Diseases of Gallbladder & Pancreas

Presented by:
Dr. Tarek ElSharkawy
Pathology Department University of Dammam 2010

Dr.Tarek ElSharkawy

EXTRAHEPATIC BILIARY SYSTEM

Congenital anomalies:

Gall bladder:

may be absent, duplicated or in aberrant location.

Choledochal cyst:

Congenital dilation of the C.B.D., Children. Recurrent abdominal pain and jaundice. Complications: Gall stones, pancreatitis and CBD ca.

in adults

Dr.Tarek ElSharkawy

Cholecystitis

Acute - Calculous - Non-calculous Chronic Acute on top of chronic

Normal Gall Bladder

Velvety dark green mucosa

Thin wall
Dr.Tarek ElSharkawy

Acute Cholecystitis
Calculous Obstructive 90%
Obstruction in the neck of gall bladder or cystic duct by a gall stone

Non-Calculous 10%
Severe septicemia
Non-biliary surgery Severe trauma Torsion of gall bladder Diabetes Mellitus Burns

Recent childbirth Dehydration

Dr.Tarek ElSharkawy

Acute Cholecystitis Gross

Gall bladder distended and tense Serosa: Congestion, fibrinous exudate & hemorrhage Mucosa: Congested and bright red Lumen: Pus, green bile, stones
Wall remarkably thick (edema)

Dr.Tarek ElSharkawy

Acute Cholecystitis
Neutrophilic infiltration Focal or extensive mucosal ulceration

Striking edema and hemorrhage

Acute Gangrenous Cholecystitis Widespread gangrenous necrosis Frank abscess in wall Rupture into peritoneal cavity
Dr.Tarek ElSharkawy

Gall Bladder Empyema

Rare Bacteria invade gall bladder wall Complete obstruction of cystic duct

Cavity distended by cloudy purulent fluid

Dr.Tarek ElSharkawy

Repeated Acute Cholecystitis

Long Standing Stones

Chronicity
Vague symptoms Female, Fertile, Fatty, Forty or fifty Abdominal distension Epigastric discomfort (fatty meals)
Shaggy exudative serosa adhesions

Size: Normal or contracted Mucosa: Intact or focally ulcerated, atrophic Stones usually seen in lumen
Thick fibrous wall
Dr.Tarek ElSharkawy

Chronic Cholecystitis
Mononuclear cell infiltration Mucosa: Normal/atrophic/hyperplastic/metaplastic Fibrosis Muscle hypertrophy Rokitansky Aschoff sinuses: Irregular tubular mucosal structures dipping deep into the wall up to muscularis
Atrophic mucosa

Muscle hypertrophy
Dr.Tarek ElSharkawy

Cholelithiasis Gall Stones

Formed from bile constituents (cholesterol, bile pigments, calcium

salts & other organic components)

Site: Gallbladder
Extrahepatic biliary passages Larger Intrahepatic bile ducts

Imaging:
Cholesterol stones (radiolucent filling defects) Ca salts renders gallstones radio-opaque)

Dr.Tarek ElSharkawy

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Gall Stones Types

Pure (10%) - Pure cholesterol

- Pure bile pigment (bilirubin) - Calcium carbonate

Mixed (80%) - Cholesterol

- Bile pigment - Calcium - Proteins Cholecystitis invariably present

Combined (10%)
Pure stone nucleus Mixed stone shell or vice versa
Dr.Tarek ElSharkawy

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Gall Stones Predisposing Factors 4F

Geographic: Entire western world Genetic: Family members of gall stone patients Age: Incidence increases above 40, presentation 50s or 60s Sex: Twice more frequent in females ( Fertile ) Drugs: Estrogen therapy or oral contraceptives Obesity: Increased cholesterol synthesis and excretion(Fatty) Diet: Deficiency of dietary fibers Hemolytic anemia (pigment stones) GIT diseases that interrupt enterohepatic circulation (Crohns disease, ileal resection, ileal bypass surgery)
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Dr.Tarek ElSharkawy

Pure Gall Stones

Cholesterol
Number Color Size Shape Single (nearly always) Yellow Few mm- 5 cms Round/oval

Pigment
Multiple Shiny Jet Black Few mms (rice grain) Irregular

Calcium
Multiple Gray-white Few mms Irregular

Surface Consistency
Location Cut surface Association X-ray

Smooth Firm

Irregular Friable

Multifaceted Hard
Gall bladder

Gall bladder (exclusive) Hartmanns Pouch Commonly bile ducts Radial crystals Cholesterolosis (Fatty fertile females forty) Radiolucent Glassy, soft Sterile bile (hemolysis) 50 % Radiopaque

