Pathology of the Mouth

Pathology of the Esophagus

Disease Cause Symptoms Buzzwords Other

Minor Aphthous UlcerMiRAU

Immunological (Cell Mediated Immunity)

Numerous Allergens

Ulcer on Non-keratinized movable mucosa~ 5 mm

Heal in 2 weeks – no scarring

Associated with Crohn’s, AIDS, Celiac, Behcet’s, Leukopenia & Vitamin DeficienciesTreat with topical steroids – Don’t cauterize!

Major Aphthous Ulcer(Sutton’s Disease)

MaRAU

Immunological (Cell Mediated Immunity)

Numerous Allergens

Ulcer on Non-keratinized movable mucosa> 5 mm (up to~3 cm)

Heal in > 2 weeks (up to 6 weeks)Scarring!

Topical steroids ineffective – Treat with stronger local steroids

Herpetiform Aphthous UlcerHeRAU

Immunological (Cell Mediated Immunity)

Numerous Allergens

Ulcer on movable or bound mucosa< 2 mm & frequently numerous

No painful or erythematous gingivaTopical steroids is treatment of choice

Herpangina Coxsackie Virus Ulcer on soft palate, tonsils or pharyngeal wallSore throat, fever, headache, nausea Back of mouth Dyclonine HCl (specially prepared is DOC)

Hand, Foot & Mouth Coxsackie Virus Ulcers on palate, tongue & buccal mucosaErythematous Rash Dyclonine HCl (specially prepared is DOC)

Behcet’s Syndrome Autoimmune Ulcers same as MiRAUOral, genital & ocular lesions Eye & Genitals

Herpetic Gingivostomitis Herpes Virus

Painful erythematous gingivalClear fluid filled vesicles

Usually unilateral recurrenceskeratinized, bound mucosa

GingivaCan cause herpetic whitlow (contagious infection of finger)Ulcers are the opposite of MiRAUExtremely Painful (primary occurance)

Herpes Zoster Herpes Virus UnilateralWhite opaque ulcers resembling RAU

Erythema Multiforme(Stevens-Johnson Syndrome) Unknown

Preceded by viral infection or allergen exposureInvolves skin & mucosal surfaces

Usually movable mucosa (but not limited to)Target Lesion

(Also another Eye & Genitals)

Extremely PainfulStevens-Johnson = skin, eye, mouth & genitals (similar to Behcet’s?)

Disease Cause Symptoms Buzzwords Other

Reflux EsophagitisReflux

Esophageal Sphincter Disorder↑ Acid & Pepsin, Bile, Lysolethicin

Heartburn & RegurgitationAlso dysphagia, odynophagia, hemorrhage &

pulmonary symptoms (cough?)

Most common esophagitisMicroscope = Eosinophils, PMN’s & hyperplasiaComplications = Barret Esophagus, Ulcer, Stricture

Barret Esophagus Chronic Esophageal Reflux Mucosa replaced with intestinal mucosa Intestinal MetaplasiaAdenocarcinoma of Esophagus Complications = risk of esophageal adenocarcinoma

Squamous Cell Carcinoma 1) Drinking & SmokingDiet, Chronic injury, Genetic

Dysphagia & ObstructionAspiration pneumonia Middle 1/3 of esophagus Most frequently found in middle 1/3 of esophagus

Microscope = Keratin Pearls

Sliding Hiatal Hernia Herniation of cardia GE Reflux Cardia Most Common Hiatal Hernia

Paraesophageal Hiatal Hernia(Rolling) Herniation of fundus Asymptomatic

Strangulation & infarction possible Fundus

Mallory-Weiss Lacerations Excessive Vomiting AlcoholicsVomiting Tears at the Gastroesophageal junction

Pathology of the StomachDisease Cause Symptoms Buzzwords Other

Acute Gastritis1) NSAIDS & Alcohol

Smoking, Stress, Uremia, InfectionChemotherapy & Radiation

Very small (numerous?) ulcersInflammation

Not associated with H. pylori!Pathogenesis = Hypoperfusion, ↓ mucus production, ↑ Gastric AcidFound in 10% of hospital admissionsOutcome dependent on correction of underlying condition!

Nonatrophic Chronic Gastritis H. pylori? Active gastritis & Lymphoid follicle Associated with Gastric Adenocarcinoma & MALT Lymphoma

Peptic Ulcer Disease

Gastric Acid & Pepsin, H. pyloriZollinger-Ellison Syndrome

NSAIDS & SmokingStress, alcohol & steroids

Ulcerations through muscularis mucosaPain at night, after meals, relieved with food

Bleeding (frequent complication)Pain relieved by eating

Zones = 1) Exudate 2) Necrosis 3) Granulation 4) ScarringDeath caused by perforationNot likely to cause cancer unlike nonatrophic chronic gastritisPUD is more common in duodenum than stomach

Autoimmune Atrophic Gastritis(Type A)

AutoimmuneAntibodies to parietal cell/intrinsic factor

Loss of parietal cellsHypochlorhydria, ↓ Intrinsic Factor (Low B12)

Pernicious AnemiaGlandular atrophy/Intestinal Metaplasia

Gastric BODY (A = Body)↑ Gastrin

Low Gastric Acid, HIGH Gastrin levelsRisk for gastric cancer

Multifocal Atrophic Gastritis(Type B) Diet & Environment? Glandular atrophy/Intestinal Metaplasia Gastric ANTRUM (B = Antrum) Low Gastric Acid, Normal Gastrin levels

Causes intestinal type gastric adenocarcinoma

Intestinal Type Gastric Adenocarcinoma

Diet & Environment(Nitrates & Pickling)

