Liver, Pancreas and Gallbladder Your tutor: Rachel Boggus Boggusrl@email.uc.edu

Review What is an exocrine gland? What is an endocrine gland?

Review What is an exocrine gland? Retains connection to original epithelial layer, secretes product into ducts that lead to lumen. What is an endocrine gland? Lose connection with epithelial layer and secrete products into surrounding CT and mesenchyme

Cont. The liver, gallbladder, and pancreas are like big glands that sprouted from the digestive tract.

Circulation to and from Liver Where does blood get to the liver from (2 spots)? What is a portal system? Why have a hepatic portal system?

Circulation to and from Liver Where does blood get to the liver from? From the hepatic artery (20%--O2 rich) From the hepatic portal vein (80%--O2 poor, nutrient rich) What is a portal system? Systemic circulation includes two capillary beds Why have a hepatic portal system? Because the liver is important for many functions including detox and packaging of the nutrients that we eat.

Liver blood supply cont. Where do the blood vessels reach the liver? Where do the portal vein and hepatic artery empty? How does blood leave the liver?

Liver blood supply cont. Where do the blood vessels reach the liver? Inferior side of liver at the porta hepatis Where do the portal vein and hepatic artery empty? Branch through CT and empty into the sinusoids (O2 Rich and poor blood MIX here!) How does blood leave the liver? Tributaries that drain into hepatic veins  inferior vena cava.

The Liver Lobule What is in the corners of the lobules? What is contained in this structure?

The Liver Lobule What is in the corners of the lobules? Portal triad What is contained in this structure? Branch of hepatic artery, branch of hepatic vein, and a bile duct (also lymph vessels and autonomic nerves)

Liver Lobule Cont. Liver lobules consist of plates of hepatocytes Where are the plates directed? What are the spaces between the hepatocytes called? Trace the venous drainage from the liver

Liver Lobule Cont. Liver lobules consist of plates of hepatocytes Where are the plates directed? Toward a central vein What are the spaces between the hepatocytes called? Bile canaliculi—they are continuous with bile ducts in portal triad. Trace the venous drainage from the liver Hepatic vessels (artery and portal vein) liver sinusoidscentral veinsublobular veinshepatic veins

Liver Sinusoids Are discontinuous—what does that mean? What is on the surface of hepatocytes close to sinusoids? What is the Space of Disse? What are Kupffer cells? Where are they found?

Liver Sinusoids Are discontinuous—what does that mean? Composed of incomplete endothelial lining with an incomplete basal lamina What is on the surface of hepatocytes close to sinusoids? Lots of microvilli What is the Space of Disse? Space created between endothelial cells of sinusoids and microvilli of hepatocytes. What are Kupffer cells? Where are they found? Macrophages of the liver, found on luminal surface of endothelial cells of liver sinusoids

1 = disse; 2 = endothelial cell

Bile Canaliculi Walls formed by hepatocytes themselves Hepatocytes have microvilli that project into lumen of canaliculi Bile flows to the outer portions of the lobules to the bile duct in the portal triad Bile tract lined by cuboidal cells w/in CT surrounding lobulebile ductules—join at right angles with bile ducts within portal triad What is the epithelium of the bile ducts?

Bile Canaliculi Terminal tubes of biliary tree Walls formed by hepatocytes themselves Hepatocytes have microvilli that project into lumen of canaliculi Bile flows to the outer portions of the lobules Bile tract lined by cuboidal cells w/in CT surrounding lobulebile ductules—join at right angles with bile ducts within portal triad What is the epithelium of the bile ducts? Cuboidal/columnar surrounded by CT sheath

Hepatic Artery, Vein and bile duct

Portal triad

Bile Canaliculus – between hepatocytes

Hepatocytes What organelles do they contain?

Hepatocytes What organelles do they contain? Mitochondriaeosinophilia RERbasophilia SER Peroxisomes Golgi Free ribosomes Glycogen Lipid droplets

What are the 9 functions of the hepatocyte Protein synthesis—albumin, prothrombin, fibrinogen, lipoproteins (products released into space of Disse) (ENDOCRINE) Bile Secretion—EXOCRINE product, secreted into biliary tree Blood Filtration—Old RBCs broken down by Kupffer cells Excretion—bilirubin (product of Hb breakdown) Metabolic Storage—carbs  glycogen Metabolic functions—lipids and AAsglucose

9 fncs of hepatocytes cont. Detoxification and inactivation—nitrogenous wastesurea (SER) Synthesis of VLDL—main carrier of lipids in the body Recycling IgA—from sinusoids to bile canaliculi (transcytosis)secretory IgA

CT Stroma W/in lobules very sparse, consisting of reticular fibers (chicken wire or tree branch appearance) Collagen borders lobules

Classic lobules, portal lobules and liver acini What is the difference between the three?

