Term
| What 3 properties, in particular, predispose the liver to disease processes? |
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Definition
1) Physiological functions
- Metabolic diseases, adverse drug reactions, perpetuation of liver disease when bile drainage is blocked.
2) Positioned downstream from intestinal venous drainage (infections, exposure to toxins, drugs and high levels of hormones.
3) Regeneration and fibrosis after injury (hepatocyte proliferation and stellate cell activation and fibrogenesis). |
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Term
| How does insulin resistance contribute to liver injury? |
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Definition
- Glycolysis is inhibited (low insulin:glucagon ratio) and serum FFA levels rise.
- hepatocyte fat storage is triggered, leading to steatohepatitis and inflammation. |
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Term
| What do Hemochromatosis, a1-anti trypsin deficiency, Wilson's disease and Glycogen storage diseases all have in common in relation to liver pathology? |
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Definition
| All involve accumulation of products (iron, protein, copper and glucose, respectively)that damage hepatocytes, cause inflammation and stimulate fibrogenesis and small portal venopathy. |
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Term
| Which viral causes of liver disease act via direct, cytopathic effects, and which ones use immune-mediated mechanisms? |
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Definition
1) Immune
- Hep B and Hep C
2) Direct
- Herpes (HSV, VZ, adenovirus) |
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Term
| What are the major autoimmune/immune dysregulation causes of liver disease? |
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Definition
1) Autoimmune hepatitis
2) Primary biliary cirrhosis (PBC)
3) Primary sclerosing cholangitis (PSC) |
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Term
| Which 3 major types vascular insults contribute to liver pathology? |
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Definition
1) Suboptimal venous drainage
- hepatic congestion causes pressure atrophy of perivenular hepatocytes and hepatic vein sclerosis
- seen in cardiac failure and hepatic vein thrombosis (Budd-Chiari syndrome)
2) Hepatic artery flow (thrombosis, chemo-ablative therapy for HCC)
3) Portal venous flow (thrombosis, hepato-portal sclerosis) |
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Term
Which liver diseases occur primarily in each of the following locations?
1) Hepatocyte
2) Biliary tree
3) Vascular
4) Mixed hepatocyte/biliary
5) Other |
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Definition
1) Viral and autoimmune hepatitis, ADR, metabolic or toxic
2) Developmental or iatrogenic atresia, or dysregulated immunity (PBC, PSC)
3) Systemic diseases or ADR (sinusoidal dilation, peliosis)
4) Autoimmune/immune diseases and ADR
5) Stellate fibrosis (storage disease), Kupffer cell (storage disease) |
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Term
| Which liver pathologies generally present acutely (<6 month) vs. chronically (> 6 month)? |
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Definition
Acute worry is severe injury and t/x, while chronic is fibrosis/cirrhosis and portal HTN
- ADR (acetaminophen, immuno-allergic to Ab)
1) Acute
- Viral hepatitis-actute phase (A-F)
- Autoimmune hepatitis
- Toxins (CCL4, alcohol)
- Ischemic insults (thrombosis)
2) Chronic
- Metabolic and developmental
- Viral hep B and C
- ADR (oral contraceptive, methotrexate)
- PBC, PSC
- TOxins and suboptimal vascular flow (portal HTN) |
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Term
| What is the basic histopathologic approach to looking at a liver biopsy? |
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Definition
1) Asess architecture
- Spacing of portal tracts and central veins
- Distortion (bridging fibrosis, nodule formation (cirrhosis), portal tract expansion, central vein fibrosis).
2) Acute vs. Chronic
- Acute (necrosis of individual hepatocytes, PMN and pigmented macrophages, no mature fibrosis)
- Chronic (Fibrosis, lymphocytes forming nodular aggregates/lymphoids, hepatocyte anisonucleosis, iron/copper deposition.
3) Location
- Hepatocytes, bile ducts or mixed?
- Zone preference? (zone 3?)
4) Response to injury
- Hepatocyte proliferation, ductal reaction/proliferation
- Fibrosis and parenchymal extinction |
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Term
What do each of the following histopathalogic terms describe in terms of hepatocyte injury?
