Normal Liver

The Liver
 The right upper quadrant of the abdomen is
dominated by the liver and its companion
biliary tree and gallbladder.

 Residing at the crossroads between the

digestive tract and the rest of the body, the
liver has the enormous task of maintaining the
body's metabolic homeostasis.
 Autopsy
➢ 1.5 kg, wedge shape
➢ 4 lobes, Right, left,
Caudate, Quadrate.
➢ Double blood
supply
➢ Hepatic arteries
➢ Portal – Venous
blood
➢ Acini / Portal triad.
➢ Lobules – central.
Normal Liver - Infant
 Sheets of connective tissue divide the liver into
thousands of small units called lobules.
 The lobule is the structural unit of the liver, with
portal triads at the vertices and a central vein in
the middle.
 The parenchymal cells of the liver are
Hepatocytes
 Hepatocytes make contact with blood in
sinusoids
•Normal Liver - Microscopy

•N
•O
•FIBROUS
•TISSUE
Hepatocytes are exceptionally active in synthesis
of protein and lipids for export
 Liver Functions:

 Metabolism – Carbohydrate, Fat & Protein

 Secretory – bile, Bile acids, salts &

pigments

 Excretory – Bilirubin, drugs, toxins

 Synthesis – Albumin, coagulation factors

 Storage – Vitamins, carbohydrates etc.

 Hepatitis:

 Hepatitis: Inflammation of Liver

 Viral, Alcohol, immune, Drugs & Toxins

 Biliary obstruction – gall stones.

▪ Specific – Heptitis A, B, C, D, E, & other

 Transmission

 Hepatitis A and E are typically caused by

ingestion of contaminated food or water.
➢ Hepatitis B, C and D usually occur as a
result of parenteral contact with infected body
fluids. Like contaminated blood or blood
products, semen, invasive medical
procedures using contaminated equipment,
drug abuse

 Hepatitis B transmission from mother to baby

 Pattern of Viral Hepatitis:

 Carrier state / Asymptomatic phase

 Acute hepatitis

 Chronic Hepatitis
▪ Chronic Persistent Hepatitis (CPH)
▪ Chronic Active Hepatitis (CAH)

 Fulminant hepatitis
 Acute Hepatitis:

 Swelling and Apoptosis

 Piecemeal or Bridging, panacinar necrosis

 Inflammation – lymphocytes, Macrophages

 Ground glass hepatocytes – HBV

 Mild fatty change – HCV

▪ Foreign bodies, organisms, and a variety of drugs may incite
a granulomatous reaction.
Acute viral Hepatitis:
Acute viral Hepatitis C:
Acute viral Hepatitis:
Acute viral Hepatitis:
 Signs and Symptoms
▪Abdominal pain
▪Joint and muscle pain
▪Change in bowel function
▪Nausea, vomiting, anorexia
▪Lethargy, malaise
▪Fever (Hepatitis A)
▪Irritability
 More Signs and Symptoms
oJaundice
oclay colored stools
odark urine
oPruritis/urticaria
oSkin abrasions
oRash
 Fulminant Hepatitis:
➢ Hepatic failure with in 2-3 weeks.
➢ Reactivation of chronic or acute hepatitis
➢ Massive necrosis, shrinkage, wrinkled
➢ Collapsed reticulin network
➢ Only portal tracts visible
➢ Little or massive inflammation – time
➢ More than a week – regenerative activity
➢ Complete recovery – or - cirrhosis.
 Chronic Hepatitis:

 Persistent & Active types. CPH/CAH

 Lymphoid aggregates

 Periportal fibrosis

 Necrosis with fibrosis – bridging fibrosis.

 Cirrhosis – regenerating nodules.

Hepatocyte necrosis is distributed
immediately around the central vein
(centrilobular necrosis).

