Oral Hairy Leukoplakia

• white patch, cannot be scraped off
• EBV induced squamous hyperplasia in HIV pts
• hyperplasia, dysplasia or squamous carcinoma
• rarely becomes malignant
• Erytrhoplakia (redpatch): dysplasia and often turns malignant (better chacne than leukoplakia)

Candida

• curdy white plaques (exudate), can be scrapped off 
• yeast, pseudohyphae
• immunocompromised, diabetics
• normal flora, can attack esophagus
• candida sepsis is a bad complication

Verrucous Carcinoma

• mouth/tongue cancer
• invasive, well differentiated from squamous carcionoma
• must excise with clear margins
• broad, pushing invasive front, not the usual ragged infiltrative pattern

Sialadenitis

• chronic inflammation of salivary glands
• possible sarcoidosis of salivary gland (chronic granulomatous infalmm
• lymphoid infiltrate, germinal center formation
• Viral causes: mumps-parotitis, benign in kids; orchitis
• Bacterial: sialoithiasis: stones obstruct duct, lead to infection and atrophy (staph, strep viridans)
• autoimmune: Sjrogens - dry mouth/eyes; involves CT dzs (RA, SLE) and may lead to MALT lymphoma

Mucocele

• most common inflammatory lesion of salivary glands
• obstructed/inflammed minor gland: mucus builds up, leads to dilated duct (like balloon)
• duct blockage or rupture
• no lining, filled with mucus, macrophages and granulation tissue

Pleomorphic Adenoma

• most common benign salivary tumor
• mixed epithelial/mesenchymal elements
• cartilage present (bluish gray areas)
• recur if incompletely excised: well circumscribed grossly but micro may have tiny tendrils of tumor extending beyond apparant borders
• rare malignancy (10% if tumor present > 15yrs)

Warthin's Tumor

• benign tumor of salivary gland
• papillary cystadenoma lymphomatosum
• papillary structures with lymphoid cores, germinal centers
• bilateral
• papillae with lymphoid core covered in double epithelium

Malignant tumors of Salivary Gland

• mixed malignant tumor: worst prognosis
• Mucoepidermoid carcinoma: most common, low grade (squamous and glandular) and high grade (aggressive squamous cell) and mucus stains pink
• Adenoid cystic carcinoma: cribriform pattern, perinerual invasion, stubborn recurrence
• Acinic cell carcinoma: best prognosis and male predominence

Reflux Esophagitis

Eosinophilic Esophagitis (Allergy)

• shows concentric rings on endoscopy
• many more eosinophils than reflux esophagitis
• allergic condition and mays how linear furrows or a peculiar concentric ring pattern, steroids may help

Acute Erosive Gastritis

• acute inflammation, superficial mucosal edema, neutrophils
• coffee ground hematemesis (alcoholics)
• mucosal erosion -> necrosis/hemorrhage -> ulcers
• Erosion = above muscularis mucosa
• Causes - NSAIDs, alcohol, smoking, drugs, uremia, infectinos, stress, chemo, shock
• may heal completely in days if underlying cause corrected

Acute Stress/Peptic Ulcers

• severe form of acute erosive gastritis producing ulcers
• Ulcer = through muscularis mucosa
• causes - NSAIDs, steroids, trauma, surgery, sepsis
• Curling's Ulcers- Burns
• Cushing's Ulcers - CNS

Stomach Polyps

• Hyperplastic (75%) - most common, mucus glands, benign
• Fundic Gland - inc due to PPIs, benign, composed of specialized glands (chielf/blue and parietal/pink) cells
• Adenomatos - least common, discrete glands, premalignant, nuclei are piled up in the glandular epithelium

Stomach Carcinoid

• hypochlorhydria
• form a submucosal nodule composed of tumor cells embedded in dense fibrous tissue 
• chromatin texture with fine and course clumps (salt and pepper pattern) 
• Gastrin secreting tumor from hyperplastic g cells
• In zollinger-ellison syndrome: a pancreatic, duodenal or other gastrin producing carcinoid gastrinoma causes hypergastrinemia; peptic ulcers result

GI Stromal Tumor

both upper and lower GI

• Size/mmitosis correlate w/ prognosis; mass protruding into gastric lumen
• umbilication ulcer often on tumor surface
• spindle cells with cigar shaped nuclei
• High mitotic activity
• CKIT (+) - CD117
• treatment - Gleevec

Drugs that modulate gastric Acidity

• Antacids: calcium carbonate, aluminum hydroxide, magnesium hydroxide
• Histamine H2 receptor Antagonists: cimetidine, ranitidine, famotidine, nizatidine
• Proton Pump inhibitors: omeprazole, iansoprazole, esomeprazole, rabeprazole
• Mucosal protective agents: sucralfate, misoprostol, bismuth

Regulation of Gastric Acid Secretion

• Stimulation: Ach, histamine, gastrin
• Inhibition: somatostatin, prostaglandins
• Ach binds to rec on ECL cells and parietl cells
• ECL cells release histamine that binds to H2 rec on parietal cells
• gastrin binds ECL cells and parietal cells
• G cells stimulated by GRP from vagus nerve (not affected by atropine) to release gastrin 

