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Pancreas: Vital Organ in Digestion and Regulation of Blood Sugar
1.
2. Pancreas
• is a glandular organ in
the digestive
system and endocrine
system of vertebrates. It is
an endocrine
gland producing several
important hormones ,also a
digestive organ,
secreting pancreatic
juice containing digestive e
nzymes that assist digestion
and absorption of nutrients
in the small intestine.
3. • Located in the concavity
of the duodenum .
• Connected with spleen
by lienorenal ligament.
• Most of pancreas
located behind
stomach.
• Connected with bilary
system at 2nd part of
duodenum .
4. • 1. Bile ducts: 2. Intrahepatic bile
ducts, 3. Left and right hepatic ducts,
• 4. Common hepatic duct
• 5. Cystic duct
• 6. Common bile duct
• 7. Ampulla of Vater
• 8. Major duodenal papilla
9. Gallbladder,
• 10–11. Right and left lobes of liver.
12.Spleen.
13. Esophagus.
• 14. Stomach.
• 15.Duodenum,
• 16. Jejunum
17. Pancreas: 18: Accessory
pancreatic duct, 19:Pancreatic duct.
20–21: Right and
left kidneys (silhouette).
5. • Under light Microscope
by H&E stain appear
two types of cell
clusters :
– Rounded large pale
cells= Islets of
Langerhans .
– Dark small berry like =
pancreatic acini
6. • Islets of Langrhans =
Endocrinal part of
pancreas ,contain four
types of cells
– Alpha: secret Glucagon rise
glucose level in blood
– Beta: secret Insulin
,lowering glucose level in
blood
– Gamma: or P.P cells secret
pancreatic polypeptide
– Delta: secret Somatostatin
which control Alpha & Beta
cells
7. Pancreatic acini :
very similar to what is seen in salivary
glands.
secretions are secreted into
the lumen of the acinus, and then
accumulate in intralobular ducts that
drain to the main pancreatic duct,
which drains directly into
the duodenum.
• Control of the exocrine function of
the pancreas is via the
hormones gastrin, cholecystokinin &
secretin, which
are hormones secreted by cells in
the stomach and duodenum, in
response to distension and/or food
and which cause secretion of
pancreatic juices.
8. • There are two main
classes of exocrine
pancreatic secretions:
– Bicarbonate ions from
centroacinair cells
,stimulus Secretin ( in
order to neutralize the
acidic chyme that the
stomach churns out.)
– Digestive Enz from
basophilic cells, stimulus
cholecystokinin
9. Pancreas & digestion.
Enzymes secreted by the acini include
proteolytic enzymes, amylases and lipases.
The proteolytic enzymes are all secreted in an
inactive form to prevent auto-digestion.
Pancreatic enz are:
Amylase breaks down carbohydrates (except
cellulose) to di-saccharides and some tri-
saccharides.
Proteolytic enzymes are secreted in the
inactive form to prevent auto digestion, they
are converted to the active form in the small
intestine. Trypsin is activated by enterokinase,
secreted by the intestinal mucosa;
Tripsin then activates Chymotripsinogen
Lipase converts fats to fatty acids and
monoglycerides
Phospholipase splits fatty acids from
phospholipids
Cholesterol esterase hydrolises cholesterol
esters
10. Phases of Digestion
•
The Cephalic phase occurs when we
think about or anticipate food. It is
mediated by the vagus nerve. It
causes secretion of about 20% of the
enzymes, but as this secretion is not
accompanied by fluid secretions, the
enzymes are not flushed out and
tend to remain in the ducts.
• The gastric phase occurs when food
enters the stomach, and again is
mediated by neural stimuli. This
accounts for another 5-10%, and
again in the absence of serous flow
these secretions tend to remain in
the ducts.
• The Intestinal phase occurs when
food enters the small intestine and
both serous pancreatic secretion
becomes copious due to the
hormone secretin.
11. Regulation of pancreatic Secretion
• Acetylcholine from the
parasympathetic nerves
of the vagus and the
cholinergic nerves of the
enteric nervous system.
• Cholecystokinin secreted
in the duodenum and the
uopper small intestine
• Secretin, also secreted in
the duodenum and upper
jejunum.
13. Signs & symptoms
• Steatorrhea is the result of fat malabsorption and is
characterized by pale, bulky, and malodorous stools.
• Weight loss & fatigue are common; however, patients may
compensate by increasing their caloric consumption, and as
a result, weight loss from malabsorption may be masked.
• Flatulence & abdominal distention are caused by bacterial
fermentation of unabsorbed food substances, which
releases gaseous products such as hydrogen and methane.
• Edema may result from hypoalbuminemia caused by
chronic protein malabsorption.
• Anemia resulting from malabsorption can be either
microcytic (related to iron deficiency) or macrocytic
(related to vitamin B-12 deficiency).
14. • Bleeding disorders are usually a consequence of vitamin K
malabsorption and subsequent hypoprothrombinemia.
