pancrease anatomy and physiology

8/7/2019 Pancrease ANATOMY AND PHYSIOLOGY

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Pancreas: Anatomy &Pancreas: Anatomy &

PhysiologyPhysiology



PancreasPancreas

Gland with both exocrine andGland with both exocrine andendocrine functionsendocrine functions

66--10 inch in length10 inch in length 6060--100 gram in weight 100 gram in weight



Location: RetroLocation: Retro--peritoneum, 2peritoneum, 2ndnd

lumbar vertebral levellumbar vertebral level

Extends in an oblique, transverseExtends in an oblique, transversepositionposition

Parts of pancreas: head, neck, bodyParts of pancreas: head, neck, body

and tailand tail



PancreasPancreas



Enzymes of PancreasEnzymes of Pancreas

ProteasesProteases essential for protein digestionessential for protein digestion secreted assecreted as proenzymesproenzymes and requireand require

activation foractivation for proteolyticproteolytic activityactivity duodenal enzyme,duodenal enzyme, enterokinaseenterokinase, converts, converts

trypsinogentrypsinogen toto trypsintrypsin TrypsinTrypsin, in turn, activates, in turn, activates chymotrypsinchymotrypsin,,

elastaseelastase,, carboxypeptidasecarboxypeptidase, and, and

phospholipasephospholipase Within the pancreas, enzyme activation isWithin the pancreas, enzyme activation is

prevented by anprevented by an antiproteolyticantiproteolytic enzymeenzymesecreted by thesecreted by the acinaracinar cellscells



InsulinInsulin

Synthesized in the B cells of the islets of Synthesized in the B cells of the islets of LangerhansLangerhans

80% of the islet cell mass must be80% of the islet cell mass must besurgically removed before diabetessurgically removed before diabetesbecomes clinically apparent becomes clinically apparent

ProinsulinProinsulin, is transported from the, is transported from the

endoplasmic reticulum to the Golgiendoplasmic reticulum to the Golgicomplex where it is packaged intocomplex where it is packaged intogranules and cleaved into insulin and agranules and cleaved into insulin and aresidual connecting peptide, or C peptideresidual connecting peptide, or C peptide



InsulinInsulin

Major stimulantsMajor stimulants

Glucose, amino acids, glucagon, GIP,Glucose, amino acids, glucagon, GIP,

CCK, sulfonylurea compounds,CCK, sulfonylurea compounds, --Sympathetic fibersSympathetic fibers

Major inhibitorsMajor inhibitors

somatostatinsomatostatin,, amylinamylin,, pancreastatinpancreastatin,, --

sympathetic fiberssympathetic fibers



GlucagonGlucagon

Secreted by the A cells of the islet Secreted by the A cells of the islet

Glucagon elevates blood glucose levelsGlucagon elevates blood glucose levelsthrough the stimulation of glycogenolysisthrough the stimulation of glycogenolysis

and gluconeogenesisand gluconeogenesis Major stimulantsMajor stimulants

Aminoacids, Cholinergic fibers, Aminoacids, Cholinergic fibers, --Sympathetic fibersSympathetic fibers

Major inhibitorsMajor inhibitors Glucose, insulin, somatostatin,Glucose, insulin, somatostatin, --

sympathetic fiberssympathetic fibers



SomatostatinSomatostatin

Secreted by the D cells of the islet Secreted by the D cells of the islet

Inhibits the release of growthInhibits the release of growth

hormonehormone Inhibits the release of almost allInhibits the release of almost all

peptide hormonespeptide hormones

Inhibits gastric, pancreatic, and biliaryInhibits gastric, pancreatic, and biliary

secretionsecretion Used to treat both endocrine andUsed to treat both endocrine and

exocrine disordersexocrine disorders



Pancreatic function testsPancreatic function tests



Exocrine functionExocrine function

Secretin testSecretin test

Overnight fast Overnight fast

Double lumen tubeDouble lumen tube

Basal secretionBasal secretion

2u/kg of Secretin2u/kg of Secretin

Four 20 min collections of secretionsFour 20 min collections of secretions

Test for volume, bicarbonate,Test for volume, bicarbonate,amylaseamylase



FLOW BICARBON ATE, AND ENZY ME CHANGES OBSERVED IN FLOW BICARBON ATE, AND ENZY ME CHANGES OBSERVED IN PATIENTS WITH VARIOUS PANCREATIC DISORDERSPATIENTS WITH VARIOUS PANCREATIC DISORDERS

