Diseases of the Liver, Gallbladder, and Pancreas, 2024, IMU University PDF

NDT2359 Pathophysiology for Dietetics 2 Diseases of the liver, gallbladder and exocrine pancreas Dr Wong Ting Xuan...

NDT2359 Pathophysiology for Dietetics 2 Diseases of the liver, gallbladder and exocrine pancreas Dr Wong Ting Xuan [email protected] 2024 Inspire Empower Elevate Lesson a) Describe the normal anatomy and physiology of the hepatobiliary system: liver, gallbladder and Outcomes pancreas b) Explain the pathophysiology of the hepatobiliary system Jaundice, portal hypertension/ ascites and encephalopathy Hepatitis, alcoholic liver disease and non- alcoholic fatty liver disease, cirrhosis and liver transplant Cholelithiasis Pancreatitis 2 Lesson a) Describe the normal anatomy and physiology of the hepatobiliary system: liver, gallbladder and Outcomes pancreas b) Explain the pathophysiology of the hepatobiliary system Jaundice, portal hypertension/ ascites and encephalopathy Hepatitis, alcoholic liver disease and non- alcoholic fatty liver disease, cirrhosis and liver transplant Cholelithiasis Pancreatitis 3 Recap: Human Biology Hepatobiliary system: Liver, gallbladder & exocrine pancreas Link: https://elearn.imu.edu.my/course/view.php?id= 4671&section=29 Gross Anatomy of the Hepatobiliary System Functions of the Liver Carbohydrate Glycogenesis, gluconeogenesis Oxidation through TCA cycle, glycolysis metabolism Lipogenesis, ketogenesis, fatty acid oxidation Lipid Synthesis/excretion of cholesterol metabolism Formation of lipoprotein Synthesis of serum proteins, prothrombin, and globin of hemoglobin Protein Degradation of some proteins metabolism Synthesis of urea Bile acid Transformation of cholesterol metabolism Heme Heme oxidised to biliverdin → reduced to bilirubin → transported to liver to be converted to bilirubin diglucuronide → excreted with bile metabolism pigments 6 Other Functions of the Liver Enzyme Synthesis of alkaline phosphatase, monoamine oxidases (MAOs), aspartate transaminase (AST), and alanine transaminase (ALT) metabolism Vitamin Hydroxylation of vitamin D to 25-OH D3 Formation of coenzyme B12 metabolism Storage Glycogen, fats, fatty acids and fat-soluble vitamins Conjugation, detoxifications and degradataion, water movement Others regulation, excretion 7 Enterohepatic Circulation Removal of water and some inorganic Storage of bile electrolytes from the bile Control of the delivery of bile salts to the duodenum Functions of the gallbladder Bile: emulsification of fat prior to digestion and absorption Anatomy of the Pancreas Pancreatic Exocrine Secretions  Think Time How are diseases of liver, gallbladder and pancreas detected? Lesson a) Describe the normal anatomy and physiology of the hepatobiliary system: liver, gallbladder and Outcomes pancreas b) Explain the pathophysiology of the hepatobiliary system Hepatobiliary tract = Jaundice, portal hypertension/ascites and “channels” encephalopathy Hepatitis, alcoholic liver disease and non- alcoholic fatty liver disease, cirrhosis and liver transplant Cholelithiasis Pancreatitis 12  Jaundice (a.k.a icterus) Types Pathophysiology Hemolytic Increased or excessive destruction of red jaundice blood cells, which leads to excessive production and rapid release of bilirubin into the blood. Urine colour: dark; stool colour: normal Hepatocellular Damaged hepatocytes leading to jaundice insufficiency in uptake, conjugation, or excretion of bilirubin Yellowish discolouration to the body Obstructive Block in the flow of bile (e.g., common bile jaundice duct, pancreatic duct) tissues that is resulted from elevated extracellular fluid concentrations of Urine colour: dark; stool colour: pale bilirubin, including both unconjugated Newborn / Immature liver is unable to metabolise and conjugated form physiologic bilirubin quickly enough (e.g., prematurity) jaundice Bilirubin Metabolism & Excretion  Class of Jaundice Aetiology Types of Associated causes