Liver pathology

spider angiomas are subcutaneous lesion.

blanch with pressure and refill centrifugally upon release.
they are dilated cutaneous arterioles that present as a central papule with
radiating blanching capillaries.the number and size of these skin lesions
generally correlate with the severity of liver disease.
........................
acquired spider angiomata may also occur with ither hyperestrogenic states (eg
pregnancy) possibly due to estrogen effects on arteiorlar dilation.

Hepatic encephalopathy

it is defined as reversible decline in neurological function..

is due to increased inhibitory neurotansmission (GABA) and decreased excitatory
neurotansmission (glutamate and acetylcholine)

in alcoholic liver disease SHBG also increases so it bind to free testosterone and
thus ratio of free testosterone/estrogen decreases
...................
due to hyperestogenism their is also decreased body hair.
.........
increase estrogen >>>androstenedione is not catabolized(in liver) so estradiol
accumulate.

also have increased adrenal production of andreostenedione with aromatization

to estrone and eventual conversion to estradiol.
estradiol induces SHBG production (primarily in the liver but also in uterus
and testes) which results in increased testosterone binding and a decreased free
testosterone/estrogen ratio.

in hepatorenal syndrome>>>>the renal involvement is due to renal

vasoconstriction.

severe cirrhosis causes high-output heart failure

(peripheral edema/ascites, bilateral bibasilar crackles,jugular venoous distension,

and hepatomegaly from venous congestion)
due to splanchnic vasodilation and intrahepatic or mesenteric
arteriovenous shunts.

Factor VII, part of the extrinsic pathway, has the shortest half-life of all
coagulation factors.PT assesses the extrinsic and common pathways of
coagulation and is the first to become abnormal in liver disease.
.............
hypoalbuminemia, elevated bilirubin levels, and prolonged PT are signs of
inadequate liver function (eg, liver failure) and indicate a poor prognosis in
cirrhotic patients.

Alkaline phosphatase increase in biliary disease,pregnancy(placenta),bone

disease(osteomalacia), malignancy(CML) and total parenteral
nutrition(intestine)
differentiation b/w liver and bone source can be done by electrophoresis,
specific monoclonal antibodies,
heat denaturation causes bone specific to denature (heat>bone=boil)

It is especially pronounced in viral-infected cells and causes mitochondrial

dysfunction. The two components of Reyes syndrome include:
1, Hepatic dysfunction manifests with vomiting and hepatomegaly, but
jaundice is rare. Liver function tests reveal increased levels of ALT, AST,
ammonia and bilirubin and a prolonged PT and PTT. Light microscopy of a liver
biopsy shows microvesicular steatosis, the presence of small fat vacuoles in the
cytoplasm of hepatocytes ( Choice C).

No necrosis or inflammation is present in the liver.

Electron microscopy findings include swelling, a decreased number of

mitochondria and glycogen depletion.

2, encephalopathy.

fatty change (steatosis) occurs in reversible hypoxic, toxic, or metabolic injury

(eg. protein malnutrition, diabetes, obesity). it affects cells involved in and
dependent on fat metabolism.
the most common cause of hepatic steatosis is alcohol abuse.

macrocytosis is specific for alcoholic liver disease, it can occur in the absence
of anemia,B12 and folate def
.............
DIT
histologically in alcoholic hepatitis we see
1, fatty infiltration (although it is not specific, we also see in non-alocholic fatty
liver disease and steatohepatitis.

2, mallory bodies. (also non speific, see in alcoholic cirrhosis,wilson,PBC,

hepatocellular carcinoma but most often in alcholic liver disease.

3, necrosis and hepatocyte swelling.

............

ascitis due to mechanical compromise to portal vein and also by vasoactive

mechanism which causes dilation of splanchnic arteries and futher
constricting arteries intrahepatically.

hepatorenal syndrome is the cause of activation of RAA system

........
Thrombocytopenia in alcoholism develops due to both direct toxic effect of
alcohol on the bone marrow and hypersplenism with splenic sequestration of
platelets
......
first line treatment is furosemide and spironolactone

the PPAR family apperars to play a significant role in the pathogenesis of

metabolic syndrome...

nbme,11,1,19
In alcohol consumption AST and ALT both are high but AST is 2 times higher than
ALT.

Nonalcoholic steatohepatitis or NASH is a common, often silent liver disease. It

resembles alcoholic liver disease, but occurs in people who drink little or no alcohol.
The major feature in NASH is fat in the liver, along with inflammation and
damage. Most people with NASH feel well and are not aware that they have
a liver problem.

