Pancreas, Bile & Jaundice Lecture Notes PDF

Block 1.2 lectures 2024-2025 lecture Highlighter key Writers Revie...

Block 1.2 lectures 2024-2025 lecture Highlighter key Writers Reviewers >> >> Khawlah AlHassan Zahra’a AlBarraqi Alzahra’a AlShakhs Doctor explanation Abbreviation Key information Book Maryam AlYahya Khawlah AlHassan Student explaintion 221-222-223 notes References Deleted Zahra’a AlBarraqi Alzahra’a AlShakhs Maryam AlYahya  College Of Medicine Academic Year 2022-23 Title: Pancreas, Bile & Jaundice CRN No: Male: 15569, Female: 15581 Block: Block1.2 (Infection and Immunity) Subject/Discipline: Biomedical Sciences (Physiology) Expert: Dr Arif Mohyudin Block Coordinator: Dr.Sayed A.Quadri “ Pancreas, Bile & Jaundice “ Dr. Arif Mohyuddin Associate Professor Department of Biomedical sciences Physiology Section College of Medicine, in Al Hassa King Faisal University, KSA Lecture Objectives Where & how is bile produced? How is it secreted? Describe the enterohepatic cycle.  Jaundice is a yellow discolouration in the skin and whites of the eyes duo to the increase levels of bilirubin in the blood Caused by liver destruction Figure Basic structure of a liver lobule.  Portal Vein DOES NOT go to the inferior vena cava, it goes from the intestines to the liver and starts branching until they open into the sinusoids, then through sinusoid they pour blood into the central vein Hepatic vein is the one that carries the processed blood to the inferior vena cava Between the two sinusoids there is Liver cell plate ( Hepatocytes ) In liver cirrhosis these cells will be damaged Between the two Liver cell plate ( in the middle ) there is a green This PIC bile structure known as Bile canaliculi which takes the bile that explains the bile cycle and has been made in the hepatocytes ( in the Liver cell plate ) to the liver function, where blood Bile duct which is connected to the gallbladder. from the intestines is processed via the portal *Don’t forget that the Bile is stored in the Gallbladder where it vein. Bile is produced in hepatocytes, transported gets concentrated as well by removing the water & salts from the through bile canaliculi, and bile stored in the gallbladder for concentration.  The blood passes from the sinusoids into a space known as The Space of Disse Plasma region absorbs the nutrients In the lining of the sinusoids we have the kupffer cells ( you already got the ‫ كفار‬cells joke, didn’t you ? ) They are originally Monocytes, they remove the bacteria that was absorbed with the blood. Thant’s why the portal vein Doesn’t go directly to the inferior vena cava; the blood needs to pass through the kupffer cells first to get purified There is a lot of lymphatic drainage in the liver, so we have the Lymphatic duct The hepatic artery brings oxygenated blood to the hepatocytes because the liver cells need oxygen  Bilirubin comes from the RBCs that have been destroyed Functions of bile after 120 days The main function of liver is to secrete bile, around 1 liter/day. In the next slides we are going to cover the functions of salts & bilirubin It mainly contains bile salts & bilirubin. The bile salts work like the soap in the kitchen, it helps in breaking fats into smaller molecules It does not contain any digestive & enzymes.Still it is important for digestion absorption of fats, primarily through the activity of bile salts. It alsonum< helps in excretion of bilirubin. >ber  Negativity charged H₂O-soluble portion Small lipid (fat) Droplet Lipid-soluble portion The bile salt has a lipid soluble portion and water soluble portion If you mix water and lipid together and ( negatively charged ) to help it entertain the fat droplet shake them, they will get separated The lipid soluble portion enters the fat droplet while the water soluble after a while, but if you added soap to portion stays out and get suspended ( the process is called suspension );that’s them, there will be a suspension just how the bile salt make the fat ( lipid ) droplet water soluble like what happened to the fat in our body after adding bile salts to it  The fat enter the intestine and the bile also then there Pancreatic lipase will be mixing of these two substances by the >> intestinal movements ( Lipid emulsion ) Is secreted by Lipid emulsion has suspended fat molecules