Pathology of Biliary Disorders.

1. Pathology of Biliary Disorders. Cognitoergo sum.…I think, therefore I am…!- -Rene Descartes

2. MB4-T2-Wk4-Biliary systemCPC 4.2.3 Professionalism & Ethics - of out of office consultations.. Abdominal problems…DD Counseling, SNAP & five A‟s… Upper abdominal discomfort with bloating & wind. after meal burps, stomach feels full & windy. ? worsening. Duration Symptoms for many months. Relation to food/fat Yes, makes it worse. Pain 3-4/10, ill defined, cramping. Nausea occasional, no vomiting. Wt loss, Anorexia, Dysphagia  No Bowel habit constipation, No pus, blood PR. Diet usually eats once a day, often fast foods. Little fruits &veggies. Lots of coffee*2CASE STUDY:Mrs. L.K is your eldest son’s high school teacher. You attend the parent-teacher interview todiscuss his school work and she asks for advice about her abdominal problems. You advise her tosee you at your rooms in the morning. She is 32 years old and married to a local police officer. MB4-T2-Wk4-Biliary systemCPC 4.2.3 Professionalism & Ethics - of out of office consultations.. Abdominal problems…DD Counseling, SNAP & five A‟s… Upper abdominal discomfort with bloating & wind. after meal burps, stomach feels full & windy. ? worsening. Duration Symptoms for many months. Relation to food/fat Yes, makes it worse. Pain 3-4/10, ill defined, cramping. Nausea occasional, no vomiting. Wt loss, Anorexia, Dysphagia  No Bowel habit constipation, No pus, blood PR. Diet usually eats once a day, often fast foods. Little fruits &veggies. Lots of coffee*2CASE STUDY:Mrs. L.K is your eldest son’s high school teacher. You attend the parent-teacher interview todiscuss his school work and she asks for advice about her abdominal problems. You advise her tosee you at your rooms in the morning. She is 32 years old and married to a local police officer.

3. MB4-T2-Wk4-Biliary systemCPC 4.2.3 Alchohol 2-3 glasses of wines/night. 12-15 onweekends, more when friends. (Hepatitis, pancreatitis, gallstones) Family: Married to an accountant, no children but has 3lap dogs. (hydatid dis, echinococcosis.) MedicationShe is on COCP, (Budd-Chiari sy) PSH: Tonsillectomy & adenoidectomy at 5 years,appendicectomy at 14y. (Viral Hepatitis)3 MB4-T2-Wk4-Biliary systemCPC 4.2.3 Alchohol 2-3 glasses of wines/night. 12-15 onweekends, more when friends. (Hepatitis, pancreatitis, gallstones) Family: Married to an accountant, no children but has 3lap dogs. (hydatid dis, echinococcosis.) MedicationShe is on COCP, (Budd-Chiari sy) PSH: Tonsillectomy & adenoidectomy at 5 years,appendicectomy at 14y. (Viral Hepatitis)3

4. MB4-T2-Wk4-Biliary systemInvestigations Upper abdominal USS – numerous gallstones in thick-walled gallbladder LFT – elevated GGT*, Alk Phos normal*…? Fasting glucose- 7.0 mmol/l Lipid profile - Total Chol 7.2, Trig. 2.8, HDL 2.0, LDL-5.1. Rectal examination – Hard stool in the rectum, nohemorrhoids or fissures.4 MB4-T2-Wk4-Biliary systemInvestigations Upper abdominal USS – numerous gallstones in thick-walled gallbladder LFT – elevated GGT*, Alk Phos normal*…? Fasting glucose- 7.0 mmol/l Lipid profile - Total Chol 7.2, Trig. 2.8, HDL 2.0, LDL-5.1. Rectal examination – Hard stool in the rectum, nohemorrhoids or fissures.4

