Liver gallbladder and pancreas Notes


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Bile secretion and enterohepatic circulation

Liver anatomy and physiology

Pancreatic secretion

NOTES NOTES LIVER, GALL BLADDER, & PANCREAS BILE SECRETION & ENTEROHEPATIC CIRCULATION SYNTHESIS OF BILE, BILIRUBIN ▪ Hemoglobin from old red blood cells taken up by macrophages → biliverdin → unconjugated bilirubin → released into plasma, combines with albumin → unconjugated bilirubin absorbed into hepatic cells, released from albumin → liver conjugates unconjugated bilirubin → conjugated bilirubin excreted from hepatocytes into intestines → some conjugated bilirubin converted by bacteria into urobilinogen (soluble) → some urobilinogen reabsorbed through intestinal mucosa back into blood → re-excreted by liver back into gut/excreted by kidneys into urine → urobilinogen becomes urobilin → stercobilin in feces RECYCLING OF BILE ▪ Bile transported from ileum into portal blood after digestion → portal blood delivers bile salts to liver → liver extracts bile salts from portal blood, adds to hepatic bile salt/acid pool → bile returned to gallbladder ▪ Some bile excreted into feces as stercobilin ▪ Only excreted bile needs to be replaced Figure 40.1 Bile synthesis to excretion/ recycling pathway. 332 OSMOSIS.ORG
Chapter 40 Gastrointestinal Physiology: Liver, Gall Bladder, & Pancreas LIVER ANATOMY & PHYSIOLOGY LIVER ANATOMY Functions ▪ Bile production, storage (e.g. glycogen), detoxification, nutrient interconversion, synthesis (e.g. albumin, clotting factors), phagocytosis (Kupffer cells) Location ▪ Located in right upper quadrant (RUQ) under diaphragm, almost entirely within rib cage ▫ Largest internal organ ▪ Covered by visceral peritoneum ▫ Except superior-most region (bare area), contacts inferior surface of diaphragm ▪ Falciform ligament: mesentery separates right, left lobes; suspends liver from diaphragm, anterior abdominal wall ▪ Round ligament/ligamentum teres: inferior to falciform ligament, remnant of fetal umbilical vein Four lobes ▪ Right lobe (largest) ▪ Left lobe ▪ Caudate lobe ▪ Quadrate lobe Blood supply ▪ 75% from nutrient rich, oxygen poor portal vein ▪ 25% from nutrient poor, oxygen rich hepatic artery ▪ Enterohepatic circulation gives liver first access to nutrients, toxins, medications from gut Liver lobule ▪ Functional unit of liver ▫ Hexagonal liver lobule made of hepatocytes ▪ Each liver lobule surrounded by six portal triads on each point withlobes central vein in center Figure 40.2 Superior and inferior view of liver. OSMOSIS.ORG 333
Major fuels ▪ Glucose, fructose, galactose (after meal); fatty acids (after fasting) ▫ Amino acids can also be used ▫ Long-chain fatty acids: major source of fuel during prolonged fasting Figure 40.3 Liver lobule. ▪ Portal triad ▫ Portal venule + portal arteriole + bile duct Sinusoids ▪ Mixing of portal vein, hepatic arterial blood ▪ Lined with leaky endothelial cells ▪ Pathway of blood flow ▫ Blood from hepatic portal vein, artery → sinusoids → central vein → hepatic vein → inferior vena cava Bile ▪ Produced by hepatocytes, excreted into bile ducts ▪ Composed of bile salts, bile pigments, cholesterol, triglycerides, phospholipids ▫ Primary bile salts: cholic, chenodeoxycholic acids (cholesterol derivatives) ▫ Function: emulsify fat (break into smaller pieces to maximize surface area for digestion); facilitate fat, cholesterol absorption ▫ Bile salts conserved via enterohepatic circulation ▫ Main bile pigment is bilirubin (waste product of hemoglobin from broken down erythrocytes), stercobilin gives feces dark color ▪ Bile flow ▫ Parallel, opposite direction flow of blood ▫ Canaliculi → bile ducts → fusion of multiple bile ducts to form common hepatic duct → fusion with cystic duct draining gallbladder → bile duct → ampulla of vater 334 OSMOSIS.ORG Cell types ▪ Hepatocytes ▫ Function: carry out most metabolic pathways ▫ Majority cell type in