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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