Lecture 5: Pancreas

Question 1

Basic Pancreas anatomy

Answer 1

endocrine and exocrine organ located retroperitoneally in the upper abdomen overlying the spine

is supplied by the gastroduodenal arteries and by branches of the splenic artery

Question 2

Describe the cells in the ENDOCRINE pancreas and what they secrete

and pancreas mass the endocrine pancreas makes up

Answer 2

Accounts for only 2% of the pancreatic mass

Nests of cells - islets of Langerhans

Four major cell types
Alpha (A) cells secrete glucagon
Beta (B) cells secrete insulin
Delta (D) cells secrete somatostatin
F cells secrete pancreatic polypeptide

Question 3

Insulin -
synthesised by what cells
Diabetes
How is insulin made

Answer 3

Synthesized in the B cells of the islets of Langerhans

80% of the islet cell mass must be surgically removed before diabetes becomes clinically apparent

Proinsulin, is transported from the endoplasmic reticulum to the Golgi complex where it is packaged into granules and cleaved into insulin and a residual connecting peptide, or C peptide

Question 4

Glucagon

• secreted by what cells
• purpose of glucagon
• Major stimulants and major inhibitors

Answer 4

Secreted by the A cells of the islet

Glucagon elevates blood glucose levels through the stimulation of glycogenolysis and gluconeogenesis

Major stimulants
Aminoacids, Cholinergic fibers, β-Sympathetic fibers

Major inhibitors
Glucose, insulin, somatostatin, α-sympathetic fibers

Question 5

Somatostatin

• Secreted by what cells
• inhibits..
• Purpose

Answer 5

Secreted by the D cells of the islet

Inhibits the release of growth hormone
Inhibits the release of almost all peptide hormones
Inhibits gastric, pancreatic, and biliary secretion

Used to treat both endocrine and exocrine disorders

Question 6

Exocrine Pancreas: CCK major stimulant of

Answer 6

Cholecystokinin is the most potent endogenous hormone known to stimulate enzyme secretion.

Question 7

Exocrine Pancreas: secretin major stimulant of …

Answer 7

Secretin is the most potent endogenous stimulant of pancreatic electrolyte secretion.

Question 8

Physiology of exocrine pancreas

• what is secreted and by what cells
• characteristic of pancreatic fluid

Answer 8

Secretion of water and electrolytes originates in the centroacinar and intercalated duct cells

Pancreatic enzymes originate in the acinar cells

Final product is a colorless, odorless, and isosmotic alkaline fluid that contains digestive enzymes (amylase, lipase, and trypsinogen)

Question 9

Why is pancreatic fluid alkaline?

Answer 9

Alkaline pH results from secreted bicarbonate which serves to neutralize gastric acid and regulate the pH of the intestine

Question 10

Exocrine Pancreas: 
Bicarbonate secretion
-how much secreted and via what cells
- purpose of fluid 
- Na, K and Cl- affected how?

Answer 10

Centroacinar cells and ductular epithelium secrete 20 mmol of bicarbonate per liter in the basal state

Fluid (pH from 7.6 to 9.0) acts as a vehicle to carry inactive proteolytic enzymes to the duodenal lumen

Sodium and potassium concentrations are constant and equal those of plasma
Chloride secretion varies inversely with bicarbonate secretion

Question 11

Major stimulants and inhibitors of bicarbonate secretion (exocrine pancreas)

Answer 11

Major stimulants
Secretin, Cholecystokinin, Gastrin, Acetylcholine

Major inhibitors
Atropine, Somatostatin, Pancreatic polypeptide and Glucagon

Question 12

Bicarbonate formed by what and what enzyme?

Answer 12

Bicarbonate is formed from carbonic acid by the enzyme carbonic anhydrase

Question 13

Acinar cells:

• secrete?
• stimulants
• created
• transported to?

Answer 13

Acinar cells secrete isozymes, trypsin, chymotrypsin, amylases, lipases, and proteases

Major stimulants
Cholecystokinin, Acetylcholine, Secretin, VIP

Synthesized in the endoplasmic reticulum of the acinar cells and are packaged in the zymogen granules

Released from the acinar cells into the lumen of the acinus and then transported into the duodenal lumen, where the enzymes are activated.

Question 14

Enzymes: Amylase
Ph
Function
Inactive or Active form?

Answer 14

secreted by the pancreas in an active form

functions optimally at a pH of 7

hydrolyzes starch and glycogen to glucose, maltose, maltotriose, and dextrins

Question 15

Enzymes: Lipase
Ph
Function

Answer 15

function optimally at a pH of 7 to 9

emulsify and hydrolyze fat in the presence of bile salts

Question 16

Enzymes: Protease

Function
Inactive or Active form?

