Beruflich Dokumente
Kultur Dokumente
DR. MAGKASI
LIVER
1,400 1,600 gms
2.5% of body weight
Dual blood supply
o Portal vein: 60% - 70%
o Hepatic artery: 30% - 40%
General Features of Hepatic Disease
Vulnerable to metabolic, toxic, microbial, circulatory,
and neoplastic insults
Dominant primary diseases
o Viral hepatitis, alcoholic liver disease, NAFLD
o Hepatic damage maybe secondary
o Enormous functional reserve
o Insidious process
o May heal without clinical detection
Patterns of Hepatic Injury
1. Degeneration and intracellular accumulation
2. Necrosis and apoptosis
3. Inflammation
4. Regeneration
5. Fibrosis
Degeneration and Intracellular Accumulation
Degeneration
Ballooning degeneration toxic or immune
Feathery degeneration cholestatic injury
Accumulation
Iron and copper
Triglyceride droplets steatosis
o Microvesicular AFLP, valproic acid toxicity, Reye
Syndrome
o Macrovesicular obese, diabetic
Necrosis and Apoptosis
Coagulation necrosis
Lytic necrosis
Apoptosis
Zonal distribution
o Centrilobular, midzonal and periportal
Inflammation
Acute or chronic inflammatory cells
Necrosis incites inflammatory reactions
Inflammation may precede necrosis granulomatous
inflammation
Regeneration
Marked by mitosis, thickening of hepatocytes cords &
some disorganization of the parenchymal structures
Canal of Hering-bile ductile unit serves as reserve
compartment for restitution, ductular reaction
Even with submassive or massive necrosis, as long as
connective tissue framework in intact, perfect
restitution
Fibrosis
Response to inflammation or direct toxic insult
Irreversible
Hepatic Failure
Most severe clinical consequence of liver disease
May be due to sudden, massive liver destruction
(fulminant hepatic failure)
Or due to insidious destruction of hepatocytes or by
repetitive waves of parenchymal damage
80-90% functional capacity destroyed
Liver transplantation only hope
80% mortality
Chronic liver disease
Most common route to hepatic failure
Endpoint of relentless chronic hepatitis leading to
cirrhosis
Hepatic dysfunction without overt necrosis
Hepatocytes are viable but unable to perform
functions
Tetracycline toxicity, acute fatty liver pregnancy
Hepatic Failure: Clinical Features
Jaundice
Hypoalbuminemia
Hyperammononemia
Fetor hepaticus
Impaired estrogen metabolism (palmar erythema,
spider angiomas, male hypogonadism and
gynecomastia)
Coagulopathy
Encephalopathy
Hepatorenal syndrome
o Drop in urine output
o Rising BUN, creatinine
o Poor prognosis
Hepatopulmonary syndrome
o Chronic liver disease
o Hypoxemia
o Intrapulmonary vascular dilations (IVPD)
Cirrhosis: Characteristics
Bridging fibrous septae
Parenchymal nodules
Disruption of liver architecture
Features to be understood:
Parenchymal and subsequent fibrosis are diffuse
Nodularity is part of diagnosis, resulting from repeated
cycles of regeneration and scarring
Vascular architecture reorganized forming bypass
channels
Fibrosis is a key feature of progressive liver damage
slow regression with cessation of injury; reversal is
rare
Pathogenesis
Death of hepatocytes
ECM deposition
Vascular reorganization
Page 1 of 6
o
o
Clinical Features
40% is asymptomatic
Nonspecific clinical manifestations
Incipient or overt hepatic failure
Hepatopulmonary syndrome
Death from:
o Progressive liver failure
o Complication of portal hypertension
o Hepatocellular carcinoma
Portal Hypertension
Increased resistance to portal blood flow
o Caused by contraction of vascular smooth muscle
cells and myofibroblasts and disruption of blood
flow, by scarring and formation of parenchymal
nodules
Increase in portal venous blood flow resulting from a
hyperdynamic circulation
o Caused by arterial vasodilation, primarily in
splanchninc circulation
Consequences:
1. Ascites
Detectable when at least 500ml
Generally serous
Pathogenesis
Sinusoidal hypertension
Percolation of hepatic lymph into the peritoneal
cavity
Splanchnic vasodilation and hyperdynamic
circulation
2. Splenomegaly
1000 gms wt
Induce hypersplenism with thrombocytopenia and
pancytopenia
3. Jaundice and Cholestasis
Causes of Jaundice:
o Bilirubin overproduction
o Hepatitis
Common Virus
Hepatitis A (HAV)
name
Common Disease
Infectious
Name
Virus
Picornavirus naked
capsid RNA
Jaundice
Occurs when equilibrium between bilirubin production
and clearance is distributed by
1. Excessibe extrahepatic production of bilirubin
2. Reduced hepatocyte uptake
3. Impaired conjugation
4. Decreased hepatocellular excretion
