GI: Gastrointestinal Pathology Flashcards by James Wren

Infection w/ Mumps Virus (Paramyxovirus) resulting in Bilateral Inflamed Parotid Glands
Parotitis, Fever, Myalgias, Headache, Anorexia, Orchitis, Pancreatitis, and Aseptic meningitis may also be present
Serum amylase is increased due to Salvary Gland or Pancreatic Involement
Orchitis infection of testicles carries risk of Sterility, especially in Teenagers (>10 y.o.)
Positive igM Ab, Rise in IgG Ab

Mumps

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Inflammation of the Salivary Gland
More common in Men
Most commonly due to an Obstructing stone leading to Staphylococcus aureus infection
Forms when saliva rich in Calcium is Stagnant
A/w Gout and Nephrolithiasis
Usually Unilateral Infection

Sialadentitis

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Benign Mixed tumor composed of Chondromyxoid Stromal and Epithelial tissue (Biphasic)
Most common tumor of Salivary gland
Usually arises in Partoid
Mobile, Painless, Circumscribed mass at Angle of Jaw
High Recurrence extension of small islands of Tumor through Tumor capsule often leads to incomplete resection
Rarely malignant –> but would present with Facial nerve damage (palsy)

Pleomorphic Adenoma

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Papillary cystadenoma lymphomatosum
Benign Cystic tumor of Salivary glands (parotid) w/ Abundant Lymphocytes and Germinal Centers (lymph node-like stroma)
2^nd most common Tumor of Salivary gland
Almost always arises in Parotid
Middle aged Males

Warthin Tumor

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Malignant tumor composed of Mucinous (mucus cells) and Squamous cells
Most commong Malignant tumor of the Salivary gland
Usually painless slow-growing mass
Painful Facial nerve involvement
Large, No Capsules, Infiltrative

Mucoepidermoid Carcinoma

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Abnormal congential connection defect Foregut abnormality –> connection between Esophagus and Trachea
Most common variant consists of proximal Esophageal atresia with the Distal esophagus arising from the Trachea
Vomiting
Polyhydramnios (cannot swallow amniotic fluid)
Abdominal Distention
Aspiration

Tracheoesophageal Fistula

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Thin Protrusion of Esophageal mucosa toward Lumen
Most often in Upper esophagus
Dysphagia for poorly chewed food
Increased risk for Esophageal SCC
Plummer-Vinson Syndrome is characterized by Severe Iron Deficiency (FE²⁺), Anemia, Beefy-red tongue (blood vessles are exposed, red coloring) due to Atrophic glossitis

Esophageal Web

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Pharyngoesophageal ‘False’ Diverticulum
Outpouching of Pharyngeal mucosa through Acquired defect in the Muscular wall (false) @ Killian triangle
Common in Elderly males
Arises above the Upper Esophageal Sphincter (UES) at the Junction of the Esophagus and Pharynx
Protrusion of Mucosa through the Muscular wall (Backwards)
Dysphagia (something in the back of throat)
Obstruction, Halitosis (Bad Breath), Achalasia

Zenker Diverticulum

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Longitudinal laceration of Mucosa at the Gastroesophageal (GE) junction
Severe vomiting, usually due to Alcoholism or Bulimia
Presents w/ Painful Hematemesis
Rupture of Esophagus leading to Air in the Mediastinum and Subcutaneous emphysema
Air bubbles beneath the skin in the neck
-> Krackling ‘Rice Krispies’

Mallory-Weiss Syndrome

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Dilated submucosal veins in the Lower esophagus
2^nd to Portal Hypertension due to increased pressure in the Left Gastric vein
Distal Esophageal Vein normally drains into Portal vein via the Left gastric vein, Thinner distal Esophagus veins
Portal Hypertension –> Left Gastric vein backs up into the Esophageal vein –> Dilation of Varices
Asymptomatic, but risk for Rupture exists
Painless Hematemesis
Common cause of death in Alcoholics and Cirrhosis (No coagulation factors)

Esophageal Varices

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“Failure to Relax”
Disordered Esophageal motility w/ inability to relax the Lower esophageal sphincter (LES)
Dmg Ganglion cells in the Myenteric plexus (Auerbach), located between the Inner circular and Outer Longitudinal layers of the Muscularis Propria and are important for Regulating bowel motility and relaxing the LES
Idiopathic or Secondary to known insult; Trypanosoma cruzi infection in Chagas disease
Dysphagia for solids and liquids
Putrid breath
High LES pressure on Esophageal manometry (Dilation w/ lower tightness)
‘Bird-beak’ sign on Barium swallow, reduced peristalsis w/ buildup
Increased risk of Esophageal SCC

