T1 L8 Secretions of liver, intestines, gallbladder & pancreas Flashcards
What are the 3 main sections of the small intestine?
Duodenum
Jejunum
Ileum
What are the functions of the duodenum?
Receives stomach contents, pancreatic juice & bile Neutralises stomach acids Emulsifies fats Increase in pH will inactivate pepsin Has pancreatic enzymes
What is the histology of the duodenum?
Brunner glands - empty into intestinal glands & secrete an alkaline fluid
Villi have a leaf-like shape
What is the function of the jejunum?
Nutrient absorption
What is the histology of the jejunum?
Extensive intestinal folds
Villi have a finger-like shape
Plicae circulares are well developed
What are peyer’s patches?
Aggregated lymphoid nodules found in the ileum
Small masses of lymphatic tissue that form part of immune system by monitoring intestinal bacterial problems & preventing growth of pathogenic bacteria in the intestine
What is the histology of the ileum?
Villi are shorter compared to the jejunum
Peyer’s patches extend throughout lamina propria & submucosa
What is the brush border?
Found on cells of small intestine & are made of microvilli.
Help with final stages of digestion
What is a crypt-villus unit?
Functional unit of the small intestine
Immature cells in the crypts of Lieberkuhn, which secrete fluid
At the tip the cells are well differentiated
What is the maturation zone in the crypt-villus unit?
Intermediate zone where cells are moving towards the tip of the villus & beginning to express enzymes & absorptive membrane transport proteins
What is the crypt?
Contains rapidly dividing stem cells that force migration of cells up the side of a villus
Crypt cells are a source of intestinal fluid secretion
What is the definition of chemical digestion?
Complex series of enzymatic reactions that convert dietary macromolecules into their corresponding sub units that fan then be absorbed by enterocytes
What cells are found in the crypts of lieberkuhn?
Paneth cells - lysozyme
Enterocytes
Enteroendocrine cells
What are the 3 types of enteroendocrine cells?
I - CCK stimulates the gallbladder to release bile
D - somatostatin
S - secretin stimulates pancreas to release bicarbonate
What cells are in the villi?
Goblet cells - secrete mucus, which lubricates & protects intestinal surface
Enterocytes - brush border which contains enzymes
What is coeliac sprue?
A malabsorption syndrome characterised by hypersensitivity to wheat gluten & gliadin
Results in immune-mediated destruction & denudation of small intestinal villi
Symptoms include diarrhoea, steatorrhoea, abdominal bloating & flatulence
What is the function/anatomy of exocrine glands in the pancreas?
80% of pancreas volume
Digestive function
Similar structure to salivary glands
Made of acinus (secrete digestive enzymes) & duct cells (secrete bicarbonate)
Delivers digestive enzymes & isotonic HCO3- rich solution into intestinal lumen
What is the function/anatomy if endocrine glands in the pancreas?
Metabolic function
4 types of Islet cells that release hormones such as insulin & glucagon
What is type 1 diabetes?
Beta cells on the pancreas no longer make insulin
Body’s immune system has attacked & destroyed beta cells
Have to take insulin daily
What is type 2 diabetes?
Usually begins with insulin resistance
Insulin production declines over time
What are the functions of exocrine secretions from the pancreas?
Alkaline fluid that neutralises acidic chyme entering small intestine
Secretes enzymes to break down the macromolecules in food & produce smaller nutrient molecules for intestinal absorption
What is the composition of exocrine secretions from the pancreas?
Water Electrolytes Proteolytic enzymes Lipolytic enzymes Amylolytic enzymes Nucleases Other enzymes - procolipase, trypsin inhibitor
What are some examples of proteolytic enzymes secreted by the pancreas?
Trypsin 1,2 & 3
Proelastase 1 & 2
Procarboxypeptidases A1, A2, B1, B2
What are some examples of lipolytic enzymes secreted by the pancreas?
Lipase
Phospholipase A
Pancreatic lipase
What is the mechanism for secretion by the pancreas?
1) Pancreatic enzymes synthesised as inactive proenzymes on ribosomes
2) Transferred into rough ER
3) Move to Golgi complex
4) Form acidic condensing vacuoles
5) Released as zymogen granules
6) Fusion & exocytosis of zymogen granules
How are zymogen granules stimulated for exocytosis?
