Liver_disorders_symptoms_causes_ sinusoidspptx

Liver

1. Liver and Gallbladder

2. FUNCTIONAL ANATOMY OF LIVER AND BILIARY SYSTEM Liver is a dual organ exhibiting both secretory and excretory functions. It is the largest gland in the body, weighing about 1.5 kg in man. It is observed in the upper and right side of the abdominal cavity, immediately beneath diaphragm.

3. LIVER Hepatic Lobes Liver consists of many lobes termed as hepatic lobes Each lobe contains many lobules known as hepatic lobules. Hepatic Lobules Hepatic lobule is the structural and functional unit of liver. There are about 50,000 to 100,000 lobules in the liver. The lobule is a honeycomb-like structure and it consists of of liver cells termed as hepatocytes. Hepatocytes and Hepatic Plates Hepatocytes are arranged in columns, which lead to the formation of t he hepatic plates. Each plate contains two columns of cells. In between the two columns of each plate lies a bile canaliculus . In between the neighboring plates, a blood space sinusoid is seen . Sinusoid is lined by the endothelial cells. In between the endothelial cells some special macrophages termed as Kupffer cells are observed.

4. Portal Triads Each lobule is surrounded by many portal triads. Each portal triad con tains three vessels: 1. A branch of hepatic artery 2. A branch of portal vein 3. A tributary of bile duct. Branches of hepatic artery and portal vein open into the sinusoid. Sinusoid opens into the central vein. Central vein empties into hepatic vein. Bile is secreted by hepatic cells and poured into bile canaliculus. From canaliculus, the bile enters the hepatic artery classifies into many branches. Each branch enters a portal triad that is tributary of bile duct. Tributaries of bile duct from canaliculi of neighboring lobules unite to form small bile ducts. These small bile ducts join together and finally form left and right hepatic ducts, which emerge out of liver

5. BILIARY SYSTEM The formation of b iliary system or extrahepatic biliary apparatus occurs by gallbladder and extrahepatic bile ducts (bile ducts outside the liver). Right and left hepatic bile ducts which come out of liver join to form common hepatic duct. It unites with the cystic duct from gallbladder and leads to the formation of bile duct . All these ducts have similar structures. Common bile duct unites with pancreatic duct to form the common hepatopancreatic duct or ampulla of Vater, which gains an entry into into the duodenum. There is a sphincter called sphincter of Oddi at the lower part of common bile duct, before it joins the pancreatic duct. It is formed by smooth muscle fibers of common bile duct. It is normally kept closed; so the bile secreted from liver enters gallbladder where it is stored. Because of an appropriate stimulation, the sphincter opens and Permits flow of bile from gallbladder into the intestine.

6. BLOOD SUPPLY TO LIVER Liver receives maximum blood supply of approximately 1,500 mL/minute. It receives blood from two sources, such as the hepatic artery and portal vein . HEPATIC ARTERY Hepatic artery arises directly from aorta and supplies oxygenated blood to liver. PORTAL VEIN The formation of p ortal vein happens by superior mesenteric vein and splenic vein. It collects deoxygenated blood from stomach, intestine, spleen and pancreas. Portal blood is rich in monosaccharides and amino acids It also con sists of bile salts, bilirubin, urobilinogen and GI hormones. Whatever it may be, , the oxygen content is less in portal blood. Flow of blood from intestine to liver through portal vein is termed as enterohepatic circulation . The blood from hepatic artery unites with blood from portal vein in hepatic sinusoids. Hepatic cells gain oxygen and nutrients from the sinusoid

7. HEPATIC VEIN Substances synthesized by hepatic cells, waste products and carbon dioxide are discharged into sinusoids. Sinusoids drain them particularly into central vein of the lobule. 3) Central veins leads to the formation of many lobules unite to form bigger veins, which ultimately form hepatic veins (right and left) which open into inferior vena cava.

8. PROPERTIES AND COMPOSITION OF BILE PROPERTIES OF BILE Volume : 800 to 1,200 mL/day Reaction : Alkaline pH : 8 to 8.6 Specific gravity : 1.010 to 1.011 Color : Golden yellow or green. COMPOSITION OF BILE Bile co nsists of 97.6% of water and 2.4% of solids. Solids include organic and inorganic substances.

9. SECRETION OF BILE The secretion of b ile occus by hepatocytes. The initial bile secreted by hepatocytes con sists of large quantity of bile acids, bile pigments, cholesterol, lecithin and fatty acids. From hepatocytes, bile is released into canaliculi. From here, it passes through small ducts and hepatic ducts and arrives the common hepatic duct. From common hepatic duct, bile is passed either into the Intestine in a direct manner or into the gallbladder. Sodium, bicarbonate and water are added to bile If it passes through the ducts. These substances are secreted by the epithelial cells of the ducts. Addition of sodium, bicarbonate and water enhances the total quantity of bile.