Achalasia

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Reflux of acid from the Stomach due to Reduced LES tone
Rx: Alcohol, Tobacco, Obesity, Pregnancy, Fat-rich diet, Caffeine, and Hiatel Hernia (cardia of the stomach herniates upward into esophagus)
Cx: Heartburn (mimics cardiac chest pain), Asthma (adult-onset) and Cough, Damage to Enamel of Teeth
Ulceration w/ Stricture and Barret Esophagus are late complications

Gastroesophageal Reflux Disease (GERD)

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Glandular Metaplasia of the Lower Esophageal Mucosa from Non-keratinized Stratified Squamous Epithelium to non-ciliated columnar epithelium w/ Goblet cells
Response to lower Esophageal Stem cells to Acidic stress
May progress to Dysplasia w/ weight loss and Adenocarcinoma
A/w Esophagitis, Esophageal ulcers, and increased risk of Esophageal Adenocarcinoma

Barrett Esophagus

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Malignant proliferation of Glands (Infiltrating glands), Desmoplasia, ‘Dirty’ Necrosis
Most common type of Esophageal carcinoma in the West
Arises from pre-existing Barrett Esophagus
Usually involves the Lower 1/3 of the Esophagus via the Dysplasia Sequence
Most common type in the West
TP53
CDKN2A (p16/INK4a)
EGFR, MET
C-ERB B2
Cyclin D1 and Cyclin E

Adenocarcinoma

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Malignant proliferation of Squamous Cells
Most common Esophageal cancer Worldwide
Upper 1/3 of the Esophagus
Alcohol and Tobacco
Very hot tea (Southern China and Iran)
Achalasia (Disordered motility w/ inability to relax the LES)
Esophageal web (Plummer-Vinson Syndrome)
Esophageal injury (lye ingestion, hair straigtener)

Squamous cell carcinoma

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Presents Late (poor prognosis)
Progressive dysphagia (Solids –> Solids and Liquids), Weight loss, Pain, and Hematemesis
Squamous cell carcinoma may additionally present with Hoarse voice (recurrent laryngeal nerve involvement) and cough (tracheal involvement)

Esophageal carcinoma

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Esophageal Lymph Node Spread

Upper 1/3 –> Cervical Nodes
Middle 1/3 –> Mediastinal or Tracheobronchial nodes
Lower 1/3 –> Celiac and Gastric nodes

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Congenital malformation of the Anterior Abdominal wall leading to Exposure of Abdominal Contents
‘Splitting’ – Hole in the Abdominal wall w/ ‘Uncovered bowel’

Gastroschisis

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Persistent herniation of bowel into Umbilical cord
Due to failure of Herniated intestines to return to the Body cavity during development
Contents are Covered by Peritoneum and Amnion of the Umbilical cord

Omphalocele

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Congenital Foregut abnormality of Hypertrophy of Pyloric Smooth Muscle
More common in Males
Cx: Normal after birth but develops after 2 weeks; Projectile Non-bilious Vomiting, Visible Peristalsis, ‘Olive-like’ mass in the Abdomen
Tx: Myotomy – cutting away muscle

Pyloric Stenosis

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“Burning the Stomach w/ Acid” Up Acid, Down Protection
Acidic damage to the Stomach mucosa w/ Neutrophils and Plasma cells
Due to imbalance between Mucosal defenses and Acidic Environment –> Inflammation
- Burns - Curling ulcer –> dec. plasma vol. –> slough
- Brain injury - Cushing ulcer –> incr. vagal stim. –> incr. ACh –> incr. H+ protection
Defenses include Mucin layer produced by Foveolar cells
Bicarbonate secretion by Surface epithelium
Normal blood supply provides nutrients and picks up Leaked acid
Severe burn (curling ulcer) – Hypovelemia –> Down Blood Supply
NSAIDs (decreased PGE₂–> decreased mucosa protect)
Heavy alcohol consumption
Chemotherapy (knockout turnover cells)
Increased Intracranial Pressure (Cushing Ulcer) – increased stimulation of Vagus nerve leads to increased produciton; (ACh, Gastrin, Histamine) –> binds parietal receptor cell –> more acid production
Shock – Multiple (stress) ulcers may be seen in ICU patients
Acid Dmg –> Superficial inflammation, Erosion (loss of superficial epithelium), or Ulcer (Loss of mucosal layer) –> red. Blood flow –> dec. protection

Acute Gastritis

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Chronic inflammation of the Stomach mucosa
Chronic Autoimmune gastritis and Chronic H pylori gastritis