5. MB4-T2-Wk4-Biliary systemCPC 4.2.3: DD – commonest first. Gastritis Peptic ulcer Liver disease.. Fatty liver * Gallstones, Cholecystitis. Constipation * Irritable bowel syndrome Diverticulosis / Diverticulitis Pancreatitis - chronic Any thing else ??5Major Learning Issues:• Gall stones• Cholecystitis Acute/Chronic• Pancreatitis Acute/Chronic• Pancreatic cancer.Minor Learning Issues:• Cholangitis• Biliary Atresia• Secondary Biliary Cirrhosis• Carcinoma of Gallbladder• Cholangiocarcinoma(bile duct ca)• Hemochormatosis,• Wilson‟s• & α1AT deficiency MB4-T2-Wk4-Biliary systemCPC 4.2.3: DD – commonest first. Gastritis Peptic ulcer Liver disease.. Fatty liver * Gallstones, Cholecystitis. Constipation * Irritable bowel syndrome Diverticulosis / Diverticulitis Pancreatitis - chronic Any thing else ??5Major Learning Issues:• Gall stones• Cholecystitis Acute/Chronic• Pancreatitis Acute/Chronic• Pancreatic cancer.Minor Learning Issues:• Cholangitis• Biliary Atresia• Secondary Biliary Cirrhosis• Carcinoma of Gallbladder• Cholangiocarcinoma(bile duct ca)• Hemochormatosis,• Wilson‟s• & α1AT deficiency

6. 6HBS:CommonClinical Presentations.Why!

7. MB4-T2-Wk4-Biliary systemPathological basis of signs and symptoms7Sign or symptom Pathological basisJaundice Haemolysis, liver disease or biliary obstructionDark urine Conjugated hyperbilirubinaemia (water-soluble)Pale faeces Biliary obstruction causing lack of bile pigmentsSpider naevi Gynaecomastia Secondary to hyperoestrogenismOedema Reduced plasma oncotic pressure - hypoalbuminaemiaXanthelasma Cutaneous lipid deposits  hypercholesterolaemia inchronic biliary obstruction.Steatorrhoea Malabsorption of fat - (e.g. biliary obstruction)Pruritus Biliary obstruction resulting in bile salt accumulationAscites Hypoalbuminaemia, portal hypertension and secondaryhyperaldosteronism.Bruising or bleeding Impaired hepatic synthesis of clotting factors – Vit K.Hepatomegaly hepatitis, infiltration (fat) or tumour (primary or secondary)Haematemesis Ruptured oesophageal varices due to portal hypertensionEncephalopathy Failure of liver to remove toxins mimicking or alteringbalance of neurotransmitters MB4-T2-Wk4-Biliary systemPathological basis of signs and symptoms7Sign or symptom Pathological basisJaundice Haemolysis, liver disease or biliary obstructionDark urine Conjugated hyperbilirubinaemia (water-soluble)Pale faeces Biliary obstruction causing lack of bile pigmentsSpider naevi Gynaecomastia Secondary to hyperoestrogenismOedema Reduced plasma oncotic pressure - hypoalbuminaemiaXanthelasma Cutaneous lipid deposits  hypercholesterolaemia inchronic biliary obstruction.Steatorrhoea Malabsorption of fat - (e.g. biliary obstruction)Pruritus Biliary obstruction resulting in bile salt accumulationAscites Hypoalbuminaemia, portal hypertension and secondaryhyperaldosteronism.Bruising or bleeding Impaired hepatic synthesis of clotting factors – Vit K.Hepatomegaly hepatitis, infiltration (fat) or tumour (primary or secondary)Haematemesis Ruptured oesophageal varices due to portal hypertensionEncephalopathy Failure of liver to remove toxins mimicking or alteringbalance of neurotransmitters

8. MB4-T2-Wk4-Biliary systemSelf Assessment Questions: most common cause of acute Cholecystitis / cholelithiasis /pancreatitis? Common types & pathogenesis of cholelithiasis? Clinical features of acute cholecystitis / cholelithiasis? Morphology of acute & Chronic cholecystitis? (gross/micro) How obesity causes cholelithiasis? Pathogenesis of alcohol induced pancreatitis? What is cholestasis? common types? PBC, PSC, neonatal. Congenital: Hemochormatosis, Wilson‟s & α1AT deficiency? Common type & clinical features of of pancreatic cancer? What is primary sclerosing cholangitis? Common causes? Hepatocellular carcinoma ? Brief notes, diagnosis, AFP.. MB4-T2-Wk4-Biliary systemSelf Assessment Questions: most common cause of acute Cholecystitis / cholelithiasis /pancreatitis? Common types & pathogenesis of cholelithiasis? Clinical features of acute cholecystitis / cholelithiasis? Morphology of acute & Chronic cholecystitis? (gross/micro) How obesity causes cholelithiasis? Pathogenesis of alcohol induced pancreatitis? What is cholestasis? common types? PBC, PSC, neonatal. Congenital: Hemochormatosis, Wilson‟s & α1AT deficiency? Common type & clinical features of of pancreatic cancer? What is primary sclerosing cholangitis? Common causes? Hepatocellular carcinoma ? Brief notes, diagnosis, AFP..