Polypoid & Well DifferentiatedIntestinal Metaplasia

Weight LossPain, Melena, Hematemesis, Anemia

MetaplasiaOccurs in older age & in males, Better outcome than diffuse typeMetastasis to lungs and liver or ovary (Krukenberg)More likely to be in antrum or pylorus (distal) than in body

Diffuse TypeGastric Adenocarcinoma

UnknownDiet, Environment, Chronic GastritisGastrectomy, Adenomas, Menetrier’sGenetics (oncogenes/suppressor gene)

Ulcerating or Linitis Plastica (Diffuse)Weight Loss

Pain, Melena, Hematemesis, AnemiaSignet Ring Cells Metastasis to lungs and liver or ovary (Krukenberg)

More likely to be in antrum or pylorus (distal) than in body

Disease Cause Symptoms Buzzwords Other

Crohn’s DiseaseDiarrhea, Abdominal Pain, FeverLoss of albumin, Malabsorption

Arthritis, Uveitis, Ankylosing spondylitis

Transmural/GranulomaString Sign

Segmental – Skip AreasFissures/Fistula/Linear Ulcers

Frequently involves terminal ileumNarrowed lumen, aphthoid ulcers to fissuresTransmural inf. / Noncaseating granulomas / Perianal FistualsLower risk of cancer than ulcerative colitis

Ulcerative Colitis Relapsing diarrhea associated with stressArthritis, Uveitis, Ankylosing spondylitis

Diffuse/Continuous from RectumMucosa/Submucosa

Lead PipeAbscess/Broad ulcers/pseudopolyps

Crypt abscessesNo granulomasCan cause perforation, toxic megacolon & cancerAssociated with Primary Sclerosing Cholangitis (liver)

Peptic Ulcer Disease

Gastric Acid & Pepsin, H. pyloriZollinger-Ellison Syndrome

NSAIDS & SmokingStress, alcohol & steroids

Ulcerations through muscularis mucosaPain at night, after meals, relieved with food

Bleeding (frequent complication)Pain relieved by eating

Zones = 1) Exudate 2) Necrosis 3) Granulation 4) ScarringDeath caused by perforationNot likely to cause cancer unlike nonatrophic chronic gastritisPUD is more common in duodenum than stomach

Transmural Ischemic Bowel Disease

Mechanical compromise of vesselsArterial Thrombus or Embolism

Venous ThrombosisVolvulus, Stricture, Herniation

Abrupt lower abdominal pain & bloody stool

Involves all of small bowel or splenic (watershed area) of colonAcute = coagulative necrosis & hemorrhage – No inflammation!Chronic = chronic inflammation, stricture, fibrosisHigh mortality

Mural or MucosalIschemic Bowel Disease

HypoperfusionCardiac Failure, Shock, Dehydration

RadiationVolvulus, Stricture, Herniation

Abrupt lower abdominal pain & bloody stool

Involves all of small bowel or splenic (watershed area) of colonAcute = coagulative necrosis & hemorrhage – No inflammation!Chronic = chronic inflammation, stricture, fibrosisHigh mortality

Pseudomembrane ColitisClostridium Dificile

Broad Spectrum Antibiotics(Clindamycin)

Diarrhea, Fever, Pain, Leukocytosis Clostridium DificileClindamycin

Raised yellow plaques (1-2 mm)Volcano or mushroom pseudomembraneTreat with metronidazole (Flazyl?)

Bacterial Overgrowth Syndrome

Blind Loop SyndromeMultiple DiverticuliAbnormal Motility

Amyloidosis & Diabetes

MalabsorptionDeconjugation of bile salts (poor micelle formation), Direct injury to cells, Direct utilization of nutrients by bacteriaTreat with intermittent antibiotics

Celiac Sprue

Autoimmune – Virus?Antigliaden Antibody

Antiendomysium AntibodyAntireticulin Antibody

Generalized MalabsorptionDiarrhea, Flatulence, Weight Loss, Fatigue Gluten-Gliaden

Villous Atrophy caused by sensitivity to gluten in foodSymptoms disappear quickly with gluten free dietMay cause intestinal lymphomaOften found in children, whites, families

Tropical Sprue Infection? Generalized MalabsorptionDiarrhea, Flatulence, Weight Loss, Fatigue

Villous Atrophy Symptoms disappear quickly with antibiotic treatment

Whipple’s Disease Tropheryma whippelii bacteriaImmune Defect? Malabsorption, Fever, Arthritis, CNS Complaints

ArthritisCNS

Large PAS + Macrophages

Large macrophages fill lamina propria of small intestine (PAS +)Usually a prompt recovery with antibiotics

Lactase Deficiency Lactose MalabsorptionDiarrhea & Flatulence Microscopically Normal

Lactase found in apical membrane of epithelial cells in villiLactase normally breaks lactose in glucose & galactoseMore commonly acquired, but can be congenitalMicroscope: Looks normal

Abetalipoproteinemia Genetic (AR)

AcanthocytesFailure to absorb fatty acids & Vitamin A,D,E,K

Diarrhea, Steatorrhea, CNS ProblemsFailure to Thrive in Infants

AcanthocyteLipid (Fat) Vacuole

Can’t synthesize or export lipoproteins from intestinal cellsTriglycerides accumulate in epithelial cell lipid vacuolesAbsence of CM, VLDL, LDL

Pathology of the Intestines

Pathology of the Intestines (contd)Disease Cause Symptoms Buzzwords Other

Collagenous Colitis Chronic Watery Diarrhea Middle Age Women Normal colonoscopic examMarkedly thickened subepithelial layer

