GI Flashcards
1
Q
T106 What is an aphthous ulcer?
A
A painful ulcer in the oral mucosa with a grayish base and erythematous rim. Self-resolving in a few days, but tends to recur. Linked to inflammatory bowel disease or Behçet syndrome.
2
Q
What causes herpes simplex in the oral cavity?
A
Caused by HSV1 (most common) or HSV2, presenting as grouped vesicles on an erythematous base. Reactivates from the trigeminal ganglion following stress or illness.
3
Q
Describe oral candidiasis
A
Caused by Candida albicans in immunosuppressed patients or those with disrupted flora. Appears as a gray to white pseudomembrane that can be scraped off. Early sign of AIDS.
4
Q
What is a fibroma?
A
A submucosal nodular fibrous tissue mass caused by chronic irritation, commonly found on the buccal mucosa. Appears as a smooth pink nodule.
5
Q
What is a pyogenic granuloma?
A
An erythematous, hemorrhagic, exophytic mass usually found on the gingiva of children and young adults. Richly vascular and often ulcerated.
6
Q
Define leukoplakia.
A
A white plaque that cannot be scraped off, often caused by hyperkeratosis. Associated with tobacco use and may transform into squamous cell carcinoma.
7
Q
Define erythroplakia.
A
Red, granular, circumscribed areas with marked epithelial dysplasia. Has a high risk of malignant transformation, with over 50% of cases becoming cancerous.
8
Q
What are the risk factors for oral squamous cell carcinoma?
A
Leukoplakia, erythroplakia, tobacco use, alcohol abuse, chronic irritation, HPV16 and HPV18, and immune suppression.
9
Q
Where are squamous cell carcinomas most commonly found in the oral cavity?
A
The ventral surface of the tongue, floor of the mouth, and lower lip.
10
Q
Describe the morphology of oral squamous cell carcinoma.
A
White to gray circumscribed thickenings of the mucosa, developing from dysplastic precursor lesions. Histologic patterns range from well-differentiated keratinizing neoplasms to anaplastic tumors.
11
Q
What are the clinical features of oral squamous cell carcinoma?
A
50% mortality rate within 5 years. Causes local pain or difficulty in chewing, may be asymptomatic, and can metastasize to cervical nodes, mediastinal nodes, lungs, and liver.
12
Q
What are the major and minor salivary glands?
A
Major salivary glands are the parotid, submandibular, and sublingual glands. Minor salivary glands are distributed throughout the mucosa.
13
Q
What is xerostomia?
A
Xerostomia is defined as a dry mouth resulting from decreased production of saliva. It is a major feature of Sjögren syndrome and can lead to increased dental caries, candidiasis, and difficulty swallowing and speaking.
14
Q
What causes sialadenitis?
A
Sialadenitis is inflammation of the major salivary glands due to trauma or infections. It can be viral (e.g., mumps affecting the parotid gland), bacterial (e.g., S. aureus), or autoimmune (e.g., Sjögren syndrome).
15
Q
What are the complications of mumps in adults?
A
In adults, mumps can cause pancreatitis or orchitis (inflammation of the testis).
16
Q
Describe a mucocele.
A
A mucocele is a cyst-like space resulting from blockage or rupture of a salivary gland duct, leading to saliva leaking into surrounding tissue. It is lined by inflammatory granulation tissue or fibrous connective tissue and filled with mucin and inflammatory cells.
17
Q
What is bacterial sialadenitis, and what causes it?
A
Bacterial sialadenitis is inflammation of the salivary glands occurring secondarily to ductal obstruction due to stone formation (sialolithiasis) or after retrograde entry of oral cavity bacteria (e.g., S. aureus, S. viridians).
18
Q
How common are salivary gland neoplasms, and where do they most often occur?
A
Salivary gland neoplasms are relatively uncommon, representing less than 2% of all human tumors. About 80% of these tumors occur within the parotid glands, usually in individuals aged 60-70 years.
19
Q
What is the relationship between the size of the salivary gland and the likelihood of malignancy?
A
The likelihood that a salivary gland tumor is malignant is inversely proportional to the size of the gland. Smaller glands have a higher likelihood of malignancy (e.g., sublingual glands).
20
Q
What is the most common tumor of the parotid gland, and what is the most common malignant salivary gland tumor?
A
The most common tumor of the parotid gland is pleomorphic adenoma, while the most common malignant tumor of the salivary glands is mucoepidermoid carcinoma.
21
Q
Describe pleomorphic adenoma
A
Pleomorphic adenoma arises at the superficial parotid, causing a painless, mobile swelling at the angle of the jaw. It consists of a mixture of ductal (epithelial) and myoepithelial cells, exhibiting both epithelial and mesenchymal differentiation, hence the name “mixed tumor.” It appears as a rounded, well-demarcated mass with a characteristic heterogeneity of epithelial cells or myoepithelial cells within a mesenchyme-like background.
22
Q
Describe mucoepidermoid carcinoma
A
Mucoepidermoid carcinoma is the most common primary malignant tumor of the salivary glands, composed of variable mixtures of squamous cells and mucus-secreting cells. Morphologically, it is a well-circumscribed, gray tumor often containing small cysts with mucin. Microscopically, it shows clusters of mucous, squamous, and intermediate cells.
23
Q
T107 What are the causes of mechanical obstruction in the esophagus?
A
Mechanical obstruction in the esophagus can be caused by developmental abnormalities, fibrotic stricture, or tumors. Common conditions include atresia and esophageal stenosis.
24
Q
Describe esophageal atresia.
A
Esophageal atresia is a condition where a thin, noncanalized cord replaces a segment of the esophagus. It most commonly occurs at or near the tracheal bifurcation and is often associated with a fistula connecting the esophagus and the bronchus/trachea.
25
What is esophageal stenosis, and what causes it?
Esophageal stenosis is generally caused by fibrous thickening of the submucosa, atrophy of the muscularis propria, and secondary epithelial damage. It often results from chronic gastroesophageal reflux, irradiation, or caustic injury, leading to inflammation and scarring.
26
What is functional obstruction in the esophagus, and what causes it?
Functional obstruction is caused by esophageal dysmotility characterized by discoordinated contraction or spasm of the muscularis propria, resulting in impaired forward movement of food to the stomach.
27
What is achalasia, and what are its characteristics?
Achalasia is the incomplete relaxation of the lower esophageal sphincter in response to swallowing, causing obstruction and dilation of the proximal esophagus. It is characterized by esophageal aperistalsis, incomplete relaxation of the lower esophageal sphincter, and increased tone of the lower esophageal sphincter.
28
What are the differences between primary and secondary achalasia?
Primary achalasia is idiopathic, caused by the failure of distal esophageal inhibitory neurons and damage to myenteric ganglions. Secondary achalasia is caused by pathological processes that impair esophageal function.
29
What are the clinical features and risks associated with achalasia?
Achalasia presents with dysphagia and stasis of food, which can lead to inflammation and ulceration. There is also a 5% risk of developing squamous cell carcinoma in patients with achalasia.
30
What is ectopia in the esophagus?
Ectopia is the presence of ectopic gastric mucosa, usually asymptomatic. The most frequent site is the upper third of the esophagus.
31
Describe a hiatal hernia and its types.
A hiatal hernia involves the separation of the diaphragmatic crura and the esophageal wall, allowing a segment of the stomach to protrude above the diaphragm. There are two types: sliding hernia (95% of cases, bell-shaped dilation) and paraesophageal hernia (a separate portion of the stomach enters the thorax through a widened foramen).
32
What is esophagitis?
Esophagitis is an injury to the esophageal mucosa with subsequent inflammation.
33
What are Mallory-Weiss tears and their pathogenesis?
Mallory-Weiss tears are longitudinal tears at the esophagogastric junction, often caused by severe vomiting with inadequate relaxation of the lower esophageal sphincter. They can result in hematemesis.
34
What is Boerhaave syndrome?
Boerhaave syndrome is characterized by transmural esophageal tears and mediastinitis. It is a rare but catastrophic event.
35
What is reflux esophagitis and its contributing factors?
Reflux esophagitis, often due to gastroesophageal reflux disease (GERD), is caused by impaired anti-reflux mechanisms, sliding hiatal hernia, increased gastric volume, obesity, pregnancy, alcohol, and tobacco use.
36
What are the clinical features and complications of reflux esophagitis?
Symptoms include heartburn, chest pain, and sour-tasting regurgitation. Complications can include esophageal ulceration, stricture development, and Barrett esophagus.
37
What causes chemical esophagitis?
Chemical esophagitis is caused by irritants such as alcohol, acids or alkalis, excessively hot fluids, and heavy smoking, leading to pain, particularly odynophagia (pain with swallowing).
38
What are common infectious causes of esophagitis?
Esophageal infections are common in immunosuppressed patients and can be caused by herpes simplex virus, cytomegalovirus (CMV), or fungal organisms like Candida.
39
What are the characteristics of eosinophilic esophagitis?
Eosinophilic esophagitis is an allergic inflammatory condition with infiltration by large numbers of eosinophils, particularly away from the gastroesophageal junction. It is often linked to food allergies and may present with other atopic conditions.
40
What are esophageal varices, and what conditions cause them?
Esophageal varices are abnormally dilated veins in the submucosal venous plexus of the distal esophagus, commonly caused by portal hypertension due to conditions like cirrhosis or hepatic schistosomiasis.
41
What are the clinical implications of esophageal varices?
Esophageal varices often produce no symptoms until they rupture, leading to massive hemorrhage into the esophageal lumen and wall. They are found in about 90% of cirrhotic patients and are associated with a high risk of bleeding and potential hepatocellular carcinoma.
42
T108 What is Barrett esophagus and how does it develop?
Barrett esophagus is a complication of long-standing gastroesophageal reflux disease (GERD) where chronic acid reflux causes metaplasia of the esophageal squamous epithelium to nonciliated columnar epithelium with goblet cells. This metaplasia occurs through the reprogramming of stem cells and can theoretically be reversed with treatment of GERD.
43
Who is more affected by Barrett esophagus and what risk does it pose?
Barrett esophagus affects males more than females and significantly increases the risk of developing esophageal adenocarcinoma.
44
What is the morphology of Barrett esophagus?
In Barrett esophagus, endoscopy reveals red mucosa extending from the gastroesophageal junction upward, correlating with the microscopic appearance of metaplastic columnar epithelium replacing the normal squamous epithelium.
45
What are the two major variants of esophageal carcinoma?
The two major variants of esophageal carcinoma are adenocarcinoma, which is common in Western countries and affects the lower third of the esophagus, and squamous cell carcinoma, which is the most common worldwide and involves the middle third of the esophagus.
46
What are the risk factors for squamous cell carcinoma of the esophagus?
Risk factors for squamous cell carcinoma of the esophagus include irritation from alcohol and tobacco use, obstructive esophageal diseases like achalasia, severe chemical injury, and chronic esophagitis.
It affects men more than women and has a higher prevalence in non-Western countries. It is also associated with HPV and abnormalities in the p16 and p53 genes.
47
What is the morphology of squamous cell carcinoma of the esophagus?
Squamous cell carcinoma of the esophagus tends to appear in the upper and middle thirds. Early lesions appear as small, gray-white plaques that can grow into tumor masses.
These masses can be polypoid exophytic, ulcerating, or diffuse infiltrative neoplasms causing wall thickening and lumen narrowing.
Microscopically, these carcinomas are composed of nests of malignant cells that partially recapitulate the stratified organization of squamous epithelium.
48
What are the clinical features of squamous cell carcinoma of the esophagus?
The first symptoms of squamous cell carcinoma of the esophagus include weight loss, difficulty swallowing, and hoarseness due to invasion of the recurrent laryngeal nerve.
At diagnosis, tumors are usually large and have invaded the esophageal wall, potentially extending into adjacent structures like the respiratory tree, aorta, mediastinum, and pericardium, causing further complications.
49
What is the origin of most esophageal adenocarcinomas?
Most adenocarcinomas arise from Barrett metaplasia or from glandular metaplasia in the esophageal mucosa.
50
What genetic mutations are involved in the progression from Barrett esophagus to adenocarcinoma?
Mutations in p53 gene, HER2/c-ERB-B2, cyclin D1, RB, and p16 genes.
51
Which demographic is more commonly affected by esophageal adenocarcinoma?
It is 7 times more common in men and has higher prevalence in western countries.
52
Where in the esophagus are adenocarcinomas usually located?
Usually in the distal 1/3 of the esophagus and may invade the gastric cardia.
53
What are the morphological characteristics of esophageal adenocarcinoma?
Moderate or well-differentiated mucin-producing tumors, often seen adjacent to Barrett mucosa with high-grade dysplasia.
54
What are the clinical features of esophageal adenocarcinoma?
Dysphagia to solids, then all food; weight loss, fatigue, weakness, and pain related to swallowing.
55
How does esophageal adenocarcinoma typically metastasize?
Metastasis occurs early due to the extensive lymphatic network, involving gastric and celiac lymph nodes. Recurrences are common.
56
T109 What is pyloric stenosis and how does it present clinically?
Pyloric stenosis is a congenital disorder caused by hypertrophy and hyperplasia of the pylorus muscle, leading to functional gastric outlet obstruction. It presents clinically around 2 weeks after birth with non-bilious vomiting, visible peristalsis on the abdominal surface, and is corrected by surgical incision of the hypertrophied muscle.
57
What are the two main causes of chronic gastritis and their complications?
Chronic gastritis is mainly caused by Helicobacter pylori infection and autoimmune gastritis. H. pylori infection can lead to peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and increased risk of gastric adenocarcinoma.
Autoimmune gastritis can cause loss of parietal cells, achlorhydria, hypergastrinemia, antral endocrine cell hyperplasia, vitamin B12 deficiency, megaloblastic anemia, and increased risk of adenocarcinoma.
58
Describe the pathogenesis and morphology of H. pylori-induced chronic gastritis.
H. pylori colonizes the mucus layer of the stomach, using urease to produce ammonia, increasing acid production. It manifests as antral gastritis with high acid production, potentially causing peptic ulcers, MALT lymphoma, and intestinal metaplasia. Morphologically, it involves superficial mucus colonization, neutrophils in the lamina propria and epithelium, lymphoid aggregates, and intestinal metaplasia.
59
What are the clinical features and complications of H. pylori-induced chronic gastritis?
Clinical features include nausea, vomiting, and a urea breath due to ammonia production by urease. Hematemesis is uncommon. Complications include peptic ulcer disease, MALT lymphoma, and increased risk for gastric adenocarcinoma.
60
How does autoimmune gastritis differ from H. pylori-induced gastritis in terms of location and effects on gastric physiology?
Autoimmune gastritis typically affects the body and fundus, sparing the antrum, and causes hypergastrinemia due to loss of parietal cells.
This leads to achlorhydria, hyperplasia of antral G cells, and vitamin B12 deficiency causing pernicious anemia. In contrast, H. pylori-induced gastritis often affects the antrum, increasing acid production without hypergastrinemia.
61
What are the morphological features of autoimmune gastritis?
Autoimmune gastritis shows diffuse atrophy of the mucosa in the body and fundus, an inflammatory infiltrate primarily composed of lymphocytes, macrophages, and plasma cells, and is deep and centered on the gastric glands.
There is extensive loss of parietal and chief cells, leading to increased risk of intestinal metaplasia and adenocarcinoma.
62
What are the complications of autoimmune gastritis?
Complications include achlorhydria, hypergastrinemia, hyperplasia of antral endocrine cells, vitamin B12 deficiency, megaloblastic anemia (pernicious anemia), and increased risk for developing gastric adenocarcinoma.
63
What is acute gastritis and what are its potential symptoms?
Acute gastritis is an acute mucosal inflammatory process that can be accompanied by nausea, vomiting, and pain. In severe cases, it may cause mucosal erosion, ulceration, hemorrhage, hematemesis (vomiting blood), and melena (black, tarry stools).
64
What causes acute gastritis?
Acute gastritis is caused by increased stomach acidity or reduced protective mechanisms of the mucosa. Risk factors include heavy use of NSAIDs (which inhibit prostaglandin formation), excessive alcohol consumption, ingestion of harsh chemicals, cancer chemotherapy drugs, increased intracranial pressure (leading to increased vagal stimulation and acid production), and severe shock or burns (causing decreased blood flow to organs).
65
What are the morphological features of mild and severe acute gastritis?
Mild gastritis shows intact surface epithelium with scattered neutrophils above the basement membrane. Severe acute gastritis features erosion and hemorrhage, known as acute erosive hemorrhagic gastritis.
66
What is an acute peptic ulcer and how does it differ from a chronic ulcer?
An acute peptic ulcer is characterized by a lack of mucosal layer, appearing as a depression with necrotic debris and neutrophils at the bottom. Unlike chronic ulcers, acute ulcers do not show granulation tissue and fibrosis underneath upon healing.
Chronic ulcers have granulation tissue and fibrosis due to ongoing repair.
67
What are the specific causes of acute peptic ulcers and their clinical presentation?
Acute peptic ulcers can be caused by:
1. NSAIDs, which inhibit prostaglandin production, reducing bicarbonate secretion and blood perfusion.
2. Curling ulcers, which occur due to hypoxia from shock or burns, often presenting as multiple ulcers in the stomach and proximal duodenum.
3. Cushing ulcers, which are associated with increased intracranial pressure (IICP).
Clinically, acute peptic ulcers present with hematemesis (coffee-ground vomit) and nausea. Treatment involves addressing the underlying cause and administering proton pump inhibitors.
68
T110 What is an ulcer, and where are peptic ulcers most commonly found?
An ulcer is a focal lack of mucosa. Peptic ulcers are most commonly found in the stomach and duodenum.
69
What are the causes of acute peptic ulceration?
Acute peptic ulceration can be caused by acute peptic injury, NSAID therapy, and severe physiological stress such as shock. Other contributing factors include excessive alcohol consumption, ingestion of harsh chemicals, and cancer chemotherapy.
70
What are the three types of acute ulcers and their associated conditions?
1. Stress ulcers: Affect patients with shock, sepsis, or severe trauma, often presenting as multiple ulcerations.
2. Curling ulcers: Occur in the stomach and proximal duodenum in severe burn victims.
3. Cushing ulcers: Arise in the stomach, duodenum, or esophagus in persons with increased intracranial pressure (IICP), associated with increased vagal stimulation and elevated gastric acid secretion.
71
How do NSAIDs contribute to acute peptic ulceration?
NSAIDs prevent prostaglandin synthesis, eliminating the protective effects of prostaglandins, which include enhanced bicarbonate secretion and increased vascular perfusion. This increases the risk of mucosal injury and ulceration.
72
What is the morphology of acute gastric ulcers?
Acute gastric ulcers range from shallow erosions to deeper lesions that penetrate the mucosa. They are typically small (<1 cm in diameter), sharply demarcated, with normal adjacent mucosa.
The ulcer base is often stained brown to black by acid-digested extravasated red cells. There is no scarring, granulation tissue, or fibrosis under the ulcer, but necrotic debris and neutrophils are present
73
What are the clinical features and potential complications of gastric ulcers?
Clinical features of gastric ulcers include nausea, vomiting, and coffee-ground hematemesis.
Potential complications include bleeding (which may be massive and require transfusion in 1-4% of patients), perforation, obstruction, and loss of function due to scarring.
