GI 4 - The Liver, Gall Bladder, and Pancreas.doc

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McMaster University
Health Sciences
Cale Zavitz

G.I. 4: The Liver, Gall Bladder, and Pancreas The Defecation Reflex • As fecal matter accumulates in sigmoid rectum, it will cause rectal wall to distend- this is sensed by stretch receptors in wall of sigmoid rectum- an afferent neural signal is sent up to spinal cord- this does two things: i. One signal is conveyed up afferent pathways to the cortex- feel urge "to go"- frontal lobe will calculate whether or not this is an appropriate time "to go" ii. At level of spinal cord, there is a local reflex- sends efferent motor information back to wall of sigmoid rectum and rectum to cause the muscle to contract, putting pressure on fecal matter and creating more pressure in large intestine- at the same time, inhibitory signals are sent to internal anal sphincter which begins loosening to accommodate fecal matter that is coming through- thankfully we have outer, voluntary anal sphincter • Because this is the enteric nervous system, muscle of sigmoid rectum is stimulated to contract through the parasympathetic nervous system • Make decision from cortex through upper motor neurons which synapse with lower motor neurons in the splanchnic region (sacral spinal cord) to determine whether or not to relax outer sphincter Liver: Relational Anatomy • Has right and left lobes- right side of diaphragm is more domed in order to accommodate right lobe • Falciform ligament: Separates left and right lobe- double fold of peritoneum, helps to suspend liver from inferior surface of diaphragm- also allows liver to be connected to anterior abdominal wall- only visceral organ that does so • Round Ligament: was ligamentum teres in fetus, remnants of umbilical vein that returned oxygen rich blood from placenta to (eventually) right side of heart- bypassed liver by hooking up to the ductus venosus • Liver produces a lot of secretions which get dumped into tubes- these tubes are called right and left hepatic ducts- will come together to form a common hepatic duct • Produces bile, which contains bile salts that emulsify fats in duodenum- produces is all day- most bile is not used, but goes up cystic duct to be stored in gallbladder • Gallbladder- muscular sac- when food is occupying duodenum, muscles in wall of gallbladder will contract, sending extra bile to duodenum to deal with extra fats ⁃ Fundus: tip ⁃ Body: where bile is stored ⁃ Neck: narrowing of gallbladder • Secretions from liver and gallbladder will combine in common bile duct- must hook up with pancreatic duct, running length of pancreas- it accepts exocrine products from pancreas (enzymes, bicarb-rich secretions)- will mix at Hepatopancreatic Ampulla (Ampulla of Vater) • Hepatopancreatic sphincter: protects opening of ampulla of Vater Liver: Anatomy • Inferior surface: two more lobes associated with right lobe ⁃ Quadrate lobe: square shape ⁃ Caudate lobe: towards back • Porta Hepatis: where duct work runs through • Hepatic portal vein: coming into liver, which is returning good from the wall of the GI tract. Also have hepatic artery- need oxygenated blood to keep liver alive • Right and left hepatic duct: also run through Porta Hepatis- are part of liver proper- form Y-shape at common hepatic duct • Gallbladder: hangs off inferior surface Liver: Duct, ducts, and more ducts! • Hepatic ducts, which are actually in liver itself, form common hepatic duct. When we are not using secretions, they are stored in the gallbladder via the cystic duct. When gallbladder contracts, can call upon reservoir through common bile duct. Secretions from pancreatic duct will join bile at hepatopancreatic ampulla, and then pass through hepatopancreatic sphincter. Liver: Blood Supply • Supplied by right and left hepatic artery which branch off of common hepatic artery, which arises from the celiac trunk. Liver is below diaphragm, so first branching of abdominal aorta (celiac trunk) supplies that region. Liver: A Dual Blood Supply • Hepatic portal vein brings oxygen-poor but nutrient-rich blood, which then mixes with blood from hepatic artery (a branch off celiac trunk)- oxygen-rich and oxygen-poor blood meet and mix in the sinusoids of the liver to meet liver's needs- this is all then drained out through hepatic veins- will dump into inferior vena cava (because we are below the heart) to return blood back to the heart • Sinusoids: Large spaces where oxygen-rich and oxygen-poor blood meets in the liver- capillary bed has incomplete walls- huge gaps between endothelial cells and the basement membrane is incomplete- where blood from hepatic portal vein and hepatic artery percolate through and mix up Liver: Cell Types • Hepatocytes: synthesize proteins, store nutrients, detoxification, and metabolism ⁃ Comprise most of the liver • Kupffer Cells: modified macrophages, tissue resident macrophages- stick around in liver, occupy sinusoids- act as a filter as blood comes by- phagocytosis of microbes, production of cytokine- septic shock- can sometimes have bacteria come across gut wall- if too many come across, will stimulate macrophages which will produce a lot of cytokines, causing inflammation throughout entire bloodstream- problem- if inflammation is occurring everywhere, blood vessels are all dilating and getting very leaky- suddenly blood pressure drops ⁃ Also responsible for