Antacids

• sodium bicarb, calcium carbonae, aluminum hydroxide, and magnesium hydroxide
• MOA: neutralize gatric acid 
• Systemic (NaHCO3): soluble and absorbed
• rest are nonsystemic and nonsoluble, not absorbed
• adverse effects: hypercalcemia, metabolic alkalosis, AlOH (constipation, osteoporosis, hypokalemia), MgOH(diarrhea and vomiting)
• Cautions: inc absorption of other drugs, avoid in renal dz, avoid Ca and Al in constipation, and avoid Na in heart/renal failure or HTN

Histamine H2 Receptor Antagonist

• Cimetidine, rantidine, famotidine, nizatidine
• MOA: competitive inh of H2 rec on parietal cells
• Adv effects: tolerance, rebound acid secretion (hypergastrinemia), IV (mental status changes)
• Cimetidine can cause gynecomastia, impotence, galactorrhea
• can cross placenta, secreted into breast milk
• cimetidine is a CYP inh (warfarin, quinidine CL reduced)

Proton Pump Inhibitors

• omeprazole, lansoprazole, esomeprazole, rabeprazole
• MOA: irreversible inh of active proton pump 
• requires acid for drug activation
• can cause, diarrhea, constipation, nausea, reduced B12 absorption, rebound acid seretion, risk of hip fracture and inc resp/enteric infection
• inhibits metabolism of warfarin and activation of clopidogrel (CYP2C19)

Mucosal Protective Ages

• Sucralfate: cross links and binds uclers; can cause consipation and caution in renal insufficiency
• Misoprostol: PGE1 analog; stimulates mucous and HCO3 secretion and inhibits acid secretion; avoid in IBD, pregnancy; can cause diarrhea and cramping
• Bismuth: coats ulcers and erosions, direct antimicrobial effects; indicated for dyspepsia, diarrhea and quadruple Hpylori therapy; can cause black stool and black tongue and avoid in aspirn allergy

GI Motility

• Enhancers: gastrin, CCK, serotonin (5HT3 and 4) and insulin
• Inhibitors: secretin, glucagon

Prokinetic Drugs

• Metoclopramide, domperidone: D2 receptor antagonists
• Macrolides - erytrhomycin: motilin agonist
• Cisapride: 5-HT4 rec agonist

Adhesions

• Trap bowel: intussesception and volvulus
• adhesions btw loops of small intestin typically follow abdominal surgery
• diffuse adhesions may also form following peritonitis; may trap loop of bowel and acuse obstruction
• volvolus most common in elderly and sigmoid/cecum
• intussesception assoc with polyps in adults

Melanosis Coli

• chronic laxative use
• antraquinone type cathartics
• lipofuscin accumulation in macrophages in lamina propria
• brownish black discoloration of colonic mucosa (dont confuse with acute ischemia)
• no symptoms; reversible-stop laxatives

Angiodysplasia

• dilated submucosal blood vessels: also htin walled
• causes 20% of significant GI bleeds
• presents in 1% of population: ectatic submucosal vessels in elderly
• assoc with CREST syndrome, HHT, osler-rendu-weber syndrome
• vascular spaces collapse and drain after tissue is removed

Causes of Malabsorption

• pancreatic insufficiency
• Celiac sprue: worse proximaly, anti-gluten Ab, flat villi, crypt hyperplasia, intraepithelial lymphocytes and large inc risk for esoph scquamous ca and assoc with dermatitis hepertiformis and T cell lymphoma
• Tropical sprue: looks like celiac but tetracycline, B12/folate can treat and involves distal small bowel
• Crhons disease
• lactose intolerance
• abetalipoproteinemia: cannot make chylomicrons (triglyceride tx protein) and acanthocytes (spiky RBCs)
• lymphocytic colitis: inc lymphs in glandular epi and lamina propria
• collagenous colitis: same but inc subepi collagin (thick band on histo) and more in females
• infections

Amoebiasis

• ingestion of entamoeba histolytica cysts, colonize colon
• flask shaped ulcers
• spread to liver - anchovy paste abscesses
• erythrophagocytosis
• entamoeba histolytica: dysentery; flask shaped ulcers in colon, etc

Neonatal necrotizing Enterocolitis

• premature infants; immature gut invaded by bacteria
• secondary intestinal ischemia damages bowel wall; may become gangrene
• allows entry of bacteria -> ulceration, necrosis, submucosal gas bubble

Non-neoplastic Polyps of Lower GI

• hyperplastic: benign, irregular tufting of epithelial cells results from epithelial overcrowding, produces serrated architecture and glands look like roadkill starfish; starfish lumen
• Hamartomatous: benign, dilated cystic glands, maybe ulcerated, torsioned, or autoamputated, kids are larger called juvenile adn adults smaller called retention
• peutz-jegher syndrome 
• Cowden syndrome: like first one, mutation in tumore suppressor gene

