ulcers
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Gallbladder
Gallstones (cholelithiasis)
Afflict 10% of adult population in Western countries Costs of management: $6 billion a year 20 million patients are estimated to have gallstones totalling several tons Made of cholesterol, bilirubin and calcium salts with different concentrations Two types: cholesterol and pigmented stones www.indiandentalacademy.com
Gallstones
Cholesterol
Western > others Advancing age Female sex Obesity Hyperlipidemia and bile stasis
Pigmented
Asian > Western Hemolytic anemia Biliary infection
Complications: empyema, perforation, fistula, inflammation, obstruction, pancreatitis www.indiandentalacademy.com
Acute cholecystitis
Calculous: acute inflammation of a gallbladder that has stones. It may represent a medical emergency; no associated infection initially Acalculous: no stones, in severely ill patients, severe trauma, burns and sepsis
Chronic cholecystitis
Almost always associated with gallstones www.indiandentalacademy.com
ď Ž
1. 2. 3. 4.
The risks factors for developing acute pancreatitis include all of the following except: Gallstones Hypocalcemia Alcoholism Shock
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ď Ž
1. 2. 3. 4.
All of the following statement about pigmented gallstones are correct except: Hyperlipidemia is a risk factor Hemolytic anemias could be a cause Biliary infections may be present They are more common in Asians
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ď Ž
1. 2. 3. 4.
A 38-year-old woman has experienced episodes of light-headedness, irritability, and difficulty concentrating at her work for the past year. On physical examination there are no abnormal findings. Laboratory studies show her hemoglobin is 14.2 g/dL. An abdominal CT scan shows a 1 cm mass in the tail of the pancreas. Which of the following is the most likely diagnosis? Pancreatic adenocarcinoma Pancreatic pseudo-cyst Insulinoma Chronic pancreatitis www.indiandentalacademy.com
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1. 2. 3. 4.
A 50-year-old man gives a history of chronic alcohol abuse. He has had bouts of abdominal pain in the past year. For the past month, he has had more frequent and worsening abdominal pain. Physical examination reveals right upper and left upper quadrant pain with guarding. An abdominal plain film radiograph reveals no free air, but there is extensive peritoneal fluid collection along with dilated loops of small bowel. An abdominal CT scan reveals a 7 to 8 cm cystic mass in the tail of the pancreas. Which of the following is the most likely diagnosis? Pancreatic adenocarcinoma Metastatic carcinoma Pancreatic pseudocyst Acute pancreatitis www.indiandentalacademy.com
The Pancreas Sherif Tawfic, MD, Ph.D. Surgical Pathology U of MN tawfi001@umn.edu
http://www.tc.umn.edu/~tawfi001/
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A 48-year-old man has a long history of chronic alcohol abuse. On physical examination his liver is firm on palpation of the abdomen, but does not appear to be enlarged. An abdominal CT scan reveals that the liver has cirrhosis. He joins a support group for persons with chronic alcohol abuse and he stops drinking. Despite his continued abstinence from alcohol, he most likely remains at risk for development of which of the following diseases? Liver cell adenoma Hepatocellular carcinoma Gallbladder stones Lymphoma www.indiandentalacademy.com
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A 28-year-old woman with recent onset of depression ingests an entire bottle (100 capsules, 500 mg each) of a medication containing acetaminophen. She becomes progressively obtunded. Which of the following microscopic findings is most likely to be present in her liver 3 days following this ingestion? Normal histology Steatosis Centrilobular necrosis Cirrhosis Chronic inflammation www.indiandentalacademy.com
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Hepatitis C infection is characterized by which one of the following: Absence of carrier status Highest incidence of chronic hepatitis among other viral hepatitis No increase risk for hepatocellular carcinoma It can be transmitted by eating contaminated food
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50 year-old male presented with jaundice and pruritus. Lab studies show elevated serum conjugated bilirubin and alkaline phosphatase. ALT and AST levels were only slightly elevated. The most likely diagnosis is: Hepatitis B Steatosis Hepatitis C Extrahepatic bile duct obstruction Autoimmune hepatitis www.indiandentalacademy.com
The Pancreas 85% exocrine: enzymes for digestion Acute and chronic pancreatitis Cystic fibrosis Tumors
15% endocrine: insulin, glucagon and others Diabetes Tumors
