Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
64 Cards in this Set
- Front
- Back
Anatomy
Acinus/lobule |
defined by peripheral portal triads and a terminal hepatic venule/central vein.
|
|
Anatomy
Portal triad |
contains a branch of the hepatic artery, the portal vein, bile duct and a lymphatic channel supported by connective tissue
|
|
Anatomy
limiting plate |
the boundry between the connective tissue matrix of triad and the liver parenchyma
|
|
Anatomy
hepatic cords |
Liver laminae as seen in sections.
|
|
Anatomy
Space of Disse |
The small space between the endothelium and the hepatocytes
|
|
Anatomy
stellate (Ito) cells |
small numbers of specialized connective tissue cells in the Space of Disse
|
|
Anatomy
Kupffer cells |
the phagocytes of the liver
|
|
Anatomy
Lymphatic canal of Hering (location; cell types) |
most proximal cells around the limiting plate
bridge between hepatocytes and bile duct |
|
Anatomy
dual blood supply - hepatic and portal circulations |
Portal venous and Hepatic arterial
Inflow: Portal Vein: Low pressure, 40% O2 Hepatic Artery: Systemic pressure, 60% O2 |
|
Anatomy
acinus vs. classical lobule |
Classic Lobule:
Centered on portal vein, forms a hexagon along portal septa (lining between lobules) Acinus: Centered on portal triad and extends to terminal hepatic venule (central vein) |
|
Anatomy
zones 1, 2, and 3 |
Zone 1
Periportal hepatocytes at the periphery of the acinus/lobule Zone 2 Mid-zonal hepatocyes between zones 1 and 3 Zone 3 Centrilobular hepatocytes closest to the central vein |
|
Patterns of Injury and Repair
interface vs. bridging |
Interface is used to describe changes at or near the interface between the limiting plate of the portal triad and the periportal hepatocytes (e.g., interface hepatitis or necrosis)
Bridging is used to describe the interconnection of portal areas or central veins by a pathologic process such as inflammation, fibrosis, or necrosis (e.g., central-central, portal-portal, or central-portal bridging fibrosis). |
|
Patterns of Injury and Repair
ductular reaction (where is it coming from?) |
When parenchymal loss is extensive, the Canal of Hering (terminal bile ductule) is the major source of hepatic progenitor cells (oval cells)
Extensive parenchymal loss is often associated with an increase in ductular structures (termed “ductular reaction”; the DR includes not only the epithelial component, but also a fibro-inflammatory component) |
|
Patterns of Injury and Repair
ballooning degeneration and lytic necrosis |
- Ballooning (hydropic) degeneration refers to clearing of the hepatocyte cytoplasm due to intracellular edema. The cell appears swollen and enlarged and the cytoplasm is clumped. These changes are common features of many types of severe hepatic injury, including acute viral hepatitis.
- Lytic necrosis refers to the rupture or dissolution of single cells or groups of cells, usually in the context of osmotic swelling and ballooning degeneration. This is sometimes referred to as drop-out. |
|
Patterns of Injury and Repair
acidophil body |
Apoptosis accompanies many types of hepatocellular injury, particularly with immune-mediated or toxic insults. The apoptotic bodies were described as acidophil or Councilman bodies.
Although this terminology is still widely used, acidophil bodies resemble other types of apoptotic cells. |
|
Patterns of Injury and Repair
cholestasis (intrahepatic vs. extrahepatic) |
categorized as obstructive or non-obstructive.