Acute Appendicitis Obstruction?Fecalith, Worms, Tumor

Usually absentPeriumbilical then RLQ Pain, Nausea, Tenderness

Fever, Leukocytosis

Neutrophilic Infiltration of Muscularis

Diagnosis depends on Neutrophils in muscularisOften in adolescents or young adults

Angiodysplasia Unknown - Aging? HematocheziaUsually found in adults past 6th decadeSignificant lower GI bleedingMost often in cecum or right colon

Bowel Obstruction Adhesions – Most commonMany others

Mechanical Obstruction: Adhesions, hernias, intussusception, tumors, strictures, volvulus, stones, bands, meconium, imperforate anusPseudo-obstruction: postoperative, infarction, myo/neuro - opathy

Hernias Inguinal, Femoral, Umbilical, IncisionalCan cause trapping (incarceration) or strangulation

IntussusceptionIdiopathic

Postviral lymphoid hyperplasiaIntraluminal mass

TelescopingMost often in children or infantsMost commonly in ileocecal regionTreated with barium enema or surgery

VolvulusAdhesions

Long MesentaryMeckel’s Diverticulum

Twisting Most often small bowel, sometimes sigmoid or cecum

Hyperplastic Polyps Asymptomatic Saw-ToothedMost common colonic polyp, usually rectosigmoidNo malignant potentialUsually < 5 mm

Juvenile Polyps Painless rectal bleeding Autoamputation

Hamartomatous, usually in children < 5Usually found in rectumLarge (>4 cm) with stalk, Surface erosion or ulcerationNo malignant potential in sporadic cases

Peutz-Jeghers Polyps Genetic (AD)PJS (STK11) gene Lips, oral mucosa, genitalia

Hamartomatous, always found in small bowel, 30% in colonMelanotic Mucosal & Cutaneous pigmentation of lips, oral mucosa, face, genitalia & palmar surfacesMalignant risk: pancreas, breast, lung, ovary & uterus – Not colon

Tubular Adenoma Rasberry-like HeadPicket Fence

Most common neoplastic polyp; usually rectosigmoidPedunculated with slender stalk, pseudostratifiedRisk of developing into cancer

Villous AdenomaRectal bleeding

HypoproteinemiaHypokalemia

Low protein & potassiumFinger-like papillae

Not common, but ominousFinger-like or branching papillaeBroad based, no stalkRisk of developing into cancer

Pathology of the Intestines (contd-2)Disease Cause Symptoms Buzzwords Other

Tubulovillous Adenoma(Villoglandular)

Usually pedunculatedRisk of developing into cancer

High Grade Dysplsia(Carcinoma in situ) Adenoma? Archetectural complexity & cytologic atypia, no invasion

Not able to metastasize, cured by removal

Familial Adenomatous Polyposis

Genetic (AD)APC mutation

Appears in 2nd & 3rd decades

Innumerable polyps in colon, stomach, duodenum and small bowelFlexible sigmoidoscopy at age 12; prophylactic proctocolectomy100% malignant by 40 years

Gardner Syndrome Genetic (FAP)APC or mismatch repair mutation

OsteomasFibromatosis FAP with osteomas, fibromatosis & epidermal cysts

Turcot Syndrome CNS FAP/HNPCC with tumors of CNS

Familial Juvenile Polyposis Genetic (AD)SMAD-4 or BMPR1A mutation High risk for GI adenocarcinoma (usually colorectal)

Heriditary Nonpolyposis Colon Cancer Syndrome (HNPCC)

Lynch Syndrome I & II

Genetic (AD)hMSH2, hMSH1, hPMS1 & hPMS2

genes (mismatch repair)(similar to bacterial mut HLS)

No adenomasProximal

More common than FAPTypically proximal location, risk of extracolonic cancer (Endometrial in Lynch II)

Colorectal CarcinomaAdenomas

FAP, HNPCC, Genetic alterationsLow fiber, High fat diet, IBD

Left Sided: Blood, Pencil Stools, ObstructionRight Sided: Anemia, Weight Loss, RLQ Pain

Pencil StoolIron Deficiency Anemia

Blood in stool

Left = Napkin Ring; Right: = Cauliflower Lesion95% AdenocarcinomasCEA: reliable marker of recurrent tumorsMost important prognostic factor is staging of tumor at diagnosis

Diverticulosis Low Fiber Diet

BleedingObstruction caused by muscular hypertrophy

Pericolic abscessPerforation, Vesicocolic fistula

Pericolic abscessCommon in elderly; Typically in sigmoid colonUsually asymptomaticOutpouching of mucosa through teniae, muscular hypertrophyNot a risk for cancer

Pathology of the LiverDisease Cause Symptoms Buzzwords Other

Acute Hepatic Failure ManyDrugs – Acetaminophen & Halothane

Increased PT due to ↓ Factor VIIEdema, JaundiceRUQ Tenderness

Telangiectasias, Gynomastia, Palmar Erythema

Excretory: HyperbilirubinemiaExocrine: Hypercholesterolemia, Steatorrhea, Pruritis, ↓ VitaminsSynthetic: Albumin, Transferrin,Cerruloplasmin, Clotting FactorsMetabolic: Glucose, Ketones, Fatty Acids, Drugs, Estrogen

Cirrhosis

Alcoholic Liver Disease (60-70%)Viral Hepatitis, Biliary DiseaseHemochromatosis, Autoimmune

