The Gastrointestinal System

 Comprises:-

 The Alimentary Canal (AC)

 The Gastro-Intestinal Tract (GIT)

 The Accessory Digestive Glands (ADG)

 The Alimentary Canal
 Comprises:

 The vestibule
 The oral cavity
 The tongue
 The mouth
 The lip
 The salivary glands

 The oesophagus
The gastrointestinal tract (GIT)
 Comprises:-

 The stomach
 The duodenum
 The jejunum
 The ileum
 The appendix
 The colon
 The rectum
 The anal canal
The Accessory Digestive Glands

 Comprises:-

 The pancreas

 The liver

 The biliary system (gall bladder)

Liver Pathology

CPD
 Anatomy – 1

 Largest gland in the body

 Constitutes 2% of body weight

 Weight – 1200-1600g

 Dual blood supply:

 Portalvein (2/3)
 Hepatic artery (1/3)
 Anatomy – 2

 Acini; lobules, duct

 Portal triad

 Sinusoids
 Space of Disse
 Histology

 Hepatocytes

 Kupffer cells

 Ito cells
Histology – High Power
 Overview of Pathology

 Cell injury and fatty change

 Inflammation
 Alcoholic liver disease
 Viral
 Protozoal
 Fungal

 Tumours
 Cell Injury – 1

 Responses to hepatocyte injury

 Degeneration & intracellular accumulation

 Necrosis & apoptosis
 Inflammation

 Regeneration

 Fibrosis
 Cell Injury – 2
 Fatty change
 Intracellular accumulation of lipid globules/fat

 Varied aetiological factors:

 Alcoholic
 Pregnancy
 Therapy for HIV
 Obesity
 Diabetes
 Drug reactions
Fatty Change/Microvascular
Steatosis
 Hepatocyte Injury

 Mallory’s body

 Irregular
intracytoplasmic
eosinophilic deposits of
cytokeratin surrounded
by neutrophils in
alcoholic liver disease
 Hepatic Injury

 Councilman body
 Single cell death.

 Type of focal necrosis in

which dead hepatocyte is
identifiable as shrunken,
eosinophilic round body with
variable nucleus

 Not accompanied by
inflammation

 Signifies nonspecific
hepatocellular injury
Hepatic Cell Injury – Necrosis

 May be:

 Bridging
 Confluent
 Focal
 Massive

Piecemeal
 Zonal - Centrilobular
 Necrosis
 Piecemeal necrosis
 Necrosis of hepatocytes
 With replacement with inflammatory cells or fibrosis

 Centrilobular necrosis
 Necrotic hepatocytes around terminal hepatic venule
 Due to ischemia, drugs or toxins
 Common finding at autopsy
 Hepatic Injury - Fibrosis

 Fibrosis in the liver

 Secondary to inflammation or toxic injury
 Irreversible fibrosis
Fibrosis-bridging  regenerating nodules  Cirrhosis
Liver Cirrhosis

Next…
 Cirrhosis – 1

 Defined as diffuse

 Nodulation of liver

 Due to fibrous bands

 Subdividing liver into regenerative nodules

 Cirrhosis – 2

 Fibrosis usually irreversible

 Alters patterns of blood flow and hepatocyte perfusion;

 Starts around portal tracts, central vein or in space of Disse

 Subdivides liver into nodules of regenerating hepatocytes
 Surrounded by scar tissue

 Nodules tend to increase in size over time

 Classification of Cirrhosis
 Micronodular

 Nodule <3mm
 Associated with alcoholism (alcoholic hepatitis)

 Macronodular

 Nodule >3mm
 Associated with viral hepatitis

 Cirrhosis represents the final common pathway of various

causes of liver disease
 Causes of Liver Cirrhosis
 Alcoholic liver disease (60%)

 Viral hepatitis (10%)

 Biliary disease (5%)

 Primary hemochromatosis (5%)

 Idiopathic (5%)

 Cancer drugs

 Not easy to pinpoint exact cause for cirrhosis, once the

cirrhosis is present
Presentation of Liver Cirrhosis
 Anorexia

 Weight loss

 Weakness

 Osteoporosis

 Debilitation

 Portal hypertension

 Hepatic failure
 Hepatopulmonary Syndrome

Imbalances of pulmonary blood flow

Sequelae
 Progressive liver failure
 Portal hypertension
 Development of hepatocellular carcinoma
 Cirrhosis

Alcoholic cirrhosis

 Larger nodules associated

with periodic alcohol
abstinence, causing more
regeneration of hepatocytes

 Microscopy:
 Micronodular cirrhosis
 Mallory bodies
 Fatty change
 Clinical Sequalae
Ascites

Port-venous systemic shunts

 Rectum>hemorrhoids
 Gastro-esophageal -> esophagogastric varices

Congestive splenomegally

Hepatic encephalopathy
 Alcoholic liver disease
Alcoholic hepatitis

Histo features;

 Alcoholic hyaline
(Mallory bodies)
 With neutrophil
aggregates

 Some fibrosis
Hepatitis

Next…
 Hepatitis
Definition: inflammation of the liver
Types:

 Infective
 Viral, bacterial, fungal, parasitic

 Alcoholic

 Autoimmune

 Drug reactions
 Viral hepatitis

 Clinico-pathological syndromes

 Carrier state

 Acute hepatitis

 Chronic hepatitis

 Fulminant hepatitis
 Viral hepatitis

Hepatotropic viruses

 HAV, HBV, HCV, HDV & HEV

 Others: CMV, EBV, HSV and Adenovirus

 Viral hepatitis
Hepatitis A
 Single stranded, RNA picornavirus
 Benign, self limited,
 incubation 2-6wks.