Pathologically, both forms are characterized by abnormal accumulation of bile within distended bile canaliculi. In the setting of severe _________ the cytoplasm of the hepatocytes often acquires a foamy, reticular appearance described as feathery (or foamy) degeneration. With prolonged obstructive _________, bile stasis and back pressure can lead to the detergent-mediated dissolution of hepatocytes and the extravasation of bile with the formation of extracellular bile lakes or bile infarcts extrahepatic: obstruction characterized by portal edema and bile lakes, a portal ductular proliferation, and periductular infiltrates of neutrophils. It can also be complicated by secondary ascending infections. |
|
Patterns of Injury and Repair
cholate stasis (chronic cholestatic liver disease) |
Inhomogenous involvement of liver parenchyma
- Destruction, loss of intralobular ducts +/- Inflammation Characteristic pattern of “biliary” and/or incomplete septal fibrosis - Biliary interface, feathery degeneration - Ductular reaction - Mallory-Denk bodies in periportal/periseptal hepatocytes - Copper in periportal/periseptal hepatocytes - Foam/pseudoxanthoma cell collections - Cholestatic rosettes |
|
Patterns of Injury and Repair
portal vs. lobular vs. interface hepatitis |
"portal hepatitis" indicates infiltration of the portal space by inflammatory cells.
"Lobular hepatitis" is the term used to indicate the presence of necroinflammatory lesions in the acinus and hepatic cords. "Interface hepatitis" describes the presence of mixed chronic inflammation that involves and “crosses” the limiting plate. Interface hepatitis used to be referred to as "piecemeal necrosis" to acknowledge the fact that ongoing hepatocellular death and dropout are also present. |
|
Patterns of Injury and Repair
Steatosis (2 types) |
Intracytoplasmic accumulations
- fatty change - Accumulation of lipids in the cytoplasm of hepatocytes is seen in a wide variety of diseases, usually reflecting abnormalities in lipid transport, degradation, oxidation, and/or apo-lipoprotein production. Can be: Microvesicular __________ (many small fat vacuoles - indicative of mitochondrial dysfunction, and the related disease processes are usually quite severe Macrovesicular ________ (one large fat vacuole - less injurious than micro) - seen in alcoholic liver disease, non-alcoholic steatohepatitis (NASH), hepatitis C, and Wilson disease |
|
Patterns of Injury and Repair
Types of Necrosis |
Cell loss - regardless of cause - is ultimately accompanied by local collapse of the associated reticulin network.
1. Ischemic coagulative necrosisis is associated with loss of cytoplasmic detail and nuclear staining. 2. Lytic necrosis refers to the rupture or dissolution of single cells or groups of cells, usually in the context of osmotic swelling and ballooning degeneration. This is sometimes referred to as drop-out. 3. Apoptosis accompanies many types of hepatocellular injury, particularly with immune-mediated or toxic insults. The characteristic nuclear fragmentation may not be evident on a given section, and cellular debris can be rapidly cleared by Kupffer cells. Usually, there is no significant inflammatory response; however, lymphocytes involved in immune-mediated apoptosis can occasionally cluster around apoptotic bodies, resulting in “spotty necrosis”. Spotty necrosis refers to the necrosis of single or small groups of hepatocytes. For our purposes, that is all you need to know. An aside. Because lytic necrosis is usually spotty, the two terms are sometimes used interchangeably. Confluent necrosis refers to loss of a large number of hepatocytes, typically in Zone 3. There is associated reticulin network collapse. This type of necrosis may occur with some viral infections (but usually NOT hepatitis C) and with autoimmune hepatitis. Submassive (bridging necrosis) and massive necrosis (self-explanatory) are the terms used when large confluent areas of the liver undergo necrosis (multiacinar or panacinar necrosis). These patterns are seen with certain drug or toxic reactions and in some forms of acute viral hepatitis. Grossly, massive necrosis is often suggested by decreased organ weight and wrinkling of the capsule. |
|
Patterns of Injury and Repair
Cirrhosis |
Stereotyped response to injury that is characterized by many severe infectious, inflammatory, immune-mediated or metabolic disorders that lead to complete and irreversible, gross remodeling of liver parenchymal structure with regenerative nodules surrounded by scar which contains aberrant vascular channels and ductules
- Alcoholism is the most common cause - increases the risk of hepatocellular carcinoma. - requires both fibrosis AND nodules - septa often accompanied by a ductular reaction as a manifestation of the regenerative process - accompanied by mechanical effects on blood flow and vascular remodeling (can lead to portal hypertension with resulting ascites, and congestive splenomegaly) |
|
Patterns of Injury and Repair
patterns of vascular compromise: artery portal vein outflow veins |
Cirrhosis: there is increased flow resistance at the level of the sinusoids, and compression of terminal hepatic veins by fibrosis and regenerative nodules.
