DSA10 - Liver III: Non-Neoplastic Bile Duct, Gallbladder, and Pancreas Pathology

Portal Vein Obstruction and Thrombosis

Define Condition:

PRE-HEPATIC

-Hx:

> Idiopathic

> Cirrhosis (portal venous stasis)

> Hypercoagulable states (myeloproliferative diseases - Ex: PV)

> Malignancy (hypercoagulable state)

> Inflammatory processes (pancreatitis, sepsis)

-Sx/PE:

> Asx

> Sx = Portal HTN & Abd Pain; NO HEPATOMEGALY

Budd-Chiari Syndrome

Define Condition:

Hepatic venous outflow obstruction d/t thrombosis OR compression of hepatic vein; POST-HEPATIC

-Hx: Hypercoagulable States

> Polycythemia Vera

> HCC

> OCP

> Pregnancy

-Path:

-Sx/PE:

> Abd Pain

> Ascites

> Hepatomegaly

-Dx:

> Gross:

>> Hepatic Congestion

>> Hepatomegaly

>> Tense Capsule

> Biopsy:

>> Severe Centrilobular congestion and necrosis

>> Passive Liver Congestion = NUTMEG LIVER

>> Major veins may have thrombi

Large Bile Duct Obstruction

Define Condition:

-Hx:

> Extrahepatic cholelithiasis (Gallstones)

> Tumor Obstruction (biliary or pancreatic)

> Postsurgical strictures

-Dx:

> Biopsy:

>> Portal Tract Edema

>> Neutrophils

>> Bile Ductular reaction/proliferation

Primary Biliary Cholangitis (PBC)

Define Condition:

Autoimmune disease causing nonsuppurative, inflammatory destruction of small and medium intrahepatic bile ducts

-Hx:

> Mostly in FEMALES

> Age = 40-50 y/o

> A/w Autoimmune diseases (Sjogren's, Hashimoto, RA, Celiac Disease)

-Path: T-cell mediated destruction of interlobular bile ducts --> Duct injury ==> Retention of bile salts ==> HEPATOCYTE INJURY = CIRRHOSIS

-Sx/PE:

> Weakness

> Fatigue

> Pruritus (d/t bile salts)

> Xanthelasma (d/t hypercholesterolemia)

> Jaundice

> Malabsorption of fat-soluble vitamins ==> Osteoporosis (d/t Vit D deficiency)

-Dx:

> Labs:

>> Elevated CB (intrahepatic cholestasis)

>> Elevated ALP

>> Elevated GGT

>> Antimitochondrial Abs (AMAs) in 90-95% pts

> Gross: Cirrhosis (End Stage)

> Biopsy:

>> Lymphoplasmacytic inflammation +/- granulomatous inflammation (florid duct lesion)

--> Loss of small intrahepatic ducts

--> Cholestasis/Cirrhosis

-Tx:

> Ursodeoxycholic acid (Ursodiol) = natural occurring bile acid (slows progression)

> Liver Transplant

-Prog: Cirrhosis --> Risk of HCC

Primary Sclerosing Cholangitis (PSC)

Define Condition:

Autoimmune condition causing inflammation and obliterative fibrosis of intrahepatic and extrahepatic bile ducts

-Hx:

> More in MALES

> Strong a/w Ulcerative Colitis

-Sx/PE:

> Fatigue

> Pruritus

> Jaundice

-Dx:

> (+) MPO-ANCA/p-ANCA (80%)

> Gross:

>> End-Stage = Cirrhosis

> Biopsy:

>> Large bile ducts with acute & chronic inflammation

>> Small ducts have little inflammation but show circumferential "onion skin" fibrosis and atrophic duct lumen --> duct obliteration --> fibrosis/cholestasis ==> Cirrhosis

> Cholangiogram: confirms Dx

>> ERCP & MRCP

>> Shows alternating strictures and dilation "beading" of intra- and extrahepatic bile ducts

-Prog:

> Chronic Pancreatitis/Cholecystitis d/t extrahepatic bile duct involvement

> Median Survival = 10-12 yrs

> Increased risk of Cholangiocarcinoma and HCC

Biliary Atresia

Define Condition:

Complete or partial obstruction of extrahepatic biliary tree that occurs in first 3 months of life