Wilson, Idiopathic

Anorexia, Weakness, Dupuytren’s ContractureAscites & Edema, Splenomegaly

Esophageal Varices & Caput MedusaTelangiectasias, Gynomastia, Palmar Erythema

Dupuytren’s ContracturesPalmar Erythema

TelangiectasiaEsophageal Varices

Portal Hypertension, FibrosisInfection due to lack of Kupfer Cells, Spontaneous peritonitisMicronodular = Alcoholic Liver Disease & HemochromatosisMacronodular = Viral, Autoimmune, Wilson’s Disease

Hepatic EncephalopathyDecreased Hepatic Function

GI Hemorrhage, Protein LoadInfection, Sedatives, Constipation

Confusion, Restlessness, AsterixisConvulsion, Com

Hepatorenal Syndrome Decreased prostaglandins? Azotemia, Hyoerkalemia, Acidosis, OliguriaConcetrated Urine with low sodium

Normal kidneys with adequate vascular volume & cardiac functionLooks like pre-renal azotemia

Alcoholic Steatosis Alcohol Abuse(Ethanol & Acetaldehyde)

AsymptomaticMalaise, Anorexia, Abdominal Discomfort Macrovesicular Reversible

Macrovesicular Fat Vacuoles

Alcoholic Hepatitis Alcohol Abuse(Ethanol & Acetaldehyde)

Malaise, Anorexia, Fever, RUQ Pain, JaundiceElevated Enzymes (AST>ALT)

Leukocytosis

Mallory BodiesRUQ

AST>ALTNeutrophil

IrreversibleNecrosis of hepatocytes in central zone, hyaline inclusionsNeutrophilic (Inflammatory) ResponsePerivenular & Sinusoidal Fibrosis

Nonalcoholic Fatty Liver Disease

(NAFLD)

ObesityDiabetes

DyslipidemiaDrugs (amiodarone, steroids)

Macrovesicular Similar to Alcoholic Fatty Liver Disease, but no history of alcoholMacrovesicular Fat Vacuoles

Acute Hepatitis A Fecal-Oral(Blood rare)

Malaise, Anorexia, Nausea, Fever, Rash, ArthritisDark Urine, RUQ pain, Jaundice (1/2), Itching

Patchy involvement of entire lobule, ballooning degeneration, Acidophil Bodies, Mononuclear InflammationShort Incubation period; Higher mortality with age >49IgM = active; IgG = Recovered

Acute Hepatits BSex

PerinatalSaliva

Malaise, Anorexia, Nausea, Fever, Rash, ArthritisDark Urine, RUQ pain, Jaundice (1/3), Itching

Ground Glass CellsSexual Intercourse

HCC

Patchy involvement of entire lobule, ballooning degeneration, Acidophil Bodies, Mononuclear InflammationIntermediate Incubation period, Serum sickness, Chronic if age <5IgG-s = recovered; IgM-c & IgG-e = infected

Acute Hepatitis D HBV Infection HBV InfectionPatchy involvement of entire lobule, ballooning degeneration, Acidophil Bodies, Mononuclear InflammationFulminant HBV (coinfected) or chronic active (superinfection)

Acute Hepatitis CInjecting Drug Use

Fecal – Oral?Perinatal

Malaise, Anorexia, Nausea, Fever, Rash, ArthritisDark Urine, RUQ pain, Jaundice (1/5), Itching

Injected Drug UseHCC

ChronicMore severe progression with age, alcohol, HIV+

Chronic Persistent Viral Hepatitis HCV or HBC Prolonged asymptomatic ↑ transaminase

Slow recover, noe sequelae Cobblestone Mild inflammation & evidence of degeneration & regenerationCobblestone appearance

Pathology of the Liver (contd)Disease Cause Symptoms Buzzwords Other

Chronic Active HepatitisHCV

HBV (esp. with HDV superinfection)Autoimmune Hepatitis

Multiple episodes of anicteric disease ↑ transaminase swings (ALT) Bridging Necrosis

May lead to liver failure & cirrhosisBridging necrosis with piecemeal necrosis & inflammation at limiting plateFibrosis

Hepatitis E Fecal-Oral High risk of mortality in pregnant women

Autoimmune HepatitisHLA B8, Dr3 & 4, Dr52Type I = ANA & ASMA

Type II = AKLM-1AType I = Infertility or endocrine disorder

Anti-Smooth MuscleAnti-KLM-1Plasma Cells

Macronodular (Cirrhosis)

Type I = Premenopausal women, Thyroiditis, Diabetes, Hemolytic Anemia; Hypergammaglobulinemia (anti smooth muscle)Type II = Female children; more aggressive; anti KLM-1Looks like viral, but with plasma cells in portal area

Drug Induced Liver Disease ManyTylenol, INH, Methyldopa, Halothane

Disproportionate Necrosis (Zonal), Fatty ChangeEosinophilia, Granulomas

Disproportionate cholestasis

AcetominphenEosinophils

Primary Biliary Cirrhosis Autoimmine

Antimitochondrial AntibodiesXanthomas, ↑ Alkaline Phosphatase, Often asymptomatic, insidious onset

Pruritis, Jaundice

Antimitochondrial antibodyMiddle Aged Women

Destruction of interlobular and septal bile ducts, slow progression to cirrhosisMiddle aged women; treated with UDCA or transplantLymphoplasmacytic infiltrate, Absence of bile ducts in portal tract

Primary Sclerosing Cholangitis Unknown Radiographic diagnosis shows stenosis and dilation of biliary tree

Young MenUlcerative Colitis

Cholangiocarcinoma

Diffuse fibrosing inflammation of all segments of biliary treeYoung Men; ulcerative colitisPeriductal fibrosis, bile duct proliferationMay cause cholangiocarcinoma