Chronic Gastritis

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Autoimmune destruction of gastric Parietal cells (Stomach body and Fundus) w/ ‘pernicious Anemia‘
A/w Ab against Parietal cells and/or Intrinsic factor (Useful for diagnosis)
Pathogenesis is mediated by T-cells (Type IV hypersensitivity)
Cx: Atrophy of mucosa w/ intestinal metaplasia, red. Parietal cell thickness,
‘Achlorhydria‘ w/ Increased Gastrin lvls and Antral G-cell Hyperplasia –> low acid production by the Stomach
Megablastic ‘pernicious’ anemia due to lack of Intrinsic factor (common cause of B₁₂ deficiency)
Increased risk for Gastric Adenocarcinoma (Intestinal Type)

Type A: Chronic Autoimmune Gastritis

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H pylori acute and chronic inflammation; most common (90%), Erythema and Thickened Rugal folds
VacA - Vacuolating cytotoxin causes cell injury by Vacuolization
CagA - cytotoxin-associated antigen - increases risk for cancer
H pylori Urease and Proteases along w/ Inflammation weaken Mucosal defenses; with the Antrum being the most common site
Epigastric abdominal pain
Increased risk for Ulceration (peptic ulcer disease)
Gastric Adenocarcinoma (intestinal type)
MALT lymphoma
Tx: Triple Therapy –> Resolves gastritis / ulcer and reverses intestinal metaplasia
Negative Urea breath test (bug has been killed) and lack of stool antigen confirm eradication of H pylori

Type B: Chronic H pylori gastritis

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* Single Mucosal Ulcer involving the Proximal Duodenum (90%) or Distal Stomach (10%)

Solitary Mucosal Ulcer

* Peptic ulcer that is almost always due to ***H pylori*** **(\>95%)**; rarely may be due to **ZE syndrome** (Gastrinoma) * Epigastric pain that **IMPROVES w/ Meals** --\> Duodenum produces acid in preperation * Decr. Mucosal protection or Incr. Gastric acid secretion * Diagnostic Endoscopic Biopsy shows Ulcer w/ **_Hypertrophy of Brunner glands_** * Usually arises in Anterior Duodenum * **Posterior Duodenum** --\> rupture may lead to bleeding from **Gastroduodenal artery** or **Acute Pancreatitis** * Dx: Almost never malignant (malignancy is extremely rare), **A/w Zollinger-Ellison syndrome**, **NSAIDs, H *pylori***

Duodenal Ulcer

* Peptic ulcer usually due to ***H pylori* (75%)**, **NSAIDs**, **Bile refulx** * Epigastric ulcer that **WORSENS w/ Meals**, **Nausea, Weight-loss** * Ulcer usually located on the **Lesser curvature of the Antrum** and **Prepyloric** regions * Rupture carries risk of Bleeding from Left Gastric artery --\> runs along the lesser curvature * Dx: A/w Gastric carcinoma (Intestinal subtype) * Benign peptic ulcers – small \< 3 cm, sharply demarcated **“punched-out”** and surrounded by radiating folds of mucosa * Malignant ulcers are Large and Irregular w/ Heapud up Margins --\> increased risk of Carcinoma

Gastric Ulcer

* Malignant proliferation of Surface Epithelial Cells (Adenocarcinoma) (Columnar cells) * Subclassified into Intestinal and Diffuse types * Presents w/ Weight Loss, Abdominal Pain, Anemia, and Early Satiety * **Often** presents w/ **Acanthosis Nigricans** or Leser-Trelat sign * **Virchow node -** involvement of Left Supraclavicular node by metastasis from Stomach (Lymphadenopathy) * **Krukenberg tumor** - (Diffuse Type) Distant metastasis most commonly involves the **Ovaries.** Abundant mucus, Signet ring cells * **Sister Mary Joseph Nodule** - (Intestinal Type) Liver, Periumbilical region , subcutaneous periumbilical metastasis * **Leser-Trelat sign:** Multiple outcroppings of sebhorrheic keratosis

Gastric Carcinoma

* A/w H. *pylori* infection * Presents as a Large, Irregular ulcer w/ Heaped up margins; most commonly involves the Lesser curvature of the Antrum (similar to margins; Most commonly involves the **Lesser Curvature of the Antrum** (similar to Gastric Ulcer) * _Risk factors_: Intestinal Metaplasia, Nitrosamines in Smoked foods (Japan), tobacco and smoking, Achlorhydria, Chronic gastritis, and Blood type A

Intestinal Type Gastric Carcinoma | (Adenocarcinoma)

* **Signet Ring cells** that diffusely infiltrate the Gastric wall * **Desmoplasia** (cancer and Rxn to that cancer --\> Rxn of **Stromal cells --\> Fibrous Rxn** results in Thickening of Stomach wall (**Linitis plastica**) or '**Leather bottle'** * NOT A/w *H pylori*, intestinal metaplasia, or Nitrosamines

Diffuse Type Gastric Carcinoma | (Adenocarcinoma)