9. MB4-T2-Wk4-Biliary systemCore Learning Issues (CLI): Major CLI:• Cholelithiasis• Cholecystitis – Acute, Chronic• Pancreatitis – Acute, Chronic• Pancreatic carcinoma Minor CLI:• Ca. gall bladder & biliary tract.• Other parasites, atresia, Autoimmune.• Congenital: Cystic fibrosis.• Hemochormatosis, Wilson‟s & α1AT deficiency• Pancreatic cysts, pseudocyst,• Other Tumours, carcinoid, MEN Types 1 & 2.9 MB4-T2-Wk4-Biliary systemCore Learning Issues (CLI): Major CLI:• Cholelithiasis• Cholecystitis – Acute, Chronic• Pancreatitis – Acute, Chronic• Pancreatic carcinoma Minor CLI:• Ca. gall bladder & biliary tract.• Other parasites, atresia, Autoimmune.• Congenital: Cystic fibrosis.• Hemochormatosis, Wilson‟s & α1AT deficiency• Pancreatic cysts, pseudocyst,• Other Tumours, carcinoid, MEN Types 1 & 2.9

10. . Thought is Powerful & Free!--William ShakespeareHuman mind is the most powerful weapon in theworld.- e.g. Osama bin laden.Great monuments & Great wars have always started in a human mind…!

11. . Pathology ofBiliary & Pancreatic DisordersDr. Shashidhar Venkatesh MurthyA/Prof. & Head of PathologySchool of Medicine.

12. . Anatomy:

13. . MB4-T2-Wk4-Biliary systemPhysiology: Bile is the main pathway for cholesterol excretion. Bile: cholesterol, bile salts & bile pigmint (bilirubin, biliverdin) Cholesterol made soluble by bile salts (soap) as micielles Excess cholesterol / low bile salt  Stone formation*.

14. . MB4-T2-Wk4-Biliary systemBiliary Obstructions: Extrahepatic Obstruction:• Dislodged gallstones• Ca. CBD, Ca. Head of pancreas.• inflammatory stricture of CBD• accidental surgical ligation of CBD. Intrahepatic Obstruction:• Biliary atresia – Congenital.• Primary Biliary Cirrhosis• Primary Sclerosing Cholangitis.• Cystic fibrosis.Common Disorders:• Cholecystitis• Cholelithiasis• Choledocholithiasis.(Adeno Carcinoma)95% - Cholelithiasis (+cystitis)

15. . MB4-T2-Wk4-Biliary systemCholelithiasis: Cholelithiasis/gall stones – 95% of GB dis. Incidence: West 20-40%, Asian 2-4%. 70-80% asymptomatic Mixed 80% - (cholesterol, ca+, bile, blood) Pure 20% - Pigment *, Cholesterol. Severe colicky Upper abdomen  Rt shoulder. Conjugated hyperbilirubinemia  Obstruction. Fat intolerance  clay stools - typical in chronic.

16. . MB4-T2-Wk4-Biliary systemRisk Factors: CholelithiasisCholesterol Stones: Race/Demo: Western Age Middle/late. Excess Cholesterol• Female sex• Oral contraceptives• Pregnancy• Obesity• Rapid weight reduction• Gallbladder stasis• Disorders of bile acidmetabolism• Hyperlipidemia syndromesPigment Stones: Race – Asians Age: early Jaundice / Infections• Hemolysis syndromes• Biliary infections• Inflammatory boweldisorders.• Ileal resection or bypass.• Cystic fibrosis• Chronic Pancreatitis.80% Idiopathic.75% in American Pima race.

17. . MB4-T2-Wk4-Biliary systemCholelithiasis:Crystallization of bile within biliary system. Risk factors:• female gender, obesity, diabetes mellitus (FFFF…!) Pathogenesis: Cholesterol is made soluble by bile salts and lecithins. More cholesterol or less bile salts  chol. Monohydratecrystals  stone. Etiologic factors.• Supersaturation – excess Cholesterol – crystals.• Calcium Microprecipitation - Nucleation.• Stasis - Mucous  trap crystals – aggregation• Stone growth environment: infection, stasis, etc.