In addition, anastomoses can form between the high pressure hepatic and low pressure portal systems. Together, these changes contribute to portal hypertension with resulting ascites, and congestive splenomegaly. Portal-systemic shunting also allows substances delivered via the portal circulation to bypass metabolism by hepatocytes, thereby contributing to clinical signs and symptoms of hepatic failure. |
|
Patterns of Injury and Repair
heart failure: right-sided; left-sided; both |
The malfunctioning heart can affect the liver either by low arterial flow (left-sided or shock) or right-sided failure with back pressure (congestion)
1. Passive congestion occurs in cases of right-sided cardiac decompensation or right heart failure. Central sinusoidal congestion and hepatocyte atrophy (Zone 3) are usually seen. 2. Left sided decompensation or hemodynamic shock can precipitate centrilobular (Zone 3) ischemic necrosis. |
|
Patterns of Injury and Repair
ischemic necrosis |
Is similar to coagulative necrosis in other tissues.
It is associated with loss of cytoplasmic detail and nuclear staining. |
|
Patterns of Injury and Repair
Zahn's infarct (just because it seems to show up on Boards) |
- A sharp to mottled area of red or red-blue discoloration produced by a recent thrombosis of an intrahepatic branch of the portal vein
- It is not a true infarct because there is no necrosis. - It results from congestion secondary to diversion of blood flow proximal to the obstructed branch. - Histologically, the only finding is congestion and atrophy. It has no clinical significance |
|
Patterns of Injury and Repair
Budd-Chiari syndrome |
Thrombotic occlusion of the hepatic veins can be acute or chronic and presents with hepatomegaly, ascites with weight gain, and abdominal pain (syndrome)
- associated with polycythemia vera (hyperviscosity secondary to overproduction of red cells), inherited disorders of coagulation, pregnancy, oral contraceptives, paroxysmal nocturnal hemoglobinuria and hepatocellular carcinoma. However, nearly a third are idiopathic. - the liver is grossly swollen and red and the capsule is tense, contributing to the clinical symptom of pain - With the more common subacute presentation, there is centrilobular congestion, centrilobular fibrosis, and fresh or organized thrombi involving central veins. Chronic obstruction can lead to "reverse lobulation" cirrhosis resembling that seen with cardiac dysfunction. The vena cava frequently exhibits intraluminal membranes reflecting reorganized thrombi. |
|
Patterns of Injury and Repair
Patterns of fibrosis |
There are three major, sometimes overlapping patterns:
1. Portal and periportal fibrosis are particularly common after the chronic hepatitides. 2. Fibrosis surrounding the central vein is common in alcoholism and circulatory disorders associated with venous obstruction or heart failure. 3. Fibrosis of the space of Disse is seen in alcoholism and in nonalcoholic fatty liver disease, and contributes to remodeling following other types of injury. This pattern is referred to as perisinusoidal, pericellular or chickenwire fibrosis. 4. Fibrosis in the liver is currently thought to be due to transformation of stellate cells into myofibroblasts with subsequent production of matrix materials. Portal myofibroblasts may or may not be derived from these cells. Bridging fibrosis refers to complete or partial fibrous bridging between portal triads and/or central veins, is usually a consequence of bridging necrosis, and contributes to the development of cirrhosis. Collagen deposition occurring as a consequence of an inflammatory process or zonal necrosis is usually an irreversible phenomenon. |
|
Veno-occlusive disease
|
aka (Sinusoidal Obstruction Syndrome)
- Patients with allogeneic bone marrow transplants develop ___________ in the first few weeks following transplantation. The mortality is quite high (approximately 30%). HIstopathology: characterized by obliteration of central veins by subendothelial swelling accompanied by centrilobular congestion and necrosis. Chronic or healed disease is characterized by perivenular fibrosis - Believed to result from the toxic injury to sinusoidal endothelial cells, which embolize toward the vein and obstuct sinusoidal blood flow, hence the name. Similar pathologic changes are seen after ingestion of specific alkaloids that injure the veins. |
|
Chronic passive congestion
Central hemorrhagic necrosis Classical gross appearance: |
The combination of marked passive congestion and hypoperfusion can lead to centrilobular hemorrhagic necrosis and a margin viable periportal hepatocytes.