10. STORAGE OF BILE Most of the bile from liver gains an entry into the gallbladder, where it is stored. It is released from gallbladder into the intestine because of the requirement. When bile is stored in gallbladder, it undergoes many changes both in quality and quantity such as:   1. Volume is reduced due to absorption of a large amount of water and electrolytes (except calcium and potassium) 2. Concentration of bile salts, bile pigments, cholesterol, fatty acids and lecithin is enhanced due to absorption of water and electrolytes 3. The pH is reducedin a slight manner. 4. Specific gravity i s enhanced 5. Mucin is added to bile

11. BILE SALTS Bile salts are the sodium and potassium salts of bile acids, which are conjugated with glycine or taurine. FORMATION OF BILE SALTS The formation of b ile salts takes place from bile acids. There are two primary bile acids in human, such as cholic acid and chenodeoxycholic acid, which are formed in liver and Gain an entry into the intestine through bile. Because of the the bacterial action in the intestine, the primary bile acids are c hanged into

12. secondary bile acids: Cholic acid → deoxycholic acid Chenodeoxycholic acid → lithocholic acid Secondary bile acids from intestine are transported back to liver through enterohepatic circulation. In liver, the secondary bile acids are conjugated particularly with glycine (amino acid) or taurin (derivative of an amino acid) and form conjugated bile acids, such as glycocholic acid and taurocholic acids. These bile acids combine with sodium or potassium ions to form the salts, sodium or potassium glycocholate and sodium or potassium taurocholate .

13. ENTEROHEPATIC CIRCULATION OF BILE SALTS Enterohepatic circulation is the transport of substances from small intestine to liver via portal vein. About 90% to 95% of bile salts from intestine are transported to liver with the help of enterohepatic circulation. Remaining 5% to 10% of the bile salts gain an entry into large intestine. Here, the bile salts are c hanged into deoxycholate and lithocholate, which are excreted in feces.

14. FUNCTIONS OF BILE SALTS Bile salts are needed particuklarly for digestion and absorption of fats in the intestine. The functions of bile salts are: 1. Emulsification of Fats a) Emulsification is the process by which the fat globules are broken down into minute droplets and led to the formation of a milky fluid known as emulsion in small intestine, by the action of bile salts. b) Lipolytic enzymes of GI tract cannot digest the fats in a direct manner because the fats are insoluble in water due to the surface tension. C) Bile salts emulsify the fats by decreasing the surface tension because of their detergent action. Now the fats can be easily digested with the help of lipolytic enzymes. d) Unemulsified fat usually passes through the intestine and then it is excreted in feces. Emulsification of fats by bile salts requires the presence of lecithin from bile.

15. 2. Absorption of Fats a) Bile salts assist regarding the absorption of digested fats from intestine into blood. b) Bile salts combine with fats and result in the formation of complexes of fats known as micelles. The fats in the form of micelles can be absorbed in an easy manner. 3. Choleretic Action Bile salts activate the secretion of bile from liver. This action is termed as choleretic action.

16. 4. Cholagogue Action a) Cholagogue is an agent which leads to contraction of gallbladder and release of bile into the intestine. b) Bile salts behave as cholagogues indirectly in an indirect manner by activating the secretion of hormone cholecystokinin. This hormone leads to the contraction of gallbladder, resulting in release of bile. 5. Laxative Action Laxative is an agent which induces defecation. Bile salts behave as laxatives by enhancing peristaltic movements of the intestine.

17. 6. Prevention of Gallstone Formation a) Bile salts inhibit the formation of gallstone by keeping the cholesterol and lecithin in solution. b) In the absence of bile salts, cholesterol precipitates along with lecithin and leads to the formation of gallstone.

18. BILE PIGMENTS Bile pigments are the excretory products in bile. Bilirubin and biliverdin are the two bile pigments and bilirubin is the major bile pigment in human beings. Bile pigments are formed especially during the breakdown of hemoglobin, which is released from the destroyed RBCs in the reticuloendothelial system

19. FORMATION AND EXCRETION OF BILE PIGMENTS Stages of formation and circulation of bile pigments: 1 The destruction of s enile erythrocytes happens in reticuloendothelial system and hemoglobin is released from them 2. Hemoglobin is broken into globin and heme 3. Heme is broken into iron and the pigment biliverdin 4. Iron goes to iron pool for the sake of reutilization. 5. First formed pigment biliverdin is reduced to bilirubin. 6. Bilirubin is released into blood from the reticuloendothelial cells 7. In blood, the bilirubin is transported with the help of the plasma protein, albumin. Bilirubin circulating in the blood is termed as free bilirubin or unconjugated bilirubin 8. Within few hours after entering the circulation, the free bilirubin is collected by the liver cells 9. In the liver, it is conjugated with glucuronic acid and results in the formation of conjugated bilirubin 10. Conjugated bilirubin is then e liminated into intestine through bile.

