Im-pancreas-procrastinotes (Edited by Jc)

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Subject: MEDICINETopic: PANCREASDate: JULY 13, 2012Lecturer: Dr. Andal-GamutanTranscriber: RSAEditor: JC LunaPages: 6

PANCREAS Pancreas is located behind the stomach Usual size is 12-15 cm length, 70 -110

grams Shape is elongated, flattened and

tapered Located at the back of the abdomen

behind the stomach

PHYSIOLOGY OF THE PANCREASThe pancreas has two types of tissues:

Exocrine tissues release enzymes that

are mainly concerned with digestionfound in the acinus and drains into ducts Endocrine tissues consist of the islet of

Langerhans and secretes hormones intothe blood stream (glucagon and insulin)that are mainly concerned with theregulation of carbohydrates

Pancreatic exocrine secretion • 1500 – 3000 ml isosmotic alkaline

(pH>8) fluid per day• 20 enzymes and zymogens• effects the major digestive activity of

GIT• provides an optimal pH for the function

of these enzymes

REGULATION OF PANCREATIC SECRETION • Gastric acid secretin p. juice rich in

H2O & elect.• Long chain FA, essential AA

(tryptophan, phenylalanine, valine,methionine) & gastric acid CCK enzyme-rich secretion (from acinar cellsin the pancreas).

• Gastrin weak stimulus for p. enzymeoutput

• Bile pancreatic secretion• Somatostatin --/pancreatic secretion

From Harrisons 18 th

editionThe exocrine pancreas is influenced by intimately interacting hormonal and neural systems. Gastric acid is the stimulus for therelease secretin from the duodenum, whichstimulates the secretion of water and electrolytes from pancreatic ductal cells.Release of Cholecystokinin (CCK) from theduodenum and proximal jejunum is triggered by long chain fatty acids, certain essential amino

acids (tryptophan, phenylalanine, valine,methionine) and gastric acid itself.

Water & electrolyte secretion

Bicarbonate – it is the ion of primary physiologicimportance within pancreatic secretion. It helpsneutralize gastric acid and creates theappropriate pH for the activity of the pancreaticenzymes.

PANCREAS Enzyme secretion - secretes amylolytic,lipolytic, and proteolytic enzymes. The acinar cell is highly compartmentalized and isconcerned with the secretion of pancreatic

enzymes.

Autoprotection - Auto digestion of thepancreas is prevented by the packaging of pancreatic proteases in precursor form and bysynthesis of protease inhibitor, which can bindand inactivate 20% of trypsin activity.

TESTS USEFUL IN THE DIAGNOSIS OFPANCREATIC DISEASES Pancreatic enzymes

amylase - elevated for 5 days lipase – obtain if more than 1 week trypsinogen pancreatic polypeptide

Pancreatic structure Radiologic and radionuclide tests Pancreatic biopsy with US or CT

guidance CT Scan is the best imaging study

From Harrisons 18

thedition

A CT Scan can confirm the clinical impression of acute pancreatitis even with less than athreefold increase in serum amylase and lipaselevels. Importantly, CT can be helpful indicating the severity of acute pancreatitis and the risk of morbidity and mortality and in evaluating the

complications of acute pancreatitis.Exocrine pancreatic function

direct stimulation – secretin indirect stimulation – nutrients followed

by assays of proteolytic, lipolytic andamylolytic enzymes

intraluminal digestion products –undigested meat, fibers, stool fat

rarely done, not available in RP measurement of fecal pancreatic

enzymes – elastase

ACUTE PANCREATITIS

Incidence: varies, depends on cause, e.g., alcohol,

gallstones, metabolic factors, drugsCommon Causes of Acute Pancreatitis

Gallstones – leading cause of AP Alcohol -2

ndmost common cause

Hypertriglyceridemia Postoperative state ERCP



Trauma Drugs Sphincter of Oddi dysfunction

CAUSES OF ACUTE PANCREATITIS Drugs for which association is definite

Azathioprine, 6-mercaptopurine Sulfonamides Thiazide diuretics Furosemide (common) Estrogen (oral contraceptives)

(common) Tetracycline (common) Valproic acid Pentamidine Dideoxyinosine

Drugs for which association is probable Acetaminophen (common) Nitrofurantoin

Methyldopa Erythromycin (common) Salicylates Metronidazole NSAIDS ACE inhibitors

UNCOMMON CAUSES OF ACUTEPANCREATITIS

Vascular causes and vasculitis Connective tissue disorders and

Thrombotic Thrombocytopenic Purpura Cancer of the pancreas

Hypercalcemia Periampullary diverticulum Pancreas divisum Hereditary pancreatitis Cystic fibrosis Renal failure

