1. GI Part 4 Flashcards
describe the liver morphologically
liver lobule – portal vein, hepatic artery, bile duct –> sinusoids, hepatocytes, bile canaliculi
endothelial wall – fenestrated –> passage of big molecules (glucose, amino acids, etc)
blood flows from portal triad to central vein
bile flows from center to portal triad
fenestrated capillaries – allow nutrients to pass from blood to cells
functions of the liver (8)
- carbohydrates metabolism - gluconeogenesis, glycolysis
- amino acids and protein metabolism - synthesis of plasma proteins
- lipid metabolism - fatty acid oxidation, ketone bodies synthesis
- storage - glycogen, lipids, vitamins, copper, iron
- synthesis and secretion of bile acids, bile formation
- biotransformation - medicaments, xenobiotics, metabolism byproducts
- synthesis of hormones and mediators
- synthesis of components of the immune system
important plasma proteins synthesized in the liver (6)
- albumins - produces oncotic pressure
- lipoproteins - transport of lipids
- glycoproteins - haptoglobin, transferrin
- prothrombin and fibrinogen - blood coagulation
- nonimmune alpha and beta globulins
- complement components also produced in the liver
different types of lipoproteins (3)
- VLDL - transport of triglycerides from the liver to other organs
- LDL (“bad”) - transport of cholesterol esters from liver to other tissues
- HDL (“good”) - remove cholesterol from peripheral tissues and transport it to liver
important hormones synthesized in the liver (4)
- angiotensinogen –> prohormone
- thrombopoietin –> hormone (growth factor); formation of blood platelets
- IGF (insulin like growth factor) –> IGF 1 and 2
- hepcidin –> small peptide hormone (iron homeostasis)
what is biotransformation
group of reactions involved in the conversion of toxic molecules in non-toxic water soluble and more excretable substances
why do most drugs need to undergo biotransformation
most drugs are liposoluble, so stay in the body long time
biotransformation is essential for the termination of their action and their elimination from the body
what is the major site for drug biotransformation
the liver – cytochrome P450 microsomal enzyme
what does drug metabolism lead to
drug metabolism leads to increased polarity
makes drugs and their metabolites more water soluble
what are the 2 phases of biotransformation
Phase I – oxidation
Phase II – conjugation with glucuronic acid
Phase I of biotransformation
what does it entail, where is it performed
oxidation
includes hydroxylation (adding -OH) and carboxylation (adding -COOH) to a foreign compound
performed in SER and mitochondria (reactions with proteins called cytochrome P450)
Phase II of biotransformation
what does it entail
what does it do to the product of Phase I
conjugation
includes the addition of glucuronic acid, glycine or taurine to the target substance
makes product of Phase I more water soluble so that it can be easily eliminated
where is bile produced and modified
bile is produced in hepatocytes
it is modified in epithelial cells of the gallbladder
what happens to bile in the gallbladder
storage and concentration through electrolyte and water resorption
why is bicarbonate needed in bile
in duodenum - helps neutralize acidic food coming from the stomach
what are bile acids synthesized from
bile acids are synthesized from cholesterol and conjugated with amino acids (glycine, taurine)
what are the most important components of bile
bile acids
bile acids are amphipathic (both hydrophobic and hydrophilic parts)
where are bile acids secreted and what do they do there
bile acids are secreted into the duodenum
they emulsify fat droplets in the small intestine to form mixed micelles
define emulsify
make fat droplets smaller for digestion
movement of bile from liver to duodenum
bile is first excreted into the bile canaliculi (small canals between hepatocytes)
bile canaliculi gradually feed into larger canals and finally into the common bile duct (ductus choledochal)
a sphincter of smooth muscle (sphincter of Oddi) guards the entrance of the bile into the duodenum
what happens to bile when there is no digestion going on in the duodenum
bile is stored in the gallbladder
bile movement after a meal
after taking a meal –> emptying of gallbladder
increased amino acids and fatty acids in duodenum –> increased CCK –> contraction of smooth muscle and relaxation of Oddi’s sphincter
reflectory –> increased Ach –> contraction of the smooth muscle
what is enterohepatic circulation of bile acids
bile acid recycling
bile acids get reabsorbed and go back to the liver via portal vein
only 5% of bile acid pool is synthesized de novo in the liver
95% recirculates between the small intestine and the liver (recycling of bile acids)
what does the exocrine pancreas do
secretion of digestive enzymes
describe the exocrine pancreas
an acinar gland connected by arborizing system of ducts
structure resembles salivary gland
what does the pancreas secretion in acinus resemble
where does HCO3 addition occur
primary saliva – CL channel apical, Na/K/2Cl cotransporter basolateral
HCO3 addition occurs in the ducts
what are zymogens and why are they needed
zymogens are the inactive forms of the enzymes produced in the pancreas
they are needed because protein digesting enzymes (proteases) produced in the pancreas are potentially harmful to pancreatic cells
digestive enzymes produced in the pancreas (4)
- peptidases - produced in inactive form
trypsinogen, chymotrypsinogen, proelastase, procarboxtypeptidase A and B - nucleases
ribonuclease, desoxyribonuclease - amylases - digestion of polysaccharides
a-amylase - lipases
regulation of the exocrine pancreas
pancreatic cells have receptors for acetylcholine, CCK, and secretin
pancreatic secretions adjustments to food composition
increased starch leads to increased amylase
increased fat and protein leads to increased lipases and peptidases
regulation of the exocrine pancreas and the 3 phases
cephalic phase - smell, sight, imagination
gastric phase - dilation of the stomach
intestinal phase - decreased pH leads to increased secretin; increased amino acids and fatty acids leads to increased CCK
the exocrine pancreas – Ach and CCK
Ach and CCK stimulate secretion of an enzyme and chloride-rich formula
the exocrine pancreas – secretin
secretin stimulates production of a bicarbonate-rich excretion
pancreatic insufficiency
insufficient production of digestive enzymes by the exocrine pancreas; maldigestion
clinical signs: greasy/oily stools (steatorrhea), polyphagia (increased eating), rapid weight loss
pancreatitis
relatively frequent in dogs – middle to old age, obese dogs
acini destroyed and replaced by connective tissue because of autodigestion
increased risk when eating too much fat, human food, or garbage