5. Impaired bile flow
Cholestasis
Etiology: impaired bile formation and blood flow
Accumulation of bile in hepatic parenchyma
Morphology
Caused by:
o Intrahepatic or extrahepatic obstruction of bile
channels
o Defects in hepatocyte bile secretion
Treatment:
o Extrahepatic biliary obstruction surgery
o Intrahepatic cholestasis medical/transplant
Elevated ALP and GGT
Infectious Disorders
Viral foremost hepatic infection
Military tuberculosis
Malaria
Staphylococcal bacteremia
Salmonellosis
Candida
Amebiasis
Viral Hepatitis
Infectious Mononucleosis (EBV)
CMV in newborn or immunosuppressed
Yellow fever virus
Hepatitis B (HBV)
Hepatitis C (HCV)
Hepatitis D (HDV)
Hepatitis E (HEV)
Serum
Post-transfusion
or non-A, non-B
Flavivirus
enveloped RNA
Delta
enteric
Calcivirus naked
capsid RNA
Acute Hepatitis
Parenternal,
Sexual
Occasionally
severe
Parenternal,
sexual
Usually subclinical
No
Yes
Yes (high)
Defective
enveloped circular
RNA
Parenternal,
sexual
Co-infection with
HBV occasionally
superinfection
with HepB
Yes
Acute hepatitis
-Acute Hepa
-Chronic Hepa
-Cirrhosis
-Hepato-cellular
carcinoma (HCC)
-Acute Hepa
-Chronic Hepa
-Cirrhosis
-HCC
-Acute Hepa
-Chronic Hepa
-Cirrhosis
-HCC
Transmission
Fecal-oral
Severity
Mild
Chronicity or
carrier state
Clinical disease
Hepadnavirus
enveloped DNA
Fecal-oral
Normal patients:
mild, pregnant
patients: severe
No
Page 2 of 6
Laboratory
diagnosis
Symptoms and
anti-HAV IgM
Prevention
Vaccine, hygiene
Symptoms and
serum levels of
HBsAg, HBeAg,
and anti-Hbc IgM
Vaccine
Symptoms and
anti-HCV ELISA
Anti-HCV
ELISA
Hygiene
Bacterial, Parasitic, and Helminthic Infections
Bacterial etiology
o S. aureus, S. typhi, & T. pallidum
o Bacterial gut flora in ascending cholangitis
Parasitic and helminthic
o Malaria, schitosomiasis, strongyloidiasis,
cryptosporidiosis,, leishmaniasis, echinococcosis,
liver flukes
Liver abscess
o Amebic, pyogenic
Liver Abscess
Solitary or multiple; echinococcal or amebic
Spread thru
portal vein
arterial supply
direct extension penetrating trauma
ascending infection
Rx: surgical drainage; antibiotics
MR: 30-90%;80% surgery with early dx
Autoimmune Hepatitis
A chronic and progressive hepatitis of unknown
etiology
Salient features
o Female predominance (78%)
o Absences of viral serologic markers
o Elevated serum IgG & gamma-globulin levels
o High serum titers of autoantibodies
Types I and II, based on the patterns of circulating
antibodies
Type I associated with HLA DR-3
o ANA, SMA, AAA, anti-SLA/LP antibodies
Type II
o ALKM-1, ACL-1
Lymphocyte and plasma cell infiltrates are prominent
May progress to cirrhosis without clinical diagnosis
Untreated, 40% die within 6 months, cirrhosis in at
least 40% of survivors
Responsive to immunosuppressive therapy
Liver transplantation for patients with severe disease
Drug and Toxin-induced Disease
Injury may result from:
o Direct toxicity to hepatocytes of biliary epithelial
cells
o Conversion of xenobiotic to active toxin, or
o Immune mechanisms
Maybe predictable (INTRINSIC) or unpredictable
(IDIOSYNCRATIC)
Predictable drug reactions:
Acetaminophen- leading cause of drug-induced acute
liver failure
Amanita phalloides toxin, CCl4, alcohol
Isoniazid, Nonsteroidal analgesics, antiseizure
medications prescription drugs with idiosyncratic
reactions
Reye syndrome
Page 3 of 6
Hemochromatosis
Excessive accumulation of body iron especially in
parenchymal organs, e.g. liver and pancreas
Result from genetic defect causing excessive
absorption (hemochromatosis) or parenteral
administration of iron, (hemosiderosis) e.g.,
transfusion.
Total iron > 50 gm (NV=2-6 gm)
Adult form of hemochromatosis is almost always
caused by mutations of HFE
Characteristic features
1. Micronodular cirrhosis in all patients
2. Diabetes mellitus in 75- 80% of patients
3. Skin pigmentation 75- 80% of patients
Iron accumulation is lifelong manifest 5th or 6th
decades
Male prominence (5 to 7:1)
Mechanisms of direct tissue toxicity of excessive iron:
1. Lipid peroxidation via iron-catalyzed free rad
2. Stimulate collagen formation
3. Reactive O2 & iron interacting with DNA causing
lethal injury or predisposition to HCC
Hepcidin- main regulator of iron absorption encoded
by HAMP gene
Transcription of hepcidin is increased by inflammatory
cytokines and iron and decreased by iron deficiency,
hypoxia and ineffective erythropoiesis
Hepcidin lowers plasma iron levels; a deficiency in
hepcidin causes iron overload.
