Lecture 32 Flashcards
Intestinal villus to liver
There is large capillary network present to transport material from small intestine using intestinal villi to the liver
Most important components, proteins, aa from intestinal villi are transported through large vein called portal vein to the liver. The liver is in a strategic location that allows it to receive a lot of nutrients, store them (specifically glucose and sugars) and detoxify components (i.e. alcohol). Then, the liver passes the nutrients back into the bloodstream
Liver
Liver is epithelially derived organ. Plates (rows) of ep cells called hepatocytes. Blood-filled spaces called sinusoids are thin-walled, leaky, have lots of gaps in the endothelial lining and is lined by endothelial cells. This arrangement allows each hepatocyte to have interactive surface with bloodstream
Liver develops from the gut but the cells are arranged in peculiar way: cuboidal shaped cell, prominent nuclei, cytoplasm stains eosinophilic, and lots of protein in cytoplasm
Major functions of hepatocytes
Metabolism and storage - smooth ER, cytosol
• Lipid soluble drugs
• Steroids
• Storage of carbohydrates as glycogen
• Detoxification
Bile formation and secretion - smooth ER
• Synthesis and recycling of bile acids
- bile important for emulsifying lipids in GI tract
- in order to breakdown lipids, bile acids and bile salts required. The liver produces and recycles these
Synthesis and secretion of … - smooth ER, rough ER, golgi
• Proteins (albumin, prothrombin, fibrinogen)
- prothrombin and fibrinogen are involved in clotting cascade
- albumin regulates osmolarity of blood (how liquid the blood is)
- liver delivers these components into bloodstream
• Cholesterol
• Lipoproteins
PAS stains liver and sugars
Venous portal system
In liver
- Mesenteric arteries
- Intestinal capillary beds that receive nutrients in the intestines
- Portal vein
- Hepatic sinusoids that release nutrients, and receive stored and modified component. In the liver.
- Hepatic vein
- Vena cava
2 veins that border a capillary network is called a venous portal system. This arrangement allows hepatocytes to modify whatever we take into our GI tract
Arteriole portal system
A portal system or capillary network b/w 2
arteries
Occurs in the kidneys
Blood and bile flow through the liver
Cells in liver are organized into hepatic lobules. Each lobule has hexagonal shape in cross section. In centre of lobule is a large blood vessel called central venule or central vein, which is where the blood leaves the lobule through hepatic vein to vena cava
Portal triad: 3 structures that communicate with hepatic lobule
- Portal venule: sends portal venules from the periphery to hepatic sinusoids (then the blood leaves through central venule to hepatic vein to inferior vena cava). This blood has nutrients from Gi tract but little oxygen b/c it is from systemic circulation
- Hepatic arteriole: arterioles carry oxygenated blood and merges into sinusoids, resulting in sinusoids that carry a mix of oxygen and nutrient-rich blood
- Bile ductule: Liver cells make bile salts. Bile ducts are at periphery to collect the bile made by the hepatocytes and send it OUT of the triad through the hepatic duct (liver has its own duct system)
Classic liver lobule
Some CT surrounds the lobules
Central vein drains blood out of the lobule
Portal triad is at corners of lobules
Portal triad
Portal venule (large, thin-walled vessel), bile ductule (round nuclei, forms ring-like structure), hepatic arteriole (smaller, thick wall of smooth muscle, small lumen)
- Sends blood to the hepatic lobule and drains bile away
- Blood goes from periphery towards the centre and bile flows from the centre towards the periphery; this occurs in separate compartments
Hepatocytes form rows OR plates of cells that are adjacent to sinusoids that are fed by portal venules. Portal venule is at periphery of lobule and sends nutrient-rich blood into lobule. Then the blood drains into the central vein
Oxygenated blood comes from hepatic arterioles. This blood mixes at the periphery of the lobule with blood in the hepatic sinusoids
Bile ductule collects bile from spaces that are separate from the blood supply via bile canaliculus
Central vein/venule and surroundings
Drains blood away from the liver lobule
Fairly large with thin walls
Sinsusoids are continuous with central venule. Hepatocytes form rows of cells, which are all in communication with the sinusoids.
Endothelial cells line a sinusoid and the
individual hepatocytes are adjacent to the endothelial cells
Sinusoids are fenestrated (leaky)
Hepatocyte
Have basolateral domain and apical domain. Apical and basolateral domain are separated by tight junctions
Basolateral domain is cell surface that interacts with sinusoids (the blood). There is traffic going to and flow b/w hepatocyte and content of sinusoid. Sinusoid also contains kupffer cell
Apical domain, in contrast, is formed by adjacent hepatocytes forming canal system, called bile canaliculus. Hepatocytes form junctions and leave a lil space, which represents the apical domain, and this is the surface where bile salts and bile acids
are excreted to be sent to the duodenum
Space of Disse
b/w endothelium and PM of basolateral side of hepatocyte (liver cell), there is a lil bit of space called Space of Disse
Space of disse is not a space, it is loose CT that is in b/w the endothelium and the hepatocyte. Within the CT, there are lots of bundles of type III collagen, called reticular fibers.
The network of reticular fibers support the hepatocytes. The hepatocytes grab on to reticular fibers with their cytoplasm.