in water the pancreas. It breaks the fat Lipid emulsion The fat droplets after that will never mix together into again because of their negative charge surfaces and monoglycerides & each droplet will remain as small particle. fatty acid Lumen Micelles Micelles diffusion Lumen Micelle Microvillus ,Fatty acids monoglycerides Aggregate and Short or coated with medium lipoprotien chain Basement membrane Epithelial cell of villus )Exocytosis( Passive absorption Capillary Central lacteal  The bile salts that enter the fat droplets earlier will help the monoglycerides and fatty acids to get close to the intestinal villi. ( finger-like projections in small intestine) and get absorbed, After the absorption process both of them will turn into triglycerides. Lipid emulsion Then it will be covered by some proteins to turn into Chylomicrones Central lacteal is a lymphatic vessel in the Lumen Micelles Micelles diffusion Lumen small intestine in the core of intestinal villi, It plays a critical role in fat absorption from the digested food Micelle Microvillus ,Fatty acids monoglycerides Aggregate and Short or coated with medium lipoprotien chain Basement membrane Epithelial cell of villus )Exocytosis( Passive absorption Capillary Central lacteal What is the main function of bile salts? Bile salts Total amount in body is 3 to 4 gms But after single meal Secretion is from 3 – 15 gms. It is only possible by enterohepatic circulation Enterohepatic circulation is the recycling of certain Daily excretion =5% substances like bile salts between the liver, gallbladder, intestine, and back to the liver again. ( will be explained in the next slide ) Figure Enterohepatic circulation of bile salts.  Bile salts Cholesterol Common bile duct Liver Cholesterol converts into bile salts in the liver, then bile salts goes all the way to the small intestine through the sphincter of oddi into the Portal Gallbladder second part of the duodenum. circulation Sphincter of Oddi Colon Duodenum Terminal ileum Lecture Objectives What is icterus (jaundice)? How does it occur? Figure what is billirubin? From where it comes? Where it goes? What is jaundice? What is obstructive Bilirubin formation and excretion. jaundice? What is hemolytic jaundice? The story begins with fragile red blood cells (RBCs). After 120 days (approximately 4 months), RBCs lose their functionality because they lack a nucleus. The enzymes produced at their formation sustain them for their lifespan, but after this period, these enzymes stop working. As a result, the RBC membrane becomes fragile, especially when passing through the narrow trabeculae of the spleen. This fragility causes RBCs to break down, releasing heme, which is then converted into biliverdin and subsequently into unconjugated bilirubin. Unconjugated bilirubin enters the liver, where it is converted into conjugated bilirubin by adding glucuronic acid. This process makes the bilirubin water-soluble. Once conjugated, bilirubin is transported to the intestines via bile. In the intestines, conjugated bilirubin undergoes bacterial action, transforming it into urobilinogen. Some urobilinogen is reabsorbed into the bloodstream and transported to the kidneys, where it is excreted as urobilin, which gives urine its yellow color. The remaining urobilinogen in the intestines is converted into stercobilinogen. This is further oxidized into stercobilin, which gives feces its characteristic brown color. Thus, the liver, spleen, and intestines work together to efficiently break down and process old RBCs while maintaining waste elimination. The reticuloendothelial system >> *A part of the immune system that removes damaged or old cells, such as: fragile RBC, and helps defend the body against infections. *It contains essential enzymes  many substances are excreted in the bile and then eliminated in the feces. One of these Once in the intestine, about half of the “conjugated” bilirubin is converted by substances is the greenish- yellow pigment bilirubin, which is a major end product of bacterial action into urobilinogen, which is highly soluble. Some of the hemo- globin degradation. However, bilirubin also provides an exceedingly valuable tool urobilinogen is reabsorbed through the intestinal mucosa back into the blood, for diagnosing both hemolytic blood