HEPATOBILIARY SYSTEM: Clinical Pathology Overview

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UNIT OUTLINE

Gall Bladder

1. Introduction to Gall Bladder and Gall Stones – 1 hour
2. Cholecystitis – 1 hour

Pancreas

3. Disorders of the Pancreas – 1 hour

Liver

4. Introduction, Manifestations, and Investigations – 2 hours
5. Circulatory Disturbances – 1 hour
6. Viral Hepatitis – 2 hours
7. Non-Viral Hepatitis – 2 hours
8. Alcoholic Liver Disease and Liver Cirrhosis – 1 hour
9. Metabolic Liver Disease and Tumours – 1 hour

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Lesson 1: Gall Bladder – Introduction and Gall Stones

Learning Outcomes:

1. Describe the structure and functions of the organs of the hepatobiliary system
2. Describe the pathology of gall stones
3. Investigate gall stones

Introduction – Hepatobiliary Anatomy and Physiology

• Components: Liver, pancreas, gallbladder, bile ducts

Gall Bladder Anatomy

• Gross Anatomy:
• Saclike, pear-shaped, 9 cm long
• Storage capacity: 35-100 ml
• Consists of fundus, body, neck
• Biliary Ducts and Tracts:
• Two hepatic ducts from liver unite to form common hepatic duct
• Joined by cystic duct to form common bile duct (CBD)
• CBD enters duodenum; 70% cases join with pancreatic duct (Ampulla of Vater)
• Histology:
• Mucosal, smooth muscle, perivascular, serosal layers

Functions:

1. Concentrates bile
2. Emulsifies fats in intestines
3. Facilitates cholesterol excretion

Bile Acids:

• Primary: Cholic acid, chenodeoxycholic acid
• Secondary: Deoxycholate, lithocholate

Pathophysiology of Gall Bladder Disorders:

• Congenital abnormalities
• Cholelithiasis (gall stones)
• Cholecystitis
• Obstruction of CBD
• Tumours

Gall Stones (Cholelithiasis)

• Formation: Cholesterol, bile pigments, calcium salts
• Risk Factors: 4F’s – Fat, Female, Fertile, Forty/Fifty
• Pathogenesis: Supersaturation, nucleation, microstone, gallstone

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Lesson 2: Cholecystitis

Learning Outcomes:

1. Describe the pathophysiology and pathology of cholecystitis
2. Investigate cholecystitis

Introduction

• Inflammation of gall bladder (acute, chronic, acute on chronic)

Acute Cholecystitis

• Mechanisms:
• Acute calculous: Obstruction, distension, inflammation
• Acute acalculous: Ischemia, severe conditions
• Pathology:
• Gross: Distended, tense, serosal congestion, lumen filled with pus
• Microscopy: Oedema, congestion, neutrophil infiltration, necrosis, ischemia

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Key Points for Study:

• Understand the anatomy and physiology of the hepatobiliary system.
• Familiarize with the types, formation, and risk factors of gall stones.
• Recognize the clinical features and complications of gall bladder disorders.
• Comprehend the pathophysiology of cholecystitis and its differentiation between calculous and acalculous types.
• Be prepared to investigate and diagnose hepatobiliary conditions through appropriate tests and imaging.

HEPATOBILIARY SYSTEM

Clinical Features

• Severe abdominal pain in the upper abdomen with features of peritoneal irritation (muscle guarding and hyperesthesia)
• Tender gall bladder (Murphy’s sign – right hypochondrial tenderness and rigidity, worse on inspiration)
• Possible palpable gall bladder, slight jaundice, fever, leukocytosis with neutrophilia, restlessness, pallor, sweating, and vomiting

Investigations

1. Plain abdominal radiograph (X-ray) for gallstones
2. Cholecystography
3. Ultrasonography for gallstones
4. Radionuclide biliary scintigraphy
5. Raised serum amylase
6. Full haemogram showing moderate leukocytosis
7. Possible bilirubinuria

Differential Diagnosis

1. Perforated peptic ulcer
2. Acute pancreatitis
3. Perforated cancer
4. Liver abscess
5. Retroperitoneal appendicitis
6. Right-sided pleurisy
7. Right basal pneumonia
8. Myocardial infarction
9. Renal colic

Complications

• Perforation, peritonitis, biliary fistula (cholecystenteric fistula), recurrent attacks, adhesions, gall bladder gangrene, cholangitis, empyema, mucocele

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CHRONIC CHOLECYSTITIS

Overview

• The most common gall bladder disease associated with gallstones
• May be insidious in onset or follow repeated attacks of acute cholecystitis

