Pathology of Biliary Disorders.

Cognito ergo sum.

…I think, therefore I am…!

- -Rene Descartes

MB4-T2-Wk4-Biliary system

CPC 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*

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CASE STUDY: Mrs. L.K is your eldest son’s high school teacher. You attend the parent-teacher interview to discuss his school work and she asks for advice about her abdominal problems. You advise her to see you at your rooms in the morning. She is 32 years old and married to a local police officer.


CPC 4.2.3 Alchohol 2-3 glasses of wines/night. 12-15 on

weekends, more when friends. (Hepatitis, pancreatitis, gall stones)

Family: Married to an accountant, no children but has 3 lap dogs. (hydatid dis, echinococcosis.)

Medication She is on COCP, (Budd-Chiari sy)

PSH: Tonsillectomy & adenoidectomy at 5 years, appendicectomy at 14y. (Viral Hepatitis)

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Investigations 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, no

hemorrhoids or fissures.

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CPC 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 ??

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Major 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

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HBS:Common Clinical Presentations.

Why!


Pathological basis of signs and symptoms

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Sign 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 in

chronic biliary obstruction.Steatorrhoea Malabsorption of fat - (e.g. biliary obstruction)Pruritus Biliary obstruction resulting in bile salt accumulationAscites Hypoalbuminaemia, portal hypertension and secondary

hyperaldosteronism.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 altering

balance of neurotransmitters


Self 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..


Core 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.

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Thought is Powerful & Free! --William Shakespeare

Human mind is the most powerful weapon in the world. - e.g. Osama bin laden.

Great monuments & Great wars have always started in a human mind…!

Pathology of

Biliary & Pancreatic Disorders

Dr. Shashidhar Venkatesh MurthyA/Prof. & Head of Pathology

School of Medicine.

Anatomy:


Physiology: 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*.


Biliary 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)


Cholelithiasis: 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.


Risk 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 acid

metabolism• Hyperlipidemia syndromes

Pigment Stones: Race – Asians Age: early Jaundice / Infections

• Hemolysis syndromes• Biliary infections

• Inflammatory bowel disorders.

• Ileal resection or bypass.• Cystic fibrosis• Chronic Pancreatitis.

80% Idiopathic.75% in American Pima race.


Cholelithiasis: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. Monohydrate

crystals stone. Etiologic factors.

• Supersaturation – excess Cholesterol – crystals.• Calcium Microprecipitation - Nucleation.• Stasis - Mucous trap crystals – aggregation• Stone growth environment: infection, stasis, etc.


Cholelithiasis: Morphology & Types:

• Mixed Chol (Ca+Bile salt)* Multiple, faceted, yellow-grey.

• Rarely Pure cholesterol: Round spiky.• Bile Pigment stones (black/brown).

Infection / Jaundice. % Calcium = radio opaque.


Gallstones + Chronic Cholecystitis


Cholesterol (Pure) Gallstones, bleeding.

20Round, yellow, spiky, bleeding. Note thickened inflammed gall bladder.


Cholecystitis + gall stones Abscess.

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Pigment stones in Infection: Inflammed, thickened gall bladder filled with pus & black gall stones. Small stone is seen obstructing neck acute pain.

Adherent Omentum

Pus & Stones (black)Stone in the neck

UNSW Museum

Pigment stones in Hemolysis - Bilirubin


Gall stones in CBD

Stones in CBD

Stonees in GB

20% of mixed chol. stones and >50% of pigment stones are radio-opaque


Complications 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


Acute 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 severe

compromising blood supply. Green-black necrotic.

http://www.emedicine.com/MED/IMAGES/LARGE/2316OP4.JPG


Chronic Cholecystitis: Females. Recurrent / Chronic. Thick fibrotic wall. Thick bile – biliary gravel. Aschoff-Rokitansky sinuses –

diverticula - Due to increased luminal pressure (obstruction)

Diffuse infiltration by chronic inflammatory cells.

What we think, we become!

--Buddha


Neoplastic Disorders: (rare) Benign tumours:

• Bile duct adenoma, cystadenoma Malignant tumours:

• Adenocarcinoma Ducts lined by cuboidal to columnar mucin secreting cells separated by desmoplastic (fibrotic) stroma.

• Cholangiocarcinoma (Bile duct carcinoma)• Presents with Jaundice.

• Early spread with very poor prognosis.


Carcinoma 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.


