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157 Cards in this Set
- Front
- Back
What is the largest glandular tissue in the body? Size?
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Liver
- 1200g to 1800g - 12-15 cm top to bottom - 15-18 cm across - Males: 1.8 kg (avg weight) - Females: 1.4 kg (avg weight) |
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What are the lobes of the liver? Which are the biggest?
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- Right
- Left - Quadrate - Caudate R and L lobes make up the bulk |
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What blood does the liver receive? Origin?
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Receives mainly venous blood, arriving directly from the spleen, pancreas, and intestine
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What are the implications of the liver receiving venous blood from the spleen, pancreas, and intestine?
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It is the first organ to encounter any ingested toxic substances as well as nutrients
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What kind of tissue makes up the liver?
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- Bulk is uniform parenchymal cells = hepatocytes
- Sparse connective tissue |
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What are the functions of the liver?
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- Detox metabolic waste products
- Synthesize plasma lipoproteins - Synthesize blood clotting factors - Synthesis, secretion, and storage of carbs and lipids - Destruction of spent RBCs and recovery of constituents - Synthesis and secretion of bile |
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What are the two types of properties of the liver? How do they differ?
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Endocrine
- From hepatocytes directly into the hepatic blood - Includes: albumin, fibronectin, transferrin, prothrombin, lipoproteins, α-1-antitrypsin, glucose (after glycogen breakdown), and thyroxin (highly active form) Exocrine - Production of bile |
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What happens to endocrine secretions from the hepatocytes? Which ones?
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- Directly enter the hepatic blood
- Albumin, fibronectin, transferrin, prothrombin, lipoproteins, α-1-antitrypsin, glucose (after glycogen breakdown), and thyroxin (highly active form of thyroid hormone) |
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What compound is produced by hepatocytes to be released for exocrine function?
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Bile
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What are the four functional groups of liver components?
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- Connective tissue
- Large vessels (including blood vessels, lymphatic vessels, nerves, and bile ducts) - Sinusoidal capillaries (sinusoids - which line the plates of hepatocytes and are responsible for blood flow through the liver) - Hepatocytes |
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What surrounds the hepatocytes and sinusoids in the liver?
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Reticular fibers composed of Collagen Type III
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What is the only connective tissue in the lobules of the liver? Organization? Functions?
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Reticular Fibers made of Collagen Type III
- Sparse - Extends outward from the central vein - Supports the hepatic parenchyma - Contributes toward keeping sinusoids open to allow normal blood flow |
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What is the origin of the reticular fibers (collagen type III) that surround hepatocytes and sinusoids?
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Stellate / Ito cells found in the Space of Disse
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Where are Stellate / Ito cells found? Function?
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- Space of Disse
- Form the reticular fibers (collagen type III) that surrounds hepatocytes and sinusoids |
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What can disrupt the reticular fiber network surrounding hepatocytes and sinusoids? How can you assess this?
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- Liver disease can cause disruption of this network
- Staining for Reticulin can aid diagnosis |
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What are the fiver major vessel systems in the liver?
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- Hepatic artery
- Hepatic portal vein - Central veins - Bile ducts - Lymphatic vessels |
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What is the function of the hepatic artery? Origin?
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- Carries oxygenated arterial blood into the liver
- Arises from the celiac trunk |
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What is the function of the hepatic portal vein?
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- Carries venous blood into the liver (high in nutrients)
- Brings blood from the intestines (contains many nutrients and toxic substances), pancreas (contains endocrine secretions like insulin and glucagon), and spleen (contains breakdown products of blood cells) |
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What is the function of the central veins?
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Carries blood away from the liver toward the hepatic veins and eventually into the IVC
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What is the function of the bile ducts?
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Transports bile from the liver
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What is the function of the lymphatic vessels in the liver?
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Carries lymph away from the liver
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What are the contents of the hepatic portal vein blood from the intestine?
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Nutrients and toxic substances
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What are the contents of the hepatic portal vein blood from the pancreas?
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Endocrine secretions like insulin and gluagon
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What are the contents of the hepatic portal vein blood from the spleen?
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Breakdown products of the blood cells
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How does blood gain access to the hepatocytes?
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Arterial capillaries and inlet venules carry blood from the hepatic artery and portal veins into a network of sinusoidal capillaries (sinusoids)
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What is the portal triad? How much blood is contributed by these components?
