Pancreas

Question 1

The adult pancreas is a transversely oriented retroperitoneal organ extending from the “C” loop
of the duodenum to the hilum of the spleen ( Fig. 19-1 ). On average, the pancreas measures
_____________ in men and 85 gm in women. [1] The vasculature adjacent to
the pancreas can be used to separate the pancreas into four parts: the head, neck, body, and
tail.

Answer 1

20 cm in length and weighs 90 gm

Question 2

The pancreatic duct system is highly variable. The main pancreatic duct, also known as the ____________most commonly drains into the duodenum at the papilla of Vater,

Answer 2

duct of Wirsung,

Question 3

whereas the accessory pancreatic duct, also known as the ___________, most often drains into the duodenum through a separate minor papilla approximately 2 cm cephalad (proximal) to the major papilla of Vater ( Fig. 19-1A ).

Answer 3

duct of Santorini

Question 4

In most adults the main pancreatic duct joins the common bile duct proximal to the papilla of Vater, thus creating the________, a common channel for biliary and pancreatic drainage. This ductal architecture can differ significantly from person to person.

Answer 4

ampulla of Vater

Question 5

The pancreas arises from the fusion of )_____________, which fuse to form a single organ. [2,] [3] The majority of the gland, including the body, the tail, the superior/anterior aspect of the head, and the accessory duct of Santorini, is derived from the ________

Answer 5

dorsal and ventral outpouchings of the foregut

dorsal primordium.

Question 6

Although the organ gets its name from the Greek pankreas, meaning “all flesh,” the pancreas is, in fact, a complex lobulated organ with distinct exocrine and endocrine components.

The __________- which produces digestive enzymes, constitutes 80% to 85% of the pancreas.

The endocrine portion is composed of about 1 million clusters of cells, the islets of Langerhans. The islet cells secrete insulin, glucagon, and somatostatin and constitute only 1% to 2% of the organ. Diseases of the endocrine pancreas are described in detail in Chapter 24 .

Answer 6

exocrine portion,

Question 7

The exocrine pancreas is composed of __________which produce the enzymes needed for digestion, and a series of ductules and ducts that convey secretions to the duodenum.

Answer 7

acinar cells,

Question 8

__________are pyramidally shaped epithelial cells that are radially oriented around a central lumen ( Fig. 19-2 ). Acinar cells contain membrane-bound zymogen granules rich in digestive enzymes.

Answer 8

[1] Acinar cells

Question 9

The pancreas secretes its exocrine products as enzymatically______-.

Answer 9

inert proenzymes

Question 10

The inert proactive enzyme secreted by the exocrine pancreas are:

Answer 10

They include

trypsinogen,

chymotrypsinogen,

procarboxypeptidase,

proelastase, kallikreinogen, and

prophospholipase A and B. [1]

Question 11

Self-digestion of pancreatic tissue is prevented by several mechanisms:

Answer 11

1. The majority of the enzymes are synthesized as inactive proenzymes (with the exception of amylase and lipase).
2. The enzymes are sequestered in membrane-bound zymogen granules in the acinar cells.
3. • Activation of proenzymes requires conversion of inactive trypsinogen to active trypsin by duodenal enteropeptidase (enterokinase). Trypsin cleaves proenzymes to yield products such as chymotrypsin, elastases, and phospholipases.
4. • Trypsin inhibitors including serine protease inhibitor Kazal type l (SPINK1, also known as pancreatic secretory trypsin inhibitor, PSTI) are present within acinar and ductal secretions.
5. • Acinar cells are remarkably resistant to the action of trypsin, chymotrypsin, and The majority of the enzymes are synthesized as inactive proenzymes (with the exception
   of amylase and lipase).
   • The enzymes are sequestered in membrane-bound zymogen granules in the acinar
   cells.
   • Activation of proenzymes requires conversion of inactive trypsinogen to active trypsin by
   duodenal enteropeptidase (enterokinase). Trypsin cleaves proenzymes to yield
   products such as chymotrypsin, elastases, and phospholipases.
   • Trypsin inhibitors including serine protease inhibitor Kazal type l (SPINK1, also known as
   pancreatic secretory trypsin inhibitor, PSTI) are present within acinar and ductal
   secretions.
   • Acinar cells are remarkably resistant to the action of trypsin, chymotrypsin, and

Question 12

The most significant disorders of the exocrine pancreas include

Answer 12

cystic fibrosis,

congenital anomalies,

acute and chronic pancreatitis,

pseudocysts, and neoplasms

. Cystic fibrosis is discussed in detail in Chapter 10 .

