SM_150b: Liver Histology and Basic Pathology

Question 1

Liver receives dual blood supply from the ____ and ____

Answer 1

Liver receives dual blood supply from the portal vein and hepatic artery

• Portal vein: 60-70%
• Hepatic artery: 30-40%

Question 2

This is the ____

Answer 2

This is the liver

Question 3

Describe general features of the liver

Answer 3

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

Question 4

Mechanisms of liver injury and repair include ____, ____, ____, ____, and ____

Answer 4

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)

Question 5

Hepatocyte degeneration and intracellular accumulation involves ____, ____, ____, ____, and ____

Answer 5

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

Question 6

Liver inflammation + hepatocytes may result from ____ or ____

Answer 6

Liver inflammation + hepatocytes may result from chronic viral hepatitis or immune-mediated processes

Question 7

Stellate cells ____ and ____ in chronic damage

Answer 7

Stellate cells proliferate and undergo fibrosis in chronic damage

Question 8

Chronic liver damage involves ____, ____, and ____

Answer 8

Chronic liver damage involves hepatic stellate cell activation and proliferation, deposition of scar matrix, and Kupffer cell activation

Question 9

Describe liver damage (such as due to fibrosis)

Answer 9

Liver damage (such as due to fibrosis)

1. Ischemic hepatocytes, obstructed veins
2. Contiguous hepatocytes die
3. Scars form
4. Scars in regions of extinction contract and condense -> become fibrous septa

Question 10

Types of fibrosis in the liver include ____, ____, and ____

Answer 10

Types of fibrosis in the liver include portal fibrosis, pericellular fibrosis, and bridging fibrosis (early nodule formation)

• Scarring: fibrosis
• Hepatocyte regeneration: nodules

Question 11

Categories of liver dysfunction include ____, ____, and ____

Answer 11

Categories of liver dysfunction include acute liver failure, chronic liver disease, and hepatic dysfunction without overt necrosis

Question 12

Describe acute liver failure

Answer 12

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)

Question 13

Acute liver failure mechanism is ____

Answer 13

Acute liver failure mechanism is massive hepatocyte necrosis

• Most commonly due to drugs, toxins, viral, autoimmune

Question 14

Acute liver failure is most commonly caused by ____

Answer 14

Acute liver failure is most commonly caused by acetaminophen

Question 15

This is ____ due to ____

Answer 15

This is acute liver failure due to acetaminophen overdose

Question 16

Chronic liver disease results from ___ or ___

Answer 16

Chronic liver disease results from continuous injury or repeated injuries over time

• Continuous injury (chronic hepatitis)
• repeated injuries over time end in liver failure

Question 17

Chronic liver disease mechanism is ____ -> ____ -> ____

Answer 17

Chronic liver disease mechanism is fibrosis -> cirrhosis -> liver failure

Question 18

Describe fibrosis to cirrhosis progressive in chronic liver disease

Answer 18

Fibrosis to cirrhosis progressive in chronic liver disease

1. Portal fibrosis
2. Pericellular fibrosis
3. Bridging fibrosis (nodule formation)

Question 19

Hepatic dysfunction with overt necrosis is when ____ and results from ____ or ____

Answer 19

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

Question 20

This is ____

Answer 20

This is cirrhosis

Question 22

Fatty liver disease can be ____ or ____

Answer 22

Fatty liver disease can be non-alcoholic fatty liver disease or alcoholic fatty liver disease

• Different etiology
• Same mechanism
• Same pathology

Question 23

Describe fatty liver disease pathophysiology

Answer 23

Fatty liver disease pathophysiology

1. Steatosis: accumulation of fat in hepatocytes
2. Steatohepatitis: inflammation associated with steatosis
3. Fibrosis (progressive): cirrhosis
4. Liver failure or hepatocellular carcinoma (HCC)

Question 24

Fatty liver will show ____, ____, and ____

Answer 24

Fatty liver will show mallory bodies, acute hepatitis, and lipogranulomas

Question 25

Alcoholic fatty liver disease results from \_\_\_

Answer 25

Alcoholic fatty liver disease results from alcohol

Question 26

Nonalcoholic fatty liver disease results from ____ and \_\_\_\_

Answer 26

Nonalcoholic fatty liver disease results from obesity / metabolic syndrome and diabetes * Metabolic syndrome: central obesity, insulin resistance, dyslipidemia, and hypertension

