Download to read offline
![C Y S T I C F I B R O S I S
CF is the most common lethal genetic disease
that affects white populations (1 in 2000 live
births)
Characterized by abnormally viscid mucous
secretions that block airways & pancreatic
ducts & are responsible for:
– 1) Recurrent chronic pulmonary infections
– 2) Pancreatic insufficiency
High level of NaCl in sweat
Pathogenesis: primary defect in transport of
Cl
_
across epithelia. The cAMP-dependent Cl
_
channels (CF transmembrane conductance
regulator [CFTR]) are defective.](https://image.slidesharecdn.com/pathologyofpancreas-1-250811071852-4579b95b/75/Pathology-of-Pancreas-notes-based-on-robbins-6-2048.jpg)
Pathology of Pancreas- notes based on robbins
- 1. Pathology of the pancreas Dr.Wangari Wambugu
- 2. ANATOMY & HISTOLOGYOF THE P A N C R E A S 15 cm in length, 60-140 gm, consists of head, body & tail; pancreatic duct empty into duodenum or common bile duct Histologically, consists of 2 components: – 1) Exocrine: 80-85%, consists of numerous glands (acini) lined by columnar basophilic cells containing zymogen granules, which form lobules; ductal system Trypsin, chemotrypsin, aminopeptidase, amylase, lipase – 2) Endocrine: islets of Langerhans, which are invaded by capillaries. Islets consist of: 4 main cell types: B (insulin), A (glucagon), D (somatostatin), PP cells (pancreatic polypeptide) 2 minor cell types: D1 (VIP) & enterochromaffin cells (serotonin)
- 3. Pathology Congenital anomalies Diseases of the exocrine pancreas – Cystic fibrosis – Acute pancreatitis – Chronic pancreatitis – Pancreatic carcinoma
- 4. CONGENITAL ANOMALIES Agenesis:usually associated with widespread severe malformations that are incompatible with life Hypoplasia: both endocrine & exocrine elements may be involved Annular pancreas: pancreas head encircle duodenum & may cause obstruction Aberrant (ectopic) pancreas: 2%; mostly in stomach, duodenum, jejunum, Meckel’s diverticulum & ileum Ducts anomalies: duct of Wirsung may drain into common bile duct or an orifice high in the duodenum
- 6. C Y ST I C F I B R O S I S CF is the most common lethal genetic disease that affects white populations (1 in 2000 live births) Characterized by abnormally viscid mucous secretions that block airways & pancreatic ducts & are responsible for: – 1) Recurrent chronic pulmonary infections – 2) Pancreatic insufficiency High level of NaCl in sweat Pathogenesis: primary defect in transport of Cl _ across epithelia. The cAMP-dependent Cl _ channels (CF transmembrane conductance regulator [CFTR]) are defective.