18. . MB4-T2-Wk4-Biliary systemCholelithiasis: Morphology & Types:• Mixed Chol (Ca+Bile salt)* Multiple,faceted, yellow-grey.• Rarely Pure cholesterol: Round spiky.• Bile Pigment stones (black/brown).Infection / Jaundice. % Calcium = radioopaque.

19. . MB4-T2-Wk4-Biliary systemGallstones + Chronic Cholecystitis

20. . MB4-T2-Wk4-Biliary systemCholesterol (Pure) Gallstones, bleeding.20Round, yellow, spiky, bleeding. Note thickened inflammed gall bladder.

21. . MB4-T2-Wk4-Biliary systemCholecystitis + gall stones  Abscess.21Pigment stones in Infection: Inflammed, thickened gallbladder filled with pus & black gall stones.Small stone is seen obstructing neck  acute pain.Adherent OmentumPus & Stones (black)Stone in the neckUNSW MuseumPigment stones inHemolysis - Bilirubin

22. . MB4-T2-Wk4-Biliary systemGall stones in CBDStones in CBDStonees in GB20% of mixed chol. stones and >50% of pigment stones are radio-opaque

23. . MB4-T2-Wk4-Biliary systemComplications of Cholelithiasis: Obstruction Sec biliary cirrhosis* Cholecystitis Cholangitis Biliary colic Jaundice Empyema Liver abscess Mucocele Pancreatitis. Peritonitis Carcinoma Fistula formation Gall stone ileus.Gallstone ileus

24. . It is not enough to have a good mind;the main thing is to use it well…!- -Rene Descartes

25. . MB4-T2-Wk4-Biliary systemAcute Cholecystitis: 90% Cholelithiasis. 10% non-calculous Females common. Outflow obstruction by a small gallstone. Infection – E.coli.  Empyema. Risk of perforation, peritonitis, fistula Gall stone ileus when stone enters GIT. Serum amylase normal (high with pancreatitis). Mild jaundice in 20% - obstructive. Acute inflammation, hemorrhage, edema, neutrophils. Gangrenous cholecystitis: when obstruction is severecompromising blood supply. Green-black necrotic.

26. . MB4-T2-Wk4-Biliary systemChronic Cholecystitis: Females. Recurrent / Chronic. Thick fibrotic wall. Thick bile – biliary gravel. Aschoff-Rokitansky sinuses –diverticula - Due to increasedluminal pressure (obstruction) Diffuse infiltration by chronicinflammatory cells.

27. . What we think,we become!--Buddha

28. . MB4-T2-Wk4-Biliary systemNeoplastic Disorders: (rare) Benign tumours:• Bile duct adenoma, cystadenoma Malignant tumours:• Adenocarcinoma Ducts lined by cuboidal tocolumnar mucin secreting cells separated bydesmoplastic (fibrotic) stroma.• Cholangiocarcinoma (Bile duct carcinoma)• Presents with Jaundice.• Early spread with very poor prognosis.

29. . MB4-T2-Wk4-Biliary systemCarcinoma Gallbladder: Females , Hispanics. Mexico & Chile 5th-7th decade Common – Lithiasis * abdominal pain, anorexia, High ALP. Commonly Adenocarcinoma Late diagnosis Poor prognosis. 5% 5 year survival.

30. . MB4-T2-Wk4-Biliary systemCa Bile duct: Cholangiocarcinoma: Adeno Carcinoma ofcholangiocytes. Thoratrast exposure? Increased incidence inulcerative colitis. Presents with obstructivejaundice – early diagnosis. Intrahepatic or extrahepatic. Increasing incidence. ? toxin

31. . 31Living becomes a glorious experienceonly when there is tolerance and love.Willingness to compromise with otherpeople’s ways of living andcooperation. These make happy andsuccessful societies.-- Baba.

32. . MB4-T2-Wk4-Biliary system32CPC 4.2.4 – HBS – Part 22 weeks later she present again to your GP practice.-Worsening abdominal pain - „The worst I ever had-It’sterrible, please do something’ Central, severe 9/10 constant, radiates to back. > 12hours. Associated with vomiting x 3 this morning. Nohaematemesis. Bowels opened yesterday no blood mucus. Hasn‟tpassed urine in 8 hours. Doesn‟t feel like drinking oreating. „I just want to lie here- Don’t make me move’ No Pale stools / dark urine. Hasn‟t passed urine sincethis morning.

