- Parietal cell: H/K ATPase --> Acid secretion

- Chief cell: Pepsinogen I

- Mucous cells: Pepsiongen I + II

- G cell: Gastrin secretion --> Endocrine stimulation of parietal cells

- D cell: Somatostatin secretion --> Inhibits acid secretion

- ECL cell: Histamine secretion --> Stimulates parietal cell --> Dominant stimulant

- Parasympathetic neurons: Acetylcholine stimulates parietal cells --> Binds M3 receptor on parietal cell

- Imbalance between the aggressive and defensive factors within the stomach

- 70% of people with ulcers secrete normal amounts of acid --> Decreased defense mechanisms would be the causative factor

- Risk Factors: H. pylori infection, NSAIDs, acid hypersecretion states, cigarette smoking, and family history/genetics

1. Local prostaglandin production --> Via COX-1, COX-2 and 5-lipoxygenase

- NSAIDs inhibit COX-1 and COX-2 pathways

2. Nitric oxide

3. Trefoil proteins

- Help protect the stomach from developing ulcers

1. Stimulate secretion of mucus and bicarbonate

2. Inhibit gastric acid secretion by inhibiting G-protein receptor on basolateral surface of parietal cell

3. Increase mucosal blood flow --> Ensures delivery of O2, bicarbonate, and nutrients

4. Prevent transmembrane and intercellular H+ ion permeation

5. Mediate surface epithelial cell restitution --> Most important protective property

1. Symptoms: Epigastric pain, burning, pain worsening at night, discomfort, and nausea

- Often times ulcer is asymptomatic

2. Complications: Pain, bleeding, perforation, and obstruction

- H. pylori infection

- NSAIDs

- Stress ulceration --> Usually in the ICU

- Viral infections (HSV1 or CMV)

- Acid Hypersecretory States --> Zollinger-Ellison syndrome, systemic mastocytosis, myeloproliferative disorders, and idiopathic basal hypersecretion

- Cocaine induced

- Crohn's disease

- Risk factors: Age, use of corticosteroid with NSAID, and prior history

1. Local/topical caustic effect --> Minor mechanism

2. Systemic anti-prostaglandin effect --> Major mechanism

- Depletion of mucosal prostaglandins --> COX pathways

- Effect independent of route of administration (IV vs. PO)

- Believed to be due to COX-1 pathway --> COX-2 specific NSAIDs created --> Lowers ulcer risk but HIGH cardio risk

- Use lowest effective NSAID dose

- Avoid using NSAIDs with low dose aspirin, glucocorticoids, and anticoagulants

- Consider pharmacological protection for NSAIDs --> PPI, H2 blockers, or misoprostol (prostaglandin analogue)

- COX-2 inhibitor --> Used only if cardio risk is outweighed by benefits

- Monitor and treat any complications

- IV administration of PPI

- Surgical intervention if necessary

- Eliminate H. pylori if present

- Discontinue NSAIDs if possible

- Quit smoking!!

- Most common human bacterial infection --> 0.3% in Western countries but higher in countries with lower sanitation

- Transmission: Fecal-oral and person-to-person

- Life long infection if not treated

- Elicits a robust inflammatory response

- Associated with peptic ulcer disease, atrophic gastritis, gastric adenocarcinoma, and gastric lymphoma

- Can also be asymptomatic

- Virulence Factors: Urease to neutralize local pH, attachment proteins for host epithelium (lectins), flagella for motility, induction of inflammation to permit nutrition, and host immune response evasion (stays in stomach)

- Toxins: Cytotoxin and antisecretory toxin

- Pathogenesis: Cytotoxin directly kills gastric cells and causes mucosal erosion

- Can also cause duodenal or prepyloric ulcers

1. Non-invasive: Stool antigen test, 14C and 13C-urea breath tests, and IgG serology

- Cannot determine active infections with IgG serology

2. Invasive: Rapid urease test, histology, and culture/sensitivity

- Test only if you plan to treat

- Always treat when test is positive

- Document eradication

- Treatment: PPI, clarithromycin and amoxicillin --> Tell patient to avoid NSAIDs too

- PPIs should be taken before breakfast and dinner

- Substitute metronidazole if penicillin allergic

- Treat for 10-14 days

- Quadruple therapy (1st line of retreatment): Bismuth, metronidazole, tetracycline, and PPI

- Hypersecretory state associated with multiple ulcer formation distal to the duodenal bulb

- Progressive, persistent, and often fatal

- Associated with "non-B islet cell tumors" --> Gastrin secreting (gastrinoma)

- Gastrinoma triangle: 2nd and 3rd portions of the duodenum, junction of the head and neck of the pancrease, and cystic duct

- Peptic ulcers in >90%

- Diarrhea in 30-50% --> High volume load due to high rate of gastric acid secretion

- Symptoms of MEN-1: Tumors present in the pancreas, parathyroid, and pituitary glands

- GERD due to high acid secretion

- Low pH present through the GI tract inactivates pancreatic digestive enzymes --> Poor absorption of all nutrients including fats

- Low pH also directly damages intestinal epithelial cells and villi

- Clinical presentation: Ulcers, diarrhea, GERD, and MEN-1

- Hypergastrinemia: Fasting >1000 pg/mL 

- Hyperchlorhydria: >15 mEq H+/h in unoperated patient

- Medical management: High dose PPI to reduce acid secretion

- Surgical management: Tumor excision --> Treatment of choice without metastatic spread

- Treatment with metastasis: Somatostatin analogs, liver directed therapy, and chemotherapy --> Most common sites of mets are liver and bone

1. Oropharyngeal Phase

- Tongue moves up towards hard palate to propel bolus to back of the throat

- Soft palate moves up to seal off the nose

- Pharyngeal constrictor muscles contract to move bolus down through UES

- Epiglottis moves downward to cover trachea

- Vocal cords close and larynx moves up

2. Esophageal Phase

- UES relaxes and bolus enters the esophagus

- Peristalsis moves bolus of food down the esophagus at 3-5 cm/sec

- Primary peristalsis begins by swallowing via CNS input to the myenteric plexus and secondary peristalsis is initiated by local distension

- LES relaxes with swallowing

3. Deglutitive Inhibition of peristalsis

- Multiple successive swallows --> Complete esophageal relaxation creating a conduit for liquid to move directly into stomach

- Distal 2-4 cm of the esophagus containing rings of circular smooth muscle

- Pre-ganglionic NT: acetylcholine

- Post-ganglionic NT: NO and VIP

- More sensitive to drugs, horomes and other compounds

- Alcohol, oral contraceptives, caffeine, fatty foods, chocolate, and smoking all relax LES

1. Dysphagia: Awareness that swallowing is difficult

2. Heartburn: Substernal burning sensation that moves up and down the chest in a wavelike fashion

3. Odynophagia: Pain on swallowing --> Due to inflammation and ulceration of the esophageal mucosa

- Can be caused by esophageal spasm though

- Symptomatic reflux disease caused by excessive acid reflux

- Causes: Low LES tone, transient LES relaxation, and hiatal hernia

- Epidemiology: Very common in the US (>60,000), 40% of Americans have heart burn at least once a month, and increases with BMI and age

- Pathophysiology: Motility disorder that can lead to reflux esophagitis --> Mucosal injury, epithelial cell erosion, ulcerations/hyperplasia and inflammation

- Pathogenesis: Impairment of LES competence, secondary peristalsis, acid neutralization, and gastric emptying

1. Low LES tone: Low resting LES pressures (<10 mmHg)

2. Transient LES relaxation: Intermittent decreases in LES pressure and crural diaphragm --> Responsible for the majority of cases

3. Hiatal hernia: Normally the diaphragm exerts external pressure around the LES --> This external pressure is gone when a hiatal hernia is present

- Clinical presentation: Heartburn, timing/alleviation features, use of antacids, etc

- Barium swallow

- Esophagoscopy

- 24-hour pH study of the distal esophagus

- Esophageal impedence testing

- Manometry

1. Phase I

- Lifestyle changes --> Weight loss, elevate head for sleeping, avoid large meals and bedtime snacks, avoid cigarettes and alcohol, and discontinue estrogen containing compounds

- Antacids

2. Phase II

- H2 receptor antagonists (cimetidine) --> Inhibits histamine which is the biggest acid production stimulator

- Prokinetic drugs --> Increases LES tone and gastric emptying

3. Phase III

- Proton pump inhibitors (omeprazole) --> Irreversibly inhibits H/K ATPase

4. Phase IV

- Surgery (Nissen fundoplication): Wraps fundus of the stomach around the LES to increase external pressure/tone

1. Oropharyngeal: Parkinson's disease, stroke, and ALS

2. Mechanical obstruction: Tumor, Schatzki's ring, stricture, or foreign body

3. Esophageal dysmotility

- Scleroderma: poor peristalsis, LES tone, and GERD

- Achalasia: Aperistalsis and poor LES relaxation

- Diffuse esophageal spasm: Stimultaneous contractions and chest pain

1. Chronic Esophagitis: Mucosal irregularities, scarring and changes in the thickness of the epithelial layer due to underlying inflammation and edema

2. Ulcers and erosions: Due to chronic reflux

3. Stricture formation: Can result from severe scarring

4. Bleeding: From erosions or ulcers

5. Barrett's Esophagus: Squamous metaplasia resulting in stem cells diffrentiating into Goblet cells --> Small intestine mucosa

- 35-50x greater risk of developing adenocarcinoma

6. Pulmonary disease: Adult-onset asthma

7. Non-cardiac chest pain

8. ENT manifestations: Chronic hoarseness, laryngitis, and vocal cord polyps

1. Esophagitis

- Mild acute: Inraepithelial leukocytes, primarily eosinophils

- Chronic: Hyperplasia of basal epithelial layer with elongation and increased vascularity of the papillae

2. Stricture: Can form during repair of an esophageal ulcer

3. Columnar metaplasia/Barrett's Esophagus: Replacement of the normal esophageal epithelium with simple columnar epithelium --> Either gastric or intestine-like

4. Columnar dysplasia and carcinoma

- Differentiated by the likelihood of progression to adenocarcinoma

- Dysplastic cells: Enlarged and hyperchromatic ovoid nucleus with increased mitotic activity --> p16 and p53 mutations

- High grade: Architectural distortion of crypts with more severe cytological abnormality --> 16-30% risk of cancer

- Low grade: Flat or elevated, hyperchromatic ovoid nuclei, and little architectural distortion 8-12% risk

- Indeterminate: <2% risk

1. Eosinophilic Esophagitis: Hypersensitivity/allergic condition presenting with dysphagia or food impaction

- Ribbed appearance/feline trachea seen on endoscopy

- Hyperplastic reparative changes of the squamous mucosa associated with dense eosinophilic infiltrates

- Responds to topical steroids

2. Infectious esophagitis: Most commonly due to candida

- Mostly in immunocompromised patients

- Candida --> Multiple white plaques on endoscopy

- Herpes simplex --> Multiple white patches seen on endoscopy and viral inclusions seen histologically

- CMV --> Similar to herpes presentation

3. Chemical esophagitis: Commonly due to doxycycline

- Pill esophagitis --> Pill impaction, swallowing without water --> Irritates and ulcerates the mucosa

1. Adenocarcinoma --> Progresses from Barrett's esophagus --> p16 and p53 mutations

- Located distally and progresses from flat or slightly raised to large infiltrative masses

- 5-year survival: <20%

- More common in caucasian males

2. Squamous carcinoma: 60% of malignant esophageal cancers --> p16 and p53 mutations

- Occurs in all segments of the esophagus

- >3 times more likely in African-American males

- Progresses from squamous dysplasia --> plaque with redness and granularity

- Rare associations: Tylosis, achalasia, Plummer-Vinson Symdrome and lye stricture

1. H. pylori gastritis

2. Chemical gastropathy

3. Autoimmune gastritis

- Most common in the antrum of the stomach

- Mechanisms of survival in the stomach: Flagella for movement, urease production, and bacterial adhesive proteins (BabA)

- Pathogenesis of gastritis: Direct injury  to cells and indirectly through toxins Cag A and Vac A --> Stimulate IL-6, TNF, and IL-8 production

- Acute histological appearance: Mucus depletion and reparative changes --> Neutrophil infiltration

- Chronic appearance: Infiltration of plasma cells, B cells, T cells, and macrophages --> Lymphoid follicles form

- Invasive diagnosis: Staining using silver stain, giemsa stain or immunohistochemistry

1. Antral gastritis and duodenal ulcer: Diffuse antral gastritis --> Duodenitis, and gastric metaplasia of the duodenum

2. Mutlifocal Gastric Atrophy (MAG): Loss of specialized glands in multiple areas of the antrum, body, and fundus

- Gastric ulcers may develop between the antrum and body

3. Dysplasia and Adenocarcinoma: Follows MAG --> Results in intestinal metaplasia of the atrophic gastric mucosa

- May progress further into gastric adenocarcinoma

- Flat dysplasia --> High risk

- Polyps --> Adenomatous and hyperplastic have risk

4. Malignant Lymphoma of the Stomach: Lymphoproliferative disorders and lymphoma

- Well differentiated B-cell lymphomas (MALTomas)

- Growth dependent on T-cell sensitized to H. pylori

- Frequently regress once H. pylori is eliminated

- Depressed and excavated apperance of the mucosa

- Hard to distinguish between this and benign ulcers

- Characteristics: Disruption of surrounding folds, irregular ulcer margins, and abnormal appearing mucosa with a dpressed area

- Symptoms: Abdominal pain, early satiety, weight loss, and anemia

- Nodular, fungating, or ulcerating

1. Diffuse: Undifferentiated or signet-ring apperance

- Desmoplasia occurs --> Thickening of stomach wall

- Signet-ring cells --> Circular ring of mucus which pushes nucleus to the side of the cell

- Not associated with H. pylori or intestinal metaplasia

2. Intestinal type: Gland formation resembling intestinal carcinoma --> Progressed from intestinal metaplasia

- Intestinal type is most common in Type A blood types and in the curvature of the antrum

- Progresses from intestinal metaplasia

- Mutations: MCC, APC, and p53 mutations --> Ras mutations uncommon

- 5-year prognosis: 10% for advanced diffuse, 80% for early gastric cancers, and 20% for advanced gastric cancers