DisorderDisorder PatternPattern Flow rateFlow rate Max. bicarbMax. bicarbconcentrationconcentration

Enzyme secretionEnzyme secretion

EndEnd--stagestagepancreatitis,pancreatitis,advancedadvanced

pancreatic cancerpancreatic cancer

Total insufficiencyTotal insufficiency DecreasedDecreased DecreasedDecreased DecreasedDecreased

ChronicChronicpancreatitispancreatitis

QualitativeQualitativeinsufficiencyinsufficiency

NormalNormal DecreasedDecreased NormalNormal

Pancreatic cancerPancreatic cancer QuantitativeQuantitative

insufficiencyinsufficiency

DecreasedDecreased NormalNormal NormalNormal

MalnutritionMalnutrition Isolated enzymeIsolated enzymedeficiencydeficiency

NormalNormal NormalNormal DecreasedDecreased

HemochromatosisHemochromatosisZollingerZollinger--EllisonEllisonsyndrome, varioussyndrome, various

cirrhosescirrhoses

HypersecretionHypersecretion IncreasedIncreased NormalNormal NormalNormal



Fecal fat test Fecal fat test

Distinguish between pancreatic dysfunctionDistinguish between pancreatic dysfunctionand intestinal malabsorptionand intestinal malabsorption

In Pancreatic disease when lipase secretionIn Pancreatic disease when lipase secretionis reduced by 90%is reduced by 90%-- 2424--hour fecal fat hour fecal fat content is elevated to more than 20 g.content is elevated to more than 20 g.

Intestinal dysfunctionIntestinal dysfunction -- Steatorrhea withSteatorrhea with

low levels of fecal fat low levels of fecal fat UseUse-- Efficacy of pancreatic enzymeEfficacy of pancreatic enzyme

replacement replacement



The dimethadione (DMO) The dimethadione (DMO) test test

Pancreas degrades TrimethadionePancreas degrades Trimethadione(anticonvulsant ), and secretes its(anticonvulsant ), and secretes its

metabolite, DMO.metabolite, DMO. TrimethadioneTrimethadione -- 0.45 g Po TID for 30.45 g Po TID for 3

days.days.

Secretin test is performed.Secretin test is performed. The duodenal output of DMO The duodenal output of DMO

measuredmeasured

Impaired in exocrine insufficiencyImpaired in exocrine insufficiency



The Lundh test The Lundh test

Based on endogenous secretion of secretin andBased on endogenous secretion of secretin andCCK in addition to pancreatic secretionCCK in addition to pancreatic secretion

Overnight fast Overnight fast

Basal collection of duodenal fluidBasal collection of duodenal fluid

Meal of 18 g of corn oil, 15 g of casein, and 40 gMeal of 18 g of corn oil, 15 g of casein, and 40 gof glucose in 300 mL of water.of glucose in 300 mL of water.

ThirtyThirty--minute collectionsminute collections -- for 2 hoursfor 2 hours

Analyzed for trypsin, amylase, and lipase Analyzed for trypsin, amylase, and lipase

Abnormal in patients with chronic pancreatitis Abnormal in patients with chronic pancreatitis

LimitationsLimitations -- Need for duodenal intubationNeed for duodenal intubation

Abnormal Abnormal -- Dis. involving the GI mucosaDis. involving the GI mucosa



Triolein breath test Triolein breath test

Noninvasive test of exocrine insufficiencyNoninvasive test of exocrine insufficiency

25 grams of corn oil containing 5 mCi of 25 grams of corn oil containing 5 mCi of [14C]triolein is given orally[14C]triolein is given orally

4 hours later4 hours later -- metabolite 14Cmetabolite 14C--carbon dioxidecarbon dioxidemeasured in breathmeasured in breath

In fat digestion or malabsorption less than 3% of In fat digestion or malabsorption less than 3% of the [14C]triolein dose per hour measured.the [14C]triolein dose per hour measured.

Test repeated after oral pancreatic enzymeTest repeated after oral pancreatic enzyme

replacement.replacement. In exocrine insufficiency achieve a normal rate of In exocrine insufficiency achieve a normal rate of

excretion of 14Cexcretion of 14C carbon dioxide, whereas patientscarbon dioxide, whereas patientswith enteric disorders show no improvement with enteric disorders show no improvement



Paraaminobenzoic(PABA) acidParaaminobenzoic(PABA) acidtest test

Noninvasive test of pancreatic insufficiencyNoninvasive test of pancreatic insufficiency

NN--benzoylbenzoyl--ll--tyrosyltyrosyl--PABA is cleaved byPABA is cleaved bychymotrypsin to form PABA.chymotrypsin to form PABA.