diseases and various types of liver diseases and most is re-excreted by the liver back into the gut, but about 5% is excreted by the kidneys into the urine. After exposure to air in the urine, urobilinogen becomes oxidized to urobilin; alternatively, in the feces, it becomes altered and oxidized to form stercobilin. Briefly, when the red blood cells have lived out their life span (on average, 120 days) and have become too fragile to exist in the circulatory system, their cell membranes rupture, and the released hemoglobin is phagocytized by tissue macrophages (also called the reticuloendothelial system) throughout the body. The hemoglobin is first split into globin and heme, and the heme ring is opened to give (1) free iron, which is transported in the blood by transferrin, and (2) a straight chain of four pyrrole nuclei, which is the substrate from which bilirubin will eventually be formed. The first substance formed is biliverdin, but this substance is rapidly reduced to free bilirubin, also called unconjugated bilirubin, which is gradually released from the macrophages into the plasma. This form of bilirubin immediately combines strongly with plasma albumin and is transported in this combination throughout the blood and interstitial fluids. Within hours, the unconjugated bilirubin is absorbed through the hepatic cell membrane. In passing to the in- side of the liver cells, it is released from the plasma albumin and soon thereafter conjugated about 80% with glucuronic acid to form bilirubin glucuronide, about 10% with sulfate to form bilirubin sulfate, and about 10% with a multitude of other substances. In these forms, the bilirubin is excreted from the hepatocytes by an active transport process into the bile canaliculi and then into the intestines. Bilirubin and jaundice Jaundice is yellowness of the skin & deep tissues. Cause is increased bilirubin in the ECF. Normal bilirubin level is around 0.5 mg/dl. It is almost entirely unconjugated bilirubin. Skin is jaundiced when the level rises to 3 times normal. Levels can increase up to 40 mg/dl & much of it can become conjugated bilirubin.  Hemolytic Jaundice: This results from excessive breakdown of red blood cells (as in sickle cell anemia). The increased breakdown leads to an oversupply of unconjugated bilirubin. The doctor mentioned that The normal unconjugated bilirubin level is 0.5 mg/dL, but it can rise to higher levels such as 5 mg/dL Bilirubin & jaundice Obstructive Jaundice: This occurs due to a blockage in the common bile duct, preventing bile from reaching the intestines. Bile is still being produced in the liver, but the obstruction causes a buildup of conjugated bilirubin, which leaks into the bloodstream, The types of jaundice are: leading to jaundice. 1) Hemolytic jaundice It is due to excessive breakdown of RBCs. Plasma concentration of unconjugated bilirubin rises. In hemolytic jaundice, urine color would be much more of darker yellow as well as the feces would be more brownish Rate of formation of urobilinogen is greatly increased in the intestines. Much of it is absorbed into the blood & later excreted in urine.  Liver canaliculi going to dilate due to this obstruction, it will lead to Bilirubin & jaundice increased permeability which will allow the conjugation to enter the blood 2)Obstructive jaundice: Carcinoma in the head of the pancreas Caused by obstruction(by gall stones or leads to pressing and blockage cancer) of bile ducts or by liver disease. Bilirubin conjugation is normal, but it cannot pass into the intestines. It returns to the blood due to the Yellowing is associated ruptured bile canaliculi. with the accumulation of bilirubin in the skin Lecture Objectives What is the relationship between hemoglobin, indirect (unconjugated) & direct (conjugated) bilirubin? How does bilirubin metabolism proceed (urobilinogen, urobilin, stercobilin)? What is the relationship between elevated hemolysis & obstructive cholestasis on the one hand & urine color on the other? Lecture Objectives What are the main components of pancreatic juice & what are their functions?  