Pancreatitis and Islet Cell tumors

Pancreatitis
1) Periductal Obstruction -> necrosis
2) Perilobar Necrosis due to ischemia
3) panlobular necrosis with hemorrhage from vessels

Interstitial inflammation, edema, proteolysis, fat necrosis, hemorrhage

PANCREAS ARISE FROM 2 DUODENAL FOLDS AS DORSAL AND VENTRAL PANCREAS THAT FUSE TO BECOME ONE

Activation of trypsinogen an important triggering event in pancreatitis

ACUTE PANCREATITIS
- SYSTEMIC ORGAN FAILURE
SHOCK
ARDS
ACUTE RENAL FAILURE
- PANCREATIC ABSCESS
- PANCREATIC PSEUDOCYST
- DUODENAL OBSTRUCTION

Pseudocyst - unilocular; multiloculation suggests a neoplastic cyst
- virtually all arise after acute/chronic pancreatitis
Cyst
- lined by flattened cuboidal epithelium with clear glycogen rich cytoplasm

Pancreatic Carcinoma
- virtually all cancers begin in the ductal epithelium

60% head of pancreas, earlier detection
15-20% body
5% tail

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ENDOCRINE PANCREAS
ALPHA - GLUCAGON
BETA - INSULIN
DELTA - SOMATOSTATIN
PP - PANCREATIC POLYPEPTIDE
small dark granules present in islets as well as in exocrine pancreas

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CHRONIC PANCREATITIS, POSSIBLE CAUSES
1) DUCTAL OBSTRUCTION BY CONCRETIONS
2) SECRETED PROTEINS - LITHOSTATHINE
3) OXIDATIVE STRESS
EtOH induced
- free radical in acinar cells
- abnormal protein secretion
- acinar cell necrosis, inflammation, fibrosis
- interstitital fibrosis
ACUTE PANCREATITIS -> NECROSIS -> FIBROSIS
also, abnormal intrapancreatic lipid metabolites

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Islet cell tumors
1) hyperinsulinism (insulinoma) - Beta cell tumor
2) hypergastrinemia / Zollinger-Ellison syndrome
3) multiple endocrine neoplasia

MEN I (for 1 and 2)
1) hyperinsulinism
- blood glucose < 50 mg/dL hypoglycemic attack
- CNS manifestation
- resolve with increased glucose
- high insulin glucose ratio
2) gastrinomas
- hypersecretion of gastrin with severe peptic ulceration
ulcer (90~95%) duodenal : gastric = 6 : 1
- diarrhea
- in duodenum, peripancreatic soft tissues or pancreas
Treatment - control of gastric acid secretion by histamine (H2) receptor blockers, resection

3) other islet cell tumors
alpha cell tumor - glucagonomas
delta cell tumor - somatostatinoma
VIPomas - VIP
pancreatic carcinoid tumors - serotonin

Liver, general dz characteristics

LFT enzymes

Liver Necrosis

Liver Disease Characteristics

Vascular Liver Dz

Acute vs Chronic Hepatitis

Bacterial Infection Route

Patterns of Chronic Hepatitis

Metabolic Liver Disease - hemochromatosis, Wilson's dz

Cirrhosis

Biliary Cirrhosis

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main rate limiting step in bilirubin metabolism is excretion by the canaliculi rather than conjugation

- alkaline phosphatase - located on the cell membrane of biliary canaliculi
- transaminase - located in the hepatocyte cytoplasm, ALT more specific for liver than AST

- conjugated bilirubin - secreted by liver cells associated with biliary obstruction or liver cell destruction

- albumen - reflects synthetic property of liver, low level => long standing disease of liver

- caeruloplasmin

- transferrin

space of Disse
between hepatocyte surface and endothelial lining of sinusoid (larger than capillaries)

Liver Necrosis

- councilman bodies - dead hepatocytes form eosinophilic shrunken structure

- spotty necrosis - patchy

- zonal necrosis - necrosis confined to zone

- piecemeal necrosis - scattered pattern immediately next to the portal-tract connective tissue

- bridging necrosis - extensive necrosis that bridge different veins/tracts

General Liver Disease Characteristics

- fatty change

- cholestasis

- extrahepatic

- intrahepatic
- liver necrosis

- liver fibrosis - cells of Ito in space of Disse

- liver storage disease

- hemochromatosis, hemosiderosis, Wilson's disease

- glycogenesis (glycogen storage dz)