Bilirubin raised Pre-hepatic/ Increased rate of RBC destruction Unconjugated Haemolysis/Abnorm Haemolytic ↓ al RBCs Increased Hb breakdown to bilirubin in Thalassaemia, reticuloendothelial system megaloblastic ↓ anaemia Exceeds the capacity of conjugation in liver Hepatic/ Inability of hepatocytes to conjugate Unconjugated & Viral/Toxic hepatitis Hepatocellular and/or excrete bilirubin conjugated Intrahepatic cholestasis Post-hepatic/ Conjugated bilirubin failed to excrete into Conjugated Extrahepatic Obstructive intestine cholestasis ↓ Gallstones Conjugated bilirubin regurgitate in Bile duct tumours circulation Carcinoma: ↓ Pancreas Urinary & Faecal urobilinogen decreased Ampulla of vater  Portal hypertension / Ascites Elevated blood pressure in the hepatic portal vein where cirrhosis is usually the primary cause Pathophysiology: Normal blood flow is disrupted if the scarred liver tissue is present Blood pressure in portal vein increases and causes the development of collateral circulation → Veins are enlarged → Varices are developed (e.g., esophagus, stomach) Varices (varicose veins): potential for ruptures → acute bleeding Spleen become enlarged  Portal hypertension / Ascites Accumulation of fluid within the peritoneal cavity Primary symptoms and complications of portal hypertension Pathophysiology: Portal hypertension causing hemodynamic shift Inadequate synthesis of serum proteins (e.g., albumin) and increased retention of sodium in blood vessels Lower oncotic pressure causing fluid Can contain as much as 15.5 L of fluid to shift from blood into peritoneal If 4L of ascitic fluid are removed, it can lose 40- cavity → edema 80g of protein via this route  Hepatic Encephalopathy Syndrome of impaired mental state and abnormal neuromuscular function that results from the consequences of liver failure Pathophysiology: Increased serum ammonia Reduced capacity to detoxify with liver failure Symptoms: 1) Changes in mental status and Accumulation in blood personality (e.g., confusion, disorientation, coma) 2) Neuromuscular changes (e.g., Carried to the brain crossing blood-brain barrier muscle stiffness, asterixis) Inflammatory response causing astrocyte swelling and cerebral edema → affecting cerebral function Lesson a) Describe the normal anatomy and physiology of the hepatobiliary system: liver, gallbladder and Outcomes pancreas b) Explain the pathophysiology of the hepatobiliary system Jaundice, postal hypertension/ascites and encephalopathy Hepatitis, alcoholic liver disease and non- Liver alcoholic fatty liver disease, cirrhosis and liver transplant Cholelithiasis Pancreatitis 19  Hepatitis Inflammation of the liver caused by a virus, bacteria, toxins, obstruction, parasites, or chemicals (chloroform, carbon tetrachloride) Common symptoms: jaundice, dark urine, anorexia, fatigue, headache, nausea, vomiting, and fever Some cases: enlargement of liver (hepatomegaly) and spleen (splenomegaly) Laboratory tests: elevations in bilirubin, alkaline phosphatase, serum AST, and ALT  Types of Viral Hepatitis WHO Fact Sheets on Hepatitis: https://www.who.int/health-topics/hepatitis#tab=tab_1  Treatments of Viral Hepatitis Hepatitis Treatments Complications A No special treatment Rarely result in acute liver Supportive treatment: rest, adequate nutrition and fluids failure B Acute infection (6months): chronic Pegylated interferon + Chronic infection: cirrhosis and Nucleoside or nucleotide analogs: tenofovir or hepatocellular malignancy lamivudine C Acute infection: supportive treatment Acute infection: 75-85% Chronic infection: become chronic Pegylated interferon + ribavirin Chronic infection: chronic liver Protease inhibitors disease, cirrhosis and liver NS5A inhibitors transplant D (Requires Hepatitis B virus to replicate) (Similar to hepatitis B virus) No special treatment E No special treatment; similar to Hepatitis A Usually acute; rarely lead to chronic infection Alcoholic Liver Disease (ALD) Characterised by chronic and/or excessive alcohol intake, which leads to steatosis, inflammation, and fibrosis, culminating in cirrhosis and potential development of hepatocellular carcinoma Irreversible when liver becomes cirrhotic Source: Way GW et al. Cells. 