Week 1 - Pancreas

endocrine

• Islets of Langerhans

  • Alpha cells - Glucagon

  • Beta cells - insulin

Exocrine

• acinar cells

• 7 digestive enzymes

  • inactive zymogens

  • duodenum activation

• non-enzymatic fluids

  • bicarbonate optimized enzyme activity

Amylase (AMS)

• hydrolyzes complex carbohydrates

• pancreas = P type

• salivary glands = S type

• ↑ s. AMS → ↑ u. AMS

  • exceptions: macroamylase, renal failure

Macroamylase

• S-type AMS + Ig

  • constant ↑↑s. AMS but u. AMS is normal

  • non-pathological, confirmed by AMS isoenzyme assay

AMS detection methods - chromogenic

• dye labeled substrate substrate (insoluble) + AMS (sample) → hydrolyzed substrate (soluble) → colored solution

AMS detection methods - Oligosaccharide-4-NP substrate

oligosaccharide-4-NP + AMS (sample) → Free 4-NP (yellow color)

AMS detection methods - coupled enzyme methods (continuous monitoring)

• substrate + AMS (sample) → maltose

• maltose → glucose

• measure glucose

  • HK

AMS methods sources of error

• false decrease

  • acid pH (acidified urine)

  • increased triglycerides (serum) - cases lipemic sreum

• false increase

  • saliva contamination

AMS isoenzymes

• electrophoresis

• wheat germ inhibition

  • inhibits S-type AMS

Lipase (LPS)

• hydrolyzes triglycerides in dietary fat digestion

  • produces alcohols and fatty acids

  • reaction rate is accelerated by colipase and a bile salt which form a complex at the surface of the substrate and stabilizes lipase

  • attacks at interface between water and lipid

LPS method

turbidimetric

• reagent is fat/water emulsion

  • bile salts + colipase

• turbid reagent + LPS → ↓ turbidity

• interferences

  • sample lipemia

    • falsely decreased

pancreatitis

• inflammation of the pancreas

• cause: autodigestion of the pancreas due to reflux of bile or duodenal contents

• acute - no permanent damage to pancreas

• chronic - irreversible injury

• relapsing/recurrent - acute or chronic

Pancreatitis consequences

• acute edema

• decrease in circulating blood volume

• cellular infiltration → necrosis of acinar cells

• necrotic blood vessels → hemorrhage

• pancreatic fat necrosis

Acute pancreatitis diagnosis

• severe abdominal pain “acute abdomen”

  • R/O appendicitis

Acute pancreatitis diagnosis lab findings

• increase AMS

• “diagnostic window”

  • rise: 2-12 hrs peak: 12-72 hrs normal: 3-5 days

• increase LPS

  • more specific than AMS

  • rise: 4-8 hrs peak: 24 hrs normal: 8-14 days

chronic pancreatitis

• multiple bouts of acute pancreatitis → progressive pancreatic damage → pancreatic insufficiency

• symptoms intermittent

• alcohol abuse

• lab findings

  • ↓AMS, LPS, ↑↑glucose

pancreatic cancer

• head - signs include jaundice, weight loss, anorexia, nausea

• tail - vague symptoms

• beta cell tumor - hyperinsulinism (resulting in low blood glucose)

• some tumors overproduce gastrin (gastrinoma) - causes Zollinger - Ellison syndrome - symptoms include watery diarrhea, recurring peptic ulcer, gastric hypersecretion, and hyperacidity

Cystic fibrosis - all exocrine glands

an inherited autosomal recessive disorder, characterized by dysfunction of mucous and exocrine glands throughout body

cystic fibrosis manifestations

• intestinal obstruction (newborn)

• excessive pulmonary infections (childhood)

• pancreatogenesis malabsorption

• causes ducts and acini to dilate and convert into small cysts filled with mucus, preventing secretions from reaching duodenum

non-pancreatic disorders

• increased AMS

  • salivary gland disorders (mumps)

    • ↑ S type

  • other abdominal disorders: trauma, ovarian abscess, etc

  • opiates↑↑AMS, ↑LPS

• ↑LPS

  • liver cirrhosis, alc poisoning

Amylase creatinine clearance ratio (A/CCR)

• specimen

  • 24 hr urine or random urine

  • serum collected simultaneously

  • normal values <3.1%

A/CCR equation

↑A/CCR

• acute pancreatitis, burns, sepsis, diabetic ketoacidosis

• renal clearance of AMS higher than creatinine clearance rate

↓A/CCr

• macroamylasemia

• renal clearance of AMS lower than creatinine clearance rate

  • confirm with AMS isoenzyme testing

Clinical aspects of gastric analysis

• mainly used to detect Zöllinger-Ellison sydrome

  • gastrin-secreting neoplasm (plasma gastrin test)

  • usually located in the pancreatic islets

• used occasionally to evaluate pernicious anemia in adults

• aid in determining the type of surgical procedure for ulcer treatment

Gastrin stimulation

• use pentagastrin

  • synthetic pentapeptide composed of the four c-terminal amino acids of gastrin

  • widely replaced by fiberoptic endoscopy and radiologic procedures