Peutz-Jegher Syndrome

• hamartomatous polyps of entire GI tract
• bundles (arborizing bands) of smooth muscle in lamina propria and complex glandular architecture help distinguish PJ from juvenile polyps
• mucocutaneous pigmentation
• high risk of cancer elsewhere (not in polyps)

Sessile Serrated Polyp/serrated adenoma

• peremalignant potential, looks like hyperplastic polyp
• hyperplastic changes extend to base of crypts
• more common in right colon (cecum, ascending)
• mismatch repair pathway (Like HNPCC/lynch)

Carcinoid Tumor 

Lower GI

• Indolent tumros
• produce hormones - serotonin, gastrin, somatostatin, insulin
• 5-HT in blood, urine
• organoid monotonous uniform nuclei
• salt and pepper chromatin
• carcinoid syndrome - flushing, cyanosis, wheezing, diarrhea, after metastisis
• liver metastasis - first pass metabolism no longer detoxifies 5-HT
• Mark with immunostains for synaptophysin, chromogranin, NSE

Appendiceal Tumors

• carcinoid
• Mucinous tumors: mucocele - B9, non neoplastic, due to obstruction with mucus buildup
• mucinous cystadenoma - B9 neoplasm
• mucinous cystadenocarcinoma malignant, with invasion, may fill abdomen with mucinous tumor "pseudomyxoma peritonei"

Metoclopramide, domperidone

• D2 receptor antagonists; inhibit smooth muscle relaxation
• inc ACh release, LES pressure acts primarily in upper GI
• indicated in gastroparesis, GERD, nausea, vomiting
• adverse: parkinsonism, tardive dyskenisia, CNS problems, seizures, hyperprolactinemia
• CI: seizure disorders, GI obstruction

Erythromycin

• prokinetic drug
• motilin agonist: inc GI motility, LES pressure
• indicated in gastroparesis (delayed gastric emptying)
• risk of dumping, tolerance, antibiotic effect

Cisapride

• prokinetic drug
• 5-HT4 rec agonist: ACh release, direct effect
• indicated in GERD, gastroparesis
• last line therapy only with ECG monitering
• risk of torsades de pointes (polymorphic vent tachycardia)
• CI: macrolides, antiarrythmics, antidepressants

Laxatives, Cathartics

• Bulking Agents: psyllium, methylcellulose, calcium plycarbophil; fiber; induces peristalsis
• Osmotic agents: draws water into lumen, MgOH, sorbitol, lactulose, polyethylene glycol
• Stimulants: aloe, senna, biscodyl, caster oil
• Choride channel activators: lubiprostone (PGE1 analog)
• Opioid rec antagonists: methylnaltrexone, alvimopan
• Stool softeners: docusate sodium, glycerin, mineral oil

Antidiarrheals

• opioids: diphenoxylate, loperamide
• Absorbents: bismuth, kaolin/pectin (absorbs bacterial toxins and fluids)
• somatostatin analogs: octreotide; antisecretory - reduces intestinal fulid secretion, slows motility
• octreotide helps in dec splanchnic pressures in pts with portal HTN assoc with variceal bleeding

IBS Treatment

• Alosetron - 5HT3 rec antagonist
• Antispasmodics (anticholinergics - dicyclomine, hyoscyamine): inhibits muscarinic rec on smooth muscle and enteric neurons -> rarely used due to side effects
• Tegaserod: 5-HT4 rec agonist - Pokinetic - treats constipation predominant IBS
• Lubiprostone - only FDA approved drug for constipation - predominant IBS

Alosetron

• IBS treatment
• 5-HT3 Rec antagonist
• inhibits 5-HT3 rec on enteric neurons
• reduces GI contractility, motility
• inc fluid absorption
• only approved for women with severe diarrhea-predominant to IBS
• risks: severe constipation, ischemic colitis; GSK requires phsyician certification to prescribe

IBD Treatment

• Aminoglycosides: 5-ASA, mesalamine; induces remission/maintenance of UC
• Glucoccorticoids: induces remission of active IBD, but not effective for maintenence
• Immunosuppresors: azathioprine, mercaptopurine, methotrexate; treatment and maintenance of remission
• Anti TNF: infliximab, abalimumab, certolizumab; used in active IBD
• Anti-integrin: natalizumab; morderate to severe crohns
• Antibiotics: metronidazole, clarithromycin; control proinflamatory gut bacteria

Anti-Integrin

• IBD drug
• natalizumab
• mAb against a4-integrin
• prevens bidning of inflammatory cells to endothelium
• used in moderate to severe Crohns
• restricted - potential for progressive multifocal leukoencephalopathy (PML) when adm with other immune modulators

Nausea/Vomiting Drugs

Anti-Emetics

• ondansetron, granisetron, dolasetron, palonosetron: 5-HT3 rec antagonist; chemo induced nausea; causes prolonged QT
• Metoclopramide, prochlorperazine: D2 rec antagonist: M-chemo; P motion sickness
• Diphenhydramine, dimenhydrinate, promethazine, cyclizine: H1-rec antagonist- motion sickness
• Scopalamine: m rec antgonist - motion sickness
• Dronabinol, nabilone: THC analogs: chemo
• Aprepitant: NK1 rec antagonist (CTZ): chemo; delayed nausa; use w/ 5HT3 antagonists; dexmeth
• glucocorticoids: dexmethasone: adjunctive for nasue in cancer pts 
• Benzodiazepines: sedative, anti anxiety, reduce anticipatory nausea

