1 Pathophysiology of GIT II Exocrine pancreas Liver Biliary tract.
Exocrine pancreas
-
Upload
marytresa-roby -
Category
Documents
-
view
81 -
download
4
Transcript of Exocrine pancreas
THE PANCREAS
.
Anatomy
Pancreas – “all flesh” Transversely oriented retroperitoneal
organ Extending from “C”loop of duodenum to
the hilum of spleen Measures 20 cm in length Weighs 90gms in men,85gms in women.
3 parts
Head Body Tail
Pancreatic duct system
Highly variable. Main pancreatic duct –duct of Wirsung-
papilla of Vater. Accessory pancreatic duct –duct of
Santorini- minor papilla MPD merges with CBD to form ampulla of
Vater.
Embryology
From fusion of dorsal & ventral outpouchings of foregut.
Dorsal primordium- body,tail superior aspect of head & accessory duct.
Ventral primordium- inferior part of head, major duct.
Functional Anatomy
Complex lobulated organ Distinct exocrine & endocrine components Exocrine -80 to 85% of pancreas. Endocrine- 1 to 2% Exocrine-acinar cells & a series of ductules &
ducts Endocrine- about 1million clusters of cells- islets
of Langerhans
Histology
Acinar cells- pyramidally shaped epithelial cells radially oriented around a central lumen.
Basal portion-deeply basophilic-abundant ER. Supranuclear golgi complex Membrane bound zymogen granules-granular
eosinophilic appearance to the apices. Smaller ductules-lined by cuboidal cells-secrete fluid rich
in bicarbonate. Larger ducts-columnar cells –mucin-express cystic
fibrosis trans membrane conductance regulator
Physiology
Secretes 2 to 2.5 liters of bicarbonate rich fluid-digestive enzymes & proenzymes
Neural stimulation- vagus nerve Humoral factors-secretin &
cholecystokinin. Secretin-water & bicarbonate Cholecystokinin-digestive proenzymes
Proenzymes
Trypsinogen Chymotrypsinogen Procarboxypeptidase Proelastase Kallikreinogen Prophospholipase A & B
Enteropeptidase –cleaves trypsinogen to trypsin
Active enzymes
Amylase Lipase
Prevention of self digestion
Inactive proenzymes Sequestered in zymogen granules Activation requires duodenal enteropeptidase Trypsin inhibitors –SPINK 1- present in acinar cells Trypsin –critical self recognition site-allows trypsin to
inactivate itseif. Lysosomal hydrolases-degrade zymogen granules when
secretion is blocked Acinar cells –resistant to trypsin, chymotrypsin &
phospholipase A 20.
Pathology –exocrine pancreas
Congenital anomalies Acute pancreatitis Chronic pancreatitis Neoplasms
Congenital anomalies
Agenesis very rareassociated with severe malformations incompatible with lifeGermline mutations in homeodomain
transcription factor –IPF 1 gene on chromosome 13q 12.1
Pancreas divisum
Most common clinically significant anomaly. Incidence- 3 to 10% Failure of fusion of fetal duct system of dorsal &
ventral primordia. Bulk of the pancreas -dorsal duct & diminuitive
minor papilla. Main duct is very short Relative stenosis- predisposes to chronic
pancreatitis
Annular pancreas
Relatively uncommon condition Associated with other anomalies Band like ring of normal pancreatic tissue
completely encircling 2nd portion of duodenum May present early in life or in adults Signs & symptoms of duodenal obstruction.
Pancreas
Ectopic pancreas
Present in 2% of careful routine autopsies Favoured sites- stomach,duodenum jejunum,Meckel
diverticula & ileum. Few mms to cms in size & situated in the submucosa. Composed of normal appearing pancreatic acini &
glands ; occasionally islet cells. Usually incidental
sessile masscause pain from local inflammationmay incite mucosal bleedingislet cell tumor -2%
Acute pancreatitis
A group of reversible lesions Characterised by inflammation of the
pancreas. Ranging in severity from edema & fat
necrosis to parenchymal necrosis with severe hemorrhage.
Acute pancreatitis
Relatively common Incidence – 10 to 20 cases per 100,000
people annually. 80% cases are associated with either
biliary tract disease or alcoholism. M :F is 1:3 in biliary tract diseases & 6:1 in
alcoholism.
Etiologic factors
Metabolic
alcoholismhyperlipoprotinemiahypercalcemiadrugsgenetic
Mechanical
traumagall stonesperiampullary tumors,pancreas divisum,choledochoceles,parasites – Ascaris lumbricoides,Clonorchis sinensisiatrogenic injury-perioperative injury,endoscopic procedures(ERCP)
Etiologic factors
VascularshockathroembolismPAN,SLE,HSP
InfectiousMumpsCoxsackieMycoplasma pneumoniae
Drugs
Thiazide diuretics Azathioprine Estrogens Sulphonamides Furosemide Methyl dopa Pentamidine procainamide
Idiopathic
10 to 20% Genetic basis
Hereditary pancreatitis
Autosomal dominant Recurrent attacks of severe pancreatitis beginning in
childhood Caused by germline mutations in the cationic trypsin
gene-PRSS 1 Affects a site on the cationic trypsinogen molecule
essential for the inactivation of trypsin by trypsin itself. Trypsinogen & trypsin become resistant to inactivation
&abnormally active trypsin activates other digestive proenzymes –development of pancreatitis
Hereditory pancreatitis
Inherited homozygous inactivating mutations in the SPINK1 gene(serine protease inhibior,Kazal type1)
SPINK1 gene codes for a pancreatic secretory trypsin inhibitor which helps to prevent autodigestion of pancreas by activated trypsin.