* Small bowel ends in a blind loop * Congenital **failure of Duodenum to Canalize** * A/w _Down Syndrome_ * Polyhydramnios, Distention of Stomach and Blind loop of Duodenum **‘Double bubble’** sign * _Bilious vomiting w/ Bile_

Duodenal Atresia

* **'****True' diverticulum** * Outpouching of all 3 layes of the Bowel wall * **Persistence /** **Failure** of the **Vitaline duct** to **Involute** * Rule of 2’s * 2% population * 2” long and located in Small bowel * 2’ from the Ileocecal valve * 2 years of life * 2 types of epithelia (Gastric / Pancreatic) * 2x Men \> Female * **RLQ Pain**, **Bleeding** (heterotopic gastric mucosa), **Volvulus**, **Intussusception**, or **Obstruction** (mimics appendicitis)

Meckel Diverticulum

* Twisting of Bowel along its Mesentery (Blood comes in via) --\> Infarction * Results in Obstruction and Disruption of the Blood Supply w/ Infarction * Sigmoid colon (Elderly) * Cecum (Young adults) * Midgut (Infants and Children)

Volvulus

* **'_Telescoping_'** of Proximal segment of Bowel forward into Distal segment, **\< 2 y.o. a/w Rotavirus** * Telescoped segment is pulled forward by Peristalsis * Results in Obstruction and Disruption of Blood supply w/ Infarction --\> commonly at **_Ileocecal junction_** * **Intermittent abdominal pain** w/ **‘Current jelly’ stools, "Sausage-shaped**" mass * A/w a Leading edge (Focus of traction) * **Children** – Idiopathic, Resp. Inf., Lymphoid hyperplasia (Payer’s patches) due to Rotavirus, usually arises in **Terminal ileum** --\> into the Cecum * **Adults** – **Tumor** acts as "**_Lead point_**" that is pulled into the lumen

Intussusception

* Small bowel is highly susceptible to Ischemic injury (needs a lot of ATP) * **Transmural infarction** – occurs w/ Thrombosis / embolism of the SMA or Thrombosis of the Mesenteric vein (Polyarteritis nodosa) --\> Atrial Fibrillation or Vasculitis risk * **Mucosal infarction** – occurs w/ marked hypotension * Abdominal pain, Bloody diarrhea, and Decreased bowel sounds

Small Bowel Infarction

* **Decreased function** of the **Lactase enzyme** found in the **Brush border of Enterocytes** * Lactase normally breaks down into **Glucose** and **Galactose** * **Lactose Test** + if Glucose rises \< 20mg/dL * Presents w/ **Abdominal Distention** and **Diarrhea** w/ **Milk** (osmotically active) and **Normal Villi** * Deficiency may be Congenital (Rare autosomal recessive disorder) or Acquired (often develops in Late Childhood) * Temporary deficiency a/w _Small Bowel Infection_

Lactose Intolerance

* Autoimmune-mediated Dmg of Small bowel villi due to **Gluten Exposure --\> 'Villous Atrophy w/ Crypt Hyperplasia'** * A/w **_HLA-DQ2_** and **_HLA-DQ8_** (Hypersenitivity), **HLA-B8, HLA-DW3** * Gluten; pathogenic component is **_Gliadin_** (wheat, oats, barley, and rye, NOT rice) * Epithelial cells produce **IL-15** --\> **CD8+ T cells w/ NK cell receptor (NKG2D)** and damage enterocytes expressing **MIC-A** * Gliadin --\> deamidated by Transglutaminase (tTG) --\> presented by Antigen presenting cells via **MHC class II** to **T-cells** --\> Helper T-cells mediate Tissue Dmg (lymphoma) * Children: Abdominal distention, Diarrhea, Failure to thrive * Adults: Chronic diarrhea and Bloating * Small Herpes-like vesicles may arise on skin (**Dermatitis Herpetiformis**), IgA deposition at the tips of Dermal papillae * IgA Ab against **Endomysium, tTG,** or **Gliadin** * **Anti-tissue transglutaminase** * **Anti-gliadin** * **Anti-endomysial antibodies** * Increased incidence of IgA deficiency is seen in Celiac disease --\> **Malignant T cell lymphoma and Adenocarcinoma** * Flattened villi on biopsy, Hyperplasia of Crypts, increased Intraepithelial Lymphocytes

Celiac Disease

* **Dmg** to **Small bowel villi** due to **Unknown organsim** resulting in Malabsorption --\> Diarrhea * Similar to Celiac disease except * Occurs in Tropical regions (Caribbean, infectous agent) * Arises after Infectious diarrhea and **Responds to ABX** * Dmg is most prominent in Jejunum and Ileum (Secondary to Vit. B₁₂ or Folate deficiency may ensue)