Destruction of entire lobules (submassive

necrosis) or most of the liver parenchyma
(massive necrosis) is usually accompanied
by hepatic failure.
Liver Biopsy
B
 LESS common than B (one fourth)

C
LESS dangerous than B in the acute phase
MORE likely to go chronic than B
MORE closely linked with hepatoma than
B
 Jaundice

 Yellow discoloration of sclera, skin, mucous

membranes due to deposition of bile pigment
 Clinically detected with serum bilirubin 2-
2.5mcg/dL or  (2 times nl)
 Common Causes of Jaundice

Pre Hepatic (Acholuric) - Hemolytic

Unconjugated/Indirect Bil, pale urine
Hepatic – Viral, alcohol, toxins, drugs
Liver damage - unconjugated
Swelling, canalicular obstruction -
Conjugated
Post Hepatic (Obstructive) – Stone, tumor
Conjugated/Direct Bil, High colored urine,
 Bilirubin Metabolism And
Elimination.

Normal bilirubin production

(0.2 to 0.3 g/day) is derived
primarily from the breakdown
of erythrocytes.
Extrahepatic bilirubin is
bound to serum albumin and
delivered to the liver.
 (1)excessive production of bilirubin, (2) reduced hepatic
uptake,

➢ (3)impaired conjugation, (4) decreased

hepatocellular excretion, and
 (5)impaired bile flow (both intrahepatic and
extrahepatic).
 The first three mechanisms produce unconjugated
hyperbilirubinemia, and the latter two produce predominantly
conjugated hyperbilirubinemia.
 PATHOPHYSIOLOGY OF
JAUNDICE
❖ Un-conjugated bilirubin is tightly
complexed to serum albumin and is
virtually insoluble in water at
physiologic pH.

❖ This un-conjugated bilirubin may

accumulate systemically and deposit in
tissues, giving rise to the yellow
discoloration of jaundice.
❖ This is particularly evident in the
yellowing of the sclerae (icterus).
➢ This form cannot be excreted in
the urine even when blood levels
are high.
➢ In contrast, conjugated bilirubin
is water soluble, nontoxic, and
only loosely bound to albumin.
•“FEATHERY” DEGENERATION
 Clinical Features

 Jaundice is an almost invariable finding.

➢Impaired hepatic synthesis and secretion of albumin leads

to hypoalbuminemia, which predisposes to peripheral edema.
➢Hyperammonemia is attributable to defective hepatic urea
cycle function.

 Fetor hepaticus is a characteristic body odor variously

described as "musty" or "sweet and sour" and occurs
occasionally.
➢ A coagulopathy develops, attributable to impaired hepatic
synthesis of blood clotting factors II, VII, IX, and X.
➢ The resultant bleeding tendency may lead to massive
gastrointestinal hemorrhage as well as petechial bleeding
elsewhere.
➢ Hepatic encephalopathy
➢ Hepatic encephalopathy is a feared complication of acute
and chronic liver failure
 Cirrhosis

Cirrhosis is a pathologically defined entity that is

associated with a spectrum of characteristic clininical
manifestation

1. Irreversible chronic injury of the hepatic

parenchyma
2. Extensive fibrosis
3. Formation of regenerative nodules
Cirrhosis
 Cirrhosis

Fibrosis

Regenerating Nodule
 Etiology of Cirrhosis
60-70%
 Alcoholic liver disease
10%
 Viral hepatitis
5-10%
 Biliary disease
5%
 Primary hemochromatosis
10-15%
 Cryptogenic cirrhosis
 Wilson’s, 1AT def rare
 Cirrhosis: Pathophysiology

➢ Primary event is injury to hepatocellular elements

➢ Initiates inflammatory response with cytokine
release->toxic substances
➢ Destruction of hepatocytes, bile duct cells,
vascular endothelial cells
➢ Repair thru cellular proliferation and
regeneration
➢ Formation of fibrous scar
 Cirrhosis: Pathophysiology
➢ The normal liver contains interstitial collagens (types I, III,
and IV) in portal tracts and around central veins, with
occasional bundles in the parenchyma.
➢ Primary cell responsible for fibrosis is stellate cell
➢ Become activated in response to injury and lead to ed
expression of fibril-forming collagen
➢ Above process is influenced by Kupffer cells which activate
stellate cells by eliciting production of cytokines
➢ Sinusoidal fenestrations are obliterated because of ed
collagen and EC matrix synthesis
 Cirrhosis: Pathophysiology

