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Transfusion Pathology

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Myenteric plexus ganglion cells or gone. Symptoms: dysphagia, regurgitation, aspiration ... Helicobacter also causes ulcers, gastric carcinoma, and MALT lymhoma ... – PowerPoint PPT presentation

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Title: Transfusion Pathology


1
Gastrointestinal and Liver Pathology
Kristine Krafts, M.D. October 27, 2009
2
GI Pathology Outline
  • Esophagus
  • Stomach
  • Intestine
  • Liver
  • Gallbladder
  • Pancreas

3
GI Pathology Outline
  • Esophagus
  • Achalasia
  • Hiatal hernia
  • Mallory-Weiss syndrome
  • Varices
  • Esophagitis
  • Barrett esophagus
  • Esophageal carcinoma

4
Normal esophageal-gastric junction
5
Achalasia
  • Lower sphincter cant relax
  • Result obstruction, dilatation
  • Myenteric plexus ganglion cells ? or gone
  • Symptoms dysphagia, regurgitation, aspiration
  • Cause unknown
  • Danger ? incidence squamous cell carcinoma

6
Hiatal Hernia
  • Dilated portion of stomach protrudes above
    diaphragm
  • Sliding or rolling pattern
  • Common! Usually asymptomatic.
  • Heartburn, reflux esophagitis
  • Danger ulceration, bleeding

7
Sliding (L) and rolling (R) hiatal hernias
8
Mallory-Weiss Syndrome
  • GE junction tears
  • Severe vomiting (chronic alcoholics)
  • Symptoms bleeding, pain, infection
  • Treatment balloon tamponade
  • Prognosis usually heals sometimes fatal

9
Mallory-Weiss tears
10
Mallory-Weiss tears
11
Esophageal Varices
  • Dilated veins in lower esophagus
  • Cause portal hypertension secondary to cirrhosis
  • Asymptomatic (until rupture and massive bleed)
  • Treatment sclerotherapy or ligation
  • Prognosis 30 mortality during first episode
    most will recur within a year

12
Esophageal varices
13
Esophagitis
  • Inflammation of esophageal lining
  • Most cases in US due to reflux
  • Cause sphincter malfunction, hiatal hernia
  • Symptoms heartburn
  • Danger bleeding, stricture, Barrett esophagus

14
Barrett Esophagus
  • Replacement of squamous epithelium by columnar
    epithelium with goblet cells
  • Complication of long-standing reflux esophagitis
  • Danger 30-100x increased risk of adenocarcinoma
  • Treatment Periodically screen for high-grade
    dysplasia

15
Normal esophagus (L) and Barrett esophagus (R)
16
Barrett esophagus
17
Barrett esophagus
18
Esophageal Carcinoma
  • Adenocarcinoma
  • More common than squamous cell CA in US
  • Risk factor Barrett esophagus
  • Distal 1/3 of esophagus
  • Symptoms insidious onset late obstruction
  • Squamous cell carcinoma
  • More common than adenocarcinoma worldwide
  • Risk factors esophagitis, smoking, alcohol,
    genetics
  • Middle 1/3 of esophagus
  • Symptoms insidious onset late obstruction

19
Adenocarcinoma of esophagus
20
Adenocarcinoma of esophagus
21
GI Pathology Outline
  • Esophagus
  • Stomach
  • Gastritis
  • Ulcers
  • Gastric carcinoma

22
Chronic Gastritis
  • Chronic Inflammation in mucosa, leading
    eventually to mucosal atrophy and epithelial
    metaplasia
  • Symptoms asymptomatic, or discomfort
  • Cause Helicobacter pylori, autoimmune gastritis
  • Helicobacter also causes ulcers, gastric
    carcinoma, and MALT lymhoma
  • Danger intestinal metaplasia (precancerous)

23
Chronic gastritis
24
Chronic gastritis
25
Helicobacter pylori organisms
26
Helicobacter pylori
27
TFSS
VacA protein
CagA protein
holes
free radicals
cytokines
immobilized T-helper cells
Type IV Secretion System
28
(No Transcript)
29
What happens after infection?
Helicobacter infection
Asymptomatic gastritis
Ulcer
Symptomatic gastritis
Carcinoma
Lymphoma
30
Acute Gastritis
  • Acute mucosal inflammation (usually transitory)
  • Causes include NSAIDS, alcohol, smoking
  • Superficial or full-thickness
  • Can lead to erosions
  • Asymptomatic or pain, vomiting, hematemesis