PABA is absorbed from the small intestinePABA is absorbed from the small intestineexcreted in the urineexcreted in the urine

One gram of BTOne gram of BT--PABA in 300 mL of waterPABA in 300 mL of wateris given orally, and urine collections areis given orally, and urine collections are

obtained for 6 hours.obtained for 6 hours. Patients with chronic pancreatitis excretePatients with chronic pancreatitis excrete

less than 60% of the ingested dose of BTless than 60% of the ingested dose of BT--PABA.PABA.



Islet hormoneIslet hormone -- PP levelsPP levels

Basal and meal stimulated levels of plasma PP measuredBasal and meal stimulated levels of plasma PP measured Overnight fast Overnight fast-- Test meal consisting of 20% protein, 40%Test meal consisting of 20% protein, 40%

fat, and 40% carbohydrate is givenfat, and 40% carbohydrate is given Basal levelsBasal levels

NormalNormal-- 100 to 250 pg/mL)100 to 250 pg/mL)Less than 50 pg/mL in severe chronic pancreatitisLess than 50 pg/mL in severe chronic pancreatitis

After meal PP After meal PP --Normally rise to 700 to 1,000 pg/mLNormally rise to 700 to 1,000 pg/mL

Reduced to 250 pg/mL in severe disease.Reduced to 250 pg/mL in severe disease. LimitationsLimitations Depends on intact pancreatic innervation, depressed inDepends on intact pancreatic innervation, depressed in

cases of diabetic autonomic neuropathy, after truncalcases of diabetic autonomic neuropathy, after truncalvagotomy and antrectomyvagotomy and antrectomy



DIFFERENTI AL DI AGNOSIS OF INTESTIN AL ANDDIFFERENTI AL DI AGNOSIS OF INTESTIN AL ANDPANCREATIC STEATORRHEAPANCREATIC STEATORRHEA

ParameterParameter Intestinal steatorrheaIntestinal steatorrhea PancreatitisPancreatitis

Fecal fat Fecal fat <20 g monoglycerides and<20 g monoglycerides anddiglycerides; soapydiglycerides; soapyconsistencyconsistency

>20 g tnglycendes; only>20 g tnglycendes; onlyseepageseepage

DD--XyloseXylose LowLow NormalNormal

Secretion test Secretion test NormalNormal Abnormal Abnormal

SmallSmall--bowel seriesbowel series Abnormal Abnormal NormalNormal

SmallSmall--bowel biopsybowel biopsy Abnormal Abnormal NormalNormal

Lunch mealLunch meal NormalNormal Abnormal AbnormalPABA test PABA test NormalNormal Abnormal Abnormal

PP response to test mealPP response to test meal NormalNormal LowLow

Treatment with pancreaticTreatment with pancreaticenzymesenzymes

No changeNo change Improvement Improvement



Endocrine functionEndocrine function

Oral GTTOral GTT

Confirm the diagnosis of diabetes.Confirm the diagnosis of diabetes.

Indirect assessment of the insulin responseIndirect assessment of the insulin response

to an oral glucose load.to an oral glucose load. Overnight fastlngOvernight fastlng

2 basal blood samples for Blood sugar2 basal blood samples for Blood sugar

Oral glucose load of 40 g/m2 is given overOral glucose load of 40 g/m2 is given over10 minutes.10 minutes.

Blood samples are drawn every 30 minutesBlood samples are drawn every 30 minutesfor 2 hoursfor 2 hours



INTERPRETATION OF ORAL GLUCOSE TOLERANCEINTERPRETATION OF ORAL GLUCOSE TOLERANCETEST RESULTSTEST RESULTS

InterpretationInterpretation FastingFasting

glucoseglucosevaluevalue(mg/dL)(mg/dL)

IntermediateIntermediate


22--HourHour


NormalNormal <115<115 andand All values All values<200<200

andand 140140

ImpairedImpairedglucoseglucosetolerancetolerance

<140<140 andand Any value Any value200200

andand 140140 199199

DiabeticDiabetic 140 or140 or<140<140

(Glucose(Glucosetolerancetolerancetest not test not

necessary)necessary)

andand Any value Any value200200

andand 200200

Non diagnosticNon diagnostic Any combination of glucose values that does not fit into another Any combination of glucose values that does not fit into another

categorycategory



Intravenous glucose tolerance testIntravenous glucose tolerance test

Eliminates the GI influences on glucoseEliminates the GI influences on glucosemetabolism that affects the oral GTTmetabolism that affects the oral GTT

I V bolus of 0.5 g of glucose per kg over 2I V bolus of 0.5 g of glucose per kg over 2to 5 minutes.to 5 minutes.

