Enzymes (Liver & Pancreatic)

Question 1

List the pancreatic enzymes and describe their production and regulation

Answer 1

The pancreas has both exocrine and endocrine functions. The exocrine pancreas secretes digestive enzymes that are essential for nutrient breakdown.

Major Pancreatic Enzymes:

Amylase – digests carbohydrates to disaccharides.

Lipase – breaks down triglycerides into fatty acids and monoglycerides.

Proteases:
Trypsinogen → Trypsin (activated in the duodenum)
Chymotrypsinogen → Chymotrypsin
Procarboxypeptidase → Carboxypeptidase
Nucleases – break down DNA/RNA.

Production:

Synthesized by acinar cells in inactive (zymogen) forms to prevent self-digestion.
Secreted into the pancreatic duct → common bile duct → duodenum.

Regulation:

Hormonal:
CCK (cholecystokinin): Released from the duodenum in response to fats and proteins; stimulates enzyme secretion.

Secretin: Released in response to acidic chyme; promotes bicarbonate secretion to neutralize acid.

Neural:
Vagal stimulation (parasympathetic) via the cephalic phase enhances secretion.

Question 2

Describe the control of blood glucose in health and outline the pathophysiology of diabetes mellitus.

Answer 2

Normal Blood Glucose Control:

Maintained between 4.0–7.8 mmol/L.

Insulin (from pancreatic β-cells):
Promotes glucose uptake (especially in muscle, adipose).
Stimulates glycogenesis, lipogenesis, and protein synthesis.
Inhibits gluconeogenesis and glycogenolysis.

Glucagon (from α-cells):
Opposes insulin; raises blood glucose during fasting by promoting gluconeogenesis and glycogenolysis.

Diabetes Mellitus (NICE Guidelines covered below):

Definition: A chronic condition characterized by hyperglycemia due to deficient insulin action or production.
Type 1 Diabetes:
Autoimmune destruction of β-cells → absolute insulin deficiency.
Onset usually in childhood or adolescence.

Type 2 Diabetes:
Insulin resistance + relative insulin deficiency.
Strongly associated with obesity and sedentary lifestyle.
More common in adults, though increasingly seen in children.

Symptoms:
Polyuria, polydipsia, fatigue, weight loss, recurrent infections, blurred vision.

NICE Guidelines (NG28):
Diagnosis (Type 2): Fasting plasma glucose ≥ 7.0 mmol/L, or HbA1c ≥ 48 mmol/mol (6.5%).
Lifestyle intervention is first-line in T2DM.
Metformin is first-line pharmacological treatment unless contraindicated.
Target HbA1c:
≤ 48 mmol/mol for lifestyle only
≤ 53 mmol/mol if on medication

Question 3

Outline the role of the liver and pancreas in the metabolism of proteins, carbohydrates and fats

Answer 3

Carbohydrate Metabolism:

Liver:
Stores glucose as glycogen (glycogenesis).
Releases glucose via glycogenolysis and gluconeogenesis.
Pancreas:
Insulin lowers blood glucose.
Glucagon raises blood glucose.

Protein Metabolism:

Liver:
Converts amino acids into urea (urea cycle).
Synthesizes plasma proteins (e.g., albumin, clotting factors).
Pancreas:
Secretes proteolytic enzymes (trypsin, chymotrypsin).
Endocrine hormones influence protein anabolism.

Fat Metabolism:

Liver:
Synthesizes and oxidizes fatty acids.
Produces lipoproteins, cholesterol, ketone bodies.
Pancreas:
Secretes lipase.
Insulin promotes fat storage; inhibits lipolysis.

Question 4

Outline the metabolism of bile acids and the physiological basis of jaundice.

Answer 4

Bile Acid Metabolism:

Synthesized in the liver from cholesterol.
Primary bile acids: cholic acid, chenodeoxycholic acid.
Conjugated with taurine or glycine → secreted into bile.
Emulsify fats in the intestine for digestion and absorption.
Most are reabsorbed in the ileum (enterohepatic circulation).

Jaundice: Yellow discoloration due to hyperbilirubinemia.

Types:

Pre-hepatic: Excess hemolysis → ↑ unconjugated bilirubin (e.g., hemolytic anemia).

Hepatic: Liver dysfunction → impaired conjugation (e.g., hepatitis, cirrhosis).

Post-hepatic (obstructive): Blockage of bile flow → ↑ conjugated bilirubin (e.g., gallstones, tumors).

Question 5

Define diabetes and describe the symptoms and physiology of this condition

Answer 5

Definition (NICE):

A metabolic disorder of multiple etiology characterized by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both.

Physiology:

In diabetes, there is:

Reduced cellular uptake of glucose.

Increased fat breakdown (lipolysis) → ketone production (especially in T1DM).

Protein catabolism for gluconeogenesis.

Hyperglycemia → osmotic diuresis → dehydration and electrolyte imbalance.

Key Symptoms:

Polyuria: Excess urination due to osmotic diuresis.
Polydipsia: Thirst from dehydration.
Polyphagia: Increased hunger (mainly in T1DM).
Fatigue, weight loss, blurred vision, recurrent infections.