1) Steatosis
2) Ballooning
3) Spotty necrosis
4) Confluent necrosis
5) Interface hepatitis
6) Mega-mitochondria |
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Definition
1) Fatty change
- microvesicular- fat smaller than nucleus (mitochondrial)
- macrovesicular- fat bigger than nucleus (metabolic)
2) Cell swelling/degeneration
3) Single, isolated group
4) Large groups of hepatocytes in a given area of a lobule
5) Inflammation at border of portal tract and lobules
6) Sign of oxidative stress |
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Term
What are the characteristic pathological features of acute hepatitis?
1) Lobes
2) Portal Tracts
3) Specific diagnostic features |
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Definition
1) Lobules
- Hepatocyte ballooning, steatosis, spotty necrosis (if confluent, think severe)
- Hepatic plate disarray (regeneration)
- Inflammation (ceroid-laden macrophages and PMNs)
- Kupffer cell hypertrophy
2) Portal tracts
- variable inflammation with Ductural proliferation ("reaction")
- No fibrous expansion
3) Specific diagnosis features
- Diagnostic inclusions (HSV, VZ, CMV, EBV, HBV)
- Patterns (centrilobular is acetaminophen and immuno-allergic to antibiotic is cholangitis) |
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Term
What are the characteristic pathological features of chronic hepatitis?
1) Lobes
2) Portal Tracts
3) Specific diagnostic features |
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Definition
Basic picture is mononuclear inflammation/lymphoid neogenesis and portal/periportal fibrosis with less severe hepatocyte injury and lobule disarray compared to acute case
1) Lobes
- Less hepatic disarray and kupffer cell hypertrophy than acute
- Low-grade, focal hepatocyte injury
2) Portal tracts
- Mononuclear inflammation- Lymphoid neogenesis
- Interface necro-inflammatory activity
- Portal/periportal fibrosis
3) Specific diagnostic markers
- General features are not specific
- Marked periportal inflammation may be autoimmune or Hep A |
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Term
| How is chronic hepatitis graded and staged histopathologically? |
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Definition
Look for mononuclear inflammation, lymphoid neogenesis and portal/peri-portal fibrosis!
1) Grading (severity and distribution of inflammation and injury) based on:
- Interface or periportal necrosis
- Confluent necrosis
- Lobular inflammation and hepatocyte injury
- Portal inflammation
2) Staging (portal fibrosis and architectural distortion)
- O (no fibrosis), 4/4 (cirrhosis) |
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Term
Patient presents with jaundice and itching on their stomach and extremities. Labs reveals elevated ALP and GGTP with only minor changes in AST/ALT.
What might you look for histologically on liver biopsy? |
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Definition
| Picture fits BIliary tract disease, so look for ductular reaction and ductopenia in portal triads. |
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Term
| Describe the natural progression of Cirrhotic disease? |
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Definition
1) "Response to injury" as a result of sclerosis and destruction of small portal vein branches (portal venopathy) and fibrosis)
2) Ongoing oxidative stress and hepatocyte injury result in impaired regeneration, which promote survival advantage of myofibroblasts and biliary epithelial cells.
3) Portal venopathy triggers HABR, which stimulates hepatocyte proliferation and causes "regenerative nodules" to form |
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Term
| What are the histological characteristics that define the most common type of benign tumor of the liver? |
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Definition
Hemangioma (usually subcapsular) of sinusoidal/endothelial cells
1) Groos
- small, solitary red-blue (blood) or white (fibrosis/scarring)
2) Under microscope
- vascular cavities with RBCs lined by flattened benign endothelial cells
- intervening fibrosis.
Treat conservatively. |
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Term
| What are the major types (4) of benign liver lesions? |
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Definition
Hemangioma most common
1) Hemangioma (sinusoids)- vascular cavities lined by flattened epithelial cells
2) Focal nodular hyperlasia (FNH)- tumor mimic of young women with central stellate scar and fibrous bands coursing through
- Due to vascular problem
3) Hepatocellular Adenoma (HA)
- Use of oral contraceptives (women) and anabolic steroids (men)
- presents with episodic abdominal pain and hemorrhage
- Associated with HNF1A mutations (50%) and beta-catenin mutations (10%)
4) Von Meyenburg complex
- Biliary microhamartoma commonly confused for metastasis
- Small, subcapsular, whitish nodule
- Microscopically, small ducts with cuboidal epithelium in fibrous bed.