Diagnosis

NASH is usually first suspected in a person who is found to have elevations in liver
tests that are included in routine blood test panels, such as alanine
aminotransferase (ALT) or aspartate aminotransferase (AST). When further
evaluation shows no apparent reason for liver disease (such as medications, viral
hepatitis, or excessive use of alcohol) and when x rays or imaging studies of the
liver show fat, NASH is suspected. The only means of proving a diagnosis of
NASH and separating it from simple fatty liver is a liver biopsy. For a liver
biopsy, a needle is inserted through the skin to remove a small piece of the liver.
NASH is diagnosed when examination of the tissue with a microscope shows fat
along with inflammation and damage to liver cells. If the tissue shows fat
without inflammation and damage, simple fatty liver or NAFLD is
diagnosed

altered mental status in hepatic encephalopathy :

is due to
impaired neurotransmittor release, astrocyte dysfunction,
neuroinflammation and/or edema
HCC is strongly associated with hep B and is often preceded by HBV-induced
cirrhosis.

it is due to integration of viral DNA in to host genome,>>>>>causes

increase synthesis of insulin-like growth factor II and receptor for insulin-
like growth factor I, thereby stimulating cell proliferation.
another effect is suppression of p53 tumor suppressor/cell cycle regulatory
gene in host cell.
chronic inflammation and regeneration also facilitates accumulation of
mutations.

Aflatoxin
common in china(asia) and africa

most common and severe type is B1.

classic G:C>>>T:A transversion on codon 249>>>causing mutation in P53.
aspergillus flavus and parasiticus.

polycythemia in HCC is less common,

also cause anemia of chronic disease (TIBC low).
so patient can be anemic or polycythemic

increased level of AFP is present in 50-75% of patients with HCC...................

hep C also have slightly elevatyed alpha-feto protein, but continuous rise
should alert more towards the hepatoellular carcinoma.
HCC can present unifocally, multifocally or as a diffusely infiltrative cancer.
..................
individuals with stable, compensated cirrhosis who suddenly decompensate
without appaaretn reason should be carefully evaluated for hepatocellular
carcinoma, especially when serum AFP levels are also elevated.
...............
serum AFP levels do not correlate well with the size, stage, or prognosis of
HCC

chronic liver disease (eg, viral hepatitis). the sensitivity of AFP in detecting HCC
ranges from 41- 65%, whole its specificity ranges from 80-94%
A rise in serum AFP to level exceeding 500 mcg/L in a high-risk patient is
considered diagnostic of HCC
sudden surge in AFP above their baselines

hepatoblastoma is the most common liver neoplasm of children and is

associated with familial adenomatous polyposis and beckwith-wiedmann
syndormes.
this neolasm is usually fatal within a few years if not surgically resected.

cholangiocarcinoma is a rare maligannacy that arises form the intra and

extrahepatic bile ducts.
intrahepatic cholangiocarcinma appears grossly as a treelike mass that grows
along the biliary system, typically resulting in extensive intrahepatic
metastasis. risk factors include primary sclerosing cholangitis, fibropolycystic
liver disease, and infection with liver flukes in endemic areas.

the prognosis is very poor

hepatic abscess in underdeveloped countries>>>>parasitic infection (eg

entamoeba, echinococcus)
hepatic abscess in developed countries>>>bacterial infection which depends on
the route of infection.
traumatic cause has mixed aerobic anaerobic etiology, staphylococcus has
hematological spread, other causes are gram negative bacilli

Hemangiomas
dilated vascular spaces with thin walled endothelial cells.>>>
soft blue compressible masses upto few centimeters in size.>>>may appear on
skin, mucosa, visceras and deep tissues.
when appear on skin most frequently based in the dermis.
cavernous hemangioma of brain and visceras are associated with VHL syndrome
..............
these benign tumor are though to be congenital malformations that enlarge by
ectaisa , not hyperplasia or hypertrophy..
hemongiomas may occur in singly or in multiples and are well circumscribed
masses of spongy consistency, typically measuring less than 5cm in width..
microscopically consist of cavernous, blood filled vascular spaces of variable size
lined by single epithelial layer,
collagenous scar or fibrous nodules may be seen in association with
thrombosis.
most are asymtopatic, although some will complain of abdominal pain and
right upper quadrant fullness..