This results in the classical gross appearance of nutmeg liver. |
|
Cardiac or "reverse lobulation" cirrhosis
|
The term cardiac sclerosis/cirrhosis has been used to describe central fibrosis resulting from severe passive congestion with central venous necrosis.
However, overall lobular architecture is maintained, and cardiac sclerosis/fibrosis would be a better term. Along with the severe venocentric fibrosis that bridges between central veins, the pattern of "reverse lobulation cirrhosis" occurs (central venous areas are linked together in a manner resembling normal portal triads). |
|
Acute pancreatitis:
Definition: |
Clinical condition characterized by abdominal pain
Caused by pancreatic inflammation and necrosis |
|
Acute pancreatitis:
Causes: |
Primarily due to:
Biliary tract disease + Alcohol abuse = 80% Other causes: trauma, ulcer disease, drugs, bacterial or viral infection, hyperlipoproteinemia, hypercalcemic states, familial disease |
|
Acute pancreatitis
General Pathogenesis |
Digestive enzymes are released and activated within the pancreatic parenchyma
This results in tissue “autodigestion.” The mechanism(s) operable in these circumstances are a matter of debate |
|
Acute pancreatitis
Pathogenesis: Initiating insults |
Causes:
Alcohol, Viruses, Drugs, Ischemia, Trauma --> Acinar Cell Injury Cholelithiasis, chronic alcoholism, obstruction lesions --> Duct obstruction Nutritional Deficiency --> Deranged intracellular transport of pancreatic enzymes |
|
Acute pancreatitis
Pathogenesis: Observed Lesions that lead to Acute Pancreatitis |
- Inflammation
- Proteolysis (active proteases) - Fat Necrosis (active lipase) - Hemorrhage (active elastase) |
|
Pathologic findings:
Acute pancreatitis Gross and Microscopic Findings: |
Gross Findings --> due to Microscopic findings:
- Grey/white areas --> Enzymatic autodigestion - Hemorrhage --> Blood vessel damage, red blood cell extravsation - Chalky white areas --> Fat necrosis, with adipocyte granular debris |
|
Acute pancreatitis
Clinical course: |
Acute abdominal pain: very severe
Jaundice develops Differential diagnosis includes gut emergencies: appendicitis, perforated ulcer, bowel infarcts, gallbladder disease Systemic problems: shock, ARDS, acute renal failure Complications include abscesses, duodenal obstruction, hemorrhage, pseudocysts Mortality rate: in the range of 5% |
|
Chronic Pancreatitis
Definition |
A condition characterized by repeated episodes of mild or subacute acute pancreatitis
Results in progressive parenchymal destruction |
|
Chronic Pancreatitis
Clinical settings: |
Alcohol abuse and biliary tract disease are the most important causes
Alcohol>>>biliary tract disease Other rarer causes include hypercalcemia, hyperlipidemia, and familial disease |
|
Chronic Pancreatitis
Pathogenesis: |
Process is that of repeated flares of acute pancreatitis
Alcoholic disease: - Ducts contain proteinaceous plugs - Also metaplasia of the ductal epithelium - Diffuse obstruction and destruction Biliary disease: - Gallstone and tumors - More localized inflammation and destruction |
|
Chronic calcifying pancreatitis (alcoholic type)
Gross and Microscopic Findings: |
Gross:
- lobular architecture largely intact, with fibrosis and calcification Microscopic: - Acinar atropy, with intra- and inter-lobular fibrosis - Mixed inflammation: lymphocytes, plasma cells, neutrophils - Dilated ducts with luminal proteinaceous plugs; ductal epithelium may be hyperplastic, atrophic, or have squamous metaplasia - Damage to the islets is variable |
|
Obstructive chronic pancreatitis
Characteristic features: |
- Localized obstruction with localized involvement
- Inflammatory infiltrate similar to calcifying pancreatitis, but involvement not clearly as lobular in nature - Ductal calculi not common |
|
Chronic pancreatitis
Clinical course: |
Repeated bouts of:
Fever, jaundice, and abdominal pain Elevations of amylase and alkaline phospahatase Pancreatic pseudocysts eventually occur - walled off collections of necrotic material Malabsorption, steatorrhea, diabetes |
|
Pancreatic Endocrine Tumors
|
Classically called “islet cell tumors”