Tropical Sprue

* Systemic tissue Dmg characterized by **Macrophages** loaded w/ ***Tropheryma whippelii*** (**G+**) organism * Partially destroyed organsims are present in **_'Foamy' Macrophage_ Lysosomes (positive for PAS) w/ Lymphatic obstruction (periodic acid-Schiff, PAS)** * Small bowel _Lamina propria_, _mesenteric nodes_ * Macrophages compress Lacteals * Chylomicrons cannot be transferred from Enterocytes to Lymphocytes * Fat malabsorption and **Steatorrhea** * Also w/in Synovium of Joints (Arthritis), Cardiac valves, Lymph nodes, and CNS * **Cardiac** symptoms, **Arthralgias**, **Neurologic** symptoms

Whipple Disease

* **Early Childhood** and **Failure to Thrive** * Autosomal recessive deficiency of **Apolipoprotein** **B-48** - -\> Inability to generate **Chylomicrons** and **B-100** * Decreased secretion of Cholesterol, VLDL, and LDL into bloodstream - -\> increase **Fat accumulation** in **Enterocytes - -\> Steatorrhea**,**Acanthocytosis**,**Ataxia**,**Night blindness** * **B-48** --\> Malabsorption – due to Defective Chylomicron formation * **B-100** --\> Absent plasma VLDL and LDL

Abetalipoproteinemia

* **Malignant** proliferation of **Neuroendocrine cells**, Low-grade malignancy * Tumor cells contain **Neurosecretory granules** that are positive for **Chromogranin** * Anywhere along the gut; Small bowel is most common site --\> Grows a **submucosal polyp-like nodule** * Often **secretes** **Serotonin** --\> Portal vein --\> Liver --\> MAO --\> 5-HIAA --\> Urine excretion w/out Carcinoid syndrome * **Metastasis** of carcinoid tumor to the Liver allows Serotonin to bypass Liver metabolism * **Serotonin** released into the Hepatic vein and leaks into Systemic circulation via Hepato-systemic shunts --\> Carcinoid syndrome and Carcinoid Heart Disease

Carcinoid Tumor

* Characterized by Bronchospasm, Diarrhea, and Flushing of skin * Triggered by Alcohol or Emotional stress, which stimulate Serotonin release from the Tumor

Carcinoid Syndrome

* Characterized by Right-sided Valvular Fibrosis (Deposition of Collagen) leading to **Tricuspid regurgitation** and **Pulmonary valve stenosis** * Left-sided valvular lesions are not seen due to Presence of Monoamine Oxidase (metabolizes Serotonin) in the Lung

Carcinoid Heart Disease

* Most common cause of **Acute Severe abdominal pain** * Related to obstruction of the Appendix by **Lymphoid Hyperplasia (children)** and **Fecalith (Adults)** * **Cribinoid necrosis** * Periumbilical pain (Right lower quadrant), **Fever**, and **Nausea** --\> Migrates to McBurney point (1/3 distance from Anterior Superior Iliac spine to Umbilicus) * Rupture results in **Peritonitis** that presents w/ Guarding and Rebound tenderness, may see **Psoas obturator** and **Rovsing signs** * **DDx**: Diverticulitis (elderly), Ectopic pregnancy (use β-hCG to rule out) * Periappendiceal abscess is common complication * A/w *E.* *vermicularis*

Acute Appendicitis

* Chronic, relapsing Inflammation of Bowel * **Abnormal Immune response to Enteric Flora** * **Young women** (teens to 30s) as Recurrent bouts of **Bloody diarrhea** and **Abdominal pain, w/ Crypt abscesses** * More prevalent in the West, particularly Caucasians and Eastern European Jews * Diagnosis of Exclusion, symptoms mimic other causes of Bowel Inflammation (i.e. infection) * Subclassified as **Ulcerative colitis** or **Crohn disease**

Inflammatory Bowel Disease (IBD)

* Autoimmune * Mucosal and Submucosal Ulcers * **_Begins in the Rectum_** and extend proximally up to the **Cecum (continuous involvement)** w/ remainder of the GI tract unaffected * Left lower quadrant pain (Rectum) w/ Bloody diarrhea * **'Cryptitis' and ‘Crypt abscesses’** **w/ Neutrophils** * Mucosal and Submucosal inflammation only * Pseudopolyps: ‘**Loss of Haustra’** and **‘Lead Pipe’** sign on imaging * **Crypt abscesses** and **Ulcer**, **'Red'** **Bleeding**, **NO Granulomas** (Th₂ mediated) * Malnutrion, Toxic Megacolon and Carcinoma (Dysplasia) based on extent of Colonic involvement and Duration of disease (worse w/ right-sided colitis or pancolitis) * **Pyoderma gangrenosum**, **Erythema nodosum, Ankylosing spondylitis, Apthous ulcers, Uveitis** * Generally not a concern until \>10 years of disease * **1º Sclerosing cholangitis** and p-ANCA * **Smoking protects** against UC