-Hx:

> Fetal = congenital defect

> Perinatal (MC) = INFLAMMATION

-Sx/PE:

> Perinatal:

>> Persistent Jaundice after 2 wks of life

>> Dark Urine

>> Acholic (pale) Stools

>> Hepatomegaly

-Dx:

> Labs:

>> Elevated CB

>> Elevated GGT

> Biopsy

>> Perinatal:

>>> Inflammation

>>> Fibrosing stricture of hepatic or CBD

> Imaging:

>> US = A/w Absent/Abnormal Gallbladder

-Tx:

> MC reason for pediatric liver transplant

-Prog:

> MCC = DEATH from Liver Disease in early childhood

Cholelithiasis (CHOLESTEROL Gallstones)

Define Condition:

Yellow/Yellow-brown stones in gallbladder

-Hx:

> MC in Western countries

> Risks that Increase Cholesterol:

>> Increased ESTROGEN

>>> Female (older)

>>> OCPs

>>> Pregnancy (biliary peristalsis --> Increase stasis)

>> Obesity (Increase total body cholesterol)

>> Rapid Weight LOSS (Increase cholesterol metabolism)

-Dx:

> Labs:

>> Low Cholesterol

>> Low Bile Salts

>> HIGH BILE STASIS ==> Supersaturation of bile w/ cholesterol --> precipitation of cholesterol in bile

> Imaging:

>> XRay = RADIOLUCENT

-Tx:

> Cholecystectomy

> Alternative = Ursodeoxycholic Acid (Bile Acid that causes less secretion of cholesteroll into bile; may dissolve cholesterol stones)

-Prog:

> Biliary Colic

> Choledocholithiasis

> Acute/Chronic Cholecystitis

> Porcelain gallbladder

> Ascending/Acute Cholangitis

> Gallstone Ileus

Cholelithiasis (PIGMENT Gallstones)

Define Condition:

Stones from UCB in bile (insoluble in H2O)

-Hx:

> Cirrhosis (less bile salts --> less soluble bilirubin)

> Crohn's Disease (Ileum inflammation --> less bile salt reabsorb)

Black Stones

-Path: Chronic Hemolysis (HS and SCD = RBC Turnover)

> Increased UCB --> Calcium Bilirubinate

-Dx: Imaging

> RADIOPAQUE d/t Calcium

Brown Stones

-Hx:

> E. coli

> Clonorchis sinensis

-Path: Infection

> Increased Beta-glucuronidase --> converts CB to UCB ==> Calcium Bilirubinate + Increased FAs

-Dx: Imaging

> RADIOLUCENT (Calcium SOAPS)

-Tx:

> Cholecystectomy

> Alternative = Ursodeoxycholic Acid (Bile Acid that causes less secretion of cholesteroll into bile; may dissolve cholesterol stones)

-Prog:

> Biliary Colic

> Choledocholithiasis

> Acute/Chronic Cholecystitis

> Porcelain gallbladder

> Ascending/Acute Cholangitis

> Gallstone Ileus

Biliary Colic

Define Cholelithiasis Complication:

-Sx/PE: Episodic RUQ Pain

> Radiate to Right Shoulder Blade

-Hx: After eating Fatty Meals

-Path:

> D/t gallbladder contracting against stone lodged in cystic duct

> CCK stimulates gallbladder contraction

Choledocholithiasis

Define Cholelithiasis Complication:

Common bile duct (CBD) stone causing biliary obstruction

-Hx: Cholelithiasis

-Path: Increased ALP --> Increased AST/ALT

-Sx/PE: Obstructive Jaundice (d/t Increased ALP/GGT +/- Increased CB)

-Prog: Cholangitis

Acute CALCULOUS Cholecystitis

Define Cholelithiasis Complication:

Stones in cystic duct causing bile obstruction

-Hx:

> 90% of Acute Cholecystitis

> MC Major complication of Gallstones

-Path:

> Gallbladder squeezes --> constricts blood supply (ischemia)

> Bile stasis --> release of inflammatory enzymes --> damages gallbladder mucosa ==> Chemical irritation of gallbladder epithelium

> Distended gallbladder wall ---> Release PGs ==> Inflammation

-Sx/PE:

> RUQ Pain (radiates to right scapula)