Less common than carcinomas that arise from the ducts or exocrine glands Mostly occur in adults More islets in the tail and body; more islet cell tumors there, as well Syndromes related to specific hormone excess Can be a component of MEN I |
|
Islet cell tumors
Distinguishing Features |
Most are “functional” (hormone-producing), and so present with hormonal syndromes
Diagnosis is then confirmed by CT or MRI scans, may also include needle biopsies Can be seen by nuclear medicine scans (octreatide), as well Treatment is surgical resection ambiguous in regard to malignant potential, we don’t always know Mitotic rate, necrosis, hemorrhage and local infiltration are worrisome features Best indicator of malignancy is still metastasis, to lymph nodes or liver Usually long survival, even with metastatic disease, in most cases Small cell carcinoma is a very aggressive variant |
|
Insulinoma
|
Insulin secreting tumor
Present with Whipple’s triad: - CNS symptoms of confusion, fatigue, weakness, - glucose less than 50 mg%, - Prompt relief of symptoms with glucose adminstration • about 3/4 of the tumors are solitary • Often times small lesions • Only rarely malignant (10% or less) |
|
Glucagonoma
|
Clinical manifestations include diabetes, necrotizing migratory skin rash, chelitis, and anemia, but more often clinically silent than insulin-producing tumors
Solitary tumors are often very large |
|
Gastrinoma
|
• Presentation includes the Zollinger-Ellison syndrome, of a gastrinoma, gastric hyperacidity, and recalcitrant gastric ulcers
• Multiple tumors are often seen in MEN I • More than half (60%) are malignant • Identical tumors can occur in the pancreas, duodenum, or nearby sites (gastrinoma triangle) |
|
T/F
Insulinoma has a greater propensity for malignant behavior than glucagonoma |
False
Glucagonoma has a greater propensity for malignant behavior than insulinomas |
|
Pancreatic Exocrine Carcinomas
Epidemiology |
Common cancer: 5th most common cause of cancer deaths (behind lung, colon, breast, prostate)
28,000 new cases per year Dismal outcome; less than 5% survival at 5 years Disease mainly of older individuals; 60-80 years Associations: Most well-established link is with cigarette smoking; claims of linkage to alcohol use or coffee drinking are not supported in large studies |
|
Pancreatic Exocrine Carcinomas
Genetic features |
Most common mutations are seen in K-RAS and CDKN2A (p16)
At least 1/2 of cases have loss of tumor suppressor genes p53 or DPC4 (deleted) Miscellaneous: MLH1, BRCA2, her2/neu |
|
Pancreatic Exocrine Carcinomas
Pathologic features |
About 3/4 arise in the head of the pancreas
Great majority are adenocarcinomas of ductal origin Head of pancreas lesions: typical impinge on the ampulla or common bile duct, obstruct bile flow, and cause biliary tract distention; will also invade the duodenum Body/tail lesions: Do not impinge on major structures in the head/ampulla, so they can be present for longer period of time before detection; will be large and disseminated at the time of discovery, with tumor invasion of adjacent structures |
|
Pancreatic Exocrine Carcinomas
Metastases Clinical features Migratory thrombophlebitis (inflammation of veins with thrombosis): known as what sign? |
Metastases: will involve peripancreatic, gastric, omental or porta hepatis lymph nodes; many cases will spread to peritoneum and cause “carcinomatosis,” liver, lungs and bone are also favorite sites for metastatic disease
Clinical features: Pain is most common presenting complaint Obstructive jaundice noted in cases in the head Migratory thrombophlebitis (inflammation of veins with thrombosis): Trousseau’s sign |
|
Other rare pancreatic tumor types
|
Acinar cell carcinoma
Intraductal papillary mucinous tumors (“IPMT) Serous and mucinous cystadenomas |
|
Other rare pancreatic tumor types
Acinar cell carcinoma: |
tumor resembles the acinar cells (with enzyme production)
Tend to be in the body or tail, and to present as large bulky tumors, with invasion of adjacent local structures. Poor outcome also |
|
Other rare tumor types
Intraductal papillary mucinous tumors (“IPMT) |
These are tumors that are limited to growth within the ducts, in analogy to intraductal breast carcinoma.