Ecchymosis usually is the manifesting symptom, though
melena and hematuria may occur on occasion.
• Metabolic bone disease caused by vitamin D deficiency can
result in osteopenia or osteomalacia. In severe cases, bone
pain and pathologic fractures occur with low calcium levels
leading to secondary hyperparathyroidism.
• Neurologic manifestations can result from electrolyte
disturbances (eg, hypocalcemia and hypomagnesemia) and
can lead to tetany. Malabsorption of certain vitamins can
cause generalized motor weakness (pantothenic acid and
vitamin D), peripheral neuropathy (thiamine), loss of a
sense of vibration and position (cobalamin), night blindness
(vitamin A), or seizures (biotin).
15. Diagnosis
A complete laboratory evaluation is required not only
to diagnose exocrine pancreatic insufficiency (EPI) but
also to determine the extent of the malabsorption and
assess manifestations of the underlying disease, if
present.
17. Chronic pancreatitis
• a continuing, chronic,
inflammatory process of
the pancreas,
characterized by
irreversible morphologic
changes. This chronic
inflammation can lead to
chronic abdominal pain
and/or impairment of
endocrine and exocrine
function of the pancreas.
(ERCP) shows advanced chronic
pancreatitis. The pancreatogram
has blunting of the lateral branches,
dilation of the main pancreatic duct,
and filling defects consistent with
pancreatolithiasis. The
cholangiogram also shows a
stenosis of the distal bile duct and a
dilated biliary tree.
18. • Alcohol is the most common etiology (60-
70%), approximately 20-30% of cases are
idiopathic (Oxidative stress - Eg, idiopathic
pancreatitis) and 10% of cases are due to rare
diseases(autoimmune chronic pancreatitis are
associated with primary biliary cirrhosis,
primary sclerosing cholangitis, and Sjögren
syndrome.)
20. •Alleviation of Abdominal
Pain
•Restoration of Digestion
and Absorption
Pharmacological
•Pancreatic duct drainage
•Pancreatic resection
•Total pancreatectomy and
islet autotransplantation
Surgical Therapy
21. Cystic fibrosis
• Cystic fibrosis is the most common lethal inherited
disease in white persons, autosomal recessive disorder,
and most carriers of the gene are asymptomatic.
• Cystic fibrosis is a disease of exocrine gland function
that involves multiple organ systems but chiefly results
in chronic respiratory infections, pancreatic enzyme
insufficiency, and associated complications in
untreated patients . Pulmonary involvement occurs in
90% of patients surviving the neonatal period. End-
stage lung disease is the principal cause of death.
22. • Cystic fibrosis is caused by defects in
the cystic fibrosis gene, which codes
for a protein transmembrane
conductance regulator (CFTR) that
functions as a chloride channel and is
regulated by cyclic adenosine
monophosphate (cAMP).
• Defective CFTR results in decreased
secretion of chloride and increased
reabsorption of sodium and water
across epithelial cells. The resultant
reduced height of epithelial lining
fluid and decreased hydration of
mucus results in mucus that is stickier
to bacteria, which promotes infection
and inflammation. Secretions in the
respiratory tract, pancreas, GI tract,
sweat glands, and other exocrine
tissues have increased viscosity,
which makes them difficult to clear..
23. Pansinusitis
•Most common cause of deathLung disease
•Meconium ileusIntestinal disease
Pancreatic disease
Liver disease
Worldwide, the median survival age in patients with cystic fibrosis varies from
country to country; it is highest in the United States. Median survival age is 36.9
years, but progress in medical and surgical treatment options have improved the
prognosis over the last few decades. An individual with cystic fibrosis born in the
United States today is expected to survive longer than 40 years.The median survival
age is higher in males than in females.
24. Treatment
• The primary goals of CF treatment include the following:
– Maintaining lung function as near to normal as possible by controlling respiratory infection
and clearing airways of mucus
– Administering nutritional therapy (ie, enzyme supplements, multivitamin and mineral
supplements) to maintain adequate growth
– Managing complications
• Mild acute pulmonary exacerbations of cystic fibrosis can be treated successfully
at home with the following measures:
– Increasing the frequency of airway clearance
– Inhaled bronchodilator treatment
– Chest physical therapy and postural drainage
– Increasing the dose of the mucolytic agent dornase alfa (Pulmozyme)
– Use of oral antibiotics (eg, oral fluoroquinolones)
• Medications used to treat patients with cystic fibrosis may include the following:
– Pancreatic enzyme supplements
– Multivitamins (including fat-soluble vitamins)
– Mucolytics
– Nebulized, inhaled, oral, or intravenous antibiotics
– Bronchodilators
– Anti-inflammatory agents
– Agents to treat associated conditions or complications (eg, insulin, bisphosphonates)
– Agents devised to potentially reverse the abnormalities in chloride transport
25.
