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Pathology of Biliary Disorders.Presentation Transcript
Cognitoergo sum.…I think, therefore I am…!- -Rene Descartes
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 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 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 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 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 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
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…!
Pathology ofBiliary & Pancreatic DisordersDr. Shashidhar Venkatesh MurthyA/Prof. & Head of PathologySchool of Medicine.
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*.
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)
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.
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.
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.
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
MB4-T2-Wk4-Biliary systemGall stones in CBDStones in CBDStonees in GB20% of mixed chol. stones and >50% of pigment stones are radio-opaque
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
It is not enough to have a good mind;the main thing is to use it well…!- -Rene Descartes
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.
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.
What we think,we become!--Buddha
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.
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.
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
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.
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.
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.
MB4-T2-Wk4-Biliary systemAcutePancreatitis:K KHemorrhage in thehead of Pancreas withedema.CT Scan appearance
AcutePancreatitis:L K KHemorrhage in thehead of Pancreas withedema.CT Scan appearanceA-StomachB-SpleenC-PeritoneumD-Pancreas
MB4-T2-Wk4-Biliary systemAcute Pancreatitis: ComplicationsPancreatic cancer
At the center of your being youhave the answer; you knowwho you are and you knowwhat you want!Lao Tzu
MB4-T2-Wk4-Biliary systemCPC 2.7- Mr J.M. 51y, depression. Mr J.M. 51 year old High School principal inTownsville. Several months - stress, anxiety and depression. Treatment for this with anti depressants andcognitive behavior therapy has been reasonablysuccessful although he remains stressed. makes an earlier appointment. „His trousers are hanging off him. No appetite. myankles have been a bit swollen recently. Could not walk…. Too tired…! Epigastric intermittent pain. „Bit dark urine … recently‟
MB4-T2-Wk4-Biliary systemChronic Pancreatitis: Clinical:• Painful, relapsing, inflammation, fibrosis & exocrine atrophy.Cystic/atrophic ducts.• Irreversible loss of pancreatic function *• Malabsorption, albumin, wt. loss – Exocrine• Type I DM – Endocrine loss.• Recurrent obstructive Jaundice – obstruction. Causes:• Toxic metabolic- 70%: Alcohol, Hyperlipidaemia, toxins, drugs,hypercalcaemia.• Idiopathic-20%: Early/Late.• Others: Genetic, autoimmune, Post necrotic. Complications:• Pseudocyst, Calcification, lithiasis & Carcinoma.
MB4-T2-Wk4-Biliary systemChronic fibrosing Pancreatitis:DuodenumFibrosispancreas (P) is atrophic and replaced by rubbery, fibrous tissue, in which dilatedducts (D) are seen (Clinically by ERCP). In many cases calculi are present in thedilated ducts. In this example the duodenum is attached (A).
MB4-T2-Wk4-Biliary systemChronic PancreatitisAtrophy, Fibrosis, CalcificationThe pancreas is shrunken and fibrotic. The main ductis dilated and filled with calcified secretions (arrows).
MB4-T2-Wk4-Biliary systemChronic Pancreatitis:Dilated DuctsIslets (endocrine)FibrosisNote: Fibrosis replacing exocrine glands. 0nly ducts & Islets remain in late stage.Inflam
MB4-T2-Wk4-Biliary systemPancreatic Cancer Increasing in incidence. 4th common (next to Colon Ca). 10-15 per 100 000, more with age >70y. Men are affected twice as often as women. Unknown etiology, Several Risk factors Smoking, Diabetes & Diet.• High calorie, fat, meat, salt, fried, soy beans & nitrosamines. Also increased incidence in Hereditary pancreatitis,MEN, hereditary non-polyposis colon cancer-HNPCC.
MB4-T2-Wk4-Biliary systemPancreatic Cancer Adenocarcinoma fibrosis stricture, Obstructivejaundice & weight loss. Advanced disease at presentation. Poorprognosis. 85% only palliative care. Palpable gallbladder + jaundice Ca Pan(Courvoisiers sign). diabetes (due to ß cell destruction) Depression*, Migratory thrombophlebitis - Trousseaus
MB4-T2-Wk4-Biliary systemPancreatic Ca with fibrosis (Chronic pancreatitis)Note: dysplastic glands infiltrating into fibro (spindle cells) myxoid (pale blue) stroma.Malignant gl.Ca. InfiltrationIslet (normal)Fibrous stroma
Ca PancreasClinical FeaturesTumour marker:CEA & CA19–9 antigenTrousseau syndrome
MB4-T2-Wk4-Biliary systemCa Pancreas & Depression Cancer pancreas has a reputation of being a deadly andoften painful disease, with very poor prognosis. Depression and anxiety occur more frequently Depression and anxiety may even precede symptoms orknowledge of the diagnosis. The etiology of depression in patients with cancer of thepancreas may be traced to more than the diseasessymptoms.Steve Jobs
A scholar who cherishes thelove of comfort is not fit to bedeemed a scholar.Lao Tzu
Give someone a fish and youfeed him for a day.Teach someone to fish and youfeed him for a lifetime!Lao Tzu
MB4-T2-Wk4-Biliary systemAcute Pancreatitis: Summary Gross: Inflammation,Hemorrhages (red arrows)and chalky white areas of fatnecrosis (white arrows). Microscopy: Hemorrhage,Acute inflam, fat necrosis. Complications:Mechanisms: Obstruction, Acinar damage, Enzyme anomaly.Pathogenesis: Activation of enzymes in the acini/ducts autodigestion Fat necrosis Ca+ soap + inflammation.