Question 27

Fatty liver involves ____ which is \_\_\_\_

Answer 27

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

Question 28

\_\_\_\_ store energy as triglycerides

Answer 28

Adipocytes store energy as triglycerides

Question 29

Describe pathology of fatty liver disease

Answer 29

Pathology of fatty liver disease 1. Fatty liver (steatosis) 2. Steatohepatitis 3. Fibrosis -\> cirrhosis 4. Liver failure or hepatocellular carcinoma

Question 30

Alcohol consumption of ____ is required for alcoholic fatty liver disease

Answer 30

Alcohol consumption of \> 20 g daily is required for alcoholic fatty liver disease

Question 31

Alcohol consumption of ____ is required for nonalcoholic fatty liver disease

Answer 31

Alcohol consumption of less than 20 g weekly is required for nonalcoholic fatty liver disease

Question 32

Excess energy results in \_\_\_\_, \_\_\_\_, and ____ that lead to fatty liver

Answer 32

Excess energy results in increased fatty acid uptake in the liver, increased fatty acid synthesis, and increased triglyceride synthesis that lead to fatty liver

Question 33

Nonalcoholic fatty liver disease two-hit hypothesis involves ____ and \_\_\_\_

Answer 33

Nonalcoholic fatty liver disease two-hit hypothesis involves fat accumulation (steatosis) and oxidative stress to hepatocytes

Question 34

Steatosis can be ____ or \_\_\_\_

Answer 34

Steatosis can be macrovesicular or microvesicular (with lipogranuloma)

Question 35

Macrovesicular steatosis is \_\_\_\_

Answer 35

Macrovesicular steatosis is large droplet

Question 36

Steatohepatitis involves ____ and \_\_\_\_

Answer 36

Steatohepatitis involves lipogranulomas and lipoapoptosis * Cell death by apoptosis * Exposure of non-adipose tissues (liver) to an excess of long-chain fatty acids

Question 37

Alcohol consumption -\> ____ -\> ____ -\> \_\_\_\_

Answer 37

Alcohol consumption -\> alcoholic fatty liver disease -\> cirrhosis -\> end-stage liver disease

Question 38

Alcohol metabolites such as ____ cause liver injury

Answer 38

Alcohol metabolites such as acetaldehyde cause liver injury * Liver metabolizes 7-10 gram / EtOH / hour

Question 39

Metabolism of alcohol is an ____ process involving \_\_\_\_

Answer 39

Metabolism of alcohol is an oxidative process involving conversion of 95% of ethanol to acetaldehyde and then to acetate

Question 40

Alcohol metabolizing enzyme systems include \_\_\_\_, \_\_\_\_, \_\_\_\_, and \_\_\_\_

Answer 40

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

Question 41

Describe hepatotoxic effects of acetaldehyde

Answer 41

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

Question 42

Alcoholic fatty liver disease is morphologically divided into 3 types in order of severity: \_\_\_\_, \_\_\_\_, and \_\_\_\_

Answer 42

Alcoholic fatty liver disease is morphologically divided into 3 types in order of severity: fatty liver steatosis, alcoholic steatohepatitis, and cirrhosis and hepatocellular carcinoma

Question 43

\_\_\_ stage of alcoholic fatty liver disease starts in centrizonal area (zone 3) and extends towards portal area (zone 1)

Answer 43

Fatty liver steatosis stage of alcoholic fatty liver disease starts in centrizonal area (zone 3) and extends towards portal area (zone 1)

Question 44

\_\_\_\_ stage of alcoholic liver disease involves ballooning cell change and Mallory bodies, inflammatory infiltrate (neutrophils), and pericellular and perivenular fibrosis

Answer 44

Alcoholic steatohepatitis stage of alcoholic liver disease involves ballooning cell change and Mallory bodies, inflammatory infiltrate (neutrophils), and pericellular and perivenular fibrosis

Question 45

These are ____ in the ____ stage of alcoholic liver disease

Answer 45

These are lipogranulomas in the alcoholic steatohepatitis stage of alcoholic liver disease

Question 46

These are ____ in ____ stage of alcoholic liver disease

Answer 46

These are Mallory bodies in the alcoholic steatohepatitis stage of alcoholic liver disease

Question 47

Liver cell regeneration becomes ___ in alcoholic hepatitis

Answer 47

Liver cell regeneration becomes 2 cell thick plates in alcoholic hepatitis

Question 48

Describe the progression of alcoholic liver disease to cirrhosis

Answer 48

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

Question 49

This is \_\_\_

Answer 49

This is pericellular fibrosis

Question 50

This is ___ in \_\_\_

Answer 50

This is fibrous septa in alcoholic steatohepatitis

Question 51

This is \_\_\_\_

Answer 51

This is alcoholic cirrhosis (with residual steatosis)