Question 13

Congenital Anomalies

Answer 13

Agenesis

Annular pancreas

Ectopic Pancreas

Pancreas Divisum

Question 14

The complex process by which the dorsal and ventral pancreatic primordia fuse during pancreatic development frequently gives rise to ________. [3] Most of these do not directly cause disease; however, such variations, especially in ductal anatomy, may present particular problems to endoscopists and surgeons.

For example, failure to recognize aberrant ductal anatomy may lead to the inadvertent ligation of a pancreatic duct during surgery, causing serious sequelae such as pancreatitis.

Answer 14

congenital variations in pancreatic anatomy

Question 15

Very rarely the pancreas may be totally absent (agenesis), a condition **associated with other severe malformations that are usually incompatible with life. **

Answer 15

AGENESIS

Question 16

___________-encodes a transcription factor critical for the development of the pancreas. [3] Homozygous PDX1 mutations on chromosome 13q12.1 have been reported in a person with pancreatic agenesis

Answer 16

PDX1 (pancreatic and duodenal homeobox-1 gene)

Question 17

______________ is the most common congenital anomaly of the pancreas, with an incidence of 3% to 10%. [4]

This anomaly is caused by a failure of fusion of the fetal duct systems of the dorsal and ventral pancreatic primordia.

[4] As a result, the bulk of the pancreas (formed by the dorsal pancreatic primordium) drains through the dorsal pancreatic duct and the small-caliber minor papilla (see Fig. 19-1B ). [4]

The duct of Wirsung in persons with this condition, normally the main pancreatic duct, is very short (1 to 2 cm) and drains only a small portion of the head of the gland through the larger caliber major papilla of Vater.

Answer 17

PANCREAS DIVISUM

Note:

Although controversy exists about the
clinical significance of pancreatic divisum, it has been suggested that the relative stenosis
caused by the bulk of the pancreatic secretions passing through the minor papilla predisposes
individuals to the development of chronic pancreatitis.

Question 18

__________ is a band-like ring of normal pancreatic tissue that completely encircles the second portion of the duodenum. This is often associated with other congenital anomalies and may present early in life or in adults with signs and symptoms of duodenal obstruction such as gastric distention and vomiting.

Answer 18

ANNULAR PANCREAS

Annular pancreas

Question 19

___________is found in about **2% of careful routine postmortem examinations. **

Answer 19

ECTOPIC PANCREAS

ECTOPIC PANCREAS Aberrantly situated, or ectopic, pancreatic tissue

Question 21

The favored sites for ectopia are the ________________________. [4] These embryologic rests are a few millimeters to centimeters in size and are located in the submucosa. Histologic examination reveals that they are composed of normal-appearing pancreatic acini, glands, and sometimes islets of Langerhans. Though usually incidental, may cause pain from localized inflammation, or, rarely, may incite mucosal bleeding.

Approximately 2% of islet cell neoplasms ( Chapter 24 ) arise in ectopic pancreatic tissue. The pathogenesis of ectopic pancreas has not been established.