Answer 16

essential for protein digestion

secreted as proenzymes and require activation for proteolytic activity

duodenal enzyme (enterokinase) converts trypsinogen to trypsin

Trypsin, in turn, activates chymotrypsin, elastase, carboxypeptidase, and phospholipase

Within the pancreas, enzyme activation is prevented by an antiproteolytic enzyme secreted by the acinar cells

Question 17

2 patterns of pancreatic secretion

Answer 17

1. basal secretion
   - every 1 to 2 hours by bursts of increased bicarbonate and enzyme secretion that last 10 to 15 minutes.

2.postprandial stage
which results from a complex interaction of neural and hormonal mechanisms

Question 18

Purpose of Trypsin and chymotrypsin and how this leads to inflammation

Answer 18

Trypsin and chymotrypsin are the initiating enzymes; their release can in turn result in the release and activation of other proenzymes (including zymogen granules, procollagenase and phospholipases).

Trypsin damages endothelial cells and mast cells, resulting in the release of histamine.

This major inflammatory mediator enhances vascular permeability, leading to edema, hemorrhage and the activation of the kallikrein system, which in turn results in the production of vasoactive peptides or kinins

Question 19

3 forms of pancreatitis and description

Answer 19

Acute Pancreatitis
- Severe abdominal pain in which the pancreas appears to digest itself.
Vomiting, nausea, pain radiating to back, chest
- It is usually caused by gallstones, alcohol or is idiopathic.

Chronic Pancreatitis
- an irreversible scarring of the pancreas with permanent loss of pancreatic function that typically causes unrelenting abdominal pain.

Hereditary Pancreatitis
- a unusual form of acute and chronic pancreatitis that runs in families.

Question 20

Acute pancreatitis causes and how this causes autodigestion

Answer 20

Alcohol
Trauma
Gall stones
ERCP

Damage to the pancreas leads to the activation of pancreatic enzymes IN THE PANCREAS

Leading to pancreatic necrosis and
autodigestion of the tissues of the abdomen

Question 21

Tests showing for pancreatitis

Answer 21

Lipase (> Sensitivity and >Specificity)
Amylase
Ca2+ Profile
Triglycerides 
(above must be done first with first episode for etiology)

CBC
BUN/Cr
LFT’s – ALT >150 IU/L high Spec for Stones
Urinalysis (lipase, amylase so high leaks into ciruclation and excreted)

Question 22

Indicators of acute pancreatitis

Answer 22

Amylase is the indicator of acute pancreatitis presence (NOT how severe)
Lipase indicates presence of acute pancreatitis but not severity, more specific than amylase.

if one increased then early pancreatitis, both then confirms

Urinary TAP (Trypsinogen activation peptide)
 specific for severe acute pancreatitis, low level excludes severe acute pancreatitis 

Only found in plasma / urine in the case of SEVERE acute pancreatitis

Question 23

Chronic pancreatitis defination

Answer 23

Chronic pancreatitis is defined as a continuing chronic inflammatory process of the pancreas, characterized by irreversible morphological changes.
Cause issues to endocrine and exocrine pancreas

Question 24

Full recovery in chronic pancreatitis? Why/why not

Answer 24

No, sustained irreversible scarring and inflammation of the pancreas leading to fibrosis and calcification.

Question 25

Diagnosis of chronic pancreatis

Answer 25

Slightly elevated amylase and lipase.
low concentrations of trypsin is typical of advanced chronic pancreatitis
Calcium and triglyceride levels

Question 26

Cystic fibrosis description

Answer 26

clogging of lungs
Plugging of bile ducts in liver and plugging of ducts in pancreas inhibiting digestion
Obstruction in small intestine
malfunctioning sweat glands.

Question 27

What mutation causes CF from chromosome level to bp and causes what affect?

Answer 27

Chromosome 7 - CFTR gene - CTT gene - Phenylalanine is deleted

Thus the protein that forms the CFTR Cl- channel is not recognized as it is not properly folded and therefore doesnt leave ER and thus no CFTR channel. So no CL can leave the cell

Question 28

CFTR affect on Na and Cl in the lung ariway and cells

Answer 28

Normal lung:
Chloride into airway; sodium out and into the epithelial cells- keeps mucus moist and thin
Normal CFTR regulates the sodium channel (inactivates it)

Chloride does not get into airway; more sodium leaves airway; More salt in cell - water comes in
This makes the mucus thick

In CF the CFTR channel is non-functional and causes increased salt
to enter the epithelial cells and lack of Cl- leaving and entering the
airway. Thus, increased salt concentration in the cells of the lung
causes osmotic changes where there is an increased water
movement into the lung cells causing dehydration of the airway
surfaces rendering ‘dry’. Therefore, the lack of water causes the
mucus unable to be thinned and the thickened muscus collapses
the cilia. Thus, thickened mucus is trapped in the airways of the lung

Question 29

Tests for CF

Answer 29

Sweat test:
Due to the incorrectly functioning CFTR channel which controls Cl- leaving cells, there is a lack of Cl- leaving the sweat glands causing highly concentrated cl- sweat/.

Mutation in CFTR region on both alleles
Abnormal nasal epithelial ion transport