Vascular causes and Vasculitis Vascular

o Ischemic hypoperfusion state(after cardiac surgery)

o Atherosclerotic embolio

Aneurysm of celiac axis/ hepaticartery Connective tissue disorders with

Vasculitiso SLEo Necrotizing angitiso Thrombotic, thrombocytopenic

purpuraPenetrating peptic ulcer Obstruction of the ampulla of Vater

Regional enteritis Duodenal Diverticulum

RARE CAUSES OF ACUTE PANCREATITIS Infections

Mumps Viral hepatitis Other viral infections (coxsackievirus,

echovirus, cytomegalovirus) Ascariasis Mycoplasma, Campylobacter,

Mycobacterium avium complex, other bacteria

Autoimmune (e. g., Sjogren’s syndrome)

CAUSES OF ACUTE PANCREATITIS Causes to be considered in patients havingrecurrent bouts of acute pancreatitis without anobvious cause:

Occult disease of the biliary tree or pancreatic ducts, especially occultgallstones (microlithiasis, sludge)

Drugs Hypertriglyceridemia Pancreas divisum Pancreatic cancer Sphincter of Oddi dysfunction Cystic fibrosis Truly idiopathic


edition

There are many causes of acute pancreatitis,but the mechanism by which these conditionstrigger pancreatic inflammation have not beenfully elucidated. Gallstones continue to be theleading cause of acute pancreatitis (30-60%) Alcohol is the second most common cause,responsible for 15-30% of cases in the US.

PATHOGENESIS Drugs: hypersensitivity reaction or generation of a toxic metabolite (in some cases it is not clear which of these mechanisms is operative)

Autodigestion theory: proteolytic enzymes areactivated in the pancreas rather than in theintestinal lumen

Autodigestion is a currently accepted pathogenic theory; according to it, pancreatitis results when proteolytic enzymes (eg. Trypsinogen,chymotrypsinogen, proelastase, and lipolytic enzymes such as phospholipase A2) areactivated in the pancreas rather than in theintestinal lumen.

Factors: endotoxins, exotoxins, viral infections,

ischemia, anoxia, direct trauma. -> Proteolyticenzyme, trypsinogen, chymotrypsinogen,protease, Phospholipase A. Once theseproteolytic enzymes are activated in thepancreas rather than in the intestinal lumen, itwill cause pancreatitis.

Activated proteloytic enzymes (trypsin) -> digestpancreatic and peripancreatic tissues -> other enzymes (elastase and phospholipase) ->digest cellular membrane -> proteolysis, edema,interstitial hemorrhage, vascular damage,coagulation necrosis, fat necrosis, parenchymalcell necrosis - > cell injury -> death- Once the proenzymes are activated it willcause a cascading catastrophic effect on thepancreas and the surrounding local and distanttissues.- Editor’s note: please read Harrison’s Principlesof Internal Medicine, 18

thEd. Chap 313, p. 2636

for a detailed discussion of “Activation of



Pancreatic Enzymes in the Pathogenesis of Acute Pancreatitis”

Cellular injury and deathLiberation of: bradykinin peptides,

vasoactive substances &histamine

- Vasodilation- Increased vascular permeability- Edema with profound effects on many organs –most notably the lung - SIRS and ARDS as well as multiorgan failure- Cascade of local as well as distant effects

Pathogenesis Activation of Pancreatic Enzymes3 Phases

1. Intrapancreatic digestive enzymeactivation and acinar cell injury -consequence of zymogen activation

2. Activation, chemoattraction andsequestration of neutrophils in thepancreas resulting in intrapancreaticinflammatory reaction of variableseverity

3. Effects of activated proteolytic enzymesand mediators, released by inflamedpancreas, on distant organs.

CLINICAL FEATURES Abdominal pain – major symptom,

steady and boring, radiating to the back

50% of the cases, lasting for severalhours, sudden in onset, severe 8/10

Nausea, vomiting, abdominal distension – due to gastric hypomotility

On physical exam patient appearsdistressed and anxious

Low-grade fever Tachycardia Hypotension Shock (uncommon): (1) retroperitoneal

burn- hypovolemia due to exudation of blood and plasma proteins into theretroperitoneal space, (2) increased

formation and release of kinin peptides – vasodilation & increased permeability,and (3) systemic effects of proteolytic &lipolytic enzymes

Jaundice – due to the edema of thehead of the pancreas with compressionof the intrapacreatic portion of thecommon bile duct.

