SM_150b: Liver Histology and Basic Pathology Flashcards
Liver receives dual blood supply from the ____ and ____
Liver receives dual blood supply from the portal vein and hepatic artery
- Portal vein: 60-70%
- Hepatic artery: 30-40%
This is the ____
This is the liver
Describe general features of the liver
General features of the liver
- Large functional reserve
- Extensive capacity to regenerate
- 80-90% of damage occurs before liver failure: disease often detected late / in chronic phase, by screening lab tests
Mechanisms of liver injury and repair include ____, ____, ____, ____, and ____
Mechanisms of liver injury and repair include hepatocyte degeneration, necrosis and apoptosis, inflammation, regeneration, and fibrosis
- Hepatocyte degeneration (potentially reversible): intracellular accumulation of fat (steatosis) and bile (cholestasis)
Hepatocyte degeneration and intracellular accumulation involves ____, ____, ____, ____, and ____
Hepatocyte degeneration and intracellular accumulation involves balloon degeneration, fat accumulation, lymphoid aggregation, nacrosis, and apoptosis
- Ballooning degeneration: clumping organelles and cytoskeleton
- Necrosis (group of ghost cells, coagulative necrosis): hepatic artery thrombosis, ischemic injury
- Apoptosis (individual mummified hepatocyte): viral hepatitis, programmed cell death
Liver inflammation + hepatocytes may result from ____ or ____
Liver inflammation + hepatocytes may result from chronic viral hepatitis or immune-mediated processes
Stellate cells ____ and ____ in chronic damage
Stellate cells proliferate and undergo fibrosis in chronic damage
Chronic liver damage involves ____, ____, and ____
Chronic liver damage involves hepatic stellate cell activation and proliferation, deposition of scar matrix, and Kupffer cell activation
Describe liver damage (such as due to fibrosis)
Liver damage (such as due to fibrosis)
- Ischemic hepatocytes, obstructed veins
- Contiguous hepatocytes die
- Scars form
- Scars in regions of extinction contract and condense -> become fibrous septa
Types of fibrosis in the liver include ____, ____, and ____
Types of fibrosis in the liver include portal fibrosis, pericellular fibrosis, and bridging fibrosis (early nodule formation)
- Scarring: fibrosis
- Hepatocyte regeneration: nodules
Categories of liver dysfunction include ____, ____, and ____
Categories of liver dysfunction include acute liver failure, chronic liver disease, and hepatic dysfunction without overt necrosis
Describe acute liver failure
Acute liver failure
- Acute onset liver illness
- Results in encephalopathy (defining condition of liver failure)
- Within 6 months: fulminant liver failure (time course < 2 weeks before the onset of jaundice), sub-fulminant liver failure (within 3 months of the onset of jaundice)
Acute liver failure mechanism is ____
Acute liver failure mechanism is massive hepatocyte necrosis
- Most commonly due to drugs, toxins, viral, autoimmune
Acute liver failure is most commonly caused by ____
Acute liver failure is most commonly caused by acetaminophen
This is ____ due to ____
This is acute liver failure due to acetaminophen overdose
Chronic liver disease results from ___ or ___
Chronic liver disease results from continuous injury or repeated injuries over time
- Continuous injury (chronic hepatitis)
- repeated injuries over time end in liver failure
Chronic liver disease mechanism is ____ -> ____ -> ____
Chronic liver disease mechanism is fibrosis -> cirrhosis -> liver failure
Describe fibrosis to cirrhosis progressive in chronic liver disease
Fibrosis to cirrhosis progressive in chronic liver disease
- Portal fibrosis
- Pericellular fibrosis
- Bridging fibrosis (nodule formation)
Hepatic dysfunction with overt necrosis is when ____ and results from ____ or ____
Hepatic dysfunction with overt necrosis is when the liver is viable but unable to perform metabolic function and results from tetracycline toxicity or acute fatty liver of pregnancy
This is ____
This is cirrhosis
Fatty liver disease can be ____ or ____
Fatty liver disease can be non-alcoholic fatty liver disease or alcoholic fatty liver disease
- Different etiology
- Same mechanism
- Same pathology
Describe fatty liver disease pathophysiology
Fatty liver disease pathophysiology
- Steatosis: accumulation of fat in hepatocytes
- Steatohepatitis: inflammation associated with steatosis
- Fibrosis (progressive): cirrhosis
- Liver failure or hepatocellular carcinoma (HCC)
Fatty liver will show ____, ____, and ____
Fatty liver will show mallory bodies, acute hepatitis, and lipogranulomas
Alcoholic fatty liver disease results from ___
Alcoholic fatty liver disease results from alcohol
Nonalcoholic fatty liver disease results from ____ and ____