Radiopaque

Dr.Tarek ElSharkawy

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Cholesterolosis
Bile supersaturated with cholesterol (no hypercholesterolemia)
Small yellow mucosal flacks Strawberry Gall Bladder

cholesterol-laden macrophages in mucosa or epithelium

Dr.Tarek ElSharkawy

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Mixed Stones
Number Color Size Shape Outer surface Consistency Location Multiple (formed in crops) Tan to gray-black 1-2 cm Multifaceted Smooth Firm Gall bladder

Cut surface Associated with

X-Ray

Laminated Cholecystitis
Hollow Ring
Concentric rings of dark pigment layer and pale white calcium layer

Hollow Ring
Dr.Tarek ElSharkawy

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Gall Stones Clinical

50% asymptomatic accidentally discovered (silent) Symptomatic (only when complicated)

Cholecystitis Mucocele / Empyema Choledocholithiasis (stone in CBD) Biliary fistula Gall stone ileus Gall bladder cancer

Suppurative

Chronic Obstruction
Dr.Tarek ElSharkawy

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Gall Stones Complications Perforation

With or without stones

Acute Suppurative Peritonitis

Dr.Tarek ElSharkawy

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Gall Stones Complications Obstruction

Hydrops Empyema
Common hepatic duct

Obstructive Jaundice Abscess Perforation Fistula (duodenum or intestine)

Pancreatitis

Cholecystoenteric fistula Intestinal obstruction (gall stone ileus)

Dr.Tarek ElSharkawy

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Tumors of Biliary System

Benign: Papilloma, adenoma, adenomyoma, fibroma, lipoma, myxoma, hemangioma Malignant Carcinoma of gall bladder Carcinoma of bile ducts & ampulla of Vater

Dr.Tarek ElSharkawy

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Gall Bladder Carcinoma Etiology

Cholecystitis (particularly porcelain gall bladder) Cholelithiasis Genetic (higher incidence in certain populations living in then same geographical area) Chemical carcinogens: Methyl cholantherene Nitrosamines Pesticides Rubber industries

Dr.Tarek ElSharkawy

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Gall Bladder Carcinoma

Site: Commonest is fundus, followed by neck 2 gross types: Infiltrating

Fungating

Microscopy
Adenocarcinoma (90%)
Papillary or infiltrative Most non-mucin producing (some colloid) Well or poorly differentiated
Infiltrative (thick leathery wall)

Adenocarcinoma

Squamous cell carcinoma (5%)

Epithelial metaplasia

Adenosquamous carcinoma
Dr.Tarek ElSharkawy

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Carcinoma of bile ducts & ampulla of Vater

More in males (unlike other biliary diseases) 6th decade No association with gall stones Associated with
Ulcerative colitis Sclerosing cholangitis Bile duct parasites: Fasciola hepatica liver fluke Ascaris lumbricoides Clonorchis sinensis

Dr.Tarek ElSharkawy

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Lies obliquely in concavity of duodenum Elongated structure 15 cm long, 100 gm

Exocrine Part

PANCREAS
Dr.Tarek ElSharkawy

Endocrine Part

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Causes stomach to produce acid (Growth hormone inhibiting hormone) Produced in pancreatic islets and CNS

Endocrine portion
Ductal cells Acinar cells digestive enzymes Islets of Langerhans

Exocrine portion

Proteases (trypsin and chymotrypsin): Protein digestion Amylase: Carbohydrate digestion Lipase: Fat digestion

Inhibits release of growth hormone from anterior pituitary

Dr.Tarek ElSharkawy

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Glucagon
Glycogen

Insulin

Glucose

Dr.Tarek ElSharkawy

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Diseases of Exocrine Pancreas

Cystic Fibrosis (fibrocystic disease)- MUCOVISCIDOSIS Pancreatitis (acute and chronic) Tumors and tumor-like lesions

Mucoviscidosis( Viscid mucus secretion Obstruct pancreatic ducts,sweat gland &salivary gland ducts )

Exocrine part is divided into rhomboid lobules composed of acini Separated by thin fibrous septa containing blood vessels, nerves, and ducts
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Dr.Tarek ElSharkawy

Acute Pancreatitis

Present clinically with acute abdomen serum amylase in first 24 hours serum lipase after 3-4 days (more specific)

Enzymatic fat necrosis (peripancreatic and omental) Released fatty acids combine with calcium = Insoluble calcium soaps (whitish-yellow calcification)
Release of pancreatic enzymes Duct rupture