Pathogenesis
Auto digestion of pancreatic tissue by inappropriately activated pancreatic enzymes.
Activation of trypsin is an important triggering event.
3 possible pathways
Pancreatic duct obstruction
Cholelithiasis,ampullary obstructionAccumulation of enzyme rich interstitial fluidLipase-local fat necrosisInjured tissues – proinflammatory cytokines-
IL-1B,IL-6, TNF, PAF, Sub-PLocal inflammtion & interstitial edema-
ischemic injury to acinar cells
Primary acinar cell injury
Viruses,drugs,alcohol,direct trauma Shock Release of intracellular proenzymes
&lysosomal hydrolases Activation of enzymes-acinar cell injury.
Defective intracellular transport
Metabolic injury,alcohol, duct obstruction Delivery of proenzymes to lysosomal
compartment Intracellular activation of enzymes Acinar cell injury
Activated enzymes
Lipase,phospholipase – fat necrosis Proteases – proteolysis Elastase - hemorrhage
Alcohol
Direct toxic effect on acinar cells Duct obstruction – protein rich secretion Sudden exacerbations of chronic
pancreatitis
Morphology
Basic alterations – microvascular leakage – edemafat necrosisacute inflammatory reactionproteolytic destruction of parenchymadestruction of blood vessels – interstitial hemorrhage
Acute interstitial pancreatitis
Mild form Interstitial edema,focal areas of fat
necrosis Released fatty acids + calcium – insoluble
salts
Acute necrotising pancreatitis
More severe form Necrosis of pancreatic tissue, hemorrhage Areas of red-black hemorrhage interspersed with
foci of yellow-white,chalky fat necrosis Foci of fat necrosis in extrapancreatic fat depots Peritoneal cavity – serous ,slightly turbid brown
tinged fluid with fat globules
Hemorrhagic pancreatitis
Most severe form Extensive parenchymal necrosis Diffuse hemorrhage
Clinical features
Abdominal pain – mild to severe Full blown Acute pancreatitis – medical
emergency – “acute abdomen” – constant & intense pain.
Systemic features – release of toxic enzymes,cytokines etc.
Lab findings
Marked elevation of s.amylase during 24hrs
Followed within 72 to 96 hours by a rising s.lipase level.
Hypocalcemia – if persistent –poor prognostic sign.
Diagnosis
Elevated s.amylase & lipase Direct visualisation of the enlarged
inflammed panceas by radiographic means
Exclusion of other causes of acute abdomen.
Complications
Systemic organ failure Shock ARDS ARF DIC Pancreatic abscess P.pseudocyst Duodenal obstruction
Management
“resting” the pancreas Supportive therapy
Chronic pancreatitis
Inflammation Destruction of exocrine parenchyma Fibrosis Destruction of endocrine parenchyma –
late stages.
Chronic vs acute pancreatitis
Irreversible impairment of pancreatic function
Causes
Long term alcohol abuse Long standing obstruction of pancreatic duct by
calculipseudocyststraumaneoplasmspancreas divisum
Tropical pancreatitis
Causes
Hereditary pancreatitis Idiopathic chronic pancreatitis – CFTR
related 40%-no cause.
Pathogenesis
Ductal obstruction by concretions-alcoholic pancreatitis
Toxic-metabolictoxins,alcohol – direct toxic effect on acinar cells
Oxidative stress – alcohol Necrosis – fibrosis in hereditary pancreatitis
repeated attacks of acute pancreatitis – perilobular fibrosis,duct distortion &altered secretions – loss of parenchyma & fibrosis
Chemokines IL-8 MCP-1 TGF-b PDGF
Morphology
Parenchymal fibrosis Reduced no & size of acini ,relative sparing of islets Variable dilatation of the ducts Chronic inflammatory infiltrate around lobules & ducts Interlobular & intralobular ducts – dilated,contain protein
plugs Ductal epithelium – atrophied or hyperplastic Ductal concretions
Morphology
Acinar cell loss – constant feature Islets of Langerhans embedded in
sclerotic tissue & may fuse Eventually islets also disappear Gross – gland is hard with extremely
dilated ducts &visible calcified concretions
Clinical features
Different presentationsrepeated attacks of moderately severe abd.painrecurrent attacks of mild painpersistent abd &back pain
Silent till pancreatic insufficiency & DM develop Recurrent attacks of jaundice or indigestion
Diagnosis
Visualisation of calcifications by CT or USG
Complications
Pseudocyst Malabsorption,steatorrhea Secondary DM Pancreatic carcinoma – 40% risk in
hereditary pancreatitis
GALL BLADDER