1) Acute pancreatitis is an inflammation of the pancreas that results from digestive enzymes activating prematurely inside the pancreas. The two most common causes are alcohol abuse and gallstones. Symptoms include severe abdominal pain, nausea, vomiting, and elevated blood levels of pancreatic enzymes. Complications can include shock, respiratory failure, and infection. 2) Chronic pancreatitis is long-standing inflammation that destroys the pancreas over time, reducing its ability to produce digestive enzymes. It commonly results from recurrent acute pancreatitis, alcoholism, or gallstones. Symptoms include abdominal pain and digestive problems like steatorrhea from reduced enzyme production. 3) Both conditions involve inflammation and damage to the pancreas from premature

1. KAZAN STATE MEDICAL UNIVERSITY
PATHOPHYSIOLOGY DEPARTMENT
Selected gastrointestinal
diseases

2. ACUTE PANCREATITIS
A clinical syndrome resulting from acute inflammation and
destructive autodigestion of the pancreas and peripancreatic
tissues
Etiology
•many causes,
(but in none of them is the exact mechanism of damage to the gland clearly understood)
•in all there is escape of activated enzymes from the
ducts, leading to tissue injury, inflammation, necrosis, and in
some cases infection
•the two most common conditions are alcohol abuse and biliary
tract disease

3. Alcohol
•may have a direct toxic effect on pancreatic acinar cells
•causes inflammation of the sphincter of Oddi, leading to
retention of hydrolytic enzymes in the pancreatic duct and
acini
• alternatively, alcohol may cause decreased tone at the sphincter
of Oddi, predisposing to reflux of bile or duodenal contents into
the pancreatic duct, leading to parenchymal injury

4. Biliary tract disease (more common in women)
•obstruction of the common bile duct and the main pancreatic
duct when a gallstone becomes lodged at the ampulla of Vater
• reflux of bile or duodenal contents into the pancreatic duct leads
to parenchymal injury
• bacterial toxins or free bile acids travel via lymphatics from the
gallbladder to the pancreas, giving rise to inflammation

5. Infectious agents
•viruses
Mumps virus,
Hepatitis A, B, and C virus,
Cytomegalovirus
Adenovirus,
Epstein-Barr virus,
Human immunodeficiency virus
•bacteria
Salmonella typhi
Mycoplasma pneumoniae,
Group A streptococci

6. •Blunt or penetrating trauma and other injuries
•Following surgical procedures near the pancreas (duodenal
stump syndrome; pancreatic tail syndrome following splenectomy)
•Infarction of the pancreas resulting from occlusion of vessels
supplying the gland
(Atheromatous thrombosis or embolism…)
•Shock may cause decreased perfusion, resulting in cellular
degeneration

7. Metabolic
1. Hyperlipidemia, hypertriglyceridemia
• free fatty acids liberated by the action of pancreatic lipase
cause gland inflammation and injury
2. Hypercalcemia (eg, hyperparathyroidism)
the high plasma calcium concentration may cause
• calcium to precipitate in the pancreatic duct, leading to
obstruction
• may stimulate activation of trypsinogen in the pancreatic duct
3. Uremia

8. Clinical Manifestations
The extent of damage is highly variable from patient to
patient, as are the clinical manifestations, ranging from
•mild episodes of epigastric pain, nausea, and vomiting
•to severe (sometimes fatal) episodes of peritonitis, shock,
respiratory failure

9. Pain:
Patients usually present with severe, constant, deep epigastric pain, due to :
•Stretching of the pancreatic capsule:
•distended ductules and parenchymal edema,
•inflammatory exudate,
•digested proteins and lipids,
•hemorrhage
• In addition, these materials may be out of the parenchyma into
the retroperitoneum, where they irritate retroperitoneal and
peritoneal sensory nerve endings and produce intense back and
flank pain
•The clinical findings of generalized peritonitis may follow