Acute Cholangitis

• inflammation of common bile duct
• Charcots triad: fever, RUQ pain, jaundice (total bilirubin)
• Reynolds pentad: same as charcots plus Mental status changes and hypotension: for obstructive ascending cholangitis
• Medical emergency: can lead to biliary sepsis, setpic shock with high mortality
• Rx: bilary decompresion - ERCP - wli 12 hrs if stable; emergent if not

Melana

• passage of black, tarry, foul smelling stools
• due to degradation of blood to hematin by bacteria
• DDx: bismuth (pepto-bismol), iron

Acute Lower GI bleeding

• definite dx - endoscopic or angiographic evidence 
• bleeding usually sops spontaneously in 80%
• diverticulosis, angidyplasia, ichemic colitis, UC, crohms, neoplasia
• Elderly - diverticulae, angiodysplasia (painless)
• Young - infections, inflammatory (painful)
• HIV: CMV most common cause
• Painsless: diverticula or agniodysplasia, painful: inflammatory or ischemic
• hard stools or constipation: stercoral uclers
• Bleeding scan done if bleed rate > 0.1-0.5ml/min; active bleeding stable pt
• mesenteric angiogram done if >.5-1 ml/min or unstable bleeding pt

Peptic Ulcer

• Mucosal defect of > 0.5cm that penetrates muscularis mucosa: 2/3 of pts with PUD are male and common in smokers
• Gastric ulcers: lesser curve, ages > 40
• duodenal uclers: in bulb (more common than gastric): ages 20-50
• Cameron's ulcers: gastric ulcers within a hiatal hernia; low iron anemia
• dieulafoy's ulcers - small mucosal defects over intramural arteriole; can cause massive bleeding
• treat with PPIs (standard) H2 antag, and cytoprotective agent sucralfate that binds to and coats sites of active ulceration

Zollinger-Ellison

• hypergastrinemic syndromes
• gastrin producing endocrine tumor
• located in small intestine or pancreas
• multiple hterapy resistant bulbar and postbulber duodenal ulcers
• may occur as part of multiple endocrine neoplasia syndrome and be assoc w/ hyperparathyroidism

Dyspepsia

• pain or discomfort in upper abdomen
• 4 specific syptoms: postprandial fullness -  feels like food still in stomach' early satiation; epigastric abdominal pain and epigastric burning
• affects 5-45% of pop w/ significant affects on Quality of life
• functional dyspepsia syndrome: absence of organic, systemic or metabolic dz; main cause of dyspepsia
• Other common causes: PUD and GERD; less common, celiac, cancer, drugs
• Symptoms indistinguishable from PUD
• Age > 45-55 is alarming: also acute or chronic gi bleeed, iron def, virchows node, palpable abd mass, persistant vomitng, progressive dysphagia

PUD Complications

• hemorrhage (most common): stimata of recent bleeding is non bleeding visible vessel, adherent clot, flat pigmented spot
• Perforation (2nd most): gastric to liver, duodenal to pancrease; abdomen xray confirms 80%, elevateed WBC, mildly elevated amylase: treatment correct shock, abdnormal electrolytes, NG tube, IV antibiotics, emergency surgery
• Stenosis: rare- relative (infalmmatory) vs fixed (fibrosis)
• intracability: persistent despite therapy

Extraintestinal manifestations of IBD

• apthous ulcers, erythema nodosum, poderma gangernosum, uveitis, iritis, episcleritis, aklyosing spondylitis
• peripheral arthritis: monoarticular, asymmetrical, large > small joints, no synovial destruction, no subcutaneous nodules, seronegative
• related to intestinal dz: peripheral arthritis, erythema, episcleritis
• unrelated to intestinal dz: ankylosing spondyltiis, uveitis
• unclear relation: pyoderma gangrenosum

Obese Levels vs non obese gut microbiota

• dec FIAF/AMPK fatty acid oxidation in obese
• in LPS inflammation in obese
• inc SCFA (lipogenase) in obese
• dec incretin secretin in epithelium in obse
• dec butyrate producitn in large intestine in obese
• might lead to insulin de-sensitivity in obese compared to lean

Drugs and toxins causing liver Damage

• fatty change - tetracyclines, aspirin, alcohol, methotrexate, amiodarone
• Necrosis: benzodiazepines, CCL4, acetaminophen, isoniazid, methyldopa, amanita mushroom
• Fibrosis: alcohol, methotrexate, amiodarone
• Cholestasis: anabolic steroids, oral contraceptives, erythromycin, aresenicals
• Veno-occlusive: cytotoxic drugs, bush tea
• Hepatic/portal vein thrombosis: estrogens, oral contraceptives
• Peliosis: anabolic steroids, oral contraceptives, danazol
• Granulomas: sulfonamides, methyldopa, quinidine