20. FATE OF CONJUGATED BILIRUBIN Stages of excretion of conjugated bilirubin:   1. In intestine, 50% of the conjugated bilirubin is changed into urobilinogen with the help of intestinal bacteria. First the conjugated bilirubin is deconjugated into free bilirubin, which is later reduced into urobilinogen. 2. Remaining 50% of conjugated bilirubin from intestine is absorbed into blood and gains an entry into the liver through portal vein (enterohepatic circulation). From liver, it is r reeliminated in bile 3. Most of the urobilinogen from intestine enters liver with the help of enterohepatic circulation. Later, it is reeliminated through bile 4. About 5% of urobilinogen is excreted by kidney through urine. In urine, due to exposure to air, the urobilinogen is c hanged into urobilin with the help of oxidation 5. Some of the urobilinogen is excreted in feces as stercobilinogen. In feces, stercobilinogen is oxidized to stercobilin.

21. NORMAL PLASMA LEVELS OF BILIRUBIN Normal bilirubin (Total bilirubin) content in plasma is 0.5 to 1.5 mg/dL. If it exceeds 1mg/dL, the condition is termed as hyperbilirubinemia. If it exceeds 2 mg/dL, jaundice occurs

22. FUNCTIONS OF BILE Most of the functions of bile are due to the bile salts. . 1. . EXCRETORY FUNCTIONS Bile pigments are the major excretory products of the bile. Other substances e liminated in bile are: i. Heavy metals like copper and iron ii. Some bacteria like typhoid bacteria iii. Some toxins iv. Cholesterol v. Lecithin vi. Alkaline phosphatase. 2. Laxative function Bile salts behave as laxatives . 3 . ANTISEPTIC ACTION Bile stops the growth of certain bacteria in the lumen of intestine due to its natural detergent action.

23. 4. . CHOLERETIC ACTION Bile salts consist of the choleretic action . 5 . MAINTENANCE OF pH IN GASTROINTESTINAL TRACT As bile is highly alkaline, it neutralizes the acid chyme which enters the intestine from stomach. Thus, an optimum pH is regulated for the action of digestive enzymes. . 6. . LUBRICATION FUNCTION The mucin in bile behaves as a lubricant for the chyme in intestine. 7. CHOLAGOGUE ACTION Bile salts behave as cholagogues

24. FUNCTIONS OF LIVER Liver is the largest gland and one of the vital organs of the body. It exhibits many vital metabolic and homeostatic f unctions . . 1. METABOLIC FUNCTION Liver is the organ where maximum metabolic reactions such as metabolism of carbohydrates, proteins, fats, vitamins and many hormones are performed. 2. STORAGE FUNCTION Many substances like glycogen, amino acids, iron, folic acid and vitamins A , B12 and D are stored in liver.

25. 3. SYNTHETIC FUNCTION Liver produces glucose via gluconeogenesis. It synthesizes all the plasma proteins and other proteins (except immunoglobulins) namely clotting factors, complement factors and hormone­binding proteins. It also synthesizes steroids, somatomedin and heparin. 4. SECRETION OF BILE Liver secretes bile which con sists of bile salts, bile pigments, cholesterol, fatty acids and lecithin. The functions of bile are mainly becaiuse of bile salts. Bile salts are needed for digestion and absorption of fats in the intestine. Bile helps to carry away waste products and breakdown fats, which are e liminated through feces or urine.

26. 5. EXCRETORY FUNCTION Liver excretes cholesterol, bile pigments, heavy metals (like lead, arsenic and bismuth), toxins, bacteria and virus (like that of yellow fever) with the help of bile. 6. HEAT PRODUCTION The production of e normous amount of heat takes place particularly in the liver Due to metabolic reactions. Liver is the organ where maximum production of heat occurs .

27. 7. HEMOPOIETIC FUNCTION In fetus (hepatic stage), liver exhibits the capability regarding the production of the blood cells. It stores vitamin B12 essential for erythropoiesis and iron necessary for synthesis of hemoglobin. Liver produces thrombopoietin that enhances production of thrombocytes. 8. HEMOLYTIC FUNCTION The senile RBCs after a lifespan of 120 days are Killed by reticuloendothelial cells (Kupffer cells) of liver.