Answer 21

stomach and duodenum, followed by the jejunum, Meckel diverticula, and ileum

Question 22

___________is inflammation in the pancreas associated with injury to the exocrine parenchyma. The clinical manifestations range in severity from a mild, self-limited disease to a lifethreatening acute inflammatory process, and the duration of the disease can range from a transient attack to a permanent loss of function. [7,] [8]

Answer 22

Pancreatitis

Question 23

In ___________-the gland can return to normal if the underlying cause of the pancreatitis is removed. [9,] [10]

Answer 23

acute pancreatitis

Question 24

By contrast, chronic pancreatitis is defined by the _______of exocrine pancreatic

Answer 24

irreversible loss

Question 25

__________ is reversible pancreatic parenchymal injury associated with inflammation. Acute pancreatitis is relatively common, with an annual incidence rate in Western countries of 10 to 20 cases per 100,000 people.

Answer 25

ACUTE PANCREATITIS

Question 26

_____________and __________ account for approximately 80% of cases in Western countries ( Table 19-1 ). [8] [9] [10] [12]

Answer 26

Biliary tract disease and alcoholism

Question 27

__________ are present in 35% to 60% of cases of acute pancreatitis, and about 5% of patients with gallstones develop pancreatitis. The proportion of cases of acute pancreatitis caused by excessive alcohol intake varies from 65% in the United States to 20% in Sweden to 5% or less in southern France and the United Kingdom. [13] The male-to-female ratio is 1 : 3 in the group with biliary tract disease and 6 : 1 in those with alcoholism.

Answer 27

Gallstones

Question 28

TABLE 19-1 – Etiologic Factors in Acute Pancreatitis

METABOLIC

Answer 28

METABOLIC
Alcoholism
Hyperlipoproteinemia
Hypercalcemia
Drugs (e.g.,
azathioprine)

Question 29

TABLE 19-1 – Etiologic Factors in Acute Pancreatitis

Genetics

Answer 29

GENETIC
Mutations in the cationic trypsinogen (PRSS1) and trypsin inhibitor (SPINK1) genes

Question 30

TABLE 19-1 – Etiologic Factors in Acute Pancreatitis

MECHANICAL

Answer 30

Gallstones

Trauma

Iatrogenic injury

Operative injury

Endoscopic procedures with dye injection

Question 31

TABLE 19-1 – Etiologic Factors in Acute Pancreatitis

VASCULAR

Answer 31

Shock

Atheroembolism

Vasculitis

Question 32

TABLE 19-1 – Etiologic Factors in Acute Pancreatitis

INFECTIOUS

Answer 32

Mumps

Question 33

Less common causes of acute pancreatitis include the following:

Answer 33

1. • Obstruction of the pancreatic duct system. Reasons for obstruction other than gallstones include periampullary neoplasms (such as pancreatic cancer), pancreas divisum (although its role is controversial), choledochoceles (congenital cystic dilatation of the common bile duct), biliary “sludge,” and parasites (particularly the Ascaris lumbricoides and Clonorchis sinensis organisms). [10,] [14] • Medications. More than 85 drugs have been implicated. These include furosemide, azathioprine, 2′,3′-dideoxyinosine, estrogens, and many others. [10,] [15]
2. • Infections, including mumps, can lead to acute pancreatitis.
3. • Metabolic disorders, such as hypertriglyceridemia, hyperparathyroidism, and other hypercalcemic states.
4. • Ischemic injury from shock, vascular thrombosis, embolism, and vasculitis.
5. • Trauma. Both blunt abdominal trauma and iatrogenic injury during surgery or endoscopic retrograde cholangiopancreatography
6. . • Inherited alterations in genes encoding pancreatic enzymes and their inhibitors, including germline mutations in the cationic trypsinogen (PRSS1) and trypsin inhibitor (SPINK1) genes. [16] [17] [18] [19] These are discussed below.

Question 34

Obstruction of the pancreatic duct system. Reasons for obstruction other than gallstones include__________-.

Answer 34

periampullary neoplasms (such as pancreatic cancer), pancreas divisum (although its role is controversial), choledochoceles (congenital cystic dilatation of the common bile duct),

biliary “sludge,” and

parasites (particularly the Ascaris lumbricoides and Clonorchis sinensis organisms)

Question 35

Metabolic disorders, such as

Answer 35

• hypertriglyceridemia,
• hyperparathyroidism, and other

hypercalcemic states.