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Combination of branches of:
- Hepatic artery (30%) - Hepatic portal vein (70%) - Common bile duct (also associated with lymphatic vessels) |
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What is the flow of blood through the portal triad and the hepatocytes?
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- Blood from hepatic arteries and portal veins flows through the sinusoids toward the central vein
- Efferent blood leaves through the central vein to join the vena cava - Flow past the hepatocytes allows for exchange of substances |
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What kind of capillaries are in the hepatocytes? Function?
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Sinusoidal (type III) - allows the exchange of substances between the blood and hepatocytes
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What are the types of cells in the sinusoids of the liver?
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- Endothelial cells (sometimes called sinusoidal cells)
- Sinusoidal macrophages (Kupffer cells) |
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What are Kupffer cells derivatives of? Function?
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- Monocytes (they are aka sinusoidal MACROPHAGES)
- Possibly involved in breakdown of senile RBCs |
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Which cells are possibly involved in the breakdown of senile RBCs?
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Kupffer cells (aka sinusoidal macrophages)
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What are the characteristics of the endothelium lining the sinusoids?
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- Discontinuous to
- Allows unobstructed transfer of plasma and its substrates to the hepatocytes and endocrine secretions from the hepatocytes to the blood - Large spaces are evident between endothelial cells and there is no continuous basal lamina |
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What is found within the sinusoidal lining?
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Large numbers of fenestrae that are arranged as sieve plates
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Where does exchange of substances between blood and hepatocytes take place?
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Peri-sinusoidal Space of Disse
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Where is the peri-sinusoidal Space of Disse?
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Lies between the basal surface of the hepatocyte and the sinusoid
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What special feature is found on hepatocytes? Function?
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Microvilli on basal surface which increases the surface area available for substance exchange
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Why do hepatocytes have microvilli?
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To increase the surface area available for substance exchange
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What is commonly found in the peri-sinusoidal Space of Disse?
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Stellate cells (Ito cells / adipose / lipocytes)
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What is the structure and function of Stellate cells (Ito cells / adipose / lipocytes)?
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- Commonly found in peri-sinusoidal Space of Disse
- Often contain large lipid droplets - Major site of vitamin A storage |
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What is the term for the "functional units" of the liver? What are the types?
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Lobules:
- Classic lobule - Portal lobule - Liver acinus |
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What is the shape of the Classic Lobule? Organization?
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- Hexagonal block of tissue
- Single central vein at core - Portal triad at each of the 6 corners - Sinusoids and hepatic plates radiate toward the portal triads |
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How do you identify the classic lobule in pig livers? Human livers?
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- Pigs: presence of CT surrounding each lobule
- Humans: very little interlobular CT, which makes it difficult to identify |
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What is at the center of a classic lobule?
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Single central vein
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What is at the corners of the hexagonal classic lobule?
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Portal triad: branches of the portal vein, hepatic artery, and bile duct
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What radiates from the central vein to the portal triad at each corner of the hexagonal classic lobule?
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Sinusoids and hepatic plates
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What is the shape of the liver acinus? Organization?
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- Lozenge shaped
- Short axis formed between two adjacent portal triads - Long axis formed between adjacent central veins |
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What does the liver acinus correlate with?
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- Liver acinus closely correlates with blood perfusion, metabolic activity, and liver pathology
- It allows description of patterns of hepatocyte cell death and regeneration following toxicity |
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What is the flow of oxygenated nutrient / toxin rich blood through the classic lobule?
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- Blood perfuses from the terminal vessel toward the central vein
- Produces a gradient of nutrients and substances encountered by hepatocytes |
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What is the organization of the zones in the acinus?
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Three concentric zones surrounding a terminal vessel
- Zone 1: encounters afferent blood first - Zone 2: second - Zone 3: last (most susceptible to ischemia) |
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How do the three zones of the acinus differ?
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Differ with respect to metabolic activity, glycogen storage, and presence of organelles
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Acetaminophen toxicity damages which part of the acinus?
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Zone 3
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What is the principal functional cell of the liver?
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Hepatocyte
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How are hepatocytes organized?
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- Makes up the liver parenchyma
- Arranged in anastomosing plates 1-2 cells thick separated by sinusoids - Plates of hepatocytes run from central vein out toward the portal triads |
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What shape are hepatocytes? Size?