31
Ulcer
  • Erosion of mucosa into submucosa
  • Causes H. pylori, NSAIDs
  • Symptoms epigastric pain, bleeding, perforation
  • Also can occur after severe physiologic stress
    (trauma, buns, CNS trauma)

32
How does Helicobacter cause ulcers?
  • Bugs hide in mucous and attract inflammatory
    cells
  • Inflammatory cells release toxins but cant kill
    bugs easily
  • Host causes damage by continual, ineffective
    immune response!

33
Ulcer
34
Stress ulcers
35
Gastric Cancer
  • Intestinal type
  • Arises in intestinal metaplasia
  • Risk factors chronic gastritis, diet (?nitrites,
    ? fruits/vegetables)
  • Glandular morphology
  • Generally asymptomatic
  • Diffuse type
  • Arises from gastric glands
  • Risk factors undefined
  • Signet ring morphology
  • Generally asymptomatic

36
Helicobacter infection
gastritis
atrophy
intestinal metaplasia
dysplasia
carcinoma
37
Intestinal-type gastric carcinoma glands
38
Diffuse gastric carcinoma signet ring cells
39
Gastric carcinoma presenting as mass
40
Gastric carcinoma presenting as ulcer
41
Gastric carcinoma presenting as linitis plastica
42
GI Pathology Outline
  • Esophagus
  • Stomach
  • Intestine
  • Diverticular disease
  • Infectious diarrhea
  • Inflammatory bowel disease
  • Tumors

43
Diverticulosis
  • Herniation of mucosa/submucosa through muscle
    wall
  • Older patients, low fiber diet, increased
    intraluminal pressure
  • Sigmoid colon
  • Asymptomatic unless infected (diverticulitis)

44
Diverticulosis
45
Diverticulosis
46
Diverticulosis
47
Infectious Diarrhea
  • Major problem worldwide
  • Viral
  • Rotavirus (60 of childhood diarrhea in US)
  • Calcivirus (older children, adults)
  • Bacterial
  • Several different organisms
  • Differing mechanisms, sources
  • Most cause mucosal damage and inflammation some
    cause massive water influx or mucosal ulceration

48
Selected causes of bacterial diarrhea
49
Hemorrhagic colitis
50
Microangiopathic hemolytic anemia
51
Pseudomembranous colitis
52
Pseudomembranous colitis
53
Inflammatory Bowel Disease
  • Crohn Disease
  • Ileum mostly (but can be anywhere)
  • Patchy involvement
  • Transmural inflammation, fistulas, strictures
  • 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

54
Crohn disease
Ulcerative colitis
55
Adenoma
  • Common! 50 of people gt60.
  • Epithelial proliferation and dysplasia
  • Tubular, villous, or tubulovillous
  • More dangerous when
  • Large (gt1 cm)
  • Villous architecture
  • Severe dysplasia

56
Colon polyp
57
Tubular adenoma of colon
58
Villous adenoma of colon
59
Dysplastic (L) vs. normal (R) epithelium
60
Colorectal Carcinoma
  • Almost always arises in adenomatous polyp
  • Peak age 60-70
  • Dietary risk factors low fiber, high fat, lots
    of unrefined carbs, not enough vitamins (A, C, E)
  • Symptoms
  • silent for years
  • fatigue, weakness, iron-deficiency anemia
  • occult bleeding, crampy pain
  • Prognosis 5ys 90 if stage 1, 4 if stage 4

61
Colon carcinoma
62
Colon carcinoma
63
GI Pathology Outline
  • Esophagus
  • Stomach
  • Intestine
  • Liver
  • Hepatitis (viral, autoimmune, alcoholic)
  • Hemochromatosis
  • Wilson disease
  • Neoplasms of the liver

64
Normal liver
65
(No Transcript)
66
Normal liver
67
Patterns of Liver Injury
  • Degeneration and intracellular accumulation
  • Necrosis and apoptosis
  • Regeneration
  • Inflammation (hepatitis)
  • Fibrosis
  • Cirrhosis