Nonalcoholic fatty liver disease results from obesity / metabolic syndrome and diabetes
- Metabolic syndrome: central obesity, insulin resistance, dyslipidemia, and hypertension
Fatty liver involves ____ which is ____
Fatty liver involves hepatic steatosis which involves triglyceride storage
- Liver is the check-point for fat: accumulates fat when adipocytes are overwhelmed -> ectopic triglyceride deposition -> steatosis
____ store energy as triglycerides
Adipocytes store energy as triglycerides
Describe pathology of fatty liver disease
Pathology of fatty liver disease
- Fatty liver (steatosis)
- Steatohepatitis
- Fibrosis -> cirrhosis
- Liver failure or hepatocellular carcinoma
Alcohol consumption of ____ is required for alcoholic fatty liver disease
Alcohol consumption of > 20 g daily is required for alcoholic fatty liver disease
Alcohol consumption of ____ is required for nonalcoholic fatty liver disease
Alcohol consumption of less than 20 g weekly is required for nonalcoholic fatty liver disease
Excess energy results in ____, ____, and ____ that lead to fatty liver
Excess energy results in increased fatty acid uptake in the liver, increased fatty acid synthesis, and increased triglyceride synthesis that lead to fatty liver
Nonalcoholic fatty liver disease two-hit hypothesis involves ____ and ____
Nonalcoholic fatty liver disease two-hit hypothesis involves fat accumulation (steatosis) and oxidative stress to hepatocytes
Steatosis can be ____ or ____
Steatosis can be macrovesicular or microvesicular (with lipogranuloma)
Macrovesicular steatosis is ____
Macrovesicular steatosis is large droplet
Steatohepatitis involves ____ and ____
Steatohepatitis involves lipogranulomas and lipoapoptosis
- Cell death by apoptosis
- Exposure of non-adipose tissues (liver) to an excess of long-chain fatty acids
Alcohol consumption -> ____ -> ____ -> ____
Alcohol consumption -> alcoholic fatty liver disease -> cirrhosis -> end-stage liver disease
Alcohol metabolites such as ____ cause liver injury
Alcohol metabolites such as acetaldehyde cause liver injury
- Liver metabolizes 7-10 gram / EtOH / hour
Metabolism of alcohol is an ____ process involving ____
Metabolism of alcohol is an oxidative process involving conversion of 95% of ethanol to acetaldehyde and then to acetate
Alcohol metabolizing enzyme systems include ____, ____, ____, and ____
Alcohol metabolizing enzyme systems include ADH / ALDH2 system, microsomal CYP2E1 system, and peroxisomal catalase
- Resulting increase in NADH/NAD+ ratio favors hepatic synthesis of fatty acids and triglycerides -> causing fatty liver
Describe hepatotoxic effects of acetaldehyde
Hepatotoxic effects of acetaldehyde
- Increases lipid peroxidation
- Binds plasma membranes
- Interferes with mitochondrial electron transport chain
- Inhibits nuclear repair
- Interferes with microtubule function
- Increases collagen synthesis: stellate cell activation
Alcoholic fatty liver disease is morphologically divided into 3 types in order of severity: ____, ____, and ____
Alcoholic fatty liver disease is morphologically divided into 3 types in order of severity: fatty liver steatosis, alcoholic steatohepatitis, and cirrhosis and hepatocellular carcinoma
___ stage of alcoholic fatty liver disease starts in centrizonal area (zone 3) and extends towards portal area (zone 1)
Fatty liver steatosis stage of alcoholic fatty liver disease starts in centrizonal area (zone 3) and extends towards portal area (zone 1)
____ stage of alcoholic liver disease involves ballooning cell change and Mallory bodies, inflammatory infiltrate (neutrophils), and pericellular and perivenular fibrosis
Alcoholic steatohepatitis stage of alcoholic liver disease involves ballooning cell change and Mallory bodies, inflammatory infiltrate (neutrophils), and pericellular and perivenular fibrosis
These are ____ in the ____ stage of alcoholic liver disease
These are lipogranulomas in the alcoholic steatohepatitis stage of alcoholic liver disease
These are ____ in ____ stage of alcoholic liver disease
These are Mallory bodies in the alcoholic steatohepatitis stage of alcoholic liver disease
Liver cell regeneration becomes ___ in alcoholic hepatitis
Liver cell regeneration becomes 2 cell thick plates in alcoholic hepatitis
Describe the progression of alcoholic liver disease to cirrhosis
Progression of alcoholic liver disease to cirrhosis
- Alcohol -> liver cell death -> hepatocyte regeneration -> regenerative nodules -> distortion of liver architecture -> functional problems
- Alcohol -> inflammation -> stellate cell activation -> fibrous scars -> distortion of liver architecture -> functional problems
This is ___
This is pericellular fibrosis
This is ___ in ___
This is fibrous septa in alcoholic steatohepatitis
This is ____
This is alcoholic cirrhosis
(with residual steatosis)