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- Large polyhedral cells
- 30 µM wide - Six surfaces - two faces the perisinusoidal space and four face other hepatocytes and the bile canaliculi |
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What do the peri-sinusoidal surfaces of hepatocytes face?
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They represent the basal aspect of the cell
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What sides of the hepatocytes face other hepatocytes?
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Lateral surfaces
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What sides of the hepatocytes face bile canaliculi?
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Apical surfaces
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Where does transfer of substances between sinusoids and hepatocytes occur?
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Across the basal surface (peri-sinusoidal surface)
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What is the shape/organization of the nuclei in hepatocytes?
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- Large spherical nucleus located in the center of the cell
- Majority are binucleate and are tetraploid (contain 4n DNA) |
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What are the features of the organelles in hepatocytes?
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- Extremely rich in organelles
- Reflects their high metabolic activity - Particularly high in RER and mitochondria - Glycogen granules are deposited throughout the cytoplasm - Lipid droplets are also prevalent |
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How can we prove that liver regeneration occurs?
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Partial hepatectomy (in rodents):
- Intact lobes of the liver are removed, leaving a single intact lobe behind - Cells in the remaining lobe re-enter the cell cycle and begin to proliferate - Dissected lobes do not grow back, instead the residual lobe enlarges enough to make up for the mass of the removed lobes |
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What cells regenerate after a partial hepatectomy?
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All liver cell types:
- Hepatocytes - Biliary epithelial cells - Sinusoidal endothelial cells - Kuppfer cells - Stellate cells |
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How long does the regeneration process from a partial hepatectomy take in rats?
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5-7 days
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How does liver regeneration occur in humans?
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- During regeneration, normal liver function is maintained
- Liver mass is precisely regulated by both positive and negative signals - Several growth factors have been identified that play crucial roles in regulating regeneration |
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What are the problems with hepatocyte transplantation?
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- Recovering enough normal donor hepatocytes that are acceptable by the host
- Donor hepatocytes from another individual will be rejected by the host without prolonged immune suppression |
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What would be the ideal way to transplant hepatocytes?
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- Isolate hepatic stem cells from an afflicted individual
- Expand them in culture - Genetically modify to correct the defects - Corrected cells could be returned to the patient whereby they could replace diseased hepatic tissues |
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Where are oval cells found? Characteristics?
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- Rare population of cells present in the biliary epithelium
- Characteristics of a stem cell, an undifferentiated cell capable of self renewal, proliferation, and production of differentiated progeny - Bipotential - differentiate to form both biliary epithelial cells and hepatocytes |
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What can oval cells become? Why?
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They can differentiate to form both biliary epithelial cells and hepatocytes because they are bipotential
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What happens during chronic liver damage when hepatocyte function and replication is severely compromised?
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Oval cells proliferate and differentiate
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How does bone marrow relate to oval cells?
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- Transplanted BM has been shown to give rise to oval cells
- May provide a source of hepatic stem cells that are bipotential (can proliferate into biliary epithelial cells and hepatocytes) |
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More recently, what have pluripotent stem cells been derived from? How can this be used for liver regeneration?
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- Pluripotent stem cells have been derived from human fibroblasts
- They have been used to generate hepatocyte-like cells that could one day be used to treat human hepatic disease |
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What is the main exocrine function of the liver?
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Production of bile
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What are the functions of bile salts?
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- Emulsification - decreases surface tension and breaks fat globules into smaller size particles
- Forms micelles (soluble in chyme) and helps absorption of fat breakdown products (FA, monoglycerides, and cholesterol) |
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Where is bile produced? How is it excreted?
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- Hepatocytes produce bile
- Bile is actively secreted by ATPases across their apical surface into the bile canaliculi |
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What is found in the bile canaliculi (where bile is excreted after being produced by hepatocytes)?
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ATPases - which means that bile secretion is an active process
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What is the organization of bile canaliculi?
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The canaliculi join together to form small terminal ductules called Canals of Herring
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What are bile ducts made of?
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- Biliary epithelial cells
- Cuboidal epithelium which forms a ductule |
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How does bile flow compare to blood flow?
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Bile flows in the opposite direction of the blood, i.e., away from the central vein toward the portal triad
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Where do bile ducts lead?
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Lead from the portal triad to join the hepatic duct that carries the bile to the gallbladder
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How much bile is secreted by the liver per day?
