SMS 2044

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. V

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

•N

•O•FIBROUS

•TISSUE

•Normal Liver - Microscopy

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.

Detoxification – toxins, ammonia, 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 at birth.

Pattern of Viral Hepatitis:

Carrier state / Asymptomatic phase

Acute hepatitis

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

Fulminant hepatitis

Cirrhosis

Hepatocellular Carcinoma

Acute Hepatitis:

Swelling and Apoptosis

Piecemeal or Bridging, panacinar necrosis

Inflammation – lymphocytes, Macrophages

Ground glass hepatocytes – HBV

Mild fatty change – HCV

Portal inflammation and Cholestasis

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

CLESS common than B (one fourth)

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) - HemolyticUnconjugated/Indirect Bil, pale urine

Hepatic – Viral, alcohol, toxins, drugsLiver damage - unconjugatedSwelling, canalicular obstruction - Conjugated

Post Hepatic (Obstructive) – Stone, tumorConjugated/Direct Bil, High colored urine,

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.

Bilirubin Metabolism And Elimination.

(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

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).

Un-conjugated bilirubin is tightly complexed to serum albumin and is virtually insoluble in water at physiologic pH.

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

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.

Clinical Features

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

Alcoholic liver disease 60-70%

Viral hepatitis 10%

Biliary disease 5-10%

Primary hemochromatosis 5%

Cryptogenic cirrhosis 10-15%

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

PathogenesisHepatocyte 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 regenerating hepatocytes ineffective.

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

CirrhosisClinical

Features

Complications:

Congestive splenomegaly.

Portal hypertension and esophageal varices

Hepatocellular failure.Hepatic encephalitis / hepatic coma.

Hepatic encephalopathy

Hepatocellular carcinoma.

Evaluation of the Cirrhotic

Physical Exam Jaundice Ascites Caput medusae Asterixis Spider angiomas Palmer erythema Testicular atrophy Gynecomastia +/- Palpable spleen (portal

HTN)

Lab tests Anemia Thrombocytopenia Coagulopathy Hypoalbuminemia Hepatitis serologies -fetoprotein

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

ClassificationClassification

HemangiomaHemangiomaFocal nodular Focal nodular hyperplasiahyperplasiaAdenomaAdenomaLiver cystsLiver cysts

Primary liver cancersPrimary liver cancersHepatocellular carcinomaHepatocellular carcinomaFibrolamellar carcinomaFibrolamellar carcinomaHepatoblastomaHepatoblastoma

Benign Malignant

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

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, sex, chemicals, viruses, hormones, alcohol, and nutrition, interact in the development of HCC.

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