prognosis is excellent with surgical resection an option for those who are
symptomatic or who have compression of adjacent structure
Hepatic adenoma :- predominantly in young or middle aged women who have a
lengthy history of OCP.
these are typically identified when pateint complain of abdominal oain in the
epigastrium or right upper quadrant, when imaging is obtained for
unreleated issues, or
when an individual suddenly collapses because of rupture and intrabdominal
bleeding

Angiosarcoma of liver
malignant endothelial cells express CD 31, which is PECAM1 (pletelet endothelial
cell adhesion molecule), PECAM is a member of the immunoglobulin family of
proteins, is expressed on the surface of endothelial cells and functions in leukocyte
migration through the endothelium.

arsenic (in insecticides), vinyl chloride (in plastic industry), thorotrast (a former
radioactive contrast medium)

Metastasis to liver is 20 times more common than hepatocelluar caricnoma,

liver is the 2nd most common site of metatstatic spread (after the lymph
nodes) because of its large size, dual blood supply, high perfusion rate, and the
filtration function of kupffer cells.
typically have mutliple nodules through out the liver that may replace more than
80% of the hepatic parenchyma, often resulting in marked hepatomegaly(non
tender)
the nodules frequently outgrow their vascular supply and become centrally
necrotic and umbilicated. even with significant metastatic involvement, patient
may have no clinial or laboraotry signs suggestive of hepatic insuffiiany.
once majority of liver parechya is destrpyed or the major bile ducts become
obstrycted with tumor, patient tend to present with jaundice or abnormla
hepatic enzyme.

A1AT inhibit several different proteolytic enzymes (including neutrophil elastase).

A1AT deficiency

2nd most common cause of death in this population.

...............
liver involvement causes cirrhosis and hepatocellular carcinoma.

PAS + intracellular granules representing globules of unsecreted A1AT are seen

within the periportal hepatocytes of affected individuals.
these globules also resist digestion by diastase.

liver disease in first 2 decades of life present with hepatomegaly or

heptasplenomegaly, cholestasis and elevation of liver enzymes.

neonatal hepatitis with cholestatic janundice in common.

attack of hepatitis in childhood and adolescense may appear to completely

resolve, or may become chronic and silently progressive.

it is not uncommone for patients to be asymtopmatic untill they have

developed end-stage liver disease.
.........
diagnoses of disease is established by measurement of the serum A1AT level.
followed by confirmatory genetic testing.
the test is infdicated in all patietns with premature onset (<50 years) of
chronic bonchitis, emphysema and dyspnea as well as in nonsmokers suffering
from COPD.

a history of neonatal hepatitis should highten suspicion for A1AT

deficiency.
.............
75-80% of individual eventually develop severe panacinar emphysema.
liver disease occur in 10-15% of patients and is of greater concern during the first
2 decades of life because pulmonary dysfunction takes decades to develop.

..........
smoking plays a synergistic role in the disease process by permanently
inactivating A1AT through oxidation of a crucial methionine residue.
thus smoker with A1AT deficiency tend to develop dyspnea at a median age of
36 years versus a median age of 51 years in nonsmokers

biliary atresia:
extrahepatic biliary atresia is a congenital obstruction of extrahepatic bile ducts.
by the 3rd week of life, there is total obstruction.
affected children will have the characteristic cholestatic picture of acholic (light)
stool and dark urine.

on physical examination there is a firm, enlarged liver.

laboratory findings include increased levels of direct bilirubin, alkaline
phosphatase and gamma-glutamyl transferase.
liver biopsy is usually diagnostic:
showing
1, marked intrahepatic bile ductule proliferation
2, portal tract edema and fibrosis
3, parechymal cholestasis.
if biliary drainage is not restored surgically, bile stasis will cause
development of biliary cirrhosis by 6 months of life.

overgrowth of bacteria(anaerobes and staphylococcus aureus) causes

deconjugation of bile acid by removing glycine and taurine making it a less
soluble,causing lipid malabsorption

Wilson's disease
likely diagnosed in a patient with younger than 30 years old with unexplained
chronic hepatitis.
................
causes cystic degeneration of putamen.