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1 L
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What is the function of the gallbladder?
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- Concentrates the dilute bile that comes from the liver 5-10x
- Stores up to 100 mL of bile / day |
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What stimulates gallbladder contraction and release of bile into the duodenum?
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- The presence of lipid in the duodenum induces secretion of the hormone CCK
- CCK: cholecystokinin-pancreozymin |
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What is the function of CCK?
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Cholecystokinin-pancreozymin stimulates gallbladder contraction and forces concentrated bile out
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What is the shape/structure of the gallbladder?
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- Muscular sac
- Empty or distended GB has numerous deep mucosal folds |
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What type of epithelium lines the gallbladder? Characteristics?
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- Mucosa made of simple columnar epithelial cells
- Resembles the absorptive cells of the intestine - Cells have numerous short apical microvilli - Basally located nucleus |
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How are the cells of the epithelium in the gallbladder connected?
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Junctional complexes to produce a barrier between the luminal and intercellular compartments
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What is the function of the epithelium of the gallbladder?
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- Concentrate bile by actively absorbing water into a capillary rich network in the lamina
- Maintain a barrier between the luminal and intercellular components |
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How big is the adult pancreas?
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- 100-150 g
- 20-25 cm |
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What are the parts of the pancreas? Location?
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- Head: nestles within the concavity of the duodenum, which is C-shaped
- Body - Tail - Main pancreatic duct: traverses the length of the organ and joins the common bile duct before entering the duodenum |
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What is the pancreas made of?
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- Highly lobular
- Loose collagenous tissue separates the lobules as septa |
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What is the path of the main pancreatic duct?
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Transverses the length of the pancreas and joins the common bile duct before entering the duodenum
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What are the functions of the pancreas?
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Exocrine (blue):
- Releases enzymes for digestion Endocrine (green): - Secretes hormones that control carbohydrate metabolism |
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What is the organization of the exocrine pancreas?
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- Consists of densely packed Acini (blue)
- Secretes into a system of ducts: intercalated, intralobular, interlobular, and pancreatic - Ducts channel the pancreatic secretions into the pancreatic duct that leads to the dudoenum |
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What is the organization of the endocrine pancreas?
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Consists of randomly distributed Islets of Langerhans (green) throughout the exocrine tissue (blue)
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What does the exocrine pancreas release?
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Enzymes involved in digestion in small intestine:
- Secretin - Cholecystokinin |
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What hormones are released when the duodenum contains food? Function?
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- Secretin
- Cholecystokinin - Induce secretion of pancreatic juice from the exocrine pancreas: contains alkaline fluid and enzymes and proenzymes (zymogens) required for digestion |
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How are digestive enzymes stored in the exocrine pancreas?
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Zymogen granules within the cytoplasm of acinar cells
- Granules allows them to be rapidly released into the gut after a meal - Zymogen form prevents their auto-digestion of pancreatic tissues - Stored with proteolytic inhibitors that block any errant activation of proenzymes in the pancreas |
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How are the zymogen forms of digestive enzymes activated?
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Proteolytic cleavage in the intestine
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How does the pancreas ensure there is no auto-digestion of its tissues?
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- Digestive enzymes exist in their proenzyme state (inactive) that only are activated in the intestine by proteolytic cleavage
- Proteolytic inhibitors are secreted by acinar cells to block any errant activation of the proenzymes |
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What is the functional unit of the exocrine pancreas? Shape?
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Acinus - roughly spherical containing 40-50 pancreatic acinar cells surrounding the lumen of a small ductule
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What induces acinar cells to secrete pancreatic enzymes into the lumen?
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Cholecystokinin, stimulated by fatty foods in the duodenum
ACh from vagus nerve is a weaker stimulus |
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What is the organization and function of centroacinar cells?
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- Extend from the end of the duct into the acinus as a discontinuous epithelium
- Low squamous epithelial cells responsible for secretion of alkaline fluid component of pancreatic juice |
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What induces centroacinar cells to secrete the alkaline fluid component of pancreatic juice?
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Secretin
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What is the function of Cholecystokinin?
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- Results in gallbladder contraction and emptying in under 1 hour
- Induces acinar cells to secrete pancreatic/digestive enzymes in the form of zymogen granules into the lumen - Relaxes Sphincter of Oddi |
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What is the function of Secretin?