33. . MB4-T2-Wk4-Biliary systemHistory & Examination: Abdomen distended, tender. Guarding ++epigastrium. Investigations.• FBP –WCC↑, Plt 100 10x9• urea 7.4 mmol/l [2.5-6.6mmol/l]• decreased eGFR 70 [>90]• Crea 140umol/l [60-120umol/l]• LFT glucose 7.8, Ca+ Decreased, ALT & GGT ↑↑↑• Amylase lipase - ↑↑33DD: Acute Abdomen, Pancreatitis, perforated pepticulcer, appendicitis, diverticulitis,

34. . “Outer world is the reflection ofour inner world (thoughts)”--Baba

35. . Pathology ofPancreatic DisordersShashidhar Venkatesh MurthyAssoc. Prof & Head of Pathology

36. . MB4-T2-Wk4-Biliary systemIntroduction: Pancreas Exocrine & Endocrine gland.• Develops from two embryonic buds (dorsal & ventral)• Head, neck & body, Portal circulation*• Susceptible to Obstruction, ischemia, trauma, toxins.• Highly destructive “lytic” enzymes Disorders:• Congenital: annular, divisum, ectopic, cysts.• Acute & Chronic pancreatitis.• Cysts & Tumors: Adenocarcinoma. Diagnosis:• Serum amylase, lipase & ERCP/MRCP*• Biopsy is hazardous. – don’t mess with pancreas...!

37. . MB4-T2-Wk4-Biliary systemAnatomyHistology

38. . MB4-T2-Wk4-Biliary systemCongenital Disorders: Pancreatic Divisum:• Most common 3-10%• Failure of fetal duct union.• Congenital chronicpancreatitis. Cystic Fibrosis:• CFTR gene mutation– thick secretions. Annular Pancreas• 2nd part duodenumobstruction. Ectopic Pancreas• stomach and duodenum.

39. . MB4-T2-Wk4-Biliary systemAcute Pancreatitis Acute Inflammation of pancreas leading to enzymaticautodigestion & Hemorrhage, fat necrosis of surroundingtissue with systemic effects & multiorgan failure. Release & activation of pancreatic enzymes. Defectiveinactivation of trypsin. Common Etiology Alcohol & Gall stones (& Idiopathic). Trauma, Viral infection, Hyperlipidemia, hypercalcemia,shock, trauma, drugs, infections, snake bite – rare causes. Autoimmune disorders  immune pancreatitis. Blacks 10 times common than other races * Outcome: Heal, complications or chronic.

40. . MB4-T2-Wk4-Biliary system

41. . MB4-T2-Wk4-Biliary systemAcute Pancreatitis:Pathogenesis of clinical features:SUMMARY:Trypsin  Kallikrein  Thrombosis - NecrosisProtease  Blood Vessel injury – Bleeding.Lipase  Fat necrosis  Inflammation.

42. . MB4-T2-Wk4-Biliary systemGrey Turner Sign - Cullen‟s SignSevereMild

43. . MB4-T2-Wk4-Biliary systemAcute Pancreatitis:a: The pancreas edematousand hemorrhagic (H). Pancreatictissue becomes necrotic andmay become semi-liquid.b: fat necrosis seen as whitespots (F) in mesenteric andretroperitoneal fat.Histologically these foci arecomposed of necrotic adiposetissue, with adjacent reactiveinflammation.

44. . MB4-T2-Wk4-Biliary systemAcutePancreatitis:K KHemorrhage in thehead of Pancreas withedema.CT Scan appearance

45. . AcutePancreatitis:L K KHemorrhage in thehead of Pancreas withedema.CT Scan appearanceA-StomachB-SpleenC-PeritoneumD-Pancreas

46. . MB4-T2-Wk4-Biliary systemAcute Hemorrhagic Pancreatitis:Head

47. . MB4-T2-Wk4-Biliary systemAcute Hemorrhagic Pancreatitis:Fat NecrosisAcini NecrosisHemorrhageNormal Acini

48. . MB4-T2-Wk4-Biliary systemAcute Hemorrhagic Pancreatitis:Fat NecrosisAcini NecrosisHemorrhageNormal Acini

49. . MB4-T2-Wk4-Biliary systemAcute Pancreatitis: ComplicationsPancreatic cancer

50. . At the center of your being youhave the answer; you knowwho you are and you knowwhat you want!Lao Tzu