liver disease 18 Flashcards
what are the classic anatomical features of liver?
Coronary ligament
right lobe
left triangular ligament
Left lobe
Falciform ligament
ligament of teres
Gallbladder
what is the normal histology of liver?
hexagonal lobular structure
hepatocytes arranged concentrically around central vein
at the periphery of each lobule lies the portal triad which consists of hepatic artery, portal vein, bile duct
Oxygenated blood is supplied to the liver primarily via hepatic artery within the portal triad
at the periphery, entering and gradually mixing with the deoxy blood from the portal veins as it flows toward the central vein
The central region surrounding the central vein is the most susceptible to ischemic injury and hypoxia due to it being predominantly deoxy blood supply
these vascular arrangement explains the distribution of pathological changes where fatty changes are more prominent in the peripheral regions while necrosis predominantly occurs in the centrilobular area
what can diseases of liver affect?
Hepatic diseases can attribute to dysfunction in any of the livers diverse physiological role
what is the pattern of hepatic injury?
1- Degeneration and intra-cellular accumulation –> ballooning( swelling ), feathery degeneration, fat, pigment
2- inflammation –> influx of acute or chronic inflammatory cells into portal tracts or the parenchyma
3- Cell death—> Coagulative necrosis is due to ischemia , apoptosis due to toxic , viral , immunological injury
Lesion may be focal, zonal, submissive or massive
4- Regeneration
5- Fibrosis –> develops after inflammation or direct toxin insults
Fibrosis divides the liver into nodule of regenerating hepatocyte surrounded by scar tissue
Neoplasm –> 99% metastatic , 1% primary
compare alcoholic and non alcoholic fatty liver disease ?
Alcohol is well known cause of fatty liver disease in adults
can manifest histologically as :
1- steatosis ( fat accumulation within hepatocyte )
2- Steatohepatitis ( inflammation in liver with fat )
3- Cirrhosis ( Advances liver fibrosis with nodular regeneration )
Non alcoholic fatty liver disease :
Mimic the spectrum of hepatic changes associated with alcohol abuse –> metabolic –> insulin resistance, obesity, diabetes mellitus, hypertension, dyslipidemias
describe alcoholic liver disease ?
Excessive ethanol consumption cause more than 60% of chronic liver disease in western countries
accounts for 40-50% of death due to cirrhosis
alcohol abuse is the 5th leading cause of death
From 25% to 30% of hospitalized patients have problems related to alcohol abuse
what are 3 changes observed in fatty liver disease ?
hepatic steatosis
Alcoholic hepatitis
Fibrosis and cirrhosis ( irreversible )
can present in any combination^^
what can cirrhosis lead to?
Liver failure –> jaundice, coagulation
Portal hypertension —> varcies , ascites, etc
Hepatocellular carcinoma
how does alcohol cause fatty liver?
it causes shunting of normal substrates away from catabolism TOWARDS lipid biosynsthesis due to :
1-Excess NADH generation from alcohol dehydrogenase and acetaldehyde dehydrogenase
2- IMPAIRED ASSEEMBLY /SECRETION OF LIPOPROTEINS ( lead to accumulation within the liver)
3- Increased peripheral fat catabolism (more moves toward the liver)
Where does fat accumulate in steatosis ?
fat accumulates begins at :
CENTRILOBULAR HEPATOCYTES
then it will be expanding until reaching portal triad
Lipid droplets range from small microvesicular to large macrovesicular
describe steatohepatitis ?
typicall more pronounced with alcohol use than NAFLD but can seen with variable degrees of prominence in fatty liver disease due to any cause
what can cause alcoholic hepatitis ?
acetaldehyde
alcohol
reactive oxygen species ( generated during alcohol metabolism )
cytokines- mediated inflammation and cell injury
describe morphology of steatohepatitis ?
1- Hepatocyte ballooning —> cell death increase in size ( considered a form of apoptosis )
2- Mallory denk bodies ( intermediate filaments , keratins 8 and 18 ) –> visible as eosinophilic cytoplasmic inclusions in degenerating hepatocyte
3- neutrophil infiltration
describe steathepatitis with fibrosis ?
Fibrosis appear in the CENTRILOBULAR region as CENTRAL VEIN SCLEROSIS
PERISINUSOIDAL SCAR appear next in the space of diss of centrilobular region
then spread outward encircling individuals or small clusters of hepatocyte in a pattern of chicken wire fence
these TENDRILS OF FIBROSIS eventually link to PORTAL TRACTS and then begin to condense to create CENTRAL PORTAL FIBROUS SEPTA
what are the clinical features of hepatic steatosis ?
Asymptomatic
hepatomegaly with mild elevation serum bilirubin and alkaline phopshpatase
Alcohol withdrawal an adequate diet are sufficient treatment
Alcoholic hepatitis can occur after js weeks or month of consistent use
15-20 years of drinking excessive are necessary to develop alcoholic cirrhosis
clinical features of end stage alcoholic liver disease?
immediate cause of death :
hepatic failure
massive GIT hemorrhage
Intercurrent infection
hepatocellular carcinoma in 3-6% cases
describe non alcholic fatty liver disease ?
fatty liver disease Develop in person who do not drink acholol
the name is used to describe overt clinical features of liver injury :
elevated transaminases and histologic features of hepatitis
what is NAFLD associated with ?
Insulin resistance
metabolic syndrome
Type 2 diabetes
Obesity
Dyslipidemia
Hypertension
what does does insulin resistance do?
Accumulation of triglycerides by 3 mechanism :
1- Impaired oxidation of fatty acids
2- Increased synthesis and uptake of fatty acids
3- Decreased hepatic secretion of very low density lipoproteins
features of NAFLD?
Most common cause of incidental elevation of serum transaminases
asymptomatic
Fatigue , malaise, right upper quadrant discomfort
REQUIRES LIVER BIOSPYS FOR DIAGNOSIS
Progression from steatosis to active steatohepatitis then cirrhosis is low
Significant contributor to the pathogenesis of CRYPTOGENIC cirrhosis