- Develops in 45% of patients taking NSAIDs

- Reparative hyperplasia of surface epithelium without MALT involvement

- Gastric ulcers are more common than duodenal in this presentation

- Autoantibodies directed against components of the specialized cells of the glands of the fundus and the body of the stomach

- Autoantibody targets: H/K ATPase, gastrin receptor, and intrinsic factor

- Link between Vit B12 malabsorption and pernicious anemia --> Most common cause of Vit B12 deficiency

- Achlorhydria (reduced acid production) is usually present

- Increased gastrin levels in serum due to low acid secretion and loss of feedback inhibition

- Also G-cell hyperplasia

- Marked hyperplasia of histamine producing ECL cells in some patients --> May progress into small carcinoid tumors

- Atrophic corpus and fundus may develop

- High association between autoimmune gastritis and gastric cancer due to induction of intestinal metaplasia

- 

- Stool weight >200 g/day

- Clinically --> Patients with changes in stool frequency or consistency as well as increased volume

- Normal frequency of defecation --> 3 times per day to 3 times per week

- Normally about 200 mL of water are excreted in the stool

- Acute: >3 weeks, usually infectious, and usually self-limited

- Chronic: >3 weeks, multiple causes, and variable in severity

- Occurs when the distal stomach and pylorus are removed

- Large amounts of hypertonic chyme enter the duodenum all at once

- Results in abdominal cramps and dizziness

1. Small intestine

- Na/Glu co-transporter on apical surface

- H/Na and HCO3/Cl antiports on apical surface

- Na/K ATPase on basolateral surface

- Intercellular Na, Cl and H2O diffusion

2. Large intestine

- Na+ channel on apical surface

- H/Na and HCO3/Cl antiports on apical surface

- Na/K ATPase on basolateral surface

- Intercellular Na, Cl, and H2O diffusion --> Less than small intestine though

1. Cl Secretion

- NKCC2 cotransporter on the basolateral surface

- Apical Cl channel (CFTR)

- Na/K ATPase on basolateral surface

- K+ efflux channel on basolateral surface

- Increased levels of cAMP activate K+ and Cl- efflux channels

2. HCO3 Secretion

- HCO3/Cl- antiport on apical surface

- Na/HCO3 cotransporter on basolateral surface

1. Duodenum: Similar to plasma

- Na 140 mEq/L, Cl 110 mEq/L, and HCO3 24 mEq/L

2. Ileum: Na and Cl decrease while HCO3 increases

- Na 125 mEq/L, Cl 80 mEq/L, and HCO3 80 mEq/L

3. Distal colon: All ion concentrations decrease and K added

- Na 40 mEq/L, Cl 15 mEq/L, HCO3 30 mEq/L, and K 90 mEq/L

- Additional anions are usually from organic acids produced by bacterial breakdown of indigestible carbohydrates

1. cAMP: Na/Cl absorption is blocked by intestinal villi and chloride secretion via CFTR is stimulated

2. cGMP: Similar affects to cAMP

3. Intracellular Calcium: Diminished Na/Cl absorpiton and increased Cl secretion --> Serotonin increases Ca

- Multiple external signals modify the levels of these 2nd messangers within enterocyte

- Pathophysiology due to decreased absorption and increased colonic secretion

- Leads to high volumes of stool

- Potentially due to increased levels of cAMP, cGMP, and Ca

- Many pathogens act by increasing levels of these 2nd messangers --> Cholera activates adenyl cyclase

- Other exogenous toxins may also cause this

- Watery diarrhea, hypokalemia, and acidosis

- Pancreatic cholera --> Due to a pancreatic tumor secreting VIP

- Due to increased levels of VIP --> Similar effect to increased cAMP levels

- Treatment: Tumor resection

1. Secretagogues: Serotonin (5HT), gastrin, neurotensin, PG, histamine, PAF, BK, ACh, VIP, substance P, and calcitonin

- CT, LT, histamine, VIP, and PGE --> cAMP

- Ach, serotonin, BK, SP, and NT --> Ca

- STa --> cGMP

2.  Absorptagogues: Somatostatin, norepinephrine, neuroprotein Y, epinephrine, and steroids

1. Increased secretion

- Stimulated anion secretion

- Tonic secretion from crypts --> IBD and Celiac

2. Decreased absorption of fluid and electrolytes

- Decreased absorptive mechanisms

- Luminal presence of osmotically-active substances --> Lactose, malabsorption, Mg/Phos antacids, and laxatives

- Increased propulsive activity with decreased contact time --> IBS

- Causes: Cholera toxin, E. coli heat-labile enterotoxin (LT), and E. coli heat-stable enterotoxin (ST)

- Stimulates net Cl secretion and variously inhibits Na absorption

- Causes no morphological changes or damage to the epithelium

- Does not impair Na-dependent nutrient transport --> Use glucose containing electrolyte fluids for rehydration

- Cholera --> cAMP and Heat Stable E. coli --> cGMP

- Carcinoid syndrome --> Increases serotonin, BK, substance P, neurotensin, tachykinin, and prostaglandin

- VIPoma --> Pancreatic cholera 

- Directly stimulate anion secretion, indirectly stimulate submucosal cells/neurons to produce more secretagogues, and directly stimulate smooth muscle cells

- Neurohormonally-stimulated secretion of Cl and inhibition of absorption of Na

- Propulsive contractions triggered by direct enteric nerve stimulation

- Disruption of the mucosal integrity --> Increased permeability (Weepy gut)

- Impairment of nutrient uptake causing malabsorptive osmotic diarrhea

- Presence of unabsorbed osmotically active substances that force water into the intestinal lumen

- Causes: Antacids, low-calorie foods and drinks, and laxatives

- Malabsorption

- Hypermotility

- 48-hour fast --> Secretory fast continues without food

- Measurement of stool osmolarity --> Secretory has no change in osmolarity but osmolar diarrhea does

- Normal osmolar gap is <50 mOsm/L

- Ileal dysfunction --> No bile acid absorption

- Results in an increased osmolar gap

- Increased bile acids causes choleretic Cl secretion in the colon

- Can progress into fatty acid diarrhea

- Non-pancreatic steatorrhea

- Hydroxy fatty acids not usually in diety

- FA enter the colon due to malabsorption/BA deficiency

- Bacteria then hydroxylate lipids

- Increased fatty acid content causes reversible jejunal and colonic secretion

- Increased mucosal permeability

- Induce morphological changes

- Alter motor activity of the intestine

- Inhibited or defective enterocyte absorption of fluid and electrolytes --> Heat stable toxin from E. coli

- Luminal presence of osmotically active agents --> Carbohydrate malabsorption (solvent drag)

- Increased propulsive activity --> Functional disorders (IBS)

- Osmotic carbohydrate diarrhea

- Antibiotics kill normal flora

- Lipids and undigested foods remain that way and are no longer broken down by bacteria

- Causes osmolar gap

- Autoantibodies directed to gliadin of gluten result in epithelial cell death

- Decreased brush border hydrolases

- Villus atrophy --> Reduced absorption

- Crypt hyperplasia --> Increased secretion

- Inflammation

- Associated with peripheral neuropathy or other more severe disease symptoms

- Decreased enteric nervous system activity

- Gut has abnormal motility

- Increased secretion and reduced absorption result

1. Secretory Cathartics: Mimic endogenous secretory stimuli --> Plant extracts (bisacodyl)

2. Bulk laxatives: Act as a sponge and increase stool H2O --> Metamucil

3. Emollients: Lubricate/stool softeners --> Docusate

4. Osmotic agents: Increased stool H20 with poorly absorbed osmoles --> Polyethylene glycol solutions

- Used as colonoscopy preps

5. Stimulates: Stimulate smooth muscle activity and increase peristalsis

1. Small bowel and colonic diarrhea

- Large stool volume --> Watery

- Moderate increase in number of bowel movements

- Minimal urgency

- No tenesmus

- Little mucus

2. Recto-sigmoid

- Small amount of stool

- Lower frequency

- Urgency

- Tenesmus

- Mucus and blood

- Diagnosis: Stool analysis for ova, parasites, leukocytes, blood, and mucus

- Treatment: Electrolyte/fluid rehydration solutions (with glucose) and treat underlying etiology

- Ex. Lactose-free diet for lactose deficiency and cholestyramine for bile acid diarrhea/ileal dysfunction 

- Complex reflex action involving the gastroduodenal system, musculoskeletal system and glottis

- Gastroduodenal: Reverse peristalsis

- Muscular: Abdominal and diaphragmatic contraction

- Glottic: Opens to let vomitus out of the esophagus

- Nausea: Sensation of needing to vomit

- Vomiting center --> Central pattern generator

- Chemoreceptor trigger zone (CTZ) --> Located in the area postrema --> Break in the BBB where the brain can sample the blood stream

- Parasympathetic and sympathetic afferents

- Afferents and CTZ all feed into vomiting center

- Retching: Inspiratory motions of chest wall and diaphragm, expiratory motions of the abdominal muscles all performed against a closed glottis --> Gastric antrum contracts while the fundus relaxes

- Emesis: Forceful evacuation of gastric contents --> Cardia is elevated and relaxed, pylorus is closed, and abdominal muscles and diaphragm undergo forceful sustained contractions

- Regurgitation: Effortless flow of esophageal contents into the mouth

1. Toxins

- Alcohol --> Stimulates area postrema

- Bacterial toxins

- Opiate analgesics

- Chemotherapy

- Digoxin

- Dopaminergic agents

- Erythromycin

2. Disease States

- Uremia

- Diabetic ketoacidosis

- Pregnancy

- Hypercalcemia

- Hyperemesis gravidum: Intractable vomiting leading to dehydration and metabolic disturbances

- Viral

- Obstructive

- Pancreatitis

- Biliary dysfunction

- Gastric ulcers

- Hepatitis

- Dysmotility

- Enterochromaffin cells encounter pathogen --> Pass signal to parasympathetic afferents --> CTZ

- Acute MI and vestibular problems can also stimulate

- Migraine

- Trauma

- Increased intracranial pressure: Tumor, abscess, hemorrhage

- Acute: Usually infectious

- Chronic: Often due to marijuana use and gets better with hot shower, perform upper endoscopy, and abdominal imaging

- Vomiting vs. regurgitation

- Look at the vomit!

- Lab tests: Glucose, BUN/creatinine, Calcium, hCG, liver enzymes and pancreatic enzymes

- Delayed gastric emptying due to autonomic dysfunction

- Symptoms: Nausea, vomiting, abdominal discomfort, early satiety, and bloating

- Diagnosis: Gastric Scintigraphy

- Often due to severe diabetes with other symptoms (neuropathy)

- Acetylcholine drugs --> Scopolamine (motion sickness treatment)

- Antihistamines --> Diphenhydramine

- Neuroleptic agents --> Block D2 receptors

- Prokinetic agents: Metoclopramide (dopamine receptors), ondansetron (serotonin inhibitor), and erythromycin

- Others: Benzodiazepines, corticosteroids, and cannabinoids

1. H2 receptor antagonists (ranitidine) --> Once daily at bedtime

- Mechanism: Competitively inhibits H2 receptors on parietal cells

- Side effects: Slight risk of CYP enzymes, drug interactions (P450), and increased pulmonary infection

2. Proton Pump Inhibitors (Omeprazole) --> Once daily before breakfast

- Mechanism: Irreversibly inhibits H/K ATPase

- Absorption: Oral, prodrugs with enteric coating --> Activated by 0.8 pH in cannaliculus

- Clearance: Short elimination and cleared by P450 (CYP2C19 and CYP3A5)

- Side effects: Drug interactions, increased risk of C. diff, and increased risk of hip fractures in post-menopausal smokers

- Increased effect and half life in CYP2C19 deficiency mutants

- Basic salts containing Na, Ca, Mg, and Al

- Neutralize gastric acid

- Used primarily to supplement acid inhibitors or as monotherapy for heartburn

- Differences: Potency, formulation, duration of action, and side effects

- GI side effects: Diarrhea with Mg and Constipation with Al

- Systemic alkalosis

- Systemic effects of excess cation absorption --> Volume expansion (Na) and impaired renal function and weakness (Ca)

- Switch to COX-2 inhibitor

- Add PPI

- Add misoprostol (prostaglandin analog) --> May cause secretory diarrhea though

- Increase smooth muscle contraction and peristalsis

- Metoclopramide --> Stimulates ACh release and D2 antagonist

- Uses: Gastric stasis, GERD, and N/V

- All help to decrease the feeling of nausea and reduce the likelihood of vomiting being initiated by the brain

1. H1, D2, M, and 5HT3 receptor antagonists --> Targets are in the gut, vestibular apparatus, CTZ, and vomiting center

2. Glucocorticoids

3. Cannabinoid Receptor Agonists --> Dronabinol (Delta-9-THC analog)

4. Substance P Receptor Antagonist --> Aprepitant

- Used to counteract the effects of drugs such as opioids and Ca channel blockers

- Used to manage chronic constipation

- Used prior to diagnostic examination --> Colonoscopy

- Mechanisms: Increase bulk contents of intestinal lumen by retaining fluid and gel formation, increase osmolarity, decrease net electrolyte and fluid absorption, and stimulate intestinal motility

- Analgesic induced constipation via u receptor activation

- Increased sphincter tone, decreased peristalsis, and increased fluid and electrolyte absorption

- Slower gastric emptying rate and intestinal transit

- Treatment using naltrexone or methylnaltrexone (quaternary ammonium) --> No CNS effects

- Opioid agonists limited from the CNS

- Not analgesics or drugs of abuse

- Loperamide (imodium) --> Substrate for a CNS efflux pump --> Doesn't enter CNS

- 5-aminosalicylic acid (mesalamine): Formulated for distal release and prodrug forms --> Immune inhibition and decreased leukocyte adhesion/migration

- Glucocorticoids: Rectally administered or oral but have a high first-pass effect

- Antimetabolite immunomodulators (azathioprine and 6-mercaptopurine)

- TNF-a antagonists (infliximab): Immunosuppression --> Increased infections (TB) and hypersensitivity reactions

