© 2003 science press internet services fisiologÍa digestiva (bcm ii) clase 16- páncreas dr....

© 2003 Science Press Internet Services

FISIOLOGÍA DIGESTIVA (BCM II)Clase 16- Páncreas

Dr. Michel Baró A.


Major discoveries in pancreatic exocrine physiology


Physiologic function of the pancreas


Pancreatic exocrine secretion

sólido

líquido


Pancreatic control system


Overview of the pancreatic gland

InsulinaGlucagónSomatostatinaPolipéptido pancreático

10%

10%

80%


Electron micrographs of pancreatic acinar cells (a)

RER

Golgi

VacuolasCondensantes

GránulosZimógeno

Lumen

(estímulo)


Electron micrographs of pancreatic acinar cells (b)


Overview of the neural innervation of the pancreas

ACTHVIPGRP

Neurotransmisores:T5 – T9

Inerva:vasos sanguíneosGanglios

Fibras dolorosas

(sensorio-motor)

+ señales delPlexomientérico


Overview of the duodenum

I

S

Aferentes vagales que responden a

pH, aminoácidos, lípidos

Expresan receptores de CCK y secretina.


Feedback: control mechanisms


Sensation and amplification


Neurohormonal control of pancreatic bicarbonate secretion


The vagus and bicarbonate secretion


Cholecystokinin and pancreatic secretion

(TirosinaSulfatada en pos.7)

ReceptoresCCK-A (alimentary)CCK-B (brain)

-COOH


Origin of cholecystokinin (a)

Origen:Cel. Endocrinas intestinales (I)Neuronas SNC y SNENeuronas del Páncreas

lumen


Origin of cholecystokinin (b)

Lumen intestinal

apical

basal


Actions of cholecystokinin

EnzimasBicarbonato


Neurohormonal control of digestive enzyme secretion


Cholecystokinin and pancreatic enzyme secretion


Cholecystokinin receptors and afferent vagal fibers


Modifying mechanism controlling pancreatic secretion

amplificación


Duodenal release of cholecystokinin


Neurohormonal feedback system controlling enzyme secretion


Most fundamental work came from work of Pavlov and students


Inhibitory neuromodulators

TABLE 1 - 28. INHIBITORY NEUROPEPTIDES

Peptide Mode of Action Mechanism

Glucagon Endocrine/paracrine Unknown

Somatostatin Endocrine/paracrine Multiple neural

Pancreatic polypeptide Endocrine/paracrine ( - ) Cholinergics

Peptide YY Endocrine/paracrine ( - ) Cholinergics

Neuropeptide Y Neurocrine ( - ) Cholinergics

Enkephalin Neurocrine ( - ) Cholinergics

Calcitonin gene - related peptide Neurocrine Unknown

Pancreastatin Unknown ( - ) Cholinergics


Role of inhibitory peptides and impairing their action

+30-40% sin inhibidores


Somatostatin inhibits pancreatic secretion


The somatostatin receptor agonist, octreotide


Pancreatitis aguda


Etiologic classification of acute pancreatitis

TABLE 3 - 1. ETIOLOGIES Obstructive Toxins/drugs Metabolic Infection Vascular Trauma Idiopathic


Obstructive causes of acute pancreatitis

TABLE 3 - 2. OBSTRUCTIVE CAUSES Gallstones Ampullary/pancreatic cancer Worms in pancreatic duct–ascaris Choledochocele Periampullary duodenal diverticula Foreign body obstructing duct Pancreas divisum with obstruction of accessory papilla Hypertensive sphincter of Oddi


Toxins causing acute pancreatitis

TABLE 3 - 3. TOXINS Ethyl alcohol Methyl alcohol Scorpion toxin Organophosphorus insecticides


Drugs that can cause acute pancreatitis

TABLE 3 - 4. MAJOR DRUGS THAT CAUSE PANCREATITIS

With rechallenges With consistent latencies

Alpha methyl dopa Acetaminophen

5 - Aminosalicylate (dDl)

Azathioprine/6 mercaptopurine

Estrogens

Cimetidine

Furosemide

Metronidazole

Pentamidine

Sulfa drugs

Sulindac

Tetracycline

Valproic acid

Erythromycin


Metabolic causes of acute pancreatitis

TABLE 3 - 5. METABOLIC CAUSES Hypercalcemia–rare Hypertrigliceridemia–type I, type IV, type V


Inherited forms of acute pancreatitis

TABLE 3 - 6. INHERITED (HEREDITARY) PANCREATITIS

Autosomal dominant–abnormal gene or chromosome 7g Associated with chronic pancreatitis and cancer of the pancreas


Infectious causes of pancreatitis

TABLE 3 - 7. INFECTIOUS CAUSES OF ACUTE PANCREATITIS

Viruses Mumps, cytomegalovirus Herpes, hepatitis A,B,C Bacteria Mycobacteria (tuberculosis, Mycobacterium - avium complex) Leptospirosis Fungi Cryptococcus, Candida, coccidioidomycosis