EXOCRINE PANCREAS The pancreas can act as TWO types of glands: Duodenum Bile duct Endocrine gland Exocrine gland from liver Stomach The pancreas consists of TWO types of cells: Blood Acinar cells: Duct cells: The acinar cells of the pancreas are The duct cells of the pancreas are responsible for enzyme secretion responsible for Aqueous NaHCO3 secretion when partially digested food ( Chyme ) moves from the Stomach to the Small- intestine, it is highly acidic ( with a pH ranging from 2-4 ) With the high acidity of food, the intestines would burn, so the first requirement is to neutralize the acidity. That is why the pancreas has cells called Duct cells that secrete bicarbonate, and Acinar cells N O T E Acinar cells that are responsible for secreting enzymes, but in their Inactive form Duct cells secrete aqueous secrete digestive Bicarbonate “NaHCO” enzymes 3 Why are they in their inactive form? >> NaHCO₃ solution Is an alkaline substance that helps neutralize the high acidity of the food. If they were secreted in an active form in your body, they would Acini & Acinar cells both are the same; damage the pancreas, and you would die within hours. Exocrine portion of panaceas Don’t be confused! )Acinar and duct cells(  A protein may have 10,000 dimmers that attach each other , which are divided into small chains resembling wires connected to each other: The main components of pancreatic juice A chain containing 500 bonds A chain containing 300 bonds A chain containing 50 bonds 1. Proteolytic Enzymes: And so on… All these will be called the peptides A peptide has TWO ends: Enzyme Functions Trypsin Split partially digested An amino end ( contains NH₂ ) A carboxyl end ( contains COOH ) proteins into peptides of A doctor mentioned an example that also has TWO ends: Chymotrypsin various sizes but not into A Polyglucide also has TWO ends: (Activated by trypsin) amino acids An amino end A carboxyl end Carboxypeptidase ( contains NH₂ ) ( contains COOH ) A Polyglucide is a type of polysaccharide Splits some peptides into Trypsin & Chmotropsin (Activated by >> amino acids They split the partially digested protein into Peptides Carboxypeptidase trypsin) >> It breaks the carboxyl end (CHO) in the protein and converts it into amino acids.  What happens in the first step of digestion in the stomach? 1-After the proteins reach the stomach Protein is partially digested in the stomach Carbohydrate is partially digested in the oral cavity These steps occur FIRST in the stomach Pepsin ces Jui stric Ga HCl, Pepsin & Gastric juices are found in the stomach 2- Pepsin forms in the stomach when pepsinogen( zymogen) reacts with HCl To clarify the unclear words: Pepsinogen ( zymogen ) 3- Pepsin breaks the peptide bonds in proteins to break them down into >> Inactive form of pepsin Prptide bond smaller molecules such as proteoses, peptones, and polypeptides >> A bound connects amino acid to each other  What happens in the second step of digestion in the duodenum ? The partially digested food will move to the small intestine” Duodenum “,to continue the digestion process that started in the stomach 1- pancreatic juices containing digestive enzymes are secreted into the small intestine to continue the digestion process These steps occur in the small-intestine “ Duodenum “ 2- Pancreatic enzymes such as: To clarify the TWO steps Trypsin Chymotrypsin N O T E Carboxypeptidase Proelastase proelastase >> It converts into Elastase Enzyme These enzymes break the proteins into Polypeptide + Amino acids Peptidases found on the surface of Small- intestine,break down the polypeptide into >> Di & Tri peptides and Amino Acids 3-At the brush border ( found in intestinal border ) , peptidases break Partially digested food down polypeptides into peptides and amino acids, then release them into >> Chyme - Food has not been fully digested yet the blood.  The main components of pancreatic juice 2. Enzymes for Carbohydrates: Enzyme Functions Between the brush borders there are enzymes Pancreatic Digest the starches and glycogen called: disaccharidases ,which break disaccharide into monosaccharides, amylase to mainly disaccharides. such as: Sucrase ,Lactase ,Maltase and peptidases 3. Enzymes for Fats: Pancreatic Neutral fat into fatty acids and Microvill Microvilli i on Lipase monoglycerides small on intestine ’s small surfase intestine’s surfase Lecture Objectives How does exocrine pancreatic secretion occur?  