Massive Hepatic Necrosis

• occurs in fulminant hepatic failure; progresses to encephalopathy in 2-3 wks
• viral hepatitis - common cause
• drugs and toxins - less common cause
• other causes: hepatic vein obstruction, wilsons, fatty liver of pregnancy, malignancy, autoimmune hepatitis
• no stigmata of chronic liver dz
• gross - shrunken, soft organ
• micro: complete destruction of hepatocytes w/ only reticular network, triads remain, little inflammation, central-central vein fibrosis
• can regenerate if pt survives, scarring may be variable

Hepatitis Virus

• HAV: picornavirus (ssRNA): fecal oral, shellfish, not toxic to hepatocytes (immune medi dmg of infected)
• HBV: hepadnavirus (dsDNA): blood/bodily fluids, vertical transmission, risk of cancer, few get chronic and can have carriers
• HCV: flavivirus (ssRNA): high chance for chronic and hepatocellular carcinoma, poor development of immunity, cant develop vaccine
• HDV: rna virus thats needs co or superinfection with HBV (super leads to chronic hep)
• HEV: calcivirus - ssRN: fecal oral route, self limited by high mortality in pregnant women (20%)

Autoimmune Hepatitis

• chronic hep in pts with immune abnormalities (RA, UC, hashimotos, etc)
• Female predominant
• Type I - anti smooth muscle Ab (85%)
• Type II - anti liver/kidny microsomal Ab
• Type III - soluble liver Ab
• good response to immunesuppression but remission rare
• similar histo to acute/chronic hep but neg viral serologies, interface hepatitis, increased plasma cells

Primary Biliary Cirrhosis (PBC)

• chronic, progessive cholestatic dz with: destruction of intrahepatic bile ducts, portal inflammaiton and scarring, and eventual cirrhosis and liver failure
• females; 40-50 yrs old, pruritis
• autoimmune destruction of bile duct epithelium: abnormal location of mitochondrial protein, assoc wutoimmune dz, sjrogens, RA, thyroiditis, celiac dz
• anti-mitochondrial Ab in 90%; inc alk phos, bilirubin (late)
• florid duct: lesion, non suppurative granulomatous destruction of medium sized intrahepatic bile ducts
• similar to autoimmune hepatitis

Budd-Chiari

• hepatic vein thrombosis (outflow obstruction)
• subacute and chronic occlusive syndrome
• large liver, ascites, abdominal pain, weight gain
• pregnancy, oral contraceptives, myeloproliferative disorder, mech obstruction
• swollen liver with centrilobular necrosis, venous thrombi

Hepatic Adenoma

• young females, on oral contraceptives
• well demarcated; risk of rupture during pregnancy
• Sheets and cords of liver cells with NO portal Triads
• 3 subtypes: inflammatory (50%), HNF1A or CYP1B1 mutations, B catenin mutation

Clinical Presentation of 

Cholestasis 

• cholestasis is impairmed bile flow from hepatocyte to duodenum
• prutitis (bile acids interacte with opioidergic nerves and cause itching)
• jaundice: more common in extrahepatic cholestasis
• Dark urine: water soluble conjugated bilirubin in urine
• Pale Stool: due to lack of bile pigment in stool
• RUQ pain: hallmark of secondary ascending cholangitis (stones); biliary emergency
• can also get ADEK deficiencies, Xanthomas (deposits of cholesterol around eye lids), biliary cirrhosis

Cetaminophen Toxicity

(10-15gm or above)

• fatal fulminant dz >25mg
• blood levelsl of actetaminophen correlate with severity of hepatic injury (4hr mark)
• early manifestations: nausea, vomiting, diarrhea, abdominal pain, shock
• hepatic injury after 24-48 hrs after acute sx resolve
• renal failure occurs as well (may not be evident for 4-6 days)
• hepatic injury potentiated by alcohol (Induces C'YP2E1 whichinc NAPQI levels, supresses glutathione production, and chronic alcoholics may have toxic dose at 2gm), prior adm of phenobarbital, and starvation (reduces glutathione)
• treatment: gastric lavage, activated cahrcoal or cholestyramine (if given 30 mins after dose), N acetylcystine to reduce severity of hepatic necrosis, and liver transplant

Granulomatous Liver Disease

• hepatic dysfunction is usually limited
• inc ALP (common; mild to marked)
• needle biopsy provides 1st definitive evidence or systemic or disseminated granulomatous
• Systemic dz: sarcoidosis, hodgkins and non hodgkins lymphoma, PBC, crohns, wegners and idiopathic granulomatous hepatitis
• infections: TB, m avium, brucellosis, leprosy, EBV, CMV, chicken pox, schistosomiasis (extensive necrosis and scaring), reckettsia (Q fever), syphillis, and drugs (sulfonamides, isoniazid, allopurinol)

Serum-ascites albumin gradient

(SAAG)