28. 9. INACTIVATION OF HORMONES AND DRUGS Liver catabolizes the hormones namely growth hormone, parathormone, cortisol, insulin, glucagon and estrogen. It also inactivates the drugs, especially the fat­soluble drugs. The fat­soluble drugs are c hanged into watersoluble substances, which are e liminated through bile or urine

29. 10. DEFENSIVE AND DETOXIFICATION FUNCTIONS Reticuloendothelial cells (Kupffer cells) of the liver play an important role related to the defense mechanism of the body. Liver plays an important role in the detoxification of the foreign bodies. i. Foreign bodies namely bacteria or antigens are swallowed and digested by reticuloendothelial cells of liver with the help of of phagocytosis. ii. Reticuloendothelial cells of liver also produce substances namely interleukins and tumor necrosis factors, which activate the immune system of the body . iii. Liver cells are involved in the removal of toxic property of various harmful substances. Removal of toxic property of the harmful agent is termed as detoxification. Detoxification in liver happens in two ways: a. Total destruction of the substances with the help of metabolic degradation. b. Conversion of toxic substances into non toxic materials with the help of conjugation with glucuronic acid or sulfates

30. References 1. Saxena R, Theise ND, Crawford JM. Microanatomy of the human liver-exploring the hidden interfaces. Hepatology. 1999 Dec;30(6):1339-46. [ PubMed ] 2. Si-Tayeb K, Lemaigre FP, Duncan SA. Organogenesis and development of the liver. Dev Cell. 2010 Feb 16;18(2):175-89. [ PubMed ] 3. Almazroo OA, Miah MK, Venkataramanan R. Drug Metabolism in the Liver. Clin Liver Dis. 2017 Feb;21(1):1-20. [ PubMed ] 4. O'Brien L, Hosick PA, John K, Stec DE, Hinds TD. Biliverdin reductase isozymes in metabolism. Trends Endocrinol Metab. 2015 Apr;26(4):212-20. [ PMC free article ] [ PubMed ] 5. Stec DE, John K, Trabbic CJ, Luniwal A, Hankins MW, Baum J, Hinds TD. Bilirubin Binding to PPAR α Inhibits Lipid Accumulation. PLoS One. 2016;11(4):e0153427. [ PMC free article ] [ PubMed ]

31. 6. Hoekstra LT, de Graaf W, Nibourg GA, Heger M, Bennink RJ, Stieger B, van Gulik TM. Physiological and biochemical basis of clinical liver function tests: a review. Ann Surg. 2013 Jan;257(1):27-36. [ PubMed ] 7. Scheidler J, Fink U, Steiner W, Steitz HO. [3-phase spiral CT--a new noninvasive procedure for the differentiation of multifocal liver lesions]. Aktuelle Radiol. 1995 Jan;5(1):15-8. [ PubMed ] 8. Brehmer K, Brismar TB, Morsbach F, Svensson A, Stål P, Tzortzakakis A, Voulgarakis N, Fischer MA. Triple Arterial Phase CT of the Liver with Radiation Dose Equivalent to That of Single Arterial Phase CT: Initial Experience. Radiology. 2018 Oct;289(1):111-118. [ PubMed ] 9. Nishikawa H, Osaki Y. Liver Cirrhosis: Evaluation, Nutritional Status, and Prognosis. Mediators Inflamm. 2015;2015:872152. [ PMC free article ] [ PubMed ] 10. Peng Y, Qi X, Guo X. Child-Pugh Versus MELD Score for the Assessment of Prognosis in Liver Cirrhosis: A Systematic Review and Meta-Analysis of Observational Studies. Medicine (Baltimore). 2016 Feb;95(8):e2877. [ PMC free article ] [ PubMed ]

32. 11. Kumar A, Hashmi MF, Mehta D. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Feb 19, 2023. Rotor Syndrome. [ PubMed ] 12. Thuener J. Hepatitis A and B Infections. Prim Care. 2017 Dec;44(4):621-629. [ PubMed ] 13. Ramachandran S, Groves JA, Xia GL, Sa á P, Notari EP, Drobeniuc J, Poe A, Khudyakov N, Schillie SF, Murphy TV, Kamili S, Teo CG, Dodd RY, Khudyakov YE, Stramer SL. Recent and occult hepatitis B virus infections among blood donors in the United States. Transfusion. 2019 Feb;59(2):601-611. [ PMC free article ] [ PubMed ] 14. Isakov V, Chulanov V, Abdurakhmanov D, Burnevich E, Nurmukhametova E, Kozhevnikova G, Gankina N, Zhuravel S, Romanova S, Hyland RH, Lu S, Svarovskaia ES, McNally J, Brainard DM, Ivashkin V, Morozov V, Bakulin I, Lagging M, Zhdanov K, Weiland O. Sofosbuvir/velpatasvir for the treatment of HCV: excellent results from a phase-3, open-label study in Russia and Sweden. Infect Dis (Lond). 2019 Feb;51(2):131-139. [ PubMed ] 15. Tsuneyama K, Baba H, Morimoto Y, Tsunematsu T, Ogawa H. Primary Biliary Cholangitis: Its Pathological Characteristics and Immunopathological Mechanisms. J Med Invest.