Gall stone or metaplasia

Autodigestion of pancreas

Dr.Tarek ElSharkawy

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Acute Pancreatitis Causes

Alcoholism In >80% of cases Cholelithiasis Trauma Ischemia Shock Extension of inflammation from adjacent tissues Blood-borne bacterial infections and viral infections Drugs (thiazides, sulfonamides, oral contraceptives) Hypothermia Hyperlipoproteinemia Hypercalcemia due to hyperparathyroidism
Dr.Tarek ElSharkawy

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Acute Pancreatitis Gross

Early: Swollen and edematous Black-red hemorrhagic necrosis

Chalky whitish-yellow nodules of fat necrosis

Peritoneal cavity typically contains blood-stained ascitic fluid White flecks of fat necrosis can involve omentum. mesentry & peripancreatic tissue

Dr.Tarek ElSharkawy

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Acute Pancreatitis Microscopy

Fat necrosis

Neutrophilic infiltration (acute inflammation)

Dystrophic calcification on fat necrosis

Necrosis of pancreatic lobules and ducts Necrosis of arteries with areas of hemorrhage Fat necrosis Inflammatory infiltrate, mostly polymorphs, around necrosis and hemorrhage
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Dr.Tarek ElSharkawy

Acute Pancreatitis

High mortality (20-30%) Cause of death: Hypotensive shock Infection Acute renal failure DIC

Dr.Tarek ElSharkawy

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Acute Hemorrhagic Pancreatitis Acute Pancreatic Necrosis

Severe form of acute pancreatitis Acute inflammation with fat necrosis and hemorrhage In and around the pancreas

Dr.Tarek ElSharkawy

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Chronic Relapsing Pancreatitis

Repeated mild and subclinical pancreatitis progressive destruction of pancreas Weight loss and Jaundice Etiology: alcohol consumption Common bile duct stones or stenosis Familial hereditary pancreatitis (uncommon)

Dr.Tarek ElSharkawy

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Chronic Relapsing Pancreatitis Gross

Pancreas enlarged, firm and nodular Cut surface smooth gray (loss of lobulations) Foci of calcification Tiny concretions or larger stones (frequent) Pseudocysts may be seen

Fibrotic and hard Main duct is dilated and filled with calcified secretions

Dr.Tarek ElSharkawy

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Chronic Relapsing Pancreatitis Microscopy

Ducts: Fibrosis of wall Luminal protein plugs or stones Obstruction Squamous metaplasia Mild dilatation of some inter and intra-lobular ducts Acini: Atrophy with increase in interlobular fibrous tissue Chronic inflammatory infiltrate around lobules and ducts Islet tissue (involved in late stages only)

Dr.Tarek ElSharkawy

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Chronic Pancreatitis

Duct dilatation

Loss of islets = Diabetes Loss of acini = Steatorrhea (fat in stools)

Chronic inflammatory cells

Dr.Tarek ElSharkawy

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Pancreatic Carcinoma
Predisposing Factors: Smoking Diet ( calories & protein) Chemicals ( naphthylamine, benzidine, nitrosamines) Diabetes Mellitus Hereditary Chronic Pancreatitis Gallbladder diseases

Body

Tail

Frequency: Head Body Tail

Head 7o%

Dr.Tarek ElSharkawy

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Ductal Adenocarcinoma
Serous & Mucinous

Head

Extension to ampulla and common bile duct

Liver

Body and Tail

Spleen Hard fixed mass with poorly defined infiltrative margin Silent growth and early metastases Multiple thrombosis in superficial and deep veins

Progressive obstructive jaundice (early detection)

Dr.Tarek ElSharkawy

Migratory Thrombophlebitis

Trausseau sign

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Ductal Adenocarcinoma
Invasive disordered malignant glands Usually poorly differentiated

Dr.Tarek ElSharkawy

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Islet Cell Neoplasms Adenoma/Carcinoma

Insulinoma ( cells) Insulin 5-10% malignant Glucagonoma ( cells) Glucagon Gastrinoma (G cells) Gastrin Somatostatinoma ( delta cells) Somatostatin
Smooth homogeneous appearance

60-90% malignant

Sharply circumscribed margins

Behavior is not predicted by morphology, tumors < 2 cm tend to behave in a benign fashion
Dr.Tarek ElSharkawy

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Islet Cell Adenoma

Encapsulated

Similarity of cells to normal

Nests of homogenous endocrine cells Round uniform nuclei and granular eosinophilic cytoplasm

Dr.Tarek ElSharkawy

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Insulinoma
Hypoglycemia Mental confusion Loss of consciousness

Glucagonoma
Mild diabetes mellitus Anemia Necrotizing skin erythema

Somatostatinoma
compress neighboring cells
Diabetes mellitus Steatorrhea Hypochlohydria

Gastrinoma
Gastric hyperacidity Peptic ulceration

Usually have Zollinger-Ellison Syndrome

Gastric Hyperacidity Gastrinoma

Duodenum with scattered ulcers

(also stomach and jejunum)