2022.  Alcoholic Liver Disease (ALD) Common Nausea, malaise, and low-grade fever symptoms Jaundice, hepatomegaly Clinical Occasionally: Ascites, portal hypertension bleeding, and Manifestation hepatic encephalopathy Acetaldehyde toxicity, metabolic competition, induced Consequences metabolic tolerance, cerebellar degeneration, and malnutrition Pathophysiology of ALD Acetaldehyde 2 1 3  Pathophysiology of ALD Alcohol (Ethanol) is metabolised by alcohol dehydrogenase (ADH) into acetaldehyde & 1 metabolites, then further metabolised by aldehyde dehydrogenase (ALDH) into acetic acid/acetate, generating NADH. High NADH/NAD+ ratio decreases fatty acid oxidation and induces fatty acid synthesis. High levels of fatty acids signal the liver cells to compound it to glycerol to form triglycerides. These triglycerides accumulate in the liver, resulting in fatty liver (steatosis). The metabolites from alcohol metabolism damages the liver cells: 2 Reactive oxygen species (ROS) of free radicals cause oxidative stress, resulting in hepatic injury/damage Kupffer cells (resident macrophages) in liver is activated during early ethanol-induced 3 liver injury: Frequent activation ultimately leads to hepatocytes death, leading to formation of alcoholic liver disease and development of fibrosis  Pathophysiology of ALD Cirrhosis formation: 4 Exposure of acetaldehyde causes excessive collagen produced by liver’s hepatic stellate cells. ↓ The abnormal accumulation of collagen formed fibrous tissue within the hepatic parenchyma and disrupt normal hepatic vasculature. ↓ Fibrotic tissue accumulates causing abnormal liver function and distorts normal hepatic architecture.  Non-alcoholic Fatty Liver Disease (NAFLD) NAFLD Hepatic steatosis (dietary fat) NASH No other cause of secondary Presence of hepatic fat accumulation steatosis and inflammation No evidence of hepatocellular with hepatocyte injury injury in the form of (ballooning) with or without ballooning of hepatocytes fibrosis No evidence of fibrosis High risk of progression to Low risk of progression to cirrhosis and liver failure cirrhosis and liver failure  Risk factors of NAFLD Type 2 Diabetes OSA Overweight or Obesity Hypopituitarism Hypogonadism Dyslipidaemia Pancreato-duodenal resection Hypothyroidism Central obesity Age Metabolic syndrome/Insulin resistance Ethnicity Genetic predisposition PCOS Drugs and toxins Hypothyroidism Sedentary lifestyle Pathophysiology of NAFLD  Pathophysiology of NAFLD & NASH Begin with hepatic steatosis 1st hit is usually due to insulin resistance that causes massive metabolic dysregulation in liver fat metabolism leading to hepatic steatosis formation 4 types of mechanisms in 1st hit: Increase fat supply from high fat diet + increased adipose lipolysis Decrease fat export in the form of VLDL & TAGs Decrease free fatty acid ꞵ-oxidation Increase de novo lipogenesis Transitions of NAFLD → NASH in 2nd hit: Inflammation, fibrosis & cellular death due to lipotoxicity, oxidative stress, mitochondrial dysfunction and endoplasmic reticulum stress  Clinical Manifestation of NAFLD Abdominal Pain Biochemical elevated: Abdominal swelling Liver Aminotransferases Alanine Visible Spider-Like Blood aminotransferase (ALT) Vessels Aspartate Yellow Hue skin aminotransferase (AST) Clinical Alkaline phosphatase (ALP) Manifestation Yellowing of eyes Gamma-glutamyl transferase Brittle nails (GGT) Enlarged Breasts in men Serum ferritin concentration Weakness Transferrin saturation Fatigue Medical Treatment for NAFLD Diet & Lifestyle intervention: Weight loss Exercise Dietary – low fat & calories diet Avoid fructose & alcohol Insulin sensitising agents: Metformin Thiazolidinediones Other medications: Statin  Cirrhosis End of the pathophysiology spectrum for chronic liver diseases Damaged hepatocytes are replaced by fibrotic scar tissue → blocking the flow of blood through the organ → resulting in the loss of liver function Etiology: Hepatitis C Alcoholic liver disease Hepatitis C plus alcoholic liver disease NAFLD Hepatitis B, may be coincident with hepatitis D Congenital condition Autoimmune hepatitis Primary biliary cirrhosis Primary sclerosing cholangitis (multiple stricture in CBD) Haemochromatosis Wilson’s disease  Clinical Manifestation of Cirrhosis Digestive Skin Brain & Nervous system Pain & swelling in the Yellow (Jaundice) Problems with thinking, abdomen (hepatomegaly) Small, red spider-like memory and mood Decreased appetite & veins Fainting & light weight loss Very dark/pale skin headedness Nausea & vomiting Redness on the feet or Numbness in legs & feet Fatigue hands Dry mouth & increased Itching thirst GI bleeding Oesophageal varices Biochemical AST, ALT, GGT, ALP, Bilirubin, PT Complications of Cirrhosis Jaundice Ascites Portal hypertension Varices Hepatic Encephalopathy Foetor hepaticus Asterixis Hepatocellular cancer Malnutrition  Liver Transplantation Common medical conditions required liver transplantation: Chronic active hepatitis Cirrhosis Biliary related disorders Liver transplant waiting list depends on Model of End stage Liver Disease (MELD) After transplant, all patients require scoring system. immunosuppressive drugs to prevent rejection of the new liver. Lesson a) Describe the normal anatomy and physiology of the hepatobiliary system: liver, gallbladder and Outcomes pancreas b) Explain the pathophysiology of the hepatobiliary system Jaundice, postal hypertension/ascites and encephalopathy Hepatitis, alcoholic liver disease and non- alcoholic fatty liver disease, cirrhosis and liver transplant Biliary system (bile) Cholelithiasis Pancreatitis 38 Disorders of biliary system Diagnosis Description Cholelithiasis Formation of stones (calculi) within the gallbladder or biliary duct system. Cholecystitis Inflammation of the gallbladder; usually develops secondary to obstruction, infection and ischemia of the gallbladder. Choledocholithiasis Occurs when a gallstone passes from the gallbladder through the cystic duct and lodges in the common bile duct or in the head of the pancreas. Cholangitis Inflammation of the biliary ducts; usually secondary to obstruction of the common bile duct leading to infection.  Types of Gallstones Cholesterol Pigment Mixed Most common type Excess of unconjugated Combination of cholesterol & Incidence increases with bilirubin pigment stones or other age Black colour (associated with substance Female > male haemolysis & cirrhosis Calcium carbonate, Smooth & whitish yellow Earthy calcium bilirubinate phosphate, bile salts & to tan colour (associated with infection) palmitate Formation of Gallstones Cholesterol is insoluble in water, but the bile salts and lecithin keep it in solution in the form of micelles. Because bile salts and lecithin are concentrated with cholesterol in the gallbladder, cholesterol remains in solution. In abnormal conditions, however, cholesterol precipitates as gallstones.  Cholelithiasis Eiology Risk Factors Gallbladder stasis Metabolic syndrome Supersaturation of bile with Inflammatory bowel disease cholesterol Cystic fibrosis Infection and tissue injury Rapid weight loss Genetics Fat-restricted diets Bariatric surgery Statin medications Prolonged parenteral nutrition Short bowel syndrome Others: multiple pregnancy, use of hormone estrogen, gender, age  Pathophysiology Supersaturation of cholesterol or calcium in bile Precipitation of solute from solvent to form solid crystal Cholelithiasis Crystals come together & fuse & formed calculi Venous & lymphatic drainage impaired Proliferation of bacteria occur Cholecystitis Localised cellular irritation & infiltration Ischaemia & necrosis  Clinical manifestation & Medical