Does not cause chronic hepatitis or carrier state.

 Prevalent in poor sanitation areas
 Fecal-oral transmission
 Outbreaks crowded unhygienic conditions eg schools,
nurseries

Blood borne transmission rare

 Viral hepatitis
Hepatitis B
DNA virus, member of the Hepadnaviridae family
Double stranded DNA

Can cause;
 Acute hepatitis
 Non-progressive chronic hepatitis
 Progressive chronic hepatitis  cirrhosis
 Fulminant hepatitis with massive liver cell necrosis
 Has a carrier state
 Hepatitis B

 Incubation period 4-26wks

 Present in all physiologic and pathologic body fluids
 Not in stools
 Transmission mode
 Transfusion, blood products, dialysis, needle stick accidents, sexual
transmission.
 May also spread by saliva, tears, breast milk, vertical transmission
 Vertical mode often  carrier state for life
 Hepatitis C
 Member of Flaviviridae, single stranded RNA
virus

 Major cause of liver disease world wide

 Main mode of transmission

 Blood transfusion (90-95%) and inoculation.

 High rate of chronic disease or cirrhosis

 Characteristic feature
 Repeated bouts of hepatic damage due to reactivation or
emergence of mutants
 Viral hepatitis

 Investigations
 Serology

 Virology

 Biopsy
 Liver Tumours

Benign and malignant both important

 Liver tumors

Benign:

 Angiomas
 Association with
PVC/thorotrast
 Hemangiomas

 Adenoma
 Liver cell adenoma
 Common in young women who
have used OCPs
 Tend to be responsive to
hormones
Hepato-cellular carcinoma
(HCC)

Defined as malignancy of the

hepatocyte, generally leading to
death within 6-20 months
 HCC

 Incidence:

 5th most common cancer in men globally

 8th most common cancer in women globally

 HCC

 Age: 30-40yrs and >65yrs

 Sex: M>F: 3 to 1

 Geographical variations: East > Africa > West

 Ethnic variations: Oriental > Blacks > Caucasian

Cancer Incidence World-wide: Current Estimates
Lung 12.5%
11 million
New cases
Other 34.9%
Breast
10.5%

Colon / rectum 9.4%

Bladder 3.3%
Stomach 9.4%
Oesophagus 4.1%
Cervix Uteri 4.6% Prostate 6.1%
Liver 5.9%
GLOBOCAN 2002
The Global Cancer Burden
International Variation in Liver Cancer Incidence
 Liver tumors
Malignant

Primary
 Hepatocellular
carcinoma
 90% of all liver cancers
 Cholangicarcinoma
 Hepatoblastoma
 Angiosarcoma

Metastatic
 Sites; breast, colon,
lung
CT Scan Diagnosis
 Hepatocellular carcinoma
Epidemiology;
 Strongly linked to prevalence of HBV infection
 Vertical acquisition confers risk of 200x by adulthood (20-40yrs)

Causal/pathogenetic factors
 Repeated cell death and regeneration
 HB Viral DNA integration, induces genomic instability

 Aflatoxins – most potent environmental factor – sub-Saharan Africa

and China

 Cirrhosis. The next major risk for HCC, after HBV

 Vaccination of children against HBV shown to decrease incidence
 Hepatocellular carcinoma
 Morphology

 Unifocal

 Multifocal

 Diffusely infiltrative

 Cholangiocarcinoma

 Fibro-lamellar
Metastatic disease
 Hepatocellurar carcinoma -
Microscopy

 Range from well differentiated to highly

anaplastic

 Well differentiated to moderately differentiated:-

 Cells recognisable

 Has various patterns

 Trabecullar, acinar or pseudoglandular patterns

 Known for bile formation

Hepatocellurar carcinoma -
Microscopy
 Liver Cancer
Fibrolamellar variant

 Young, male & female (20-40yr)

 HBV & Cirrhosis NOT risk factors.

 Hard “cirrhous” with dense fibrous bands.

 Well diff polygonal cells, nests or cords

 Liver Cancer

Cholangiocarcinoma variant

 Young, male & female (20-40yr)

 HBV & Cirrhosis NOT risk factors.

 Association with PVC and thorotrast

 Association with liver flukes (Opsthorchis)

General Clinical Presentation

 Cachexia

 Oesophageal varices

 GI bleeding

 Liver failure with hepatic coma

 HCC – Diagnostic workup

 Clinical presentation

 Laboratory tests (LFTs)

 Radiological tests

 Histological tests
 Prognosis

 Most patients do not survive beyond 6months

 Fibro-lamellar has better prognosis

 Cholangiocellular carcinoma has the worst

prognosis
 100% die within 6months
Checklist for data completeness
 Incidence
 Age
 Sex
 Geographical distribution
 Ethnic variations
 Aetiology
 Pathogenesis
 Macroscopy
 Microscopy
 Sites (tumour site in an organ)
 Spread (mode & target organ)
 Clinical presentation
 Clinical course
 Prognosis
 End!

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