> (+) Murphy's Sign (inspiratory arrest on RUQ Palpation d/t pain)

> Fever

> Nausea

> Vomiting

-Dx:

> Gross:

>> Distension/edema of gallbladder

>> Bright red/blotchy, bluish-purple color (subserosal hemorrhage)

> Thickened gallbladder wall

> Biopsy:

> Acute inflammation (Neutrophils)

> Edema

> Mucosal erosion and hemorrhage

-Tx: Most Frequent indication of EMERGENT CHOLECYSTECTOMY

-Prog: If left untreated = RISK OF RUPTURE

Acute ACALCULOUS Cholecystitis

Define Cholelithiasis Complication:

Acute inflammation of gallbladder WITHOUT gallstones

-Hx:

> Older pts AFTER non-biliary tract surgery

-Path: D/t bile stasis and ischemia

> Critically ill pts in ICU (long fasting, total parenteral nutrition) --> Gallbladder not stimulated to empty ==> Bile stasis & build up ==> Inflammation

-Sx/PE:

> RUQ Pain (radiates to right scapula)

> (+) Murphy's Sign (inspiratory arrest on RUQ Palpation d/t pain)

> Fever

> Nausea

> Vomiting

-Dx:

> Gross:

>> Distension/edema of gallbladder

>> Bright red/blotchy, bluish-purple color (subserosal hemorrhage)

> Thickened gallbladder wall

> Biopsy:

> Acute inflammation (Neutrophils)

> Edema

> Mucosal erosion and hemorrhage

-Tx: 5-10% of Cholecystectomies done for acute cholecystitis

-Prog: If left untreated = RISK OF RUPTURE

Chronic Cholecystitis

Define Cholelithiasis Complication:

Chronic inflammation of gallbladder

-Path: Chemical irritation from long standing cholelithiasis with or without superimposed bouts of acute cholecystitis

-Dx:

> Gross: Nearly normal to thickened gallbladder wall (may seem shrunken d/t marked fibrosis)

> Biopsy: Rokitansky-Aschoff sinuses (pseudodiverticula or herniation of gallbladder mucosa into muscular wall)

-Prog: Porcelain gallbladder

Porcelain Gallbladder

Define Cholelithiasis Complication:

Calcified gallbladder d/t chronic cholecystitis

-Path: Chronic inflammation, fibrosis & dystrophic calcification --> SHRUNKEN & HARD GALLBLADDER

-Dx: Incidental finding on Imaging

-Tx: Prophylactic Cholecystectomy

-Prog: Risk of Gallbladder Carcinoma

Ascending Cholangitis (Acute Cholangitis)

Define Cholelithiasis Complication:

Infection of bile ducts d/t obstruction leading to stasis/bacterial overgrowth

-Path: Stone blocks flow of bile --> GI bacteria able to ascend biliary tree

-Sx/PE:

> Charcot Triad

>> Jaundice

>> Fever

>> Abd Pain

> Reynolds Pentad (SEPTIC!)

>> Jaundice

>> Fever

>> Abd Pain

>> AMS

>> Shock (Hypotension)

-Dx:

> Labs:

>> Increased WNC

>> Cholestasis = Increased ALP = Increased AST/ALT

>> Increased Tbili & CB

>> Gram (-): E. coli, Klebsiella, Enterobacter

> Biopsy: Neutrophils in bile duct lumen

-Tx:

> Abx

> Biliary Drainage

Gallstone Ileus

Define Cholelithiasis Complication:

Gallstone obstructs small bowel

-Path:

> Cholecystits w/ fistual between gallbladder & small bowel --> stone enters GI lumen ==> OBSTRUCTION at ILEOCECAL VALVE (narrowest point)

> Pneumobilia (air in biliary tree) = Fistula --> AIR from intestine fills biliary tree

-Dx: Imaging (XRAY)

> Rigler Triad = Pneumobilia, SBO, Gallstone outside gallbladder (ectopic)

Acute Pancreatitis

Define Condition:

Acute inflammation of pancreas d/t autodigestion of pancreas by pancreatic enzymes that are prematurely activated

-Hx: ("I GET SMASHED")

> Idiopathic

> Gallstones (mostly FEMALES)