Dr.Tarek ElSharkawy

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Diabetes Mellitus (DM)

Metabolic disorders of glucose utilization Characterized by:

Glycosuria Hyperglycemia

Dr.Tarek ElSharkawy

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Dr.Tarek ElSharkawy

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Primary DM
Type I (Juvenile, insulin dependent) 10-20% Type II (Adult, non-insulin dependent) 80-90%

Secondary DM
Chronic pancreatitis Pancreatectomy Hormone-producing tumors Drugs (corticosteroids) Hemochromatosis
Pituitary Adenoma Acromegaly growth hormone

Hyperthyroidism

Cushing Syndrome cortisol

Dr.Tarek ElSharkawy

Glucagonoma

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Hemochromatosis
iron absorption
iron is stored in tissues, specifically liver, heart, pancreas

Arthritis Liver (enlargement, cirrhosis, cancer, liver failure) Pancreas (possibly causing diabetes) Heart (arrhythmia or congestive heart failure) Abnormal skin pigmentation (gray or bronze) Thyroid deficiency/adrenal glands damage

Iron deposited in Kupffer cells and hepatocytes

Dr.Tarek ElSharkawy

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Primary Diabetes Mellitus

Type I

Type II

>30 <20 Normal weight Severe & absolute lack of insulin

cell mass

Autoimmunity (anti-insulin antibodies) Genetic susceptibility Environmental (viruses, chemicals) Patient depends on insulin for survival

Relative insufficiency of insulin relative to glucose load And / or Inability of peripheral tissues to respond to insulin (insulin resistance)

Dr.Tarek ElSharkawy

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Insulin Resistance

? in number of insulin receptors

Dr.Tarek ElSharkawy

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Islets Changes in Diabetes

in number and size of islets (Type I) cell degranulation and depletion of insulin secretory stores (Type I) Insulitis: Lymphocytic infiltration & edema of islets (Type I) Pink material between cells Amyloid deposition (Type II) Fibrosis

Insulitis

Normal Amyloid Deposits

Dr.Tarek ElSharkawy

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Type II Diabetes

Thirst

Polyuria

Nocturia

Blurring of vision

Weight loss

Malaise

Dr.Tarek ElSharkawy

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Complications of Diabetes CVS

Atherosclerosis Hypertension

Myocardial infarction
Gangrene of limbs (ischemia)

Diabetic Foot
Dr.Tarek ElSharkawy

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Complications of Diabetes CNS

Cerebral Hemorrhage Infarction

Coma (Ketosis) Peripheral Neuritis

Dr.Tarek ElSharkawy

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 fatty acids

Ketoacids

Glycogenolysis Ketogenesis

Dr.Tarek ElSharkawy

Acidic pH of blood (toxic)

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Complications of Diabetes Ocular

Diabetic Retinopathy
Glaucoma Cataract
Macula Optic Disc Hemorrhage Microaneurysms

Cataract Opacification of lens Progressive in insoluble proteins

Rupture Multiple retinal detachments Blindness

Dr.Tarek ElSharkawy

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Complications of Diabetes Respiratory

Bronchitis and Bronchopneumonia Lung Abscess and Gangrene

Pulmonary TB

Dr.Tarek ElSharkawy

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Complications of Diabetes Diabetic Nephropathy

Glomerulosclerosis

Nephrotic Syndrome
Proteinuria Hypoalbuminemia Edema

Apex of pyramid

Pyelonephritis Necrosis of Renal Papillae Renal arteriolosclerosis

Chronic Renal Failure

Dr.Tarek ElSharkawy

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Diabetic Glomerulosclerosis Nodular Kimmelsteil-Wilson Lesion

Nodular deposits of matrix within mesangial core

Obliterating capillary lumen

In periphery of glomerulus

The only lesion specific for diabetes mellitus, yet only seen in 10-35% of cases
Dr.Tarek ElSharkawy

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Diabetic Glomerulosclerosis Diffuse

Linear hyalinized thickening of basement membrane Diffuse mesangial matrix + mesangial cell proliferation

Normal

Dr.Tarek ElSharkawy

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Diabetic Glomerulosclerosis Exudative

Hyaline deposits with eosinophilic material in capillary lumen and glomerular capsule (hyaline cap) or Bowmans capsule (capsular drop)

Hyaline cap

Massons trichrome Capsular drop

Dr.Tarek ElSharkawy

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Complications of Diabetes Skin

liability to Infection (Carbuncle/Cellulitis) Stress of infection insulin requirements

Dr.Tarek ElSharkawy

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THANK YOU

Dr.Tarek ElSharkawy

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