74
What are the primary causes of peptic ulcer disease (PUD)?
Peptic ulcer disease (PUD) is most often associated with Helicobacter pylori infection or NSAID use.
75
What is the pathogenesis of peptic ulcer disease (PUD)?
PUD is caused by imbalances of mucosal defenses and damaging forces, often developing on a background of chronic gastritis.
Key factors include gastric hyperacidity, H. pylori-induced hyperchlorhydric chronic gastritis, chronic NSAID use, parietal cell hyperplasia, excessive secretory response, and impaired inhibition of stimulatory mechanisms like gastrin release.
Zollinger-Ellison syndrome, caused by a gastrin-secreting tumor, also leads to PUD.
76
What are the common locations and histological features of peptic ulcers?
Peptic ulcers commonly appear in the proximal duodenum near the pyloric valve and in the stomach on the small curvature in the antrum.
- Histologically, they show a base with necrotic debris, underlying granulation tissue rich in blood vessels, and fibrosis beneath.
77
What are the clinical features of peptic ulcer disease?
Peptic ulcer disease presents with epigastric pain that resolves after a meal in the case of duodenal ulcers and worsens after a meal in the case of gastric ulcers.
78
What are the complications of chronic peptic ulcer disease?
Complications include:
Upper gastrointestinal bleeding due to arterial erosion.
Perforation, leading to communication between the stomach and peritoneal space.
Penetration into adjacent organs (liver, pancreas, greater omentum) without peritoneal cavity communication.
Gastric stenosis from extensive fibrosis.
Rare malignant transformation with irregular, anfractuous ulcer borders.
79
T111 What is the most common type of primary malignant tumor in the stomach?
The most common type of primary malignant tumor in the stomach is gastric adenocarcinoma, accounting for about 90% of cases.
80
What are the types of gastric adenocarcinoma according to the Lauren classification?
The Lauren classification of gastric adenocarcinoma includes three types: intestinal type, diffuse type, and mixed type.
81
What is the key genetic mutation associated with diffuse-type gastric adenocarcinoma?
The key genetic mutation associated with diffuse-type gastric adenocarcinoma is the loss of the CDH1 gene, which encodes E-cadherin.
82
What role does the CDH1 gene play in diffuse gastric cancer?
The CDH1 gene encodes E-cadherin, a cell adhesion molecule crucial for normal cell differentiation and tissue architecture. Its mutation leads to loss of cell adhesion, contributing to the development of diffuse gastric cancer.
83
What is the progression sequence for developing gastric cancer?
The progression sequence for developing gastric cancer includes atrophic gastritis, followed by dysplasia, adenoma, and then adenocarcinoma. This process involves multiple genetic mutations, including mutations to the p53 tumor suppressor gene.
84
What are the environmental risk factors associated with intestinal-type gastric cancer?
Environmental risk factors for intestinal-type gastric cancer include diets high in nitrosamines (e.g., smoked foods), low consumption of fresh fruits, leafy vegetables, ascorbic acid, and beta-carotene. There is an increased prevalence in regions like Japan and Eastern Europe.
85
What condition is associated with the development of intestinal-type gastric adenocarcinoma?
Intestinal-type gastric adenocarcinoma often arises in the setting of atrophic gastritis, a condition characterized by chronic inflammation and destruction of stomach glands, leading to intestinal metaplasia.
86
How does Helicobacter pylori infection contribute to gastric adenocarcinoma?
Helicobacter pylori infection can cause chronic atrophic gastritis, leading to the destruction of stomach glands and the development of intestinal metaplasia, which increases the risk of gastric adenocarcinoma.
87
What are gastric polyps, and how are they related to gastric cancer?
Gastric polyps are growths on the lining of the stomach. Hyperplastic polyps, which are the most common, have increased malignant potential if larger than 0.5 cm. Adenomatous polyps also have a significant risk of cancer and require endoscopic follow-up after removal.
88
What percentage of gastric adenocarcinomas is associated with Epstein-Barr virus (EBV) infection, and what is the characteristic morphology?
About 10% of gastric adenocarcinomas are associated with Epstein-Barr virus (EBV) infection. EBV-positive tumors tend to occur in the proximal stomach, have a diffuse morphology, and are characterized by a marked lymphocytic infiltrate.
89
What are the two types of gastric adenocarcinoma according to the Lauren classification?
The Lauren classification separates gastric adenocarcinomas into intestinal and diffuse types.
90
Describe the macroscopic appearance of intestinal-type gastric adenocarcinoma.
Intestinal-type gastric adenocarcinoma typically presents as an elevated mass with heaped-up borders and central ulceration, usually involving the lesser curvature of the antrum.
91
What histological features characterize intestinal-type gastric adenocarcinoma?
Histologically, intestinal-type gastric adenocarcinoma displays irregular tubular structures with stratification and multiple lumens surrounded by reduced stroma, invading the gastric wall, and often associated with intestinal metaplasia in adjacent mucosa.
92
Describe the macroscopic appearance of diffuse-type gastric adenocarcinoma.
Diffuse-type gastric adenocarcinoma presents as "linitis plastica," with a markedly thickened gastric wall due to desmoplasia and partially lost rugal folds.
93
What histological features characterize diffuse-type gastric adenocarcinoma?
Histologically, diffuse-type gastric adenocarcinoma consists of discohesive tumor cells that secrete mucus, forming "signet-ring cells," and lacks glandular structures. The mucus may accumulate in the interstitium, producing large pools of mucus/colloid.
94
What are the common clinical features of gastric adenocarcinoma?
Gastric adenocarcinomas are generally asymptomatic initially but can present with abdominal discomfort, weight loss, early satiety, and anemia as they advance.
95
What is the most significant prognostic factor for gastric adenocarcinoma?
The most significant prognostic factor for gastric adenocarcinoma is the depth of tumor invasion at the time of diagnosis.
96
Describe the TNM classification used for staging gastric adenocarcinoma.
The TNM classification reflects the depth of tumor infiltration (T), lymph node involvement (N), and the presence of distant metastases (M). Early stages are confined to the mucosa and submucosa, while advanced stages extend into the muscularis propria and serosa, with potential invasion of adjacent organs.
97
What is Virchow node, and why is it significant in gastric adenocarcinoma?
Virchow node is the earliest lymph node metastasis involving the supraclavicular lymph nodes, significant in gastric adenocarcinoma for indicating regional and distal lymph node spread.
98
What is a Krukenberg tumor, and how is it related to gastric adenocarcinoma?
A Krukenberg tumor is a metastasis of gastric adenocarcinoma to the ovaries, characterized by signet-ring cells and desmoplasia.
99
What other types of tumors can arise in the stomach besides adenocarcinoma?
Other types of tumors that can arise in the stomach include extranodal lymphoma (e.g., marginal zone B-cell lymphoma, EBV-derived B-cell lymphoma) and carcinoid tumors (malignant proliferation of neuroendocrine cells).
100
What is a polyp?
A polyp is any nodule or mass that originates from the mucosa and projects above its level.
101
How common are gastric polyps, and what can cause their development?
Gastric polyps are uncommon. They may develop due to epithelial or stromal cell hyperplasia, inflammation, ectopia, or neoplasia.
102
What are hyperplastic polyps, and what causes them?
Hyperplastic polyps (80%-85%) arise in response to chronic gastritis and are composed of hyperplastic mucosal epithelium and inflamed edematous stroma. They are not true neoplasms.
103
What are fundic gland polyps, and what causes them?
Fundic gland polyps (~10%) occur sporadically and in persons with familial adenomatous polyposis (FAP). They are associated with the use of proton pump inhibitors, which reduce acidity, leading to increased gastrin secretion and glandular hyperplasia.
104
Where are fundic gland polyps typically located, and what are their characteristics?
Fundic gland polyps are typically located in the gastric body and fundus. They are well-circumscribed, often multiple, and composed of cystically dilated, irregular glands lined by flattened parietal and chief cells.
105
What are gastric adenomas, and what background do they commonly occur on?
Gastric adenomas (10%) almost always occur on a background of chronic gastritis with atrophy and intestinal metaplasia.
106
What is the risk associated with gastric adenomas, and where are they commonly located?
The risk for developing adenocarcinoma in gastric adenomas is related to the size of the lesion. They are commonly located in the antrum.
107
What type of epithelial change is exhibited by gastrointestinal adenomas?
Gastrointestinal adenomas exhibit epithelial dysplasia.
108
T112 What is atresia and how does it differ from stenosis?
Atresia is the complete failure of development of the intestinal lumen, most commonly affecting the duodenum (associated with Down syndrome). Stenosis is the narrowing of the intestinal lumen with incomplete obstruction.
109
What is intestinal duplication?
Duplication refers to saccular to tubular cystic structures pinched off from the intestine, which may or may not communicate with the lumen of the small intestine. Tubular duplication communicates with the lumen, while cystic duplication is completely pinched off.
110
What is Meckel diverticulum and what are its complications?
Meckel diverticulum results from failure of involution of the omphalomesenteric duct, creating a blind-ended tubular protrusion in the ileum. Complications include bleeding (especially if ectopic gastric mucosa is present), volvulus, infection, intussusception, and pernicious anemia if bacterial overgrowth depletes vitamin B12.
111
What is an omphalocele and how does it differ from gastroschisis?
Omphalocele is a congenital defect of the periumbilical abdominal musculature that creates a membranous sac into which the intestines herniate. Gastroschisis is the lack of formation of part of the abdominal wall, causing herniated intestines to be exposed to the external environment without a sac.
112
What is malrotation of the intestine and its potential complications?
Malrotation is the abnormal rotation of the developing bowel, preventing the intestine from assuming its normal intra-abdominal position. This can lead to volvulus or misdiagnosis of appendicitis, as pain may present in an atypical location.
113
What causes Hirschsprung disease and what are its key characteristics?
Hirschsprung disease is caused by the disrupted migration of neural crest cells to the lower rectum, resulting in an aganglionic segment that lacks the Meissner submucosal and Auerbach myenteric plexuses. This leads to a lack of peristaltic contractions and functional obstruction, causing dilation of the proximal, normally innervated colon.
114
What are the morphological features of Hirschsprung disease?
The aganglionic region may appear normal or contracted, while the proximal colon undergoes dilation due to distal obstruction. The critical lesion is the absence of ganglion cells and ganglia in both the muscle wall and submucosa.
115
What is megacolon?
Megacolon is the distension of the colon to a diameter greater than 6-7 cm. It can be either congenital or acquired.
116
What is Hirschsprung disease and what are its clinical features?
Hirschsprung disease is a congenital megacolon caused by the absence of the Meissner and Auerbach plexuses in segments of the colon (aganglionic segments). Clinical features include delayed passage of meconium, vomiting within 48-72 hours, and the principal threat of superimposed enterocolitis with fluid and electrolyte disturbances.
117
What are the causes of acquired megacolon?
Acquired megacolon may result from:
Chagas disease (Trypanosoma cruzi invasion destroys plexuses)
Organic obstruction (e.g., neoplasm or inflammatory stricture)
Toxic megacolon (complication of ulcerative colitis or Crohn disease)
Functional psychosomatic disorder (stool retention due to psychological reasons or long-term laxative abuse)
118
What is an abdominal hernia?
An abdominal hernia is a weakness or defect in the wall of the peritoneal cavity, allowing protrusion of a serosa-lined pouch of peritoneum called a hernia sac.
119
Where do acquired hernias most commonly occur?
Acquired hernias most commonly occur anteriorly through the inguinal and femoral canals, umbilicus, or at sites of surgical scars.
120
What complications can arise from a hernia?
Visceral protrusion into the hernia sac can lead to external herniation, which may become entrapped, impair venous drainage causing stasis and edema, leading to permanent entrapment (incarceration), and potentially resulting in arterial and venous compromise and infarction.
121
T113 What is the main blood supply to the intestines and how do collaterals help?
The main blood supply to the intestines comes from the celiac, superior mesenteric, and inferior mesenteric arteries. Collaterals from the proximal celiac, distal pudendal, and iliac circulations make it possible to tolerate the loss of blood supply from one artery.
122
What are the different extents of ischemic bowel disease?
Ischemic bowel disease can range from:
Mucosal infarction (extending no deeper than the muscularis mucosa)
Mural infarction (involving the mucosa and submucosa)
Transmural infarction (involving all three layers of the wall)
123
What typically causes mucosal or mural infarctions versus transmural infarctions?
Mucosal or mural infarctions are often secondary to acute or chronic hypoperfusion (e.g., cardiac failure, shock, dehydration, or vasoconstrictive drugs). Transmural infarction is generally caused by acute vascular obstruction (e.g., thromboembolism, vasculitis, thrombosis due to lupus anticoagulant or polycythemia vera).
124
What are the two phases of intestinal responses to ischemia?
Initial hypoxic injury: Occurs at the onset of vascular compromise; intestinal epithelial cells are relatively resistant to transient hypoxia.
Reperfusion injury: Initiated by the restoration of blood supply, associated with the greatest damage involving free radical production, neutrophil infiltration, and release of inflammatory mediators like complement proteins and cytokines.
125
What are watershed zones in the context of ischemic bowel disease?
Watershed zones are intestinal segments at the end of their respective arterial supplies that are particularly susceptible to ischemia due to their limited collateral blood supply.
126
What is the morphologic signature of ischemic intestinal disease?
The morphologic signature of ischemic intestinal disease is surface epithelial atrophy or necrosis with sloughing, accompanied by normal or hyperproliferative crypts.
127
What are the morphological characteristics of mucosal and mural infarctions in ischemic bowel disease?
Mucosal and mural infarctions may involve any level of the gut from the stomach to the anus. The disease frequently is segmental and patchy in distribution. The mucosa is hemorrhagic and often ulcerated, and severe disease includes extensive mucosal and submucosal hemorrhage and necrosis.
128
Describe the morphology of transmural infarction in ischemic bowel disease
Transmural infarction is characterized by coagulative necrosis of the muscularis propria within 1 to 4 days, often associated with purulent serositis and perforation.
129
What are the microscopic features of ischemic bowel disease?
Microscopic examination shows atrophy or sloughing of surface epithelium with hyperproliferative crypts. Reperfusion leads to acute inflammatory infiltrate, edema, and hemorrhage in the lamina propria. Chronic ischemia is accompanied by fibrous scarring, and acute ischemia may induce pseudomembrane formation due to superinfection and enterotoxin release.
130
What are the predisposing conditions for ischemic bowel disease?
Predisposing conditions include:
- Arterial thrombosis: Atherosclerosis, hypercoagulable states, aortic reconstructive surgery.
- Arterial embolism: Cardiac vegetations, myocardial infarction with mural thrombosis.
- Venous thrombosis: Hypercoagulable states induced by oral contraceptives or antithrombin III deficiency, cirrhosis, abdominal trauma.
131
Who is most at risk for ischemic bowel disease, and what are the acute clinical features?
Ischemic bowel disease tends to occur in older persons with coexisting cardiac or vascular disease. Acute transmural infarction typically manifests with sudden, severe abdominal pain and tenderness, and may progress to shock and vascular collapse within hours as a result of blood loss. Bacteria can enter the circulation as the mucosal barrier breaks down, potentially leading to sepsis. The mortality rate may exceed 50%.
132
What are the clinical implications of mucosal and mural infarctions in ischemic bowel disease?
Mucosal and mural infarctions may not be fatal by themselves but can progress to transmural infarctions, which are more severe. These types of infarctions can also result in radiation enterocolitis, where radiation-induced vascular injury produces changes similar to those seen in ischemic disease.
133
What is angiodysplasia, and how does it typically present?
Angiodysplasia is characterized by acquired structural abnormalities of submucosal and mucosal blood vessels, leading to tortuous dilation.
It is usually seen in the cecum and ascending colon due to high wall tension and typically presents after the sixth decade of life.
It often manifests as hematochezia, which is the passage of fresh blood through the anus.
134
What are the risk factors for angiodysplasia?
Risk factors for angiodysplasia include Osler-Weber-Rendu syndrome (autosomal dominant hereditary hemorrhagic telangiectasia) and CREST syndrome of scleroderma.
135
What are hemorrhoids, and how do they develop?
Hemorrhoids are variceal dilations of the anal and peri-anal submucosal venous plexuses.
They develop due to elevated venous pressure within the hemorrhoidal plexus, commonly after the age of 50.
Predisposing conditions include straining upon defecation, chronic constipation, venous stasis, pregnancy, and hypertension due to liver cirrhosis.
136
How are hemorrhoids classified, and what are their characteristics?
Hemorrhoids can be classified as:
External: Varices of the inferior hemorrhoidal plexus that occur outside the anus, covered by anal mucosa; more prone to thrombosis and very painful.
Internal: Varices of the superior and middle hemorrhoidal plexuses that occur inside the rectum; non-painful but may prolapse outside the anus.
137
What is the histological appearance of hemorrhoids?
On histologic examination, hemorrhoids consist of thin-walled, dilated, submucosal vessels that protrude beneath the anal or rectal mucosa.
138
T114 What are the two major entities of Inflammatory Bowel Disease (IBD)?
1. Ulcerative colitis: Inflammation limited to the mucosa and submucosa, usually extending to the distal colon and rectum.
2. Crohn disease: Transmural inflammation, usually found in the ileum and proximal colon but can affect any part of the gastrointestinal tract from mouth to anus.
139
What is indeterminate colitis?
Indeterminate colitis refers to the histopathologic and clinical overlap between ulcerative colitis and Crohn disease.
140
What are the demographics of IBD?
IBD is more common in young females, typically presenting in teenage years to 30s. It is more prevalent in Western countries, especially North America, Europe, and among Ashkenazi Jews.
141
What genetic predispositions are associated with Crohn disease?
First-degree relatives have a 13-18% increase in incidence.
Concordance rates of 50% in monozygotic twins.
NOD2 gene is a susceptibility gene in Crohn disease, encoding a protein that binds to intracellular bacterial peptidoglycans and activates NF-κB.
142
What is the role of mucosal immune response in IBD pathogenesis?
T-helper cell type 1 (TH1) polarization is a feature of Crohn disease.
TH1 cells produce interferon-gamma, IL-2, and TNF-beta, activating macrophages and cell-mediated immunity.
TH17 cells also contribute to disease pathogenesis.
Ulcerative colitis involves TH-2 and polymorphisms of the IL-10 gene.
143
What epithelial defects are associated with Crohn disease?
Defects in intestinal epithelial tight junction barrier function, leading to increased permeability and inflammation. Paneth cell granules, which contain antimicrobial materials, may also alter microbiota composition, linking to IBD development.
144
How does microbiota contribute to IBD pathogenesis?
Transepithelial flux of luminal bacterial components activates innate and adaptive immune responses. In genetically susceptible individuals, TNF and other inflammatory cytokines increase epithelial permeability, creating a cycle of inflammation.
145
What environmental factors are involved in IBD?
Cigarette smoking and diet are significant environmental factors.
Tobacco smoking doubles the risk of Crohn disease but appears to have a protective effect in ulcerative colitis.
146
What is Crohn disease and where is it usually found?
Crohn disease is a chronic inflammatory condition characterized by transmural inflammation, usually found in the ileum and cecum (proximal colon) but has the potential to affect any part of the gastrointestinal tract from mouth to anus.