Neural or hormonal stimulus causes zymogen granules to move to apical membrane. Fuse with plasma membrane & express their contents into the luminal space by exocytosis
Works with intracellular second messenger
What are some examples of stimuli that cause zymogen granules to be released?
Agonists such as:
CCK (cholecystokinin)
Acetylcholine
Secretin
How are enzyme secretions from the pancreas regulated?
Acetylcholine - binds muscarinic receptors on acing cells. Vasoactive intestinal peptide that increases blood flow & gastrin
Cholecystokinin - major agonist released from duodenal I cells when food enters duodenum. Responds to fats, monoglycerides, fatty acids & phenylalanine & tryptophan
How are alkaline secretions from the pancreas regulated?
Secretin - released by S cells in the duodenum. S cells are stimulates by a low pH as the food enters. Enters blood via duct cells.
Why do duct cells become hypersensitive to low levels of hormones?
pH is rarely low enough to stimulate high levels of secretion
CCK & Ach potentiate the action of secretin
What is the mechanism of isotonic NaCl primary secretion by acinar cells?
1) Na+/k+ pump creates inward directed Na+ gradient across basolateral membrane
2) Na+/K/Cl cotransporter produces net Cl- uptake, driven by Na+ gradient
3) Rise in intracellular K+ results from pump & cotransporter gets shunted by basolateral K+ channels that provide exit pathway for K+.
4) Intracellular accumulation of Cl- establishes electrochemical gradient that drives Cl- secretion into acinar lumen through apical membrane Cl- channels
5) Movement of Cl- into lumen makes the transepithelial voltage more negative, driving Na+ into the lumen via tight junctions
What is the mechanism of HCO3- secretion by ductal cells?
1) Cl- is recycled from the lumen into the cell via CFTR channel
2) Na+ is secreted into the duct lumen
3) Water follows by osmosis to produce a fluid secretion
What effects the rate of pancreatic juice secretion?
Ionic composition of pancreatic juice depends on the rate of secretion
Greater the rate of secretion the greater the HCO3- levels & the lower the Cl- levels
In unstimulated state - flow is low & electrolyte composition is similar to that of plasma
In stimulated state - flow rate increases & rise in bicarbonate in the secondary secretion is matched by a reciprocal decline in Cl- ion
What is cystic fibrosis?
Lack of a functional Cl- channel in the luminal membrane resulting in defective ductal fluid secretion
Ducts become blocked with precipitated enzyme & mucus which impairs secretion of needed pancreatic enzymes for digestion
Pancreas undergoes fibrosis
What is an example of the treatment given for CF?
Oral pancreatic enzyme supplements taken with each meal
What are the 3 phases that regulate pancreatic juice secretion?
Cephalic - 20%
Gastric - 10%
Intestinal - 70%
How does the cephalic phase regulate pancreatic juice secretion?
Sight, smell, taste of food trigger action potentials
Stimulates preganglionic fibres to transmit action potentials to postganglionic fibres
Acetylcholine increases primary secretion from acing cells
Acetylcholine increases bicarbonate secretion from the duct cells into the intercalated ducts
How does the gastric phase regulation pancreatic juice secretion?
Peptones in stomach Antrum stimulate gastrin release from G cells. This increases acing secretion.
Increase in gastrin release from G cells via vagal peptidergic, postganglionic efferents that stimulate pancreatic acing cells to increase secretion of enzymes via CCK receptor
Gastric distention - vago-vagal reflex
What do protons from stomach gastric acid stimulate?
Duodenal S cells to increase secretions of secretin, which increases HCO3- secretions from duct cells
Monoglycerides, fatty acids & amino acids induce CCK release from duodenal I cells
Lipids & proteins trigger vago-vagal reflex that increases pancreatic juice secretions
How does the pancreas prevent auto-digestion?
Zymogens are made in the inactive form
Cellular sequestration of zymogens in the membrane-limited vesicles throughout synthesis to the point of exocytosis to avoid contact with acinar cell cytoplasm
Activation of zymogens in the small intestine
Process depends on conversion of proenzyme trypsinogen to trypsin
Pancreas produces trypsin inhibitor to prevent activation of zymogens within pancreas
What is pancreatitis?
Pancreatic enzymes are activated within pancreas & surrounding tissue leading to auto digestion of the tissue
Epigastric pain radiating from epigastrium to back & is often relieved by leaning forwards
Most common causes are gender specific:
Gallstones in women
Alcohol in men
What are the functions of bile?