.............
many progressive neurologic diseases may be associated with cystic
degeneration of the putamen, but Wilsons disease is the most likely

Hemochromatosis
missense mutation in the HFE gene (eg, C282Y), which is most common found
in Caucasian.

ethanol (also cause redistribution of bosy iron),

Vit c and citric acid (of inorganic iron) increase intestinal absorption of
iron>>so exacerbate hemochromatosis

micronodular cirrhosis>>>>pigement cirrhosis with hepatomegaly

.............
mildly elevated liver fucntion tests

exocrine pancreatic function is usually preserved in patients with

hemochromatosis. Therefore, fat malabsorption and osteoporosis (due to
decreased vitamin D) would not typically be seen.

Inactivation of the HFE protein results in decreased hepcidin synthesis by

hepatocytes and increased DMT1 expression by enterocytes, leading to iron
overload.
.........
the increased iron accumulation in the bodu through the 2 mechanism,

1, enterocytes repsond by increasing apical expression of divalent metal

transpoter 1(DMT1), increasing iron absorption from the intestinal lumen.
2, Hepatocytes respond by decreasing hepcidin synthesis, low hepcidin levels
result in increased ferroportin expression on the basolateral surface of
enterocytes. This allows increased iron secretion into the circulation, leading
to iron overload.
.........
This HFE protein normally interacts with the transferrin receptor o increase
endocytosis of the iron-transferrin complex. once inside the cell, transferrin
is degraded and the released iron is added to the labile iron pool, which controls
the expression of proteins involved in iron absorption and storage. Mutations
that inactivate the HFE protein cause enterocytes and hepatocytes to
detect falsely low iron levels.
.......
Primary biliary cholangitis

insidious in onset.
............
pruritis (usually worse at night) is normally the first symptoms. fatigue is
also often reported
as the disease progresses hepatosplenomegaly and cholestasis (eg jaundice,
pale stool and dark urine) can develop.
reduce bile flow result in malabsorption .reduced biliary cholesterol
excretion may also promote hypercholesterolemia with xanthelasma
formation. late manifestation include cirrhosis and portal hypertension.
.........
chronic cholestatic processes including obstrutive biliary lesions ans primary
biliary cirrhosis result in subsequent hypercholesterolemia, leading to the
formation of xanthelasma.

correction of underlying lipid defect can lead to slow resolution of these

lesions.

.......
abnormalities on laboratory testing ae consistent with cholestasis and include
elevated ALK phosphatase and cholesterol, as well as elevated IgM.
ALT and AST are normal
...........
also has kayser fleisher ring

eventually progressive hepatic damage secondary to the obstruction in

intraheaptic bile flow is observed.upstream portal tracts undergo bile ductular
proliferation, inflammation and necrosis of adjacent parenchyma.
generalized cholestasis develops, and the liver gradually grossly stained
green and uniformly micronodular.
ultimately the end-stage liver findings in PBC cannot be distinguised from
those in seconndary biliary cieehosis or chronic hepatitis.
.............
dense portal track infiltrate of macrophages, lymphocytes, plasma cells and
eosinophils that results granulomatous destruction of intrahepatic,interlobular
bile ducts (florid duct lesion)>>>>>>>>>>>.similarity of these finding also seen
in graft versus host disease.

Gall stones disease of middle age or elderly,

young people only when have a predisposing condition eg sickle cell disease.

normally chlolesterol is solubilized by bile acids and phospholipids.

medical treatment in patients who do not go for cholecytectomy is hydrophilic
bile acids (ursodeoxycolic acid) which reduce bile cholesterol secretion and
increase biliary bile acid concentration, which promotes gallstone dissolution.
.............
nbme>>>3,339
Ursodeoxycholic acid helps regulate cholesterol by reducing the rate at which
the intestine absorbs cholesterol molecules while breaking up micelles
containing cholesterol. Because of this property, ursodeoxycholic acid is used to
treat (cholesterol) gallstones non-surgically.

The drug reduces cholesterol absorption and is used to dissolve

(cholesterol) gallstones in patients who want an alternative to surgery. The
drug is very expensive, however, and if the patient stops taking it, the gallstones
tend to recur if the condition that gave rise to their formation does not
change.