68
Clinical Syndromes
  • Hepatic failure
  • Cirrhosis
  • Portal hypertension
  • Jaundice

69
Clinical Syndromes
  • Hepatic failure
  • Jaundice, edema, hyperammonemia
  • Toxin accumulation damages organs
  • Coagulopathy leads to bleeding
  • Hepatic encephalopathy
  • Hepatorenal syndrome

70
Clinical Syndromes
  • Hepatic failure
  • Cirrhosis
  • Fibrosis, nodules in liver
  • Alcoholism, hepatitis
  • Anorexia, weakness, liver failure, liver carcinoma

71
Clinical Syndromes
  • Hepatic failure
  • Cirrhosis
  • Portal hypertension
  • Ascites
  • Portosystemic venous shunts
  • Congestive splenomegaly
  • Hepatic encephalopathy

72
Consequences of portal hypertension

73
Clinical Syndromes
  • Hepatic failure
  • Cirrhosis
  • Portal hypertension
  • Jaundice
  • Elevated bilirubin
  • Conjugated (decreased liver excretion of
    bilirubin) or unconjugated (excess production of
    bilirubin)
  • Congestive

74
Bilirubin metabolism and elimination

75
Clinical Consequences of Liver Disease
  • Severe liver dysfunction
  • Jaundice, cholestasis
  • Hypoalbuminemia
  • Hyperammonemia
  • Hypoglycemia
  • Hypogonadism
  • Weight loss
  • Muscle wasting
  • Portal hypertension
  • Ascites
  • Splenomegaly
  • Esophageal varices
  • Hemorrhoids
  • Caput medusae
  • Complications of liver failure
  • Coagulopathy
  • Hepatic encephalopathy
  • Hepatorenal syndrome

76
Oral Manifestations of Liver Injury
  • Hematomas, gingival bleeding
  • Jaundiced mucosa
  • Glossitis (in alcoholic hepatitis)
  • Reduced healing after surgery

77
Laboratory Tests
78
Infectious Hepatitis
  • Viral hepatitis is the most common liver
    infection
  • Asymptomatic
  • Acute viral hepatitis (jaundice)
  • Chronic viral hepatitis (fatigue may ?
    cirrhosis)
  • Fulminant viral hepatitis (massive liver
    necrosis)

79

Acute viral hepatitis
80

Chronic viral hepatitis
81

Chronic viral hepatitis ground-glass hepatocytes
82

Cirrhosis
83
Cirrhosis
84
Ridiculously Oversimplified Summary
85
Hepatitis B outcomes
86
Hepatitis C outcomes
87
Autoimmune Hepatitis
  • FgtgtM
  • No viral hepatitis markers
  • High titers of autoantibodies (antinuclear,
    anti-smooth muscle, anti-microsomal)
  • Associated with other autoimmune diseases
    (rheumatoid arthritis, ulcerative colitis)
  • Risk of cirrhosis 5
  • Treatment immunosuppressive drugs

88
Alcoholic Liver Disease
  • Alcohol abuse causes 100,000 -200,000 deaths
    annually (20,000 due to end-stage liver
    cirrhosis)
  • Effects on liver steatosis, hepatitis, cirrhosis
  • Short-term ingestion of 8 beers/day (7 oz. 80
    proof liquor) leads to reversible steatosis
  • Long-term ingestion of 5-6 beers/day leads to
    severe injury
  • Beer and binge drinking are risky

89

Alcoholic liver disease
90

Alcoholic steatosis
91

Alcoholic hepatitis inflammation and Mallory
bodies
92

Alcoholic cirrhosis
93
Alcoholic Liver Disease Prognosis
  • Abstinence 5ys is 90 (if jaundice, ascites, or
    hematemesis have not developed)
  • Continued drinking 5ys drops to 50-60
  • Causes of death in end-stage alcoholism
  • Liver failure
  • Massive GI bleed
  • Infection
  • Hepatorenal syndrome
  • Hepatocellular carcinoma