At their baso-lateral surface hepatocytes interact with the sinusoidal circulation
Endothelium is leaky, allowing components to pass through into and out of sinusoids. All kinds of traffic goes across the Space of Disse: sugar, toxins and nutrients
Kupffer cell
In liver, monocytes differentiate into Kupffer cells, which enter sinusoids via fenestrated endothelium of the sinusoids. But they are also migratory; macrophages can move about. They phagocytose remnants of RBCs
In the spleen in the red pulp, old RBC are destroyed. All components will enter the portal vein, which carries blood from small intestine or gut, as well as from the spleen. So in the liver, kupffer cells break down these components even further, and some of those components are taken up by hepatocytes
Hepatocyte function
Hepatocytes have 2 functions: endocrine and exocrine
- interact with blood stream (endocrine)
- hepatocytes store carbohydrates as glycogen and makes plasma proteins
- interact with bile canaliculi (exocrine)
Hepatocytes take up glucose, which gets degraded in the SER, then it gets stored as glycogen within the hepatocyte cytoplasm.
- can identify if the liver has stored a lot of sugars via PAS staining (i.e. just after eating, your liver is filled with glycogen)
- liver stores glycogen but also makes glucose again and sends it back into the bloodstream
Lots of protein synthesis occuring in the hepatocytes. Production of plasma proteins like albumin, thrombin, etc. is sent into sinusoids across the space of disse. This
is endocrine function
Glycogen storage in hepatocytes (compared to ribosomes)
Glycogen appears as irregular dark blobs, which is stored within hepatocytes
Glycogen is significantly bigger than ribosomes
Ribosomes are all of the same size
Glycogen is clumps of dark material of diff size
Junctional complexes in normal epithelium vs in hepatocytes
In normal epithelium, there are junctional complexes close to the apex (desmosomes, tight junctions, etc.) that separate the apical membrane from the rest of the PM.
In hepatocytes, tight junctions and adherens junctions form around a space, so that the apical PM is forming a lil canal b/w adjacent hepatocytes.
Each hepatocyte has at least 2 apical domains and 2 basolateral domains.
Apical surface receives material that the hepatocyte generates but is not going to enter bloodstream; Instead, the material enters bile system AKA bile canaliculi system
Bilirubin
Kupffer cells can only be identified if they phagocytose something colourful.
Animal was injected with toludine blue, which was taken up by macrophages; All blue material is found in kupffer cells
Kupffer cells detoxify a component called
bilirubin. Bilirubin is pigment formed by hemoglobin breakdown in spleen and livers. Important to remove bilirubin b/c it is a neurotoxin (unless it is conjugated
with water and removed out of blood stream).
This is important function of liver. It detoxifies the breakdown product of hemoglobin by an
enzyme system located in the SER. Glucuronyltransferase is the main enzyme that makes bilirubin water soluble. Then, water-soluble bilirubin glucuronide is the compound excreted in an exocrine fashion into the bile duct. Then it is sent to the duodenum. Overall, hepatocytes detoxify bilirubin by conjugation with glucuronide, and excrete it into bile canaliculi
The reason why our poop is brown is due to bilirubin. Poop is orange-ish brown pigment.
Bile acids
Exocrine function: hepatocytes make and recycle bile acids. Transport bile acids
Bile acids
- 10% de novo synthesis by liver
- synthesis of cholic acid and conjugation with glycine and taurine in sER
- 90% recirculation
Hepatocytes take up bile acids, process it, and send it back into bile canaliculus to be sent to duodenum.
Once the bile is sent to periphery of a liver lobule, some of the hepatocytes differentiate to form duct cells. Bile is transported away from liver via bile canaliculi to bile ductules to bile ducts
Endocrine functions of hepatocytes
Endocrine functions involves basolateral domain
- Carbohydrate uptake from sinusoid to inside of hepatocyte. This is for glycogen storage
- Glycogen breakdown inside hepatocyte is released as glucose into sinusoids
- Protein synthesis inside hepatocytes is released as plasma proteins into sinusoids
Exocrine functions of hepatocytes
Exocrine functions involve bile ducts via bile canaliculi on the apical domain
- Bilirubin from sinusoids is broken down inside hepatocytes and goes into bile canaliculi
- Bile from sinusoids is made and recycled inside hepatocytes and goes into bile canaliculi
Liver to gall bladder to duodenum
- The bile leaves the liver via the right and left hepatic ducts.
- Then, it goes through common hepatic duct.
- Then, it goes through cystic duct to go to gall bladder, where the bile becomes concentrated and water is removed.
- Once the bile is highly concentrated (allows it to perform better in duodenum), it exits gallbladder via cystic duct, and travels through common bile duct to arrive duodenum
The common hepatic duct and common bile duct is continuous and the same thing, but is separated by cystic duct in the middle.
3 ways of describing organization in the liver
- Classic lobule
- based on blood drainage
- centre of lobule is central venule that drains blood and receives things from all different directions - Portal lobule
- based on bile drainage
- bile duct is at periphery of several classic lobules; it receives bile from adjacent classic lobules - Liver acinus
- based on blood supply
- blood supply comes from periphery and is sent into adjacent classic lobules
- cells close to central venule are deprived of oxygen
- there are lots of hepatocytes dying or turning over around the vicinity of the central venule
- there are also diff zones here depending on how the blood flows. In diff zones of the live acinus, hepatocytes perform diff functions.