147
What are the extra-intestinal complications associated with Crohn disease?
Extra-intestinal complications of immune origin include uveitis, sacroilitis, migratory polyarthritis, erythema nodosum, bile duct inflammatory disorders, and obstructive uropathy.
148
What is the macroscopic morphology of Crohn disease?
-Patchy lesional distribution with sharply delineated areas of disease surrounded by normal mucosa.
-Transmural involvement with thickening of the mucosal wall, resulting in a rubbery and thick intestinal wall due to edema, inflammation, fibrosis, and hypertrophy of
muscularis mucosae.
-Cobblestone appearance of the mucosal surface.
- "Creeping fat" formation within the fissures.
- Focal ulceration in early stages, progressing to elongated linear ulcers
149
What is "creeping fat" in Crohn disease?
"Creeping fat" refers to the formation of granulation tissue within the fissure that involves the stricture of the fissure, pulling up the fat of the mesentery.
150
What are the microscopic features of Crohn disease?
-Transmural inflammation with inflammatory cells extending from mucosa through submucosa and muscularis.
-Presence of non-caseating granulomas.
- Crypt abscesses with clusters of neutrophils and associated crypt
destruction.
- Epithelial metaplasia including pseudo pyloric metaplasia and Paneth cell metaplasia.
151
What are the clinical features of Crohn disease?
Recurrent episodes of diarrhea, cramps with abdominal pain, fever (lasting days to weeks), and malabsorption with nutritional deficiency.
152
What are the potential consequences of Crohn disease?
Fistula formation to other segments of the bowel, urinary bladder, vagina, or perianal skin.
Abdominal abscesses or peritonitis.
Intestinal stricture or obstruction.
Perforations and peritoneal abscesses.
Increased risk for colonic adenocarcinoma.
153
What is Ulcerative Colitis and where is it typically found?
Ulcerative Colitis is an ulcero-inflammatory disease limited to the colon and rectum, affecting only the mucosa and submucosa. It begins in the rectum and extends proximally, potentially involving the entire colon (pancolitis).
154
Describe the macroscopic morphology of Ulcerative Colitis.
No skip lesions, meaning colonic involvement is continuous.
Mucosal ulcers rarely extend beyond the submucosa.
Mural thickening is absent.
Serosal surface appears normal.
Strictures do not occur.
Isolated islands of regenerating mucosa bulge upward, forming pseudopolyps.
155
What are the microscopic features of Ulcerative Colitis?
Inflammatory infiltrates, crypt abscesses, crypt distortion, and epithelial metaplasia.
Ulcers extending to the submucosa.
Absence of granulomas.
156
What are the clinical features of Ulcerative Colitis?
Attacks of bloody mucoid diarrhea that can persist for days, weeks, or months, then subsides only to recur after an asymptomatic interval.
- Risk of developing toxic megacolon due to inflammation and damage to the muscularis propria, causing neuromuscular damage.
- High risk of carcinoma development, which depends on the extent of colonic involvement and the duration of the disease.
157
T115 What is Enterocolitis?
Enterocolitis is an inflammation of the colon (colitis) and small intestine (enteritis).
158
What is Infectious Enterocolitis?
Infectious Enterocolitis is an intestinal inflammatory disease of microbial origin, presented by diarrhea and ulcero-inflammatory changes in the small or large intestine.
159
How significant is Infectious Enterocolitis in global child mortality?
Infectious Enterocolitis is responsible for approximately half of the deaths before the age of 5 worldwide.
160
What factors influence the prevalence and severity of Infectious Enterocolitis?
The prevalence and severity of Infectious Enterocolitis are influenced by the sanitary conditions and the host's immune defense system
161
What are the three mechanisms of bacterial infection in the intestines?
1. Ingestion of preformed toxin (e.g., S. aureus, Vibrio, Clostridium perfringens).
2. Infection by toxigenic organisms (adhere to mucosa, proliferate, and release enterotoxins).
3. Infection by enteroinvasive organisms (proliferate, invade, and destroy mucosal epithelial cells).
162
What are the bacterial virulence factors involved in intestinal infections?
Adherence to epithelial cells (via fimbriae or pili, e.g., C. jejuni, E. coli).
Enterotoxins (e.g., cholera toxin, enterotoxigenic E. coli).Invasion factors (e.g., enteroinvasive E. coli).
Cytotoxicity (e.g., Shiga toxin, enterohemorrhagic E. coli).
163
What are the morphological features of bacterial enterocolitis?
Hyperemia, edema, erosion, and ulceration of the lamina propria.
Lamina propria and intraepithelial neutrophil infiltrates.
Cryptitis (neutrophil infiltration of the crypts) and crypt abscesses (crypts with luminal neutrophils).
Preservation of crypt architecture, distinguishing from inflammatory bowel disease.
164
What are the clinical features of bacterial origin enterocolitis?
More severe than viral or parasitic enterocolitis.Acute self-limited colitis (ASLC) with diarrhea and abdominal distress.
Complications include massive fluid loss, dehydration, and intestinal mucosa destruction leading to perforation.
Diagnosed by stool culture.
165
What is the pathogenesis of cholera?
Caused by Vibrio cholerae, transmitted primarily by contaminated water.Noninvasive, remains in the intestinal lumen.
Cholera toxin (A and B subunits) causes disease by ADP ribosylation of G protein, activating adenylate cyclase, increasing cAMP, and opening CFTR channels, leading to chloride and water secretion (excretory diarrhea).
166
What are the clinical features of cholera?
Asymptomatic in most cases.
Severe cases present with massive watery diarrhea leading to hypovolemia.
167
What causes Campylobacter enterocolitis and how is it transmitted?
Caused by Campylobacter jejuni.
Transmitted through undercooked chicken, unpasteurized milk, or contaminated water.
168
What are the four main virulence factors of Campylobacter jejuni?
Motility (flagella).
Adherence factor.
Toxin production (cholera-like toxin, cytotoxins).
Invasion.
169
What are the potential complications of Campylobacter enterocolitis?
Dysentery, enteric fever, reactive arthritis, erythema nodosum, Guillain-Barré syndrome.
170
What are the clinical features of Campylobacter enterocolitis?
Watery diarrhea, which may progress to dysentery in 15-50% of patients.
171
What is Shigellosis and its primary cause?
Caused by Shigella, gram-negative bacilli, transmitted via fecal-oral route.Most common cause of bloody diarrhea.
172
What is the pathogenesis of Shigellosis?
Shigella is acid stable, invades via M cells, infects epithelial cells, and can produce Shiga toxin leading to dysentery
173
What are the different types of pathogenic Escherichia coli and their features?
Enterotoxigenic E. coli (ETEC): Causes traveler’s diarrhea, produces heat-labile (LT) and heat-stable (ST) toxins.
Enterohemorrhagic E. coli (EHEC): Produces Shiga-like toxins, can cause dysentery and hemolytic-uremic syndrome.
Enteroinvasive E. coli (EIEC): Invades gut epithelial cells, produces bloody diarrhea.
Enteroaggregative E. coli (EAEC): Adheres to enterocytes with fimbriae, produces LT and Shiga-like toxins, minimal histologic damage.
174
What is the impact of viral infection on the small intestine's superficial epithelium?
Viral infection leads to the destruction of enterocytes, reducing absorptive function. This causes repopulation of villi with immature enterocytes and relative preservation of crypt secretory cells, leading to net secretion of water and electrolytes into the lumen and osmotic diarrhea from incompletely absorbed nutrients.
175
What are the most common viral agents causing enterocolitis?
The most common viral agents are rotavirus, calicivirus, and adenovirus.
176
What is the most common cause of severe childhood diarrhea and diarrhea-related deaths worldwide?
Rotavirus is the most common cause of severe childhood diarrhea and diarrhea-related deaths worldwide.
177
Which age group is most vulnerable to rotavirus infection, and why is there protection in certain age groups?
Children between 6 and 24 months of age are most vulnerable. Protection in the first 6 months of life is likely due to antibodies in breast milk, while immunity beyond 2 years develops after the first infection.
178
How does rotavirus affect the small intestine?
Rotavirus selectively infects and destroys mature absorptive enterocytes in the small intestine, leading to repopulation of villi by immature secretory cells. This results in a loss of absorptive function and net secretion of water and electrolytes.
179
Why are oral rotavirus vaccines less effective in developing countries?
For unknown reasons, oral rotavirus vaccines have been less effective in developing countries where they are most needed.
180
What is a diverticulum, and where is it most commonly located in the colon?
A diverticulum is a blind outpouching in the wall of the gut. It is most commonly located in the sigmoid colon (95% of cases).
181
What are the differences between congenital and acquired colonic diverticula?
Congenital diverticula (e.g., Meckel diverticulum) include all layers of the bowel wall (mucosa, submucosa, muscularis externa) and are uncommon. Acquired diverticula usually lack the muscularis mucosae or have a thin muscularis mucosae and are often pseudodiverticula of mucosa and submucosa penetrating the muscularis propria.
182
Why are diverticula most common in the colon?
Diverticula are most common in the colon due to its structure. The outer longitudinal layer of muscularis externa (teniae coli) creates focal defects when nerves and blood vessels penetrate to reach the inner layer of circular muscles.
183
What factors may contribute to the formation of diverticula?
Factors contributing to diverticula formation include constipation (often from a low-fiber diet leading to reduced stool bulk and increased difficulty in passage) and other conditions that increase intraluminal pressure.
184
Describe the morphology of diverticula in the colon.
Diverticula are small, spherical outpouchings (0.5-1cm in diameter) that penetrate between fibers of the circular muscle.
They are composed of atrophied, flattened mucosa and submucosa pushed into the circular layer. Inflammation can lead to diverticulitis, with the thin wall of the diverticulum potentially rupturing and causing peridiverticulitis, abscess formation, or peritonitis.
185
What are the clinical features of diverticulitis?
Diverticulitis produces continuous left-sided lower quadrant discomfort, a sensation of never being able to empty the rectum, left lower quadrant tenderness, and fever.
Less common complications include bleeding (hematochesia), perforation, and fistula formation.
186
T116 What are the main manifestations of malabsorption conditions?
Defective absorption of fat, carbohydrates, proteins, vitamins, electrolytes, and water. It commonly results in chronic diarrhea, with a hallmark of steatorrhea (fatty feces). The three most common chronic malabsorptive disorders in the US are pancreatic insufficiency, celiac disease, and Crohn disease.
187
How is diarrhea defined and what are its potential severities?
Diarrhea is defined as an increase in stool mass, frequency, or fluidity, typically to volumes greater than 200 mL per day. In severe cases, it can become life-threatening due to hypovolemia. It can be classified as secretory, osmotic, malabsorptive, or exudative.
188
What are the four primary digestive functions involved in malabsorption?
Intraluminal digestion: Enzymatic digestion of nutrients beginning in the mouth and continuing in the stomach and duodenum.
Terminal digestion: Hydrolysis of carbohydrates and peptides in the brush border of the small intestine.
Transepithelial transport: Transport of nutrients, fluid, and electrolytes across the epithelium.
Lymphatic transport: Transport of absorbed lipids.
189
How does cystic fibrosis cause intraluminal digestion defects?
Cystic fibrosis involves a defect in the CFTR gene, leading to defective intestinal and pancreatic chloride secretion. This results in exocrine pancreatic insufficiency, affecting intraluminal digestion due to the lack of pancreatic enzymes, and meconium ileus in newborns due to defective hydration.
190
What triggers celiac disease, and what genetic predispositions are associated with it?
Celiac disease is triggered by the ingestion of gluten-containing cereals in genetically predisposed individuals, particularly those of European origin. It is associated with HLA-DQ2 and HLA-DQ8 genotypes.
191
Describe the pathogenesis of celiac disease
Gluten is digested into gliadin peptides, which are transported across the epithelium.
In genetically predisposed individuals, gliadin is presented by antigen-presenting cells, leading to an inflammatory response involving CD8+ T cells and B cells.
This causes villous atrophy, loss of brush borders, increased turnover of enterocytes, and malabsorption.
192
What are the histopathological features of celiac disease?
Biopsy from the duodenum and proximal jejunum shows increased intraepithelial CD8+ T lymphocytes, intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy.
193
What are the clinical features and risks associated with celiac disease?
Histological features similar to other diseases; diagnosis is confirmed with biopsy and serum antigens. Treatment involves a gluten-free diet.
There is an increased risk of malignancy, including enteropathy-associated T cell lymphoma and small intestinal adenocarcinoma.
194
What is environmental (tropical) enteropathy and what are its impacts?
A syndrome of stunted growth and impaired intestinal function common in developing countries due to frequent intestinal infections. It leads to chronic nutrient absorption problems, malnutrition, and growth stunting in children, particularly during the first 2-3 years of life, critical for growth and brain development.
195
What is the histological appearance of environmental enteropathy?
The intestine in environmental enteropathy appears similar to that of celiac disease, making supplementary diets and vitamin administration insufficient to completely overcome the syndrome.
196
What causes lactose intolerance and what are its types?
Lactose intolerance is due to lactase deficiency, impairing terminal digestion of lactose and causing osmotic diarrhea. It has two types: congenital lactase deficiency (autosomal recessive mutation in the lactase gene) and acquired lactase deficiency (downregulation of lactase gene expression).
197
What is abetalipoproteinemia and what are its effects?
Abetalipoproteinemia is a deficiency of apoprotein B, which is required for chylomicron formation. Mucosal cells cannot export lipids, leading to diarrhea and steatorrhea. Microscopically, lipid vacuoles may be seen in enterocytes.
198
What characterizes irritable bowel syndrome (IBS)?
IBS is characterized by chronic and relapsing abdominal pain, bloating, and changes in bowel habits (diarrhea and constipation). Its pathogenesis involves psychological stressors, diet, and abnormal gastrointestinal motility, typically affecting individuals aged 20-40 with a female predominance.
199
What is microscopic colitis and its types?
Microscopic colitis causes chronic watery diarrhea with a normal macro appearance but identifiable by histology:
Collagenous colitis: Dense subepithelial collagen layer, increased intraepithelial lymphocytes, mixed inflammatory infiltrate in the lamina propria.
Lymphocytic colitis: Similar histology, normal thickness of the subepithelial collagen layer, and greater increase in intraepithelial lymphocytes.
200
What are the general symptoms and signs of malabsorption?
Symptoms and signs include diarrhea, flatus, abdominal pain, and weight loss due to nutrient malabsorption and excessive intestinal secretion.
201
What are the hematopoietic system effects of malabsorption?
Anemias result from deficiencies in iron and/or vitamin B12, and bleeding disorders result from vitamin K deficiency.
202
What are the musculoskeletal system effects of malabsorption?
Defective absorption of calcium, magnesium, vitamin D, and proteins results in osteopenia and tetany.
203
What are the endocrine system effects of malabsorption?
Amenorrhea, impotence, and infertility result from generalized malnutrition, and hyperparathyroidism results from prolonged calcium and vitamin D deficiencies.
204
What are the skin-related effects of malabsorption?
Purpura and petechiae from vitamin K deficiency, edema due to protein deficiency, and hyperkeratosis due to vitamin A deficiency
205
What are the nervous system effects of malabsorption?
Peripheral neuropathies due to deficiencies in vitamins A and B12.
206
T117 What is the most commonly affected part of the bowel in obstruction?
The small intestine is most commonly affected due to its small lumen, with about 80% of obstructions occurring there.
207
What is a hernia and how does it cause bowel obstruction?
A hernia is a weakness in the peritoneal wall that allows a serosa-lined sac of peritoneum to protrude. External herniation occurs when viscera intrude through the weakened wall, and incarceration happens when the herniated viscera become permanently trapped, impairing venous drainage and causing stasis and edema.
208
What are intestinal adhesions and how do they cause bowel obstruction?
Intestinal adhesions are fibrous bridges formed during healing after surgery or infection. The intestine can slide and become trapped by these adhesions, leading to internal herniation and obstruction.
209
What is intussusception and how does it cause bowel obstruction?
Intussusception occurs when a segment of the intestine telescopes into an adjacent distal segment, often due to peristalsis. This can lead to obstruction, compression of mesenteric vessels, and infarction. In adults, it may indicate an intraluminal mass such as a tumor.
210
What is volvulus and how does it cause bowel obstruction?
Volvulus is the twisting of a loop of bowel (or other structures like the ovary) around its base of attachment. This twisting constricts venous outflow and may also damage the arterial blood supply, leading to obstruction and infarction.
211
Which part of the digestive system hosts the most primary neoplasms?
The colon and rectum host more primary neoplasms than any other organ, while the small intestine is an uncommon site for benign or malignant tumors.
212
What are the two major types of polyps found in the intestine?
The two major types of polyps are sessile polyps (without a stalk) and pedunculated polyps (with stalks).
213
What are hyperplastic polyps and where are they commonly found?
Hyperplastic polyps are the most common polyps of the colon and rectum, typically found in the distal colon and rectum, and usually have no malignant potential.
214
What is a juvenile polyp and who does it typically affect?
A juvenile polyp is a hamartomatous polyp that usually arises in children under the age of 5.
215
What is Peutz-Jeghers syndrome?
Peutz-Jeghers syndrome is an autosomal dominant inherited syndrome characterized by hamartomatous polyps in the GI tract and hyperpigmented macules on the lips and oral mucosa.
216
What type of polyp is associated with inflammatory bowel disease?
Inflammatory polyps occur with acute or chronic inflammation and may be present in conditions such as ulcerative colitis.
217
What are adenomas and what is their malignant potential?
Adenomas are benign polyps with glandular origin. Although benign, they have the potential to become malignant (adenocarcinoma).
218
What are the classifications of GI stromal tumors?
GI stromal tumors can be classified as:
Tumors that show smooth muscle cell differentiation.
Tumors with neural differentiation.
Tumors with smooth muscle/neural dual differentiation.
Tumors lacking differentiation towards these lineages.
219
What is a carcinoid tumor?
Carcinoid tumors are neoplasms that arise from endocrine cells of the GI tract.
220
How can lymphomas involve the GI tract?
Lymphomas can involve the GI tract due to secondary spreading of non-Hodgkin lymphomas (extra-nodal location) or can arise as primary tumors in gastric MALT (mucosa-associated lymphoid tissue).
221
Are neoplasms of the small intestine common?
Neoplasms of the small intestine are uncommon. The most common neoplasm in the small bowel is metastasis, often from nearby organs such as the colon, ovary, pancreas, and stomach.
222
What are some benign tumors of the small intestine?
Benign tumors of the small intestine can include leiomyomas, fibromas, and lipomas. Most benign tumors are incidental submucosal lesions, though rarely they can be large enough to obstruct the lumen
223
What percentage of small-bowel tumors are malignant?
Approximately 64% of all small-bowel tumors are malignant.
224
What is the most common malignant tumor of the small intestine?
The most common malignant tumor of the small intestine is adenocarcinoma, particularly in the region of the papilla of Vater.
225
How do small-bowel adenocarcinomas resemble large-bowel adenocarcinomas?
Small-bowel adenocarcinomas share a similar geographic distribution with large-bowel adenocarcinomas, predominating in Western countries, and tend to co-occur in the same individuals.
They arise from premalignant adenomas, accumulate genetic mutations, and progress to carcinomas in situ and invasive adenocarcinomas, similar to the process in the colon.