Ascending CholangitisObstruction of bile flow

Choledocholithiasis, stents, cathetersTumors, acute pancreatitis, strictures

Fever, chills abdominal pain, jaundice Choledocholithiasis Acute inflammation of wall of bile ducts with PMNs in lumen

Extrahepatic Biliary Atresia Obstructive type jaundiceDark urine & pale stools Kasai Procedure

50% of infants with prolonged cholestasisProgressive fibrosis and cirrhosisPeriportal ductular proliferation & fibrosis, cholestasis or no ductsTreated with Kasai procedure or transplant

Secondary Hemochromatosis

Thallassemia Major, TransfusionsAlcoholic Cirrhosis, Iron Ingestion

Sideroblastic Anemia

ThalassemiaSideroblastic Anemia

Kupffer Cells

↑ Iron causes activation of Ito (Stellate) cells to produce collagenHemosiderin deposits in Kupffer cells

Heriditary Hemochromatosis

Genetic (HFE)Upregulation of iron transport in crypt

cells and absorption by duodenal villous cells

Micronodular Cirrhosis, Diabetes, Skin Pigmentation, Cardiac failure, Testicular Atrophy

MicronodularSkin Pigmentation

Diabetes

Appears in 5th or 6th decade of life, more frequent in men↑ Iron causes activation of Ito (Stellate) cells to produce collagenHemosiderin deposits in hepatocytesHigh incidence of hepatocellular carcinoma

Wilson DiseaseGenetic (WD)

Defective biliary excretion by copper ATPase

Fulminant Hepatitis, CirrhosisKayser-Fleischer Ring, CNS signs

Coombs-negative hemolytic anemia↑ Copper, ↓ Cerruloplasmin

Kayser-Fleischer Ring Kayser-Fleischer Ring, Coombs-negative hemolytic anemiaTreat with copper chelators, zinc, or transplant

Alpha-1-AntitrypsinDeficiency

Genetic (AR)A1AT gene (75 variants)

↓ alpha-1-antitrypsinEmphysema

PAS+/diatase resistant globules in hepatocytesEmphysema Commonest inborn metabolic error causing chirrosis/cholestasis

Pathology of the Liver (contd-2)Disease Cause Symptoms Buzzwords Other

Hepatocellular Carcinoma

CirrhosisHepatitis B & C

AflatoxinAlcohol?

Elevated AFP AFP

Metastatic Cancer Breast, Lung, Colon Cancer The most common cancer of the liver

CholangiosarcomaLiver Flukes

Primary Sclerosing CholangitisUlcerative Colitis

Liver Flukes Adenocarcinoma with substantial fibrosis

AngiosarcomaVinyl Chloride

ArsenicThorotrast

Vinyl ChlorideArsenic

ThorotrastVery hemorrhagic

Hepatocellular Adenoma Oral Contraceptives Abdominal Pain (hemorrhage)Rupture Oral Contraceptives Most often in young women taking oral contraceptives

No central veins or portal areas

Focal Nodular Hyperplasia Central Scar Benign hamartoma

Hemangioma Most common benign tumor of the liver

Pathology of the Pancreas

Pathology of the Gallbladder and Biliary TractDisease Cause Symptoms Buzzwords Other

Cholethiasis(Gallstones)

Cholesterol = Age & Obesity(4F’s)

Pigment = Hemolysis & Infection

Majority are assymptomaticExtremely Painful (Angel’s Sign)

Cholesterol Stone or Pigment (bilirubin) stoneComplications: cholecystitis, choledocholethisasis, ascending cholangitis, acute pancreatitis, fistula, porcelin gallbladder

Acute Calculous Cholecystitis Stones in neck or cystic ductCauses chemical irritation and ischemiaMay result in enlarged gallbladder with fibrionus exudates, gangrene, empyema, or porcelin gallbladder

Acute Acalculous Cholecystitis

Post-operative stateTrauma, Burns, Sepsis

Systemic VasculitisS. typhi

Caused by ischemic compromise

Chronic Cholesystitis GallstonesRepeated bouts of acute cholesystitis Rokitansky-Aschoff Fibrosis and variable degree of chronic inflammation

Rokitansky-Aschoff Sinuses – herniation of mucosa (diverticuli)

Cholesterolosis Strawberry Gallbladder Triglyceride & Cholesterol-laden macrophages within mucosal folds

Carcinoma of the Gallbladder CholelithiasisChronic Cholesystitis

Adenocarcinoma with marked desmoplastic reactionUncommon, but poor survival

Carcinoma of the ExtrahepaticBile Ducts

Cholecodal cystsUlcerative colitis

Chronic Biliary Parasites

JaundiceGallstones in about 1/3 of cases Adenocarcinoma with marked desmoplastic reaction

Small, but usually not resectable

Disease Cause Symptoms Buzzwords Other

Acute PancreatitisAlcoholism

Biliary Tract Disease (Gallstones)Idiopathic

Abdominal Pain (after meal or alcohol binge)↑ Pancreatic Enzymes (Amylase & Lipase)

Peripheral vascular collapse & shockHypocalcemia (saponification)

AlcoholismGallstones

Hypocalcemia

Hemorrhagic (Necrotizing) is more serious than interstitial Outcome: Pseudocysts, ARDS, Renal FailurePathology: Proteolytic destruction; blood vessel necrosis (hemorrhage); fat necrosis; neutrophilic inflammation

Pseudocysts Acute or Chronic Pancreatitis

Abdominal PainHemorrhagePeritonitis

Mass

No epithelial lining

Chronic Pancreatitis

AlcoholismIdiopathic

HypercalcemiaOpiates

AlcoholismCalcification

Pathology: Acinar atrophy, fibrosis, inflammation; CalcificationMay cause Diabetes or steatorrhea/malabsorption