Aetiology & Pathogenesis

• Associated with gallstones and repeated acute cholecystitis

Pathology

Gross (Macroscopic) Appearance

• Generally contracted (small) but may be normal or enlarged; shrunken with marked fibrous thickening (Courvoisier’s sign – palpable gall bladder); thickened walls with an irregular lining, mucosal folds (intact, thickened or flattened and atrophied); lumen containing stones and fluid (clear, turbid, or purulent)

Microscopic Appearance (Histology)

• Thickened and congested mucosa; Rokitansky-Aschoff sinuses (gland-like structures formed as a result of penetration of epithelial down growths through the muscular layer); chronic inflammatory cells (lymphocytes, plasma cells, and macrophages); fibrosis

Complications

• Acute exacerbations (acute cholecystitis), pancreatitis, cholecyst-enteric fistula, gallstone ileus, ca gall bladder, mucocele, pyemia

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CHOLEDOCHOLITHIASIS AND ASCENDING CHOLANGITIS

Overview

• Choledocholithiasis: Presence of stones within the biliary tree
• Cholangitis: Bacterial infection of the bile ducts

Clinical Features

• Fever, chills, abdominal pain, and jaundice accompanied by acute inflammation of the wall of the bile ducts

Pathogenesis

• Obstruction of bile flow mainly due to stones in the biliary tract
• Common bacteria include enteric Gram-negative aerobes (E. coli, Klebsiella, Clostridium, Bacteroides, Enterobacter) and Group D streptococci

Investigations

• As acute cholecystitis

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DISORDERS OF THE PANCREAS

Learning Outcomes

1. Outline the anatomy and physiology of the pancreas
2. Outline the developmental abnormalities of the pancreas
3. Describe the pathology of pancreatitis
4. Investigate pancreatitis

Anatomy

Position

• Lies transverse within the posterior deep abdominal cavity across the upper lumbar vertebrae
• Head tucked into the loop of the duodenum with the tail reaching the hilus of the spleen
• Intimate contact with organs (stomach, duodenum, transverse colon, spleen, kidneys, and suprarenal glands) and blood vessels (aorta, vena cava, hepatic artery, portal vein, and splenic vessels)

Gross Anatomy

• The name pancreas is derived from the Greek word “ankreas” meaning “all flesh”
• Soft, lobulated, glandular organ with both exocrine and endocrine functions
• Divided into four parts – head, neck, body, and tail weighing 2-3 gm (neonates), 7 gm (first year), 40 gm (15 years), 70-150 gm in adults, and length 15-25 cm

Histology

• Secretory units are small glands called acini that join to form lobules and eventually lobes
• The acinar cells synthesize the pancreatic enzymes

Physiology

Exocrine

• Pancreatic juices contain enzymes, water, and electrolytes. There are at least 22 enzymes including proteolytic enzymes (elastase, amylases), trypsin, chymotrypsin, lipase, phospholipase, carboxypeptidase, cholesteristerase, ribonuclease, and deoxyribonuclease

Endocrine

• Islets of Langerhans secrete hormones
• Major cell types: Beta cells (70%) secrete insulin, alpha cells (20%) secrete glucagon, delta cells (5-10%) produce somatostatin (suppresses both insulin and glucagon release), pancreatic polypeptide cells (1-2%)
• Minor cell types: D1 cells elaborate vasoactive intestinal peptide (VIP) inducing glycogenolysis and hyperglycemia, enterochromaffin cells synthesize serotonin

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CONDITION OF THE PANCREAS

Overview

• Conditions include benign tumors, pancreatic cancer, cystic fibrosis, diabetes (covered in endocrine pathology), exocrine pancreatic insufficiency, hemosuccus pancreaticus, and pancreatitis (acute and chronic)

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DEVELOPMENTAL ANOMALIES

Overview

• Congenital anomalies include agenesis, hypoplasias, annular pancreas, and aberrant pancreas

Cystic Fibrosis

• Hereditary autosomal recessive disorder characterized by viscid secretions in all exocrine glands (mucoviscidosis) and increased concentration of electrolytes in eccrine organs
• Secretions obstruct passages resulting in fibrosis, affecting multiple organs and systems (pancreatic insufficiency, intestinal obstruction, steatorrhea, malnutrition, hepatic cirrhosis, and respiratory complications)

Pathology

Macroscopy

• Visible cysts, fat replacement of pancreatic tissues

Microscopy

• Architecture of pancreatic parenchyma maintained, increased interlobular fibrosis, atrophy of acinar ducts, rarely inflammation, fat necrosis, intact Islets of Langerhans

