Week 11 Pancreatic Disorders

Location of the Pancreas

Behind the stomach and is close to the duodenum, the first part of the small intestine.

Pancreas exocrine function

Produces digestive enzymes that break down food in the duodenum.

Secretes bicarbonate to neutralize stomach acid.

Pancreas endocrine function

Produces hormones that regulate blood sugar and other functions:

• Insulin and glucagon: Regulate blood glucose levels

• Somatostatin: Prevents the release of insulin and glucagon

Pancreas exocrine tissue

95% of the pancreas consists of this tissue. This tissue produces pancreatic enzymes for digestion.

Acinar cells

Special cells are produced by exocrine tissue in the pancreas, which are essential for digestion. These cells produce, store, and release digestive enzymes.

Digestive enzymes (juice)

• Vesicles

  • Amylase, lipase, nucleases, proteolytic enzymes

• Zymogen or proenzyme

  • Trypsin, chymotrypsin and carboxypeptidase

Delivered into the small intestine. It breaks down food (sugars, fats, starches) into nutrients. It helps by speeding up the chemical reaction in the body.

Bicarbonate (ductal cells)

Cells produced by the pancreatic duct cells to neutralize stomach acid, maintain duodenal pH and acidic content secreted by acinar cell.

Pancreatitis

Inflammation of the pancreas is caused by digestive juices or enzymes attacking the pancreas—the activation of zymogens within pancreatic acinar cells.

Can be acute or chronic.

It can be caused by gallstones, heavy alcohol consumption and, less commonly, trauma, infections, or unknown causes.

Zymogens

Also known as a proenzyme, an inactive protein that can be transformed into an active enzyme through a biochemical change. Found in all living organisms and play a critical role in controlling when and where enzymes become active.

ALT is associated with

Liver function and damage

Digestive Enzymes - Amylase

• Converts starch into sugar

• Produced by salivary glands

• Measured as a marker for acute pancreatitis

Amylase - Levels in the serum

• 2 to 12 hours after onset of acute pancreatitis (8X RI)

• Normal levels 3 to 4 days after onset of symptom

These are less specific than serum lipase. The reference interval is 30-110 IU/L (LifeLabs).

Digestive Enzymes - Lipase

Breaks down triglycerides

An enzyme that helps break down fats into fatty acids and glycerol, facilitating the digestion of dietary lipids.

Lipase - Levels in the serum

• 4 to 8 hours after onset of acute pancreatitis (2 to 50X RI)

• Normal levels 8 to 14 days after onset of symptoms

More specific and sensitive than serum amylase. The reference interval is < 60 U/L (LifeLabs).

Acute Pancreatitis

• Sudden Inflammation

  • can be life-threatening due to possible hemorrhage.

• Causes

  • Gallstones and alcohol use

  • Trauma

  • Medications

  • Infections

  • Tumour

• Around 80% of cases resolve on their own or treatment

• It can lead to chronic pancreatitis

Acute Pancreatitis Causes

• Gallstones

• Alcohol use

• Trauma

• Medications

• Infections

• Tumour

Acute Pancreatitis Symptoms

• Pain

• Fever

• Nausea

• Vomiting

Acute Pancreatitis - Diagnosis

• Most important markers:

  • Serum amylase assay

  • Serum lipase assay

• Trypsinogen activation peptide (TAP)

• Other tests

  • Phospholipase A2 (inflammation)

  • Procalcitonin (e.g., infection)

  • C-reactive protein (CRP)

Acute Pancreatitis Diagnosis -Trypsinogen activation peptide (TAP)

• Released during activation of trypsinogen

• Blood and urine

• Early diagnosis

• Determination of severity

  • associated with a severe form of acute pancreatitis

Chronic Pancreatitis

• Destruction of pancreas by digestive enzymes

• Inflammation progresses over time

• Causes

  • Heavy alcohol consumption

  • In children: cystic fibrosis

Chronic Pancreatitis - Inflammation progresses

• Permanent damage

• “Digestion” of the pancreas

• Severe pain/loss of function due to scar tissue and calcium

• Slow destruction of the pancreas due to diabetes or pancreatic insufficiency

Chronic Pancreatitis - Diagnosis

• Common pancreatic enzymes measured:

  • Trypsin, amylase, lipase, chymotrypsin, and elastase

• Consequences: diabetes and pancreatic insufficiency

  • Pancreatic insufficiency detected when 50% acinar cells destroyed

• Test interpretation:

  • Medical history (persistent enzyme elevation/flare-ups)

Very Challenging to diagnosis

Maldigestion

• Abnormalities in proximal part of digestive tract (pancreas)

  • Reduction or lack of digestive enzymes and bicarbonate

• Food not broken down properly

Malabsorption

• Abnormalities in distal part of digestive tract

  • Food not properly absorbed

Maldigestion and Malabsorption

• Decrease the ability of body to absorb nutrients.

• Symptoms/Sign:

  • Weight loss, fatigue, abdominal discomfort, flatulence, steatorrhea, etc.

• Causes:

  • Chronic pancreatitis, medications, tumours, celiac disease, etc.

Pancreatic Insufficiency

• Deficiency of digestive enzymes: Maldigestion and malabsorption

• Early malabsorption condition

  • i.e., fatigue and anorexia

• Laboratory tests

  • Antibody tests for celiac disease

  • Hemoglobin, MCV, folate, ferritin, calcium

  • Albumin

Fecal Fat Test

• Non-specific

• Looks for fat in the stool

• Indicates malabsorption or maldigestion

Qualitative test

Sudan stain IV

Quantitative test

• 72-hour fecal test

• High-fat diet for 4 days

• Utilize pre-weighted collection container

  • Nuclear magnetic resonance spectroscopy (Reference Interval: Less than 7g fat in 24 Hrs)

  • Elevated level of fecal fat indicates malabsorption disorder

Fecal pancreatic elastase 1 test

• Good indicator of exocrine pancreatic insufficiency

  • Sensitive and specific

  • Non-invasive

  • ELISA: detects certain antibodies, antigens and other substances in your blood, pee or other bodily fluid.

• Low levels

  • Indicative of pancreatic insufficiency

• Less expensive than the “gold standard” secretin-cholecystokinin

Secretin-cholecystokinin test

• “Gold standard”

  • Used to help diagnosing pancreatic malfunction

  • Combination of the secretin test and cholecystokinin test

• Assesses the function of the pancreas and gallbladder

  • Secretin (duodenum)

  • Cholecystokinin (duodenum and jejunum)

Secretin (duodenum)

Acidic chyme - bicarbonate-rich pancreatic juice is stimulated

Cholecystokinin (duodenum and jejunum)

Stimulates amylase, trypsin and lipase release and bile (gallbladder)

Trypsin Test

An enzyme that helps digest proteins in the small intestine

• Stool test

• Tests function of this enzyme

• Indicates pancreatic function

Trypsinogen (blood test)

A protein produced in the pancreas

• Released by the pancreas

  • Converted into trypsin

• Blood measurements

  • Low levels in blood

  • Indicator of pancreatic insufficiency