It is the only FDA approved drug to treat primary biliary cirrhosis

removal of excess cholesterol from the body occurs via 2 mechanisms; excretion
of free cholesterol into bile and conversion of cholesterol into bile acids.
In the liver, free cholesterol is converted into cholic and chenodeoxycholic
acids through a series of chemical reactions beginning with cholesterol 7a-
hydroxylase (rate limiting step in bile acid synthesis). These bile acids are then
conjugated to either glycine or taurine (improving solubility and
emulsifying ability) to create the bile salts that are actively secreted into
the bile canaliculi,

As water-insoluble cholesterol is secreted in bile it is rendered soluble in small

amounts by the detergent action of these amphipathic (eg, hydrophobic and
hydrophilic) bile salts and phosphatidylcholine (a phospholipid).. when
there is more cholesterol than can be made soluble, it precipitates into crystals
that eventually grow and merge to form gallstones.

hypomotility associated with pregnancy, advanced age, fasting,

hypertriglyceridemia and prolonged total parenteral nutrition.
also associated with glucose intolerance
..........
gallbladder actively absorbs water from bile.
hypomotility of gallbladder results from pregnancy, rapid weight loss,
octreotide,prolonged use of TPN and high spinal cord injuries>>>>results
in biliary sludge (due to precipitation of cholesterol monohydrate crystals,
calcium bilirubinate and mucin)>>>>>increases the risk of cholesterol stone
formation

increase cholesterol synthesis by upregulating hepatic HMG-CoA reductase

enzyme.
progesterone causes hypomotility of gallbladder and also causes decrease bile
acid production
..........
decrease the activity of aromatase enzyme would indirectly reduce the
cholesterol gallstone formation.
cause androgen is not converted to estrogen, and estrogen does not stimulate HMG
CoA reductase.
clofibrate, octreotide or ceftriazone,
......
drug induced cholestasis with OCPs , anabolic steroid and chlorpromazine

.......
7-alpha hydroxylase convert cholesterol (insoluble) to bile acid (soluble).
fibrate medication (as bezafibrate, fenofibrate, and ciprofibrate) reduces the
conversion of cholesterol to bile acids by inhibiting 7-alpha hydroxylase resulting
in increased concentration of cholesterol with in bile..
when gall bladder is hypomotile or there is more cholesterol than dissolve into bile
salts, the cholesterol precipitates into insuloble crystals.

Rapid weight loss and gall stones ?

very low calorie diet with decreased caloric intake and rapid weight loss
can lead to bile stasis and increased cholesterol mobilization,

Pigment gallstones
most common in rural asia, with an increased incidence in women and elderly.

only 10-25% in US.

Brown stones
this is due to production of beta-glucuronidase by the infected hepatocytes
and bacteria.

this enzyme causes hydrolysis of bilirubin glucuronides and increases the

amount of unconjugated bilirubin in bile.
therefor biliary infection with E.coli, ascaris lumbricoides or the liver fluke
opisthorchis sinesis significantly elevates the risk of developing brown pigment
stone.

Choledochal cysts are congenital dilations of the common bile duct that
typically present during childhood (age<10) with recurrent abdominal pain
and jaundice.

cholycystitis >>> 2ry infection

mechanical disruption of gallbladder mucosa and release of infammatory mediators
(eg lysolecithin, PGs) cause the obstructed gallbladder to be inflammed and
edematous>>>blood supply to the distended organ is compromised and secondary
bacterial infection results.>>>causes gangrene or perforation>>formation of
pericholestetic abscess or generalized peritonitis
...................
Persistent gallbladder outflow obstruction promotes hydrolysis of luminal
lecithins to lysolecithins, which disrupts the protective mucus layer. The
luminal epithelium is then exposed to the detergent action of the bile salts,
resulting in chemicals irritation and prostaglandin release. Inflammation of
the mucosa and deeper tissues causes gallbladder eventually result in
ischemia. Finally, bacteria (eg, Escherichia coli, enterococcus, Klebsiella,
Enterobacter) invade the injured and necrotic gallbladder wall, causing an
infection.

The gallbladder is vulnerable to ischemic injury as the cystic artery lacks

collateral circulation
Acalculous cholecystitis most commonly, occurs in critically ill patients (eg,
those with sepsis, severe burns, trauma, immunosuppression) and is associated
with high mortality, The condition is thought to arise secondary to
gallbladder stasis and ischemia, which causes inflammation of and injury to
gallbladder wall.

the presence of echogenic stucture within gallbladder can be suggestive of

acute cholescystitis in the setting of fever and abdominal pain but is not
diagnostic>>>>>it can be an incidental asymptomatic finding in the setting
of other abdominal pathology>>>more specific US signs for acute
cholecystitis are gallbladder wall thickening, pericholecystic fluid, and
positive sonographic murphy sign

porcelain gallbladder
although patient are asymtomatic, some may present with right upper quadrant
pain, or with a firm non-tender mass in the right upper quadrant.