Classic lobules, portal lobules and liver acini What is the difference between the three? Classic lobules—central structure central vein, portal triads at corners Portal lobule—triangle with portal triad in center and central vein at each corner—used when thinking of exocrine (biliary) function of the liver Liver acinus—oval shaped with central veins at apices (blood flow model)

Why do we care about the crap on the previous slide? Because it helps you realize what hepatocytes are exposed to what things. I.E. hepatocytes closer to the wall of the classic lobule will get more levels of O2 and nutrients and hepatocytes closer to central vein will see more of the endocrine products

Regeneration Your liver is cool because if you take out 75% of it, it will grow back BUT, if you are an alcoholic you get too much CT regeneration which is called cirrhosisfewer hepatocytes and poor liver structure. Too much CT, too few functional cells

In other words…

Gallbladder What are gallstones? Why are they bad?

Gallbladder What are gallstones? Why are they bad? Gallstones are precipitations of cholesterol, calcium carbonate, and bilirubin. Bad cause they can block bile flowjaundice and pain.

G bladder

No goblet cells and no crypts not intestine

Gallbladder mucosa Innermost layer—simple columnar epithelium—cells responsible for? How? Lamina propria—what is it like? Why?

Gallbladder mucosa Innermost layer—simple columnar epithelium—cells responsible for? How? Concentration of bile by active transport of Na+ ions across basolateral memb. and into interstitial tissue. H20 follows by osmosis Lamina propria—what is it like? Why? Highly vascular to allow for H20 reabsorption

Gallbladder muscular and outer layers Muscular layer—thin and irregular What causes contraction of muscular layer? Outer layer—serosa or adventitia?

Gallbladder muscular and outer layers Muscular layer—thin and irregular What causes contraction of muscular layer? CCK Outer layer—serosa or adventitia? This is a TRICK, its BOTH adventitia when buried against the liver serosa on side facing viscera

Pancreas Also mixed exocrine/endocrine function like liver Exocrine pancreas: What are the secretory cells of the pancreas? What do they secrete?

Pancreas Also mixed exocrine/endocrine function Exocrine pancreas What are the secretory cells of the pancreas? Acinar cells What do they secrete? Digestive enzyme precursors

Acinar cells What do they look like? What causes them to release their product?

Acinar cells What do they look like? Typical protein secreting cells Round nucleus in lower ½, prominent nucleolus, basophilic basal cytoplasm b/c of tons of RER, large supranuclear golgi which make zymogen granules near apical surface. What causes them to release their product? CCK

Pancreatic Acinar cells – RER and zymogen galore

Pancreas Ducts Beginnings intercalated ducts composed of centroacinar cells What do these cells do? Trace the flow of products from the intercaleted ducts to the intestine

Pancreas Ducts Beginnings intercalated ducts composed of centroacinar cells What do these cells do? Respond to secretin and release bicarb to buffer acidic chyme Trace the flow of products from the intercaleted ducts to the intestine Intercalatedintralobularinterlobular (in septa)

Endocrine Pancreas Islets of Langerhans Very pale b/c they contain less RER, contain fenestrated capillaries What are the three types of secretory cells?

Endocrine Pancreas Islets of Langerhans Very pale b/c they contain less RER, contain fenestrated capillaries What are the three types of secretory cells? Alpha—secrete glucagon Beta—secrete insulin Delta—secrete somatostatin

Islet of endocrine pancreas

Islet of langerhans

The Pancreas and Disease What is diabetes mellitus? What are its symptoms? What is the difference between type I and II? What is pancreatitis and what causes it?

The Pancreas and Disease What is diabetes mellitus? Breakdown in one of the steps of insulin synthesis/secretion or recognition What are its symptoms? Polyuria (lots of peeing) polydypsia (really thirsty), polyphagia (eating a lot) glycosuria (sugar in the urine-they used to drink it to test for diabetes), hyperglycemia—high blood glucose What is the difference between type I and II? Type I have low levels circulating insulin from autoimmune destruction of beta cells, II the target cells don’t respond to insulin What is pancreatitis and what causes it? Inflammation of the pancreas, may result from reflux of bile into pancreatic ducts due to hepatopancreatic ampulla obstruction (gallstone)

Image Review

A portal triad is at the left A portal triad is at the left. Blood in the branches of the hepatic artery and portal vein enters the sinusoids, between the cords of liver cells, and courses toward the central vein, which is a tributary of the hepatic vein. Bile flows in the opposite direction, from the center out, toward the tributaries of the bile duct. Bile canaliculi are tiny channels which exist between the cell surfaces of neighboring hepatic parenchymal cells.

Liver – portal triads surround central vein

A PORTAL LOBULE is represented as that liver tissue with the BILE DUCT, HEPATIC ARTERY and PORTAL VEIN in the center. 