226
What genetic mutations are common in small-bowel adenocarcinomas?
Kras mutation and p53 overexpression are common in small-bowel adenocarcinomas, similar to colorectal carcinomas.
However, mutation of the APC tumor suppressor gene, which is characteristic of colorectal carcinoma, does not commonly occur in small-bowel adenocarcinoma.
227
What percentage of small-bowel malignancies are sarcomas?
Sarcomas account for approximately 15% of small-bowel malignancies in the United States.
228
What are GI stromal tumors (GISTs)?
GI stromal tumors (GISTs) are mesenchymal neoplasms believed to be derived from the interstitial cells of Cajal in the GI tract.
They may exhibit partial differentiation with incomplete expression of muscle-associated antigens, and the term GIST is a more general term used for these tumors.
229
What are some histologic features of small-bowel sarcomas?
While some small-bowel sarcomas may exhibit clear histologic features of smooth muscle origin, many tumors display only partial differentiation with incomplete expression of muscle-associated antigens.
230
How can GI stromal tumors (GISTs) be classified?
GI stromal tumors can be classified as:Tumors that show smooth muscle cell differentiation.Tumors with neural differentiation.Tumors with smooth muscle/neural dual differentiation.Tumors lacking differentiation towards these lineages.
231
T118 What is a polyp and where are they most commonly found?
A polyp is a mucosal outward raised protrusion, commonly found in the colon. They can be sessile (without a connecting stalk, broad-based) or pedunculated (with a connecting stalk).
232
How are polyps classified?
Polyps are classified as non-neoplastic or neoplastic.
233
What is an inflammatory polyp?
An inflammatory polyp is a polypoid mass made up of inflamed and reactive mucosal tissue, caused by chronic cycles of injury and healing. The solitary rectal ulcer syndrome is an example.
234
What is solitary rectal ulcer syndrome and its clinical triad?
Solitary rectal ulcer syndrome is caused by impaired relaxation of the anorectal sphincter, creating a sharp angle at the anterior rectal shelf.
The clinical triad includes rectal bleeding, mucus discharge, and an inflammatory lesion of the anterior rectal wall.
235
What are hamartomatous polyps and how can they be classified?
Hamartomatous polyps are disorganized, tumor-like growths of mature cells normally present at the site. They can be sporadic or part of hamartomatous polyposis syndromes, which may include extra-GI involvement.
236
Describe juvenile polyps and their potential risks.
Juvenile polyps are hamartomatous and can be sporadic (solitary, no malignant potential) or syndromic (multiple lesions, increased risk for colonic adenocarcinoma and pulmonary arteriovenous malformation).
They mostly occur in children under 5 and are pedunculated, smooth-surfaced, small, and reddish
237
What is Peutz-Jeghers syndrome and its associated risks?
Peutz-Jeghers syndrome is an autosomal dominant disorder with multiple gastrointestinal hamartomatous polyps and mucocutaneous pigmented lesions.
It increases the risk of several malignancies, including colorectal, breast, gynecological, lung, and pancreatic cancers.
238
Describe the morphology of Peutz-Jeghers polyps.
Peutz-Jeghers polyps are large, pedunculated with a lobulated contour, and have a complex glandular architecture with bundles of smooth muscle.
239
What are hyperplastic polyps and their significance?
Hyperplastic polyps are the most common type of polyp, usually appearing in the 6th-7th decade of life with no malignant potential. They mostly occur in the left colon, rectum, and sigmoid colon, and are characterized by a serrated, saw-tooth appearance with a pileup of mature goblet and absorptive epithelial cells.
240
What is an adenoma?
An adenoma is a benign tumor formed from glandular structures in epithelial tissue.
241
How do colonic adenomas arise and what is their potential risk?
Colonic adenomas arise due to neoplastic proliferation and are benign lesions with the potential to become malignant. They are the second most common type of polyp after hyperplastic polyps, found in ~50% of older adults in the western world. Most colon adenocarcinomas arise from adenomas.
242
What factors increase the risk of a colonic adenoma developing into malignancy?
The risk of a polyp developing malignancy depends on its size (most important, >2 cm), sessile growth, villous histologic architecture, and the severity of epithelial dysplasia.
243
Describe the morphology of colonic adenomas.
Colonic adenomas range from 0.3 to 10 cm in diameter and can be pedunculated or sessile. The stalk is usually covered by non-neoplastic epithelium, but dysplastic epithelium is sometimes present. Histologically, they show dysplasia with pseudostratification, increased nuclear size, elongation, and hyperchromasia.
244
How are adenomas classified based on their histologic architecture?
Adenomas are classified as tubular, tubulovillous, or villous. Tubular adenomas are small and pedunculated with tubular glands. Villous adenomas are larger, sessile, and covered by slender villi. Tubulovillous adenomas have a mixture of both elements. Sessile serrated adenomas have a serrated appearance involving crypts.
245
What are the clinical features of smaller adenomas?
Smaller adenomas are asymptomatic until they cause bleeding. Tubular adenomas may secrete mucin rich in proteins and potassium, potentially leading to hypoproteinemia and hypokalemia.
246
What is familial adenomatous polyposis (FAP) and its risk?
FAP is an uncommon, autosomal dominant disorder characterized by multiple adenomatous polyps that carpet the colon mucosal surface, most of which are tubular adenomas. The risk of colorectal adenocarcinoma is nearly 100% by midlife unless prophylactic colectomy is performed. At least 100 polyps are necessary for a diagnosis of classic FAP.
247
What genetic defect is associated with familial adenomatous polyposis (FAP)?
FAP is associated with a mutation in the APC (adenomatous polyposis coli) gene, a tumor suppressor located on chromosome 5.
248
What is Gardner syndrome?
Gardner syndrome is a variant of FAP characterized by the presence of multiple adenomatous polyps along with osteomas (benign bone tumors usually seen in the skull), dental abnormalities, thyroid tumors, and fibromatosis (non-neoplastic fibrocyte proliferation usually in the mediastinum that destroys adjacent structures).
249
What is Turcot syndrome?
Turcot syndrome is a variant of FAP that includes the presence of multiple adenomatous polyps along with CNS tumors such as medulloblastoma and glial tumors.
250
What is Peutz-Jeghers syndrome?
Peutz-Jeghers syndrome is characterized by uncommon hamartomatous polyps in the gastrointestinal tract and melanin pigmentation of mucosal and cutaneous surfaces.
251
What is Cowden syndrome?
Cowden syndrome is characterized by hamartomatous polyps in the GI tract and an increased risk of neoplasms in the thyroid, breast, uterus, and skin
252
What is Lynch syndrome (Hereditary Nonpolyposis Colorectal Cancer - HNPCC)?
Lynch syndrome, also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC), is an autosomal dominant disorder caused by mutations in DNA mismatch repair genes, usually leading to microsatellite instability. It has a high risk of developing into colon cancer and other cancers.
253
What cancers are associated with Lynch syndrome?
Lynch syndrome is associated with a high risk of developing colon cancer, endometrial cancer, ovarian cancer, stomach cancer, small intestine cancer, hepatobiliary tract cancer, upper urinary tract cancer, brain cancer, and skin cancer.
254
Where in the colon do cancers associated with Lynch syndrome typically occur?
Cancers associated with Lynch syndrome often occur in the right colon and tend to develop at younger ages.
255
T119 What is the most common malignancy of the GI tract?
The most common malignancy of the GI tract is colorectal cancer, which is the 3rd most common site of cancer and the 3rd leading cause of cancer-related death.
256
What factors contribute to the development of colorectal cancer?
Factors contributing to colorectal cancer include:
Age (incidence peaks at 60-70 years)
Pre-existing conditions (e.g., ulcerative colitis, polyposis syndromes)
Lynch syndrome (hereditary non-polyposis colorectal cancer)
Dietary factors (low fiber, high carbohydrates and fats, low vitamins A, C, and E)
Genetic factors (overexpression of COX-2, mutations in specific oncogenes and tumor suppressor genes)
257
What is the APC/β-catenin pathway in colorectal carcinogenesis?
The APC/β-catenin pathway (adenoma-carcinoma sequence) involves chromosomal instability with stepwise accumulation of mutations in oncogenes and tumor suppressor genes, leading to colorectal cancer.
Key steps include:
Loss of APC tumor suppressor gene
Mutation of K-RAS
Loss of tumor suppressor genes (SMAD2, SMAD4, p53)
258
Describe the role of APC in the APC/β-catenin pathway.
APC is a tumor suppressor gene that promotes the degradation of β-catenin in the cytosol.
Loss of APC leads to β-catenin accumulation, nuclear translocation, and transcription of growth-promoting genes such as cyclin D1 and MYC, contributing to cell proliferation and polyp formation.
259
What happens when K-RAS is mutated in colorectal cancer?
Mutation of K-RAS results in the molecule remaining in an active state, constantly signaling for cell growth.
This leads to the formation of adenomatous polyps due to unchecked cell proliferation.
260
How does the loss of tumor suppressor genes like SMAD2, SMAD4, and p53 contribute to colorectal cancer?
Loss of SMAD2 and SMAD4 disrupts TGFβ signaling, leading to unrestrained cell proliferation. Loss of p53 prevents the induction of apoptosis, allowing neoplastic cells to evade death and continue growing.
261
What is the mismatch repair pathway in colorectal carcinogenesis?
The mismatch repair pathway (microsatellite instability) involves the accumulation of mutations in microsatellite repeats due to loss of mismatch repair genes, leading to colorectal cancer.
262
What is microsatellite instability?
Microsatellite instability refers to the accumulation of mutations in microsatellite repeats due to a deficiency in DNA mismatch repair. This condition disrupts coding sequences of genes, contributing to colorectal cancer development.
263
Which genes are commonly affected by mutated microsatellite sequences in colorectal cancer?
Mutated microsatellite sequences commonly disrupt the coding sequences of:
TGF-β receptor (leading to uncontrolled cell growth)
Pro-apoptotic protein BAX (enhancing survival of abnormal clones)
264
What are the key genetic alterations in the mismatch repair pathway of colorectal carcinogenesis?
Key genetic alterations include:
Mutation in the oncogene BRAF
Hypermethylation of CpG islands
Mutations in mismatch repair genes
Disruption of genes like TGF-β receptor and BAX
Typically, KRAS and TP53 are not mutated in this pathway
265
What is the significance of microsatellite instability, BRAF mutation, and CpG island methylation in colorectal cancer?
The combination of microsatellite instability, BRAF mutation, and methylation of specific targets like MLH1 characterizes the mismatch repair pathway of colorectal carcinogenesis.
266
T120 What type of tumors do the vast majority of colorectal cancers consist of?
The vast majority of colorectal cancers are adenocarcinomas, which arise from the mucosa cells of the colon.
267
How are well or moderately differentiated adenocarcinomas different from poorly differentiated ones in terms of prognosis?
Well or moderately differentiated adenocarcinomas generally have a better prognosis compared to the approximately 15% of poorly or undifferentiated tumors, which are associated with a poorer prognosis.
268
What is the characteristic feature of mucinous or colloid carcinomas in colorectal cancer?
Mucinous or colloid carcinomas produce moderate to prodigious amounts of mucin and are associated with less favorable five-year survival rates.
269
Describe the macroscopic appearance of colorectal carcinoma in the proximal colon.
In the proximal colon, colorectal carcinomas tend to grow as polypoid, exophytic masses that extend along one wall of the cecum and ascending colon but rarely cause obstruction.
270
Describe the macroscopic appearance of colorectal carcinoma in the distal colon.
In the distal colon, colorectal carcinomas tend to encircle the lumen, producing a constrictive ring that narrows the lumen.
271
What are the microscopic features of colorectal adenocarcinomas?
Microscopically, colorectal adenocarcinomas are composed of tall columnar epithelium with elongated, hyperchromatic nuclei and increased nuclear size.
They may present with three degrees of differentiation: well, moderate, and poorly differentiated.
Features include necrotic debris in gland lumens and a strong stromal desmoplastic response.
272
What is the histological appearance of well-differentiated colorectal adenocarcinoma?
Well-differentiated colorectal adenocarcinoma features neoplastic glands that are long and frond-like, similar to those seen in a villous adenoma.
There is a loss of goblet cells and normal gland architecture, and the tumor may induce a strong stromal desmoplastic response.
273
What is a common histological characteristic of invasive colorectal adenocarcinoma?
Invasive colorectal adenocarcinoma often shows strong stromal desmoplastic response, which gives the tumors their characteristic firm consistency.
274
What type of cancer is most common in the anus?
Cancers of the anus are most commonly squamous cell carcinomas.
275
Why is early screening for colon cancer important?
Colon cancer may remain asymptomatic for years, with symptoms developing gradually and slowly, making early screening from age 50 (or younger with a family history) crucial.
276
What are the common clinical features of cecal and right colonic cancers?
Cecal and right colonic cancers commonly present with fatigue, weakness, and iron deficiency anemia. Iron deficiency anemia in older men is particularly suspicious for GI cancer until proven otherwise.
277
What are the typical symptoms of left-sided colon cancer lesions?
Left-sided colon cancer lesions typically cause changes in bowel habits, left lower quadrant discomfort, and bleeding.
278
What are the two most important prognostic factors for colon cancer?
The two most important prognostic factors are the depth of invasion and the presence or absence of lymph node metastases.
279
How does colorectal cancer typically spread?
Colorectal tumors may spread by direct extension into adjacent structures and by metastasis through the lymph and blood vessels.
280
What are the preferred sites of metastasis for colorectal cancer?
The preferred sites of metastasis for colorectal cancer are the liver, regional lymph nodes, lungs, and bones. Note: The rectum usually does not metastasize to the liver as it does not drain via the portal circulation.
281
What does the TNM staging system for colorectal cancer stand for?
The TNM staging system stands for Tumor (depth of penetration into the colon wall), Nodes (lymph node involvement), and Metastasis (spread to other body parts).
282
How does the staging of colorectal cancer correlate with cancer mortality?
There is a close correlation between advancing stage and cancer mortality. Tumor size does not significantly impact the outcome, but the ability of colorectal cancer to grow and invade the colonic wall and lymphatic system determines its aggressiveness.
283
What are the methods used for detection and diagnosis of colorectal cancer?
Detection and diagnosis of colorectal cancer involve digital rectal examination, fecal testing for blood presence, barium enema, sigmoidoscopy, colonoscopy, biopsy for final confirmation, and radiographic studies (CT) to assess metastatic spread.
284
T121 What is the appendix and what conditions is it prone to?
The appendix is a normal true diverticulum of the cecum and is prone to acute and chronic inflammation. Rarely, tumors may also appear in the appendix.
285
Who is most commonly affected by acute appendicitis?
Acute appendicitis is most commonly seen in adolescents and young adults, but it can occur at any age. Males are affected more often than females with a ratio of 5:1.
286
What is the pathogenesis of acute appendicitis?
Acute appendicitis is commonly associated with obstruction in 50%-80% of cases. Continuous secretion of mucinous fluid after obstruction builds intraluminal pressure, compromising venous outflow.
Obstruction can be due to a fecalith, gallstone, tumor, or ball of worms. This leads to ischemic injury, bacterial proliferation, and inflammatory responses.
287
What are the microscopic features of acute appendicitis?
Acute appendicitis is marked by mucosal inflammation and necrosis.
Early acute appendicitis shows neutrophilic infiltration into mucosa, submucosa, and muscularis propria, and congestion of sub-serosal blood vessels.
Progression can lead to abscess formation (acute suppurative appendicitis), hemorrhagic ulceration, and gangrenous necrosis (acute gangrenous appendicitis). If it extends transmurally, it may result in acute peritonitis.
288
What are the macroscopic features of acute appendicitis?
Macroscopically, an inflamed appendix shows a dull, granular, red membrane on the serosa. The cut surface demonstrates yellowish-tan exudation with hyperemic mucosa.
289
What are the clinical features of acute appendicitis?
Clinical features include mild peri-umbilical discomfort, deep constant pain in the right lower quadrant (McBurney's point), anorexia, nausea, vomiting, low-grade fever, and mild elevated peripheral white cell count.
290
What disorders can present similar clinical features to acute appendicitis?
Disorders that may present similarly include mesenteric lymphadenitis (often secondary to Yersinia infection or viral enterocolitis), acute salpingitis, ectopic pregnancy, Mittelschmerz (pain associated with ovulation), and Meckel diverticulitis.
291
What are the most common tumors of the appendix?
The most common tumors of the appendix are carcinoids, which rarely metastasize. These tumors arise from endocrine cells of the GI tract and may appear at any age, usually during the 6th decade.
292
What is a mucinous neoplasm of the appendix and what can it cause?
Mucinous neoplasms of the appendix range from benign cystadenoma to mucinous cystadenocarcinoma. Mucinous cystadenocarcinoma can invade the wall to form intra-peritoneal cancer, leading to pseudomyxoma peritonei, a condition where cancerous cells produce abundant mucin, resulting in gelatinous ascites.
293
What are adenomas or non–mucin-producing adenocarcinomas of the appendix, and what can they cause?
Adenomas or non–mucin-producing adenocarcinomas can occur in the appendix and may cause obstruction and enlargement that mimics the changes of acute appendicitis.
294
What is a mucocele of the appendix?
A mucocele is a cystic dilation of the lumen of the appendix caused by mucinous secretion. It may result from non-neoplastic obstruction, such as a fecalith, leading to the accumulation of mucinous secretion, atrophy of mucin-secreting mucosal cells, and can be asymptomatic unless it ruptures.
It can also be a consequence of mucinous cystadenoma or mucinous cystadenocarcinoma.
295
What is a carcinoid tumor and where do most occur?
Carcinoid tumors are malignant tumors that arise from neuroendocrine secretory cells. The majority occur in the GI tract, with 40% found in the small intestine or stomach (from G cells). They can also be found in the lungs, tracheal-bronchial tree, and pancreas.
296
What are carcinoid tumors associated with?
Carcinoid tumors may be associated with Zollinger-Ellison syndrome and multiple endocrine neoplasia syndrome.
297
What are the morphological characteristics of carcinoid tumors?
Macroscopically, carcinoid tumors appear as intramural or submucosal masses creating small polypoid lesions, typically yellow or tan, with an intense desmoplastic reaction.
Microscopically, they have thin fibromuscular septa enclosing nests of tumor cells with a typical "salt and pepper" appearance of the nucleus due to chromatin and nucleoli.
298
How are carcinoid tumors graded and what is a high-grade neuroendocrine tumor?
Carcinoid tumors are graded based on mitotic activity. Low- or intermediate-grade neuroendocrine tumors are referred to as carcinoids.
High-grade neuroendocrine tumors are known as neuroendocrine carcinomas and frequently display necrosis, being most common in the jejunum in the GI tract.
299
What are the clinical features of carcinoid tumors?
Carcinoid tumors usually do not elicit paraneoplastic symptoms due to their secretion.
Symptoms depend on location, such as obstructive bronchial symptoms, recurrent infections, hemoptysis, or acute appendicitis in the upper GI tract.
Carcinoid syndrome, caused by vasoactive substances, occurs in less than 10% of patients due to liver metabolism of these substances.
300
How are carcinoid tumors classified based on embryonic gut derivation?