- Integrin a4 antagonists (Natalizumab): Blocks lymphocyte interaction with adhesion molecules --> No migration to site of inflammation --> Now used in Crohn's

- Gram-negative rods

- Facultative anaerobes

- Most have flagella and are motile

- Many have pili (attachment) --> Some have sex pili

- Oxidase-negative, all ferment glucose and some ferment lactose

- Grow on blood agar and MacConkey agar

- Classification based on O polysaccharides, capsular K antigen, and flagellar H proteins

- Virulence factors: LPS, capsule, antigenic phase variation, type III secretion systems, sequestration of growth factors, and genetic acquisition of antibiotic resistance by mutation/plasmids

- Most medically relevant species

- Motile via flagella, facultative anaerobe, and encapsulated

- Transmission: Normal flora or exogenously (gastroenteritis)

- Pathogenesis: Specific adhesins and exotoxins (endotoxins) depending on disease presentation

- Disease Presentations: Septicemia, UTIs, neonatal meningitis, and gastroenteritis

- Diagnosis: Culture using MacConkey agar --> Lac + (pink) and strain-specific toxin detection

- Treatment: Supportive, antibiotic for severe/disseminated infections, prevention, and no vaccine

- Affects infants in developing countries

- Person-to-person transmission

- Causes watery, non-bloody diarrhea,

- Attaches to mucosal epithelial cells, produces cytoskeletal changes and cell death via type III secretion systems

- Causes traveler's diarrhea --> Watery non-bloody diarrhea

- Serious disease in infants of developing countries

- Needs large inoculum to cause disease

- Produces heat labile (HT) and heat stable (ST) enterotoxins --> Causing hypersecretion but no tissue damage

- Most common cause of gastroenteretis in developed countries

- This strain kills infants and elderly --> O157:H7

- Starts with watery, non-bloody diarrhea but can progress to bloody diarrhea with abdominal cramps

- Can progress to hemolytic uremic syndrome (HUS) too

- Attacks the large intestine

- Toxins: Cytotoxic Shiga-like toxins --> Inhibit protein synthesis and lead to death of absorptive cells --> Shiga-like 2 toxin destroys glomerular endothelial cells

- Rare but more common in developing countries

- Starts with watery diarrhea, fever and cramping

- May progress to dysentery with low volume bloody diarrhea

- Attacks large intestine

- Bacterial genes carried on plasmid

- Invades epithelial cells --> Cell destruction and inflammation --> Ulceration in the colon

- Occurs in infants or travelers to developing countries

- Persistent watery diarrhea with vomiting, dehyration, and low-grade fever

- Organism attaches to epithelium of small intestine and forms biofilm

- Microvilli become shorteened and hemorrhage can occur

- Two species: S. typhi (typhoidal) and S. cholerasuis (non-typhoidal) --> >2500 O serotypes

- Facultative anaerobes, motile (flagella), Lac -, and Ox -

- Animal sources: Poultry and eggs but also beef, pork, and turtles

- Human-to-human transmission before or after gastroenteritis

- Disease presentations: Gastroenteritis, typhoid/enteric fevers, and bacteremia

- Diagnosis: Stool samples, culture on MacConkey agar, and Slide agglutination tests

- Treatment: Supportive, antibiotics but resistance is a problem, and vaccines

- Invasion of epithelial and subepithelial tissue of small and large intestines --> Inflammation and diarrhea

- Bacteremia not common

- Large inoculum necessary (>100,000) 

- Incubation: 12-24 hours

- Symptoms: Nausea/vomiting, then abdominal pain and diarrhea --> Usually self-limiting

- Most common form of Salmonella

- Infection begins in the small intestine with few GI symptoms

- Organisms replicate in phagocytes --> Liver, gallbladder, and spleen --> Bloodstream

- Bacteremia associated with fever and other endotoxin-associated symptoms

- Carrier state: Carried in gallbladder and excretion in feces

- Symptoms: Slow onset of fever and constipation, bacteremia presenting with high fever, delirium, tender abdomen, enlarged spleen, and maculopapular rash (rose spots)

- Resolution usually by week 3 but patients can become chronic carriers

- 5-10% of Salmonella infections --> Usually in patients with pre-existing chronic disease

- Osteomyelitis, pneumonia, and meningitis

- Symptoms: Fever, little or no gastroenteritis, and then organ-specific

- Facultative anaerobe, non-motile, Lac -, and Ox - --> Only infects humans (shigellosis or bacillary dysentery)

- Tramission: Fecal-oral route --> Fingers, flies, food, and feces (Four F's)

- Infection with very low inoculum --> Food borne outbreaks

- Pathogenesis: Limited to GI tract --> Invades mucosa of distal ileum and colon --> Inflammation and ulceration occurs

- Toxin producing strains cause more severe disease

- Incubation: 1-4 days

- Severity of disease depends on the Shigella species and age of patient

- S. dysenteriae causes most severe disease --> A/B exotoxin (Shiga toxin)

- Shiga toxin: Damages intestinal epithelium --> Encoded by a lysogenic phage

- S. sonnei: Milder disease and no Shiga toxin production --> Most common in the US

- Diarrhea is usually self-limiting within 2-3 days

- No protective immunity results

- Diagnosis: Isolation of organism in stool, Lac - colonies on MacConkey agar, and slide agglutination

- Treatment: Supportive treatment, antibiotics but resistance is a problem, and no vaccine or recommended prophylaxis

- Encapsulated and Lac +

- Normal flora of respiratory tract in 10% of people

- Most commonly causes disease in patients with other chronic diseases (diabetes, CF, alcoholism)

- Pathogenesis: Anti-phagocytic capsule

- Presentation: Thick, bloody sputum --> Can progress to necrosis and abcess formation

- Can also cause complicated UTIs

- Diagnosis: Culture on MacConkey agar and biochemical tests

- Treatment: Antibiotics but resistance is high and no vaccine

- Motile and "swarm" on agar plates --> Lac -

- Found in soil and water or normal flora of colon

- Presentation: UTIs, pneumonia, wound infections, and septicemia

- Diagnosis: Swarming on blood agar, Lac - on MacConkey agar, and urease-positive

- Treatment: Antibiotics, catheter care and removal

- Not part of the enterobacteriaceae family

- Curved, comma shaped G- --> Facultative anaerobe

- Transmission: Ingestion of contaminated water/food

- Outbreaks with overcrowding, poor sanitation, and malnutrition

- Must be ingested in very large numbers --> Large inoculum

- Pathogenesis: Secretion of mucinase for adherence, exotoxin (cholera toxin) secretion --> Stimulates adenyl cyclase --> Increased CFTR Cl secretion

- Toxin genes encoded by lysogenic phage

- Large volumes of watery diarrhea (rice water stool) --> No WBCs or blood --> 10-15 per day

- No abdominal pain

- Symptoms are related to severe dehydration

- If severe enough, can lead to heart and kidney failure

- 40% mortality in untreated cases

- Diagnosis: Clinical presentation --> Especially in outbreaks

- Treatment: Rapid, adequate fluid/electrolyte replacement (with glucose), antibiotic therapy usually not necessary

- Prevention: Vaccines in other countries --> Oral, killed whole-cell vaccines

- Curved, comma/S-shaped, microaerophilic, and grows at 42 C

- Transmission: Contaminated water/food with animal (cattle, poultry, and dogs) feces

- Pathogenesis: Gastroenteritis through unkonwn mechanism --> No toxin

- Diagnosis: Gram staining, oxidase-pos, sensitive to nalidixic acid, and urease-neg

- Treatment and prevention: Supportive care, antibiotics if serious, and no vaccine

- Foul-smelling diarrhea --> Bloody stools with leukocytes

- Fever and abdominal pain

- Self-limiting

- Guillan-Barre syndrome and reactive arthritis is rare but possible

- Curved G- rods

- Transmission: Present in the stomach of many people

- Pathogenesis: Attaches to mucus-secreting cells, produces urease to neutralize local pH, and ammonia and inflammation results in mucosal damage 

- No disease dissemination

- Clinical presentation: Usually asymptomatic but can induce peptic ulcer disease and gastric cancers

- Diagnosis: Gram staining of biopsy, isolation in culture, urease-positive, urea breath test, antigen in stool, and specific IgG in serum

- Treatment: Triple therapy treatment

- Pleomorphic rods with LPS, and capsule (sometimes)

- Anaerobic and growth stimulated by 20% bile

- Transmission: Normal flora of GI, GU, and Resp tracts

- Pathogenesis: Only causes disease when it is moved from the normal site --> Usually in polymicrobial infections and opportunistic infections

- Presentation: Intraabdominal, pleuropulmonary, genital, skin, and soft tissue infections, bacteremia, and gastroenteritis

- Diagnosis: Isolation in culture, growth with 20% bile, biochemical/molecular tests

- Treatment: Antibiotics, surgical intervention/debridement if necessary and antibiotic prophylaxis prior to surgery

- Non-enveloped dsRNA segmented genome (11 segments) --> Group A-G

- Groups classified based on VP6 capsid protein --> Mostly A and B&C are rare in the US

- Icosahedral capsid with two concentric shells

- Unusually stable to heat, pH, and lipid solvents --> Inactivated by ethanol, phenol, and chlorine

- Replicate in the cytoplasm and produce inclusion bodies --> Never fully uncoats in the cytoplasm

- Virions contain RNA-dependent RNA polymerase

- Released by cell lysis

- Transmission: Oral-fecal route, fomites, and hands

1. Presentation

- Main cause of diarrhea in infants 6-24 months old

- Infects small intestine --> Midabdomen pain with large volume non-bloody watery stool

- Incubation: 2-4 days --> Fever abdominal pain and vomiting

2. Pathogenesis: Infects cells at the tip of the villi, spreads to neighboring cells --> Viruses released by lysis

- Infected cells are damaged or killed --> Immature cells replace and have reduced absorptive function

- Fluid accumulates in the lumen --> Diarrhea

- Short-lived mucosal (IgA) and incomplete systemic immunity

- Re-infections occur but lessens symptoms

- Adults can be asymptomatic carriers

- Diagnosis: "dipstick" test, stool study, and clinical presentation

- Prevention: Blocking fecal-oral route of transmission

- Treatment: Supportive but no anti-viral treatment

- Vaccines: Two live-attenuated oral vaccines --> Protects against 4 most common types

- Found in animals and humans --> ~23 million cases of gastroenteritis/year

- Noroviruses and Sapoviruses

- Structure: Non-enveloped, icosahedral capsid, stable, + sense ssRNA genome

- Replication: In cytoplasm --> Single polyprotein cleaved into viral proteins

- Transmission: Fecal-oral, shellfish, and person-person --> Cruise ship outbreaks

- Pathogenesis similar to rotavirus --> Infects villi tips

- Five genogroups (GI, GII, GIV are human genotypes)

- Immunity: Antibody production but immunity is brief

- Diarrhea with nausea and vomiting --> Especially in children

- No bloody stools

- Fever in 1/3 of patients

- Incubation: 24-48 hours --> Resolves in 12-60 hours

- Diagnosis: Virus detection in stool sample, serological assays for antibodies, but RT-PCR most commonly used

- Treatment: Supportive can use probiotics too

- Prevention: Good hygiene and avoid shellfish

- Vaccine: Based on capsid protein --> Under evaluation, no vaccine currently on the market

- Second to rotaviruses as cause of actue diarrhea in children

- Types 40 and 41 associated with diarrhea

- Very difficult to culture in vitro

- Diagnosis: Antigen assay, culture, PCR, and serology

- Treatment: Illness is usually self-limiting, treatment is supportive

- Trophozoite and cyst forms --> Cyst ingested fecal-orally

- Other Entamoeba strains are found in normal gut flora

- Trophozoite is the active, replicating form --> Amebiasis

- Replication: Binary fission

- Diagnosis: Trophozoites or cysts in stool, antigen detection, and aspiration of abcess material in extraintestinal disease --> Organisms engulf RBCs so seen on staining

- Treatment: Metronidazole to kill trophozoites and iodoquinol to eliminate cysts

- Prevention: Adequate sanitation, clorination, and filtration of water --> No vaccine

- Ingestion of cysts --> Stimluated by gastric acid

- Trophozoites released --> Penetrate mucosal layer of colon and multiply

- Produce tissue necrosis by lysing colonic cells, neutrophils, lymphocytes and monocytes

- Mechanism of killing not well understood --> Release of proteinases and production of small pores in lipid bilayers

- Mucosa shows flask-like ulcerations, inflammation, and hemorrhage

- Organism can invade deeper and infect other organs --> Extraintestinal amebiasis

- Encystation: Occurs in the large intestine and cysts are excreted in feces

- Partial immunity formed to lectin adhesin molecules

- Incubation: 1-4 weeks

- Asymptomatic (90%): Due to infection with low inoculum, less virulent strains, and effective host immune response

- Intestinal amebiasis: Subacute onset for 1-3 weeks, results in tissue destruction and inflammation

- Extraintestinal amebiasis: Fever, leukocytosis, rigors and liver abcess formation --> "Anchovy-paste" containing abcesses

- Flagellate

- Trophozoite and cyst forms --> Cyst is ingested and trophozoite is active

- Trophozoite looks like it's looking back at you!