10. Nausea, vomiting, and Ileus:
• Stretching of the pancreatic capsule may produce nausea and
vomiting
•Abdominal pain,
•peritoneal irritation,
•electrolyte imbalance (especially hypokalemia)
•may cause a paralytic ileus - the intestinal musculature is
paralyzed while the intestinal lumen is not obstructed
•with marked abdominal distention
•if gastric motility is inhibited and the gastroesophageal sphincter is relaxed,
there may be emesis
Both small and large bowel often
dilate during an acute attack
Sometimes only a localized segment
dilates

11. Fever:
Mechanism involves:
•The extensive tissue injury, inflammation, and necrosis
•the release of endogenous pyrogens (IL-1, IL-6, TNF) from
polymorphonuclear leukocytes into the circulation
In most cases fever does not indicate a bacterial infection
•However, persistent fever, spiking temperatures to 40 °C or
more—may be the result of infectious complications - pancreatic
abscess or ascending cholangitis

12. Shock:
Hypovolemia, hypotension, and shock may occur as a result of:
•massive exudation of plasma into the retroperitoneal space and
from accumulation of fluid in the gut due to ileus —>Hypovolemia
•release of kinins into the general circulation —> Hypotension,
shock
•activation of the proteolytic enzyme kallikrein results in peripheral vasodilation via
liberation of the vasoactive peptides, bradykinin and kallidin
•vasodilation causes the pulse rate to rise and the blood pressure
to fall
• Decreased intravascular volume combined with the hypotension may lead to
myocardial and cerebral ischemia, respiratory failure, and decreased urinary output or
renal failure due to acute tubular necrosis

13. Elevated enzymes levels in plasma:
•The cardinal laboratory finding is elevation of the serum amylase
level, often up to 10-20 times normal
• The sensitivity of the serum amylase for acute pancreatitis is
estimated to be 70-95%, meaning that 5-30% of patients with
acute pancreatitis have normal or minimally elevated serum
amylase values
•In addition, the specificity of the test is considerably lower
•An elevated serum amylase can be found in a variety of other conditions

14. •The pancreas and salivary glands have much higher
concentrations of amylase than any other organs and contribute
almost all of the serum amylase activity in normal persons
• Hyperamylasemia can result from either an increased rate of
entry or a decreased metabolic clearance of amylase from the
circulation
•Pancreatic hyperamylasemia results from injuries to the pancreas
•Injuries to the bowel wall (infarction or perforation) cause
pancreatic hyperamylasemia due to enhanced absorption of
amylase from the intestinal lumen

15. Salivary hyperamylasemia is observed in salivary gland diseases
(parotitis)
Hyperamylasemia can also result from decreased metabolic
clearance of amylase due to renal failure
Patients with marked elevations of serum amylase (more than 3
times the upper limit of normal) usually have acute pancreatitis
Patients with lesser elevations of serum amylase often have other
conditions
The serum lipase measurement is more specific for acute
pancreatitis

16. Coagulopathy:
Tissue factor expression during proteolysis may cause activation
of the plasma coagulation cascade and may lead to disseminated
intravascular coagulation (DIC)
Hypercoagulability of the blood is thought to be due to elevated
concentrations of several coagulation factors, including factor VIII,
fibrinogen, and factor V
Clinically affected patients may present with hemorrhagic discoloration
(purpura) in the subcutaneous tissues around the umbilicus (Cullen's sign) or of
the flanks (Grey Turner's sign)
Grey Turner's sign reflects the retroperitoneal hemorrhage, or bleeding behind
the peritoneum, which is a lining of the abdominal cavity.