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Acute pancreatitis
CP: abdominal pain radiating to the back, elevated serum and urine amylase, hypocalcemia Most important causes: Gallstones, alcoholism, shock, hypercalcemia Mechanism: Interstitial edema ⇒ impaired blood flow and ischemia ⇒ acinar cell injury with release and activation of trypsinogen and lipases ⇒ proteolysis + fat necrosis + hemorrhage (destruction of blood vessels by elastases) Complications: infections, abscess, pseudocyst Mortality is high: 20-40%, from shock, sepsis or acute respiratory failure www.indiandentalacademy.com
Chronic pancreatitis
Progressive destruction of pancreatic parenchyma and its replacement by fibrosis Predisposing factors: alcohol, hypercalcemia or idiopathic 30% of idiopathic cases have been found to have mutation in CFTR gene Fibrosis, chronic inflammation and protein plugs within ducts Diagnosis: abdominal pain, malabsorption, calcifications on X-ray www.indiandentalacademy.com
Pancreatic adenocarcinoma
The 5th most frequent cause of death from cancer Risk factors: smoking CP: symptoms are late; pain and jaundice Prognosis is poor: 5% survive for 5 years
Some of the adverse effects of smoking to remember: Cancer of the oral cavity, lips, tongue, larynx, lungs, esophagus, pancreas, kidney, bladder and vulva Emphysema and chronic bronchitis, atherosclerosis and myocardial infarction www.indiandentalacademy.com
Islet cell tumors
Rare compared to adenocarcinoma Insulinomas: secrete insulin ⇒ hypoglycemia ⇒ behavioral changes, confusion and coma. Over 90% are benign Gastrinomas: secrete gastrin ⇒ increase acid production ⇒ duodenal and gastric ulcers
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Gallbladder
Gallstones (cholelithiasis)
Afflict 10% of adult population in Western countries Costs of management: $6 billion a year 20 million patients are estimated to have gallstones totalling several tons ! Made of cholesterol, bilirubin and calcium salts with different concentrations Two types: cholesterol and pigmented stones www.indiandentalacademy.com
Gallstones
Cholesterol
Western > others Advancing age Female sex Obesity Hyperlipidemia and bile stasis
Pigmented
Asian > Western Hemolytic anemia Biliary infection
Complications: empyema, perforation, fistula, inflammation, obstruction, pancreatitis www.indiandentalacademy.com
Acute cholecystitis
Calculous: acute inflammation of a gallbladder that has stones. It may represent a medical emergency; no associated infection initially Acalculous: no stones, in severely ill patients, severe trauma, burns and sepsis
Chronic cholecystitis
Almost always associated with gallstones www.indiandentalacademy.com
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The risks factors for developing acute pancreatitis include all of the following except: Gallstones Hypocalcemia Alcoholism Shock
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All of the following statement about pigmented gallstones are correct except: Hyperlipidemia is a risk factor Hemolytic anemias could be a cause Biliary infections may be present They are more common in Asians
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Hepatitis C infection is characterized by which one of the following: Absence of carrier status Highest incidence of chronic hepatitis among other viral hepatitis No increase risk for hepatocellular carcinoma It can be transmitted by eating contaminated food
www.indiandentalacademy.com
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A 38-year-old woman has experienced episodes of light-headedness, irritability, and difficulty concentrating at her work for the past year. On physical examination there are no abnormal findings. Laboratory studies show her hemoglobin is 14.2 g/dL. An abdominal CT scan shows a 1 cm mass in the tail of the pancreas. Which of the following is the most likely diagnosis? Pancreatic adenocarcinoma Pancreatic pseudo-cyst Insulinoma Chronic pancreatitis www.indiandentalacademy.com
ď Ž
1. 2. 3. 4.
A 50-year-old man gives a history of chronic alcohol abuse. He has had bouts of abdominal pain in the past year. For the past month, he has had more frequent and worsening abdominal pain. Physical examination reveals right upper and left upper quadrant pain with guarding. An abdominal plain film radiograph reveals no free air, but there is extensive peritoneal fluid collection along with dilated loops of small bowel. An abdominal CT scan reveals a 7 to 8 cm cystic mass in the tail of the pancreas. Which of the following is the most likely diagnosis? Pancreatic adenocarcinoma Metastatic carcinoma Pancreatic pseudocyst Acute pancreatitis www.indiandentalacademy.com
Thank you www.indiandentalacademy.com Leader in continuing dental education
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