Provides alkali to neutralise gastric acid
Provides bile salts to facilitate absorption of fats
Acts as vehicle for the excretion of blood cell breakdown components
What is the function of bile salts?
Promote emulsification & solubilisation by forming mixed micelles
These enhance lipase action & assist in the delivery of digestive products to be absorbed by enterocytes
How is bile released?
1) Secreted by hepatocyte canaliculus
2) Undergoes modification in bile ducts
3) Concentrated & stored in gallbladder
4) Excreted into duodenum
What is the composition of bile?
Water
Ions
Bilirubin & biliverdin
Bile salts - synthesised from cholesterol
What are the 2 mechanisms of bile secretion?
Bile-acid dependent fraction
Bile-acid independent fraction
What is the bile-acid dependent fraction
Made from hepatocytes when sufficient bile acids are available for secretion. Come from cholesterol metabolism which generates cholic acid & chenodeoxycholic acid. Conjugated with taurine or glycine & Na+ to make water-soluble bile salts that are secreted from hepatocytes.
In the intestine a small amount of secondary bile acids are formed by bacteria converting a small amount of primary acids.
What is the bile-acid independent fraction
Produced by duct epithelium by the secretion of water & electrolytes
How is bile release controlled?
Minor role of vagus
Major role is from CCK, which is released from the duodenum in the presence of fatty & acidic chyme
What is enterohepatic circulation?
Circuit where solutes are secreted by the liver & returned to the liver via intestinal reabsorption
What is the process of enterohepatic circulation?
1) Molecules are secreted into the bile by hepatocytes
2) Delivered to the small intestine via the biliary tract
3) Reabsorbed from the small intestine
4) Returned to the liver via the portal venous system to become available again for uptake & secretion by hepatocytes
Why is enterohepatic circulation important?
Bile acid pool isn’t large enough to assimilate the lipid content of a typical meal
Bile salts & acids are recycled twice each meal & 6-8 times per day
95% of the bile salts that arrive in the intestine are reabsorbed
Deconjugated bile salts revert to bile acids
How are deconjugated bile salts reverted to bile acid?
Most are undissociated & reabsorbed by simple diffusion in the jejunum
Most primary & secondary bile salts are reabsorbed via Na+ bile salt cotransport when they reach the distal ileum
Small amount of bile acid is lost in faecal excretion each day
Describe the biliary tree
1) Hepatocytes secrete bile into canaliculi
2) Canaliculi join together & convey hepatic bile toward small terminal ductules at the periphery of liver lobules
3) Bile moves through a sequence of progressively larger ducts in each lobe of the liver & emergences in a hepatic duct
4) Hepatic ducts from each lobe join to form common hepatic duct
5) Cystic duct from gallbladder joins common hepatic duct to form common bile duct
What does hepatic bile that is secreted into bile Canaliculi contain?
Bile salts Bile pigments Cholesterol Lecithin Mucus Electrolytes Isotonic pH
What are bile pigments?
Acid-dependent fraction contains bile pigments
Excretory function
Breakdown of haemoglobin in the spleen produces insoluble bilirubin
Hepatocytes conjugate bilirubin & excrete it via bile
What happens to conjugated bilirubin in the colon?
It gets covered to urobilinogen for recirculation & excretion via the kidneys.
The remainder is lost in the faeces
What is hepatic jaundice?
Accumulation of bilirubin in the blood
Impaired uptake by hepatocytes
Failure to conjugate bilirubin
Seen in hepatitis & cirrhosis
Describe the gallbladder
Sac found on underside of the liver
Around 10cm long
500-1000ml bile secreted daily from the liver
Gallbladder stores & concentrates bile
Where does the bilirubin pigment come from?
Haemoglobin breakdown
Intestinal bacteria convert to urobilinogen - brown colour
What is gallbladder disease?
Common
Occurs in several forms from asymptomatic cholelithiasis to biliary colic
Different areas of the biliary tract can be involved
Which part of the biliary tract does cholecystitis effect?
Blockage of cystic duct with associated infection of the gallbladder
Which part of the biliary tract does choledocholithiasis effect?
Blockage of common bile duct
Which part of the biliary tract does ascending cholangitis effect?
Blockage of common bile duct with associated infection of the bile duct