Carinoma of the Pancreas(Ductal Adenocarcinoma)

SmokingDiet (Fat & Meat)

2-napthylamine, BenzidineHeriditary & Alcohol = controversial

Weight LossProgressive Jaundice

Migratory Thrombophlebitis (Trousseau)

Trousseau’s SignCA-19

Arises from exocrine duct epitheliumPoor prognosis; Usually in adults > 60More frequent in head of pancreasDiagnosed by CA-19 marker; Treated by Whipple’s operation

Pathology of the KidneyDisease Cause Symptoms Buzzwords Other

Prerenal Acute Renal Failure

Primary Cardiac AbnormalitiesInadequate fluid volume/vascular tone

Arterial Obstruction (bilateral)Abnormal regulation (hepatorenal)

↑ Urine Creatine, ↓ Urine Sodium, ↑ BUN Loss of GFR, Endocrine Function PreservedReversible

Postrenal Acute Renal Failure Urinary ObstructionOliguria then Diuresis if obstruction removed

↓ GFR, ↑ Sodium reabsorptionUrea induced diuresis

Tubule damage over timeReversible

Chronic Renal Failure Numerous

Uremia/AzotemiaCNS dysfunction, Sallow Skin, Nausea, Vomiting

Platelet dysfunction, GI Bleeding, Anemia, Bone Disease, Acidosis, Hyperkalemia

Small/shrunken kidneys

Nephrotic Syndrome

Lipoid Nephrosis (NIL)Membranous Nephropathy

Diabetes MellitusFSGS, SLE

Proteinuria > 3.5 g/day; EdemaHypoalbuminemia <3g/dayHyperlipidemia, Lipiduria

Oval Fat BodiesOnly in glomerular diseaseComplications: Infection, Thrombosis, Atherosclerosis, Deranged Calcium Metabolism

Nephritic Syndrome

Anti GBM DiseasePost Infectious Glomerulonephritis

SLEPolyarteritis Nodosum

Hematuria, Proteinuria (2g/day)Hypertension, RBC Casts

Oliguria, Azotemia

Only in glomerular disease

Uremia

Azotemia, Anemia, Water/Electrolyte ImbalanceAcid-Base Abnormalities

Metabolic/Endocrine AbnormalitiesWater Intoxication

HypersplenismElevated PTH

Lipoid Nephrosis(NIL)

Nephrotic SyndromeNothing on slides

EM shows foot process effacement

ChildrenNormal Looking Slides Steroid Responsive

Focal Segmental Glomerular Sclerosis(FSGS)

HIVHeroin

Nephrotic SyndromeScarred Glomeruli with IgM & C3

Foot Process Effacement

Membranous Glomerulopathy Hepatitis BColon Cancer

Nephrotic SyndromeCapillary Wall Thickening

Subepithelial Deposits Spikes Renal Vein Thrombosis

Acute Post Streptococcal Glomerulonephritis Strep Infection

Nephritic SyndromePMN or Monocyte proliferation

Subepithelial Humps

StrepHumps Complete Recovery

Goodpasture’s Syndrome Nephritic SyndromePulmonary Symptoms (Hemoptosis)

CrescentsSmooth Line

IgA Nephropathy(Berger’s Disease) Mesangial Deposits & Proliferation IgA

Common Most Common Glomerulonephropathy

Pathology of the Kidney (contd)Disease Cause Symptoms Buzzwords Other

Membranoproliferative Glomerulonephritis

Type I

Hepatitis CCryoglobulins

Mesangial ProliferationThickened, Duplicated BM (tramtrax)

LobulesGranular Deposits

TramtraxGranular

Membranoproliferative Glomerulonephritis

Type II

Mesangial ProliferationThickened, Duplicated BM (tramtrax)

LobulesPseudolinear Deposits

TramtraxPseudolinear Causes decreased complement

Rapidly Progressive Glomerulonephritis

(Crescentic GN)

Goodpasture’sANCA

Fibrin in Bowman’s SpaceBreaks in glomerular basement membrane Crescents Rapid progression - fatal

Diabetes Mellitus(Kimmelstiel-Wilson)

Increased mesangial matrixThickened BMKW Nodules

KW Nodules

Systemic Lupus Erythematosus(SLE) Granular Deposits of all types (full house) Young Women

Full House

Chronic Glomerulonephritis

HypertensionUremia

Granular, Scattered small complexesObliteration by collagen protein

Collagen

Acute Pyelonephritis

Enteric BacteriaHematogenous (Staph & E. coli)

Ascending (E. coli, Proteus, Enterobacter)

Fever, Chills, Malaise, CVA TendernessDysuria, Frequency

Painful at end of voiding

CVA TendernessVesicoureteral Reflux

Papillary Necrosis

Usually associated with a cystitis, often undiagnosedPredisposed: Vesicoureteral Reflux, Pregnant, Females, Catheters, DiabeticsCan cause papillary necrosis, pyonephrosis & perinephric abscess

Chronic Pyelonephritis Vesicoureteral RefluxObstruction (catheter)

Interstital & Cortical ScarringMonocytes (chronic inflammation)

Scarred CortexCompound PapillaeThyroidization Casts

Important cause of chronic renal failureThyroidization casts, fibrosis, xanthogranulomatous pyelonephritisStaghorn calculus, foam cells