Blood samplesBlood samples -- every 10 minutes for 1every 10 minutes for 1hour.hour.

The decline in glucose concentrationThe decline in glucose concentration(percentage of disappearance per minute) (percentage of disappearance per minute) is called the K value.is called the K value.

A K value of 1.5 or higher is normal. A K value of 1.5 or higher is normal.



Intravenous arIntravenous argginine test inine test

Arginine stimulates the secretion of islet hormones Arginine stimulates the secretion of islet hormones

Diagnosis of hormoneDiagnosis of hormone--secreting tumorssecreting tumors

Overnight fast, and given a 30Overnight fast, and given a 30--minute infusion of minute infusion of

0.5 g of arginine per kilogram.0.5 g of arginine per kilogram. Blood samples are taken every 10 minutesBlood samples are taken every 10 minutes

Radioimmunoassays are performed for the specificRadioimmunoassays are performed for the specifichormones in question.hormones in question.

This test is particularly useful for the diagnosis of This test is particularly useful for the diagnosis of

glucagonglucagon--secreting tumorssecreting tumors Elevations of plasma glucagon to above 400Elevations of plasma glucagon to above 400

pg/mL usually indicate apg/mL usually indicate a glucagonomaglucagonoma



Tolbutamide response test Tolbutamide response test

Useful in detecting hormoneUseful in detecting hormone--secreting tumors.secreting tumors. Sulfonylurea stimulates insulin secretion.Sulfonylurea stimulates insulin secretion. Overnight fasting, basal blood samples are drawn.Overnight fasting, basal blood samples are drawn. One gram of sodium tolbutamide is given intravenouslyOne gram of sodium tolbutamide is given intravenously

Blood glucose level is monitored for 1 hour.Blood glucose level is monitored for 1 hour. Blood samples for radioimmunoassay of insulin or otherBlood samples for radioimmunoassay of insulin or other

suspected hormones, such as somatostatin obtained.suspected hormones, such as somatostatin obtained. In normal patients, the blood glucose level falls to 50% of In normal patients, the blood glucose level falls to 50% of

basal values after 30 minutes.basal values after 30 minutes. Sustained hypoglycemia with hypersecretion of insulin isSustained hypoglycemia with hypersecretion of insulin is

consistent with anconsistent with an insulinomainsulinoma.. In the case of aIn the case of a somatostatinomasomatostatinoma, somatostatin levels are, somatostatin levels are

more thanmore than twice as hightwice as high as the prevailing normal valuesas the prevailing normal valuesfor the particular somatostatin radioimmunoassayfor the particular somatostatin radioimmunoassay



Acute pancreatitis Acute pancreatitis

Blood InvestigationsBlood Investigations CBC,LFT, serumCBC,LFT, serumcalcium, serum amylase andcalcium, serum amylase and lipaselipase, ABG, ABG

Chest Xray (for exclusion of perforatedChest Xray (for exclusion of perforatedviscus) viscus)

Abdominal Xrays (for detection of "sentinel Abdominal Xrays (for detection of "sentinelloop", gallstones which are radioopaque inloop", gallstones which are radioopaque in

10%) 10%) CT abdomenCT abdomen

U/S abdomenU/S abdomen

MRI /MRAMRI /MRA



Chr. PancreatitisChr. Pancreatitis

Study of exocrine pancreatic functionStudy of exocrine pancreatic function

CTCT-- size, duct, stone, mass lesionssize, duct, stone, mass lesions

ERCPERCP--Duct size, stenosis, obstruction,Duct size, stenosis, obstruction,stones, therapeutic stentingstones, therapeutic stenting



Pancreatic neoplasm'sPancreatic neoplasm's

CBC, LFT, Amylase, LipaseCBC, LFT, Amylase, Lipase

CaCa--1919--99-- 80% accurate, prognosis and f/u80% accurate, prognosis and f/u

Genetic testingGenetic testing-- Genetic syndromeGenetic syndrome

associated with hereditary pancreaticassociated with hereditary pancreaticcancercancer--(Peutz(Peutz--Jeghers, HereditaryJeghers, Hereditarypancreatitis, FAMMM, HNPCC)pancreatitis, FAMMM, HNPCC)

Genetic MutationsGenetic Mutations--DPC4 gene(18Q)DPC4 gene(18Q)--

missing in 90% of pancreatic cancers. K missing in 90% of pancreatic cancers. K--ras mutations common. Also changes inras mutations common. Also changes inp53 and p16 tumor suppressor genes.p53 and p16 tumor suppressor genes.