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- Stimulates secretion of alkaline fluid, rich in sodium bicarbonate, from the centroacinar cells
- Helps neutralize acids and optimizes pancreatic function |
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What is the importance of the alkaline fluid released from centroacinar cells?
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- Solubilization of zymogen granules
- Helps neutralize acidic chyme as it enters the duodenum (prevents inactivation of enzymes and protects epithelium) |
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What is the shape and organization of the acinar cells of the pancreas?
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- Pyramidal shape
- Basally located nucleus - Cells are extremely active so the basal cytoplasm is packed with RER to synthesize exported proteins - Proenzymes are modified in the Golgi to form zymogen granules |
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How are the zymogen granules released into the lumen?
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Exocytosis at the apical surface of the acinar cell
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How is pancreatic juice transported to the duodenum?
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Network of pancreatic ducts:
- After entering the centroacinar lumen, juice moves through a series of Intralobular ducts - These ducts merge and transport the uice into the larger interlobular lobes - These then join the main pancreatic duct to transport the fluid to the duodenum |
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What is the organization of the bile ducts in the liver and gallbladder?
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- R hepatic duct drains R lobe and L hepatic duct drains L lobe
- R and L hepatic ducts combine to form Common Hepatic Duct - Gallbladder drained by the Cystic Duct - Cystic Duct and Common Hepatic Duct combine to from the Common Bile Duct |
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What does the round ligament separate? What is it a remnant of?
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- Anatomically, the round ligament divides the left part of the liver into medial and lateral sections.
- The round ligament represents the remnant of the fetal umbilical vein. |
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What does the coronary ligament of the liver do?
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The coronary ligament of the liver refers to parts of the peritoneal reflections that hold the liver to the inferior surface of the diaphragm
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What is the porta hepatis?
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Gateway to the liver - where the portal triad enters the liver (portal vein, hepatic artery, and common bile duct)
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What separates the right and left lobes of the liver?
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Obliterated ductus venosus and and obliterated umbilical vein
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What area of the liver is not covered in peritoneum? What does this part attach to?
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- The superior bare area on the right lobe
- Attaches directly to the diaphragm |
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What are the functions of the ligaments on the liver?
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- Keeps the liver from moving around
- Fastens it to the diaphragm and posterior abdominal wall |
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What is the function of the Left Triangular Ligament?
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- Fold that connects the posterior part of the upper surface of the left lobe of the liver to the diaphragm
- Anterior layer is continuous with the left layer of the falciform ligament |
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What is the location and function of the Right Triangular Ligament?
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- Situated at the right extremity of the bare area
- Small fold which passes to the diaphragm - Formed by the apposition of the upper and lower layers of the coronary ligament |
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If planning to resect part of the liver, how do you approach the task?
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Hepatic Segments: based on arterial, venous, and biliary supply, in addition to the drainage of the liver
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What drains the liver?
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Hepatic veins (right, middle, and left) that empty into the IVC
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What separates the L and R lobes clinically?
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Middle hepatic vein
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What do the segments of the liver represent?
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- Caudate lobe: segment 1
- L lobe: segments 2, 3, and 4 - R lobe: segments 5, 6, 7 and 8 |
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What is special about segment 1 of the liver?
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- Represents the caudate lobe
- Receives arterial and venous blood from both R and L sides - Directly empties into the IVC |
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If you are transplanting a liver, which segments do you take?
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- Adult: R lobe (segments 5, 6, 7 and 8)
- Child: part of L lobe (segments 2 and 3) |
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What is the route of bile from the gallbladder to the small intestine?
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- Cystic duct drains gallbladder
- Flows into Bile duct - Empties into Duodenum at the hepatopancreatic ampulla |
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What is the flow of blood leaving the midgut?
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- Branches of Superior Mesenteric Vein
- Flows into the Portal Vein to the liver - Flows through Hepatic Sinuses - Enters IVC via Hepatic Veins |
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What is the flow of blood leaving the hindgut?
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- Branches of Inferior Mesenteric Vein
- Flows into the Portal Vein to the liver - Flows through Hepatic Sinuses - Enters IVC via Hepatic Veins |
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What can happen to the portal circulation if there is liver disease?
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Liver disease can cause blood flow to back up and reverse direction to the spleen, causing the spleen to enlarge
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How does fresh blood get to the liver? What percent of the blood comes via this route?