Question 36

Notably, 10% to 20% of individuals with acute pancreatitis have no known associated processes. Although this condition is currently termed idiopathic, a growing body of evidence suggests that some of these cases actually have a genetic basis.

Answer 36

Hereditary Pancreatitis.

Question 37

The genetic alterations associated with the development of pancreatitis therefore deserve special note. [17] Hereditary pancreatitis is characterized by ______________. [16,] [17]

Most cases are caused by germline (inherited) mutations in the cationic trypsinogen gene (also known as PRSS1). [16] These mutations abrogate a critical fail-safe mechanism by altering a site on the cationic trypsinogen molecule that is essential for the cleavage (inactivation) of trypsin by trypsin itself. [17] When this site is mutated, trypsin becomes resistant to cleavage by another trypsin molecule, and if a small amount of this tryspin is inappropriately activated in the pancreas, it can activate other digestive proenzymes, resulting in the development of pancreatitis.

Answer 37

recurrent attacks of severe pancreatitis usually beginning in childhood

Question 38

Only______________- mutated allele is required for cleavageresistant trypsin to be produced; thus, this form of hereditary pancreatitis has an autosomal dominant mode of inheritance.

Answer 38

one

Question 39

The serine protease inhibitor ____________- gene codes for a pancreatic secretory trypsin inhibitor that, as the name suggests, inhibits trypsin activity, helping to prevent the autodigestion of the pancreas by activated trypsin. [17] As one might suspect, inherited inactivating mutations in this gene can also lead to the development of pancreatitis. This form of hereditary pancreatitis has an autosomal recessive mode of inheritance, as both alleles must be inactivated.

Answer 39

Kazal type 1 (SPINK1)

Question 40

Morphology. The morphology of acute pancreatitis ranges from trivial inflammation and edema to severe extensive necrosis and hemorrhage.

The basic alterations are

Answer 40

(1) microvascular leakage causing edema,
(2) necrosis of fat by lipolytic enzymes,
(3) acute inflammation,
(4) proteolytic destruction of pancreatic parenchyma, and
(5) destruction of blood vessels and subsequent interstitial hemorrhage. The extent of each of these alterations depends on the duration and severity of the process.

Question 41

In the milder form, acute interstitial pancreatitis, histologic alterations are limited to ____________ in the substance of the pancreas and in peripancreatic fat ( Fig. 19-3 ). Fat necrosis, as we have seen, results from enzymatic activity of lipase. The released fatty acids combine with calcium to form insoluble salts that impart a granular blue microscopic appearance to the fat cells ( Chapter 1 ).

Answer 41

mild inflammation, interstitial edema, and focal areas of fat necrosis

Question 42

In the more severe form, ____________-, the acinar and ductal tissues as well as the islets of Langerhans are necrotic. Vascular injury can lead to hemorrhage into the parenchyma of the pancreas.

Macroscopically, the pancreatic substance shows areas of redblack hemorrhage interspersed with foci of yellow-white, chalky fat necrosis ( Fig. 19-4 ).

Answer 42

acute necrotizing pancreatitis** **

redblack hemorrhage interspersed with foci of yellow-white, chalky fat necrosis

Question 43

Foci of fat necrosis may also be found in_____________ In the majority of cases the peritoneal cavity contains a serous, slightly turbid, brown-tinged fluid in which globules of fat (derived from the action of enzymes on adipose tissue) can be identified. In its most severe form, hemorrhagic pancreatitis, extensive parenchymal necrosis is accompanied by dramatic hemorrhage within the substance of the gland. [20,] [21]

Answer 43

extra-pancreatic collections of fat, such as the omentum and

the mesentery of the bowel, and even

outside the abdominal cavity, such as in the subcutaneous fat.

Question 44

Answer 44

Acute pancreatitis. The microscopic field shows a region of fat necrosis on
the right and focal pancreatic parenchymal necrosis (center).