17. Pleuropulmonary Complications:
Pleuropulmonary complications include
•pleural effusion,
•pulmonary edema,
•respiratory failure - acute respiratory distress syndrome [ARDS]
•The effusion may be secondary to a direct effect of the inflamed, swollen
pancreas on the pleura abutting the diaphragm or to tracking of exudative fluid
from the pancreatic bed retroperitoneally into the pleural cavity through defects
in the diaphragm
•The pleural fluid is an exudate with high protein, LDH, and
amylase levels

18. •The effusion may contribute to segmental atelectasis of the
lower lobes, leading to ventilation/perfusion mismatch and
hypoxia
•Pulmonary edema is attributed to the effects of circulating
activated proteolytic enzymes on the pulmonary capillaries,
leading to transudation of fluid into the alveoli
•The most dangerous pulmonary complication is the development
of ARDS.
•This is most often seen 3-7 days after the onset of severe
hemorrhagic pancreatitis and is thought to be related to
hypotension ("shock lung")

19. Jaundice:
Jaundice and bilirubinuria occur in about one-fifth of patients with acute
pancreatitis
•A gallstone underlying the pancreatitis may cause transient
common bile duct obstruction
•Partial obstruction of the common bile duct may also
result from swelling of the head of the pancreas
•In other cases, more protracted and severe jaundice may result
from compression of the common bile duct by inflammatory
pseudocysts, non-epithelium-lined cavities that contain plasma,
blood, pus, and pancreatic juice

20. Hypocalcemia:
• Lipolysis of the peripancreatic, retroperitoneal, and mesenteric
fat releases free fatty acids that combine with ionized calcium to
form soaps
Severe hypocalcemia is clinically manifested by tetany, stupor,
seizures, and even coma
Hyperkalemia and Hypokalemia:
•In the initial phase - tissue necrosis causes release of potassium
into the circulation
•Combined with hypovolemia and acidosis, this results in
hyperkalemia
Later, the fluid repletion and correction of acidosis, the serum potassium may
fall to dangerously low levels

21. Acidosis:
•The acidosis is primarily a lactic acidosis resulting from
hypotension and shock
• With extensive pancreatic necrosis and hemorrhage, there may
be destruction or dysfunction of the pancreatic islets,
•causing deficient insulin production and acute diabetic
ketoacidosis
•Hyperglycemia is seen in about 25% of patients and transient
glycosuria is seen in about 10%

22. Inflammatory pseudocysts - non-epithelium-lined cavities that contain
plasma, blood, pus and pancreatic juice
• Some acini continue to secrete pancreatic juice,
• It is unable to drain normally, collects,
forming the pseudocysts
The cyst may grow progressively and cause
•compression of nearby structures –
• the portal vein (producing portal hypertension),
• common bile duct (producing jaundice or cholangitis),
• gut (producing gastric outlet or bowel obstruction)
With direct connection of pseudocysts and peritoneal cavity,
pancreatic ascites develops

23. Chronic pancreatitis
Is a continuous inflammatory disease of the pancreas
characterized by irreversible structural changes that
typically cause pain and permanent loss of function
In chronic pancreatitis, there is
•chronic inflammation of the parenchyma,
•leading to progressive destruction of the acini,
•stenosis and dilation of the ductules,
•fibrosis of the gland

24. Chronic pancreatitis can result from
• recurrent attacks of acute pancreatitis
• chronic alcoholism
• biliary tract stones
More rare causes include
•Hyperparathyroidism
•Hyperlipidemia
•Trauma
•Malnutrition
•In many cases, no cause can be identified

25. •Those are secreted in the bile
•The bile is refluxed into the pancreatic ducts and causes
oxidative damage at the level of the acinar and ductile cells
•Chronic exposure to oxidative stress leads to fibrosis
Pathogenesis of Chronic
Pancreatitis
The oxidative stress
hypothesis
•Oxidized by-products (free
radicals) are generated within
the hepatocytes

26. Accumulation of stones within the acinar cell complex produces
ulceration and inflammation of the ductules
Ductular obstruction from epithelial inflammation and the stones
themselves leads to atrophy, exocrine insufficiency, and fibrosis.
The stone and duct-obstruction theory.
In predisposed individuals,
pancreatic fluid is
lithogenic,
leading to protein plug and
stone formation