They may diffusely involve the ducts throughout the pancreas, and would require total pancreatectomy for therapy in those cases. May be eventually associated with development of invasive ductal adenocarcinomas |
|
Other rare tumor types
Serous and mucinous cystadenomas |
Multicystic lesions, most with benign outcome.
May present as incidental findings. |
|
Chronic Pancreatitis
Chronic calcifying (alcohol-related) vs. Obstructive (stones or neoplasia) |
Chronic calcifying (alcohol-related)
- All areas of pancreas may be involved - Calcifications along the duct and in affected parenchyma Obstructive (stones or neoplasia) - Lesions are proximal, near the ampulla - Calcification usually absent, unless obstructing lesion calcifies |
|
Chronic Pancreatitis
T/F Diabetes is a complication of chronic pancreatitis that can be predicted from the severity of the acinar injury. |
False
Damage to islets is variable. In some cases, extensive acinar loss and fibrosis is not accompanied by islet injury, while in other patients, islet loss may coincide with acinar injury. Therefore, diabetes is a complication of chronic pancreatitis, but NOT one that can be predicted from the severity of the acinar injury. |
|
Complications of pancreatitis
Localized destruction may result in the formation of a fluid filled cavity that is lined by chronically-inflamed fibrous tissue called __________ (they do not have an epithelial lining, and do not communicate with the pancreatic ducts) They may enlarge over time to sizes in excess of 10 cm; compression of adjacent structures (including the stomach) may occur. Because these _________ are filled with tissue debris, they are fertile soil for bacterial infection. However, because they usually present as a mass, the differential diagnosis always includes neoplasia |
pseudocysts
|
|
The typical islet in the body and tail contains three primary endocrine cell populations:
|
+ alpha cells (peripheral location) produce glucagon
+ beta cells (central location) produce insulin + delta cells (few, scattered throughout the islet) produce somatostatin + other cell populations are considerably smaller - produce gastrin, VIP, others |
|
The electron microscopic morphology of the secretory vesicle is characteristic for a given hormone peptide:
glucagon granules: insulin granules: somatostatin granules: |
+ glucagon granules: targetoid with a central electron dense zone and clear halo; the limiting membrane is sharply defined
+ insulin granules: angular paracrystalline deposits in vesicle somewhat larger than that of alpha cells + somatostatin granules: homogeneous electron density in a large vesicle; the limiting membrane is not always clearly visible. |
|
T/F
Lymph node or distant (often liver) metastases are still the most reliable indicators that a given pancreatic tumor is in fact malignant. |
True
|
|
T/F
Except for small cell carcinoma-like tumor, most malignant islet cell tumors have a relatively fast pace of disease; patients may only live for a few months or more with metastatic disease |
False
Except for small cell carcinoma-like tumor, most malignant islet cell tumors have a relatively SLOW pace of disease; patients may live for a DECADE or more with metastatic disease |