Acute Drug-InducedInterstital Nephritis

MethicillinThiazidesNSAIDS

Fever, Rash, Hematuria, ProteinuriaMethicillinNSAIDS

Eosinophils

Occurs 2 weeks post exposure, brisk response on drug withdrawalInterstitial edema, tubule necrosis, monocytes & eosinophils

Chronic Analgesic Nephropathy

AcetaminophenAspirin

Phenacetin

Chronic Renal FailureHypertension

Anemia

Papillary NecrosisTransitional Cell Carcinoma

Aspirin inhibits prostaglandin synthesis; acetaminophen binds cellsEspecially problematic with combinations & decreased H2O intake

Ischemic Acute Tubular Necrosis

(ATN)

Septic Shock, Burns, Crush InjuryTrauma, Heat Stroke

Exercise

Patchy necrosis of proximal tubule & ascending limb Patchy Necrosis

ATN is most common cause of ARF & is ReversiblePoor recovery – worse if BM is lost↓ GFR, tubular back leak, tubular obstruction, altered permeability1) Injury 2) Oliguria, Acidosis, ↑ K+, BUN, etc 3) Polyruria, ↓ K+

NephrotoxicAcute Tubular Necrosis

(ATN)

Antibiotics, Anesthetics, Contrast Media, Cyclosporine, Heavy Metals

Organic Solvents, MushroomsConfluent necrosis of proximal tubule Confluent Necrosis

Great prognosisATN is most common cause of ARF & is Reversible↓ GFR, tubular back leak, tubular obstruction, altered permeability1) Injury 2) Oliguria, Acidosis, ↑ K+, BUN, etc 3) Polyruria, ↓ K+

Pathology of the Kidney (contd-2)Disease Cause Symptoms Buzzwords Other

Anion Gap Metabolic Acidosis(Renal Failure) Renal Failure

Increased Respiration No osmol gap

Retained: Sulfuric Acid, Phosphoric AcidOrganic Acid

Anion GapNo Osmol Gap

Sulfuric, Phosphoric, Organic(1 mmHg ↓ pCO2/ HCO3

-)

Anion Gap Metabolic Acidosis(Lactic Acidosis)

Type A= Hypotension/HypoxiaType B = Drugs, Toxins

Increased RespirationNo Osmol Gap

Retained: Lactic Acid

Anion GapNo Osmol Gap

Lactic Acid(1 mmHg ↓ pCO2/ HCO3

-)

Anion Gap Metabolic Acidosis(Toxins)

MethanolEthylene Glycol

Aspirin

Increased RespirationAnion Gap

Osmol Gap (except Aspirin)Formic, Glycolic, Organic

Methanol, Aspirin, Ethylene Glycol

Osmol Gap > 15No osmol gap for aspirinOsmol Gap = 2(Na+) + (Glucose/18) + (UN/2.8)(1 mmHg ↓ pCO2/ HCO3

-)

Anion Gap Metabolic Acidosis(Ketoacidosis)

DiabetesStarvationAlcohol

Increased RespirationOsmol Gap

Retained: Acetoacetic & -Hydroxybutyric Acid

Anion GapOsmol Gap

Acetoacetic & & -HydroxybutyricDiabetes, Starvation, Alcohol

Osmol Gap < 25Osmol Gap = 2(Na+) + (Glucose/18) + (UN/2.8)(1 mmHg ↓ pCO2/ HCO3

-)

No Gap Metabolic AcidosisRenal Tubule Acidosis

Type 1-1(H+ Secretory Defect)

Sjogren, 1º Biliary Cirrhosis, RA, SLE, Thyroiditis, Sickle Cell,

Wilson’s, Analgesics, Toluene, ↑ Ca2+

Bence Jones Proteins, Pyelonephritis

Increased RespirationHypokalemia (K+ secreted instead of H+)

Urine pH > 5.5Urine Anion Gap (UAG) positive

Hyp O kalemia with urine pH > 5.5 (1 mmHg ↓ pCO2/ HCO3-)

No Gap Metabolic AcidosisRenal Tubule Acidosis

Type 1-2(Permeability Defect)

Amphotericin B

Increased RespirationBack diffusion of H+ from lumen

Hypokalemia, Urine pH > 5.5Urine Anion Gap positive

AmphotericinHyp O kalemia with urine pH > 5.5 (1 mmHg ↓ pCO2/ HCO3

-)

No Gap Metabolic AcidosisRenal Tubule Acidosis

Type 1-3(Voltage Dependent)

Volume Depletion (Diarrhea, Laxative Abuse)

Amiloride, Triamterene

Increased RespirationHyperkalemiaUrine pH > 5.5UAG Positive

Hyp ER kalemia with urine pH > 5.5 (1 mmHg ↓ pCO2/ HCO3-)

Either ↓ Na+ delivery to distal tubule or blockage of reabsorption

No Gap Metabolic AcidosisRenal Tubule Acidosis

Type 2

Cystinosis, Tyrosinemia, Wilson’sGalactosemia, Multiple Myeloma

Amyloidosis, SjogrenDrugs & Heavy Metals, ↓ Ca2+

Increased RespirationHypokalemia

Urine pH dependent on amount of HCO3-

Hyp O kalemia Urine pH > 5.5 or < 5.5

UAG negative

(1 mmHg ↓ pCO2/ HCO3-)

Defect in HCO3- reabsorption

Hypokalemia due to ↑ Na+ absorption in distal tubule

No Gap Metabolic AcidosisRenal Tubule Acidosis

Type 4

Aldosterone DeficiencyAddison’s Disease, Diabetes, Nephrosclerosis, Amyloidosis

Sickle Cell, Spironolactone

Increased Respiration Hyp ER kalemia & acidosisUrine pH < 5.5

(1 mmHg ↓ pCO2/ HCO3-)