- Within spectrum of ADPKD |
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Term
Which type of benign liver lesion is described by each of the following? How should each be managed?
1) Gross, stellate lesion due to vascular problem with nodules of "normal-appearing" hepatocytes and plates of normal thickness
2) Vascular cavities lined by flattened epithelial cells
3) Biliary microhamartoma (small, solitary white lesion with small ducts lined with cuboidal epithelium in fibrous tissue bed) commonly confused for metastasis
4) Solitary, hemorrhagic lesions with large thick-walled arteries, dilated veins and absent portal tracts found in young women taking oral contraceptives |
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Definition
1) Focal Nodular Hyperplasia (FNH)
- Treat only if pain
2) Hemangioma
- Don't treat
3) Von Meyenburg Complex
- No treatment
4) Hepatocellular Adenoma (HA)
- Resect it because of bleeding and HCC risk. |
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Term
| What is the etiological basis of HCC? |
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Definition
Tumor arises from hepatocytes due to cyclic damage (long-latency) and repair from infection (Hep B and C), alcohol and/or metabolic disease
- associated with p53 and Beta-catenin mutations. |
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Term
Describe the histological appearance of a general HCC tumor.
How can it be treated most effectively? |
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Definition
Liver t/x in patients with good LFTs and small tumors is best treatment
1) Grossly looks pale or greenish
2) Microscopically
- Moderately differentiated hepatocytes- Polygonal shape with large nucleoli
- 'Shoulder-to-shoulder' in thick rows
- Vascular invasion and bile production often seen. |
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Term
| What are the 2 types of important liver carcinomas? |
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Definition
1) Hepatocellular
- Moderately differentiated hepatocytes- Polygonal shape with large nucleoli
- 'Shoulder-to-shoulder' in thick rows
2) Cholangiocarcinoma (CC)- RARE
- Intra-hepatic bile ducts associated with fluke infestation
- Normal serum AFP appearing as solitary, firm, white tumor (like adenocarcinoma) |
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Term
| What are the 2 types of important liver carcinomas? |
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Definition
1) Hepatocellular
- Moderately differentiated hepatocytes- Polygonal shape with large nucleoli
- 'Shoulder-to-shoulder' in thick rows
2) Cholangiocarcinoma (CC)- RARE with no jaundice
- Intra-hepatic bile ducts associated with fluke infestation
- Normal serum AFP appearing as solitary, firm, white tumor (like adenocarcinoma) |
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Term
| Describe the 2 malignant liver-associated lesions that occur outside of the liver |
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Definition
Rare in US (5000 annually), but hard to treat!
Both have jaundice, but differentiate by pain
**Extra-hepatic bile duct has no pain, but Gallbladder with have pain**
1) Carcinoma of the extra- hepatic bile duct (men > women)
- associated with congenital biliary tree malformation or PSC in 6th decade of life
- Present with painless obstructive jaundice and pruritis
- Well-differentiated adenocarcimona with perineural invasion.
- Resection is hard and survival is poor.
2) Carcinoma of gallbladder (women > men)
- Linked to gallstones and bile duct malformation
- 7th to 8th decade with painful jaundice
- Most commonly adenocarcinoma with infiltrating malignant columnar epithelium in glandular structures.
- Most patients die within 1 year of diagnosis. |
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Term
| What are the associated molecular targets of Hepatocellular Adenoma? |
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Definition
1) HNF1A transcription factor (50%)
- benign prognosis
2) Beta-catenin (proto-oncogene) (10%)
- May "transform" to HCC |
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Term
| What exposures are associated with HCC? |
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Definition
1) HBV infection
- X protein acts as t-factor and inhibits p53 tumor suppression
2) Aflatoxin (fungal metabolite)
- hepatocarcinogen induces p53 mutations and beta-catenin over-expression
3) HCV
- Core protein in ongogenic (US and Japan particularly)
4) Cirrhosis (hereditary or alcohol) |
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Term
65 year old patient presents with RUQ pain and weight loss. Serum AFP is elevated.
What do you do? |
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Definition
| Get ultrasound or CT to confirm HCC and get them on transplant list! |
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Term
| How can you tell between HCC and Cholangiocarcinoma based on clinical presentation alone? |
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Definition
| Both will have RUQ pain and weight loss late in life, but CHolangiocarcinoma will NOT HAVE JAUNDICE |
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