MB4-T2-Wk4-Biliary systemCholesterolosis of gallbladder mucosaCholesterol filled Foamymacrophages in mucosalfolds
To attain knowledge, addthings every day.To attain wisdom, removethings every day.Lao Tzu
MB4-T2-Wk4-Biliary system5 A‟s & SNAP74• Ask: 1. patients with diabetes, hypertension,hyperlidaemia, obesity or existing vascular disease• Assess: 2.Number of cigarettes or equivalent/day,Dependance 3.readiness to change/motivation• Advise: 4.provide written information, 5.motivationalinterviewing• Assist: 6.NRT ? Bupropion(Zyban) 7.Support• Arrange: 8.referral to QUIT 9.follow up with the GPSNAP Counseling: Smoking, Nutrition, Alcohol &Physical Activity.
MB4-T2-Wk4-Biliary systemAcute Pancreatitis: Clinical Features Mild (edema) & Severe (Hemorrhagic) forms. Constant severe epigastric pain radiating to the back Fever, Nausea and/or vomiting Respiratory & circulatory failure DIC, Shock, Fat necrosis, hemorrhage. Abdominal tenderness, distension, guarding, and rigidity,Mild jaundice, Diminished or absent bowel sounds. Hypocalcemia, High Amylase-P (early) High Lipase >24h – (only lipase ↑ in chronic) CT Scan – diagnostic. ? Grey Turner‟s sign ? Cullen‟s sign
MB4-T2-Wk4-Biliary system“acute abdomen” Differential Diagnosis: Acute Pancreatitis: medical emergency ofthe first magnitude. Multiorgan failure – fatal. Differential diagnosis:• Perforated acute appendicitis.• Perforated Acute diverticulitis.• Perforated peptic ulcer.• Acute cholecystitis & Rupture.• Infarction of the bowel.• Intestinal Obstruction.
MB4-T2-Wk4-Biliary systemAcute Pancreatitis: Principles of Lab Diagnosis: Full blood count: neutrophil leukocytosis. Serum amylase: greatly elevated. Serum Lipase: Elevated after 24h. (72-96h) Serum albumin: falls (severe inflam. Exud) Serum calcium: falls - Complex with necrotic Fat. Blood sugar: hyperglycemia if severe – loss ofendocrine part. Alkaline phosphatase: mild elevation obstruction oflower end of bile duct (gall stone) Bilirubin: mild direct Bil, oedema & obstruction of lowerend of bile duct.
MB4-T2-Wk4-Biliary systemCPC 4.2.7- May, 35y woman. May, 35y, indigenous woman, lives in a remoteAboriginal community. After hour visit… “I’ve got terrible gut pains”, since 2h. Students must specifically ask about…? Alcohol, DM.. (PUD, IHD, Gall bl, Drugs) Tenderness & guarding in epigastrium. Absent bowel sounds. Social & family History of alcohol abuse. Diabetes not well controlled.
MB4-T2-Wk4-Biliary systemPancreatic CancerPleomorphic glands (A) in a denselyfibrotic (desmoplastic) stroma (B)Section of head of pancreas showingan ill-defined mass in the pancreaticsubstance (arrowheads) and the greendiscoloration of the CBD due toobstruction of bile flowAB
MB4-T2-Wk4-Biliary systemSilence…81To the question "Who am I?" the only relevant answer is silence. Youneed to discard all answers in words, including "I am Nothing" or "Iam the Cosmic Self" or "I am the Self" - and just stick to the question"Who am I?". All other answers are just thoughts. Thoughts cannever be complete. Only Silence is complete.Thoughts are not the goal in themselves. Their goal is Silence. Whenyou ask the question "Who am I?" you get no answer, there issilence. That is the real answer. For your soul is solidified silence.This solidified silence is wisdom, is knowledge.The easy way to silence the thoughts is to arouse the feelings. For,through feelings only peace, joy and love dawn. And they are allyour very nature.- Sri Sri Ravishankar