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PANCREATITIS

Introduction

• Pancreatitis is inflammation of the pancreas, which can be acute or chronic
• Diagnostic criteria include abdominal pain characteristic of acute pancreatitis, serum amylase and/or lipase ≥3 times the upper limit of normal, and characteristic findings of acute pancreatitis on CT scan

Classification

• Classified according to Marseilles, Cambridge, Revised Marseilles, Atlanta International Symposium (IAS), etiological, or pathological basis
• IAS (1992) clinical-based classification reflects on acute pancreatitis: mild acute pancreatitis and severe acute pancreatitis

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ACUTE PANCREATITIS

Definition

• Sudden inflammation of the pancreas associated with necrosis of intrahepatic fat and acini

Predisposing Factors

1. Biliary tract disease (gallstones, cholecystitis)
2. Excess alcohol intake
3. Abdominal surgery on the biliary tract, pancreas, and stomach
4. Trauma (abdominal injuries, stab wounds)
5. Metabolic disorders (hyperparathyroidism, hypervitaminosis D)
6. Infections (mumps, hepatitis, Coxsackie’s virus)
7. Drugs (thiazide diuretics, paracetamol overdose, high steroid doses)

Aetiology

• Alcoholism and gallstones are the most important causes of acute pancreatitis

Common Causes – Mnemonic “I GET SMASHED”

• I: Idiopathic
• G: Gallstones
• E: Ethanol (alcohol)
• T: Trauma
• S: Steroids
• M: Mumps (paramyxovirus), other viruses (Epstein-Barr virus, Cytomegalovirus)
• A: Autoimmune disease (Polyarteritis nodosa, Systemic lupus erythematosus)
• S: Scorpion sting (e.g., Tityus trinitatis), snake bites
• H: Hypercalcemia, hyperlipidemia/hypertriglyceridemia, hypothermia
• E: ERCP (Endoscopic Retrograde Cholangio-Pancreatography)
• D: Drugs (SAND – steroids & sulfonamides, azathioprine, NSAIDS, diuretics such as furosemide and thiazides, & didanosine), duodenal ulcers

Pathogenesis

• Occurs in three phases:

1. First phase: Premature activation of trypsin
2. Second phase: Activated trypsin causes inflammation within the pancreas
3. Third phase: Inflammation spreads to other organs (e.g., lungs – ARDS), mediated by cytokines and other inflammatory mediators

Pathophysiology

• Destruction of the pancreas due to liberation and activation of pancreatic enzymes

Enzyme Production

• Proteases such as trypsin and chymotrypsin cause proteolysis
• Lipases and phospholipids degrade lipids and membrane phospholipids
• Elastases destroy the elastic tissue of blood vessels

Activation of Pan

creatic Enzymes

• Activation is normally under the control of trypsin, and when disrupted, enzymes can autodigest the pancreas

Pathology

• Macroscopy: Swollen, edematous gland with fat necrosis and areas of hemorrhage
• Microscopy: Edema, fat necrosis, hemorrhage, neutrophilic infiltration, and necrotic pancreatic tissue

Clinical Features

• Sudden severe epigastric pain radiating to the back
• Nausea and vomiting
• Abdominal distension
• Fever and tachycardia
• Hypotension and shock in severe cases
• Cullen’s sign: periumbilical ecchymosis
• Grey-Turner’s sign: flank ecchymosis

Investigations

• Serum amylase and lipase (elevated)
• Liver function tests
• Complete blood count
• Serum calcium
• Ultrasound and CT scan

Complications

• Systemic: ARDS, renal failure, metabolic disturbances
• Local: Pancreatic necrosis, abscess, pseudocyst

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CHRONIC PANCREATITIS

Definition

• Prolonged inflammation of the pancreas resulting in irreversible structural damage and loss of function

Aetiology

• Chronic alcoholism, hereditary, idiopathic, tropical pancreatitis

Pathogenesis

• Chronic inflammation leads to fibrosis, calcification, and atrophy

Pathology

• Macroscopy: Firm gland with calcifications and fibrosis
• Microscopy: Loss of acinar cells, fibrosis, and chronic inflammatory cell infiltrate

Clinical Features

• Recurrent episodes of abdominal pain
• Steatorrhea and malabsorption
• Diabetes mellitus

Investigations

• Serum amylase and lipase (may be normal)
• Fecal elastase
• Imaging: Ultrasound, CT scan, MRI

Complications

• Pancreatic pseudocyst, pancreatic cancer, biliary obstruction, diabetes

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This summary captures the key points about hepatobiliary and pancreatic disorders, focusing on clinical features, investigations, differential diagnosis, complications, and specific conditions such as acute and chronic pancreatitis. Let me know if there’s anything more specific you need!