Hyperkalemia inhibits NH3 synthesis in proximal tubule

Metabolic AlkalosisContraction Alkalosis

Saline Responsive

Diuretics, Sweat Loss (CF)Vomiting, Nasogastric Suction (Decreased Respiration)

Urine Cl < 10 mmoL

Hyp O kalemia with urine pH < 5.5Vomiting

Cystic Fibrosis

(0.6 mmHg ↑ pCO2/ HCO3-)

Excess HCO3-

↑ delivery to distal tubule & aldosterone cause ↑ K+ & H+ secretionVomiting = ↑ delivery of HCO3

-

Metabolic AlkalosisContraction Alkalosis

Saline Resistant

Bartter’s SyndromeAldosterone Secreting Tumor (Conn)

Glucocorticoid Excess

(Decreased Respiration)Urine Cl > 20 mmoL

Hyp O kalemia with urine pH < 5.5Bartter’s Syndrome

(0.6 mmHg ↑ pCO2/ HCO3-)

Excess HCO3-

↑ delivery to distal tubule & aldosterone cause ↑ K+ & H+ secretionBartter’s = defect in Na+ Cl- reabsorption

Respiratory Acidosis

Narcotics & BarbituratesCNS Trauma, COPD, ARDS

Pulmonary InfectionsPneumothorax, Status Asthmaticus

COPDNH3 production NOT increased with chronic compensationAcute = 0.1 ↑ HCO3

-/ mmHg pCO2Chronic = 0.35 ↑ HCO3

-/ mmHg pCO2

Pathology of the Kidney (contd-3)Disease Cause Symptoms Buzzwords Other

Respiratory Alkalosis

Anxiety, Fever, CNS InfectionsHypoxia, Salicylate, PregnancyHyperthyroidism, Liver Failure

VQ Mismatch (Asthma & Pneumonia)

Acute = 0.2 ↓ HCO3-/ mmHg pCO2

Chronic = 0.5 ↓ HCO3-/ mmHg pCO2

Bilateral Kidney Agenesis Stillborn

Unilateral Kidney Agenesis Progressive glomerular sclerosisUncommonHypertrophyProgressive glomerular sclerosis

Hypoplasia Unilateral is more common6 pyramids or less

Ectopic Pelvic Kidney Kinking Kinking ureter causes obstruction and infection

Horseshoe Kidney 90% Lower PoleCommon

90% Lower Pole, anterior to great vesselsCommon

Adult Polycystic Kidney Disease

(ADPKD)Genetic – PKD gene (AD)

Dragging SensationLiver Cysts, also spleen, pancreas & lungBerry Aneurysms, Mitral Valve Prolapse

Hypertension

Dragging SensationBerry Aneurysms

CommonBilateral, grossly enlargedCysts at all levels of nephronAppears in 4th or 5th decades

Infantile Polycystic Kidney Disease

(ARPKD) Genetic – (AR) Perpendicular to capsule

More serious = Perinatal & NeonatalHepatic Fibrosis = Infantile & JuvenileKidneys crossly enlargedDilated collecting ducts radiate perpendicular to capsule

Medullary Sponge Kidney Asymptomatic AsymptomaticMedullary Cysts

Diagnosed radiographicallyCuboidal & transitional epithelial lined

NephronopthisisUremic Medullary Cystic

Disease(UMCD)

Polyuria, PolydipsiaSmall contracted kidneys

Renal Retinal – Retinitis Pigmentosa

Medullary CystsRetinitis Pigmentosa

ChildhoodCortical Tubule Atrophy, Interstitial Fibrosis, Medullary CystsSporadic, Familial Juvenile, Renal-Retinal, Adult OnsetSclerosed glomeruli, tubular atrophy, chronic inflammation

Acquired Cystic Disease Dialysis Bleeding Medullar CystsRenal Cell Carcinoma

Adenomas, Renal Cell Carcinoma in cyst wallsMedullar Cysts - .5-2.0 cm

Simple Cysts Single or multiple, Common

Pathology of the Kidney (contd-4)Disease Cause Symptoms Buzzwords Other

Developmental(Cystic Renal Dysplasia)

Abnormal Metanephric Differentiation

SporadicObstruction Cartilage

Undifferentiated Mesenchyme

Unilateral or BilateralCartilage, Undifferentiated MesenchymeImmature Collecting ductules, Abnormal lobular organization

Cortical Adenoma < 3 cmCommon in elderly, benignTubule origin, cells are lacelikeLess than 3 cm

AngiomyolipomaVessels

Smooth MuscleFat

BenignTuberous sclerosisComposed of vessels, smooth muscle & fat

Oncocytoma Central ScarBenignCentral ScarGranular cytoplasm

Renal Cell Carcinoma TobaccoVon Hippel-Lindau Syndrome

HematuriaCVA, mass, Metastasis

Paraneoplastic (Erythropoietin, PTH, Renin, Steroids, Gonadal Hormones)

TobaccoVon Hippel-Lindau Syndrome

Hematuria> 3 cm

Most common renal malignancy in adults; originates in tubulesVon Hippel-Lindau Syndrome = RCA, Hemangioblastomas, cystsFrequently metastasis before symptoms appear; usually at polesClear cells most common, invades right heart

Wilms Tumor Abdominal MassLarge sphere Blastema Anaplasia = unfavorable

Transitional Cell Carcinoma ObstructionIn renal pelvisPapillary LesionResembles bladder and ureter epithelium

Metastatic TumorsMelanomaLeukemia

Lymphoma