Erythematous skin nodules –subcutaneous fat necrosis

Pulmonary findings (10-20%) – basilar rales, atelectasis, and pleural effusion(most frequently left-sided)

Cullen’s sign – faint blue discolorationaround the umbilicus, may occur as aresult of hemoperitoneum

Turner’s Sign – A blue-red-purple or green-brown discoloration of the flanks;reflects tissue catabolism of hemoglobin

LABORATORY DATA 1. Amylase and Lipase - 2 most important

2. Trypsin3. Leukocytosis (15,000 – 20,000/µL)4. Hemoconcentration – because of

exudation of plasma5. Hyperglycemia – impairment of islet cell

functioning decreased insulin andglucagon

6. Hypocalcemia – because of saponification

7. Hyperbilirubinemia8. Alk. Phos, ALT, AST9. LDH >500U/dL – poor prognosis10. Hypoalbuminemia11. Hypertriglyceridemia Lipid profile usually

more than 1,00012. Hypoxemia

DIAGNOSIS – 2 of the following: Typical abdominal pain

threefold or greater elevation in serumamylase and / or lipase level and / or

Confirmatory findings on cross-sectionalabdominal imaging

Markers of severity –hemoconcentration (hct>44%),azotemia(BUN>22mg/dL) and signs of organ failure

DIFFERENTIAL DIAGNOSIS 1. Perforated viscus2. Acute cholecystitis and biliary colic

3. Acute intestinal obstruction4. Mesenteric vascular occlusion5. Renal colic6. Myocardial infarction7. Dissecting aortic aneurysm8. Connective tissue disorders with

vasculitis9. Pneumonia10. Diabetic ketoacidosis

Factors that Adversely Affect the Survival inAcute PancreatitisRanson/Imrie criteria

- poor predictive value; many clinicians nolonger use this; very hard to apply.1. At admission or diagnosis

a. Age >55 yearsb. Leukocytosis>16,000/uLc. Hyperglycemiad. Serum LDH>400IU/Le. Serum AST>250IU/L

2. During initial 48 ha. Fall in hematocrit by >10%b. Fluid deficit of >4000mlc. Hypocalcemia(<8 mg/dLd. Hypoxemia (PO2<60mmHg)e. Increase in BUN to > 1.8mmol/L

after IV administrationf. Hypoalbunemia

>3 Ranson’s signs Acute physiology and chronic health evaluation(APACHE II) score >8 Hemorrhagic peritoneal fluidObesity(BMI>29)



Risk Factors for Severity- Age > 60 years- Obesity, BMI > 30- Comorbid disease (DM increases the

risk for severity )

Markers of Severity within 24 hrs SIRS (temp>38 or 36 C, pulse>90 PR,

tachypnea>24 RR, elevatedWBC>12,000

Hemoconcentration BISAP (bedside index of severity in

acute pancreatitis) – BUN>22mg%,Impaired mental status, SIRS:2/4present, Age>60yrs, Pleural effusion

*3 or > associated increased risk of in hospitalmortality*

Organ Failurea. Cardiovascular hypotension (BP <

90mmHg) or tachycardia>130 beats/minb. Pulmonary: PaO2<60mmHgc. Renal: oliguria(<50ml/h) or increasing BUN,

creatinine >2mg%d. Gastrointestinal bleeding>500ml/24hours

*Single organ system failure 3-10%mortality*Multisystem organ failure 47%mortality

Local complicationsa. necrosisb. pseudocystc. abscess

Markers of Severity During Hospitalization Persistent organ failure Pancreatic necrosis Hospital – acquired infection

RISK FACTORS THAT ADVERSELY AFFECTSURVIVAL IN ACUTE PANCREATITIS

CT SEVERITY INDEX IN ACUTEPANCREATITIS Points

Grade of acute pancreatitis A. Normal pancreas 0

B. Pancreatic enlargement 1C. Inflammation compared with p.&peripancreatic fat 2

D. One peripancreatic fluid collection3

E. Two or more fluid collections 4Degree of pancreatic necrosis

A. No necrosis 0B. Necrosis of one-third of pancreas

2C. Necrosis of one-half of pancreas

4D. Necrosis of more than one-half of

pancreas 6----------------------------------------------------------------3-6 scores --- negligible7-10 --- 92% morbidity rate & 17%mortality ratePresence of necrosis – morbidity >20%With out necrosis - morbidity<10%, negligiblemortality rate