1. SAAG > 1.1 = hepatic sinusoids

• Sinusoidal HTN - cirrhosis
• Post sinusoidal HTN - cardiac ascites, veno occlusive dz

1. SAAG <1.1 = peritoneum

• peritoneal pathology - malignancy, TB

Hepatic Encephalopathy

• bacterial action -> protein load
• failure to metabolize NH3; shunting -> GABA rec -> toxic
• ammonia has poor correlation with dx; not neccesary
• number connectin test
• slow dominant rhythm on EEG
• confusion -> drowsiness -> somnolence -> coma
• asterixis
• treatment: identify and treat precipitating factor, dec ammonia production in gut (lactulose and protein restriction), inc ammonia fixation in liver (ornithine aspartate, benzoate)

Islets of Langerhans

• 70% B cells - insulin
• 5-20% A cells - glucagon
• 5-10% Delta cells - somatostatin
• PP cells - increase enzymes, dec GI motility

Ransons Criteria

• early predictor of acute pancreatitis severity > 3
• on admission: age > 55, hyperglycemic, leukocytosis, inc LDH (hemolysis), inc AST
• during inital 48 hours: hematocrit drop, serum calcium, BUN inc, inc in fluid sequestation

Serous Cystadenoma

• neoplastic pancreatic cyst
• benign, sponge-like central stellate scar
• females > males 2:1, mean age 60-70 yrs old
• many have vHL tumor suppressor gene mutation
• cuboidal to flattened cells, round small nuclei, clear glycogen rich cytoplasm
• pitfalls: rarely coexist with ductal adenocarcinoma

Mucinous Cystic Neoplasm

• neoplastic pancreatic cyst
• benign, borderline malignant (cellular prol, mitosis, stromal invasion)
• 95% - females, more common body and tail
• ovarian type stroma (even in males

Intraductal papillary mucinous neoplasm

(IPMN)

• arise in pancreatic ducts, present as chronic pancreatitis 2" duct obstruction
• Males > females 2:1 (reverse of serous cyst adenoma)
• cyst lining can be smooth, granular or papillary

Cholesterolosis

• inc lipids that get phagocytized into mucosa of gallbladder
• strawberry gallbladder
• foamy macrophages
• cholesterol polyps

Exocrine Function of Pancreas

• secretin and CCK stimulates the pancreas
• secretin is stimulated by low pH; stimulates release of enterokinase
• CK is stimulated by low pH, amino acids, and fatty acids
• Pancreatic enzymes secreted as inactive zymogens, activated by trypsin

Systemic Complications of

Acute Pancreatitis

• Phospholipase A, which digests lecithin, can induce ARDS
• vasoactive peptides leads to myocardial depression
• hypoalbuminemia and hypomagnesemia can cause hypocalcemia
• pancreatic necrosis from translocation of bacteria from colon

Esophageal Atresia

• faulty division of foregut by esophagotracheal septum (almost always accompanied by tracheoesophageal fistula)
• associated anomalies: congenital heart disease (VSD, PDA, TOF), imperforate anus, VATER/VATERL/VACTERL assoc
• clinical presentation: prenatal polyhydraminos, inc oropharyngeal secretions, chocking, coughing, regurgitations, aspiration of gastric contents - air into stomach

Extrahepatic Biliary Atresia

• inflammatory destruction of extrahepatic hiliary tree
• onset at 4-8 wks of life
• progressive destruction -> cirrhosis and death
• unknown cause
• liver biopsy: cholestasis, bile duct proliferation, portal fibrosis; large portal areas 
• cytokeratin IHC highlights ductal proliferation
• Therapy/prognosis: portoenterostomy (Kasai procedure) by 8 wks age
• most develop biliary cirrhosis and require transplant

Pediatric Unique Conditions

• Milk-soy protein intolerance (MSPI): inflammatory response to ingested proteins that cross the immature GI mucosa (can occur in breast fed)
• Colic: episodes of crying lacking a cause
• Cyclic vomiting syndromes (CVS): recurrent, stereotypical bouts of severe vomiting with intervening periods of normal health and no identifiable cause
• Eosinophilic esophagitis: more common in boys, especially teens; eosinophils invade mucosa and lamina propria and creates rough surface in esophagus that food can get stuck or impacted
• functional abdominal pain

Vitamin B1 (Thiamin)

• functions as coenzyme in krebs cycyle
• deficiencys lead to dry beriberi (peripheral neuropathy), wet beriberi (CV symptoms) and wernicke-korsakfoff syndrome
• Wernickes: opthalmoplegia, nystagmus, ataxia
• Korsakoff psychosis: short term memory loss, confabulation

Vitamin B2 (riboflavin)

• conenzyme for flavin mononucleotide and FAD
• defeciency leds to oral buccal lesions, seborrheic dermatitis and scrotal, vaginal skin changes
• Oral buccal lesions: cheilosis (inflam, cracking of corners of mouth), glossitis, angular stomatitis
• seborrheic dermatitis - flaky white to yellowish scales to form in oily areas of skin

Vitamin B3 (niacin)