treatment Indigestion feeling after eating high fat foods Pain in R upper quadrant epigastric region Pain Antiemetics management Mimic of heart attack Low grade fever Mild jaundice Gallstone Antibiotics Steatorrhoea dissolution Clay coloured stools Tea coloured urine Elevated Biochemical: Endoscopic Lithotripsy sphincterotomy Leukocyte count Conjugated bilirubin Alkaline phosphate Serum amylase Cholecystectomy Lipase  Acute Cholecystitis Definition: Acute inflammation of the gallbladder wall Pathophysiology Aetiology: Aetiological factors ▪ Gallstone in cystic duct ▪ Obstruction in cystic duct ▪ Bacterial infection (gram positive and gram- Venous & lympathic drainage impaired negative aerobes and anaerobes) Risk factors: ▪ Sedentary lifestyle Proliferation of bacteria takes place ▪ Obesity Clinical Manifestation: ▪ Pain: Epigastric, R upper quadrant & Cellular irritation & inflammation subscapular, Onset sudden, peak in 30 mins ▪ Nausea ▪ Vomiting Acute cholecystitis ▪ Low grade fever ▪ Mild jaundice  Chronic Cholecystitis Definition: Pathophysiology Repeated inflammation & infection of gallbladder Occlusion of the cystic duct/malfunction of Aetiology: the mechanics of gallbladder emptying ▪ Recurrent episodes of acute cholecystitis or ▪ Chronic irritation from gallstones → inflamed Gallbladder wall inflamed and oedema gallbladder wall ▪ Gallbladder emptying dysfunction Risk factors: Lithogenic bile ↑ free radical-mediated ▪ Female gender damage (hydrophobic bile salts) ▪ Obesity, rapid weight loss ▪ Pregnancy Low levels of prostaglandin E2 ▪ Advanced age ▪ Hispanic or Pima Indians Cholecystokinin receptors of smooth muscle Clinical Manifestation: affected & impaired gallbladder contraction ▪ Similar pain as Acute cholecystitis ▪ Indigestion, Nausea/vomiting ▪ Fat intolerance, Heart burn Gallbladder wall inflamed ▪ Fibrosis of gall tissues ▪ Inability to concentrate bile, Clay coloured stools ▪ Fever, Jaundice, Pruritus Chronic cholecystitis  Medical treatment Acute Cholecystitis Chronic Cholecystitis ▪ NPO ▪ Cholecystectomy ▪ Ryles Tube Feeding ▪ Low fat diet ▪ IV Fluids ▪ Antibiotics ▪ Analgesics ▪ Monitoring ▪ Possible surgery: Cholecystectomy Lesson a) Describe the normal anatomy and physiology of the hepatobiliary system: liver, gallbladder and Outcomes pancreas b) Explain the pathophysiology of the hepatobiliary system Jaundice, postal hypertension/ascites and encephalopathy Hepatitis, alcoholic liver disease and non- alcoholic fatty liver disease, cirrhosis and liver transplant Cholelithiasis Pancreas Pancreatitis 48  Pancreatitis Definition: An inflammation of the pancreatic parenchyma Acute Chronic An acute condition of diffuse pancreatic Continuous prolonged, inflammatory & inflammation & autodigestion. fibrosing process of the pancreas. Reversible parenchymal damage Irreversible parenchymal damage Degree of inflammation varies from mild Fibrotic tissue replaced pancreatic cells → oedema to severe haemorrhagic necrosis. strictures & calcifications in pancreas Pathophysiology of Acute Pancreatitis When acinar cells is injured by sources, it impairs the release of proenzymes (in zymogen granules) ↓ Inappropriate activation of pancreatic enzymes especially trypsinogen ↓ Trypsin activated & activated other pancreatic enzymes e.g. phospholipase and elastase and more trypsin leading to autodigestion ↓ Damages pancreatic parenchyma Haemorrhage (Elastase) Fat necrosis (Phospholipase)  Acute Pancreatitis Etiology: Medical treatment ▪ Pancreatic duct obstruction – cholelithiasis, ampullary obstruction, chronic alcoholism, ductal concretions IV fluids ▪ Alcohol Medications: Analgesics, anti-emetics, ▪ Drugs, ischemia, viruses antibiotic ▪ Defective intracellular transport – metabolic injury, Nil by mouth alcohol, duct obstruction Nasogastric tube insertion Clinical Manifestation: ▪ Nausea ▪ Vomiting ▪ Abdominal distention ▪ Steatorrhea ▪ Hypotension ▪ Dehydration ▪ Jaundice ▪ Tachycardia ▪ Hypovolemia ▪ Biochemical: abnormal serum Amylase and/or lipase  Pathophysiology of Chronic Pancreatitis 1. Ductal obstruction by protein: 3. Oxidative stress Inciting agents in chronic pancreatitis Free radicals cause oxidative stress to (e.g. alcohol) increase the protein acinar cells → membrane damage → concentration of pancreatic secretions chemokines expression (IL-8) which and these proteins can form ductal plugs recruits inflammatory cells 2. Toxic metabolic Promotes fusion of lysosomes and Toxins can exert a direct toxic effect on zymogen granules resulting acinar cell acinar cells, leading to lipid necrosis, inflammation & fibrosis accumulation, acinar cell losses and 4. Inappropriate activation of pancreatic eventually parenchymal fibrosis enzymes Mutations in the cationic trypsinogen & trypsin inhibitor  Chronic Pancreatitis Etiology Clinical Manifestation Medical Treatment Chronic alcoholism Chronic abdominal pain Endoscopic therapy Smoking Lost endocrine & (dilating, stenting a Hereditary disorders exocrine functions stricture in Hypertriglyceridaemia Weight loss pancreatic/biliary duct, Hypercalcaemia Malnutrition stone removal) Biliary tract disease Steatorrhoea Nerve block Gallstones Diabetes Surgical Certain medications Diarrhoea Behaviour modification Viral infections Jaundice Medications: Autoimmune Calcification Analgesics Idiopathic Biochemical: Insulin Elevated pancreatic Enzyme replacement enzymes (e.g. serum amylase)  References Textbooks Marieb, E. N. and Hoehn, K. (2018) Human Anatomy and Physiology, 11th edition, Hoboken, New Jersey: Pearson Education, Inc. Nelms, M. N. and Sucher, K. (2020) Nutrition Therapy and Pathophysiology, 4th edition, Boston, MA, USA: Cengage Learning. Mahan, L. K., Escott-Stump, S. and Raymond, J. L. (2012) Krause’s Food & the Nutrition Care Process, 13rd edition, St. Louis, Mo: Elsevier/ Saunders. Escott-Stump, S. (2015) Nutrition and Diagnosis-related Care, 8th edition, Philadelphia: Wolters Kluwer. Academic Journals Yu J et al. (2016) The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background. Gastroenterology Research and Practice, Volume 2016, Article ID 2862173, pp 1-13 http://dx.doi.org/10.1155/2016/2862173  Case Study on Liver Cirrhosis Mr N. 56 year old male, admitted to hospital medical ward on 22/03/21. He was confused, disoriented, drowsy, slurred speech. Jaundice, clubbing, foetor hepaticus, flapping tremour were present. He was diagnosed with hepatic encephalopathy. 1 month history of abdominal distention (ascites), confusion, inability to concentrate and constant short of breathe. Past Medical History: Diagnosed with alcohol- induced liver cirrhosis in March 2020 and defaulted treatment since August 2020. Social history: Retiree. Not married. Sedentary. Excessive alcohol use for approximately 20 yrs  Medication: Biochemical Results (22/03/19) Normal range Random 3.9 3.5 - 11.1 mmol/L Furosemide 80mg t.d.s (diuretic) blood sugar Aldactone 100mg b.d (diuretic) Sodium 125 135 - 145 mmol/L Potassium 4.8 3.5 - 5.0 mmol/L Thiamine 100mg o.d Urea 8.8 1.7 - 8.3 mmol/L Vit B12 1000µg o.d Creatinine 257 64 - 122 µmol/L ALP 220 M: 40-129 µL; F: 35- Pregamal 1 b.d (iron, folic acid) 105µL Vit K 10mg o.d Bilirubin 65 ≤ 17 µmol/L Albumin 25 34 - 48 g/L Lactulose 30ml b.d (laxative) GGT 137 0-45 µL Flagyl 400mg t.d.s (antibiotic) ALT 21 M: ≤41µL; F:≤ 31 µL Total Protein 80 66 - 87 g/L Hb 11.7 M:13-17 g/dL; F:12- Anthropometry: 15 g/dL MCV 104.9 80-100 fL Height: 170cm MCH 38.1 27-34 pg Current weight: 56.8kg (dry weight) Platelets 263 150-400 x 103 µL WBC 7.4 4.5-11 x 103 µL Usual weight: 65.8kg (1 year ago) I.N.R 2.2 0.9-1.2 Thank you. For more information please contact: Wong Ting Xuan Lecturer, Nutrition & Dietetics [email protected] IMU Education Sdn Bhd No. 126, Jalan Jalil Perkasa 19 199201005893 (237397-W) Bukit Jalil, 57000 Kuala Lumpur, Malaysia 603 8656 7228 Formerly known as International Medical University. imu.edu.my