Foregut: Includes lung, bronchial, gastric, and duodenal carcinoids, rarely metastasizing and often cured by resection.
Gastrinomas (duodenal gastrin-producing carcinoid tumors) have been associated with proton pump inhibitor therapy.
Midgut: Includes small intestine and appendiceal carcinoids, which tend to be aggressive, though appendiceal carcinoids are almost uniformly benign.
Hindgut: Includes rectal carcinoid tumors, which tend to produce polypeptide hormones and may present with abdominal pain and weight loss; they only occasionally metastasize.
301
T122 What role does the liver play in regulating the composition of blood?
The liver regulates the composition of blood, including the amounts of sugar (glucose), protein, and fat that enter the bloodstream
302
What toxins does the liver remove from the blood?
The liver regulates the composition of blood, including the amounts of sugar (glucose), protein, and fat that enter the bloodstream.
303
What toxins does the liver remove from the blood?
The liver removes bilirubin, ammonia, and other toxins from the blood.
304
How does the liver process nutrients absorbed during digestion?
The liver processes most of the nutrients absorbed by the intestines during digestion, converting them into forms that can be used by the body. It also stores some nutrients, such as vitamin A, iron, and other minerals.
305
How does the liver process nutrients absorbed during digestion?
The liver processes most of the nutrients absorbed by the intestines during digestion, converting them into forms that can be used by the body. It also stores some nutrients, such as vitamin A, iron, and other minerals.
306
What important proteins and substances are produced by the liver?
The liver produces cholesterol, albumin, and clotting factors (chemicals needed to help blood clot).
307
How does the liver handle alcohol and drugs?
The liver breaks down (metabolizes) alcohol and many drugs.
308
What are the major clinical syndromes of liver disease?
The major clinical syndromes of liver disease are hepatic failure, cirrhosis, portal hypertension, and cholestasis.
309
What causes acute liver failure with massive hepatic necrosis?
Acute liver failure with massive hepatic necrosis is often caused by drugs or viral hepatitis and can lead to hepatic encephalopathy within 2-3 weeks.
310
What is the most common route to hepatic failure?
The most common route to hepatic failure is chronic liver disease, often manifesting as cirrhosis.
311
What is jaundice and what causes it in liver failure?
Jaundice is a yellow discoloration of the skin and sclerae, caused by systemic retention of bilirubin with serum levels above 2.0 mg/dL.
312
What are some clinical features of chronic liver failure?
Clinical features of chronic liver failure include jaundice, hypoalbuminemia, hyperammonemia, hyperestrogenemia, palmar erythema, and spider angiomas.
313
What are some complications of hepatic failure?
Complications of hepatic failure include multiple organ systems failure, coagulopathies leading to massive GI bleeding, respiratory/renal failure, pneumonia, and sepsis.
314
What is hyperammonemia and what causes it in liver failure?
Hyperammonemia is elevated levels of ammonia in the blood, caused by defective urea cycle function in the liver.
315
What clinical signs distinguish acute liver failure from chronic liver failure?
Acute liver failure may present as jaundice or encephalopathy without the clinical signs of chronic liver failure such as gynecomastia or spider angiomas.
316
What is hepatic encephalopathy?
Hepatic encephalopathy is a clinical syndrome of impaired brain function occurring in patients with advanced liver failure, manifesting in neuropsychiatric disturbances such as behavioral abnormality, confusion, deep coma, and death.
317
What are some neurologic signs associated with hepatic encephalopathy?
Neurologic signs of hepatic encephalopathy include rigidity, hyperreflexia, EEG changes, seizures, and asterixis (flapping tremor).
318
What is asterixis?
Asterixis, or flapping tremor, is a non-rhythmic, rapid extension-flexion movement of the head and extremities, characteristic of hepatic encephalopathy.
319
What is the main factor responsible for the brain abnormalities in hepatic encephalopathy?
Hyperammonemia, the accumulation of ammonia in the blood, is the main factor responsible for brain abnormalities in hepatic encephalopathy.
320
What are the two factors important in the genesis of hepatic encephalopathy?
The two important factors in the genesis of hepatic encephalopathy are severe loss of hepatocellular function and shunting of blood from portal to systemic circulation around the chronically diseased liver.
321
How does ammonia contribute to hepatic encephalopathy?
Ammonia bypasses the liver, accumulates in the systemic circulation, crosses the blood-brain barrier, and is metabolized by astrocytes to synthesize glutamine.
This increases osmotic pressure within astrocytes, causes mitochondrial dysfunction, and depletes glutamate and GABA.
322
How does hepatic encephalopathy manifest in acute settings?
In acute settings, elevation in blood ammonia impairs neuronal function and promotes generalized brain edema.
323
How does hepatic encephalopathy manifest in chronic settings?
In chronic settings, deranged neurotransmitter production leads to neuronal dysfunction.
324
T123 What does hepatitis describe in terms of liver pathology?
Hepatitis describes specific histopathologic patterns of hepatocyte injury associated with inflammation and, when chronic, with scarring.
325
What are the common causes of hepatitis?
Hepatitis viruses (A-E), autoimmune conditions, and drug- or toxin-induced hepatitides.
326
What is the main distinguishing factor between acute and chronic hepatitis?
The pattern of cell injury and severity of inflammation; acute hepatitis has less inflammation and more hepatocyte death than chronic hepatitis.
327
What characterizes the mononuclear infiltrates in hepatitis?
Mononuclear infiltrates predominate in all phases of most hepatitis diseases because they invoke T cell–mediated immunity.
328
Describe the macroscopic appearance of the liver in mild acute hepatitis.
The liver appears normal or slightly enlarged, red, and greenish if there is cholestasis.
329
Describe the macroscopic appearance of the liver in massive hepatic necrosis.
The liver may shrink to 500-700 g, becoming a limp, red organ covered by a wrinkled, baggy capsule.
330
What are the microscopic features of lobular disarray in hepatitis?
Lobular disarray involves the loss of normal architecture, hepatocyte swelling (ballooning degeneration), and hepatocyte necrosis (isolated cells or clusters or apoptosis).
331
What inflammatory changes are seen in the sinusoids during hepatitis
Inflammatory influx of mainly mononuclear cells into sinusoids, with inflammatory spillover into adjacent parenchyma, indicating lobular hepatitis. Kupffer cells undergo hyperplasia and hypertrophy.
332
What characterizes acute viral hepatitis?
Acute viral hepatitis is an infection of the liver caused by a small group of viruses, characterized by initial nonspecific flu-like symptoms followed by jaundice and abdominal discomfort.
333
How long does acute hepatitis typically progress before it's classified differently?
Less than 6 months.
334
What are the initial symptoms of acute viral hepatitis?
Nonspecific flu-like symptoms including malaise, muscle and joint pain, fever, nausea, and vomiting.
335
Which hepatitis viruses cause only acute hepatitis and not chronic hepatitis?
Hepatitis A virus (HAV) and Hepatitis E virus (HEV).
336
What indicates an acute HAV or HEV infection serologically?
The presence of IgM antibodies.
337
What does the presence of IgG antibodies against HAV or HEV indicate?
Resolution of the infection or past immunization (for HAV)
338
How are HAV and HEV transmitted?
By contaminated water and food.
339
What is a severe complication associated with HEV infection?
Fulminant hepatitis, which involves liver failure with massive liver necrosis.
340
What percentage of Hepatitis B virus (HBV) cases progress to chronic hepatitis?
Approximately 20% of HBV cases may progress to chronic hepatitis.
341
What is a significant complication of HBV-induced chronic liver disease?
It can be a precursor for the development of hepatocellular carcinoma.
342
What role does HBV-X play in the development of hepatocellular carcinoma?
HBV-X regulates p53 degradation and expression, which may contribute to the development of hepatocellular carcinoma.
343
How is HBV transmitted?
HBV is transmitted by blood and body fluids and vertically from mother to child. It is not present in stool.
344
What is the incubation period for HBV?
The incubation period ranges from 4 to 26 weeks.
345
What does the presence of Hepatitis B surface antigen (HBsAg) in the blood indicate?
HBsAg in the blood indicates an active HBV infection and is the initial serologic marker of acute infection.
346
What serological markers indicate a resolved HBV infection?
Presence of IgG against both HBcAg and HBsAg indicates a resolved HBV infection.
347
What serological markers are present in chronic HBV infection?
In chronic HBV infection, HBsAg is present for more than 6 months, and there is IgG against HBcAg but not against HBsAg. HBeAg or viral DNA indicates infectivity.
348
What serological marker indicates vaccination against HBV?
IgG against HBsAg indicates vaccination or resolved disease.
349
What serological marker is used to confirm HBV infectivity in chronic patients?
HBeAg or viral DNA in the blood confirms that the patient is infective.
350
How is Hepatitis C virus (HCV) transmitted?
HCV is transmitted by blood and intravenous drug use.
351
What is the incubation period for HCV?
The incubation period ranges from 2 to 26 weeks.
352
What percentage of acute HCV cases are asymptomatic?
75% of acute HCV cases are asymptomatic.
353
What is the hallmark of HCV infection?
Persistent infection, occurring in 80% to 85% of patients with subclinical or asymptomatic acute infection, is the hallmark of HCV infection.
354
What is the likelihood of HCV progressing to chronic liver disease and cirrhosis?
HCV is more likely to progress into chronic liver disease and eventual cirrhosis.
355
How does HCV infection affect the risk of hepatocellular carcinoma?
HCV infection confers a significantly increased risk for hepatocellular carcinoma.
356
What is required for Hepatitis D virus (HDV) replication?
HDV replication is dependent on HBV infection and requires encapsulation by HBsAg.
357
What is the difference between HDV coinfection and superinfection?
Coinfection: Simultaneous infection by both HBV and HDV, usually results in complete recovery.Superinfection: Initial HBV infection followed by HDV, leading to more severe hepatitis and chronic hepatitis.
358
What is the most reliable indicator of recent HDV exposure?
IgM anti-HDV antibody is the most reliable indicator of recent HDV exposure.
359
What are the possible clinical outcomes of viral hepatitis?
Asymptomatic acute infection (serologic evidence only)Acute hepatitis (anicteric or icteric)
Fulminant hepatitis (submassive to massive hepatic necrosis with acute liver failure)
Chronic hepatitis (with or without progression to cirrhosis)
Chronic carrier state (asymptomatic without apparent disease)
360
Which hepatitis virus is more likely to progress to a chronic state, HBV or HCV?
HCV is more likely to progress to a chronic state compared to HBV.
361
What are the four stages of acute viral hepatitis?
Incubation period
Symptomatic pre-icteric phase (fatigue, nausea, loss of appetite)
Symptomatic icteric phase (jaundice, conjugated hyperbilirubinemia, dark urine, possible hepatocellular damage)
Convalescence
362
T124 What characterizes chronic hepatitis?
Chronic hepatitis is characterized by persistent inflammatory injury to hepatocytes lasting longer than 6 months, associated with progressive fibrosis that can ultimately lead to liver cirrhosis.
363
Which viral hepatitis is most likely to cause chronic hepatitis?
Hepatitis C virus (HCV) is most likely to cause chronic hepatitis, which can evolve into cirrhosis. Hepatitis B virus (HBV) can also cause chronic hepatitis.
364
What is Wilson's disease and how does it relate to chronic hepatitis?
Wilson's disease is an autosomal recessive disorder of copper metabolism, resulting in copper accumulation in tissues such as the liver and brain due to defective excretion. This accumulation can lead to chronic hepatitis.
365
How does α1-antitrypsin deficiency contribute to chronic hepatitis?
α1-antitrypsin deficiency leads to a lack of the protease inhibitor A1AT, causing uncontrolled tissue destruction and contributing to chronic hepatitis.
366
How does chronic alcoholism lead to chronic hepatitis?
Chronic alcoholism leads to hepatic steatosis (fatty change) which can progress to liver cirrhosis and chronic hepatitis.
367
Which drugs are known to cause chronic hepatitis?
Isoniazid (used for TB treatment) and methyldopa (used for high blood pressure treatment) are known to cause chronic hepatitis
368
What role does autoimmunity play in chronic hepatitis?
Autoimmunity can lead to chronic hepatitis through persistent immune-mediated inflammation and injury to hepatocytes.
369
What type of infiltrates predominate in most hepatitis diseases?
Mononuclear infiltrates predominate in all phases of most hepatitis diseases due to T cell–mediated immunity.
370
How is the distinction between acute and chronic hepatitis made?
The distinction is based on the pattern of cell injury and the severity of inflammation. Chronic hepatitis has more inflammation and less cellular death compared to acute hepatitis.
371
What are the gross morphological features of the liver in chronic hepatitis?
The liver may appear normal or show focal scarring. As cirrhosis develops, it may feature widespread nodularity surrounded by extensive scarring.
372
What is the defining lesion of chronic hepatitis at the microscopic level?
Dense mononuclear and lymphocyte portal infiltrates in distended portal veins are the defining lesion of chronic hepatitis.
373
What is interface hepatitis?
Interface hepatitis is characterized by inflammatory infiltrates at the interface between hepatocellular parenchyma and portal stroma/scar.
374
What are the hallmark features of severe chronic liver damage?
The hallmark features include scarring and nodular masses of regenerating hepatocytes with interfering scar tissue, leading to cirrhosis.
375
What is a "ground glass" cell and in which hepatitis is it found?
A "ground glass" cell, characterized by the accumulation of HBsAg in the cytoplasm (large pale pink cytoplasm), is found in Hepatitis B virus (HBV) infection.
376
What microscopic changes are commonly seen in Hepatitis C virus (HCV) infection?
HCV infection commonly shows fatty change (altered lipid metabolism) and bile duct injury due to infection of cholangiocytes by the virus.
377
What are the clinical features of chronic hepatitis?
Mostly asymptomatic with some serum enzyme elevations (AST, ALT). Persistent elevations of serum aminotransferase levels indicate hepatocyte destruction.
Laboratory studies may show prolonged prothrombin time, and during hepatic decompensation, hypergammaglobulinemia, hyperbilirubinemia, and mildly elevated alkaline phosphatase levels.
378
What is autoimmune hepatitis and its main features?
Autoimmune hepatitis is a syndrome of chronic hepatitis with immunologic abnormalities,
characterized by female predominance (70%), no serologic markers for viral infection, elevated serum IgG (>2.5g/dL), presence of auto-antibodies (e.g., antinuclear, anti-smooth muscle cell),
and often associated with other autoimmune diseases (e.g., rheumatoid arthritis, thyroiditis, Sjogren syndrome, ulcerative colitis).
379
Who are the main effectors of cell damage in autoimmune hepatitis?
CD4+ helper cells are believed to be the main effectors of cell damage in autoimmune hepatitis.
380
How does autoimmune hepatitis typically manifest?
Autoimmune hepatitis can manifest as mild to severe chronic hepatitis.
381
How can you differentiate between viral and autoimmune hepatitis based on time course?
Autoimmune hepatitis often presents with an early onset compared to viral hepatitis.
382
What are the laboratory findings in chronic hepatitis?
Chronic hepatitis often shows persistent elevations of serum aminotransferase levels, prolonged prothrombin time,
hypergammaglobulinemia, hyperbilirubinemia, and mildly elevated alkaline phosphatase levels, especially during hepatic decompensation.
383
T125 What is the major function of the liver related to alcoholic liver disease?
The liver is the major detoxifying organ, making it subject to injury by drugs and toxins, including ethanol.
384
What are the pathways involved in the metabolism of ethanol?
Ethanol is oxidized to acetaldehyde by three different routes: alcohol dehydrogenase (ADH) in the cytosol, the cytochrome P-450 system (CYP2E1 isoform) in the endoplasmic reticulum, and catalase in peroxisomes.
Acetaldehyde is further oxidized to acetic acid by aldehyde dehydrogenase (ALDH) in the mitochondria.
385
What are the three different forms of alcoholic liver disease?
The three forms of alcoholic liver disease are:
Hepatic steatosis (intracellular fat accumulation)
Alcoholic hepatitis
Alcoholic cirrhosis
386
What causes hepatic steatosis in alcoholic liver disease?
Hepatic steatosis is caused by:
NADH production from ethanol metabolism by ADH, signaling the body to stop glycolysis and produce lipids, leading to lipid accumulation in hepatocytes
Impaired assembly and secretion of lipoproteins.
Increased peripheral catabolism of fat.
387
Describe the gross and microscopic morphology of hepatic steatosis.
Grossly, the liver is enlarged (4-6 kg), soft, yellow, and greasy. Microscopically, fatty liver disease shows steatosis most prominent around the central vein, extending outward to the portal tracts.
Intracytoplasmic fat appears as clear vacuoles: smaller ones as microvesicles, and larger ones as macrovesicles, which may push the nucleus aside.
388
Is hepatic steatosis reversible?
Yes, fatty change is a reversible state if alcohol consumption is stopped before fibrosis develops.
389
What are the clinical features of hepatic steatosis?
Hepatic steatosis presents with hepatomegaly and mild elevation of serum bilirubin and alkaline phosphatase.
390
What causes alcoholic hepatitis?
Alcoholic hepatitis is usually associated with acute episodes of excessive drinking and may result from the toxic by-products of ethanol and its metabolites:
acetaldehyde, alcohol itself, and reactive oxygen species (ROS).
391
What are the key toxic by-products involved in alcoholic hepatitis?
The key toxic by-products are:
Acetaldehyde: Disrupts cytoskeleton and lipid membranes, induces lipid peroxidation.
Alcohol: Direct injury to the cytoskeleton, mitochondria, and membrane fluidity.
Reactive Oxygen Species (ROS): Produced from ER metabolism and cytokine-mediated inflammation, especially TNF.
392
Describe the pathologic features seen in alcoholic hepatitis.
Pathologic features include:
Ballooning degeneration: Swelling and necrosis of hepatocytes.
Mallory-Denk bodies: Eosinophilic cytoplasmic inclusions of damaged intermediate filaments.
Neutrophil infiltration: Accumulation around degenerating hepatocytes, with lymphocytes and macrophages also entering portal tracts and parenchyma.
Steatohepatitis with fibrosis: Maximal generation of acetaldehyde and free radicals in the centrilobular region, leading to pericellular and sinusoidal fibrosis.
393
What are Mallory-Denk bodies, and in which condition are they found?
Mallory-Denk bodies are eosinophilic cytoplasmic inclusions composed of damaged intermediate filaments. They are found in alcoholic hepatitis.
394
What are the clinical features of alcoholic hepatitis?
Clinical features include:
Malaise and anorexia.
Painful hepatomegaly.
Elevated liver enzymes (AST > ALT).
Fever.
Hyperbilirubinemia.
Elevated alkaline phosphatase.
Neutrophilic leukocytosis.
395
What is alcoholic cirrhosis?
Alcoholic cirrhosis is the final and irreversible end-stage form of alcoholic liver disease, characterized by a brown, shrunken, non-fatty liver.
It results from chronic alcohol abuse and leads to fibrous scarring and nodular regeneration.
396
What is the significance of concurrent viral hepatitis in alcoholics?
Concurrent viral hepatitis, particularly hepatitis C, significantly accelerates the progression of liver disease in alcoholics.
Approximately 30% of alcoholics have hepatitis C, which exacerbates liver damage and speeds the development of cirrhosis.
397
What are the characteristic morphological changes in alcoholic cirrhosis?