Hemochromatosis: Diagnosis and treatment
Very high serum iron and ferritin, exclude secondary
causes, liver biopsy
Screening of family members
Diagnosed in the subclinical, precirrhotic stage
Regular phlebotomy with normal life expectancy
Autosomal recessive, mutation of ATP7B gene
Impaired excretion of copper into bile and failure to
incorporate copper into ceruloplasmin
Marked by accumulation of toxic levels of copper in
many tissues or organs, principally liver, brain and eye.
Treatment:
Alcohol withdrawal and proper nutrition
Cause of death:
1. Hepatic coma
2. Massive GIT hemorrhage
3. Intercurrent infection
4. Hepatorenal syndrome
5. Hepatocellular carcinoma (1-6%)
Alpha-1-AT Deficiency
Autosomal recessive
Marked by abnormally low serum levels or A1AT
protease inhibitor (PI)
Inhibits proteases, elastase, cathepsin G, and
proteinase 3
Gene located in chromosome 14
PIMM, 90% genotype, normal A1AT
Page 4 of 6
Malignant tumors
Can be primary or secondary
Primary liver CA, uncommon in N. America and w.
Europe (0.5-2%) but 20-40% other countries
Hepatocellular CA: arise from hepatocytes
Cholangiocarcinoma: from bile ducts
Hepatoblastoma: young childhood
Angiosarcoma: PVC arsenic, thorothrast
Hepatoblastoma
Most common liver tumor of young childhood
1-2 in 1 million births
Fatal if not treated
Two variants
Epithelial type
Mixed epithelial and mesenchymal type
Hepatocellular carcinoma
Third most common frequent cause of cancer death
Male predominance, 2,4:1
Four major etiologic factors associated with HCC
o Chronic viral infection (HBV, HCV)
o Chronic alcoholism
o Non alcoholic steatohepatitis (NASH)
o Food contaminants (aflatoxin)
HCC: Pathogenesis
Other conditions
Tyrosinemia- 40% develop HCC despite adequate
important but not requisite for HCC
HCC: clinical features
Masked by those related to cirrhosis of chronic
hepatitis
Ill-defined upper abdominal pain, malaise, fatigue,
weight loss, abdominal mass orr fullness
Jaundice, fever, GIT or esophageal bleed
Inc. AFP,
USG,
Hepatic angiography
CT, &MRI
Death from: cachexia, GIT or esophageal variceal
bleeding, liver failure with hepatic coma, & tumor
rupture.
Fibrolamellar Carcinoma
Young males and females
Patients do not have underlying chronic liver disease
Unknown etiology
Cholangiocarcinoma
Malignancy of the Biliary tree, arising from bile ducts
within and outside of the liver
Risk conditions: primary sclerosing cholangitis,
congenital fibropolycystic disease of biliary system,
previous exposure to thorotrast & previous infection
by liver fluke, O. sinensis
Morphology: adenocarcinoma
Mixed variants with HCC & cholangiocarcinoma may
occur
Hematogenous metastasis to lungs, bones (mainly
vertebra), adrenals, brain, etc present on autopsy in
50% of cases
Detected late in its course
Median time from Dx to death: 6 months
Page 5 of 6
Metastatic Tumors
More common than primary liver CA
Breast, lung & colon, pancreas
Any site, leukemias and lymphomas
Hepatomegaly + nodularity of free edge
Central necrosis and umbilication
Congenital Anomalies
Congenitally absent
Duplication
Aberrant locations
Folded fundus phrygian cup
Agenesis of hepatic or CBD
Hypoplastic narrowing of biliary channels
Disorders of the Gallbladder
1. Cholelithiasis (Gallstones)
2. Cholecystitis
Acute
Chronic
Risk Factors of Gallstones
Cholesterol Stones
Demorgraphy: N. Europe, N. and S. America, native
Americans, Mexican Americans
Advancing age
Female sex hormones
o Female gender
o Oral contraceptives
o Pregnancy
Obesity
Rapid weight reduction
Gallbladder stasis
Inborn disorders of bile acid metabolism
Hyperlipidemia syndromes
Pigment Stones
Demography: Asian > Western, rural > urban
Chronic hemolytic syndromes
Biliary infection
GIT disorders: ileal disease (e.g. Crohn disease), ileal
resection or bypass, cystic fibrosis with pancreatic
insufficiency
Cholelithiasis: Clinical Features
80% are silent
90% - cholesterol stones: the rest are pigment stones
composed of bilirubin calcium salts
Sx: excruciating colicky or constant biliary pain
Complications: empyema, perforation, fistula,
cholangitis, and obstructive cholestasis or pancreatitis,
intestinal obstruction, risk for cholangiocarcinoma
Cholecystitis
Acute, chronic or acute superimposed on chronic
Almost always in association with gallstones
Most common indications for abdominal surgery
Acute calculous cholecystitis: 90% precipitated by
obstn of the ncek or cystic duct
Acute acalculous cholecystitis: severely ill patients
without gallstones
o Postoperative state after major nonbiliary surgery
o Severe trauma/burns, MOF, prolonged IV
hyperalimentation, postpartum state
Page 6 of 6