Parasites Ascaris, Clonorchis, Pneumocystis


Vascular causes of pancreatitis

TABLE 3 - 8. VASCULAR/HYPOTENSION

Atherosclerotic emboli Ischemia–hypoperfusion Vasculitis–systemic lupus erythematosus, polyarteritis


Traumatic causes of acute pancreatitis

TABLE 3 - 9. TRAUMATIC CAUSES OF ACUTE PANCREATITIS

Blunt trauma Penetrating trauma Postoperative Endoscopic retrograde cholangiopancreatography Sphincter of Oddi manometry


Biliary drainage of idiopathic acute pancreatitis


Summary of main etiologies for acute pancreatitis


Pathogenetic sequence of acute pancreatitis

TABLE 3 - 14. PATHOGENESIS OF ACUTE PANCREATITIS: INITIATING EVENT

UNKNOWN ? Intra - acinar activation of trypsin, which in turn activates chymotrypsin, elastase, and phospholipase A2 ? Accumulation of lipase in interstitium, which leads to peripancreatic fat necrosis


Possible pathogenetic sequence of acute pancreatitis


Pathology of acute interstitial pancreatitis


Pathology of necrotizing pancreatitis


Fat necrosis


Pathology of necrotizing/hemorrhagic pancreatitis


Diagnosis of acute pancreatitis

TABLE 3 - 20. DIAGNOSIS OF ACUTE PANCREATITIS Serum lipase Serum amylase Urinary trypsinogen - 2 Serum alanine aminotransferase/aspartate aminotransferase Sonography of gallbladder, common duct Dynamic (bolus) computed tomographic scan


Serum C reactive protein levels in acute pancreatitis


Trypsinogen activation peptide levels in acute pancreatitis


Peritoneal aspirates in acute pancreatitis


Dynamic computed tomography scan of the pancreas


Local and systemic complications of acute pancreatitis

TABLE 3 - 29. COMPLICATIONS OF ACUTE PANCREATITIS Local Systemic Necrosis Shock Pseudocysts Respiratory failure Abcess Renal failure

Ileus Metabolic–hypocalcemia, hyperglycemia

Fistulization Coagulopathy–disseminated intravascular coagulation

Gastrointestinal hemorrhage–pseudoaneurysm


Scan of pancreas indicating gas bubbles within pancreas


Major causes of death in acute pancreatitis delineated

TABLE 3 - 33. MAJOR CAUSES OF DEATH IN ACUTE PANCREATITIS

Sepsis–infected necrosis/asbscess Renal Multiorgan failure Cardiovascular Pulmonary (adult respiratory distress syndrome)

Single - organ failure


Infected necrosis can occur within first week of illness


Severe necrosis


Pseudocysts (A)


Pancreatitis crónica


Marseilles-Rome classification


Classification by etiology


Classification by pancreatic duct morphology


Pathophysiology (A)

OH: consumo excesivo por 6 a 12 añosEfecto tóxico directo cel. acinares? Excesiva estimulación secretora?Interferencia flujo proteínas intracelular? Formación de trombos proteicos ductales (litostatina)?


Pathophysiology (B)


Histology (A)

normal

islotes

acinos


Histology (B)

Destrucción de acinosFibrosis

islotes

Pancreatitis crónica


Steatorrhea and diabetes mellitus (A)


Steatorrhea and diabetes mellitus (B)


Tests of structure: plain abdominal radiograph

Idiopática: 20-40%, Alcohólica 70%, (a los 15 años)


Tests of function: simple markers


Natural history


Basis for pain relief by reducing pancreatic secretion (A)


Basis for pain relief by reducing pancreatic secretion (B)


Octreotide: reducing pancreatic secretions, relieving pain


Enzyme use for pain

TABLE 4 - 24. PANCREATIC ENZYMES FOR THE TREATMENT OF STEATORRHEA OR

PAIN

Conventional Enzyme Preparations

Enteric - Coated Enzyme Preparations

Brand Name Units of lipase/pill Brand Name Units of lipase/pill

Lipase (Viokase) 8000 Pancrelipase (Cotazym - S) 5000

Pancrelipase (Cotazym)

8000 Enteric - coated pancrelipase (Pancrease MT4, MT10, MT16)

4000, 10,000, 16,000, respectively

Amylase (Ku - Zyme HP)

8000

Porcine pancreatic enzyme (Creon)

10,000

Pancrelipase (Ultrase MT6, MT12, MT18, MT20)

6,000, 12,000, 18,000, 20,000, respectively


Steatorrhea and diabetes

© 2003 science press internet services fisiologÍa digestiva (bcm ii) clase 16- páncreas dr....

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