Characteristic changes include:
Diffuse nodularity of the liver surface.
Small nodules with unorganized architecture entrapped by fibrous tissue.
Absence of fatty accumulation in the "burned-out" stage.
Transformation from a micronodular to a macronodular cirrhotic liver upon regeneration.
398
What are the clinical features of alcoholic cirrhosis?
Clinical features include:
Signs of portal hypertension (e.g., ascites, wasted extremities, Caput medusa).
Potential presentation with life-threatening variceal hemorrhage or hepatic encephalopathy.
The condition may also be clinically silent, discovered only at autopsy or when stress (e.g., infection, trauma) tips the balance toward hepatic insufficiency.
399
What can trigger the clinical presentation of alcoholic cirrhosis?
Triggers for clinical presentation can include complications of portal hypertension, such as ascites or variceal hemorrhage, as well as hepatic encephalopathy.
Stress factors like infection or trauma can also tip the balance toward hepatic insufficiency.
400
What are the laboratory findings in developing hepatic disease due to chronic alcoholism?
Laboratory findings include:
Elevated serum aminotransferase (AST and ALT)
Hyperbilirubinemia
Variable elevation of alkaline phosphatase
Hypoproteinemia (including globulins, albumin, and clotting factors)
Anemia
401
What nutritional deficiencies are common in chronic alcoholics and why?
Chronic alcoholics often suffer from malnutrition and vitamin deficiencies (e.g., thiamine, vitamin B12) because alcohol becomes a major caloric source, displacing other nutrients in the diet.
402
What are the immediate causes of death in end-stage alcoholic liver disease?
Immediate causes of death in end-stage alcoholic liver disease include:
Hepatic failure
Massive gastrointestinal hemorrhageIntercurrent infection
Hepatorenal syndrome
Hepatocellular carcinoma (in 3% to 6% of cases)
403
What is Non-Alcoholic Fatty Liver Disease (NAFLD)?
NAFLD is a condition where fatty liver disease develops in individuals who do not consume alcohol.
The liver can show steatosis, steatohepatitis, and cirrhosis. It is associated with insulin resistance and obesity.
404
What are the types of liver changes seen in NAFLD?
The types of liver changes in NAFLD include:
Steatosis (fat accumulation in liver cells)
Steatohepatitis (inflammation and fat accumulation in liver cells)
Cirrhosis (advanced scarring of the liver)
405
What conditions are associated with NAFLD?
NAFLD is associated with insulin resistance and obesity.
406
What are the two primary mechanisms of drug- and toxin-induced liver disease?
1. Direct toxic damage to hepatocytes (conversion of xenobiotic to active toxin).
2.Immune-mediated destruction of hepatocytes (acting as hapten).
407
What is the most common condition caused by drug-induced liver disease, and what is the most important agent?
Drug-induced liver disease is a common condition that may manifest as mild reactions or serious conditions like acute liver failure or chronic liver disease. The most important agent causing toxic liver injury is alcohol.
408
How are drug reactions classified in liver disease?
Predictable – occur in anyone who accumulates a sufficient dose of the drug (e.g., Acetaminophen toxicity).
Unpredictable – depend on the host's metabolic rate and immune response (e.g., Chlorpromazine and halothane reactions).
409
What is the morphology of massive necrosis in drug-induced liver disease?
The entire liver or only random areas may be involved.
Necrotic areas appear red and may be depressed.Massive loss of hepatic substance can shrink the liver to 500-700g.
Complete destruction of hepatocytes in continuous lobules leaves only the reticulin framework.
410
What are some drugs that induce hepatitis and how can drug-induced hepatitis be distinguished from chronic viral or autoimmune hepatitis?
Acetaminophen can lead to acute failure & transplantation.Isoniazid can cause chronic hepatitis.
Other drugs can induce autoimmune hepatitis.
Drug-induced hepatitis cannot be distinguished from chronic viral hepatitis or autoimmune hepatitis by clinical and histological means alone; serologic markers are critical for diagnosis.
411
What is Reye syndrome and what is its morphology?
Reye syndrome is a condition where children with viral illnesses take aspirin, leading to fulminant liver failure and encephalopathy.
It presents with hypoglycemia, elevated liver enzymes, nausea, vomiting, and may progress to coma and death.
Morphology includes hepatocellular microvesicular steatosis, cerebral edema, and mitochondrial alterations in electron microscopy (EM).
412
Which drugs can induce steatosis or steatitic hepatitis similar to alcohol?
Methotrexate and corticosteroids can induce steatosis.
Amiodarone can induce steatitic hepatitis similar to alcohol-induced liver disease.
413
T126 What is liver cirrhosis and what are its main characteristics?
Liver cirrhosis is the end-stage process of repeated liver injury and attempts at regeneration, characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules.
Main characteristics:
Fibrous septa – fibrous bands and scars around multiple adjacent lobules.
Parenchymal nodules – spherical lobules of hepatocytes in different stages surrounded by fibrosis.
Diffuse damage involving major parts of the liver.
414
What are the primary causes of liver cirrhosis?
Alcohol abuse – occurs in 10-20% of alcoholics.
Hemochromatosis – excess body iron leading to tissue damage.
Chronic infections – HBV/HCV, autoimmune hepatitis.
Biliary disease – e.g., primary biliary cirrhosis, primary sclerosing cholangitis.
Wilson disease – autosomal recessive defect in ATP-mediated hepatocyte copper transport.
415
What are the three central processes in the pathogenesis of cirrhosis
Death of hepatocytes – replaced by regenerating or newly formed hepatocytes encircled by fibrotic bands.
ECM deposition – types I and III collagen and other ECM components are deposited in the space of Disse.
Vascular reorganization – loss of sinusoidal endothelial cell fenestrations and development of vascular shunts contribute to hepatic dysfunction and portal hypertension.
416
What role do stellate cells play in liver cirrhosis?
Stellate cells, found in the space of Disse, transform into myofibroblasts upon inflammation (triggered by cytokines and growth factors from injured hepatocytes and Kupffer cells), becoming a source of collagen in cirrhosis.
417
Describe the morphology of a liver affected by cirrhosis.
The liver shows regenerative nodules surrounded by fibrous connective tissue extending between portal regions.
It has a shrunken, firm appearance with a nodular surface.
Nodules can be:
Micronodules: less than 3 mm.
Macronodules: over 1 cm.
418
What are the early symptoms and fatal complications of cirrhosis?
Nonspecific and include anorexia, weight loss, and weakness.
Fatal complications:
Progressive liver failure.
Complications associated with portal hypertension.
Development of hepatocellular carcinoma.
419
What are the different types of portal hypertension?
1. Pre-hepatic: Blockage of the portal vein due to occlusion, thrombosis, or vascular invasion of primary or secondary cancer.
2. Intra-hepatic:Cirrhosis (most common cause), massive fatty change, diffuse granulomatous disease (sarcoidosis).
Increased resistance to portal flow at the level of the sinusoids and compression of central veins by perivenular fibrosis and expanded parenchymal nodules.
3. Post-hepatic:Right-sided heart failure, Budd-Chiari syndrome (thrombosis of hepatic veins).
420
How does portal hypertension in cirrhosis develop?
Portal hypertension in cirrhosis results from:Increased resistance to portal flow at the level of the sinusoids.
Compression of central veins by perivenular fibrosis and expanded parenchymal nodules.
Another major cause is the increase in portal venous blood flow due to bacterial absorption from the gut bypassing the Kupffer cells, leading to increased production of NO and arterial vasodilation in the splanchnic circulation.
421
What is Budd-Chiari syndrome?
Budd-Chiari syndrome results from thrombosis of the hepatic veins, leading to post-hepatic portal hypertension. This condition can cause liver congestion, hepatomegaly, and ascites.
422
What are the clinical features and pathogenesis of ascites?
Clinical Features:Collection of excess fluid in the peritoneal cavity. The fluid is serous with a high albumin content.
Pathogenesis:Sinusoidal hypertension and hypoalbuminemia lead to movement of intravascular fluid into the extravascular space of Disse.
Leakage of fluid from the hepatic interstitium into the peritoneal cavity. With cirrhosis, hepatic lymphatic flow may approach 20 L/day, exceeding thoracic duct capacity.
423
What are porto-caval anastomoses, and what complications can they lead to?
When portal venous pressure rises, bypasses develop where systemic and portal circulation anastomose.
This can lead to:
Hemorrhoids: Veins around the rectum.
Esophageal varices: Veins in the esophageal venous plexus (rupture can cause hematemesis).
Caput medusa: Periumbilical veins.
Retroperitoneal venous plexus: Engorgement of veins.
424
What is hepatorenal syndrome, and what are its characteristics?
Hepatorenal syndrome is rapidly developing renal failure secondary to cirrhosis without any predisposing renal damage.
Characteristics:Increase in splanchnic blood flow.Increased peripheral resistance leads to marked decrease in renal blood flow, mainly affecting the renal cortex.
425
What are the complications of long-lasting congestion in the spleen due to cirrhosis?
Splenomegaly:Enlargement of the spleen, potentially reaching 1 kg.
May be accompanied by hypersplenism, which can lead to anemia, leukopenia, and thrombocytopenia due to increased destruction of blood cells within the enlarged spleen.
426
How does hepatic encephalopathy relate to cirrhosis and portal hypertension?
Hepatic encephalopathy results from:Accumulation of toxic metabolites (mainly ammonia) due to impaired liver function.
Shunting of blood from the portal to systemic circulation bypassing the liver, reducing detoxification.
It manifests as neuropsychiatric disturbances such as behavioral abnormalities, confusion, and coma.
427
What pulmonary complications can arise secondary to hepatic failure?
Changes in pulmonary blood flow due to hepatic failure can lead to:Portopulmonary hypertension: Increased pressure in the pulmonary arteries.
Hepatopulmonary syndrome: Abnormal oxygenation and blood flow in the lungs due to liver disease.
428
T127 What is hemochromatosis, and what are the two types?
Hemochromatosis: Disorders characterized by excessive accumulation of body iron.
Types:
Genetic (Hereditary Hemochromatosis):Genetic disorder, most commonly autosomal recessive.
Caused by mutation of the HFE gene (chromosome 6).Leads to accelerated iron absorption and deposition, primarily in the liver, pancreas, and heart.
Acquired (Secondary Hemochromatosis):Results from multiple blood transfusions, ineffective erythropoiesis (e.g., β-thalassemia), and increased iron intake.
429
What is the pathogenesis of hemochromatosis?
The body’s iron content is regulated by gastrointestinal absorption as there is no excretory pathway for excess iron.
Hepcidin: A liver-produced hormone that reduces plasma iron levels by downregulating iron transporters on enterocytes and macrophages.
HFE Mutation: In hereditary hemochromatosis, the HFE gene is mutated, leading to insufficient hepcidin production and unchecked iron absorption.
Iron Toxicity: Iron is directly toxic to tissues by:Lipid peroxidation due to free radicals.Stimulation of collagen formation.Direct interaction with DNA.
430
What are the morphological changes seen in hereditary hemochromatosis?
Morphological Changes:
Cirrhosis: Most patients show cirrhosis with deposition of hemosiderin as golden-yellow granules in hepatocytes, bile duct epithelium, and Kupffer cells, leading to micronodular cirrhosis without inflammation.
Diabetes Mellitus 1: Hemosiderin deposition in acinar cells and islets of Langerhans.
Skin Pigmentation: Due to hemosiderin in macrophages and fibroblasts, and increased melanin production.
Heart: Enlarged with hemosiderin granules in myocardial fibers, resulting in brown pigmentation and diffuse interstitial fibrosis
Joints: Hemosiderin deposition in the synovial lining leading to acute synovitis.
431
What are the clinical features of hemochromatosis?
More common in men, typically late onset around age 50.
Symptoms: Hepatomegaly, diabetes mellitus 1, cardiac dysfunctions (arrhythmias, cardiomyopathy), arthritis.
Blood Tests: Increased total plasma iron, reduced iron-binding capacity, increased transferrin saturation, increased ferritin production.
Risk: Significantly higher risk (200 times) for hepatocellular carcinoma development compared to the general population.
432
What is Wilson disease and what causes it?
Wilson Disease: An autosomal recessive disorder marked by the accumulation of toxic levels of copper in various tissues and organs, primarily the liver, brain, and eye.
Cause: Mutation in the ATP7B gene (chromosome 13), which encodes an ATPase metal ion transporter localized in the Golgi of hepatocytes.
433
Describe the pathogenesis of Wilson disease.
Normal Copper Physiology:
Absorption of ingested copper (2-5 mg/day).
Plasma transport in complex with albumin.
Hepatocellular uptake, binding to apoceruloplasmin to form ceruloplasmin.
Secretion of ceruloplasmin-bound copper into plasma (~95% of plasma copper).
Hepatic re-uptake from plasma and excretion of free copper into bile.
434
Pathogenesis in Wilson Disease
Normal initial steps of copper absorption and transport to the liver.
Defective ATP7B activity prevents binding to apoceruloplasmin and excretion into bile.
Copper accumulates in the liver, causing toxic injury by forming free radicals, binding to cellular proteins, and displacing metals from metalloproteins.
Excess copper escapes from damaged hepatocytes into circulation, depositing in other tissues and causing further damage
435
What are the morphological features of Wilson disease?
Liver: Mimics fatty liver disease, acute/chronic hepatitis, and may progress to cirrhosis.
Brain: Toxic injury primarily affects the basal ganglia, leading to atrophy.
Eyes: Kayser-Fleischer rings (green-brown rings) upon deposition in the basement membrane of the cornea, usually accompanying neurological involvement.
Note: Copper can be demonstrated with stains such as orcein, but its morphology is indistinguishable from other copper overload diseases like chronic obstructive cholestasis.
436
What is α1-antitrypsin deficiency?
An inherited metabolic disorder characterized by abnormally low serum levels of α1-antitrypsin (AAT), a protease inhibitor.
The major function of AAT is to inhibit proteases, particularly neutrophil elastase released at sites of inflammation.
It mainly affects the lungs (leading to pulmonary emphysema) and the liver (due to accumulation of mutated AAT).
437
Describe the pathogenesis of α1-antitrypsin deficiency.
The AAT gene, located on chromosome 14, is polymorphic. The most severe form is autosomal recessive and appears in patients homozygous for the Z allele of the AAT gene (PiZZ genotype), producing only 10% of normal AAT levels.
The PiZ polypeptide contains a substitution that causes misfolding of the protein in the hepatocyte endoplasmic reticulum, leading to accumulation, unfolded protein response, and apoptosis.
438
What are the morphological features of α1-antitrypsin deficiency?
Hepatocytes contain round to oval cytoplasmic globules composed of retained AAT, a glycoprotein that is strongly positive in a periodic acid–Schiff (PAS) stain.
Under electron microscopy, these globules lie within the smooth endoplasmic reticulum.
439
What are the clinical features of α1-antitrypsin deficiency?
Hepatic injury: Ranges from marked cholestasis with hepatocyte necrosis in newborns, to childhood cirrhosis, to chronic hepatitis or cirrhosis apparent later in life.
Cholestasis.
Pulmonary emphysema.
Chronic hepatitis.Cirrhosis.Hepatocellular carcinoma.
440
T128 What is biliary cirrhosis?
Biliary cirrhosis is a type of liver damage characterized by the retention and accumulation of bile during cholestasis, leading to liver cell injury and apoptosis.
This process can disrupt cell membranes, generate reactive oxygen species (ROS), and stimulate fibrogenesis by hepatic stellate cells, ultimately resulting in cirrhosis.
441
T128 What is biliary cirrhosis?
Biliary cirrhosis is a type of liver damage characterized by the retention and accumulation of bile during cholestasis, leading to liver cell injury and apoptosis.
This process can disrupt cell membranes, generate reactive oxygen species (ROS), and stimulate fibrogenesis by hepatic stellate cells, ultimately resulting in cirrhosis.
442
What is primary biliary cirrhosis (PBC)?
Primary biliary cirrhosis (PBC) is an autoimmune chronic, progressive cholestatic disease characterized by the nonsuppurative destruction of small and medium-sized intrahepatic bile ducts.
It mainly affects middle-aged women and is associated with other autoimmune diseases.
443
Describe the pathogenesis of primary biliary cirrhosis.
The exact pathogenesis is unclear, but approximately 90% of PBC patients have high levels of anti-mitochondrial antibodies.
It is suggested that exposure to certain xenobiotics may modify mitochondrial proteins, leading to decreased immunologic tolerance and triggering an immune response.
444
What are the morphological features of primary biliary cirrhosis?
Dense lymphocytic infiltrate in portal tracts with granulomatous or non-granulomatous destruction and loss of interlobular bile ducts.
Florid duct lesion: interlobular bile ducts are destroyed by poorly formed portal epithelioid granulomas, lymphocytes, plasma cells, and macrophages.
Portal-portal septal fibrosis due to necrosis of adjacent periportal parenchyma.
Two paths to end-stage liver disease:Portal hypertension leading to nodular regenerative hyperplasia.
Widespread duct loss leading to chronic cholestasis and eventual cirrhosis.
Mallory-Denk bodies (periportal location).
Vivid green discoloration of the liver.
445
What are the morphological features of primary biliary cirrhosis?
Dense lymphocytic infiltrate in portal tracts with granulomatous or non-granulomatous destruction and loss of interlobular bile ducts.
Florid duct lesion: interlobular bile ducts are destroyed by poorly formed portal epithelioid granulomas, lymphocytes, plasma cells, and macrophages.
Portal-portal septal fibrosis due to necrosis of adjacent periportal parenchyma.
Two paths to end-stage liver disease:Portal hypertension leading to nodular regenerative hyperplasia.
Widespread duct loss leading to chronic cholestasis and eventual cirrhosis.
Mallory-Denk bodies (periportal location).
Vivid green discoloration of the liver.
446
What are the clinical features and complications of primary biliary cirrhosis?
Occurs mainly in middle-aged women.
Associated with other autoimmune diseases such as celiac disease.
Progressive portal inflammation and scarring, leading to cirrhosis and liver failure over years to decades.
Portal hypertension and hepatomegaly due to nodular regenerative hyperplasia.
Chronic cholestasis with periportal or periseptal bile accumulation.
Development of cirrhosis and liver failure.
447
What are the clinical features and complications of primary biliary cirrhosis?
Occurs mainly in middle-aged women.
Associated with other autoimmune diseases such as celiac disease.
Progressive portal inflammation and scarring, leading to cirrhosis and liver failure over years to decades.
Portal hypertension and hepatomegaly due to nodular regenerative hyperplasia.
Chronic cholestasis with periportal or periseptal bile accumulation.
Development of cirrhosis and liver failure.
448
What is secondary biliary cirrhosis?
Secondary biliary cirrhosis occurs when the accumulation of bile is secondary to a prolonged obstruction of the extrahepatic biliary tree, leading to significant liver damage and cirrhosis.
449
What is secondary biliary cirrhosis?
Secondary biliary cirrhosis occurs when the accumulation of bile is secondary to a prolonged obstruction of the extrahepatic biliary tree, leading to significant liver damage and cirrhosis.
450
What are the common causes of secondary biliary cirrhosis?
The most common cause is extrahepatic cholelithiasis (gallstones). Other causes include biliary atresia, malignancies of the biliary tree, and tumors of the head of the pancreas.