Ca Bile duct: Cholangiocarcinoma: Adeno Carcinoma of

cholangiocytes. Thoratrast exposure? Increased incidence in

ulcerative colitis. Presents with obstructive

jaundice – early diagnosis. Intrahepatic or extrahepatic. Increasing incidence. ? toxin

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Living becomes a glorious experience only when there is tolerance and love. Willingness to compromise with other

people’s ways of living and cooperation. These make happy and

successful societies.

-- Baba.


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CPC 4.2.4 – HBS – Part 2

2 weeks later she present again to your GP practice.-Worsening abdominal pain - ‘The worst I ever had-It’s terrible, please do something’

Central, severe 9/10 constant, radiates to back. > 12 hours.

Associated with vomiting x 3 this morning. No haematemesis.

Bowels opened yesterday no blood mucus. Hasn’t passed urine in 8 hours. Doesn’t feel like drinking or eating.

‘I just want to lie here- Don’t make me move’ No Pale stools / dark urine. Hasn’t passed urine since

this morning.


History & 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 - ↑↑

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DD: Acute Abdomen, Pancreatitis, perforated peptic ulcer, appendicitis, diverticulitis,

“Outer world is the reflection of our inner world (thoughts)”

--Baba

Pathology of Pancreatic Disorders

Shashidhar Venkatesh MurthyAssoc. Prof & Head of Pathology


Introduction: 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...!


Anatomy Histology


Congenital Disorders:

Pancreatic Divisum:• Most common 3-10%• Failure of fetal duct union.• Congenital chronic

pancreatitis.

Cystic Fibrosis: • CFTR gene mutation

– thick secretions.

Annular Pancreas • 2nd part duodenum

obstruction.

Ectopic Pancreas • stomach and duodenum.


Acute Pancreatitis Acute Inflammation of pancreas leading to enzymatic

autodigestion & Hemorrhage, fat necrosis of surrounding tissue with systemic effects & multiorgan failure.

Release & activation of pancreatic enzymes. Defective inactivation 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.


Acute Pancreatitis:Pathogenesis of clinical features:

SUMMARY:Trypsin Kallikrein Thrombosis - NecrosisProtease Blood Vessel injury – Bleeding.

Lipase Fat necrosis Inflammation.


Grey Turner Sign - Cullen’s Sign

Severe

Mild


Acute Pancreatitis:a: The pancreas edematous and hemorrhagic (H). Pancreatic tissue becomes necrotic and may become semi-liquid.

b: fat necrosis seen as white spots (F) in mesenteric and retroperitoneal fat.

Histologically these foci are composed of necrotic adipose tissue, with adjacent reactive inflammation.


Acute Pancreatitis:

K K

Hemorrhage in the head of Pancreas with edema.CT Scan appearance

Duodenum

Acute Pancreatitis:

L K K

Hemorrhage in the head of Pancreas with edema.CT Scan appearance

A-StomachB-SpleenC-PeritoneumD-Pancreas

Duodenum


Acute Hemorrhagic Pancreatitis:

Duodenum

Head



Fat NecrosisAcini Necrosis

Hemorrhage

Normal Acini



Fat Necrosis

Acini Necrosis

Hemorrhage

Normal Acini


Acute Pancreatitis: Complications

Pancreatic cancer

At the center of your being you have the answer; you know who you are and you know

what you want!

Lao Tzu


CPC 2.7- Mr J.M. 51y, depression.

Mr J.M. 51 year old High School principal in Townsville.

Several months - stress, anxiety and depression. Treatment for this with anti depressants and

cognitive behavior therapy has been reasonably successful although he remains stressed.

makes an earlier appointment. ‘His trousers are hanging off him. No appetite. my

ankles have been a bit swollen recently. Could not walk…. Too tired…! Epigastric intermittent pain. ‘Bit dark urine … recently’


Chronic 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.


Chronic Pancreatitis:


Chronic fibrosing Pancreatitis:

Duodenum

Fibrosis

pancreas (P) is atrophic and replaced by rubbery, fibrous tissue, in which dilated ducts (D) are seen (Clinically by ERCP). In many cases calculi are present in the dilated ducts. In this example the duodenum is attached (A).


Chronic PancreatitisAtrophy, Fibrosis, Calcification

The pancreas is shrunken and fibrotic. The main duct is dilated and filled with calcified secretions (arrows).


Chronic Pancreatitis:

Dilated Ducts

Islets (endocrine)

Fibrosis

Note: Fibrosis replacing exocrine glands. 0nly ducts & Islets remain in late stage.