Ulcerative Colitis

* Full-thickness inflammation w/ **‘Knife-like fissures**’ * Anywhere from mouth to Anus w/ Skin lesions; Terminal Ileum is the most common site, Rectum is least common * Right lower quadrant -\> **_Skip lesions_** and **_Rectal sparing_** * Right lower quadrant pain (ileum) w/ non-bloody diarrhea * **_Lymphoid aggregates_ w/ _Noncaseating Granulomas_** (40% of cases)(Th₁ mediated) * Transmural inflammation * **_Cobblestone mucosa_** (healing process), **_Creaping fat_** and strictures **‘_String-sign_’** on imaging - **'Rake ulcers'** * Malabsorption w/ Nutritional deficiency, Calcium oxalate nephrolithiasis, **Fistula** formation, and Carcinoma (if colonic disease is present) * Ankylosing spondylitis, Sacroiliitis, Migrating Polyarthritis, Uveitis, Erythema nodosom, Pyroderma gangrenosum, Aphthous ulcers, and Kidney stones * Diarrhea that may or may not be bloody * Smoking increases risk of CD

Crohn Disease

* Complete Functional Obstruction of Large bowel * Defective relaxation and Peristalsis of Rectum and Distal sigmoid colon, resulting in a '**Transition zone'** * A/w **Down Syndrome, Waardenburg Syndrome, Cardiac defects, Cystic fibrosis** and ***RET* proto-oncogene** * Congenital failure of Ganglion cells (neural crest-derived) to descend into myenteric and submucosal plexus, derived from Neural crest * **Myenteric (Auerbach) plexus** – is located between the inner circular and outer longitudinal muscle layers of the muscularis propria and regulates motility * **Submucosal (Meissner)** **plexus** – located in the submucosa and regulates blood flow, secretions, and absorption * Clinical features based on Obstruction * Failure to pass meconium * Empty recal vault on digital rectal exam * Massive dilation (megacolon) of bowel proximal to obstruction w/ risk for rupture * **‘Rectal suction biopsy’** reveals Lack of Ganglion cells * Tx: resection of the involved bowel

Hirschsprung Disease

* **Outpouchings of Mucosa** and **Submucosa** through the Muscularis propria false diverticulum * Related to **Wall Stress** * A/w **Constipation, Straining,** and **Low-fiber diet**, commonly seen in Older Adults (risk increases w/ Age) * Arise where the **Vasa Recta traverse** the **Muscularis propia** (weak point in colonic wall); **Sigmoid colon** is the most common location * Usually Asymtomatic * **Rectal bleeding (Hematochezia**, “Bright Red Blood”) * **Diverticulitis** – obstructing fecal material; presents w/ “appendicitis-like” symptoms in the ***left* Lower Quadrant** * **Fistula** – inflamed diverticulum ruptures and attaches to a Local Structure * **Colovesicular Fistula** – presents w/ Air or Stool in Urine

Colonic Diverticula

* Acquired malformation of **Mucosal** and **Submucosal** caplillary beds * Usually arises in the **Cecum and Right colon** due to **High wall Tension** * Rupture classically presents as **Hematochezia** in an **Older adult**

Angiodysplasia

* Autosomal dominant disorder resulting in Thin-walled blood vessels; esp. in the **Mouth** and **GI tract** * **Rupture** presents as **Bleeding** --\> Lots of Small Telangietasia vessels

Hereditary Hemorrhagic Telangiectasia

* Reduction in Intestinal blood flow --\> Ischemia * Ischemic damage to the Colon, usually at the **Splenic flexure** (watershed area of SMA) and **Distal colon** * Pain after eating --\> Weight loss * **Atherosclerosis of SMA** is the most common cause * **Postprandial pain** and **Weight loss** * Infarction results in Pain and Bloody diarrhea * Eating increases Blood requirement --\> Pain, like Angina but in the Colon * **\> Elderly**

Ischemic Colitis

* Recurrent abdominal Pain w/ Bloating, Flatulence, and Change in Bowel habits (diarrhea or constipation) that **_Pain Improves w/ Defecation_** * **_Change in stool frequency_** * **_Change in Appearance of Stool_** * **_Middle-aged females_** * Related to Disturbed Intestinal motility * No identifiable pathologic changes * Increased Dietary fiber may Improve symptoms

Irritable Bowel Syndrome

* Hyperplasia of Glands; **‘Serrated’** polyp appearance on microscopy * Most common type of **Benign** Polyp * Usually arise in the **Left Colon (Rectosigmoid) (50%)** * **Benign**, w/ no malignant potential