> Chronic Excessive EtOH (mostly MALES) Consumption

> Trauma

> Steroids

> Mumps

> Autoimmune

> Scorpion Sting

> Hypercalcemia/Hypertriglyceridemia

> Recent ERCP

> Drugs (Sulfa, Protease Inhibitors)

-Path:

> Alcohol:

>> Increased Pancreatic Exocrine secretion ==> PROTEIN PLUGS

>> Increased contraction of Sphincter of Oddi (prevents enzymes from leaving pancreas)

>> Induces oxidative stress in acinar cells (membrane damage)

>> May deliver proenzymes to lysosomal compartment ==> Intracellular activation of enzymes

> HyperTGs (>1000): TGs hydrolyzed into FFAs in pancreas --> Acinar cell injury

> Microvascular leakage from cytokines & Inflamm mediators ==> EDEMA/Hypovolemia --> SHOCK/Organ Fail

> Lipase ==> FAT NECROSIS

> Proteolytic destruction of pancreatic parenhcyma/blood vessels --> INTERSTITIAL HEMORRHAGE

-Sx/PE:

> Mild/Self-Limiting Epigastric Abdominal Pain

> EMERGENT = Constant, INTENSE Epigastric Pain radiating to back

>> Nausea/Vomiting

>> Skin Changes

>>> Cullen's Sign = Ecchymoses/Bruising around umbilicus

>>> Grey Turner's Sign = Ecchymosis in 1 or both flanks

-Dx:

> Labs:

>> LIPASE = MOST SENSITIVE/SPECIFIC (elevated for 8-14 days)

>> Amylase = normal by 3-5 days

>> Lipase & Amylase elevated (3x ULN) 4-12 hrs after pain

> Gross:

>> Fat Necrosis

>> Hemorrhage

> Biopsy:

>> Interstitial Edema

>> Fat Necrosis

>> Hemorrhage

>> Parenchymal Necrosis

-Tx:

-Prog:

> POOR if progresses to EMERGENT

> Acute Resp Distress Syndrome (ARDS)

> DIC (inflammation/endothelial injury --> consumption of clotting factors)

> Sepsis

> Pancreatic pseudocyst

> Hypocalcemia - POOR PROGNOSTIC FACTOR (precipitation of Ca soaps w/ fat necrosis)

Pancreatic Pseudocyst

Define Condition:

Encapsulated collection of fluid formed by fibrous/granulation tissue surrounding liquefactive necrosis and pancreatic enzymes (no epithelial lining of cyst)

-Hx: Weeks after episode of Acute Pancreatitis

-Prog: Usually resolves spontaneously but may be infected & ruptured --> release of enzymes into abdominal cavity

Chronic Pancreatitis

Define Condition:

Prolonged pancreatic inflammation --> Irreversible destruction of exocrine pancreas + Fibrosis

-Hx:

> MCC = Chronic Excess EtOH use

> May be Idiopathic

> 25% have GENETIC PREDISPOSITION = Cystic Fibrosis, SPINK1 (encodes trypsin inhibitor) mutation

> Repeated episodes of Acute Pancreatitis

> More in MALES

-Path: Chronic Pancreatic Injury --> Inflammatory Mediators (TGF-Beta & PDGF) ==> Activation/Proliferation of Pancreatic Stellate Cells --> More Periacinar Myofibroblasts ==> Collagen Deposition & Fibrosis

-Sx/PE:

> Chronic/recurrent Abd Pain

> Steatorrhea & Malabsorption

>> Pancreatic Burnout of enzymes (Pancreatic Insufficiency) --> Less Proteases/Lipases --> Can't Absorb Fat ==> Fat Soluble Vitamin Deficiencies

-Dx:

> Imaging (CT): Multiple pancreatic calcifications

> Gross:

>> FIRM w/ dilated ducts

>> Calcified concretions

> Biopsy:

>> Parenchymal fibrosis

>> Smaller size/number of acini --> Acinar Loss

>> Variable dilation of ducts +/- Inspissated concretions

>> Chronic Inflammation

>> Eventual loss of islet of langerhans

-Tx:

-Prog:

> Secondary D2M (loss of Islet of Langerhans)

> Pancreatic Insuffiency

> Pancreatic Pseudocysts

> Increased risk of Pancreatic Carcinoma