Pathology of the liver, gallbladder

and pancreas
Biliary atresia
 Pathology of the liver

Disorders of circulation
venous congestion
portal hypertension: liver cirrhosis
Budd-Chiari syndrome (intrahepatic vein thrombosis)
thrombosis of the portal vein
infarction
pylephlebothrombosis
subcapsular haemorrhages

Disorders of metabolism:
protein metabolism
lipid metabolism
amyloidosis
hemosiderosis, hemocromatosis
glycogenosis, lipoidosis
Wilsons disease
 Liver congestion (1,2)
subcapsular haemorrhages (3) and post-trauma necrosis (4)

1 2

3 4
Pylephlebothrombosis
 Liver necrosis

- necrosis of individual hepatocytes

- piece meal necrosis (focal, interface, spotty necrosis)

- zonal necrosis
centrilobular necrosis hypoxia, shock
healing with complete regeneration
peripherical necrosis intoxications
healing with complete regeneration or fibrosis
bridging necrosis hepatitis
healing with fibrosis or cirrhosis

- diffuse necrosis severe hepatitis, intoxications

death or cirrhosis
Diffuse necrosis
3 months old girl
Piece meal and bridging necrosis
 Inflammations of the liver

1. Non-specific inflammations
acute and chronic hepatitis
liver cirrhosis
liver abscesses
2. Secondary (satellite) hepatitis
inflammations of the GI tract and billiary channels
rheumathic diseases, collagen diseases
leptospirosis
EBV, CMV, herpes viruses
3. Intrahepatic cholangitis
4. Specific inflammations
sarcoidosis, tuberculosis
typhoid fever, syphilis
 Acute viral hepatitis

Viruses: A (RNA), B (DNA), C (RNA), D (RNA), E (RNA)

Macroscopy: enlarged soft liver

Microscopy: - apoptotic necrosis of individual hepatocytes (Councilman bodies)

- hepatocytes regeneration
- inflammatory infiltrate
- bridging necrosis HBV, HCV

Evolution: - healing with complete regeneration (HAV, HEV)

- transformation in chronic hepatitis (HBV, HCV, HDV)
- diffuse liver necrosis - severe (fulminated) forms
- glomerulonephritis, polyarteritis nodosa (HBV)
Acute viral hepatitis
Clinical features of the acute viral hepatitis

Classical form
Anicteric hepatitis
Recurrent hepatitis
Prolonged hepatitis
Malignant (fulminant) hepatitis
Giant cell hepatitis (newborns and infants)
 Chronic hepatitis

- more than 6 months

Types: 1. Chronic persistent (mild) hepatitis

- periportal inflammatory infiltrate
Evolution: healing, fibrosis (rare)
2. Severe (aggressive) hepatitis
- periportal and intralobular inflammatory infiltrate
- peri- and intralobular fibrosis
- piece-meal and bridging necrosis

Etiology: HBV, HCV

drugs
metabolic diseases (Wilsons disease high cooper, low caeruloplasmin)
autoimmune hepatitis
idiopathic hepatitis
Chronic persistent (mild) hepatitis
Severe (aggressive) hepatitis
Severe (aggressive) hepatitis
HBV antigen in hepatocytes
 Evolution of the acute and chronic hepatitis

Healing (90-95%)

Chronic persistent hepatitis

Acute Chronic
hepatitis hepatitis

Chronic agressive hepatitis

Hepatocellular Cirrhosis Death

carcinoma

Acute fulminant
hepatitis Healing (rare)
 Liver abscesses

Cholangitic abscesses

Pylephlebitic abscesses

Metastatic abcesses

Lymphogenic abcesses

Rare causes: trauma, superinfection

Evolution, complications:
- healing fibrosis or capsulling of pus
- perforation peritonitis or subphrenic abscess
- systemic spread septicopyemia death
Cholangitic abscesses
Pylephlebitic and metastatic abscesses
 Liver cirrhosis
(kirrhos, gr.= yellow)

- chronic diffuse fibrous inflammation of the liver characterized by irreversible

damage of the liver arhitecture

Pathogenesis
1. piece-meal and bridging necrosis
2. chronic fibrous inflammation
3. nodular regeneration of hepatocytes

Classification
atrophic (Laennecs) cirrhosis
postnecrotic cirrhosis
billiary cirrhosis
other causes: hemocromatosis, Wilson disease
-1 antitrypsin deficiency
syphilis, metabolic congenital diseases, etc.
 Atrophic cirrhosis (Laennecs cirrhosis)

Etiology: HBV, HBC

alcohol, toxic substances, diabetes mellitus

Macroscopy: hard and shrunken liver, sharp edges

nodular surface

Microscopy: - regenerative hepatocytic nodules

- fibrous septa

Pathogenesis:
chronic inflammation zonal necrosis and fibrosis pathological regeneration
Atrophic cirrhosis
Atrophic cirrhosis
Atrophic cirrhosis
Postnecrotic cirrhosis

Etiology: - fulminant hepatitis

- intoxications
- autoimmune diseases

Morphology: macronodules
expanded fibrosis
 Billiary cirrhosis

Types:
- primary and secondary biliary cirrhosis
- primary sclerosing cholangitis