- Animal reservoirs: Beavers, cattle, and sheep

- At risk patients: Infants, young children, travelers, immunocompromised, and patients with hypochlorhydria/CF

- Transmission: Fecal-oral

- Diagnosis: Stool sample examination

- Treatment: Usually spontaneous recovery but can be  use metronidazole, tinidazole, or nitazoxanide, and supportive care

- Prevention: Hand washing and good hygiene

- Ingestion of cysts

- Release of trophozoites in small intestine

- Attachment to mucosal epithelium via adhesive disk

- No invasion of tissue

- Villi become flattened without necrosis

- Binary fision --> Reproduction

- Encystation: Occurs in small intestine

- Incubation: 1-3 weeks

- ~50% are asymptomatic

- Symptoms: Mild diarrhea to severe maladsorption

- Sudden, foul-smelling, watery diarrhea --> Greasy stools that may float

- Lactose intolerance may result --> Destruction of brush border enzymes

- Many species but C. parvum and C. hominis are most common in humans

- Sporozoan --> Sexual and asexual reproduction

- Oocyte and sporozoite forms

- Animal reservoirs: Cattle, sheep, birds, and rodents

- Transmission: Fecal-oral via contaminated water

- Presentations: Sporadically in immunocompetent, chronic/severe cases in immunocompromised, and causes diarrhea and malnutrition in children in resource-poor countries

- Diagnosis: Examination for cysts in stool sample with modified acid-fast stain

- Treatment: Usually none needed but nitazoxanide if needed

- Prevention: Hand washing and good hygiene with water treatment

- Ingestion of oocyst --> Sporozoites released via gastric acid

- Sporozoites attach to surface of columnar cells --> Asexual reproduction occurs

- Sexual reproduction: Microgamont fertilizes macrogamont to produce fertilized oocyte

- Each oocyst contains 4 sporozoites

- Incubation: 7-10 days

- Possible outcomes: Asymptomatic, mild diarrhea, and severe enteritis with/without biliary involvement

- Recovery is usually spontaneous

- Urogenital flagellate

- Only exists as trophozoite

- More common in women --> Men are usually asymptomatic

- Humans are the only natural host

- Symptoms: Purulent, malodorous, thin vaginal discharge

- Complications can be serious 

- Diagnosis: Wet mount examination of discharge

- Treatment: Treat all including carriers with metronidazole or tinidazole

- Prevention: Good personal hygiene and protected sex

- Trophozoite is introduced into the vagina during intercourse

- Trophozoites live in the prostate and urethra of males

- Trophozoites live in the vagina in females and change the ectocervix epithelium

- Free-living Amoeba --> "Brain-eating" amoeba

- Exists in trophozoite and cyst forms

- Transmission: Inhalation of aerosolized droplets into the nose usually during swimming in a fresh water lake

- Found in soil and contaminated fresh water

- Pathogenesis: Invade nasal mucosa and gain access to the brain causing extensive tissue destruction

- Clinical findings: Amoebic meningoencephalitis rare but almost always fatal

- Symptoms: Severe frontal headache, sore throat, blocked nose with altered senses, vomiting, confusion, stiff neck, positive Kernig sign, fever, coma and death

- Diagnosis: Microscopic examination of nasal discharge and CSF

- Treatment: None

- Prevention: Difficult to prevent and control infections

- Large, rectangular G+ rod --> Spore producing

- Strict anaerobe, non-motile, and classified as 5 different types

- Ubiquitous in soil, water, and sewage 

- Transmission: Through skin breaks

- Part of normal fora in the vagin and colon of some humans

- One of the most common causes of foodborne illness in the US

- Presentation: Gastroenteritis or gas gangrene

- a-toxin: Lethal necrotizing lecithinase

- b-toxin: Intestinal stasis, mucosal loss and necrotic lesions --> Can progress to necrotizing enteritis

- e-toxin: Increased vascular permeability of GI tract

- i-toxin: Increased vascular permeability and necrosis

- Enterotoxin: Superantigens that alters membrane permeability in the small intestine --> Fluid and ion loss

- Gas gangrene: Muscle necrosis, exotoxin production, and organism spread leads to edema, gas pockets, and necrosis

- Clostridial cellulitis

- Food poisoning: 8-24 hour incubation, water diarrhea with cramps, no fever, N/V

- 24-48 hour duration

- Diagnosis: Detection of baterium from patient or contaminated food --> Immunologic detection of enterotoxin in food

- Treatment: Debridement and antibiotics for soft tissue infections, but food poisoning is usually self-limiting

- Prevention: Proper food prep and storage and proper wound care

- Large, rectangular, G+ rod --> Spore producing, strict anaerobe, and motile

- Transmission: Through skin breaks --> Found in soil and transient colonizer in the GI tract

- Toxin mediated --> Tetanospasmin (A/B toxin) binds motor neurons and inhibits the release of inhibitory NTs (GABA and glycine) and tetanolysin which is an oxygen-labile hemolysin

- Results in spastic/rigid paralysis

- Generalized tetanus: trismus (lockjaw), risus sardonicus (sardonic smile), and opisthotonos (arching of the back)

- Neonatal tetanus: Occurs when the umbilical stump becomes infected and pregresses to generalized disease --> Opishtotonos

- Diagnosis: Clinical presentation and history

- Treatment: Would care with active and passive immunization

- Active immunization: Vaccine

- Passive immunization: Immunoglobulin injections

- Prevention: Regular vaccination with DTaP vaccine

- Large, rectangular, G+ rod --> Spore producing, strict anaerobe, and fastidious --> 8 immunologic types

- Found in soil

- Transmission: Improperly prepared canned foods or honey

- Toxin mediated --> Botulinum toxin: Blocks release of ACh from nerve terminal --> Flaccid paralysis

- Toxin produced by organisms in the gut --> Absorbed into the blood stream

1. Foodborne botulism: Weakness and dizziness after 1-2 days, double vision, blurred vision, fixed, dilated pupils, dry mouth, slurred speech, drooping eyelids, progressing to muscle weakness and flaccid paralysis --> 3-5% mortality

2. Infant botulism: Limp baby syndrome, C. botulinum colonizes GI tract --> Lethargy, constipation, weak cry, poor muscle tone, and poor feeding

3. Wound botulism: Toxin production in contamianted wounds --> Associated with injection of black tar heroin

- Diagnosis: Detection of toxin in patient or contaminated food

- Treatment: Antibiotics and antitoxin and respiratory support if needed

- Clinical uses: Alleviating persistent neck and upper back pain, migraines, excessive perspiration, Dupuytren's contracture, clubfeet, and dystonia

- Large, G+ rod --> Strict anaerobe and spores

- Ubiquitous and colonizes the intestines of <5% of normal healthy people

- Endogenous infection resulting from antibiotic therapy

- Exogenous infections due to exposure to spores

- Toxins: Toxin A (enterotoxin) stimulates inflammation and increases permeability and Toxin B (cytotoxin) which inhibits GTPases inhibiting signal transduction

- Pseudomembranous colitis possible

- Antibiotic-associated gastrointetinal diseases

- Acute diarrhea usually develops 5-10 days after antibiotic therapy (clindamycin, penicilins, and cephalosporins)

- Pseudomembranous colitis: Profuse diarrhea, addominal pain, and fever

- Diagnosis: Exotoxin identification in stool and PCR assays --> Stool specimen must be refridgerated!!

- Treatment: Discontinue antibiotic therapy, metronidazole and fidoxomicin (flagyl) for recurrent disease, and fecal microbiota transplant

- Prevention: Difficult to prevent due to eliminated spores

- Large, G+ rods with square ends found in chains

- Facultative anaerobe, produces spores, encapsulated, and non-motile

- Infects herbivores --> Humans are accidental hosts

- Pathogenesis: Polypeptide capsule of poly D-glutamic acids, edema factor (A/B toxin) causing edema, lethal factor (A/B toxin) which inhibits the MAPK signaling pathway, and protective antigen forms pores in cell membranes

1. Cutaneous anthrax: Most common, painless ulcer with a black eschar and pronounced local edema --> Can lead to bacteremia and death

2. Pulmonary anthrax: Initial respiratory symptoms similar to influenza, and rapidly progresses to fulminant bacteremic phase with severe dyspnea, hypoxemia, shock, and death

3. Gastrointestinal anthrax: Flu-like illness, sore throat, neck swelling, difficult swallowing, nausea, loss of apetite, mild to severe vomiting, mild to severe diarrhea, and abdominal pain

- Diagnosis: Immunohistochemical staining, PCR, and antibody detection in late infections

- Treatment: Antibiotics

- Prevention: Antibiotic prophylaxis and vaccine for at-risk populations

- Large, G+ rod with square ends in chains

- Facultative anaerobe, produces spores, and motile

- Ubiquitous in soil --> Ingestion of contaminated food, injuries, and IV injections

- Diagnosis: Stool culture and enterotoxin

- Treatment: Supportive and antibiotics

- Prevention: Eating food soon after cooking and storing properly

1. Emetic form of gastroenteritis: Heat-stable, proteolysis-resistant enterotoxin (superantigen) --> Consumption of contaminated rice

2. Diarrheal form of gastroenteritis: Heat-labile enterotoxin similar to E. coli --> Fluid loss via adenylate cyclase in gut epithelium --> Contaminated meat, vegetables, or sauces

3. Ocular disease: After penetrating injuries to the eye --> Loss of light perception within 48 hours of injury

- Three toxins: necrotic toxin (heat-labile), cerolysin (hemolysin), and phospholipase C (lecithinase)

- Shigella

- Campylobacter jejuni

- Enteroinvasive E. coli

- Salmonella

- Clostridium difficile

- Vibrio parahemolyticus

- Yersinia enterocolitica

- Viruses: Rotavirus, Norovirus, Calicivirus, Coronavirus, Astrovirus, and Adenovirus

- Bacteria: Yersinia, Vibrio cholera, ETEC, EPEC, Aeromonas hydrophilia, Listeria, Plesiomonas shigelloides

- Toxin producers: Staphylococcus aureus, Bacillus cereus, and Clostridium perfringens

- Anaerobes: Bacteria for which 10% O2 is toxic

- Foul smelling pus

- Deep abcess formation

- Infection close to mucosal surfaces

- Gas in tissue

- Negative routine cultures

- Presence of "sulfur" granules --> Actinomyces

- Infections after bites --> Except cat bites

- Oral: 10^7-10^8 --> Aerobes and Anaerobes

- Stomach: 10-1,000 --> Lactobacilli

- Cecum: 10^4-10^6 --> Streptococci, Lactobacilli, and Enterobacteriaceae

- Colon: 10^11 --> Aerobic and anaerobic microbial populations --> 1000:1 ratio of anaerobes/aerobes

- Roles of indigenous flora: Vitamin K production, deconjugation and dehydroxylation of bile acids, and production of H2O2

- Most anaerobes are commensals

- some have important virulence factors --> Superoxide dismutase, beta-lactamase, capsule, enzymes, adherence factors, and toxins

- Gram-negative rods: Fusobacterium, Bacteroides fragilis, Prevotella sp, and Campylobacter 

- Gram-negative cocci: Veillonella

- Gram-positive rods: Clostridia, Proprionobacterium, and Actinomyces

- Gram-positive cocci: Peptostreptococcus, Peptococcus, Streptococcus, and Staphylococcus

- Meningitis

- Acute sinopulmonary infections

- Cholecystitis

- Spontaneous peritonitis

- Urinary tract infections

- Osteomyelitis (acute)

- CNS infections --> Brain abcesses

- Head and neck infections

- Oral infections

- Pleuropulmonary infections --> Lung abcesses and aspiration pneumonia

- Bacteremia --> Endocarditis and Post-anginal sepsis (carotid infection)

- Intra-abdominal infections --> Peritonitis, appendicitis

- Infections of the female genital tract

- Soft-tissue infections

- Most common organisms: Bacteroides fragilis, Fusobacterium, Anaerobic cocci, Actinomyces israelii, and Clostridia

- Presenting symptoms: Headache, Nausea/vomiting, lethargy, fever, focal sign, seizure, and nuchal rigidity

- Bartlett's model: E. coli --> Sepsis and eary mortality and B. fragilis --> Late abcesses

- Aerobic flora: E. coli, Proteus, Klebsiella, and Streptococci

- Anaerobic flora: B. fragilis, other Bacteroides, Peptostreptococcus, and Clostridia

- Can result from diverticulitis or other colitis

- Can progress to liver or psoas abcesses

- Collection and transport: Special anaerobic container with needle and syringe

- Processing: Direct examination of the clinical specimen and gram stain --> Sulfur granules, gas, foul odor, and mixed flora in the stain

- Isolation and identification: Anaerobic, non-selective, selective and blood culture media

- Cultures: Blood and MacConkey Agar

- Incubation: Minimum of 48 hours at 35 C for anaerobes and 24 hours at 35 C for aerobes

- Above the Diaphragm: Penicillin and B-lactam/B-lactamase inhibitor combinations

- Below the diaphragm: Metonidazole and clindamycin

- Mild-Moderate Disease: Ampicillin/sulbactam, piperacillin/tazobactam, ticarcillin/clavulanate, ertapenem, cefoxitin, cefotetan, and ciprofloxacin with metronidazole

- Severe Disease: Imipenem, meropenem, ampicillin/metronidazole/antipseudomonal aminoglycoside, ampicillin/Metronidazole/Ciprofloxacin

- Usually caused by C. perfringens

- Associated with traumatic wounds/vascular insufficiency

- Fulminant infection

- Both local and systemic findings

- Presentation: Pain, rapid progression, gas/crepitus in tissue, magenta discoloration, hemmorhagic bullae, and "dish-water fluid"

- Systemic Findings: Sepsis, prostration, alert patient, intravascular hemolysis, renal failure, and myoglobinuria

- Treatment: Supportive, debride muscle, penicillin, hyperbaric oxygen, and antitoxin no longer available

- Non-spore forming delicate Gram-positive rods

- Branching in morphology

- Anaerobic, endogenous flora

- Polymicrobial infection --> Sulfur granules

- Slow progression, "cold" abcess

- Proclivity to cross tissue planes

- Production of sinus tracts

- "Woody" induration

- Treatment: Penicillin and tetracyclin

- Most common locations: Cervicofacial, thoracic, abdominal, and pelvic

- 2-10/100,000 (incidence) and 35-100/100,000 (prevalence)

- More prevalent in whites than blacks and in Jews over Non-Jews

- Usual age of onset: 15-30 years old

- Smoking shows a protective effect

- Usually begins in the rectum and moves proximally to the transverse colon

- Proctitis, proctosigmoiditis, distal colitis, left-sided colitis, and pancolitis

- Symptoms: Diarrhea, crampy abdominal pain, weight loss, fever, urgent and frequent defecation, passage of mucus, and rectal bleeding

- Complex genetic disorder --> Increased likelihood in monozygotic twins

- Combination of genetic susceptibility, environmental triggers, and immune dysregulation

- 75-80% of multiply affected families concordant for disease type

- 1-6/100,000 (incidence) and 10-100/100,000 (prevalance)