• coenzyme: NAD
• can be synthesized in the body from tryptophan
• deficiency is pellagra (3 Ds): dermatitis (glossitis, stomatitis, vaginitis), diarrhea (and vomiting), dementia (headache, dizziness, insomnia, irritability)
• Toxicity: nicotinic acid: may caus vascular dilation or flushing

Vitamin B12 (cobalamin)

Deficiency

Folate Deficiency

• coenzyme = tetrahydrofolic acid
• megaloblastic anemia: like B12 deficiency, but no peripheral neuropathy
• Neural Tube Defects: anencephaly, spina bifida in newborns of mothers not taking folate supplement 

Vitamin A

• stimulates production of rhodopsin
• deficiency: night blindness, follicular hyperkeratosis, also bitots spots on conjunctiva
• acute toxic: inc intracranial pressure, skin exfoliation, and hepatocellular necrosis
• Chronic toxic: bone malformations, fractures, pseudotumor cerebri with headaches, dermatitis
• Early pregnancy toxic: spontaneous abortions, birth defects and learning disabilities

Iodine

• incorporated into thyroid hormones, T3 and T4
• deficiency newborns: spontaneous abrotions, stillbirths, hypothyroidism, cretinism (severe mental retardation) dwarfism
• Adult deficiency: hypothyroidism and goiter

Iron

• gastric hypoacidity can dec iron absorption (need acid to convert Fe3 to Fe2 for absorption)
• higher iron requirements for females and pregnancy
• defiency: microcytic, hypochromic anemia: tachycardia, fatigue, pallor, altered mental/motor development
• Hemosiderosis or siderosis: excessive total body iron with inc iron stores, accumulation in reticuloendothelial tissues, little consequence
• Hemochromatosis: iron deposits into parenchymal organ tissues; triad- cirrhosis, diabetes, hyperpigmentations of skin (gray tinge)

Zinc Deficiency

• skin rash - face, groin, hands, feet
• alopecia
• growth retardation
• delayed sexual development
• impaired wound healing, immune function

Psyllium

(metamucil)

• treats constipation (swelling agent)
• part used: seed, husk
• constituents - rich in polysaccharides
• side effect is malabsorption
• MOA - bulk laxative
• can treat diarrhea if given with little fluid

Senna

• treats constipation
• part used - leaf, fruit/pod
• constituents - anthaquinone glycosides
• MOA - stimulant laxative, irritant purgative
• side effects: dependency, hypokalemia, abuse potential (rapid weight loss)
• toxicity - severe damage to renal tubules
• stimulant laxatives aloe and castor oil are banned over the counter

Ginger

• treats nausea/vomiting
• part used - rhizome
• constituents - gingerols, shogaols, zingerone
• MOA - antiemetic, spasmolytic, antiflatulent
• side effects - mild heart burn, diarrhea and irritaiton

Peppermint

• treats IBS
• part used - leaf
• constituents - menthol, menthone
• MOA - unclear, assists in elimination of gas by relaxing sphincter
• contraindicated in GERD

Milk Thistle

• treats liver diseases
• part used - seed, fruit, leaf, flowering head
• constituents - silymarin, silybin
• MOA - potent liver protecting subs; antioxidant, inhibits free radicals, inc glutathione, inhibits LOX
• avoid in pregnancy

Horse Chestnut

• treats chronic venous insufficiency
• Part Used - seed, bark
• constituents - saponins (Bescin)
• MOA - inc venous tone, dec capillary permeability, reduces skin edema
• Toxicity - capsules have many adverse effects 9topical/gel is fine)

Garlic

• CV diseases
• Part used - bulb
• constituents - sulfer compounds (alliin, allicin, allyl cysteine)
• MOA - antioxidant, destroy free radicals
• drug interactions - antiplatelets, anticoagulants, protease inhibitors

Ginko

• Treats alzheimers, dementia
• part used - leaf
• constituents - terpinoids, gingkolides
• MOA - improves blood circulaiton, antioxidant
• drug interactions - anticoagulants, antidepressents

St Johns Wort

• treats depression
• part used - flowering top
• constituents - phenolic acids, hypericin, hyperforin
• MOA - MAO inhibitor, 5-HT uptake inhibitor 
• drug interactions CYP inducer

Lapacho

• treats parasitic diseases
• part used - inner back
• constituents - naphthaquinones (lapachelo, lapachone)
• MOA - anti-protozoal, antimicrobial, anti fungal, anti viral

Echinacea

• treats common cold
• part used - roots, flowerin tops
• constituents - caffeic acid
• MOA - immunostimulant
• uses - common cold, sore throat, athletes foot, ear infections

Soybean

• treats menopause
• part used - bean (seed)
• constituents -genistein, diadzen
• MOA - estrogenic properties
• avoid soy with breast cancer

Evening Primrose Oil

• treats premenstrual sndrome, menopause
• part used - seed
• constituents - essential FA, linoleic acid (omega 6 FAs)
• MOA - source of omega 6 fatty acids, NO estrogenic properties