Hyperplastic polyps

* **Neoplastic proliferation** of **Glands** forms a Polyp * 2^nd most common type of Colonic Polyp * **Benign** but **Premalignant** for **Colorectal cancer (CRC)** * May progress to **Adenocarcinoma** via the **Adeno-carcinoma sequence** * **Size** * **Number** * **Type** * **Dysplagia** * **Villous histology**

Adenomatous polyps

* Sequence describes the molecular progression from Normal colonic mucosa to Adenomatous polyp to Carcinoma * Normal Colon --\> No Risk * ***APC mutation*** – adenomatous polyposis coli gene (sporadic or germline) --\> Increase **Risk** for formation of Polyp (tumor suppressor gene, chrom. 5 - 5q21) - *decreased* intercellular adhesion and *increased* proliferation * APC mutation of **β-catenin - 'second hit'** * **K-*ras* *mutation*** – leads to **Formation of Polyp** - unregulated intracellular signal transduction * **p53, DCC** – and increased expression of **COX** allow for **progression** to Carcinoma; Asprin impedes **progression** from Adenoma to Carcinoma - *increased* tumorigenesis

Adenoma-Carcinoma sequence

* _Autosomal dominant_ disorder characterized by **100s to 1000s** of **Adenomatous colonic** **Polyps** * Inherited **_APC mutation_** (Chrom. 5) * Increases propensity to develop Adenomatous polyps throughout Colon and Rectum * Colon and Rectum are removed Prophylactically * 100% progress to CRC unless Colon is resected * Pancolonic, always involves the Rectum * Almost all Pts. develop Carcinoma by 40 y.o.

Familial Adenomatous Polyposis (FAP)

* **FAP w/ Fibromatosis and Osteomas and Soft-tissue tumors** * Congenital hypertrophy of **Retinal pigment epithelium** * Fibromatosis – is a non-neoplastic proliferation of fibroblasts; arises in Retroperitoneum (desmoid) and Locally destroys tissue * Osteoma – is a benign tumor of Bone that usually arises in the Skull

Gardner Syndrome

* **FAP w/ maliginant CNS tumors** (Medulloblastoma and Glial tumors) * **Tur**cot = **Tur**ban

Turcot Syndrome

* Sporadic, Hamartomatous (disorganized benign tissue) polyp * Arises in Children (\< 5 y.o.) * **Solitary Rectal polyp** that Prolapses and Bleeds (**Benign**) * Multiple polyps in the Stomach and Colon * **Large numbers of polyps** increases the risk of progression to **Adenocarcinoma**

Juvenile Polyp

* **Hamartomatous Bening polyps** throughout **GI tract** and **Mucocutaneous _hyperpigmentation_** (freckle-like spots) on _lips_, Oral mucosa, hands, and Genital skin * Autosomal dominant disorder * Increased risk for Colorectal cancer (CRC), Breast, and Gynecologic cancer

Peutz-Jeghers Syndrome

* Carcinoma of the Colonic or Rectal Mucosa * 3^rd most common site for Cancer * 3^rd most common cause of Cancer-related Death * 60 – 70 y.o. * Arises from **Adenoma-carcinoma sequence** --\> Microsatellite instability (MSI) * Microsatellite --\> repeating sequences of noncoding DNA; instability indicates Defective DNA copy mechanism (DNA mismatch repair enzymes) * A/w increased risk of **Streptococcus bovis endocarditis** * **CEA** is a **Serum tumor marker** --\> used for assessing treatment response and detecting recurrence

Colorectal Carcinoma

* Autosomal dominant - **Microsatellite instabiiity pathway** * Inherited **mutations** in **DNA mismatch repair enzymes** * ~80% risk of Colorectal cancer (CRC), Ovarian, and Endometrial carcinoma * Proximal colon is always involved * Colorectal carcinoma arises *de novo* (not from Adenomatous polyps) at a relatively early age; usually **Right-sided** * Remove adenomatous polyps before carcinoma develops

Hereditary Nonpolyposis Colorectal Carcinoma (HNPCC)

* Grows as a **‘Napkin-ring’ lesion** * Presents w/ Decreased stool caliber * Left Lower Quadrant pain * Blood streaked stool * A/w Adenoma-Carcinoma

Left-sided Colorectal Carcinoma

* Grows as a **‘Raised lesion’** * Presents w/ **Iron deficiency Anemia** (occult bleeding) and **Vague pain** * Small amounts of bleeding --\> A/w Microsatellite instability pathway * Older adult pts. w/ Iron deficiency anemia HAVE Colorectal Carcinoma until proven otherwise