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- Abdominal aorta supplies the Celiac Trunk
- The common hepatic artery is one of the branches - The proper hepatic artery and R and L hepatic arteries enter the liver and supply 30% of the total blood |
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Once blood enters the liver via the hepatic artery or the portal vein, how does it flow through the liver?
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- The blood flows through the hepatic sinuses / sinusoids
- Blood leaves via the hepatic vein to get to the IVC |
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What kinds of cells line the bile canaliculi?
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Liver cell plates
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Where is the space of Disse?
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Located between the sinusoids and the liver cell plates that line the bile canaliculi
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How does the concentration of bile in the liver compare to that in the gallbladder? How does this change occur?
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- Liver bile is more dilute than gallbladder bile
- Bile is concentrated once it gets to the gallbladder via absorption of water, Na+, and Cl- - Leaves concentrated salts, cholesterol, lecithin, and bilirubin - Volume goes from 500 mL to 50 mL |
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What happens to the volume of bile that leaves the liver to that which is stored in the gallbladder?
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Volume goes from 500 mL to 50 mL via absorption of water, Na+, and Cl-
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What happens to cholesterol and lecithin in the gallbladder?
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They are solubilized by bile salts
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Where are bile acids reabsorbed?
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Ileum where they are taken via the portal blood back to the liver
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What enzymes are released by the pancreas to digest proteins?
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- Trypsinogen
- Chymotrypsinogen - Procarboxypeptidase All released in inactive form to prevent self-digestion |
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How are the enzymes released from the pancreas to digest proteins activated?
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- Trypsinogen is activated to Trypsin by Enterokinase
- Trypsin further activates Trypsinogen as well as converts Chymotrypsinogen to Chymotrypsin and Procarboxypeptidase to Carboxypeptidase |
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What activates Trypsinogen to Trypsin?
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- Enterokinase
- Other Trypsin molecules |
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What activates Chymotrypsinogen to chymorypsin?
|
Trypsin
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What activates Procarboxypeptidase to Carboxypeptidase?
|
Trypsin
|
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What prevents activation of the pancreatic enzymes?
|
Trypsin inhibitor prevents activation until secretions reach the small intestine
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What are the three forms of carbohydrates in our diet?
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- Starches
- Lactose - Sucrose |
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How do you digest starches?
|
Starch → Maltose and 3-9 glucose polymers
- Ptyalin from the saliva (20-40%) - Pancreatic Amylase from the pancreas (50-80%) Maltose and 3-9 glucose polymers → Glucose - Maltase and α-dextrinase from the intestine |
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How do you digest lactose?
|
Lactase from the intestine breaks Lactose down into Galactose and Glucose
|
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How do you digest Sucrose?
|
Sucrase from the intestine breaks down Sucrose into Fructose and Glucose
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What is the form of the dietary fats?
|
- Majority are Triglycerides (TG): glycerol nucleus + 3 FA side chains
- Small amounts of Phospholipids, Cholesterol, and Cholesterol Esters |
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What digests Triglycerides?
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Pancreatic Lipase - can digest all TG it can reach within 1 minutes (requires emulsification by bile salts)
|
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What is the function of Pancreatic Lipase?
|
Digests Triglycerides into Free Fatty Acids and 2-Monoglycerides
|
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How do you digest Phospholipids?
|
Phospholipase
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How do you digest Cholester esters?
|
Cholesterol Esterase
|
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What happens to the digested fat remnants?
|
Bile salts form micelles and remove monoglycerides and fatty acids and transports them to the brush border for absorption
|
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Where is bicarbonate secreted from?
|
Bile ducts and pancreatic ducts
|
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How does bicarbonate get formed?
|
- CO2 diffuses in and combines with H2O to form H2CO3
- H2CO3 breaks down to form H+ and HCO3- - HCO3- goes into the lumen and associates with Na+, which causes a gradient into the lumen with water |
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Which hormone has the greatest effect on Sphincter of Oddi relaxation?
|
Cholecystokinin
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In a 40-yo male with Hepatitis C, which hepatic acinus zone would be exposed to the greatest number of viral particles?
|
Zone 1 (this receives the greatest amount of blood flow)
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Which zone of the hepatic acinus would be affected most by ischemia?
|
Zone 3
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