Saw Palmetto

• benign prostatic hyperplasia
• part used - berry
• Constituents - FA, plants sterols
• MOA - inhibits 5a-reductase 
• Uses - BPH

Yohimbe

• treats male impotence
• part used - bark
• constituents - indole alkaloids (yohimbine)
• MOA - a2-adrenergic antagonist
• uses = male impotence, ED

Willow Bark

• treats arthritis, rhematism, muscle pain
• part used - Bark
• constituents - Salicin
• MOA - prostaglandin synthase inhibitor
• acts just like aspirin (dont combine with other salicylates)

Turmeric

• treats arthritis
• part used - Rhizome
• Constituents - curcumin
• MOA - anti inflammatory

Chili pepper

• treats topical inflammation, pain
• part used - fruit, seed
• constituents - capsaicin
• MOA - acts on vanilloid rec (inflammation), desensitizes sensory nerve endings

Oats

• treats dry skin, eczema
• Part used - seed
• constituents - avenin, starch, vitamin E
• MOA  anti inflammatory emollient
• Aveeno

Eye Bright

• treats eye irritation
• part used - aerial parts (flower, leaf, stem)
• constituents - iridoid glycosides, tannins
• Uses - eye strain, irritaitno, itching, redness, cojunctivitis

Clove 

• treats dental ailments
• part used - flower bud
• constituents - eugenol
• MOA - anti inflammatory, antiseptic 

Kwashiorkor

• protein deficiency relative to calories
• hallmarks - edema, lethargy, anorexia
• Primary (childhood) - edema, ascites, apathy, anorexia, fatty hepatomegaly, flaky paint dermititis, hair sparse and depigmented
• Secondary (adult) - acute, lifethretening complications, may occur in obese, pitting edema,effusions, electrolyte abnormalities
• serum albumin low < 2.8, low transport proteins, low lymphocytes, low lvls of lipid, BUN, UUN, electrolytes, hypochloremic metabolic acidosis

Marasmus

• protein and calorie deficit
• appetite and mental astatu relatively preserved
• primary (childhood): growth failure, wasting without edema (particularly temporalis, peripheral), less dull mental status (almost normal), good appetite, poor skin turgor (baby monkey eyes), thin, dry hair
• secondary (adults): wasting without edema, intact mental status, variable appetite, poor skin turgor, hair thin dry and dull
• Albumin low but > 2.8g/dl, minimal effects on transport proteins and lymphocytes, anemia common

Weir Equation

• way to measure calorimetry - indirect O2 and CO2
• Respiratory quotient (RQ) = VCO2/CO2
• RQ = 0.7 for fat
• RQ = .81 for protein
• RQ = 1 for carbohydrates
• Goal RQ is btw 0.8 - 0.9 
• Avoid RQ > 1

Disease Specific Diets

• renal failure - essential AA
• hepatic failure - branched AA, low in aromatic AA
• Pulmonary Failure - High fat
• immune failure - supplemental nucleotides, arginine, glutamine, omega 3, MCT oil

Total Parenteral Nutrition (TPN)

Solutions

• protein given as elemental AA
• Carbohydrate given as concentrated dextrose
• Fat given as lipid emulsion
• 2 in 1 TPN = AA, dextrose
• 3 in 1 TPN = AA, dextrose, lipids 

Evaluation of Malabsorption

• Fecal Fat - 72 hour collection, random or spot determination
• D-xylose Test - evaluates small bowel absorptive function independent of enzymes, bile salts or HC1
• Bentiromide Test (NBT-PABA) - assess pancreatic exocrine function, non invasive
• Lundh Test Meal - most physiologic test to evaluate pancreatic function, invasive
• Bile Salt Breath Test - measure C14 CO2; evaluates bile salt absorption and bacterial overgrowth
• Breathy Hydrogen Test - malabsorption of carbs, measures H2 produced from bacterial degradation of substrate
• Schilling Test: evaluate absorption of VB12

Whipple Disease

• uncommon systemic disease
• infiltration of involved tissue with large lgycoprotein containing macrophages
• characteristic small rod shaped gram pos bacilli (not acid fast)
• weight loss, diarrhea, abdominal pain, fever, arthralgia/arthritis, inc skin pigmentation, anemia, lymphadenopathy, pleuritic, pericarditis, valvular endocarditis, CNS Symptoms
• diagnosed with small bowel biopsy
• antibiotic treatment

Factors That affect Glycemic Index

• processing: milling and refining (remove bran and germ) have higher index
• physical form: finely ground grain is more rapidly digested than whole grain
• Fiber content: high fiber foods digest slowly
• Ripeness: ripe fruits and veggies have higher glycemic index
• Fat content and acid content: meals w/ fat or acid converted more slowly to sugar

Prevention of Cancer

• high food temps and overweight/obesity risk for oral, pharynx and esophagus cancer
• salted foods (meats and pickles) risk for stomach cancer
• 3 fold higher risk of endometrial cancer in obese women
• preserved meat and obesity/overweight risk factor for colorectal (exercise protective)
• obesity does not inc risk of breast cancer in premenopausal women
• overweight and obesity risk factor for kidney cancer