Macroscopy: hard, large and green liver

PSC
Microscopy: periportal fibrosis
regenerative nodules
 Haemochromatosis
(Pigmentary cirrhosis)
 Consequences of cirrhosis

Portal hypertension
vascular decompensation generalized edema and ascites

Liver failure
parenchymatous decompensation jaundice, encephalopathy, hepatic coma
Normal liver Liver failure Clinical feature

synthesis of proteins hypoalbuminaemia, decreased plasma colloid edema, serosal effusions, ascites
osmotic pressure malnutrition (cachexia), hypoproteinemic
cardiomiopathy

synthesis of clotting factors hypocoagulability purpura, spider nevi, bleeding, anemia

synthesis of lipid enzymes hypercholesterolemia xanthelasma, steatorrhoea

Bilirubin conjungation hyperbilirubinaemia jaundice

metabolism of estrogens hyperestrogenism gynecomastia, testicular atrophy, hormonal disorders

metabolism of aldosterons hyperaldosteronism sodium and water retention edema, ascites

elimination of toxic brain toxicity (amonium) hepatic encephalopathy, coma, fetor hepaticus
metabolits

Glycogen storage hypoglycemia Fatigue, neurologic disorders, hypoglycemia

coma
splenomegaly and hepatocellular carcinoma
ascites
 Cirrhosis

Causes of death: - bleeding

- heart failure
- liver failure hepatic coma
- infections
- encephalopathy
- portal vein thrombosis
- hepatocellular carcinoma
63 years old woman, obesity
abdominal esthetic surgery February
reccurent infections with Acinetobacter
April - obesity, liver cirrhosis
- meningitis
 Alcoholic liver injury

1. steatosis

2. alcoholic hepatitis

3. liver fibrosis
centrilobular periphery

4. liver cirrhosis (Laennec)

 Alcohol consumption

Disorders of lipid metabolism

Disorders of intestinal
digestion and malabsorption

Steatosis
Direct damages
of the hepatocytes low level of the
lipotropic substances
Alcoholic hepatitis

Ethanol Acetaldehyde

Collagen synthesis ALCOHOLIC (ATROPHIC) CIRRHOSIS

Steatosis and alcoholic hepatitis
Steatosis and alcoholic cirrhosis
 Tumors of the liver

Pseudotumors: hamartomas
focal nodular hyperplasia
cysts
Hydatid disease (Echinococcus granulosus)

doughter
(vezicule fiice)
cysts

opalescent
outer laminated fluid (proligera)
inner germinative layer
layer
(cuticulara)
scolices (scolecsi)

liver

dogs sheeps humans

 Hydatid cysts

outer layer

inner layer

doughter
cysts
 Tumors of the liver

Benign: hemangioma
adenoma
Premalignant: hepatic cirrhosis, chronic hepatitis, hepatobiliary parasitosis,
intrahepatic lithiasis, cholangitis, primary sclerosing cholangitis

Malignant: liver cell (hepatocellular) carcinoma (HBV, cirrhosis)

uni- or multifocally
short survival
cholangiocarcinoma, bile duct cystadenocarcinoma
undifferentiated carcinoma
angiosarcoma
hepatoblastoma

Metastases

Leukaemic infiltrates
Liver cell (hepatocellular) carcinoma
Liver cell (hepatocellular) carcinoma and cholangiocarcinoma
Liver cell (hepatocellular) carcinoma after heart transplantation
Liver cell carcinoma + Angiosarcoma and metastases
thrombosis of the hepatic vein
Metastases from colon, cervical and lung tumors
esophageal cancer with liver metastases
leukaemic infiltrates 17 years old boy
 Pathology of gallbladder
Gallstones(cholelitiasis)

80-90 % in gallbladder
rarely in biliary ducts

Risk factors: 4 F Female, Fat, Forty, Fertile

Complications:
- cholecystitis
- cholangitis liver abscess
- mucocele or empyema of gallbladder
- mechanical jaundice and biliary colic
- obstruction hydrops of the gallbladder
- pancreatitis
- biliary cirrhosis
- carcinoma of the gallbladder
- intestinal obstruction (very rare)
Gallstones
Hydrops and empyema of gallbladder
 Pathology of gallbladder and biliary tract
Colecystitis. Cholangitis

Acute cholecistitis
- catarrhal, phlegmonous, gangrenous
Evolution, complications:
- healing
- transformation in chronic cholecystitis
- pericholecystitis peritoneal abscess
- perforation peritonitis
- ascending infection cholangitis liver abscess
- septicemia

Chronic cholecistitis
- fibrous, atrophic or porcelain gallbladder
Cholangitis
- acute, chronic
Acute gangrenous and chronic fibrous and atrophic cholecystitis
Chronic cholecystitis (porcelain gallbladder)

Rokitansky-Aschoff sinuses
 Tumors of the gallbladder and biliary tract

Benign
adenoma, papilloma, fibroma, etc.