451
What are the common causes of secondary biliary cirrhosis?
The most common cause is extrahepatic cholelithiasis (gallstones). Other causes include biliary atresia, malignancies of the biliary tree, and tumors of the head of the pancreas.
452
How does secondary biliary cirrhosis develop?
While the initial damage from cholestasis is reversible, secondary inflammation resulting from biliary obstruction leads to periportal fibrogenesis.
This fibrogenesis eventually causes scarring and nodule formation, resulting in secondary biliary cirrhosis.
453
How does secondary biliary cirrhosis develop?
While the initial damage from cholestasis is reversible, secondary inflammation resulting from biliary obstruction leads to periportal fibrogenesis.
This fibrogenesis eventually causes scarring and nodule formation, resulting in secondary biliary cirrhosis.
454
What is primary sclerosing cholangitis (PSC)?
Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder characterized by progressive fibrosis and destruction of extrahepatic and intrahepatic bile ducts of all sizes.
It is more common in middle-aged men and often associated with inflammatory bowel disease, especially ulcerative colitis.
455
What is the pathogenesis of primary sclerosing cholangitis (PSC)?
The exact cause of PSC is unknown (idiopathic), but it is associated with inflammatory bowel disease, particularly ulcerative colitis, and often presents with p-ANCA antibodies.
456
What are the key morphological features of primary sclerosing cholangitis (PSC)?
Patchy changes in the ducts showing "beading" due to narrow strictures alternating with normal or dilated segments.
Extrahepatic and large intrahepatic ducts show chronic and acute inflammation, edema, and scarring leading to narrowing.
Smaller ducts exhibit circumferential fibrosis ("onion skinning") with little inflammation, eventually leading to duct obliteration and scarring.
Bile ductular proliferation, portal-portal septal fibrosis, and cirrhosis in response to duct loss.
457
What are the key morphological features of primary sclerosing cholangitis (PSC)?
Patchy changes in the ducts showing "beading" due to narrow strictures alternating with normal or dilated segments.
Extrahepatic and large intrahepatic ducts show chronic and acute inflammation, edema, and scarring leading to narrowing.
Smaller ducts exhibit circumferential fibrosis ("onion skinning") with little inflammation, eventually leading to duct obliteration and scarring.
Bile ductular proliferation, portal-portal septal fibrosis, and cirrhosis in response to duct loss.
458
What are the clinical features and late complications of primary sclerosing cholangitis (PSC)?
Symptoms include fatigue, pruritus (itching), and obstructive jaundice. Late complications include cirrhosis and an increased risk of cholangiocarcinoma.
459
T129 What is the impact of hepatic artery inflow occlusion on the liver?
Occlusion of the hepatic artery does not usually produce ischemia due to the liver's dual blood supply (hepatic artery and portal vein).
However, thrombosis of the hepatic artery in a transplanted liver can lead to organ loss.
Localized parenchymal infarction may result from occlusion of an intrahepatic branch of the hepatic artery due to thrombosis, embolism, tumor, polyarthritis nodosa, or sepsis.
460
What are the consequences of portal vein obstruction and thrombosis
Portal vein obstruction and thrombosis can cause abdominal pain, portal hypertension (with ascites and esophageal varices), and bowel infarction due to congestion of blood in the bowel.
Acute intrahepatic obstruction of the portal vein leads to a demarcated area of red-blue discoloration (infarct of Zahn) characterized by hepatocellular atrophy and congested, distended sinusoids without necrosis.
Causes include peritoneal sepsis, pancreatitis, splenic vein thrombosis, and vascular invasion by cancer.
461
What is the most common intrahepatic cause of portal blood flow obstruction, and what are other causes?
The most common intrahepatic cause of portal blood flow obstruction is cirrhosis. Other causes include sickle cell disease and disseminated intravascular coagulation (DIC).
462
What is passive congestion and centrilobular necrosis of the liver, and what causes it?
Passive congestion and centrilobular necrosis result from right-sided cardiac dysfunction, leading to liver congestion.
Persistent congestion can cause centrilobular necrosis and, rarely, centrilobular fibrosis, creating a border that mimics mini-lobules around the central vein (cardiac sclerosis).
463
What are the morphological features of passive congestion and centrilobular necrosis in the liver?
Macro: Enlarged and cyanotic liver with rounded edges; "nutmeg liver" on the cut surface shows a mottled red appearance in the centrilobular areas due to hemorrhagic necrosis with pale periphery.
Micro: Centrilobular congested sinusoids and necrotic hepatocytes.
464
What is peliosis hepatis, and what are its causes and risks?
Peliosis hepatis is a condition characterized by primary sinusoidal dilation creating multiple blood-filled cavities.
The exact mechanism is unknown, but it is associated with exposure to anabolic steroids.
Lesions usually disappear after stopping the drug treatment, but there is a risk of hemorrhage if the lesions rupture.
465
What is Budd-Chiari syndrome, and what are its primary causes?
Budd-Chiari syndrome is characterized by the obstruction, primarily by thrombosis, of one or more major hepatic veins, leading to hepatomegaly, ascites, and abdominal pain.
It is associated with myeloproliferative disorders (especially polycythemia vera), pregnancy, use of contraceptives, and intra-abdominal cancers such as hepatocellular carcinoma.
466
What are the morphological features of Budd-Chiari syndrome?
Macro: The liver is swollen, congested, red-purple in color, and has a tense capsule.
Micro: Hepatic parenchyma shows centrilobular congestion and necrosis.
467
What causes sinusoidal obstruction syndrome, and what are its clinical manifestations?
Sinusoidal obstruction syndrome is caused by toxic injury to the sinusoidal endothelium, leading to cells sloughing off and creating emboli that block blood flow.
This is accompanied by blood cells entering the space of Disse, proliferation of Ito cells, and fibrosis of terminal branches of the hepatic vein.
It is seen mainly 20-30 days after bone marrow transplantation, typically due to chemotherapy injury during preparation for transplantation, and clinically manifests as Budd-Chiari syndrome.
468
Which visceral organs are most often involved by metastatic cancers, and what is the most common primary hepatic malignancy?
The liver and lungs are the visceral organs most often involved by metastatic cancers. The most common primary hepatic malignancy is hepatocellular carcinoma.
469
Which visceral organs are most often involved by metastatic cancers, and what is the most common primary hepatic malignancy?
The liver and lungs are the visceral organs most often involved by metastatic cancers. The most common primary hepatic malignancy is hepatocellular carcinoma.
470
Which visceral organs are most often involved by metastatic cancers, and what is the most common primary hepatic malignancy?
The liver and lungs are the visceral organs most often involved by metastatic cancers. The most common primary hepatic malignancy is hepatocellular carcinoma.
471
Which visceral organs are most often involved by metastatic cancers, and what is the most common primary hepatic malignancy?
The liver and lungs are the visceral organs most often involved by metastatic cancers. The most common primary hepatic malignancy is hepatocellular carcinoma.
472
Describe cavernous hemangiomas.
Cavernous hemangiomas are the most common benign lesions of the liver. They consist of endothelial-lined vascular channels and intervening stroma. These are red-blue, soft nodules, usually less than 2 cm in diameter, often directly beneath the capsule.
473
What are Von Meyenburg complexes?
Von Meyenburg complexes are congenital bile duct hamartomas, common benign liver lesions. They usually present as isolated or in small numbers, containing bile ducts and collagenous stroma. Multiple lesions may indicate polycystic liver disease and are linked to polycystic kidney disease.
474
What is focal nodular hyperplasia?
Focal nodular hyperplasia is a localized, well-demarcated, poorly encapsulated lesion appearing in an otherwise normal liver. It consists of hyperplastic hepatocyte nodules with a central fibrous scar and poses no risk of malignancy. It is not a true neoplasm but rather a response to abnormal vascular flow.
475
Describe hepatic adenomas and their clinical significance.
Hepatic adenomas are benign hepatocellular neoplasms that usually occur in women using oral contraceptive pills and may regress upon stopping the pills. They are well-demarcated, unencapsulated tumors up to 30 cm, pale yellow to bile-stained, composed of sheets and cords of cells resembling hepatocytes. They are significant because:
1. They can be mistaken for hepatocellular carcinoma.
2. Sub-capsular adenomas may rupture, causing life-threatening intra-abdominal hemorrhage.
3. They may carry β-catenin mutations, increasing the risk of developing cancer.
476
What are macro-regenerative nodules, and what is their clinical importance?
Macro-regenerative nodules appear in cirrhotic liver and are larger than surrounding cirrhotic nodules, but they do not have atypical features. They do not seem to be precursors for malignancy.
477
What are the most common precursors of hepatocellular carcinoma?
The most common precursors are cellular changes and nodular lesions found in the setting of chronic liver disease, particularly chronic viral hepatitis, alcoholic liver disease, and metabolic diseases.
478
Describe large cell change in hepatocellular dysplasia.
Large cell change involves very large hepatocytes with large pleomorphic nuclei found scattered among normal hepatocytes.
These cells are not believed to be on the pathway to malignant transformation but serve as a marker for molecular change.
479
Describe small cell change in hepatocellular dysplasia.
Small cell change is characterized by smaller-than-normal hepatocytes with normal-sized nuclei and oval hyperchromatic nuclei, situated in nodular clusters.
These cells are considered to be directly premalignant.
480
What are dysplastic nodules in the liver, and why are they significant?
Dysplastic nodules represent the major pathway to hepatocellular carcinoma in chronic liver disease.
Present in cirrhotic livers as nodules 1-2 cm in size, encompassing many adjacent hepatic lobules without displacing all of the portal tracts.
Hepatocytes in these nodules are highly proliferative with atypical features.
High-grade dysplastic lesions are considered precursors of hepatocellular cancers.
481
What is the most common type of primary liver cancer, and with what conditions is it highly associated?
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, highly associated with chronic viral infections (HBV or HCV), alcoholic cirrhosis, and aflatoxin exposure.
482
Describe the pathogenesis of hepatocellular carcinoma (HCC).
HCC development is influenced by various factors including viral infections (HBV or HCV), alcohol, and aflatoxin exposure.
It often arises from high-grade dysplastic nodules in a cirrhotic liver, which are monoclonal and carry chromosomal aberrations.
Chronic inflammation leads to DNA damage in tumor suppressor genes (e.g., tp53), oncogenes (e.g., beta-catenin), and DNA repair genes, contributing to genetic instability.
HCC frequently invades vascular structures such as the portal vein and IVC, leading to extensive intrahepatic metastases.
483
What are the morphological features of hepatocellular carcinoma (HCC)?
Macro: HCC can appear as a unifocal massive tumor, multifocal variable-sized nodules, or diffusely infiltrative cancer.
Micro: The tumor ranges from well-differentiated neoplastic cells to poorly differentiated lesions with multinucleated anaplastic giant cells.
In more differentiated forms, intracellular bile and pseudo-canalicular structures are recognized. The tumor is typically soft with a minor stroma amount.
Variant: Fibrolamellar carcinoma, a rare variant occurring in young adults without cirrhotic background, resembles nodular hyperplasia and includes stromal fibrous bands, carrying a better prognosis.
484
What are the clinical features of hepatocellular carcinoma (HCC)?
Clinical features of HCC include a rapid increase in liver size, sudden worsening of ascites, fever, and pain.
Serologically, alpha-fetoprotein is elevated in approximately 50% of patients. Radiologic screening of cirrhotic patients is primarily used to detect neoplastic lesions.
485
What is the most common tumor of the biliary tract and its associated risk factors?
Carcinoma of the gallbladder is the most common tumor of the biliary tract, often associated with gallstones, which are present in 60%-90% of cases, causing recurrent trauma and chronic inflammation that may promote the development of cancer.
486
Describe the morphology of gallbladder carcinoma.
Gallbladder carcinoma can appear in two forms:
Exophytic: Grows into the lumen as an irregular, cauliflower-like mass, while invading the underlying wall.
Infiltrative (more common): Appears as a poorly defined area of diffuse thickening of the gallbladder wall, which may involve the entire gallbladder.
487
What are the clinical features of gallbladder carcinoma?
Clinical features of gallbladder carcinoma include abdominal pain, jaundice, anorexia, nausea, and vomiting. These symptoms are similar to those of cholelithiasis (gallstones). The cancer is rarely detected early, and by the time it is diagnosed, it often has invaded the liver or extended to the cystic duct.
488
What is cholangiocarcinoma and where does it typically arise?
Cholangiocarcinoma is an adenocarcinoma that arises from the lining of the intrahepatic and extrahepatic biliary ducts. Extrahepatic cholangiocarcinoma may develop at the hilum of the liver (Klatskin tumors) or more distally in the biliary tree.
489
What are the key morphological features of cholangiocarcinoma?
Cholangiocarcinoma features well-differentiated adenocarcinomas with abundant fibrous stroma, giving the tumors a firm consistency. They present clearly defined glandular and tubular structures lined by anaplastic cuboidal epithelial cells.
490
Describe the typical clinical presentation and prognosis of cholangiocarcinoma.
Cholangiocarcinoma has a poor prognosis as it is typically asymptomatic until late stages. Symptoms of extrahepatic cholangiocarcinoma include jaundice, nausea, vomiting, and weight loss due to biliary obstruction. Intrahepatic cholangiocarcinoma may present with a liver mass and nonspecific symptoms.
491
What are the risk factors and genetic changes associated with cholangiocarcinoma?
Risk factors for cholangiocarcinoma include chronic cholestasis and inflammation, promoting mutations in cholangiocytes. Genetic changes commonly seen in cholangiocarcinoma include activating mutations in the KRAS and BRAF oncogenes and loss-of-function mutations in the TP53 tumor suppressor gene.
492
T130 What is cholangitis, and what is its most common cause?
Cholangitis is acute inflammation of the bile duct wall, most commonly caused by bacterial infection resulting from any lesion obstructing bile flow, typically cholelithiasis (presence of stones within the biliary tree).
493
How do bacteria typically enter the bile ducts to cause cholangitis?
Bacteria typically enter the bile ducts through the sphincter of Oddi rather than via the hematogenous route.
494
What is ascending cholangitis?
Ascending cholangitis refers to the tendency of bacteria, once within the biliary tree, to infect intrahepatic biliary ducts.
495
Which pathogens are commonly associated with cholangitis?
Common pathogens include E. coli, Klebsiella, Clostridium, Bacteroides, and Enterobacter.
496
What are the symptoms of cholangitis?
Symptoms of cholangitis include fever, chills, abdominal pain, and jaundice.
497
What is suppurative cholangitis, and what is the primary risk associated with it?
Suppurative cholangitis is the most severe form of cholangitis where purulent bile fills and distends bile ducts, posing a high risk of liver abscess formation and sepsis.
498
What are the primary causes of liver abscesses?
Liver abscesses primarily result from parasitic infections (more common in developed countries) or bacterial infections, often as a complication of infections elsewhere.
499
Which organisms are commonly responsible for liver abscesses?
Common organisms include amoebic parasites such as Entamoeba histolytica and Echinococcus, as well as bacterial agents like E. coli, Klebsiella, and Pseudomonas.
500
How can organisms reach the liver to cause abscesses?
Organisms can reach the liver through:
- Ascending infections in the biliary tree (ascending cholangitis).
- Vascular seeding (portal or arterial), mainly from the GI tract.
- Direct invasion from a nearby source.
- Penetrating injury.
501
What factors increase the risk of developing liver abscesses?
Immune deficiency and old age are common settings that increase the risk of developing liver abscesses.
502
What is the typical morphology of pyogenic hepatic abscesses?
Pyogenic hepatic abscesses can be solitary or multiple lesions, ranging from millimeters to centimeters in size, consisting of liquefactive necrosis with abundant neutrophils.
503
What are the clinical features of liver abscesses?
Clinical features include fever, right upper quadrant pain, and tender hepatomegaly. The abscess may also compress bile ducts or hepatic veins.
504
What is cholecystitis, and how is it classified?
Cholecystitis is the inflammation of the gallbladder, which can be acute or chronic and is almost always associated with gallstones.
505
What are the morphological characteristics of acute cholecystitis?
In acute cholecystitis, the gallbladder is enlarged, and the serosa is covered by fibrin.
In 90% of cases, stones obstruct the neck of the gallbladder or the cystic duct.
The lumen is filled with bile containing fibrin, blood, and pus. In mild cases, the wall is thickened and hyperemic; in severe cases, the gallbladder can become necrotic (gangrenous cholecystitis).
506
What is acute calculous cholecystitis, and what causes it?
Acute calculous cholecystitis is inflammation of the gallbladder containing stones that obstruct the neck or cystic duct.
It occurs due to the mucosal epithelium being exposed to the detergent action of bile salts and increased intraluminal pressure, which can compromise blood flow to the mucosa.
507
What are the morphological characteristics of chronic cholecystitis?
In chronic cholecystitis, changes are variable. If there is no superimposed acute inflammation, histology may show lymphocyte infiltration and submucosa thickening from scarring. The gallbladder size typically remains unchanged.
508
What is acute non-calculous cholecystitis, and what causes it?
Acute non-calculous cholecystitis is inflammation of the gallbladder without stones, caused by postoperative states, severe trauma, severe burns, or sepsis.
509
What are the clinical features of acute calculous cholecystitis?
The clinical features include severe pain in the upper abdomen and right shoulder, fever, nausea, leukocytosis, and conjugated hyperbilirubinemia.
510
What are the clinical features of chronic cholecystitis?
The clinical features include recurrent upper abdominal pain, nausea, vomiting, and intolerance for fatty food.
511
What are the two main types of gallstones in cholelithiasis?
The two main types of gallstones are:
Cholesterol stones (80%) – contain crystalline cholesterol monohydrate.
Pigment stones – composed of bilirubin calcium salts.
512
What is the pathogenesis of cholesterol gallstones?
Cholesterol gallstones form when cholesterol exceeds the solubilization capacity of bile and aggregates into solid crystals. This is enhanced by:
Supersaturation of bile with cholesterol.
Hypomobility of the gallbladder (stasis).
Mucous hypersecretion to trap crystals and enhance their aggregation.
513
What is the pathogenesis of pigment gallstones?
Pigment stones form due to an increase in unconjugated bilirubin, which increases the likelihood of stone formation. They are associated with hemolytic anemia and infections of the biliary tract.
514
What are the risk factors for gallstones?
Risk factors for gallstones include:
Age and gender (more common in older individuals and women).
Ethnic and geographic factors (more common in developed countries and Native Americans).
Heredity (family history).
Environmental factors (estrogen increases hepatic cholesterol uptake and synthesis).
Acquired disorders (conditions decreasing gallbladder motility, such as pregnancy, rapid weight loss, and spinal cord injury).
515
Describe the morphology of cholesterol and pigment gallstones.
Cholesterol stones: Arise only in the gallbladder, consist of 50%-100% cholesterol, are pale yellow, and radiolucent unless they contain sufficient calcium carbonate.
Pigment stones: Can arise anywhere in the biliary tree, classified as black or brown.
Black stones: Found in sterile gallbladder bile, small, numerous, radiopaque.
Brown stones: Found in intra/extrahepatic bile ducts, single or few, radiolucent, with a greasy, soap-like consistency.
516
What are the clinical features of gallstones?