Acid in Fat and protein duodenal products in lumen duodenal lumen How does the pancreas respond based on what enters the duodenum? Secretin release CCK release 1-whenever the contents of the duodenum are Acidic , the cells from duodenal from duodenalin the duodenal mucosa secrete the hormone Secretin mucosa mucosa Secretin carried( Neutralizes CCK carried( Digests )by blood 2-The blood )by blood will carry the hormone Secretin and deliver it to the pancreatic duct cells. Pancreatic duct Pancreatic acinar cells cells 3-The pancreatic duct cells secrete a solution containing NaHCO3 (sodium bicarbonate-‫)بيكربونات الصوديوم‬, and this solution moves to the duodenum to reduce the acidity of the solution (neutralizing the acid). Secretion of aqueous Secretion of NaHCO₃ solution into pancreatic digestive NaHCO3 + HCl = NaCl + CO2 + H2O duodenal lumen enzymes into duodenal lumen  How are fats and proteins digested in the duodenum ? 1-When proteins and fats come into the duodenum, they stimulate the duodenal mucosa to secrete the hormone CCK (cholecystokinin) 2-The blood carries the hormone CCK and moves it to the enzyme-secreting cells in the pancreas, known as Acinar cells 3-The acinar cells secrete digestive enzymes that move to the duodenum and initiate the digestion of fats and proteins Lecture Objectives What is the difference between exocrine and endocrine pancreas? What hormones are secreted by pancreas? What stimulates their production & what are their effects?  ENDOCRINE PANCREAS We have to know : Hormones Endocrine glands are ductless ( no duct ) Insulin )1 Exocrine glands have ducts Glucagon )2 Stomach Blood The Islets have got Alpha and Beta cells , so Insulin and Glucagon will be their Endocrine portion 3-The blood carries the hormone CCK and moves of pancreas it to the enzyme-secreting cells in the pancreas, known as Acinar cells )Islets of Langerhans(  Endocrine Pancreas After eating , Once glucose enters the blood , It stimulate Beta cells of (Islets of Langerhans). Stimuli for Beta cells will start producing Insulin. Hormones Effects production Without Insulin the glucose can’t enter the cell, it will remain in the blood. Decreases the blood As a result >> Hyperglycemia Increased blood glucose glucose, free fatty Insulin concentration by acids, amino acids storing the excess (energy abundance) energy. stored in muscles , and the liver as (glycogen) When you are fasting ,Glucose in the blood will Increases the blood decrease, Glycogen will be broken down into Glucagon Hypoglycemia glucose Glucose(To be utilized for vital organs ,ex: the brain) ,then The concentration of glucose will be concentration increased How the glucose concentration will increase in the blood? By Gluconeogenesis Conversion of amino acid into glucose. Lecture Objectives Discuss the intake, digestion, absorption and secretion of carbohydrates, proteins and fats.  1-Saliva will carry 20-40% Of digesting starch (in the mouth ), and the rest of it by pancreatic amylase. This converts it into Disaccharide maltose and (3-9 Glucose polymers). 2- By the help of the enzymes (Maltase ,Lactase, Sucrase), Disaccharides will be broken into Monosaccharides. 3-Now monosaccharides are absorbed immediately into the Extra information to illustrate the graph: blood , because it’s water soluble. Lactose splits into a molecule of galactose and a molecule of glucose. Sucrose splits into a molecule of fructose and a molecule of glucose. Maltose and other small glucose polymers all split into multiple molecules of glucose. Thus,the final products of carbohydrate digestion are all monosaccharides. They are all water soluble and are absorbed immediately into the portal blood. Explained in the previous slides 1-Fat should be Emulsified (broken into parts)by Bile and agitation. Agitation by Peristaltic movement ‫الحركة الدودية للأمعاء‬ Bile: digestive fluid produced by the liver and stored in the gallbladder Agitation: a process of physical mixing , ex: shaking and stirring. 2-The emulsified fats will be digested by the pancreatic lipase Pancreatic lipase will break them down into their basic building blocks: fatty acids and glycerol Further Reading References. Guyton & Hall, Textbook of Medical Physiology, 14th Edition, Elsevier, Philadelphia PA, 2021 Chapter 66. Page: 823-832 Chapter 67. Page: 833-839 Chapter 71. Page: 871-876  team Wishes you the best