Pathophysiology of the
exocrine pancreas
Anatomy of the pancreas
Cell types in the pancreas
 Endocrine – islets of Langerhans
α-cells – producing glucagon
β-cells – producing insulin and
amylin
δ-cells – producing somatostatin
ε-cells – producing ghrelin
PP-cells – producing pancreatic
polypeptide
G-cells – producing gastrin
 Exocrine – acini and ducts
acinar (basophilic) cells –
producing pancreatic enzymes
(trypsin, amylase, lipase)
centroacinar cells –
producing HCO3
ductal
cells – producing HCO3
-
Exocrine pancreas in protein
digestion
 Proteases – are secreted in
inactive form: trypsinogen,
chymotrypsinogen
 Trypsinogen is converted into
trypsin by enterokinase in the
small intestine
 Trypsin then converts
chymotrypsinogen into
chymotrypsin
 Each enzyme then cleaves
peptidic bonds between
different aminoacids
 Both act inside the protein -
endopeptidases
Exocrine pancreas in lipid digestion
 Pancreatic lipase (LPS)
- converts TAG into monoacylglycerol and FFA
- acts together with bile acids, which emulsify lipids
 Lysophospholipase, Phospholipase A2
- cleave phospholipids
 Cholesterol esterase
- de-esterifies cholesterol and helps its transport into enterocytes
Exocrine pancreas and saccharide
digestion
 Pancreatic amylase (AMS-pancr.)
- catalyses cleavage of starch or glycogen into
oligosaccharides (dextrin, maltotriose, maltose)
- cleavage by both salivary and pancreatic AMS
represents the initial stage in saccharide digestion
- Its products are further cleaved by intestinal enzymes
(glucosidases, maltase) into monosaccharides, which are
transported into blood
Diseases of exocrine pancreas
 Congenital malformations
 Acute pancreatitis
 Chronic pancreatitis
 Cystic fibrosis
 Tumours
Congenital malformations
 During development,
pancreas is formed through
the fusion of ventral and
dorsal bud
 Ventral bud turns into most
of the head of pancreas,
while dorsal bud turns into its
body and tail
 Initially, they both have
separate ducts, in most
cases, the ducts are joint
together during development.
Ventral duct (duct of
Wirsung) drains most of
pancreas.
 Usually, it has common orifice
with biliary duct
Pancreas divisum
 In some cases, the
fusion of both buds is
incomplete
 Smaller dorsal duct is
sometimes incapable
to drain pancreatic
juice effectively
 The condition can
lead into repeated
acute pancreatitis
Annular pancreas
 In other cases, ventral bud can pinch the duodenum
during its abnormal rotation and fusion, causing vomiting
and duodenal ulcers
Acute pancreatitis
 Various factors lead into the damage of acinar cells
 Granules with trypsinogen are overpresented in cells and
trypsinogen can react with lysosomal enzymes
 The reaction can lead into conversion of a small amount
of trypsinogen into trypsin
 Trypsin can activate other enzymes (as chymotrypsin or
phospholipase A)
 This leads into the autodigestion of the pancreas and
consequent complications
Causes of acute pancreatitis
 Obstruction of pancreatic ducts (most often)
- obstruction of common biliary and pancreatic orifice
(ampulla Vateri) – usually together with icterus
- tumours
- pancreas divisum
 Alcoholic excess
 Metabolic causes (e.g.hypertriglyceridemia)
 Idiopatic
Manifestation of acute pancreatitis
Mild form
- interstitial oedema
- inflammation of
interstitium
Severe form
- necrosis
- haemorrhage
- necrosis of surrounding
tissue
- sepsis
- circulatory shock
- DIC
Clinical and laboratory findings
 Severe stomach ache (usually after alcohol
intake or fatty meal)
 Fever, CRP and leukocytes elevation
 Elevation of LPS, pancreatic AMS (within several
hours after onset
Late complications
Pancreas divisum...
A. Results from an abnormal rotation of the
ventral pancreatic bud
B. Leads into the hyperviscosity of pancreatic
juices
C. Manifests by obstructive icterus
D. Manifests by obstructive acute pancreatitis
without the icterus
E. Leads regularly to the ulcerations of upper
duodenum
Chronic pancreatitis
 Various causes, exact pathophysiology is not always
clear
 Chronic irritation of pancreas by alcohol or other
causes leads into chronic monocyte and lymfocyte
infiltration
 Occassional reaction of pancreatic proenzymes with
lysosome hydrolases (as in acute pancr.)
 Necrosis of acinar cells and subsequent fibrosis is
present
 In final stage, endocrine pancreas is also affected
Causes of chronic pancreatitis
 Abuse of alcohol (most often)
 Idiopatic
 Toxic or radiation damage
 Hereditary
- congenital anomalies (e.g. pancreas divisum)
- cystic fibrosis
- α-1 antitrypsin deficiency
 Acute pancreatitis
Development of chronic pancreatitis
Clinical finding
 Stomach ache (very variable)
 Diarrhoea, steatorrhoea
 Malabsorption
- vitamin carence
- hypoproteinemia with oedemas
 Secondary diabetes
 Obstruction of biliary duct with icterus
 Ascites (rare)
Chronic pancreatitis - diagnosis
 Pancreatic AMS or LPS are useless (elevated just
in acute exacerbations)
 Imaging methods: ultrasonography, CT, MR
 Secretin-CCK test (invasive, measures amylase,
trypsin and acidity in the duodenum)
 Secretin and CCK can be replaced by lipidsaccharide-protein
solution (but with lower
sensitivity and specifity)
Choose a suitable marker of
acute pancreatitis
A. Total amylase
B. α1-antitrypsin
C. Pancreatic alkaline phosphatase
D. Enterokinase
E. Lipase
Tumours of pancreas
 Exocrine: adenocarcinoma
- bad prognosis (5-years survival <10%)
- 90% of tumours are practically untreatable due to late diagnosis
 Endocrine: both benign or malign
- usually with endocrine activity
Cystic fibrosis (mucoviscidosis)
 Monogenic disease with autosomal recessive
inheritance
 Mutation in the gene for CFTR (Cystic Fibrosis
Transmembrane conductance Regulator)
 Its product is a chloride channel, present in most
tissues
 Gene for CFTR is located in 7q31.2. locus
 In Czech and most other European populations,
approximately 4% of population are carriers of
mutated allele
Various manifestations of CF
 The retention of chlorides leads into increased viscosity of
secretions
 In the sweat glands, chloride (and sodium) re-uptake is blocked
Cystic fibrosis in the pancreas
 The viscous secretion blocks pancreatic ducts
 This leads into chronic pancreatitis and malabsorption
 In late stages, the disease leats to total obstruction of
the ducts, fibrosis and atrophy
 Average life expectancy is less than 40 years