recycling heme- protein that helps to stabilize the central iron in hemoglobin- when old red blood cells die, Kupffer cells will phagocytose them, break down protein component and create waste product- bilirubin- will be handled by liver, excreted into lumen of gut, to be eliminated with feces • Sinusoid endothelial cells: large gaps between endothelial cells, incomplete basement membrane- need liver to be able to dump really large proteins that it makes (clotting proteins, albumin) into blood stream. Cells also have fenestrations- little holes in the plasma membrane that allow solutes to go past- holes aren't through cytosol, cells aren't leaking everywhere Liver: Histology (lobule) • Lobule: six-sided (less obvious in humans)- blood tends to come in from outside, percolates across sinusoids to central vein in middle, and is taken away- central veins will begin to coalesce and form hepatic veins which drain the liver- at the same time, hepatocytes are creating bile- it gets dumped into a separate duct work that exists between hepatocytes- bile goes out through bile duct sitting at each corner, along with a portal vein and a hepatic artery- form hepatic triad Liver: Lobule • Bile canaliculi bring bile to bile ducts The Roles of the Liver • Process intestinal nutrients- sugars, amino acids, fats and vitamins • Synthesis of proteins • Detoxification of wastes, drugs, etc. • Storage of iron, excretion of bilirubin • Deals with microbes (Kupffer cells) • Aids in digestion (bile) Liver: Processing of Sugars • Stores glucose from dietary sources as glycogen ⁃ Monosaccharide -> Polysaccharide ⁃ Glucose is a monosaccharide- when it is stored as glycogen, monosaccharides are attached end to end to create a long chain which we can store within the hepatocytes- reason for this- if it was just stored as simple sugar, water likes to follow glucose- if hepatocytes were storing glucose, they would swell with water- storing as glycogen prevents cell swelling ⁃ Can provide 1-2 days worth of glucose in form of glycogen ⁃ The nervous system almost exclusively derives energy from glucose- need to maintain glucose levels to meet needs of brain ⁃ Other tissues can break down fatty acids or proteins for energy • Can convert glucose into fatty acids or triglycerides ⁃ Excess glucose- liver has finite capacity- extra is converted to fats, most of which is stored in greater omentum • Can convert galactose and fructose to glucose as needed • Can create "new" glucose ⁃ Gluconeogenesis ⁃ From lactic acid (byproduct of anaerobic respiration in skeletal muscle) and pyruvate (Krebs cycle?) ⁃ Amino acids- once you've used stored glycogen, muscles begin to waste- utilizing protein for amino acids to convert to glucose ⁃ Glycogenolysis- breaking down glycogen stored in liver • Skeletal muscle- other key tissue that helps with blood-glucose homeostasis- more lean skeletal muscle means more glucose storing capacity- once skeletal muscle grabs glucose, cannot be returned to blood stream, strictly for muscle at that point Liver: Processing of Amino Acids • Essential amino acids are used for protein synthesis- Important proteins generated by liver include: ⁃ Albumin- major plasma protein, produces colloid osmotic pressure- helps to draw all the fluids back at the venous end of capillary beds- not losing plasma to tissues ⁃ Fibrinogen- clotting protein • Deamination- removes amino group (nitrogen containing) to allow for oxidation of amino acid in Krebs cycle- ATP from amino acids- results in formation of toxic ammonia- liver hepatocytes will convert it to harmless urea • Non-essential amino acids can be formed by transamination- amino group transferred from one carbon skeleton to another to make non-essential amino acid Liver: Processing of Fats • Ingested fats are usually large fat globules- has to mix with bile salts secreted by the liver and stored in the gallbladder- this helps to emulsify the fat, makes it into smaller fat droplets • Lipases can now work on this to break it down into fatty acid chains or monoglycerides- when fat components break down, they will reassemble with the bile salts to form micelles • Absorbed by absorptive cell and repackaged with a protein to form a chylomicron which goes into the lacteal sitting within intestinal villi- will then flow through lymphatics, get into circulation via left thoracic duct, and make its way to the liver to be further processed • The liver packages fatty acids into forms that can be transported or stored (lipoproteins) ⁃ VLDL to be delivered to adipocytes for storage ⁃ LDL to transport cholesterol to tissues- some tissues will use this cholesterol to make steroid hormones (estrogen, progesterone, testosterone) ⁃ Don't want too much in tissues- if left there, can accumulate under endothelium of blood vessels and begin atherosclerosis ⁃ HDL returns excess cholesterol from tissues to liver (catabolized and secreted in bile salts)- every time you excrete bile salts, you are getting rid of cholesterol Transportation of Fats • From intestine: ⁃ Chylomicron- 80-95% triglyceride, 3-6% phospholipid, 2-7% cholesterol, 1-2% protein • Made by Liver: ⁃ VLDL- 55-65% triglyceride, 15-20% phospholipid, 10-15% cholesterol, 5-10% protein ⁃ LDL- 10% triglyceride, 20% phospholipid, 45% cholesterol, 25% protein • Returned to Liver: ⁃ HDL- 5% triglyceride, 30% phospholipid, 20% chol
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