Vascular liver disease
- true infarct - rare, from trauma, arterial embolization, bacterial endocarditis, eclampsia, polyarteritis nodosa(Kussmaul disease)

- R sided heart failure -> passive venous congestion of liver -> nutmeg appearance (chronic passive venous congestion)

- portal HTN

- increase in portal venous pressure

=> splenomegaly, ascites

- new channels may open up betweeen portal and systemic venous circulation

- variceal bleeding

- caput medusa

- hemorrhoids

- classified: pre-sinusoidal, sinusoidal or post-sinusoidal

EXAMPLES: PRE-SINUSOIDAL - PORTAL VEIN THROMBOSIS

SINUSOIDAL - HEPATIC FIBROSIS, CIRRHOSIS

POST SINUSOIDAL - HEPATIC VEIN THROMBISIS, CENTRAL VEIN THROMBOSIS

Clinical Picture: Budd-Chiari Syndrome (post sinusoidal)

TRIAD: 1) ABD PAIN

2) ASCITES

3) HEPATOMEGALY

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ACUTE HEPATITIS

- INCREASED BILIRUBIN

- INCREASED ALT/AST - LIVER CELL NECROSIS

- ALBUMEN ~ NORMAL

- DECREASED COAGULATION DUE TO DECREASE IN COAGULATION FACTOR PRODUCTION

Hepatrophic Virus

A, E = fecal, oral

B, C, D = parenteral, histologically ground glass apperance of hepatocytes (accumulation of antibodies)

Route of Bacterial Infection

- ascending from biliary tract

- ascending in the portal vessels from a focus of sepsis in abdomen

- systemic septicemia

3 histological Patterns of Chronic Hepatitis

- chronic active hepatitis

- continued necrosis of hepatocytes

- development of cirrhosis

- necrosis extends from one portal area to another, portal tract to parenchyma

- chronic persistent hepatitis

- confined to portal tract

- not associated with progressive fibrosis or cirrhosis

- chronic lobular hepatitis

- portal tract inflammation(no piecemeal necrosis), spotty parenchymal inflammation

Metabolic Liver disease

Iron - hemochromatosis

primary - excessive absorption of iron(accumulates as hemosiderin) from gut

- chromosome 6, HLA locus

- cells look rusty brown due to hemosiderin in cells

- great increase transferrin in blood, increase of iron, ferritin

secondary - also called hemosiderosis

- due to other disease (alcoholism) or repeated blood transfusion

Copper - Wilson's disease

- decrease in ceruloplasmin (Cu binding) in blood

- liver fails to excrete

- Cu-ceruloplasmin complex

- overspills into blood, deposited in brain, cornea

Cirrhosis hx

- long destruction of liver cell

- chronic inflammation stimulating fibrosis

- regeneration of hepatocytes to form nodules

Biliary Cirrhosis

- Secondary - obstructed extrahepatic duct

- Primary - Autoimmune, Slow destruction of bile canaliculi

- sclerosing cholangitis

- associated with inflammatory bowel disease

- both intra/extra hepatic duct

- medium sized ducts, ducts in portal tract => concentric fibrosis and inflammation, small ducts => replaced by collagen, fibrous stricture with segmental dilatation

Breast Pathology NOT COMPLETE

Innate vs. Adaptive Immunity

INNATE - neutrophil, macrophage, dendritic cells, complement
ADAPTIVE - T, B-cells, circulating antibodies

T-cell differentiation (figure)

T-cell activation
MHC - signal 1
recognized by TCR
B7-CD28, IL-2 - signal 2
costimulatory molecule
activation requires 2 signals





















Lymphocytes

T cell (60~70%)
- CD4+ help B cells make antibody and activate macrophage
- CD8+ kill virus infected cells directly
- allergy (type IV sensitivity)
- slow organ rejection
B cell(10~20%); found in superficial cortex of lymph nodes, white plulp in spleen
- make antibody, form plasma cells
- IgG antibodies to oppose bacteria, viruses
- allergy (type I hypersensitivity); IgE
- antibodies reject organ fast

Kidney Anatomy

Herpes Virus

Herpes Virus
- double stranded DNA ~ 70 proteins
- types
a. neutropic alpha-group viruses
HSV1, HSV2, VZV
b. lymphotropic beta-group viruses
CMV, HHV6, HHV7
c. gamma group viruses
EBV, HHV8 (Kaposi's Sarcoma)

HSV1, HSV2
- cause vesicular lesions of the epidermis
- infect neurons
- primary HSV infection in immunocompetent resolve in few weeks (VIRUS LATENT IN NERVE CELLS)