Right-sided Carcinoma

Diseases of Benign Polyp

* Hyperplastic Polyp

Diseases of Neoplastic Polyp

* Adenomatous * Villous

Diseases of Hamartoma Polyps

* Peutz-Jeghers Syndrome * Juvenile Polyp * Cowden Sydnrome * Cronkite-Canada Syndrome

Disease of Inflammatory Polyps

* Solitary Rectal Ulcer Syndrome * Uclerative Colitis * Crohn Disease * Lymphoid Disease * Schistosomiasis

* Finger-like processes * Uncommon * Sessile * Larget than Tubular Adenoma * Precancerous w/ Moderate risk * Endoscopic resection is difficult

Villous Adenoma

* Glandular tumor * Relatively frequent * Pedunculated, Small * Precancerous * Endoscopic polypectomy * Component of Familial Adenomatosis coli

Tubular Adenoma

* Different pattern * Individual **Tumor cells** in a **"Sea of Mucin"** * Poor prognosis

Mucinous Adenocarcinoma

* Hyperplasia of **Mucous-secreting cells** resulting in **Rugal hypertrophy** and **Hypoproteinemia** * Gastric hypertrophy w/ Protein loss * Atrophy of Parietal cells --\> results in **Achlorhydria** * *Increased* risk for **Adenocarcinoma** * Precancerous * Rugae of Stomach are so Hypertrophied that they look like Brain gyri

Menetrier disease

* Due to Cystic fibrosis, Obstructing cancer, and Chronic pancreatitis * **Malabsorption** of **Fat** and **Fat-soluble vitamins** (Vitamins **A, D, E, K**) * *Increased* neutral fat in Stool * **D-xylose abosrption te**st: Normal urinary excretion in Pancreatic insufficiency; *decreased* excretion w/ intestinal mucosa defects or Bacterial overgrowth

Pancreatic Insufficiency

* Many false diverticula of the Colon, **"Pulsion"** * Commonly Sigmoid colon (~50% of people \> 60 y.o.) * Caused by ***increased* Intraluminal pressure** and **Focal weakness** in '**_Colonic wall'_** * A/w Low-fiber diets * **Asymptomatic** or A/w **Vague discomfort** * Common cause of "**Painless** **Hematochezia" \> 60 y.o.** * Complications: **Diverticulitis, Fistulas**

Diverticulosis

* "_Inflammation of Diverticula_" * **LLQ Pain, Fever, Leukocytosis, Guarding, Rebound tenderness** * May Perforate --\> Peritonitis, Abscess formation, or Bowel stenosis * **GIVE Antibiotics** (ABX) * Stool occult blood is common +/- Hematochezia * A/w **Colovesical fistula** (Fistula w/ Bladder) --\> Pneumaturia * Sometimes called **"Left-sided Appendicitis"** due to overlapping Clinical presentation

Diverticulitis

* Fibrous band of Scar tissue * Forms after Surgery * Most common cause of Small Bowel obstruction * Can have well-demarcated Necrotic zones

Adhesion

* Tortuous dilation of vessels --\> Hematochezia * Most often found in Cecum, Terminal ileum, and Ascending colon * \> Older pts. * Confirmed by Angiography

Angiodysplasia

* Intestinal Hypomotility w/out Obstruction - -\> Constipation and *decreased* Flatus * Distended / Tympanic abdomen w/ *decreased* bowel sounds * A/w Abdominal surgeries, Opiates, Hypokalemia, and Sepsis

Ileus

* In Cystic fibrosis, Meconium plug obstructs Intestine - -\> Preventing stool passage at Birth

Meconium Ileus

* Necrosis of Intestinal mucosa and possible Perforation * A/w Colon, but can involve the entire GI tract * In Neonates, more common in preemies (*decreased* immunity)

Necrotizing Enterocolitis

* Abnormal lymphcytic infiltration of exocrine glands - -\> Salivary and Lacrimal glands - -\> Dry mouth (**xerostomia**) and - -\> Dry eyes (**keratoconjuctivitis**) * Multisystem: Skin, Lung, Heart, Kidney - -\> *Increased* risk of Lymphoma * **Anti-Ro/SSA** or **Anti-La/SSA** **antibodies** * Schirmer test is a measure of Tear production * Rose Benal stain shows Corneal or Conjuctival epithelial cell damage * **Salivary gland biopsy** shows focal collection of Lymphocytes

Sjogren Syndrome

* Spontaneous Esophageal rupture w/ exit of Gastric contents into the Mediastinum * A/w overindulgence in Food and Alcohol * High Mortality Rate

Boerhaave Syndrome

* Multiple Peptic ulcerations in the **Stomach and Duodenum** due to **Excess Gastrin** secretion by a **Gastrinoma - -\> Excess Gastric Acid** production

Zollinger-Ellison Syndrome

GI: Gastrointestinal Pathology Flashcards

(84 cards)