Course of acute pancreatitis 2 phasesFirst phase – 1-2wks, severity is defined byclinical parameters rather than morphologicfinding persistent organ failure(>48hrs) – causeof deathSecond phase – both clinical parameters(organ failure) and morphologic criteria(necrotizing pancreatitis). Median prevalence of organ failure is 54% in necrotizing pancreatitis(10% of acute pancreatitis)

Complications of Acute Pancreatitis

1. Local

a. Necrosis

i. Sterile

ii. Infected

iii. Walled-off necrosis

b. Pancreatic fluid collectionsi. Pancreatic abscess

ii. Pancreatic pseudocyst

iii. Pain

iv. Rupture

v. Hemorrhage

vi. Infection

vii. Obstruction of

gastrointestinal tract

(stomach, duodenum,

colon)

c. Pancreatic ascites

i. Disruption of main

pancreatic duct

ii. Leaking pseudocyst

d. Involvement of contiguous organs

by necrotizing pancreatitis

i. Massive intraperitoneal

hemorrhage

ii. Thrombosis of blood

vessels (splenic vein,

portal vein)

iii. Bowel infarction

e. Obstructive jaundice

2. Systemic

a. Pulmonary

i. Pleural effusion

ii. Atelectasis

iii. Mediastinal abscess

iv. Pneumonitis

v. Acute respiratory distress

syndrome

b. Cardiovascular

i. Hypotension

ii. Hypovolemia

iii. Sudden death

iv. Nonspecific ST-T changes

in electrocardiogram

simulating myocardial

infarction

c. Pericardial effusion



d. Hematologic

i. Disseminated

intravascular coagulation

e. Gastrointestinal hemorrhage

i. Peptic ulcer disease

ii. Erosive gastritisiii. Hemorrhagic pancreatic

necrosis with erosion into

major blood vessels

iv. Portal vein thrombosis,

variceal hemorrhage

f. Renal

i. Oliguria

ii. Azotemia

iii. Renal artery and/or renal

vein thrombosis

iv. Acute tubular necrosis

g. Metabolic

i. Hyperglycemia

ii. Hypertriglyceridemia

iii. Hypocalcemia

iv. Encephalopathy

v. Sudden blindness

(Purtscher's retinopathy)

h. Central nervous system

i. Psychosis

ii. Fat emboli

i. Fat necrosis

i. Subcutaneous tissues

(erythematous nodules)

ii. Bone

iii. Miscellaneous

(mediastinum, pleura,

nervous system)

TREATMENT Conventional Measures

1. Analgesics for pain – Meperidine does

not cause spasm of the sphincter of oddi2. Intravenous fluids and colloids to

maintain normal intravascular volume3. No oral alimentation (NPO) – food can

stimulate pancreatic secretion4. Nasogastric suction to decrease gastrin

release from the stomach and preventgastric contents from enteringduodenum

*Prophylactic antibiotics for severe pancreatitis

COMPLICATIONS

Infected pancreatic necrosis Diffuse infection of an acutely inflamed,necrotic pancreas

Occurring in the first 1-2 weeks after theonset of acute pancreatitis

Should be treated by surgicaldebridement

Clinical clues that should alert theclinician to the possibility of infected

necrosis are persistent fever,leukocytosis, and organ failure in apatient with necrotizing pancreatitis

Pancreatic abscess ill-defined , liquid collection of pus that

evolves over a longer period, often 4-6weeks

Pseudocyst Collections of tissue, fluid, debris,

pancreatic enzymes and blood develop over a period of 1-4 weeks

after the onset of acute pancreatitis

Walled-off necrosis organized necrosis coalescence of the pancreatic necrosis

and peripancreatic fat necrosis intostructure that is encapsulated by fibrous

tissues contains semisolid necrotic tissue

together with a considerable amount of dark fluid representing liquifaction of devitalized pancreatic andperipancreatic tissue as well as someblood

Walled-Off necrosis and a pancreaticpseudocyst may look very similar on firstinspection of a contrast-enhanced CTscan

On closer inspection, serial imagesshow that a portion of the pancreas as

well as variable amounts of peripancreatic tissue are necrotic

Pancreatic ascites due to disruption of the main pancreatic

duct, often by an internal fistula betweenthe duct and the peritoneal cavity or aleaking Pseudocyst

Elevated serum amylase level in whomthe ascites fluid has both increased levelalbumin & markedly elevated level of amylase

ERCP/MRCP confirms the clinical

suspicion and radiologic findings andoften demonstrates passage of contrastmaterial from a disrupted major pancreatic duct or Pseudocyst into theperitoneal cavity.