HSV morphology
- formation of large, pink to purple (Cowdry type A) intranuclear inclusions that contain intact and disrupted virions and push darkly stained host cell chromatins to the edge of nucleus
inclusion-bearing multinucleated syncitia

Manifest
- cold sore, fever blister
- gingivostomatitis
- genital herpes
- corneal lesions (herpes epithelial keratitis, herpes stromal keratitis)

Lymph Node, Spleen, Lymphoid Disorder

HODGKIN'S

MIXED CELLULARITY



NODULAR SCLEROSIS

A diagnostic (multi-nucleated) Reed-Sternberg cell lies dead-center. Just below it is a non-diagnostic, uninuclear cell that has been called a "Reed-Sternberg variant" or a "Hodgkin" cell. Although this cell is characteristic of hodgkin lymphoma, the pathologist who plays by the rules will scrutinize a node suspected of Hodgkin lymphoma involvement until a diagnostic cell is found.

Lacunar cells are a feature of nodular sclerosis Hodgkin lymphoma and are not found in other subtypes. In formalin-fixed tissue, the cytoplasm around Reed-Sternberg cell nuclei retracts, leaving a cleared space possibly spanned by a few shreds of cytoplasm. The nuclei are also contracted and have diminished nucleoli.

LYMPHOCYTE DEPLETED

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IMPORTANT PRINCIPLES REGARDING LYMPHOID NEOPLASM

- VAST MAJORITY(80~85%) B-CELL ORIGIN
REMAINDER ARE T-CELL, RARELY ARE NK OR HISTIOCYTIC ORIGIN
MAY REPRESENT CELLS ARRESTED AT AY STAGE OF DIFFERENTIATION
- AS TUMORS OF IMMUNE SYSTEM DISRUPTING NORMAL REGULATORY FUNCTION,
INCREASE SUSCEPTIBILITY TO INFECTION OR AUTOIMMUNITY
- ALL LYMPHOID NEOPLASMS DERIVED FROM A SINGLE TRANSFORMED CELL AND ARE MONOCLONCAL
- NEOPLASTIC B AND T CELLS TEND TO HOME IN AND GROW IN AREAS WHERE THEIR NORMAL COUTNERPARTS RESIDE
- HD SPREADS IN ORDERLY FASHION, NHL LESS PREDICTABLE






































































































ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOMA (ALL)
- VERY IMMATURE CELLS WITH LARGE NUCLEOLI
- FEWER NUCLEOLI THAN DO MYELOBLASTS
- NUCLEAR CHROMATIN MORE CONDENSED
- CYTOPLASMIC GRANULES ABSENT


ACUTE MYELOBLASTIC LEUKEMIA (AML)
- VERY LARGE, IMMATURE MYELOBLASTS
- LINEAR RED, AUER ROD, COMPOSED OF CRYSTALLIZED GRANULES
- DELICATE NUCLEAR CHROMATIN
- PROMINENT NUCLEOLI
- FINE AZUROPHILIC GRANULES IN THE CYTOPLASM

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5 most common NHL



SMALL LYMPHOCYTIC LYMPHOMA (SLL, PROLYMPHOCYTES, BELOW: SMUDGE CELL)



FOLLICULAR LYMPHOMAS (TWO TYPES OF CELLS: CENTROCYTIC, CENTROBLASTIC)
a mixture of small lymphocytes with scanty cytoplasm and irregular nuclei (centrocytes) mixed with a population of larger lymphocytes with scanty cytoplasm with rounded nuclei and single or multiple small nucleoli (centroblasts).


DIFFUSE LARGE B-CELL LYMPHOMA(CELL SIZE 5 X A SMALL LYMPHOCYTE)



BURKITT LYMPHOMA(STARRY SKY DUE TO APOPTOSIS, MOST EXTRANODAL)
TWO TYPES, 1)AFRICAN(EBV), 2)NON-ENDEMIC

MANTLE CELL LYMPHOMA

- TOP: Note that the cells in the germinal center, which are not neoplastic, bear no resemblance to the small lymphocytes of the tumor.

- TWO PATTERNS, 1) MANTLE ZONE PATTERN, 2) DIFFUSE PATTERN
- REGARDLESS OF PATTERN, THE PROLIFERATION CONSISTS OF A HOMOGENOUS POP'N OF SMALL LYMPHOCYTES WITH ROUND TO IRREGULAR TO OCCASIONALLY DEEPLY CLEFTED(CLEAVED) NUCLEAR COUNTOURS