Question 45

Answer 45

Acute pancreatitis. The pancreas has been sectioned longitudinally to
reveal dark areas of hemorrhage in the head of t

Question 46

Pathogenesis.

The anatomic changes of acute pancreatitis ___________of the pancreatic substance by inappropriately activated pancreatic enzymes.

This hypothesis is supported by the hereditary forms of pancreatitis described above. Here we focus on the more common, acquired forms of acute pancreatitis. As has been discussed, pancreatic enzymes, including trypsin, are synthesized in an inactive proenzyme form. If trypsin is inappropriately activated it can in turn activate other proenzymes such as prophospholipase and proelastase, which then degrade fat cells and damage the elastic fibers of blood vessels, respectively. [8] [9] [10] [12] Trypsin also converts prekallikrein to its activated form, thus bringing into play the kinin system and, by activation of Hageman factor (factor XII), the clotting and complement systems as well ( Chapters 2 and 4 . In this way inflammation and small-vessel thromboses (which may lead to congestion and rupture of already weakened vessels) are amplified. Thus, the inappropriate activation of trypsinogen is an important triggering event in acute pancreatitis.

Answer 46

strongly suggest autodigestion

Question 47

The mechanisms by which the activation of pancreatic enzymes is initiated are not entirely clear, but there is evidence for three possible events ( Fig. 19-5 ):

Answer 47

1. Pancreatic duct obstruction.
2. ** Primary acinar cell injury**
3. Defective intracellular transport of proenzymes within acinar cells

Question 48

Gallstones or biliary sludge impacted in the region of the
ampulla of Vater can raise intrapancreatic ductal pressure and lead to the accumulation
of enzyme-rich fluid in the interstitium.

Since lipase is one of the few enzymes secreted
in an active form,this cancause local fat necrosis. Injured tissues, periacinar
myofibroblasts, and leukocytes then release proinflammatory cytokines including IL-1β,
IL-6, tumor necrosis factor, platelet-activating factor, and substance P, initiating local
inflammation and promoting the development of interstitial edema through a leaky microvasculature (see Fig. 19-5 ). [22] [23] [24] [25] Edema may further compromise
local blood flow, causing vascular insufficiency and ischemic injury to acinar cells. [26]

Answer 48

Pancreatic duct obstruction

Question 49

What are the 2 exception of rnzymes in pancreas that is in active form?

Answer 49

Lipase and Amylase

Question 50

This mechanism is most clearly involved in the pathogenesis of acute pancreatitis caused by certain viruses (e.g., mumps), drugs, and direct trauma to the pancreas, as well as pancreatitis following ischemia or shock.

Answer 50

Primary acinar cell injury .

Question 51

. [27] In normal acinar cells, digestive enzymes and lysosomal hydrolases are transported in separate pathways. In animal models of acinar injury, the pancreatic proenzymes are inappropriately delivered to the intracellular compartment containing lysosomal hydrolases. Proenzymes are then activated, the lysosomes disrupted, and activated enzymes released. The role of this mechanism in human acute pancreatitis is not clear. [28]

Answer 51

Defective intracellular transport of proenzymes within acinar cells

Question 52

Pathogenesis and 3 causes of pancreatitis

Answer 52

Question 53

____________- results in the secretion of protein-rich pancreatic fluid, which leads to the deposition of inspissated protein plugs and obstruction of small pancreatic ducts. Alcohol also transiently increases pancreatic exocrine secretion and contraction of the sphincter of Oddi (the muscle at the ampulla of Vater), and it has direct toxic effects on acinar cells

Answer 53

Chronic alcohol ingestion

NOTE :Alcohol consumption may cause pancreatitis by several mechanisms.

Question 54

Clinical Features.

___________ is the cardinal manifestation of acute pancreatitis. [8] [9] [10] [12] Characteristically, the pain is constant and intense and is often referred to the upper back and occasionally can be associated with referred pain to the left shoulder

Its severity varies from mild and uncomfortable to severe and incapacitating. Anorexia, nausea, and vomiting frequently accompany the pain.

Answer 54

Abdominal pain