Treatment: nasogastric suction &parenteral alimentation, paracentesis,long acting Somatostatin analogueoctreotide

CHRONIC PANCREATITIS Chronic inflammatory disease of the

pancreas Characterized by irreversible damage to

the pancreas as distinct from thereversible changes noted in acutepancreatitis

o presence of histologicabnormalities, including chronicinflammation, fibrosis, andprogressive destruction of both



exocrine and eventuallyendocrine tissue

Pathophysiology Alcohol-induced – precipitation of

protein (inspissated enzymes) in theducts

There is a strong association of smoking and chronic pancreatitis. Cigarettesmoking leads to an increased susceptibility to pancreatic self-digestion. Smoking is an independent,dose dependent risk factor for chronic pancreatitis.

duct dilatation, diffuse atrophy of acinar cells, fibrosis & calcification

Direct toxic effects on the pancreas

CAUSES 1. Alcohol, chronic alcoholism2. Idiopathic pancreatitis3. Cystic fibrosis4. Hypertriglyceridemia5. Severe protein-calorie malnutrition w/

hypoalbuminemia6. Pancreatic and duodenal neoplasm7. Pancreatic resection8. Gastric surgery9. Gastrinoma10. Hereditary pancreatitis11. Traumatic pancreatitis

12. Abdominal radiotherapy13. Hemochromatosis14. Enterokinase deficiency

CLINICAL FEATURES Symptoms identical to acute pancreatitis Pain may be continuous, intermittent or

absent Weight loss Abnormal stools, malabsorption


edition

Patients with chronic pancreatitis seek medical attention predominantly because of twosymptoms: abdominal pain or maldigestion and weight loss.The abdominal pain may be quite variable inlocation, severity and frequency. The pain canbe constant or intermittent with frequent pain-free intervals. Eating may exacerbate pain,leading to a fear of eating with consequent weight loss. Many patients have impaired glucose tolerance with elevated fasting blood glucose levels. The diagnostic test best sensitivity and specificity is the hormonestimulation test utilizing secretin.

DIAGNOSIS 1. Amylase and lipase – not elevated2. Classic triad

pancreatic calcification – 1/3 steatorrhea diabetes mellitus

3. Intubation test – secretin stimulation test4. Cobalamin malabsorption – pancreatic

enzymes5. Marked excretion of fecal fat – p.

enzymes6. Decreased serum trypsinogen level7. Radiographic hallmark – calcification8. Sonography, CT, ERCP

Abdominal USG, CT scanning, and MRCP greatly aid in the diagnosis of pancreatic disease. In addition to excluding Pseudocyst and Pancreatic CA, CT may show calcification,dilated ducts or an atrophic pancreas. MRCP provides direct view of the pancreatic duct and isnow the diagnostic procedure of choice.

COMPLICATIONS 1. Cobalamin malabsorption2. Effusions – pleural, pericardial, or

peritoneal space

3. GI bleeding – peptic ulceration,gastiritis, pseudocyst eroding toduodenum, esophageal varices

4. Cholangitis5. Subcutaneous fat necrosis6. Bone pain7. Pancreatic cancer 8. Addiction to narcotics

TREATMENT Directed to two major problems

Pain Malabsorption

Painabstinence: alcohol & fatty mealsuse of narcoticspancreatic enzymes ,surgery

Malabsorptionpancreatic enzyme replacementsupportive measures

PANCREATIC CANCER 90% moderately differentiated mucinous

adenocarcinoma derived frompancreatic duct epithelium

5% islet cell origin

More common in men than in women Risk factors: cigarette smoking, alcoholconsumption gallstones, animal fat-richdiet, DM, chronic pancreatitis

Clinical manifestations are related tocompression or invasion the adjacentvital structures jaundice, pruritus, abd.pain, wt. loss

Diagnosiso No single laboratory testo Ultrasound and CTscano ERCP

Managemento Surgeryo Palliative management

For more info, read Harrison’s Principles of InternalMedicine, 18

thEd. Chap 313

END OF TRANSCRIPTION

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Im-pancreas-procrastinotes (Edited by Jc)

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