Session 5 Flashcards
What protects cells lining duodenum from acidic chime?
Chyme is low pH, hypertonic and partially digested so is damaging to GI tract mucosa outside of the stomach.
Brunner’s glands secrete alkaline mucus, protecting cells lining duodenum from acidic chime.
How is the hypertonicity of chyme dealt with in the duodenum?
Hypertonic chyme exits stomach and isotonic chyme exits duodenum
- Initial digestion of food in stomach creates solutes that make the chyme hypertonic
- Stomach wall largely impermeable to water – Water cannot move into stomach to dilute chyme
- Duodenum relatively permeable to water – Hypertonic chyme draws movement of water from ECF/circulation into duodenum to make it isotonic.
- Chyme release must be controlled so as not to overwhelm duodenum.
What mechanisms allow neutralisation and further digestion in the duodenum?
Partially digested (still many proteins, fats and CHOs to breakdown). Achieved through secretions from pancreas and liver Enzymes (pancreas), bicarbonate (both) and bile (liver)
What does the duodenum secrete in response to the presence of chyme?
Duodenum secretes secretin and cholecystokinin (CCK) in response to presence of chyme.
Secretin acts on pancreas to stimulate release the aqueous bicarbonate (HCO3-) component of the pancreatic secretion. Secretin also acts on the liver to release its bicarbonate component.
CCK acts on the pancreas to stimulate release of enzyme component of pancreatic secretion. CCK also acts on the gallbladder causing contraction and relaxes sphincter of oddi
Describe the pancreas’ major function
- 90% pancreas is exocrine function – vs much smaller proportion for endocrine function
- Pancreatic secretions (exocrine function) stimulated via gut hormones (secretin and CCK) but also autonomics – Sympathetic inhibits – Parasympathetic (vagus) stimulates
Describe the structure of the pancreas
Macro: Head of pancreas located between the C shape of duodenum, neck sits behind first part of duodenum and is attached to head, pancreas then continues with a body and then a tail orientated towards and adjacent to the spleen. Ducts that drain the pancreas join together and go onto join the common bile duct to form the ampulla of vater which drains its contents out through the sphincter of oddi so that bile and pancreatic secretions are secreted simultaneously together.
Micro: Origins of the pancreatic duct have branches of smaller ducts that terminate in small sacs called Acini (Acinus singular) (Not too disimilar to structure of lungs in terms of shape)
Acinus: Within the sacs we have Acini cells which surround a terminal duct which is lined with duct cells. Within acinar cells we can see granules containing the enzymatic component of the pancreatic secretions.
The aqueous component with the bicarbonate is produced by duct cells.
We also have collections of cells called islets of Langerhans which contain alpha (secrete glucagon), beta (secrete insulin) and delta (secrete somatostatin) cells which drain directly into blood vessels.
How is the exocrine pancreas stimulated and what can go wrong?
- CCK (and vagus) stimulate acini (singular = acinus) to produce enzymes – Amylases and lipases (active-ready to go) – Proteases (inactive-stored in zymogen granules)
- Proteases (when activated in intestinal lumen) include: – Trypsin – Chymotrypsin – Elastase – Carboxypeptidase
If proteases were stored in their active form they would begin to digest the pancreas itself so must be stored as zymogens.
If pancreas gets blocked proteases can stay in pancreas and get activated and cause pancreatitis.
What happens when exocrine pacreatic duct cells are stimulated?
Stimulation of duct cells releases aqueous component (isotonic) containing bicarbonate. This will act to neutralise the acidic chyme.
How do liver and pancreatic secretions reach the duodenum?
Out of liver via common hepatic duct where it meets cystic duct to form common bile duct where it meets the pancreatic duct to form Ampulla of Vater / hepatopancreatic duct then exits via sphincter of oddi
What does the liver secrete in response to chyme? What is it and what does it do?
- Liver secretes bile (stored in gallbladder) into the duodenum – Secretion of bile (250mL-1000mL/day)
- Bile consists of bile acids and bile pigments and alkaline solution
- Bile plays two key roles in digestion by emulsifying fats (lipids) in duodenum so that they can be readily digested by lipases secreted by pancreas; and aids in absorption of digested end products of fat through intestinal wall. Bile also allows for waste products from blood to be excreted e.g. through bilirubin.
Give a small overview of the liver as an organ
- Liver is largest single organ
- Hepatocytes are chief functional cell of liver – Form 80% of liver mass
- Liver is highly metabolically active producing proteins and lipids for export – Lots of rough/smooth ER – Stacks of Golgi membranes
- Stores lots of glycogen • All blood from gut drains into liver via portal vein
- Produces bile drains from liver into gut
Describe the macro anatomy of the liver
Larger right lobe than left lobe which is separated by the falciform ligament. Two accessory lobes of right lobe called caudate and quadrate lobes (only anatomical lobes not different in function)
Describe the microanatomy of the liver
Arranged into lobules which have are a hexagonal arrangement of cells, bile ducts and blood vessels.
Within that lobule we have sheets of hepatocytes arranged along a number of venous channels which drain into a central hepatic venule
Describe the structure of a liver lobule
- Hexagonal arrangement
- Triad of structures at each corner: - Portal vein (branch) - Hepatic artery (branch) - Bile duct (branch)
- Central vein in middle
- Blood enters a lobule via hepatic artery and portal vein (branches of)
- Blood flows in towards central vein via sinusoids
Bile flows out Along canaliculi to the Bile duct through Into duodenum
Describe the functional area of a liver lobule
Functional area of the lobule is called the ‘acinus’ - contains two adjacent but opposite triangles.