Malignant
Carcinoma of the gallbladder
- 90% of cases - gallstones
Macroscopy: infiltrating or exophytic tumor
Microscopy: adenocarcinomas (90% of cases), adenosquamous carcinomas
squamous cell carcinomas, undifferentiated carcinomas
Poor prognosis

Carcinoma of the extrahepatic bile duct

Carcinoma of the ampulla of Vater

mechanical jaundice, pancreatitis
Papilloma Carcinomas
 Carcinoma of the ampulla of Vater

Carcinomas

choledocus

metastasis

tumor
metastasis pancr. duct

duodenum
Pathology of the pancreas
Atrophy

Lipomatosis

Cysts
Cystic fibrosis
 Pancreatitis

Acute pancreatitis
1. infective: mumps, Coxsakie viruses
2. non-infective pancreatitis
Etiology: bile stasis, stones, tumors, alcohol, trauma, genetic factors

Morphology: - minimal changes: steatonecrosis + inflammation

- severe pancreatitis: .+ haemorhages
Evolution: mild pancreatitis - healing, chronic pancreatitis, recurrences
severe pancreatitis - shock death
- healing with fibrosis

Chronic pancreatitis
Etiology: alcohol, genetic causes, LES, gallstones, autoimmune, idiopathic
Diagnosis: ERCP, MRCP
 Pathogenesis of chronic pancreatitis

mild acute pancreatitis severe acute pancreatitis

Pathogenesis of non-infective
pancreatitis

Chronic pancreatitis
normal pancreas post-cardiac transplant
soaps hemorrhages
 Tumors of pancreas

exocrine

glucagon
insulin
somatostatine
endocrine Pp
G1 - VIP
EC serotonine
G
 Tumors of pancreas
Exocrine
Cystadenoma, papilloma
Ductal adenocarcinoma
head (65-70%), tail, body
scarring-like tumor
poor prognosis!!!
Cystadenocarcinoma
tail
favorable prognosis
Acinar cell carcinoma poor prognosis

Endocrine
insulinoma, glucagonoma
gastrinoma (Zollinger-Ellison syndrome)
vipoma (achlorhidria+diarrhea - Werner-Morrison syndrome)
somatostatinoma
carcinoid tumor
Carcinoma - head
 HE

CEA

Trousseaus sign
DIABETES MELLITUS
 Diabetes mellitus
complex metabolic disease glucose intolerance disorders of beta Langerhans cells

Type 1: destruction of beta cells

insulinodependent diabetes

Type 2: reduction of the number of receptor for insulin!

non-insulinodependent diabetes

Secondary diabetes (type 3)

- destruction of pancreas
- hypersecretion of: glucagon (glucagonomas)
glucocorticoids (Cushings syndrome)
growth hormone (acromegaly)
adrenaline (phaechromocytoma)
noradrenaline (phaechromocytoma)
insulinodependent diabetes

Type 4 (Gestational diabetes)

 Diabetes mellitus

Consequences:

hyperglicaemia polyuria, glycosuria dehydration polydispsia

decreased protein synthesis
lipolysis and hyperlipidemia: free fatty acids ketone bodies metabolic acidosis
severe consequences: diabetic ketoacidotic coma

Complications:

atherosclerosis myocardial infarction, stroke, limb gangrene or death

microangiopathy retinopathy blindness
glomerulopathy: Kimmelstiel-Wilson lesion
neuropathy
repeated infections death
disorders of pregnancy: large babies, neonatal hypoglycaemia, toxemia (eclampsy)
hyperglicaemic coma death
insulin overdosage hypoglicemic coma death
 Coronarosclerosis

Nephrosclerosis Kimmelstiel-Wilson

Diabetic retinopathy (aneurysms)

Kimmelstiel-Wilson glomerulosclerosis
impotence amputation
dialysis
30-year-old woman with diabetes who had poor glucose control,
hypertension, and hyperlipidemia was referred for the evaluation of a rash
of 1-month duration. She reported no history of fevers, chills, or joint pain,
nor had she taken glucocorticoids or had contact with anyone with similar symptoms.
Her medications included insulin, pioglitazone, labetalol, fenofibrate, and
n3 fatty acid esters. On physical examination, the lesions were reddish yellow,
pruritic, and painful and were present on the backs of both legs and on the buttocks
and knees (Panels A and B). The blood glucose level was 260 mg per deciliter
(14.4 mmol per liter), the triglyceride level was 8168 mg per deciliter (92.2 mmol per
liter), and the total cholesterol level was 611 mg per deciliter (15.8 mmol per liter).
Levels of glycated hemoglobin and rheumatoid factor and other cholesterol levels
(low-density lipoprotein, very-low-density lipoprotein, and the ratio of low-density
to very-low-density lipoprotein) could not be assessed because of a grossly lipemic
specimen. Histologic analysis of a lesion-biopsy specimen (Panel C) showed foamy
macrophages and loose lipids, which confirmed the suspicion that the lesions were
eruptive xanthomas. One week later, the patient was hospitalized for acute pancreatitis.
As a result of this admission, she underwent 6 months of strict glycemic and
lipid control. During this period, the lesions began to resolve. If the skin signs of
systemic disease had been recognized earlier, however, the episode of pancreatitis
might have been avoided.
Copyright 2012 Massachusetts Medical Society.