- More common in whites than blacks and Jews than Non-Jews

- Age of presentation: 15-30 years old

- Smoking is associated with development of disease

- Autoimmune disorder affecting the intestine sporadically

- Symptoms: Diarrhea, right sided abdominal pain, weight loss, fever, and anal disease (fissures, etc)

- Ileocecal (40%), confined to small intestine (30%), and confined to colon (30%)

- Clinical history, laboratory, endoscopic, radiologic, and histologic features

- GI specific complaints

- Extraintestinal manifestations: Skin, eyes, joints, liver, etc

- Diagnosis of CD can be more difficult than UC

- Crohn's Disease: Inflammation, obstruction, and fistulization

- Ulcerative Colitis: Obstruction and inflammation

- Arthritis: Colitic arthritis, ankylosing spondylitis, and sacroilitis

- Liver: Primary sclerosing cholangitis (PSC)

- Skin: Pyoderma gangrenosum and erythema nodosum

- Eye: Uveitis and episcleritis

- Others: Autoimmune anemia, clotting disorders and thyroid inflammation

- Induce remission

- Maintain remission

- Maintain quality of life

- Prevent complications, hospitalizations and surgery

- Optimize timing of surgery

- Disease location and severity may dictate treatment

- Usually used for mild disease only

- Sulfasalazine: Linked to sulfa carrier so it becomes active in colon

- Topical administration via suppository or enemas

- Safe and effective in mild to moderate UC

- Data is limited for Crohn's

- Formulations: Vary depending on location of release

- Used to treat Moderate to Severe Disease

- Oral: Prednisone

- Parenteral: Methylprednisolone and hydrocortisone

- 60-80% of patients go into remission over 1-3 month course

- Not used for maintenance therapy --> Systemic side effects

- Budesonide: Undergoes extensive first pass effect by liver when absorbed --> Primary effect directly in the lumen --> Reduces side effects

- Azathioprine, 6-mercaptopurine, and methotrexate

- More effective for Crohn's disease

- Slow onset of action (weeks)

- Used to try and avoid use of corticosteroids

- Methotrexate: Administered SC or IM --> Benefit in CD patients --> Unclear effect in UC and teratogenic for pregnant women

- Anti-TNF Agents: Various different preparations but all the same idea

- Combination therapy with azathioprine and Anti-TNF agents are the most effective

- Adverse Effects: Immunogenicity, infection (TB), autoimmunity, lymphoproliferative disorders, neoplasm, psoriaform lesions, demyelinating disorders, worsening CHF, and hepatotoxicity

- Complex fistula

- Deep ulceration on endoscopy

- Young age

- Steroid-dependence/resistance

- High risk anatomy

- Severe disease activity

- Serological burden

- Most Crohn's patients will need surgery --> Not curative, can relapse

- Surgery for Ulcerative Colitis is curative as long as the entire length of involved bowel is removed

- Indications: Perforation, hemorrhage, intractable/fulminant disease, suspicion/identification of cancer, growth retardation in children, systemic complications of disease/meds, anorectal disease (Crohn's), intra-abdominal abscess (Crohn's), and obstruction due to stricture (Crohn's)

- Maldigestion: Impaired nutrient hydrolysis

- Malabsorption: Defective mucosal absorption of nutrients

- Fat, carbohydrate, proteins, vitamins, and minerals may be malabsorbed

- Symptoms: Diarrhea with/without steatorrhea, weight loss, anorexia, malaise and/or fatigue

- Steatorrhea: Sign of fat malabsorption --> excretion of >6 g/day on an adequate fat intake

- Skin: purpura (vit K), clubbing (inflammatory disease), and anemia (iron/folate/B12)

- Mouth: angular stomatosis (iron), glossitis (iron, vit B), and aphthous ulcers (Crohn's and celiac)

- Edema: Hypoproteinemia

- Peripheral neuropathy: Vit B12 and thiamin deficiency

- Vitamin B12/Folate/Iron: Anemia, glossitis, cheilitis, angular stomatitis, diarrhea, paresthesias, and ataxia

- Vitamin D/Ca/Mg: Osteoporesis, osteomalacia, paresthesias, and tetany

- Zinc: Anorexia, diarrhea, rash and alopecia

- Vit A: Night blindness, dry eyes, hyperkeratosis, and diarrhea

- Vit K: Ecchymoses and bleeding

- Vit E: Paresthesias, ataxia, and retinopathy

- Salivary and pancreatic amylases

- Malabsorption: Unabsorbed sugars in the lumen cause osmotic diarrhea

- Symptoms: Abdominal pain and distension

- Sugars undergo bacterial fermentation --> Short-chain Fatty Acids --> Bloating/distension

- Hydroxy fatty acids (OHFA) are not normally in diet

- Fatty acids enter the colon due to malabsorption/BA deficiency

- Bacteria hydroxylate non-absorbed lipids to OHFA

- Hydroxy stearic acid is the most common cause of steatorrhea

- Pathogenesis: 

1. OHFAs cause reversible jejunal and colonic secretion

2. Increased mucosal permeability

3. Induces morphological changes

4. Alters motor activity

- Most common brush border hydrolase deficiency

- States: Congenital, constitutional, and secondary lactase deficiency (post-infectious)

- Diagnosis: Lactose hydrogen breath testing

- Leads to carbohydrate malabsorption and osmotic diarrhea

- Symptoms: Abdominal distension, bloating, pain, diarrhea, and flatulence

- Treatment: Lactose free diet or lactase supplementation therapy

- Pancreatic lipase: Converts triglycerides to long-chain fatty acids and medium-chain fatty acids

- Fatty acids combine with bile salts

- Long-chain + bile salts --> Micelles --> Lacteal

- Medium-chain + bile salts --> Capillary

- Chronic pancreatitis and cystic fibrosis

- Pancreatic function must be reduced to 10% in order to see steatorrhea and true fat malabsorption

- No triglyceride breakdown --> Excreted in stool

- 7.5 mmol BA pool size in the gall bladder

- .75 mmol/24 hour synthesis in liver

- Reabsorption in the terminal ileum

- Impaired bile salt activity: Bacterial overgrowth, Zollinger-Ellison Syndrome, drug effects, and disease in the terminal ileum (Crohn's or ileal resection)

1. Mechanisms of pathogenesis

- Bacteria proliferate in the intestine and deconjugate or dehydroxylate bile acids

- Deconjugated bile acids fall out of solution and cannot produce micelles

- Bacterial impair enzyme activity

- Bacteria metabolize nutrients before we can absorb

- Bacteria cause direct enterocyte damage

2. Causes: Jejunal diverticulosis, IBD, previous surgery, and impaired GI motility from diabetes, scleroderma, etc

3. Diagnosis: Culture and count bacteria, 14C-D-xylose breath test, and hydrogen breath testing

4. Treatment: Antibiotics to reduce bacterial load and treat underlying cause

- Damage to terminal ileum will reduce the amount of bile acids that are reabsorbed --> Depletion of stores

1. Post-extensive surgical resection --> Decreased absorptive area

2. Diffuse intestinal disease: Celiac's disease, tropical sprue, Whipple's disease, and intestinal infections

- Duodenum: Iron, water, Na/Cl, and glucose

- Jejunum: Carbohydrates, proteins, fat, iron, folate, calcium, vitamins

- Ileum: Bile salts and Vit B12

- 1/120-1/300 individuals of Europena descent

- Auto-IgA production against TTG --> Binds to gliadin from gluten

- >70% concordance with identical twins

- Symptoms: Diarrhea with or without steatorrhea, weight loss, malaise, weakness, iron deficiency, osteoporosis/osteomalacia, and failure to thrive in children

- Diagnosis: Anti-TTG antibodies and endoscopy/biopsy

- Treatment: Gluten-free diet

- Rare systemic disorder caused by an infection with Tropheryma whippelii

- Most commonly affects middle-aged males

- Presentation: malabsorption, arthritis, pleurisy, CNS and CVS involvement

- Diagnosis: Biopsy and PCR

- Treatment: Prolonged antibiotic therapy

- Biopsy findings: Foam-laden macrophages within the lamina propria --> Actually engulfed bacteria

- Causes fat malabsorption because macrophages invade and close the lumen of lacteals

- Needed for malignancy, bleeding, ischemia, and IBD

- Consequences depending on extent of resection, function of resected area, and adaptation of remaining bowel

- Smaller resections result in better adaptation of remaining bowel

- Presentation: Increase in BA excretion causing reduced fluid absorption in the colon --> Osmotic diarrhea

- Small resection: Normal micelle production and flow rate

- Large resection: Decreased micelle production and increased flow rate

- Malabsorption depends on what portion of the small intestine was removed --> BA diarrhea, deficiency and vit B12 deficiency

- Jejunal adapation is less complete after ileal resections

- True diverticula: Includes all layers of the bowel wall

- False diverticula: Includes the serosa and mucosal layer --> Perforates through the muscle layer

- Usually occur between the taenia coli

- Disease of Western society --> Diet low in fiber and high in refined sugars

- Age: 30% of Americans over 50 and 50-70% over 80

- Symptomatic disease occurs in patients > 50 years old

- Occurs in 15-25% of patients with diverticulosis

- Clinical features: Abdominal pain (LLQ), fever and chills, with or without constipation

- Labs: Leukocytosis

- Imaging: CT scan showing pericolonic inflammation and may show abcesses

- 10^12-10^14 bacteria per gram

- 60% of stool solids

- Important metabolic and protective functions

- Anaerobes >99%: Bacteroides, Bifidobacteria, Clostridia, Eubacteria, and Peptostreptococcus

- Aerobes <1%: Escherichia, Enterobacter, Entercoccus, Klebsiella, and Lactobacillus

- Cover anaerobes and enteric gram negative bacteria

- Treat with a fluoroquinolone/3rd gen. cephalosporin (G-) and metronidazole (anaerobes)

- Treat for 7-14 days

- Abcess

- Bowel obstruction

- Perforation

- Fistula --> Bladder, vagina, and intestine

- Bleeding --> Determine via bleeding scan, angiogram, and CT angiogram

- Treatment: Fluoroquinolone and metronidazole for 7-14 days

- Drain abcess, treat with antibiotics for longer, and surgical resection if necessary

- Surgical intervention for bleeding: Endoscopic injection, cautery or clipping, radiologic embolization, and surgical resection

- Villous atrophy

- Increased intraepithelial lymphocytes

- Crypt hyperplasia

- Increased stromal plasma cells

- All due to injury and repair

- Mimicking presentations: Tropical sprue, Crohn's disease, bacterial overgrowth, viral gastroenteritis, HIV enteropathy, immune deficiencies, and acid hypersecretion

1. Lymphocytic colitis

2. Lymphocytic gastritis

3. Dermatitis Herpetiformis --> Pruritic vesicular/bullous skin rash on scalp, shoulders, and knees

- IgA deposition under skin

4. Enteropathy Associated T-cell Lymphoma

- T-cell lymphoma of the small intestine

5. Adenocarcinoma of GI tract

1. Infectious and non-specific colitis

2. Ischemic and toxin-induced colitis

3. Collagenous or lymphocytic colitis

- Intraepithelial lymphocytes and thickened collagen plate

4. Idiopathic Chronic Inflammatory Bowel Disease (IBD) --> Ulcerative colitis, Crohn's disease, and indeterminate colitis

1. Bacteria: Shigella, Salmonella, Campylobacter, E. coli O157:H7, and C. difficile

- Shigella --> Edema and crypt abcesses

- Campylobacter --> Beaded necklace glands, edema, neutrophil infiltration, and cryptitis

- E. coli: Hemorrhagic necrosis, proximal > distal, and mimics ischemic colitis

2. Protozoal: Amebiasis, Schistosomiasis, and Cryptosporidiosis

- Amebic ulcer: Mucosal necrosis and amebae engulfing RBCs

- Schistosomiasis: Parasites seen in lamina propria

3. Viral: CMV and Herpes

- Nuclear inclusions seen in macrophages

4. Chlamydial: Lymphogranuloma Venereum

- Cytopathic Toxin: C. difficile and E. coli O157:H7

- Ischemic

- Pseudo-polyps develop

- Necrosis due to toxin production, inflammation, and edeam that eventually can lead to ischemic areas

- Cryptitis and crypt abcesses

- Gland branching --> Indicates chronic inflammation

- Pseudopolyps can form --> Giant pseudo-polyps

- Toxic megacolon can also result --> Hugely dilated and necrotic

- Increased plasma cells basally in the mucosa

- Fissuring ulcers and submucosal fibrosis --> Strictures may result

- Cobblestoning seen on the luminal surface

- Granulomatous disease in 1/3 of people

- Transmural inflammation --> Patch lymphoid aggregates in the wall

- Submucosal fibrosis

- Abetalipoproteinemia

- Amyloidosis

- Lymphangiectasia

- Mastocytosis

- Lymphoma

- Splenic flexure and the sigmoid colon --> Watershed areas

- Lots of collaterals can open up to compensate for loss of blood flow --> Vasoconstriction often develops after a few hours and may become constricted even after restoring flow

- 75% of blood flow to mucosa and 25% to muscle layers

- Villi slough off first and muscle layers are damaged later

- Lots of collaterals between SMA and IMA (marginal artery) and some collaterals between celiac and SMA (pacreaticoduodenal/gastroduodenal and gastric arteries)

- Blood flow is regulated by local changes in arteriolar pressure and alterations in tissue oxygenation --> Mediated by sympathetic fibers, norepinephrine, vasoconstriction, and vasodilation

- Colonic ischemia (60%)

- Acute Mesenteric Ischemia (~30%)

- Chronic Mesenteric Ischemia (10%)

- 70-90% mortality with truly infarcted bowel

1. SMA embolus (50%): Cardiac source

2. Non-occlusive Mesenteric Ischemia (NOMI) (25%): Vasospasm

3. SMA Thrombosis (10%): Atherosclerosis of the systemic vessels

4. Mesenteric Venous Thrombosis (10%)

5. Focal segment ischemia (5%): Very rare and not discussed further

- Presents with sudden onset of pain (knife-like) --> Out of proportion to exam (more severe pain than tenderness)