26. Treatment
• Management approaches to exocrine pancreatic
insufficiency include the following:
– Lifestyle modifications (eg, avoidance of fatty foods, limitation
of alcohol intake, cessation of smoking, and consumption of a
well-balanced diet)
– Vitamin supplementation (primarily the fat-soluble vitamins A,
D, E, and K)
– Pancreatic enzyme replacement therapy (PERT), which is the
therapeutic mainstay
• Long-term monitoring of patients with EPI should focus on
the following 2 issues:
– Correction of nutritional deficiencies
– Treatment of causative diseases (when possible); such
treatment will vary according to the specific disease present
27. PERT
• The goal of supplemental enzyme therapy in EPI is to
minimize nutrient malabsorption, especially of lipids, and
to do this it is important to achieve an adequate
concentration of active pancreatic enzymes in the
duodenum at the same time that food is delivered
• The pancreatic enzyme products , contain all 3 pancreatic
enzymes (ie, amylase, protease, and lipase) in varying
proportions. However, it is lipase that plays the paramount
role in therapy.
• The pancreatic lipase replacement dose should be adjusted
on the basis of body weight, clinical symptoms, and stool
fat content. Several days should be allowed between dose
adjustments.
30. N.B
•
With the exception of Viokace, all PEPs have enteric
coatings and are used to treat EPI due to cystic fibrosis
or other conditions. Viokace is used in combination
with a proton pump inhibitor to treat pancreatic
insufficiency due to chronic pancreatitis or
pancreatectomy.
• The PEPs are not interchangeable. When a patient is
switched to a new PEP, the dose must be started at a
similar amount of lipase units and then titrated
according to patient response. It may take 1-2 weeks
for the patient to adjust to new PEP dose, which can
vary.
31. • Because exogenous pancreatic enzymes
should exert their action on the ingested meal
and because gastric emptying of nutrients
should occur in parallel with pancreatic
enzymes reaching the duodenum, PEPs are
administered together with meals and snacks.
When a sufficient enzyme concentration is
delivered into the duodenal lumen
simultaneously with a meal, fat absorption is
enhanced.
32. • The composition and various formulations of pancreatin
and pancrelipase affect their use and ability to deliver
appropriate amounts of active enzyme to the duodenum.
Pancreatin, a crude mixture, is derived from swine or ox
pancreas, and each milligram contains no less than 2 USP
(United States Pharmacopeia) units of lipase and 25 USP
units of amylase and protease activity. Pancrelipase is
obtained from swine pancreas and is a more concentrated
and purified enzyme preparation. Each milligram contains
no less than 24 USP units of lipase and 100 USP units of
amylase and protease activity. Because of its higher enzyme
content, pancrelipase formulations are favored over
pancreatin preparations
33. Calculate the dose
• Dosing for pancreatic insufficiency is as follows:
– Initial oral lipase dose, 500 units/kg/meal
– Lipase dose range, 500-2500 units/kg/meal
– Maximum lipase dosage, 10,000 units/kg/day or 4000
units per gram of fat daily
• Dosing for pancreatic insufficiency due to chronic
pancreatitis or pancreatectomy is as follows:
– Oral lipase dose, 72,000 units/meal with consumption of
at least 100 g of fat daily
– Alternatively, lower initial lipase doses (500 units/kg/meal)
with individualized dose titration may be considered
34. Safety and side effects
• The most commonly reported side effects for
recently approved enzymes are
• headache (6%)
• dizziness (6%)
• abdominal pain (9%)
• flatulence
• Historically, hyperuricemia, and hyperuricosuria,
which leads to dysuria and uric acid crystaluria,
have been reported in cystic fibrosis patients with
older formulations. Folic acid deficiency has been
associated with use of pancreatin extracts
Editor's Notes
Pancreatic poly peptide increased by fasting, exercise , acute hypo glycemia ,protein meal ingestion
Decresed by somatostatin releasing & IV glucose
Stimulate gastric juice secretion
Pathological increase in pp indicate hormon secreting tumour in pancrease
Cholecystokinin: a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein.
synthesized by I-cells in the mucosal epithelium of the small intestine and secreted in the duodenum, the first segment of the small intestine, and causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively. It also acts as ahunger suppressant.
Secretin is a hormone that both controls the environment in the duodenum by regulating secretions of the stomach and pancreas, and regulates water homeostasis throughout the body.
In diagram :
Acetylcholin and Cholecystokinin cause secretion of digestive enzymes, but these tend to remain in the gland, as there are no secretions to flow them out.
Secretin causes copious secretions of sodium bicarbonate rich fluids which wash the enzymes into the small intestine, and also neutralize the Hydrochloric acid from the stomach.
2HCl + Na2CO3 --> 2NaCl + H2CO3 --> H2O + CO2 The carbonic acid (a weak acid) immediately dissociates into Carbon Dioxide and water The Carbon dioxide is absorbed into the blood stream.
Pancreatic enzymes work best between a pH of 7-8. Sodium Bicarbonate has a pH of about 8.