94
Hereditary Hemochromatosis
  • Autosomal recessive disease ? body iron
  • Cause mutations in hemochromatosis gene
    (regulates iron absorption)
  • MgtF, 50-60 years old
  • Liver cirrhosis, skin pigmentation, diabetes,
    increased risk of hepatocellular carcinoma
  • Early detection and treatment (phlebotomy, iron
    chelators) normal life expectancy

95
Wilson Disease
  • Autosomal recessive disease ? body copper
  • Cause mutation in gene regulating copper
    excretion
  • Symptoms acute and chronic liver disease
    neuropsychiatric manifestations, Kayser-Fleisher
    rings in cornea
  • Diagnosis increased hepatic copper levels,
    decreased serum ceruloplasmin
  • Treatment copper chelation therapy

96

Kayser-Fleischer Rings
97
Biliary Disease
  • Secondary biliary cirrhosis
  • due to bile obstruction by stones, atresia, tumor
  • Primary biliary cirrhosis
  • immune-mediated destruction of bile ducts
  • women, 40s 50s
  • anti-mitochondrial antibodies
  • Primary sclerosing cholangitis
  • chronic fibrosis of bile ducts
  • men, 20s 40s
  • associated with ulcerative colitis

98
Primary biliary cirrhosis
99
Primary sclerosing cholangitis
100
Hepatic Adenoma
  • Women of childbearing age on oral contraceptives
  • Regresses with discontinuation of hormones
  • May be mistaken for carcinoma
  • May rupture during pregnancy, leading to
    life-threatening intra-abdominal hemorrhage

101
Hepatic adenoma
102
Hepatic adenoma
103
Hepatocellular Carcinoma
  • Strongly associated with hepatitis B and C,
    chronic liver disease, and aflatoxins
  • Rapid increase in liver size, worsening ascites,
    fever and pain
  • Very elevated alpha fetoprotein level
  • Median survival 7 months (death from bleeding,
    liver failure, profound cachexia)

104
Hepatocellular carcinoma
105
Hepatocellular carcinoma
106
Metastatic Carcinoma
  • The most common malignant tumor in the liver
  • Usually multiple lesions
  • Most common primaries colon, lung, breast,
    pancreas, stomach.

107
Metastatic carcinoma
108
GI Pathology Outline
  • Esophagus
  • Stomach
  • Intestine
  • Liver
  • Gallbladder
  • Cholelithiasis
  • Cholecystitis

109
Cholelithiasis
  • Common! (10 of adults in US)
  • Cholesterol stones Female, Fat, Fertile, Forty
  • Pigment (bilirubin) stones Asian countries,
    hemolytic anemia and biliary infections
  • Symptoms None, or excruciating pain
  • Complications cholecystitis, empyema,
    perforation, fistula, obstruction, pancreatitis

110
Cholesterol gallstones
111
Pigmented gallstones
112
GI Pathology Outline
  • Esophagus
  • Stomach
  • Intestine
  • Liver
  • Gallbladder
  • Pancreas
  • Pancreatitis
  • Pancreatic carcinoma

113
Normal Pancreas
  • Exocrine pancreas
  • Makes enzymes for digestion
  • Diseases Pancreatitis, cystic fibrosis, tumors
  • Endocrine pancreas
  • Makes insulin, glucagon, other stuff
  • Diseases Diabetes, tumors

114
Acute Pancreatitis
  • Acute inflammation and reversible destruction of
    pancreas
  • Symptoms abdominal pain radiating to back
  • Main causes alcoholism, gallstones
  • Labs elevated serum amylase and lipase
  • Complications DIC, ARDS, shock, endotoxemia,
    infection
  • Prognosis Most recover 5 mortality in first
    week

115
Obstruction (gallstones)
Cell injury (alcohol)
116
Chronic Pancreatitis
  • Longstanding, irreversible pancreatic destruction
  • Most are alcohol related, some idiopathic
  • Symptoms silent, or bouts of jaundice and pain
  • Diagnosis difficult
  • Complications secondary diabetes, malabsorption,
    severe chronic pain
  • Prognosis poor (50 mortality over 20 years)

117
Pancreatic Adenocarcinoma
  • 4th leading cause of cancer death in US
  • Risk factor smoking
  • Highly invasive
  • Silent until late then pain, jaundice
  • Very high mortality 5ys lt5

118
Pancreatic carcinoma
119
Pancreatic carcinoma
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