➢ Portal vein-to-hepatic vein and hepatic artery-to-

portal vein vascular shunts also develop.
➢ Prevents normal flow of nutrients to hepatocytes
and increases vascular resistance
➢ Initially, fibrosis may be reversible if inciting events
are removed
➢ With sustained injury, process of fibrosis becomes
irreversible and leads to cirrhosis
 Pathogenesis

 Hepatocyte injury leading to necrosis.

▪ Alcohol, virus, drugs, toxins, genetic etc..

 Chronic inflammation - (hepatitis).

 Bridging fibrosis.

 Regeneration of remaining hepatocytes

Proliferate as round nodules.

 Loss of vascular arrangement results in

 Cirrhosis Features:

 Liver Failure

 Portal obstruction, Portal systemic shunts…

 Portal hypertension, Splenomegaly

 Jaundice, Coagulopathy, hypoproteinemia,

toxemia, Encephalopathy,
 Clinical Features

 Hepatocellular failure.
▪ Malnutrition, low albumin & clotting factors,
bleeding.
▪ Hepatic encephalopathy.

 Portal hypertension.
▪ Ascites, Porta systemic shunts, varices,
splenomegaly.
Ascitis in Cirrhosis
Micronodular cirrhosis:
Micronodular cirrhosis
Macronodular Cirrhosis
Liver Biopsy – Cirrhosis:
Nutmeg Liver-Cardiac Sclerosis
Cirrhosis
Clinical
Features
 Complications:

 Congestive splenomegaly.

 Portal hypertension and esophageal

varices

 Hepatocellular failure.

 Hepatic encephalitis / hepatic

coma.
 Evaluation of the Cirrhotic

➢ Physical Exam ➢ Lab tests

 Jaundice  Anemia
 Ascites  Thrombocytopenia
 Caput medusae  Coagulopathy
 Asterixis  Hypoalbuminemia
 Spider angiomas  Hepatitis serologies
 Palmer erythema ▪ -fetoprotein
 Testicular atrophy
 Gynecomastia
 +/- Palpable spleen
(portal HTN)
 Prevention Teaching

 What would you teach?

• Adequate sanitation and hygiene
• Wash hands before eating and after
using the toilet
• Drink only purified or bottled water
• No sharing of eating utensils,
needles, toothbrushes, razors, etc.
• Choose your tattoo or piercing
person carefully. Inspect the facility
 Classification
 99% are metastatic, i.e., SECONDARY, esp. from
portal drained organs
 Just about every malignancy will wind up eventually in
the liver, like the lungs

Benign Malignant

Hemangioma Primary liver cancers

Focal nodular Hepatocellular carcinoma
hyperplasia Fibrolamellar carcinoma
Adenoma Hepatoblastoma
Liver cysts
 Primary Carcinoma
of the Liver
 Most arise from hepatocytes
and are termed Hepatocellular
Carcinoma (HCC).

Hepatocellular Carcinoma
 Pathogenesis

❖ Several factors relevant to the pathogenesis of HCC.

❖ Three major etiologic associations have been established:

infection with HBV, chronic liver disease.
❖ Many factors, including age, chemicals,
hormones,
sex, alcohol, and nutrition, viruses, interact
development of HCC. in the
❖ The development of cirrhosis appears to be an important,
but not requisite, contributor to the emergence of HCC.
Treatment
■ Liver transplatation

■ Surgical resection (best prognosis for

long-term survival, but possible in only
10-15% of cases)
 Radiotherapy