Most individuals with gallstones remain asymptomatic (70%-80%). Symptoms include strong pain (constant or periodic), inflammation, empyema, perforation, and fistula formation.
517
T131 neoplasia of tumors
518
T132 What is pancreatitis and how does it range in severity?
Pancreatitis is inflammation of the pancreas, ranging in severity from mild, self-resolving cases to severe, destructive events.
Acute pancreatitis can lead to a return to normal function if the cause is removed, while chronic pancreatitis involves irreversible destruction of the exocrine pancreatic parenchyma.
519
What are the main causes of acute pancreatitis?
The main causes of acute pancreatitis are:
Biliary tract disease.
Alcoholism.
Genetic mutation in PRSS1 gene leading to hyperactivation of trypsin.
20% of cases are idiopathic.
520
What are the basic alterations seen in acute pancreatitis?
The basic alterations in acute pancreatitis include:
Microvascular leakage causing edema.
Necrosis of fat by lipases.
Acute inflammatory reaction.
Proteolytic destruction of pancreatic parenchyma.
Destruction of blood vessels leading to interstitial hemorrhage.
521
Describe the morphology of mild and severe acute pancreatitis.
Mild form: Edema and fat necrosis, with fat necrosis resulting from enzymatic destruction of fat cells, leading to the formation of insoluble calcium salts.
Severe form (acute necrotizing pancreatitis): Necrosis of pancreatic parenchyma and vascular damage causing hemorrhage.
Macro: Red-black hemorrhagic areas interspersed with yellow-white, chalky fat necrosis.
Most severe form (hemorrhagic pancreatitis): Extensive parenchymal necrosis accompanied by diffuse hemorrhage within the pancreas.
522
What is the clinical significance of hemorrhagic pancreatitis?
Hemorrhagic pancreatitis is the most severe form of acute pancreatitis, characterized by extensive parenchymal necrosis and diffuse hemorrhage within the pancreas, leading to significant clinical complications.
523
What is the pathogenesis of acute pancreatitis?
The pathogenesis of acute pancreatitis involves the autodigestion of pancreatic tissue by inappropriately activated pancreatic enzymes. Activation of trypsin is critical as it can activate other proenzymes, leading to autodigestion. Trypsin also activates the kinin system, clotting, and complement systems.
524
What are the three pathways that can cause enzyme activation in acute pancreatitis?
1. Pancreatic duct obstruction: Gallstone or tumor blockage increases intraductal pressure, leading to enzyme-rich fluid accumulation, fat necrosis, inflammation, and ischemic injury to acinar cells.
Primary acinar cell injury: Caused by ischemia, viral infections (e.g., mumps), drugs, and direct trauma, resulting in enzyme activation.
Alcohol consumption: Increases pancreatic exocrine secretion, causes sphincter of Oddi contraction, has direct toxic effects on acinar cells, and results in protein-rich fluid secretion that obstructs small pancreatic ducts.
525
What are the clinical features of acute pancreatitis?
Abdominal pain is the major manifestation.
Full-blown acute pancreatitis is a medical emergency.
Severe cases involve systemic release of digestive enzymes and inflammatory response activation, leading to leukocytosis, DIC, ARDS, diffuse fat necrosis, and shock.
526
What is a pancreatic pseudocyst?
A pancreatic pseudocyst is a walled-off area of liquefied necrotic pancreatic tissue surrounded by fibrous tissue, lacking an epithelial lining.
527
What distinguishes chronic pancreatitis from acute pancreatitis?
The chief distinction is the irreversible impairment in pancreatic function seen in chronic pancreatitis, which involves long-standing inflammation, fibrosis, and destruction of the exocrine pancreas, and in late stages, the endocrine parenchyma.
528
What are the common causes of chronic pancreatitis?
Long-term alcohol abuse (most common).
Pancreatic duct obstruction (e.g., tumor, stone).
Hereditary pancreatitis (mutation in PRSS1 gene).
Associated with CFTR mutation (decreased bicarbonate secretion leading to increased viscosity of secretion and plugging).
529
Describe the morphology of chronic pancreatitis.
Parenchymal fibrosis, reduced number and size of acini, variable dilation of pancreatic ducts.
Ductal epithelium may be atrophied or hyperplastic.
Islets of Langerhans are surrounded by sclerotic aggregates.
The gland is hard, sometimes with extremely dilated ducts and visible calcified concretions.
Autoimmune pancreatitis shows lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis.
530
What are the proposed hypotheses for the pathogenesis of chronic pancreatitis?
Ductal obstruction: Alcohol increases protein concentration in secretions, leading to plugs.
Toxins: Direct toxic effect causing injury to acinar cells, followed by inflammation and fibrosis.
Oxidative stress: Alcohol generates reactive oxygen species (ROS) leading to membrane damage, chemokine expression, recruitment of inflammatory cells, lysosomal and proenzyme granule fusion, and subsequent enzyme activation causing further cell damage.
531
What are the clinical features of chronic pancreatitis?
Severe pancreatic exocrine insufficiency and chronic malabsorption.
Development of diabetes mellitus.
Severe chronic pain may dominate the clinical picture.
532
T133 What are the general characteristics of pancreatic exocrine neoplasms?
Pancreatic exocrine neoplasms can be cystic or solid and can be benign or malignant. They constitute 5% of all pancreatic tumors.
533
Describe serous cystadenomas.
Composed of glycogen-rich cuboidal cells surrounding small cysts containing clear, straw-colored fluid.
More common in females, especially in the seventh decade of life.
Almost uniformly benign and curable by surgical removal.
Associated with somatic mutation of the von Hippel-Lindau tumor suppressor gene, which affects the degradation of hypoxia-induced factor alpha-1.
534
What are the characteristics of mucinous cystic neoplasms?
Vast majority arise in women and occur in the body or tail of the pancreas, presenting as painless, slow-growing masses.
Cysts are large and filled with sticky-viscous mucin, with walls lined by columnar mucinous epithelium and dense cellular stroma (similar to the ovary).
Benign types categorized by degree of dysplasia: low-grade, moderate, and high-grade dysplasia, all curable when completely removed.
About a third progress to malignant invasive types, designated as mucinous cystic neoplasm with an associated invasive carcinoma.
535
Describe intraductal papillary mucinous neoplasms (IPMNs).
Tumors that grow within the pancreatic ducts and produce thick mucinous fluid.
Arise in the main pancreatic duct or its major branches as papillary tumors, distending the lumen.
Histologically, cysts contain mucin and lack the cellular stroma seen in mucinous cystic neoplasms.
Benign types categorized by the severity of dysplasia; malignant types are associated with adenocarcinoma components.
More frequent in males and commonly involve the head of the pancreas.
536
What are the common sites for mucinous cystic neoplasms and IPMNs?
Mucinous cystic neoplasms commonly occur in the body or tail of the pancreas.
Intraductal papillary mucinous neoplasms (IPMNs) more frequently involve the head of the pancreas.
537
What are the main types of pancreatic exocrine neoplasms?
Serous cystadenomas
Mucinous cystic neoplasms
Intraductal papillary mucinous neoplasms (IPMNs)
Pancreatic adenocarcinoma
538
Describe pancreatic adenocarcinoma.
Very high mortality rate
Most common in older age around 70
Risk factors: smoking, chronic pancreatitis, diabetes mellitus
539
What is the pathogenesis of pancreatic adenocarcinoma?
Genetic disease due to inherited and acquired mutations in cancer-associated genes.
Progressive accumulation of genetic changes from non-neoplastic to non-invasive lesions (PanIN, MCN, IPMN) to invasive carcinoma.
Key genes affected: K-RAS, P16, SMAD4, P-53
PanIN-3 shows significant nuclear pleomorphism
540
What are the clinical presentations of pancreatic adenocarcinoma?
Abdominal pain and weight loss
Obstructive jaundice (especially in the head of the pancreas)
Pancreatitis
Migratory thrombophlebitis (Trousseau sign)
541
Describe the morphology of pancreatic adenocarcinoma.
Common sites: head (60%), body (15%), tail (5%), diffuse (20%)
Highly invasive, metastasizing to nearby organs and distant sites (lung, bone)
Poorly formed glands surrounded by dense fibrotic stroma (desmoplasia)
Variants: adenosquamous carcinoma, undifferentiated carcinoma with osteoclast-like giant cells
542
How is pancreatic adenocarcinoma screened and treated?
Screening: Endoscopic ultrasound (US) and CTT
reatment: Surgical excision (Whipple procedure)
Prognosis: Very poor, 1-year survival rate
Tumor markers: CEA and CA19-9 (not specific and not sensitive)
543
What are pancreatic neuroendocrine tumors (PanNETs)?
A type of neuroendocrine tumor found in the pancreas, also known as islet cell tumors or islet cell carcinoma.
Only 2% of pancreatic tumors arise in islet cells; the vast majority are adenocarcinoma.
All PanNETs, except insulinomas, are regarded as having malignant potential.
544
What are the key genes involved in PanNETs?
MEN1 (Multiple Endocrine Neoplasia type 1)
PTEN (tumor suppressor gene, negative regulator of TOR signaling pathway)
545
Describe insulinomas.
Most common type of islet cell tumor.
Produce insulin, causing hypoglycemia.
Symptoms: hypoglycemia, sweating, hunger, confusion; elevated insulin and C-peptides in labs.
Usually small (<2 cm), localized, and solitary.
Morphology: resemble giant islets, may have amyloid deposition; neoplastic beta-cells have round granules under EM.
546
What is Zollinger-Ellison syndrome and its association with gastrinomas?
Tumor produces gastrin, leading to elevated serum gastrin and gastric hyperacidity.
Symptoms: intractable peptic ulcers, potentially in unusual locations like the jejunum.
Can occur in the pancreas or duodenum, often locally invasive or metastatic at diagnosis.
Often associated with MEN-1 syndrome.
547
Describe glucagonomas.
Typically large tumors occurring within the pancreas.
Secrete excessive glucagon, causing glucose intolerance, weight loss, and necrolytic migratory erythema.
Symptoms: hyperglycemia (diabetes), anemia, and skin rash.
548
What are the effects of somatostatinomas?
Tumor produces somatostatin, leading to:Inhibition of insulin secretion -> diabetes
Inhibition of gastric secretion -> hypochlorhydriaInhibition of cholecystokinin secretion -> gallstones and steatorrhea
549
Describe VIPomas and the WDHA syndrome.
Tumor produces vasoactive intestinal peptide (VIP).
WDHA syndrome: watery diarrhea, hypokalemia, and achlorhydria.
Effects on digestive system: smooth muscle relaxation, stimulation of water and bicarbonate secretion in pancreatic juice and bile, inhibition of gastric acid secretion, dilation of peripheral blood vessels.
550
T134 What are the primary mechanisms by which hyperglycemia causes tissue damage?
Non-enzymatic glycosylation
Activation of protein kinase C (PKC)
Intracellular hyperglycemia
551
Describe the effects of non-enzymatic glycosylation in hyperglycemia.
Formation of advanced glycosylation end products (AGE) on collagen and extracellular matrix proteins.
Trapping of LDL and cholesterol, leading to atherosclerosis.
Glycosylated basement membrane binds albumin, contributing to diabetic nephropathy.
AGE residues on plasma proteins activate endothelial cells, mesangial cells, and macrophages, increasing permeability, coagulation, fibroblast proliferation, and inflammation
552
What is the role of protein kinase C (PKC) activation in hyperglycemia-induced damage?
PKC activation leads to increased synthesis of vascular endothelial growth factor (VEGF).
Results in increased synthesis of extracellular matrix and basement membrane components.
553
How does intracellular hyperglycemia cause tissue damage?
Affects cells not requiring insulin for glucose uptake (nerve, lens, kidney, endothelial cells).
Leads to increased osmolarity and oxidative stress.
Causes alternative glucose metabolism, resulting in sorbitol and fructose accumulation.
554
What are the important morphologic changes in the pancreas associated with diabetes mellitus?
Reduction in the number and size of islets (mainly in type I DM).
Leukocytic infiltration of islets, predominantly mononuclear cells (lymphocytes, macrophages).
Amyloid replacement of islets in long-standing type II DM.
Hyperplasia of islets in non-diabetic newborns of diabetic mothers.
555
What morphologic changes occur in the pancreas in long-standing type II diabetes mellitus?
Amyloid deposition in islets, appearing as pink, amorphous material in capillaries and between cells.
Advanced stages show obliteration of islets and possible fibrosis.
556
What are the key characteristics of diabetic macrovascular disease?
Accelerated atherosclerosis affecting the aorta and medium-sized arteries.
Most common cause of death is myocardial infarction.
Increased risk of gangrenes in lower extremities (diabetic foot).
Narrowing of the renal artery.
AGEs induce crosslinking of collagen, causing vascular stiffening and promoting atherosclerosis.
557
How do advanced glycation end products (AGEs) promote atherosclerosis in diabetes?
AGEs induce crosslinking of collagen in blood vessel basement membranes, causing vascular stiffening.
AGEs trap LDL particles in artery walls.
Glycation and oxidation of LDL promote atherosclerosis.
AGEs bind to RAGE receptors, causing oxidative stress and activating inflammatory pathways in endothelial cells.
558
What is diabetic microangiopathy and which organs does it affect?
Diabetic microangiopathy is characterized by diffuse thickening of basement membranes.
Most evident in the capillaries of the skin, skeletal muscle, retina, renal glomeruli, and renal medulla.
Also affects renal tubules, peripheral nerves, and placenta.
Despite increased thickness, capillaries are more leaky to plasma proteins.
559
Describe hyaline arteriosclerosis and its association with diabetes.
Hyaline arteriosclerosis involves amorphous hyaline thickening of arteriolar walls, leading to lumen narrowing.
Commonly associated with hypertension.
More severe and prevalent in diabetic patients.
560
What are the clinical consequences of diabetic microangiopathy?
Underlies the development of nephropathy, retinopathy, and neuropathy.
Leads to increased capillary permeability to plasma proteins, contributing to organ damage.
561
What are the primary mechanisms by which hyperglycemia damages the vascular system in diabetes?
Non-enzymatic glycosylation (AGE formation).
Activation of protein kinase C (PKC).
Intracellular hyperglycemia and oxidative stress.
562
What is diabetic nephropathy and what structures does it affect in the kidney?
Diabetic nephropathy is a complication of diabetes involving the kidneys.
Affects glomeruli, arterioles, and renal papillae.
Includes diabetic glomerulosclerosis, arteriolosclerosis, and papillary necrosis.
563
What is diabetic glomerulosclerosis and how does it present?
Diabetic glomerulosclerosis is characterized by thickening of the glomerular basement membrane.
Increased permeability leads to protein deposits (collagen IV) in the mesangial space.
Presents as either diffuse or nodular glomerulosclerosis.
564
Describe the characteristic lesion of nodular diabetic glomerulosclerosis.
Nodular diabetic glomerulosclerosis, also known as Kimmelstiel-Wilson lesion, features PAS-positive nodules.
Contains hyaline, mucopolysaccharides, fibrils, and collagen.
Nodules appear in the mesangial space, at the periphery of the glomerulus, pushing capillaries.
565
What are the features of diffuse diabetic glomerulosclerosis?
Characterized by thickening of the basement membranes of glomerular capillary loops.
Deposits also appear on basement membranes of tubules and arterioles.
Leads to increased permeability and proteinuria.
566
How does diabetic nephropathy contribute to renal failure?
Diabetic nephropathy can lead to chronic renal failure through progressive glomerulosclerosis.
Arteriosclerosis and recurrent pyelonephritis further damage kidney function.
Can result in small, scarred kidneys with granular surfaces.
567
What is the significance of hyaline arteriosclerosis in diabetic nephropathy?
Hyaline arteriosclerosis affects afferent and efferent arterioles, leading to hypertension.
Contributes to glomerulosclerosis and renal damage.
Preferential involvement of efferent arterioles leads to glomerular hyperfiltration injury and microalbuminuria.
568
What is necrotizing papillitis and how is it related to diabetic nephropathy?
Necrotizing papillitis is a severe form of acute pyelonephritis affecting renal papillae.
Common in diabetic nephropathy due to recurrent pyelonephritis.
Involves inflammation and necrosis of renal papillae.
569
What role does recurrent pyelonephritis play in diabetic nephropathy?
Recurrent pyelonephritis is an acute or chronic inflammation of the kidney, starting in the interstitial tissue and spreading to the tubules.
Leads to necrotizing papillitis and further renal damage.
Increases the risk of chronic renal failure.
570
What is diabetic retinopathy and why is it significant?
Diabetic retinopathy is a leading cause of new blindness in persons aged 25-74 in the United States.
It is characterized by damage to the retinal blood vessels due to chronic hyperglycemia.
Can lead to vision loss if not managed properly.
571
Differentiate between non-proliferative and proliferative diabetic retinopathy.
Non-proliferative retinopathy: Involves microangiopathy, microaneurysms, hemorrhages, and exudates.
Early stage.
Proliferative retinopathy: Involves angiogenesis and fibrosis, leading to retinal detachment. Advanced stage.
572
What causes microaneurysms in non-proliferative diabetic retinopathy?
High blood glucose levels lead to accumulation of sorbitol in retinal capillaries.
Affects intramural pericytes, leading to loss of capillary autoregulation.
Results in weakness and saccular outpouching of capillary walls, forming microaneurysms.
573
Explain the pathogenesis of proliferative diabetic retinopathy.
Caused by retinal ischemia and hypoxia, leading to the release of angiogenic factors like VEGF.
Results in the formation of new, fragile blood vessels that can bleed and cause vision problems.
Fibrovascular proliferation can lead to tractional retinal detachment.
574
How does diabetic retinopathy lead to cataracts?
Intracellular accumulation of sorbitol leads to osmotic changes in the lens fibers.
Hydropic lens fibers degenerate, forming sugar cataracts.
Changes affect the optical properties of crystallins in the lens.
575
What is glaucoma and how is it related to diabetes?
Glaucoma is an optic neuropathy characterized by optic nerve damage and visual field loss.
Often caused by increased intraocular pressure due to impaired aqueous humor outflow.
In proliferative retinopathy, new blood vessels can grow into the anterior chamber angle, causing neovascular glaucoma.
576
Describe the flow of aqueous humor in the eye.
Produced by the pars plicata of the ciliary body.
Discharged into the posterior chamber, flows between the lens and iris, through the pupil, into the anterior chamber.
Exits via the trabecular meshwork into Schlemm's canal and then through intrascleral and episcleral veins.
577
What is diabetic neuropathy?
Diabetic neuropathy is peripheral nerve involvement, typically symmetric neuropathy of the lower extremities affecting both motor and sensory function.
Can also present as autonomic neuropathy, causing disturbances in bowel, bladder function, and sexual impotence.
578
What are the causes of diabetic neuropathy?
Diabetic microangiopathy, leading to poor blood supply to nerves.
Direct toxic effects of glucose metabolism, such as sorbitol accumulation in Schwann cells.
Sorbitol causes osmotic damage to Schwann cells which myelinate peripheral nerves.
579
How does sorbitol contribute to diabetic neuropathy?
Glucose freely enters Schwann cells.
Aldose reductase converts glucose to sorbitol.
Sorbitol causes osmotic damage to Schwann cells, impairing their function in myelinating peripheral nerves.