liver ▫ Contain large amounts of rough, smooth endoplasmic reticulum (ER), Golgi bodies, peroxisomes, mitochondria ▪ Endothelial cells ▫ Location: sinusoidal lining ▫ Function: release growth factors; secrete cytokines, endocytose ligands ▫ Contain fenestrations → free diffusion of blood, nutrients between sinusoids, hepatocytes ▪ Kupffer cells ▫ Location: sinusoidal lining ▫ Function: macrophages specific to liver protect against gut-derived pathogens, release cytokines, secrete mediators of inflammatory response, remove damaged erythrocytes from circulation ▪ Stellate (Ito) cells ▫ Location: scattered amongst hepatocytes ▫ Function: primary vitamin A storage site; regulate contractility of sinusoids; control turnover of extracellular matrix, hepatic connective tissue ▫ Responsible for tissue cirrhosis ▪ Pit cells (liver-associated lymphocytes) ▫ Function: natural killer cells specific to liver GALLBLADDER ANATOMY ▪ Muscular sac ▫ Stores, concentrates bile produced by liver ▪ Located under inferior surface of right liver lobe ▪ Inner mucosa (with rugae) → allows expansion ▪ Smooth muscle layer → allows contraction
Chapter 40 Gastrointestinal Physiology: Liver, Gall Bladder, & Pancreas to occur in response to cholecystokinin (produced by duodenum) → bile released into small intestine ▫ Also contracts in response to vagal stimulation ▪ Flow of bile ▫ Cystic duct → common bile duct → ampulla of vater → duodenum Acinar gland ▪ Exocrine gland ▪ Acinar cells ▫ Contain zymogen granules full of proenzymes for digestion ▪ Stimulated by secretin, cholecystokinin (from duodenum), vagus nerve ▪ Secretes digestive enzymes into duodenum ▫ Amylase, lipase, nuclease secreted as active enzymes ▫ Proteases (trypsinogen, chymotrypsinogen, procarboxypeptidase) secreted in zymogen form, must be cleaved to be activated Figure 40.4 Gallbladder. PANCREAS ANATOMY Figure 40.6 Acinar gland. Four regions ▫ Head: right side nestled into curve of duodenum ▫ Neck: thin portion between head, body ▫ Body: tapered left side ▫ Tail: ends near spleen Islets of Langerhans ▪ Endocrine gland ▪ Responsible for glucose homeostasis ▫ Beta cells → insulin ▫ Alpha cells → glucagon ▫ Delta cells → somatostatin → inhibits insulin, glucagon secretion ▪ Located retroperitoneal posterior to stomach, duodenum Ducts ▪ Main pancreatic duct: located centrally, fuses with bile duct to drain into duodenum ▪ Accessory pancreatic duct: smaller duct; empties directly into duodenum ▪ Ductal cells: responsible for aqueous secretions (water, HCO3-, sodium) ▫ Secretion of bicarbonate ions neutralizes acidic chyme entering duodenum, provides optimal pH for activation of digestive enzymes Figure 40.5 Pancreatic location relative to stomach and duodenum. OSMOSIS.ORG 335
LIVER PHYSIOLOGY Efficient exchange of compounds between sinusoidal blood, hepatocytes ▪ Fenestrated endothelial cells ▪ Lack of basement membrane between endothelial cells, hepatocytes ▪ Slow blood flow Biotransformation of xenobiotics ▪ Principal site for processing xenobiotics, toxins ▪ Phase I reactions: oxidation, reduction, hydroxylation, hydrolysis ▫ Introduces reactive functional groups to increase compound polarity ▪ Phase II reactions: conjugation, sulfation, glucuronidation, methylation ▪ Detoxification: xenobiotic → phase I reaction → primary metabolite → phase II reaction → secondary metabolite → excretion ▪ Cytochrome P450 system: major xenobiotic metabolizer in body; oxidizes substrates, adds oxygen to structures ▫ First pass effect for pharmaceuticals Regulation and maintenance of blood glucose levels ▪ ↑ blood glucose: → secretion of insulin by pancreas → ↑ uptake of glucose, amino acids by cells; inhibition of glycolysis, activation of glycogen synthesis, inhibition of gluconeogenesis, inhibition of glycogenolysis, inhibition of fatty acid oxidation → ↓ blood glucose ▪ ↓ blood glucose: ↑ breakdown of glycogen → secretion of glucagon, activation of