Download Metabolism and Digestion-Lecture 4

Human Form & Function 2
Exocrine Secretory Functions of
The Liver and Pancreas
Dr. Neil Docherty Teaching Objec5ves •  Describe the structure of the exocrine pancreas and identify
the major acinar and ductular secretions
•  Discuss key aspects of the cellular physiology of exocrine
pancreatic secretion
•  Describe the lobular structure of the liver and the fundamental
aspects of bile production, storage and recirculation, and its
role in digestion and absorption.
•  Highlight the causes of choleostasis and its consequences for
the digestive and absorptive processes.
The Sphincter of Oddi Delivers Pancreatic
and Biliary Secretions to the Duodenum
Sphincter of Oddi
EXOCRINE
PANCREATIC SECRETIONS
1)Ductular
-Bicarbonate solution
2) Acinar
-Enzyme rich secretion
Duodenal Cluster Unit
ACINAR SECRETIONS REACH
DUCTS AND ARE CARRIED
TOWARDS THE DUODENUM
WHERE THEY ARE DELIVERED
ALONG WITH BILE
Basics of Pancreatic Secretion
ACINUS
Enzymes
/zymogens
INTERCALATED DUCT
H 2O
HCO3
-
ALKALINE ENZYME
MIX
Acinar Cell Secretions
• Digestive enzymes
• Stored as granules
• Released by regulated compound exocytosis
PROTEASES
Trypsinogen
AMYLOLYTICS
NUCLEASES
OTHERS
Lipase
DNase
Procolipase
Chymotrypsinogen
Esterase
RNase
Trypsin
inhibitor
Proelastase
Phospholipase A2
Procarboxypeptidase
A
Procarboxypeptidase
B
Amylase
LIPASES
Regulated Exocytosis
Pancreatic Acinar Cells
Lumen
of
Acinus
T.E.M. of Pancreatic Acinar Cell
Route from Acini to Duodenum
Acini
Intercalated ducts
Intralobular duct
Interlobular duct
Main pancreatic duct
(Wirsung’s duct)
Accessory pancreatic duct
(Duct of Santorini)
Common bile duct
Sphincter of Oddi
Duodenal Ampulla
Ductular Cell Secretions
• Secrete bicarbonate in response tp secretin
• Water follows paracellularly
• PROVIDES FOR ACID NEUTRALISATION
• AIDS IN ESTABLISHING pH OPTIMUM FOR
PANCREATIC ENZYME ACTIVITY
Secre5n and Cholecystokinin (CCK) CCK-More Detail on Effect on Pancreas
Fat and protein in duodenal lumen
CCK releasing peptide release
Duodenal I cells
CCK
Ductular cells
Potentiation
of bicarbonate
release
Direct endocrine
and vago-vagal
Acinar cells
Enzyme secretion
N.B. As levels of active trypsin elevate in
gut lumen, proteolytic cleavage of releasing peptide
Release ensues (negative feedback control)
Secretin-More Detail
Gastric acid in duodenum
Potentiation
of bicarbonate
release
Duodenal S cells Elevation in pH shuts
down secretin release
SECRETIN RELEASE
Acid neutraliztion and enzyme
activation in duodenum
Bloodstream
Stimulation of pancreatic ductular
secretion of bicarbonate
Cellular Physiology of
Ductular Bicarbonate Secretion
Mutant gene code
In Cystic Fibrosis
Ductular Epithelium
HCO3-
D
U
C
T
L
U
M
E
N
Na+/ HCO3-
Na+
Na+
2K+
ClHCO3Cl-
Na+/ K+
ATPase
H2O + CO2
Cl-/HCO3exchange
Carbonic
anhydrase II
HCO3
H
CFTR
3Na+
Na+/ H+
H+
Na+
phosphorylation PKA
K+
cAMP
H2O Transepithelial osmotic gradient
DILUTE ALKALINE SECRETION
SECRETIN
K+ channel
K+
Cystic Fibrosis
• Ireland has highest incidence in World
• Mutations in CFTR chloride channel gene
• Although lung disease most widely known correlate, named
for characteristic pancreatic lesions
• Inability to secrete bicarbonate from pancreas
• Pancreas is not flushed. In duodenum, acid remains
unneutralised and pancreatic enzymes remain inactive.
• In severe homozygous mutations, exocrine pancreas destroyed
during foetal life
• Pancreatic insufficiency=antacid and enzyme supplements
Liver
•  Largest and most important metabolic organ in the body
-metabolic processing of nutrient
-detoxification and biotransformation for excretion
-metabolic activation
-Synthesis of plasma proteins
-Immune function
-Storage of minerals and vitamins
-Production of bile
Relevant to excretory, digestive and absorptive function
Destination of Absorbed
Materials
3 circulations meet
and mingle
TAGs
Via lymphatics
And thoracic duct
Glucose
Amino acids
SCFAs
Soluble vitamins
Lobular Structure of Liver
Bile
Principal Components
-bile acids,
-cholesterol
-phosphotidylcholine
-conjugated bilirubin
digestion and absorption
Fat dispersal
Mixed micelle formation
Bile acids (200-400mg/day)
HEPATOCYTES
HIGH WATER
SOLUBILITY
LOW WATER
SOLUBILITY
INTESTINAL
BACTERIA
Bile Acid Conjugation and Deconjugation
In hepatocyte
Glycine and taurine conjugation
of primary and secondary
bile acids-Increases solubility
Bacterial deconjugation
-Decreases solubility
Bile Processing on Journey Through Liver
Canaliculi
Hyperosmotic secretion, addition of calcium,
phosphotidylcholine and cholesterol
Ductules
glucose and amino acid reabsorption, addition of
bicarbonate, free water and secretory IgA.
Renders isotonic alkaline solution
Ducts
Addition of mucus
The Gall Bladder
Bile Storage and Mobilisation
Bile Related Effects of CCK
-Gall bladder contraction
-Sphincter of Oddi Relaxation
Micelle Formation (RE: Lipid Absorption)
Allows for trapping of
lipid soluble compounds
in intestine
Enterohepatic Recirculation of Bile Acids
Apical Sodium Dependent Bile Acid Transporter
(ASBAT)
Kidney
200-400mg produced per day
However,
During feeding, 2000-3000mg/h
Cholestasis
• Production and/or excretion of bile impaired
Causes
Primary biliary
cirrhosis
Primary Sclerosing Hereditary
Cholestasis
Cholangitis
Syndromes
Consequences
pruritis, hypercholesterolaemia,
Malabsorption, hepatic fibrosis
Obstructive
Jaundice
Your Learning From Today Should focus on being able to;
1) Describe the structure of the exocrine pancreas and identify
the major acinar and ductular secretions
2) Discuss key aspects of the cellular physiology of exocrine
pancreatic secretion and the consequences and causes of
insufficiency
3) Describe the role of the liver in digestion and absorption
4) List common causes of choleostasis and describe its
consequences for the digestive and absorptive processes.