Physiology of Digestion and Absorption 1

Professor John PetersE-mail: j.a.peters@dundee.ac.uk

After this lecture students should be able to:

Describe the nature of the chyme List the hormones released from the duodenal mucosa Relate function to basic structure/cell type on drawings of the pancreas Compare salivary and pancreatic secretion - primary and modified

secondary secretion List the composition of pancreatic secretion Indicate briefly how pancreatic enzymes are activated Describe the importance of bicarbonate State the importance of bile in fat digestion Describe briefly the hormonal controls of biliary and pancreatic

secretions in the cephalic, gastric and intestinal phases of digestion

Learning Objectives

The Small Intestine Major site for digestion and absorption

Approx. 6 m long, 3.5 cm diameter (longer when relaxed - after death)3 parts Duodenum – approx. 25 cm Jejunum – approx. 2.5 m Ileum – approx. 3 m

Receives chyme from stomach pancreatic juice from pancreas bile from gall bladder

Secretes intestinal juice

Moves remaining residues to the large intestine

Duodenum secretes (into the blood) various peptide hormones from endocrine cells within the mucosa:

Gastrin – from D cells of gastric antrum (mainly) and duodenum Cholecystokinin (CCK) – from I cells of duodenum and jejunum Secretin – from S cells of duodenum

Motilin – from M cells of duodenum and jejunum Glucose-dependent (or glucagon-like) insulinotropic peptide (GIP)

– an incretin from K cells of duodenum and jejunum [note activity is potentiated by gliptins (e.g. sitagliptin) used in treatment of type 2 diabetes mellitus]

Secretions of the Small Intestine (1)

All act on G-protein coupled receptors

Glucagon-like peptide-1 (GLP-1) – an incretin from L cells of small and large intestine [note activity mimicked by extenatide and potentiated by gliptins (e.g. sitagliptin), both used in treatment of type 2 diabetes mellitus]

Succus (juice) entericus (of the intestine) – approximately 2 litre secreted per day - composition varies throughout small intestine

Secretions of the Small Intestine (2)

Control mechanisms include Distension/irritation, gastrin, CCK, secretin, parasympathetic nerve

activity (all enhance), sympathetic nerve activity (decreases) Secretion contains

mucus – for protection/lubrication (from goblet cells) aqueous salt - for enzymatic digestion (mostly from the crypts) no digestive enzymes

Secretion involves

Na+/K+ ATPase

Na+/K+/2Cl- co-tranporterChloride channel (CFTR)

Nb. Excessive activity causes secretory diarrhoea (as in cholera)

Mixing and Propulsion of Chyme (1)1. Segmentation (mixing)

“chopping” moves chyme back and forth – very vigorous after a meal (little / none between meals)

Alternating contraction and relaxation of segments of circular muscle Initiated by small intestine pacemaker cells causing the BER which is

continuous. At threshold activates segmentation which in the duodenum is primarily due to distension by entering chyme

Duodenum has frequent segmentation contractions (12 per min), ileum has fewer (9 per min) net movement is aboral

Segmentation in the empty ileum is triggered by gastrin from the stomach (gastroileal reflex)

Mixing and Propulsion of Chyme (2) Movement is slow - takes 3-5 hrs - allows time for absorption Strength of segmentation enhanced and decreased by parasympathetic

and sympathetic activity, respectively

2. PeristalsisTwo activities occur in the interdigestive, or fasting, state

A few localised contractions The migrating motor complex (MMC)

Occurs between meals every 90 – 120 minutes Strong peristaltic contraction passing length of the intestine

(stomach ileocaecal valve) Clears small intestine of undigested debris, mucus and sloughed

epithelial cells between meals – ‘housekeeper function’ Inhibited by feeding and vagal activity Triggered by motilin, suppressed by gastrin and CCK

Nb. Macrolide antibiotics (e.g. erythromycin) mimic the action of motilin and may cause unpleasant G.I. disturbances

Pancreatic Secretions Endocrine – insulin and glucagon – secreted to blood Exocrine – digestive enzymes (acinar cells), aqueous NaHCO3

- solution (duct cells) – secreted to the duodenum collectively as pancreatic juice

Pancreatic Enzymes

Trypsinogen

Acinar cellsEnzymes stored in

zymogen granules Duodenum

Enterokinase (mucosal cells)

Trypsinogen Trypsin+

Chymotrypsinogen

Procarboxypeptidase

Autocatalysis

Chymotrypsinogen

Procarboxypeptidase

Chymotrypsin

Carboxypeptidase

+

+

Proteases

AmylasesPancreatic amylase Pancreatic amylase

LipasesPancreatic lipase Pancreatic lipase

Inactive enzyme

Active enzyme

Can completely digest food in the absence of all other of enzymes

Secretion of the Pancreatic Duct Cells Duct cells secrete 1 – 2 litre of alkaline (HCO3

- - rich) fluid into the duodenum per day

Neutralises acidic chyme entering the duodenum Provides optimum pH for pancreatic enzyme function Protects the mucosa from erosion by acid

K+

Na+

Na+

H+

K+

Cl-Cl-

HCO3-HCO3

-

CO2

CO2 + H2O

Carbonic anhydrase

H2CO3

Na+, H2O Na+, H2O

Duc

tule

Secretion involves

Na+/K+ ATPase

Na+/H+ exchanger

K+/H+ ATPase

Cl-/HCO3-

exchanger

Chloride channel (CFTR)*

*Nb. Patients with cystic fibrosis have reduced fluid secretion

Control of Pancreatic Secretion

Acid in duodenal lumen

Secretin release from S cells

Pancreatic duct cells

Secretion of aqueous NaHCO3

solution into duodenal lumen

Secretin carried by blood Neutralizes

Fat and protein in duodenal lumen

CCK release from I cells

Pancreatic acinar cells

Secretion of digestive enzymes

into duodenal lumen

CCK carried by blood Digests

Three phases: Cephalic – mediated by the vagal stimulation of mainly the acinar cells (20% total

secretion) Gastric – gastric distension evokes a vagovagal reflex resulting in parasympathetic

stimulation of acinar and duct cells (5-10% total secretion) Intestinal (see below; 70-80% of total secretion)

The Biliary SystemComprises liver, gall bladder and associated ducts

Bile Produced continuously by the liver 0.6 – 1.2 litre per day

Between meals Stored and concentrated in gall bladder (sphincter of Oddi closed)

During a meal Chyme in duodenum stimulates gall bladder smooth muscle to contract Sphincter of Oddi opens Bile spurts into duodenum via cystic and common bile ducts

Bile composition Secretion of bile duct cells Secretion of hepatocytes

Secretions mix in the ducts

Bile participates in the digestion and absorption of fats

Acid in duodenal lumen

Secretin release from S cells

Pancreatic duct cells

Secretion of aqueous NaHCO3

solution into duodenal lumen

Secretin carried by blood Neutralizes

Hepatocytes and duct cells

Secretion NaHCO3 – rich bile into

duodenal lumen

Gastric secretion Gastric emptying

Integrative Activity of Secretin

Fat and protein in duodenal lumen

CCK release from I cells

Pancreatic acinar cells

Secretion of digestive enzymes

into duodenal lumen

CCK carried by blood Efficient Digestion

Gall bladder and sphincter of Oddi

Contraction of Gall bladder

Relaxation of sphincer of Oddi

Gastric secretion Gastric emptying

Integrative Activity of CCK