Bile duct = simple cuboidal cells surround it

Sinusoids continuous with central vein – blood comes here from hep Sinusoids continuous with central vein – blood comes here from hep. artery and portal vein

The HEPATIC LOBULE is defined by a radiating arrangement of liver cell plates around a CENTRAL VEIN

Central vein again Also, the hepatic parenchymal cells may be binucleate

in the SINUSOIDS are phagocytic cells called KUPFFER CELLS . 

Kupffer cell – the mac of the liver

Bile canaliculi (hepato surrounds it) vs Bile canaliculi (hepato surrounds it) vs. sinusoid (endothelial surrounds it)

Bile flows from the liver cells out through small channels between the cells called BILE CANALICULI to the BILE DUCTS located along the sides of the Hepatic lobule.  

EM of space of Disse (1) lying between sinusoidal endothelium (2) and the cell surface of an hepatocyte. Microvillous extensions of the hepatocyte surface lie in the space of Disse.

Liver lobule outlined by blue connective tissue septa Liver lobule outlined by blue connective tissue septa. Central vein is in the center. portal canals lie out at the "corners", in the connective tissue.

largest vessel is the portal vein at upper left and right of portal vein are two branches of bile duct with simple cuboidal lining; between them lies a branch of the hepatic artery with pink tunica media (smooth muscle). The irregular-shaped empty spaces with endothelial linings are lymphatics.

EM of bile canaliculus -- the empty spot between adjacent hepatocytes EM of bile canaliculus -- the empty spot between adjacent hepatocytes. Essentially, it is a widening of the intercellular space.

Another portal area with branches of the portal vein (largest), the hepatic artery (to right), and bile duct (above, center - with cuboidal epithelium)

Canaliculi have chicken-wire pattern

gallbladder In the gall bladder the epithelium is simple columnar with oval nuclei near the base. striated border (microvilli) is present. In the contracted gall bladder the mucosa exhibits extensive foldings which can be confused with villi. The muscular wall has small, pencil-like bundles of smooth muscle interspersed with connective tissue. The entire wall is thin compared with that of the intestine.

gallbladder

gallbladder Look at how thin the muscularis is compared to the intestine and NO MUSCULARIS MUCOSA No goblet cells

gallbladder No goblets so not intestine, and cant be stomach because there are no parietals or chiefs

The epithelium is simple columnar with a small brush border  The epithelium is simple columnar with a small brush border. There is no muscularis mucosa.  The muscularis externa consists of irregularly interwoven strands of smooth muscle, collagenous and elastic fibers.

Wall of gall bladder, showing high, branching mucosal folds Wall of gall bladder, showing high, branching mucosal folds. These are not villi. The rest of the wall contains connective tissue and thin strands of smooth muscle.

pancreas In addition to the exocrine portion, it also contains endocrine components called islets of Langerhans The exocrine pancreas is responsible for the synthesis of many digestive enzymes (e.g., amylase, trypsin, chymotrypsin, lipase and carboxypeptidase).

Pancreas in low power Pancreas is surrounded by a thin connective tissue CAPSULE from which SEPTA extend into the interior, thereby subdividing the parenchyma into smaller units called LOBES and LOBULES. 

Pancreas intralobular duct IN the lobule parenchyma Islet of langerhans are best seen under lower power b/c their light color is easy to pick out

PANCREAS INTERlobar ducts between lobes INTRAlobar ducts in lobes

Can sometimes see zymogen granules in the apical (nearest the lumen) portion of cells

The pancreatic tissue is composed of exocrine ACINI The pancreatic tissue is composed of exocrine ACINI.   The apical portions of their cells contain an abundance of zymogen granules which are stained bright red. The base is more basophilic, because of the rough endoplasmic reticulum.  

Up close

Centroacinar cells within the MIDDLE of the acinus – they are the beginning of the duct system

Notice that the zymogen granules of the acinar cells lie at the apical ends; nuclei are toward the base. The granules are precursors of pancreatic digestive enzymes

pancreas Just like in the salivary glands, the intercalated duct has a rim of 5-6 simple cuboidal cells surrounding it

Here you can see thin connective tissue septa dividing the parenchyma into lobules of secretory acini. The pancreas is essentially a serous gland. It is distinguishable from the parotid gland by the presence of scattered, pale islets of Langerhans, which constitute the endocrine portion of this organ.

The pancreatic islets contain three major cell types.: alpha (A) cells which synthesize glucagon, beta (B) cells which produce insulin and delta (D) cells which synthesize somatostatin. *These polypeptide hormones are discharged into the blood stream*

Boggusrl@email.uc.edu for any questions, concerns, or requests And we’re done! Boggusrl@email.uc.edu for any questions, concerns, or requests