27. • The healing phase of acute pancreatitis involves collagen
deposition in the affected periductal areas
• Extrinsic compression of the ducts by collagen obstructs the
acinar cell complex
• Worsening obstruction results in acinar cell atrophy, stasis,
and secondary stone formation
The necrosis-fibrosis theory
An episode of acute pancreatitis
produces an acute inflammatory cell
infiltrate
in the periductal areas

28. In at-risk individuals the pancreatic acinar cells are under
stimulation by alcohol, oxidative stress, and other insults
Through unregulated trypsin activation, the first episode
of acute pancreatitis occurs (sentinel event)
The sentinel event produces a massive inflammatory
response by pro-inflammatory cells (neutrophils,
lymphocytes, etc.). Cytokines (TGF-b, TNF-a, IL-6…) are
released
The attraction and activation of pro-fibrotic cells,
including stellate cells constitute the late phase of acute
pancreatitis
If inciting factors (alcohol and oxidative stress) are
removed, the pancreas heals to its normal state
If the acinar cells continue to secrete cytokines in
response to oxidative stress, alcohol use, or other insults,
activated stellate cells respond to those signals
The sentinel acute pancreatitis (SAPE) hypothesis
The stellate cells are stimulated to deposit collagen, leading to periacinar
fibrosis

29. Chronic pancreatitis is characterized by
•scarring and shrinkage of the pancreas due to fibrosis and
atrophy of acini
•ductal distortions, and the presence of intraductal calculi
•the process may be localized, most
often involving the head and body of the
gland
•or it may be diffuse
•the gland may be rock hard as a result
of diffuse sclerosis and calcification

30. The major symptom is severe abdominal pain (either constant
or intermittent)
The pain is thought to derive either from:
•dilation of the duct system, causing ductal and parenchymal
hypertension,
•or from inflammation of the parenchyma, causing pancreatic
ischemia
Patients may have recurrent attacks of severe abdominal pain,
vomiting, and elevation of serum amylase (chronic relapsing
pancreatitis)

31. Impairment of exocrine function is manifested by pancreatic
insufficiency
Failure to secrete pancreatic juice (pancreatic lipase) results in
•maldigestion and malabsorbtion of fat (steatorrhea)
•fat-soluble vitamins (A, D, E, K)
•in weight loss
Other enzymes in gastric and intestinal juice can usually
compensate for pancreatic amylase and trypsin loss
Thus, patients with pancreatic insufficiency seldom present with
maldigestion of carbohydrate and protein

32. • Normally, the activities of the various pancreatic enzymes
decrease during their passage from the duodenum to the terminal
ileum.
• However, the degradation rales of individual enzymes vary,
with lipase activity lost most rapidly and protease and amylase
activity lost more slowly.
• Lipase activity is usually destroyed by proteolysis, mainly by the
action of chymotrypsin.
• This mechanism persists in patients with pancreatic insufficiency,
helping to explain why fat malabsorption develops earlier than
protein or starch malabsorption.

33. •While the steatorrhea is mostly caused by the deficiency of
pancreatic lipase,
•The absence of pancreatic bicarbonate secretion also contributes
to its occurrence
•Without bicarbonate, acidic chyme from the stomach inhibits the
activity of pancreatic lipase
•And causes the precipitation of bile salts
• Deficiency of bile salts in turn causes failure of micelle formation
and interference with fat absorption

34. Exocrine pancreatic function can be estimated by the
CCK-secretin test
In this test, measurements are made of
• pancreatic juice volume,
• amylase output,
• bicarbonate concentration
1) in the basal state,
2) 30 minutes after intravenous injection of CCK,
3) 60 minutes after intravenous administration of secretin

35. Endocrine dysfunction produces
Hyperglicemia,
Glycosuria,
Frank diabetes mellitus in approximately 30-40% of
cases of longstanding chronic pancreatitis

36. Sclerosing pancreatitis, involving the head of the pancreas,
• leads to obstruction of the common bile and pancreatic
ducts
• common bile duct obstruction results in
• profound and persistent jaundice, resembling that produced
by pancreatic carcinoma