glycolysis, inhibition of glycogen synthesis, activation of gluconeogenesis, activation of glycogenolysis, activation of fatty acid oxidation → ↑ blood glucose Elimination of ammonia via urea cycle ▪ Liver ▫ Main organ responsible for eliminating ammonia via urea cycle ▪ Ammonia transported to liver on glutamine, alanine → converted by liver into urea for excretion in urine 336 OSMOSIS.ORG Amino acid metabolism/protein synthesis and regulation ▪ Liver produces plasma proteins (mainly albumin), coagulation factors, metal-binding proteins (transferrin, ceruloplasmin), lipid transporters (apoproteins), protease inhibitors (antitrypsin), glycoproteins, proteoglycans ▪ Can convert amino acids into glucose, fatty acids, ketone bodies ▪ Sugars produced by liver O-linked Formation of ketone bodies ▪ Liver ▫ Only organ that can produce ketone bodies ▪ Cannot use ketone bodies for energy ▪ Ketone bodies formed when glucose levels low, high rates of fatty acid oxidation ▪ Ketone bodies major fuel source for central nervous system (CNS) under starvation Cholesterol and triacylglycerol synthesis ▪ Liver synthesizes very low-density lipoprotein (VLDL) to be secreted into blood ▪ Food plentiful → liver activates synthesis of fatty acid, triacylglycerol, cholesterol → reduces hepatic cholesterol synthesis ▪ Also sends excess dietary cholesterol to peripheral tissue Nucleotide biosynthesis ▪ Liver can synthesize, salvage nucleotides for use by other cells ▪ Salvage pathway ▫ Liver converts free bases to nucleotides for secretion into circulation as needed by peripheral tissues Lipid metabolism ▪ Long-chain fatty acids ▫ Liver’s major fuel source during fasting ▫ Triacylglycerols from adipose tissue → fatty acids bound to albumin → liver → activated via fatty Acyl-coenzyme A (acyl-CoA) synthetases → fatty-acylCoA → fatty-acyl-carnitine → carnitine crosses inner mitochondrial membrane → fatty-acyl-carnitine → carnitine, fattyacyl-CoA → beta oxidation ▫ Enzymes in beta oxidation, fatty-acid activation specific for length of fatty acid carbon chains
Chapter 40 Gastrointestinal Physiology: Liver, Gall Bladder, & Pancreas ▪ Medium-chain-length fatty-acid oxidation ▫ 4–12 carbons ▫ Liver, kidney is site of oxidation ▫ Activating enzyme is medium-chainlength fatty acid-activating enzyme (MMFAE) ▫ Oxidation begins with medium-chainlength acyl-CoA dehydrogenase ▪ Very-long-chain fatty-acid oxidation ▫ > 20 carbons ▫ Oxidized by peroxisomes to octanoylCoa ▫ Generates hydrogen peroxide instead of flavin adenine dinucleotide (FADH2), in contrast to mitochondrial beta-oxidation ▪ Long-chain fatty acids ▫ 12–20 carbons ▫ Most common type of lipid used for oxidation by liver PANCREATIC SECRETION FLOW RATE, COMPOSITION OF PANCREATIC JUICE High flow rate ▪ High HCO3- concentration, low Clconcentration Low flow rate ▪ High Cl- concentration, low HCO3concentration REGULATION OF BILE, PANCREATIC SECRETION ▪ Hormones, neural stimuli regulate secretion of bile, pancreatic juice into duodenum Neural stimuli ▪ Parasympathetic stimulation by vagus nerve stimulates secretion ▫ Bile from gallbladder, pancreatic juice Bile salt ▪ Major stimulus for more bile secretion via stimulation of secretin release ACTIVATION OF PANCREATIC PROTEASES ▪ Enteropeptidase cleaves, activates trypsinogen to trypsin → trypsin activates chymotrypsinogen into chymotrypsin, procarboxypeptidase into carboxypeptidase Hormones ▪ Secretin ▫ Released by intestinal cells in response to acidic chyme; stimulates secretion of bile, pancreatic juice ▪ Cholecystokinin (CCK) ▫ Major stimulus for gallbladder to release bile into duodenum; stimulates secretion of enzyme-rich pancreatic juice OSMOSIS.ORG 337

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This Osmosis High-Yield Note provides an overview of Liver gallbladder and pancreas essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Liver gallbladder and pancreas by visiting the associated Learn Page.