Hepatocytes make bile which drains along canaliculi into a branch of the bile duct. Blood and bile drain in opposite directions.
- Blood enters from periphery of lobule to centre
- Substances to liver from gut (via portal veins) and oxygen (hepatic artery) start at periphery and work towards middle (towards central vein)
- Creates a series of zones (1,2,3) corresponding to distance from blood supply
- Certain pathological processes lead to hepatocyte damage reflecting this acinar structure.
- Toxic damage (zone 1) vs ischaemia (zone 3)
Where is bile produced and what is its function?
- Bile created by hepatocytes and duct cells in liver - continuously produced - But only needed intermittently
- Stored in the gallbladder which also concentrates bile (removes water/ions)
- Can lead to gallstones – CCK released from duodenum stimulates gallbladder contraction
- Emulsify fats aiding their digestion
What does CCK do in relation to the gallbladder?
CCK Stimulates contraction of gallbladder so bile is secreted via common bile duct, into ampulla of vater and then into the duodenum
Summarise how the emulsion droplet gets to the circulation
What are the differences between the jejunum and he ileum?
What is the blood supply to the intestines? What is the venous drainage of the intestines?
Superior mesenteric artery leaves abdominal aorta at L1 (trans pyloric plane) and branches giving the ileocolic (supplies terminal ileum and caecum), right colic (supplies ascending colon), middle colic (supplies transverse colon) and the jejunal and ileal arteries (supply the jejunum and ileum).
At the end of these terminal branches is a network of anastomoses which forms the marginal artery which runs along the margins of the gut tube.
All drains into portal vein which goes into the liver. Portal vein formed by the superior mesenteric vein meeting the splenic vein. Inferior mesenteric drains into splenic.
What are plicae circulares?
Permanent folds in small intestine.
Describe the intestinal epithelia
Epithelial cells – • Enterocytes (most of the cells in the small intestine)- absorptive cells
- Tall columnar cells
- Goblet cells- mucus producing
- Enteroendocrine cells- produce hormones
Intestinal gland (crypts of Lieberkuhn):
Stem cells at base which migrate to surface, maturing as they migrate into variety of cell types
Paneth cells at base (innate mucosal defence cells) which produce antimicrobial peptides
Mucosa is constantly shed (3-6 days)
Describe monosaccharide absorption
Na+/K+ ATPase on basolateral membrane of enterocyte - Maintains low intracellular Na+ to create gradient for
SGLT-1
SGLT-1 binds with Na+
- This allows glucose/galactose binding to SGLT-1
- Na+ is then co-transported with glucose/galactose into the cell
GLUT2 transports glucose/galactose/fructose out of enterocyte
• Diffuses down gradient into capillary blood
Fructose uses GLUT5 transporter to enter enterocyte
• Facilitated diffusion
Describe starch digestion
Starch consists of:
- Straight chains of glucose- Amylose
- Branched chains of glucose-Amylopectin
- In Amylose the chains have alpha 1-4 bonds
- In amylopectin the branched bits are alpha 1-6 bonds
- Salivary and pancreatic amylase breaks the Alpha 1-4 bonds in amylose, producing the disaccharide maltose (glucose + glucose)
- When amylase breaks the alpha 1-4 in amylopectin you liberate shorter (but still branched) chains of glucose (called alpha dextrins)
- Isomaltase is required to break the branched alpha 1-6 bonds
So from starch we end up with:
- Glucose (fine)
- Maltose (maltase) = Glucose + Glucose
- Alpha dextrins (isomaltase) = Glucose
Isomaltase and maltase are brush border enzymes
How are proteins digested?
- Stomach - (H+/pepsin)
- Intestinal lumen- (Trypsin…)
- Brush border
- Cytosol (cytosolic peptidases)
- In stomach
- Pepsinogen released from chief cells
- gets converted to pepsin by HCl
- Pepsin acts on protein
- Broken down into oligopeptides/amino acids
- They move to small intestine
- Pancreas releases proteases as zymogens –(move into intestinal lumen to be activated)
- Trypsinogen is important
- Converted to trypsin by enteropeptidase (enterokinase)
- Trypsin then activates other proteases including more of itself
Major proteases- released from pancreas: -Endopeptidases (produce shorter polypeptides) - Trypsin - Chymotrypsin - Elastase -Exopeptidases (produce dipeptides or amino acids) e.g. Carboxypeptidase (A and B)
- Brush border- also contains proteases
- The enterocytes express peptidases in their brush border
- Sometimes cannot completely digest proteins down to amino acids
- However intestine can absorb short peptides (as well as amino acids) by Peptide transporter 1 (PepT1)
- Amino acids are transported into cell (similar to glucose) using Na+-amino acid co-transporters
- Cytosol of enterocyte
- The small peptides are then acted on by cytosolic peptidases (broken down to amino acids)
- Certain di- and tri-peptides can also be absorbed into blood
Describe water secretion from the enterocyte
- Secretion is driven by chloride movement (predominantly)
- Chloride enters crypt epithelial cell
- Co-transported with Na and K
- Cyclic AMP levels increase inside cells
- Increased cAMP activate CFTR
- Cl ions are secreted
- Na is drawn into lumen across tight junctions
- NaCl secretion creates osmotic gradient
- Water moves into lumen
Defect in CFTR can cause thick mucus as not enough CL leaves so less water so you end up with thicker mucus.