- 7. C Y ST I C F I B R O S I S CF gene is located on chromosome 7 with up to 300 mutations identified in this gene so far. Pancreatic pathology: abnormalities are seen in 85% of patients: – mucus accumulation, – duct dilation & plugging, – exocrine gland atrophy. Islets usually spared. – Ducts may be converted into cysts separated only by islets of Langerhans & fibrous stroma (fibrocystic disease of pancreas) – Malabsorption syndrome: particularly fat – Squamous metaplasia of duct lining Meconium ileus, pulmonary problems Rx: gene therapy
- 8. ACUTE PANCREATITIS Inflammationof the pancreas, which is almost always associated with acinar cell injury A clinical & histologic spectrum of severity & duration Etiologic factors: – Metabolic: alcohol, hyperlipoproteinemia, hypercalcemia, drugs (e.g. thiazides), genetic – Mechanical: gallstones, traumatic & perioperative injury – Vascular: shock, atheroembolism, polyarteritis nodosa – Infections: Mumps, Coxsackie virus, Mycoplasma – Idiopathic : 10-20% ; ? Genetic basis
- 9. ACUTE PANCREATITIS Pathology: 4basic alterations: 1) Proteolytic destruction of pancreatic substance 2) Necrosis of blood vessels & interstitial hemorrhage 3) Fat necrosis by lipolytic enzymes 4) Associated acute inflammatory reaction – Pathologic lesions: Acute pancreatic necrosis Acute hemorrhagic pancreatitis Suppurative peritonitis Pancreatic pseudocysts
- 12. ACUTE PANCREATITIS Pathogenesis: –Autodigestion of pancreatic tissue by inappropriately activated pancreatic enzymes – Trypsin has a major role: Activates other proenzymes (proelastase , prophospholipase ) Converts prekallikrein to kallikrein (Kinin system) Hageman factor is activated – Mechanisms of pancreatic enzyme activation: Pancreatic duct obstruction Primary acinar cell injury Defective intracellular transport of proenzymes within acinar cells
- 14. ACUTE PANCREATITIS Clinicalfeatures: – Abdominal pain is the cardinal manifestation: epigastric, radiating to back, variable in severity – Shock: due to pancreatic hemorrhage & release of vasodilatory agents – Lab: serum amylase and lipase; Ca; bilirubin, glucose & glycosuria CT scan: inflammation, pseudocysts Px: severe cases have high mortality rate (20-40%) Death due to: 1) shock, 2) secondary abdominal sepsis, 3) adult respiratory distress syndrome
- 15. CHRONIC PANCREATITIS Repeatedbouts of mild to moderate pancreatic inflammation, with continued loss of pancreatic parenchyma & replacement by fibrous tissue Distinction from acute pancreatitis may be difficult; distinction is made if there is evidence of previous attacks Middle-aged men, mostly in alcoholics but may due to biliary tract disease, hyperlipoproteinemia & hypercalcemia; no apparent cause in 50% of cases Pathogenesis: – Protein hypersecretion from acinar cells – Precipitation of proteins forming ductal plugs – Plugs enlarge forming laminar aggregates
- 17. CHRONIC PANCREATITIS Pathology: –Hard organ with dilated ducts & calcified concretions – Fibrosis, chronic inflammatory cells, obstruction of ducts by protein plugs – Extensive atrophy of exocrine glands – Pseudocysts Clinical features: – Repeated attacks of abdominal pain or may be silent Dx: clinical suspicion, lab & CT Px: chronic disabling disease due to its major complications: pancreatic insufficiency & diabetes mellitus
- 19. PANCREATIC CARCINOMA Malignantepithelial neoplasm of exocrine portion of pancreas 5th most frequent cause of death from cancer Increasing in incidence in the West Peak incidence: 60 - 80 years Cause is unknown; more frequent in smokers Location: – Head of pancreas 60% – Body of pancreas 15% – Tail of pancreas 5% – Diffuse involvement 20%
- 20. PANCREATIC CARCINOMA Riskfactors – Smoking – Industrial exposure to β-Naphthylamine, benzidine – M>F – Genetic susceptibility
- 21. PANCREATIC CARCINOMA Grittygray hard masses Vast majority are adenocarcinomas, with poorly formed glands and densely fibrous stroma Carcinoma of pancreatic head: invasion of ampullary region with bile outflow obstruction, & distension of biliary tree Carcinoma of body & tail: no impingement on biliary tract & remain silent for longer periods Extends into retroperitoneal spaces, infiltrate nerves, abdominal organs & lymph nodes Distant metastasis to lungs, bone, ..
- 23. PANCREATIC CARCINOMA Clinicalfeatures: – Usually silent until its extension impinges on other structures – Pain is usually the first symptom – Obstructive jaundice – Trousseau’s syndrome: Migratory thrombophlebitis (phlebothrombosis) Lab: tumor markers, e.g. CEA, CA19-9 Ag are nonspecific Dx: CT scan & percutaneous biopsy Px: 1 year survival is 10%; 5 yr survival is 2.5%