CAT scanCAT scan -- Spiral CTSpiral CT-- Cuts taken throughCuts taken throughpancreas both in a arterial phase and apancreas both in a arterial phase and aportal venous phaseportal venous phase

Local disease and metastatic diseaseLocal disease and metastatic disease MRCPMRCP--Non invasive, assess biliary tract in aNon invasive, assess biliary tract in a

jaundiced pt jaundiced pt ERCPERCP--90% accurate, in pts whom no mass90% accurate, in pts whom no mass

is seen, brushings for biopsyis seen, brushings for biopsy U/SU/S EUSEUS-- Detect early lesions <2cm, L.N Detect early lesions <2cm, L.N

assessment, vascular involvement, FN ACassessment, vascular involvement, FN AC



Cystic neoplasmsCystic neoplasms

CT scanCT scan

SerousSerous mutilocular ,centralmutilocular ,central

calcification,calcification, MucinousMucinous-- more common in body andmore common in body and

tail, 30% malignant potential, needstail, 30% malignant potential, needs

to be resectedto be resected ERCPERCP-- IPMN, common in the headIPMN, common in the head

and mucin secreted from the ductsand mucin secreted from the ducts



Functional endocrine neoplasmsFunctional endocrine neoplasms

InsulinomasInsulinomas Monitored fast test Monitored fast test Insulin to glucose ratio >0.4 (N <0.3)Insulin to glucose ratio >0.4 (N <0.3) Elevated CElevated C--peptide and propeptide and pro--insulin levelsinsulin levels CT, EUSCT, EUS STS (Somatostatin receptor scintigraphySTS (Somatostatin receptor scintigraphy--

Octreotide scan)Octreotide scan)-- Local tumorsLocal tumors--75%, metastatic75%, metastatic--65%, significant false negatives65%, significant false negatives

Visceral angiography Visceral angiography-- not performed anymorenot performed anymore Selective arterial calcium stimulation test(GDA,Selective arterial calcium stimulation test(GDA,

splenic, Inferior Panc. Duo. Art )splenic, Inferior Panc. Duo. Art ) Intraop ultrasoundIntraop ultrasound



GastrinomaGastrinoma Serum gastrinSerum gastrin-- Fasting gastrin>200pgm/mlFasting gastrin>200pgm/ml >1000pgm.ml pathgnomonic>1000pgm.ml pathgnomonic Gastric acid analysisGastric acid analysis--Basal Acid Output>15mEq/hrBasal Acid Output>15mEq/hr

(Non(Non--ulcerogenic causesulcerogenic causes -- Atrophic gastritis, Atrophic gastritis,Pernicious anemia, Vagotomy)Pernicious anemia, Vagotomy)

Secretin Stimulation test Secretin Stimulation test-- Increase by 200 pgm/mlIncrease by 200 pgm/mlabove the basal levelabove the basal level

CT, EUSCT, EUS SRSSRS-- more sensitive than in Insulinomamore sensitive than in Insulinoma Selective arterial secretin stimulation test Selective arterial secretin stimulation test IntraIntra--op ultrasoundop ultrasound



VIPOMA VIPOMA

BMPBMP-- Hypokalemia, Metabolic acidosisHypokalemia, Metabolic acidosis

Elevated VIP levelsElevated VIP levels-- repeated testingrepeated testingrequiredrequired

Gastric acid levelsGastric acid levels-- Achlorohydria Achlorohydria

CT, EUSCT, EUS



GlucagonomaGlucagonoma

HyperglycemiaHyperglycemia

HypoproteniemiaHypoproteniemia Glucagon levelsGlucagon levels

CT, EUSCT, EUS



SomatostatinomaSomatostatinoma

HyperglycemiaHyperglycemia

HypocholorohydriaHypocholorohydria Somatostatin level>100pgm/mlSomatostatin level>100pgm/ml

diagnosticdiagnostic

pancrease anatomy and physiology

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