- Diagnosis: WBC >15K, non-specific labs: high gap metabolic acidosis and high amylase, thumbprinting on X-ray, doppler ultrasound, CT scan and CT angiogram

- From cardiac origin due to Afib or valve dysfunction

- Clot embolizes and travels down to the SMA --> More distal than thrombus

- Diagnosed via CT angiogram usually

- Most common type

- Some collateral from IMA but not great

- Jejunum is the most affected --> No collaterals at all

- Atherosclerotic disease 

- Thrombus forms in the proximal SMA --> More severe necrosis results

- 20-50% prior post-prandial pain along with cardiac MI

- Diagnosed by angiogram --> Occlusion 1-2 cm distal to origin of the SMA

- Most likely cause of chronic ischemia ~ intestinal angina

- Results from protective vasoconstriction due to hypovolemia or shock

- More indolent onset of symptoms --> 25% without abdominal pain --> Distension, confusion, and non-specific findings

- Also diagnosed via angiogram --> "String-of-beads" 

- Hard to diagnose --> MR angiogram best to diagnose

- Typically presents in younger patients in hypercoagulable states --> Oral contraceptives

- More indolent course --> Diagnosis made 5-14 days after onset

- Clot is usually seen on CT

- Portal venous gas can also be seen on CT

- Gold standard for AMI diagnosis

- Vascular "roadmap" of splanchnic circulation

- Advantages: Administering intra-arterial vasodilators (papaverine) and pre-operative angiography

- Disadvantages: Limited availability, potential renal toxicity, and time constraints

- Laparoscopy/laparotomy removal of non-viable tissue

- Possible second look at intestines after 12-24 hours

- Patients should then be anticoagulated

- Thrombolytics can be used in limited cases

- Stents may also be inserted through angiography, etc

- Initial: Correct precipitating cuase and broad-spectrum antibiotics

- Abdominal cramping ~ 30 minutes after eating, gradually increasing in severity and then slowly resolving over the next 1-3 hours

- Sitophobia (fear of eating) results --> Weight loss

- PHx: CVD and PVD

- Physical findings: Usually limited but patients with advanced disease appear cachectic (anorexic/wasting)

- Diagnosis: Demostration of high grade stenosis in at least 2 of the major mesenteric vessels, unexplained chronic pain, weight loss and food aversion, and high index of suspicion

- Imaging: Angiography --> 2 or more vessels occluded

- Therapy: Re-vascularization via surgery or percutaneous angioplasty/stenting

- Usually occurs in the watershed areas (Splenic flexure and sigmoid colon) --> Rectum never involved (dual blood supply)

- Frequently in older people --> Usually benign course

- Condition usually resolves before medical attention is sought

- Sometimes misdiagnosed as infectious or inflammatory bowel disease

- Usually due to atherosclerosis ~ mild/exertional angina

- Reversible colopathy (30-40%)

- Transient colitis (15-20%)

- Chronic ulcerating ischemic colitis (20-25%)

- Stricture (10-15%)

- Gangrene (15-20%)

- Fulminant universal colitis (<5%)

1. Symptoms: LLQ pain, urge to defecate, and passage of bright red/maroon colored stool --> Not massive hemorrhage

2. Physical exam: Mild to moderate abdominal tenderness over the involved segment of bowel

3. Imaging: Single strip sign seen on colonoscopy

- Symptoms usually subside within 24-48 hours --> Healing usually seen within 2 weeks

- More severe reversible damage may take 1-6 months to resolve

- Chronic sequelae are rare --> Gangrene, perforation, segmental ulcerating colitis, and stricture

1. Diagnosis

- Imaging shows bowel wall thickening

- Endoscopy can be diagnostic --> Single strip sign

- Angiography not typically needed or performed

2. Therapy

- Rehydration and optimize cardiac status

- Bowel rest

- Broad spectrum antibiotics

- Remove precipitating medications

- Recurrent abdominal discomfort or pain for at least 3 days/month in the past 3 months with 2 of 3 features:

1. Relieved with defecation

2. Onset associated with a change in frequency of stool

3. Onset associated with a change in form/consistency of stool

- Based on Rome Criteria

- Altered brain-gut communication resulting in:

1.Altered CNS responsiveness to visceral stimuli

2.Visceral hyperresponsiveness to environmental and luminal events in the gut

- Generally activated by stress

- Gut has hypermotility after meals compared to controls

- Visceral hypersensitivity to pain

- Serotonin receptors are widely distributed throughout the gut

- Most of the sertonin in the body resides in the gut

- Affects visceral perception of distension/pain

- Involved in CNS function as well

- Involved in the physiological changes present in IBS

- Gut effect: Mediates peristaltic effect of the smooth muscle --> Constricts behind bolus and relaxes in front via ACh --> 5-HT specifically detects bolus distension of the bowel

- History: Weight loss, onset in older patients, nocturnal awakening, FHx of CA/IBD

- Physical: Abnormal exam, fever, positive occult stool

- Initial labs: Decreased Hb, Increased WBCs or ESR and abnormal chemistries

- If any of these things arise look elsewhere from IBS!!

- Episodic changes in frequency or form of stool

- Usually no weight loss

- Mild abdominal pain may be present

- No blood in stools

- Can present with either diarrhea or constipation

- Usually gets worse in times of stress

- Usually eleviated by defecating

- Labs are necessary to rule out other causes --> CBC, CRP/ESR, TTG antibody, and stool O+P

- Diagnosis of exclusion!! 

- No imaging necessary

- Drugs are aimed at improving symptoms --> Pain, bloating, and altered bowel motility

- A good doctor-patient relationship is crucial for successful treatment of IBS --> These patients have been told it's all in their head and that it's all anxiety related... IT'S NOT!!

- Dietary modification: Lactose intolerance, syndromes resembling food allergies, and gluten-sensitivity may result --> Carbohydrate malabsorption may result too so specific diet may be very helpful

- Bulking agents prove not to be helpful for diarrhea IBS, very helpful for constipation IBS though

- Anticholinergics --> Dicyclomine and hyoscyamine

- Blocks ACh activity at smooth muscle

- Administration: Sublingual or long-acting oral

- Side effects: Drowsiness, dry mouth, and urinary retention

- Dicyclomine --> Once daily dosing orally

- Hyoscyamine --> Sublingual PRN or long-acting oral twice daily

1. Tricyclic antidepressants (amitriptyline and desipramine

- Low doses can be very effective for diarrheal IBS --> Changes the motility of the gut

2. SSRIs (citalopram and fluoxetine)

- Increase the available serotonin in the gut

- Good for the constipation type IBS

- Opioid receptor agonists: Loperamide (immodium) and diphenoxylate/atropine (Lomotil) --> Slow gut motility without the CNS effects

- Great for diarrheal type IBS

- Alosetron

- Slows colonic transit, decreases rectal urgency, and decreases abdominal pain

- Indication: Women with severe, diarrhea-prominent IBS who have failed other conventional therapies

- Back on the market with limited usage due to 3 deaths and 77 hospitalizations for constipation and ischemic colitis

- Tegaserod --> Partial agonists

- Stimulate peristaltic reflex in the gut

1. Increase the velocity of propulsion through the colon

2. Alters the chloride secretion in the intestine

3. Reduces visceral sensitivity

- Great for constipation type IBS!! 

- Disadvantages: Increased incidence of cardiovascular events --> AMI, stroke and angina

- Tegaserod was withdrawn from the market in 2007

- Lubiprostone (Amitiza)

- Activates colonic chloride channels and induces Cl secretion

- Effective in constipation-type IBS

- Side effects: Nausea and diarrhea

1. Linaclotide

- 14-amino acid peptide segment from heat-stable bacterial toxin of ETEC

- Peptide activates guanylate cyclase --> Increased cGMP

- Induces secretion and decreases absorption in the colon

- Effectively reduces pain and constipation

2. Rifaximin --> Decreases abdominal pain and bloating

3. Probiotics: Especially with Bifidobacterium and Lactobacillus cultures

1. Excretory function: Bile, drugs, and toxins

2. Metabolism: Carbohydrate, lipid, protein, and drugs

3. Storage: Glycogen and Vitamins D,K, and E

4. Immunological: Reticuloendothelial cell function of the Kupffer cells --> Removal of food antigens and infectious agents

- History: Weakness, anorexia, RUQ pain, jaundice, pruritis, bleeding, confusion, drowsiness, and dark urine

- Physical Exam: Palmar erythema, gynecomastia, muscle wasting, ascites, hepatosplenomegaly, and hepatic encephalopathy

- Hepatic encephalopathy findings: Memory loss, poor concentration, sleep disturbance, asterixis, and drowsiness/coma 

- Evaluate risk factors

- Viral liver disease

- Alcohol abuse/excess

- Drug induced liver disease

- Autoimmune disease

- Family history

- Gallstones

1. Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) --> Hepatocellular enzymes

- ALT is very specific to liver and is cytoplasmic

- AST is from liver, muscle, kidneys, and erythrocytes and is from both the cytoplasm and the mitochondria

- Alcohol toxicity --> Higher AST --> Alcohol is mitochondrial toxin

- Other hepatocyte damage --> Higher ALT

2. Alkaline phosphatase and GGT --> Bile cannaliculi damage

- GGT is most sensitive for the liver --> Used to determine liver from bone disease

- ALP is released from liver, bone, placenta, and intestine

- Blood types O and B release intestinal ALP after a fatty meal

- Viral hepatitis --> Hep A,B,C,D, or E, Epstein Barr virus (EBV), CMV, and Herpes virus

- Drug induced --> Acetominophen, isoniazid (TB), mushroom poisoning and cocaine

- Ischemic hepatitis

- Biliary obstruction

- Tumor masses

- Drug effect

- Infiltrative diseases --> Sarcoidosis or amyloidosis

- Granulomatous diseases --> TB

- Primary biliary cirrhosis

- Primary sclerosing cholangitis

- Autoimmune variants

1. Confirm liver origin with GGT

2. Imaging: Ultrasound or CT to rule out masses and dilated ductions

- Perform biopsy if a mass found

- Perform MRCP/ERCP if dilated ducts found

3. If neither are present, check AMA and then biopsy liver

1. Clinical features pointing towards severe disease

- Hepatic encephalopathy symptoms

- Edema

- Bruisin and bleeding

- Decreased nutritional status

2. Lab tests pointing towards severe disease

- INR

- Albumin levels

- Bilirubin levels

1. Serum albumin

- Lasts 14-21 days in the serum

- Best for evaluating chronic liver disease

- Other causes for reduced levels: Malnutrition and systemic illness

2. Coagulation Factors (INR)

- Lasts 6-12 hours in the serum

- Best for evaluating acute liver disease

- Other causes for increased levels: Vitamin K malabsorption and anticoagulant therapy --> Evaluate by giving parenteral vitamin K

1. Model of End-stage Liver Disease (MELD): Evaluates bilirubin, INR, and creatinine --> Helps rank patients on the liver transplant list

2. Child Pugh Turcotte Score: Evaluates albumin, bilirubin, INR, ascites, enecephalopathy and nutritional status --> Gives a better overall picture of disease state

- Hemoglobin from RBCs --> From spleen and reticuloendothelial cells

- Heme for hepatic enzymes (P450)

- Ineffective erythropoesis

- Myoglobin and other hemoproteins

- Heme --> Biliverdin --> Bilirubin

- Unconjugated bilirubin --> Circulates in blood to liver

- Liver conjugates bilirubin via UGT --> Bile cannaliculi

- Gut bacteria deconjugates bilirubin back to unconjugated bilirubin --> No longer water soluble

- Unconjugated bilirubin is reduced to urobilinogen

- 10% of urobilinogen is reabsorbed by small intestine and excreted by the kidneys

- Urobilinogen is oxidated to urobilin --> Excreted in the feces

- Serum bilirubin >2.5 mg/dL before jaundice is evident

- Fractioning of bilirubin --> Direct (conjugated) and indirect (unconjugated)

- Conjugated hyperbilirubinemia: Hepatocyte, small bile duct or large bile duct damage

- Unconjugated hyperbilirubinemia: Overproduction/degradation of RBCs and heme or inherited disorders

- Most common type in adults

- Presentation: Dark urine since kidney excretes conjugated bilirubin

- Hepatocyte or bile duct damage or obstruction leading to leakage of conjugated bilirubin into blood

- Most commonly caused by bile duct obstruction due to gallstones

- Other causes: Pancreatic carcinoma, hepatic metastases, and hepatic disease

- Hepatic diseases: Viral hepatitis, autoimmune liver disease, alcohol hepatitis, and metabolic liver disease

- Hemolysis: Autoimmune, drug-induced or sickle cell disease

- Ineffective erythropoeisis: Thalassemia and megaloblastic anemia

- Lasts 5-10 days --> Common condition

- Causes: Accelerated RBC destruction, immature conjugation enzymes, and enhanced enterohepatic circulation of bile

- Dangers in infants: Kernicterus --> Deposition of bilirubin in the CNS leading to neurological damage --> Immature BBB

- Therapy: Light exposure changes double bonds to single bonds (lumirubin) --> Makes unconjugated bilirubin water soluble and able to be excreted in urine

- Autosomal dominant condition

- Normal liver histology and cholangiography

- Normal ALT/AST, ALP and urine levels

- Many different mutations in the UGT gene

- Causes unconjugated hyperbilirubinemia during times of stress --> Shows signs of jaundice only during these times

- Autosomal recessive disorder --> Defect in canaliculus excretion

- Conjugated hyperbilirubinemia --> 2-5 mg/dL range

- Chronic and intermittent jaundice with a benign course

- Histology: Bilirubin granules/deposits in hepatocytes

- Type 1: Absent UGT, severe unconjugated hyperbilirubinemia, kernicterus and death within 18 months --> Requires liver transplant for survival (largest cause of liver transplant in infants)

- Type 2: Defective UGT, varying degrees of hyperbilirubinemia with no serious sequelae --> Treats with phenobarbital to induce UGT activity

- Aqueous mixture of inorganic and organic components

- Accounts for the ability to solubilize fat digestion products in chyme

- Organic components: Phospholipids (lecithins), cholesterol, bilirubin, and bile acids

- Bile acids: >50% of organic components, synthesized from cholesterol --> Cholic and chenodeoxycholic acid