heredetitary pancreatitis: is a rare disorder that results form mutations

involving the trypsinogen or SPINK1 genes.the most common mutation leads ti
the production of abnomral trypsin that is not susceptible to inactivating
cleavage by trypsin.since there is always a small amount of trypsinogen that
activates prematurely within pancreatic acini and ducts, these protective
mechanisms are critical for preventing pancreatic autodigestion.
........................
multiple protective mechanisms exist to limit the amount of trypsinogen that
becomes prematurily activated.
1, serine peptidase inhibitor kazal type 1(SPINK1) is secreted by pancreatic
acinar cells and functions as a trypsin inhibitor.it impedes the activity of trypsinogen
molecyles that become prematurely activated within the pancreas,preventing
trypsin-mediated activation of other proteolytic enzmes and autodigestion of
pancreatic tissue.
2, in addition to functioning as its own activator, trypsin can also serve as its
own inhibitr by cleaving other trypsin molecules(rendering them inactive).this
process is critical in preventing large amouns of trypsin from forming within
pancreatic tissue.............

.......
after acinar damage(either direct or indirect "due to obstruction") trypsinogen
is activated by lysosomal enzyme with in pancreas causes autodigestion

other causes of acute pancreatitis

1 structural abnormalities of duct (strictures, cancer, pancreas divisum) or
ampullary region(choledochal cyst, stenosis of sphincter of oddi)
2 surgery of stomach,biliary track or after cardiac surgery.

Ethanol causes pancreatic secretion to have more protein content and less fluid
which form plugs.
causes spasm of sphincter of oddi and direct injury of acinar cell.
MACROCYTOSIS is often seen with alcoholism due to B12 and folete
def(malnutrition) or direct toxic effect of alcohol to bone marrow.
INDICATOR OF THIS ETIOLOGY:
AST/ALT ratio increases, GGT increases (may in part be a marker of the
oxidative stress associated with ethanol metabolism), macrocytosis (even
in the absence of anemia), increase IgA to IgG ratio
macrocytosis can occur independently of folate or cobalamin deficiency
high levels of circulaitng triglycerides lead to increased produciton of free
fatty acids within the pancreatic capillaries by pancreatic lipase.

normally, fatty acids exist in serum bound to albumin.

however, if serum TGs level rise to >1000 the concentration of free fatty acids
exceeds the binding capacity of albumin and leads to direct injury to the
pacncreatic acinar cells.
this hypertriglyceridemia causes acute pancreatitis via direct tissue toxicity.

other drugs that cause acute pancreatitis

azathioprine,sulfasalzine,furosemide and valproic acid

pancreatic pseudocyst
common in lesser sac(behind the stomach), bordered by stomach,duodenum
and transverse colon.

wall closely adherent to surrounding hollow organ.

(granulation tissue )fibrosis,thickening and organization of wall occur with

time.take about 4-6 weeks
...........................
DD

glycogen-rich cubodial epothelium is seen is serious pancreatic neoplasms.

Columnar mucinous epithelium is typically found in mucinous cystic neoplasm

Atypical cells forming papillary projections are seen in the papillary variant
of pancreatic adenocarcinoma.

degree of hypocalcemia can be used as a marker of severity of acute

pancreatitis.
.............
hyperglycemia: indicator of severity.

hypernatremia: due to third spacing and decrease fluid intake

acute interstisial pancreatitis (macroscopically>>edematous,

microscopically>>intersticial edema, focal fat necrosis and calcium deposits)
can progress to acute necrotic pancreatitis (acini defect, can have
hemorrhage , macroscopically>>white chalky fat necrosis, black areas of
hemorrhage can also be seen grossly)
.......................
acute necrotizing pancreatitis has a high propensity for secondary bacterial
infection.

genetic predisposition for pancreatic cancer

hereditary pancreatitis,MEN,HNPCC,FAP
Migratory thrombophlebitis
due to release of procoagulant(mucin) causing hypercoagulable state.similar
mechanism of MARANTIC endocarditis(NBTE)..????
it occur especially with adenocarcinomas that secrete thrmboplastin-like
substance that is capable of causing chronic intravascular coagulation that is
both disseminated and migratory.

obstructive jaundice is an indicative of an adenocarcinoma in the head of

pancreas.
cancer in body and tail do not obstruct common bile duct and usually do not
produce symptoms untill they invade the splanchnic plexus and cause
midepigastric abdominal pain.