Lecture 5: Pancreas Flashcards
Basic Pancreas anatomy
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
Describe the cells in the ENDOCRINE pancreas and what they secrete
and pancreas mass the endocrine pancreas makes up
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
Insulin -
synthesised by what cells
Diabetes
How is insulin made
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
Glucagon
- secreted by what cells
- purpose of glucagon
- Major stimulants and major inhibitors
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
Somatostatin
- Secreted by what cells
- inhibits..
- Purpose
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
Exocrine Pancreas: CCK major stimulant of
Cholecystokinin is the most potent endogenous hormone known to stimulate enzyme secretion.
Exocrine Pancreas: secretin major stimulant of …
Secretin is the most potent endogenous stimulant of pancreatic electrolyte secretion.
Physiology of exocrine pancreas
- what is secreted and by what cells
- characteristic of pancreatic fluid
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)
Why is pancreatic fluid alkaline?
Alkaline pH results from secreted bicarbonate which serves to neutralize gastric acid and regulate the pH of the intestine
Exocrine Pancreas: Bicarbonate secretion -how much secreted and via what cells - purpose of fluid - Na, K and Cl- affected how?
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
Major stimulants and inhibitors of bicarbonate secretion (exocrine pancreas)
Major stimulants
Secretin, Cholecystokinin, Gastrin, Acetylcholine
Major inhibitors
Atropine, Somatostatin, Pancreatic polypeptide and Glucagon
Bicarbonate formed by what and what enzyme?
Bicarbonate is formed from carbonic acid by the enzyme carbonic anhydrase
Acinar cells:
- secrete?
- stimulants
- created
- transported to?
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.
Enzymes: Amylase
Ph
Function
Inactive or Active form?
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
Enzymes: Lipase
Ph
Function
function optimally at a pH of 7 to 9
emulsify and hydrolyze fat in the presence of bile salts
Enzymes: Protease
Function
Inactive or Active form?
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
2 patterns of pancreatic secretion
- 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
Purpose of Trypsin and chymotrypsin and how this leads to inflammation
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
3 forms of pancreatitis and description
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.
Acute pancreatitis causes and how this causes autodigestion
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
Tests showing for pancreatitis
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)
Indicators of acute pancreatitis
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
Chronic pancreatitis defination
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
Full recovery in chronic pancreatitis? Why/why not
No, sustained irreversible scarring and inflammation of the pancreas leading to fibrosis and calcification.
Diagnosis of chronic pancreatis
Slightly elevated amylase and lipase.
low concentrations of trypsin is typical of advanced chronic pancreatitis
Calcium and triglyceride levels
Cystic fibrosis description
clogging of lungs
Plugging of bile ducts in liver and plugging of ducts in pancreas inhibiting digestion
Obstruction in small intestine
malfunctioning sweat glands.
What mutation causes CF from chromosome level to bp and causes what affect?
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
CFTR affect on Na and Cl in the lung ariway and cells
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
Tests for CF
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