- Secondary bile acids: Deoxycholic and lithocholic acid

- Bile salts: Conjugated with taurine or glycine --> Increase hydrophilicity, acidity, and resistance to hydrolysis

- Secreted continuously by the liver and bile ductules

- 250-1100 cc/day

1. Bile acid-dependent flow: Volume of bile produced by stimulation of bile acid return to the liver from the portal vein

- Recycled bile acids are taken up by hepatocytes and actively secreted by canalicula

- Water flows down osmotic gradient into bile

- Decreased bile acid synthesis with increased bile acid recirculation

- Bile salts are actively absorbed in the terminal ileum via ATP dependent Na/bile cotransporter --> 95% reabsorbed

- Bile cycles 2-3 times per meal 

2. Bile acid-independent flow: Controlled by secretin

- Fluid and electrolytes from the bile ductule cells

- Fluid has a high concentration of HCO3-

- Stores and concentrates bile during interdigestive state

- 20-60 mL storage capacity

- Actively reabsorbs Na, Cl, HCO3 and water --> Concentrates bile

- Secretion stimulated by CCK and ductule secretion stimulated by secretin

- >75% of cases in Western populations

- Complex interactions between genetic and environmental factors

- Problem: Failure of constituents of bile to maintain cholesterol in solution

1. Supersaturation of bile with cholesterol: Due to hypersecretion of cholesterol or hyposecretion of bile acids

2. Nucleation and precipitation of cholesterol monohydrate crystals

3. Gallbladder stasis and sludge formation --> Common during pregnancy: GB dysmotility due to inflammation and cholesterol accumulation

4. Crystal agglomeration and macroscopic stone formation

- Insoluble in aqueous environment

- Packaged in mixed micelles and vesicles

- Micelles: Bile salt micelles develop above a critical micellar concentration --> Cylindrical structure with hydrophilic regions oriented outward --> Solubilize lipids

- Vesicles: Phospholipid bilayer interdigitated with cholesterol --> Dynamic equilibrium between mixed micelles --> Thermodynamically unstable

- 4 F's: Fat, fertile, female of forty

- Increased age

- Female gender

- Multiparity/pregnancy

- Obesity

- Rapid weight loss

- Ileal disease --> Hyposecretion of BAs

- Family history of gallstones

- Meds: OCPs, clofibrate, estrogen, and octreotide

1. Black: Calcium bilirubinate polymer

- Risk factors: Chronic hemolysis, age, long-term TPN, cirrhosis, and cystic fibrosis

2. Brown: Unconjugated bilirubin, calcium soaps of fatty acids, cholesterol and mucin

- Risk factors: Biliary stasis and infection/inflammation/infestation, choledochal cysts, periampular diverticulum

1. Asymptomatic: Most common (>2/3) --> Benign course

2. Biliary colic: Most common symptomatic presentation

- Severe, steady pain of sudden onset, rises steadily to plateau --> Up to several hours

- RUQ/epigastric pain --> Radiating to upper back/scapula

- May be provoked by food intake

- Transient obstruction of cystic duct

3. Acute cholecystitis: Most common sever complication

- Persistent cystic duct obstruction --> GB inflammation

- Symptoms: Prolonged pain with fever, N/V and RUQ tenderness (Murphy's sign)

4. Choledocholithiasis and acute cholangitis

- Primary (brown stones) and secondary (cholesterol)

- Blockage of duct

- Presentation: Asymptomatic, obstructive jaundice, cholangitis, pancreatitis, and biliary cirrhosis

- Acute cholangitis: Bacterial infection of bile duct --> Charcot's triad (50-75%) --> Fever, jaundice and RUQ pain

5. Gallstone pancreatitis: Obstruction of pancreatic duct

6. Other complications: Mirizzi syndrome, GB carcinoma, fistulas, gallstone illeus, and Bouveret syndrome

- Diagnosis of gallstones/cholecystitis: Abd. US, cholescintigraphy, abd. CT scan, and oral cholecystography

- Cholesterol stones often not seen on CT scans!!

- Diagnosis of choledocholithiasis: ERCP, MRCP, endoscopic ultrasound

- Therapy: Cholecystectomy (surgery), oral dissolution, contact dissolution, extracorporeal shock wave lithotripsy, and ERCP intervention (sphincterectomy and stone extraction)

- Acute inflammatory process of the pancreas with variable involvement of other local tissues and remote organ systems

- Epidemiology: >200,000 annual US admissions and ~5% mortality

- Pathophysiology: Premature or inappropriate activation of digestive enzymes within pacreatic acinar cells --> Autodigestion of pancreas and surrounding tissues due to inappropriate combination of lysosomal enzymes and pancreatic enzymes

- Anatomy: Loops around duodenum and located right near SMV, aorta, and portal vein --> Lots of bleeding possible

- Complications: Necrotizing pancreatitis and splenic vein thrombosis

- Etiology: Obstructive, toxic, metabolic, infectious, vascular, traumatic, and medications

- Cationic trypsinogen activation peptide (PRSS1) mutation --> Chromosome 7q35

- Reduced ability for trypsin to cleave itself and turn itself off --> Prolonged activation and activity

- Autosomal dominant --> 80% penetrance

- Causes acute and chronic pancreatitis

- Calcification and cancer are common

- GB stone obstructs both the common bile duct and pancreatic duct at the ampulla

- Risk factors: Older age, female gender, absence of other risk factors (alcohol), stones or sludge on ultrasonography, high serum amylase, and increased ALT/AST, and ALP

1. Urgent: Biliary obstruction/cholangitis and severe pancreatitis without BD obstruction

2. Elective: Choledocholithiasis in imagin and biliary sphincterotomy for patients unfit for cholecystectomy

- Failure of embryonic dorsal and ventral ducts to fuse

- Major papilla drains into smaller/minor Santorini duct and minor papilla drains into larger Wirsung ducts

- Most common congenital variant of the pancreas --> 3-7% of the population

- 75% improve with endoscopic therapy --> Minor papillotomy and stenting

- Really doesn't cause acute pancreatitis

- Direct effects: Produces toxic metabolites, abnormal blood flow and secretion, hypersensitivity to CCK, and spasm of the Sphincter of Oddi

- Alcohol directly stimulates CCK and secretin release --> Hypersecretory state in the pancreas

- Hypercalcemia --> Enzyme activation

- Hypertriglyceridemia --> Lipase activation

- Renal failure

- Viruses: Mumps, CMV, Herpes, and hepatitis A,B, and C

- Bacteria: Mycobacteria and Leptospirosis

- Fungi: Cryptococcus, Candida, and Coccidiomycosis

- Parasites: Ascaris and Clonorchis

1. Vascular

- Atheroembolic

- Hypoperfusion

- Vasculitis

2. Traumatic

- Blunt trauma

- Penetrating trauma

- Postoperative

- ERCP

- SO manometry

1. Amylase levels rise and fall sooner

- Levels rise in many other conditions other than pancreatitis --> Cholecystitis, cholangitis, kidney stones, peptic ulcers, ectopic pregnancy

2. Lipase levels rise and fall slower

- More specific to the pancreas

- Only slightly elevated in biliary tract and renal disease

- Must have two of the three following characteristics:

1. Abdominal pain characteristic of AP

2. Serum amylase and/or lipase > 3 times the upper limit of normal

3. Characteristic findings of AP on CT scan

1. Pancreatic injury: Edema, hemorrhage, necrosis and atrophy

- Reduced exocrine and endocrine function

- Local spread via peripancreatic fat necrosis and fluid

- Retroperitoneal hemorrhage

- Erosion into adjacent structures

2. Systemic Effects: Cytokine release and hypocalemia

- Pulmonary --> ARDS, renal failure, CNS, DIC and acidemia, and multiorgan failure

- Supprotive care: Fluid and electrolyte replacement, vital sign monitoring, and analgesia and anti-emetics

- Urgent ERCP

- Antibiotics to prevent secondary bacterial infection

- Acid suppression

- NG tube

- Nutritional support

- Pharmacological reduction of chemokines, inflammation and pancreatic secretions

- Early (<one week): SIRS and multisystem organ dysfunction

- Late (> one week): Pancreatic infections and sepsis due to secondary bacterial infections

- On admission: >55 years, WBC > 16, Glucose >200, LDH >350, and AST >250

- Within 48 hours: Fall in HCT >10%, Ca <8, base deficit >4, increased BUN >5, fluid sequestration of >6 L, and PaO2 <60 mmHg

- Microcirculation of the pancreas still intact

- Uniform enhancement of the parenchyma on CT

- Microcirculation of pancreas absent in areas

- Systemic complications

- Local complications: Hemorrhage and infection

- Infection occurs in 30-50%

- Mortality: 10% in sterile and 30% in infected

- Infected necrosis: Non-specific, fever, increased WBCs, and unresolved organ failure

- Diagnosis: Necrosis on CT and infrequent gas seen

- Most commonly monomicrobial infection

- Mortality is 15-50% in infected necrotic pancreatitis

- Sterile Necrotizing Pancreatitis: Medical therapy and possible debridement in the future

- Infected Necrotizing Pancreatitis: Antibioitics and extensive debridement --> Now often performed via step up approach

- Cystic cavity with a fibrous capsule

- Lacks epithelial lining

- Filled with pancreatic fluid

- Present within or adjacent to the pancreas

- Occurs in 20-40% of acute pancreatitis

- Inflammatory process characterized by irreversible destruction of pancreatic parenchyma and ductal structures leading to permanent functional impairment

- Predominant symptom (80-85%) is abdominal pain

- 75% of CP patients are male

- Etiologies: Alcoholic, idiopathic, non-obstructive and obstructive causes

- Non-obstructive causes: Hyperparathyroidism, hyperlipidemia, hereditary, CF, tropical and autoimmune

- Obstructive causes: Pancreas divisum, SOD, and tumors

- Can lead to malabsorption due to decreased pancreatic enzyme secretion into the duodenum

- Pancreatic function needs to decrease to 10% for malabsorption to result

- Common bile duct stenosis

- Pleural effusion

- Pseudocyst

- Pancreatic ascites

- Splenic vein thrombosis

- Duodenal obstruction

- Pancreatic cancer

- CT, ERCP/MRCP, EUS, 72-hour stool fast, and tube tests are good for severe disease

- ERCP/MRCP, EUS, and tube tests are good for mild disease

- Calcifications can be seen on CT --> Classic sign of chronic pancreatitis

- Pain management with behavioral modification, dietary modification, and analgesics

- Surgery to relieve pancreatic duct obstruction --> Endoscopically or surgically

- Oxidative stress reduction

- Neural modification for pain signaling

- Initial symptoms: General malaise, low-grade fever, N/V, muscle and joint pain, headache, dark urine, and clay-colored stools

- Late symptoms: Jaundice, hepatomegaly, elevated LFTs

- Causes: Multiple agents, most commonly due to viruses and viruses are very diverse

- Heparnavirus: Fecal-oral transmission

- Non-enveloped, icosahedral capsid with + sense ssRNA

- Single viral polypeptide --> Cleaved by viral proteases

- Released via exocytosis

- ~40% of acute hepatitis cases --> From common source

- Found worldwide and all year-long

- Pathogenesis: Intestinal mucosa --> Blood --> Liver --> Gallbladder --> Bile

- Incubation: 2-7 weeks

- Causes milder disease in children than in adults

- Initial symptoms appear 15-50 days post exposure and intensify for 4-6 days --> Fever, fatigue, nausea, loss of appetite, and abdominal pain

- Icteric phase: Daruk urine, pale feces, and elevated liver enzymes

- Jaundice occurs in 2/3 of adults but only 1/5 of children

- Virus is shed up to 2 weeks before symptoms appear

- 99% recovery in cases --> 1-3/1,000 cases develop fulminant hepatitis

- Diagnosis: Clinical symptoms, identification of common source, and anti-HAV IgM vs. IgG --> Current vs. past infection

- Treatment: Prophylaxis with serum Ig (passive) and inactivate vaccine (active) in 2 doses within 6 months

- Prevention: Good hygiene and avoid comtaminated water/food

1. Choestatic hepatitis: Prolonged cholestatic phase --> Persistent itch and jaundice

- Treat with short course of steroids

2. Relapsing hepatitis: 2nd episode of acute hepatitis usually 30-90 days after the first episode

- Patient with being re-excreting virus

- Always resolves

- Flaviviridae family: Enveloped, icosahedral capsid, + sense ssRNA genome

- Replication: In cytoplasm, translated into a large polyprotein cleaved by viral proteases, and virions bud from ER but release mechanism unkonw

- Transmission: Primarily via blood, IVDU, mother to infant, healthcare workers, and blood transfusions

- Replicates within hepatocytes but not cytopathic

- Disease due to immune response to infected hepatocytes --> Cytotoxic (CD8) T-cells

- Associated with high incidence of hepatocellular carcinoma (HCC) due to high hepatocyte turn over

- Antibodies to HCV are made but are not protective

1. 70% develop chronic infection --> Most are asymptomatic

- Chronic hepatitis --> Liver failure (6%), cirrhosis (20%), and HCC (4%)

2. Rapid onset cirrhosis (15%)

3. Recovery and clearance of virus (15%)

- Virus does not really cause acute hepatitis

1. Diagnosis: ELISA detection of anti-HCV, RT-PCR, and elevated liver enzymes

- Seroconversion for antibodies takes 7-31 weeks

- Chronic infection must have elevated LFTs, anti-HCV-Ab and HCV RNA for at least 6 months

2. Treatment: Alpha-IFN, pegylated IFN (increased t1/2), and ribavirin

- New FDA drugs: Telaprevir and boceprevir --> Lots of strides in these!!