Inflam


Chronic Pancreatitis: Complications


Chronic Pancreatitis- PseuocystSpleen

Control your senses and you are beyond trouble.

Let them loose and you are beyond help…!

- - Lao Tzu


Pancreatic tumours:

Cysts:• True cysts • Polycystic diseases, MEN syndromes:• Von-hippel-lindau disease.

Adenoma:• Cystadenoma • Endocrine - Insulinoma, gastrinoma etc.

Carcinoma:• Adenocarcinoma – common.

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Pancreatic 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.


Pancreatic Cancer

Adenocarcinoma fibrosis stricture, Obstructive jaundice & weight loss.

Advanced disease at presentation. Poor prognosis. 85% only palliative care.

Palpable gallbladder + jaundice Ca Pan (Courvoisier's sign).

diabetes (due to ß cell destruction) Depression*, Migratory thrombophlebitis - Trousseau's


Ca. Pancreas : Pathogenesis


Pancreatic Cancer

Tumor

Head

Body Tail


Pancreatic Ca with fibrosis (Chronic pancreatitis)

Note: dysplastic glands infiltrating into fibro (spindle cells) myxoid (pale blue) stroma.

Malignant gl.Ca. Infiltration

Islet (normal)

Fibrous stroma

Ca PancreasClinical Features

Tumour marker:CEA & CA19–9 antigen

Trousseau syndrome


Ca Pancreas & Depression

Cancer pancreas has a reputation of being a deadly and often painful disease, with very poor prognosis.

Depression and anxiety occur more frequently Depression and anxiety may even precede symptoms or

knowledge of the diagnosis. The etiology of depression in patients with cancer of the

pancreas may be traced to more than the disease's symptoms.

Steve Jobs

A scholar who cherishes the love of comfort is not fit to be

deemed a scholar.

Lao Tzu

Give someone a fish and you feed him for a day.

Teach someone to fish and you feed him for a lifetime!

Lao Tzu


Acute Pancreatitis: Summary

Gross: Inflammation, Hemorrhages (red arrows) and chalky white areas of fat necrosis (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.


Cholesterolosis of gallbladder mucosa

Cholesterol filled Foamy macrophages in mucosal

folds

To attain knowledge, add things every day.

To attain wisdom, remove things every day.

Lao Tzu


Chronic Pancreatitis- Pseuocyst


5 A’s & SNAP

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• 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.motivational

interviewing • Assist: 6.NRT ? Bupropion(Zyban) 7.Support• Arrange: 8.referral to QUIT 9.follow up with the GP

SNAP Counseling: Smoking, Nutrition, Alcohol & Physical Activity.


Acute 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


“acute abdomen” Differential Diagnosis:

Acute Pancreatitis: medical emergency of the 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.


Acute 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 of

endocrine part. Alkaline phosphatase: mild elevation obstruction of

lower end of bile duct (gall stone) Bilirubin: mild direct Bil, oedema & obstruction of lower

end of bile duct.


CPC 4.2.7- May, 35y woman.

May, 35y, indigenous woman, lives in a remote Aboriginal 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.


CPC 4.2.7- May, 35y woman.

Differential diagnosis Perforated ulcer, Acute Gastro-enteritis,

/infarction, pancreatitis, gall bladder disease, peptic ulcer.• Heart – MI

• Lung – pleurisy, PE,

FBC (Hb 132, WCC 21.9), RFT (Na 136, urea 6.1, creatinine 0.07, Ca 1.8)

AXR, USG, CXR, ECG, Lipase- 2400 U/L Amylase* lipase *


Pancreatic Cancer

CBD

Pleomorphic glands (A) in a densely fibrotic (desmoplastic) stroma (B)

Section of head of pancreas showing an ill-defined mass in the pancreatic substance (arrowheads) and the green discoloration of the CBD due to obstruction of bile flow

AB


Silence…

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To the question "Who am I?" the only relevant answer is silence. You need to discard all answers in words, including "I am Nothing" or "I am the Cosmic Self" or "I am the Self" - and just stick to the question "Who am I?". All other answers are just thoughts. Thoughts can never be complete. Only Silence is complete.

Thoughts are not the goal in themselves. Their goal is Silence. When you ask the question "Who am I?" you get no answer, there is silence. 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 all your very nature.

- Sri Sri Ravishankar

Pathology of Biliary Disorders.

Health & Medicine

Transcript of Pathology of Biliary Disorders.