3. Prevention: Screening of blood supply, eliminate risky behavior, no vaccine, passive Ig injection ineffective and must treat HIV-infected patients

- IV drug use

- Receipt of clotting factor before 1987

- Immigration from areas without universal precautions

- Occupational exposure (healthcare)

- Transfusion after 1992

- Intranasal cocaine use

- Sex with multiple partners

- Body piercing/scarification

1. Hematologic: Cryoglobulinemia and B-cell lymphoma

2. Renal: Glomerulonephritis and nephrotic syndrome

3. Dermatologic: Lichen planus and cutaneous necrotizing vasculitis

4. Endocrine: Diabetes mellitus and anti-thryoid antibodies

5. Salivary: Sialadenitis

6. Ocular: Uveitis and corneal ulcer

- Secondary generation protease inhibitors

- HCV RNA polymerase inhibitors: Nucleotide and non-nucleotide

- NS5a Replication Complex Inhibitors

- Cyclophylin inhibitors

- Hepevirus: Non-enveloped with + sense ssRNA genome

- Major cause of enterically transmitted hepatitis in Asia, Africa, India, and Mexico

- Many of the same symptoms as HAV

- No standard lab tests, treatments or vaccines

- Prevention: Avoid drinking water, uncooked shellfish and uncooked fruit/vegetables

- Flavivirus: Enveloped + sense ssRNA genome

- Isolated from a patient with post-transfusion hepatitis

- Not shown to cause hepatitis

- Chronic infection lasting decades --> 60-70% clear virus and develop antibodies

- Transmission: Sexual contact and blood

- Patients also infected with HIV seem to have a better prognosis --> Interferes with HIV replication??

- Hepadnavirus: Enveloped, partially segmented dsDNA genome, with core protein

- Dane particle: Surface protein, core protein, e antigen, DNA genome, and reverse transcriptase

- Decoy particles: Spherical and tubular --> HBeAg are secreted

- Genome: 4 genes but produces many different mRNAs due to multiple reading frames

- Reverse transcriptase activities: RNA-dependent DNA polymerase, RNAase H, and DNA-dependent DNA polymerase

- Transmission: Blood, sexual contact, and neonatal infections during birth

- Receptor mediated entry

- Uncoating in cytoplasm

- DNA enters nucleus --> DNA gap filled

- Host polymerase forms CCC DNA

- Transcription of viral mRNAs via various reading frames

- Translation of viral mRNAs in cytoplasm

- Viral proteins and genomes packaged into core particles

- pgRNA-Pol packaged into core particles

- 1st-strand of DNA synthesis via RT

- DNAase H activity of RT digests RNA portion of genome

- 2nd strand of DNA synthesis via DNA-polymerase function of RT

- Envelope added at the ER

- Released by exocytosis

- Infection during infancy has a higher likelihood of becoming chronic

- Adult infection has a lower likelihood of becoming chronic

- Blood --> Liver --> Viremia --> Saliva, semen, blood, vaginal secretions, and mother's milk --> Transmission

- HBV is not directly cytopathic to hepatocytes

- Most acute infections are cleared resulting in protective immunity

- Antibodies may be diluted/soaked up by the decoy particles that contain HBsAg on the surface

- Chronic infections are associated with cirrhosis and HCC

- Incubation: 45-120 days

- Many are asympatomatic

- Prodromal phase: Malaise, anorexia, and RUQ pain

- Icteric phase may follow

- Convalescent period

- Chronic infection occurs in 5-10% of infected adults and 80-90% of neonatal exposures

1. Diagnosis: HBsAg, HBeAg, elevated ALT/AST

- HBcAg-Ab are first to appear

- HBsAg-Ab are neutralizing and protective --> Indicates clearance of virus

- "Window phase": HBsAg - and HBsAg-Ab - but HBcAg-Ab +

- HBcAg-Ab do NOT form after vaccination, only HBsAg-Ab form

2. Treatment: None 100% effective, only entecavir and tenofovir currently in use

- Goals: Mimic carrier state by reducing viral load --> Improves histology, prevents progression, and prevents HCC incidence

- Treat those with high viral count, low viral count with elevated ALT or decompensated disease

3. Prevention: HBsAg purified vaccines --> 3 vaccines in 6 month period for children and HBIG after exposure (passive)

- Not an infective virus on it's own

- Requires HBsAg antigen for envelope --> Requires HBV

- Delta antigen --> Capsid protein

- - sense ssRNA genome --> circular/rod-shaped genome

- Only infectious in cells infected with HBV --> Replication not well understood

- Co-infection: HBV and HDV acquired at the same time

- Superinfection: HDV infection on top of already HBV infected individuals --> Much more serious disease course

1. Diagnosis: HDAg-Ab, HDV RNA, and HDAg detection in serum

2. Treatment: None are 100% effective

3. Prevention: HBV vaccination --> Cannot infect without HBV so protecting against HBV protects against HDV

- Patients develop antibodies to surface, core, and e antigens

- Core antigen never leaves the cell though

- E antigen is crucial for developing chronic disease in HBV patients

- Acute infection: HBsAg +, HBcAg-Ab +, HBeAg-Ab +, and HBsAg-Ab -

- HBsAg-Ab only becomes present once virus is cleared

- HBV early antigen/Pre-core (HBeAg): Correlates with positive viral load and infectivity --> + usually has a high DNA viral load along with it

- Seroconversion from HBeAg + to HBeAg- --> Loss of infectivity --> Carrier state

- Mutation in early/pre-core antigen not detected by the conventional HBeAg serology

- Usually results after patients have become carriers (HBeAg - from +)

- Occurs when DNA viral load increases but patient stays HBeAg - --> Indicates reactivation but as a pre-core mutant

- These patients need treatment that will likely be life long because there is no marker to determine carrier state anymore

- HBeAg - and HBeAg-Ab + --> 8-12% per year

- HBV DNA <2,000 IU/mL

- ALT normal or low --> No liver disease

- Minimal histological activity and fibrosis may actually regress a little

- HBsAg + --> Has not cleared virus!!

- May last a lifetime, patient may clear virus, or reactivation may occur

- Reactivation usually occurs in a time of immunosuppression

- No need for treatment! 

- Usually only occurs in infected neonates/infants

- HBeAg+ and HBeAg-Ab - 

- HBV DNA >20,000 IU/mL --> High viral count but no real disease activity

- ALT/AST normal or low

- Minimal histologic activity

- Lasts until adolescence of young adulthood in these patients

- HBV DNA positive and fluctuating

- ALT elevated --> Active liver disease and immune response

- Moderate to severe histological activity

- Lasts months to many years

- Usually skips to this phase in adult infections

- HBsAg - and HBsAg-Ab+ --> Indicates complete clearance of virus

- HBV DNA negative

- ALT normal

- Minimal histologic activity --> CCC DNA still present in the nuclei of hepatocytes

- Even so CCC DNA really doesn't facilitate any kind of reactivation unless severe immunocompromised

- Cirrhosis: 2-6% per year --> Carriers with normal ALT are about 0.7%

- Decompensated: 3% per year --> 15-30% 5-year survival

- Compensated: 85% 5-year survival

- Likelihood of developing cirrhosis correlates directly with HBV DNA viral load

- Likelihood of developing HCC also correlates directly with viral load

- Occurs when patient is immunocompromised

- Most patients will develop HBeAg+ but some may stay HBeAg- --> Pre-core mutant

- Can't go just by HBeAg status for reactivation

- Treat anyone with an elevated viral load --> Unless a child and potentially in the immune tolerant phase

- Can tell if in immune tolerant phase because HBeAg-Ab -

- Definitive: Species in which the parasite reaches sexual maturity and produces progeny

- Intermediate: Required by the parasite for complete its life cycle

- Paratenic/transport: Parasite infects but doesn't develop

- Pinworm --> Eggs don't need to develop in soil before infecting host

- Transmission: Direct fecal-oral and airborne

- Infective form: Ova/eggs

- Most prevalent intestinal nematode in the US --> Most prevalent in kids and crowded conditions

- Perianal nocturnal pruritis --> Worm climbs out of the anus at night to lay eggs on the perianal skin

- Excoriations and secondary infection due to scratching

- Many asymptomatic cases

- Eosinophilic enterocolitis and appendicitis

- Vulvovaginitis

- Diagnosis: Scotch tape test

- Eggs ingested by human

- Eggs become infective in a few hours

- Larvae hatch and mature in the large intestine

- Adult worms grow to be ~ 1 cm long and live in the ileum, cecum, and colon --> Live about a month

- Life cycle takes ~ 1 month

- Transmission: Modified direct --> Eggs develop in soil before they are ingested --> Fecal-oral

- Larvae migrate throughout the body

- Common in warm and wet tropical countries

- More prevalent in kids

- Infective form: Ova/eggs

- Most are asymptomatic

- Abdominal pain or discomfort

- Pulmonary: Loeffler's syndrome: Cough, dyspnea and wheezing --> Hypersensitivity reaction in lungs

- Nutritional: Malabsorption, malnutrition, vitamin deficiencies, and stunting of growth in children

- Obstruction of the intestine, biliary duct and pancreatic duct

- Eosinophilic response and granuloma formation in response to worms

- Diagnosis: Ova in stool, none will be present if only infected by the male, and larvae/adult worms in stool

- Presence of eosinophilia is also a sign of a parasitic infection

- Treatment: Albendazole

- Ingestion of eggs in food, water or soil

- Eggs become infective after 2-3 weeks of incubation in the soil --> Can survive for months

- Adult worms grow in the lumen of the small bowel and grow to be 20-30 cm long --> Produce 200,000 eggs/day

- Larvae penetrate duodenum --> Bloodstream --> liver,heart --> Lungs --> Cough up --> Swallow --> Small intestine --> Male fertilizes female --> Eggs

- Full cycle takes 2 months and adults can live for 1-2 years

- Ancylostoma duoadenale and Necator americanus

- Eggs hatch into larvae in soil --> Larvae penetrate skin

- Rhabditiform larvae (non-infective) develop into filariform larvae within 2 weeks

- Transmission: Percutaneous (N.a.) and percutaneous and oral (A.d)

- Infective form: Filariform larvae

- Persistent in warm, moist rural areas with poor sanitation

- Persistent foci in the southeastern US

- Major symptoms due to chronic blood loss --> Iron-deficiency anemia

- Ground itch: Papulovesicular rash due to hypersensitivity towards larval antigens

- Loeffler's pneumonia: When larvae migrate to the lungs

- Acute intestinal phase: Colicky epigastric pain, anorexia, diarrhea, weight loss, and eosinophilia that may persist for months

- Filariform larvae penetrate skin of host usually through hair follicle

- Larvae enter blood stream --> lung capillaries --> trachea --> Esophagus --> mature in small intestine

- Adult worms have sharp mouth parts to help them attach to the small intestine

- Produces proteinase inhibitor to prolonge blood flow and blood meal

- Worms lay eggs --> Out in feces

- Very similar life cycle to hookworms

- Rhabditiform larvae can become filariform larvae within the intestine or on the parianal skin within 48 hours --> Autoinfection possible!!

- Free-living cycle --> Outside of human host where they produce eggs and larvae

- Infective form: Filariform larvae

- Endemic throughout the tropics and subtropics

- Transmission: Fecal-oral and exposure of bare skin to contaminated soil

- Infections may persist for longer than 50 years

1. Uncomplicated

- Many are asymptomatic

- Gastrointestinal: Abdominal pain, cramping, diarrhea, and weight loss

- Skin: Larva currens around butt and back and urticaria

- Pulmonary: Loeffler's syndrome

- Young children: Malabsorption, malnutrition, and protein-losing enteropathy

2. Complicated

- Hyperinfection/Disseminated disease in immunocompromised patients

- GI: N/V, diarrhea, abdominal pain, massive GI bleeding, severe malabsorption and peritonitis

- Lungs: Cough, bloddy sputum, and respiratory failure

- Others: Meningitis, brain abcess, diffuse invasion of the brain, hepatitis, invasion of the heart, kidneys, lymph nodes, etc

- Mortality if left untreated is 100% and 50-80% with treatment

- Mucosal damage and chronic inflammation due to adult worms in tissues

- Involved tissues: Skin, lung, and intestine

- Rhabditiform larvae in stool or duodenal fluid

- Agar plate testing --> Shows path of larvae

- Serology --> High sensitivity and specificity

- Prevention: Screen patients for strongyloidiasis before immunosuppressing patients

1. Cutaneous Larva Migrans: "Creeping eruption"

- Migration of larvae of the dog or cat hookworm (Ancylostoma) 

- Diagnosis: Clinical presentation or biopsy

2. Visceral Larva Migrans: Toxocara canis

- Cycle resembles Ascaris in humans

- Commonly present in puppies because of transplacental infection

- Transmission to humans: Accidental ingestion of eggs --> Hatch in intestine --> Liver, lungs, CNS --> Does NOT return to intestine

- Extremely common in dogs in the US

- Important cause of asymptomatic eosinophilia

- Pathogenesis: Eosinophilic granulomatous reaction, visceral larva migrans syndrome, and ocular toxocariasis

- Diagnosis: Clinical, epidemiological, and serological findings --> ELISA test

- Prevention: Deworming dogs, destruction of stray dogs, and keep children away from contaminated feces

- Due to Wuchereria bancrofti and other species

- Infection acquired early in life --> Delayed 10-20 years

- Geographic distribution: Asia, Africa, Mediterranean, Brazil, Costa Rica, Haiti, and Trinidad

- Transmission: Mosquito vectors injecting L3 larvae

- Mosquitos inject L3 larvae into humans

- L3 larvae mature into adult worms (male/female)

- Adults migrate to the lymph nodes of groin, axillae and breasts --> Grow to 10 cm in length

- Adults can survive 10-15 years

- Mating worms release millions of L1 microfilariae into the blood stream --> Released on circadian rhythms --> Peaks at 1-2 am

- Mosquito: L1 larvae mature into L2 then L3 --> Migrate to the mosquito's salivary glands

1. Acute infection --> Non-specific, flu-like symptoms

2. Recurrent lymphadenitis --> Intermittent fever, chills, lymph node tenderness coinciding with the death of the adult worms

3. Chronic lymphedema --> Immune response leads to lymphatic channel dilation and dysfunction followed by lymphatic fibrosis and massive lymphedema (elephantiasis)

4. Secondary bacterial infections

5. Chornic debiliating and highly disfiguring anatomic distortions

6. Early lymphatic dysfunction

7. Chornic lymphatic sclerosis and elephantiasis --> Irreversible

8. Other symptoms: Acute adenolymphangitis, chyluria, and tropical pulmonary eosinophilia