Gastrointestinal Physio L4-6 Flashcards
What can you find in the liver lobule?
- Portal Triad - Portal venule, Arteriole of hepatic artery, Bile duct
- Sinusoids, hepatocytes, & bile canaliculi
What kind of capillaries are found in the liver?
Fenestrated - This allows the passge of big molecules (glucose, amino acids, etc.)
What are the functions of the liver?
- Carbohydrates metabolism via gluconeogenesis & glycolysis
- Amino acid & protein metabolism (synthesis of plasma proteins)
- Lipid metabolism (fatty acids oxidation, ketone bodies synthesis0
- Storage (glycogen, lipids, vitamins, copper, iron)
- Synthesis & secretion of bile acids, bile formation
- Biotransformation (medicaments, xenobiotics, metabolism byproducts)
- Synthesis of hormones & mediators
- Synthesis of components of the immune system
True or False. The liver does not produce circulating plasma proteins.
False
* The liver does produce circulating plasma proteins.
What are the components the liver produces that is part of the plasma proteins?
- Albumins
- Glycoproteins –> haptoglobin, transferrin
- Nonimmune alfa- and beta-globulins
- Complement facators
- Prothrombin & fibrinogen
- Coagulation factors
- Lipoproteins (VLDLs, IDLs, LDLs, HDLs)
What are the lipoprotein classes according to their density?
- Chylomicrons
- VLDLs
- IDLs
- LDLs
- HDLs
What are VLDLs and what do they do?
- Lipoprotein
- Transport of triglycerids from the liver to adipose tissue/other organs
What are IDLs and what do they do?
- Lipoproteins
- VLDLs remnants after the FFAs have been releases
- 50% become VLDLs & 50% become LDLs
What are LDLs and what do they do?
- Lipoproteins
- Transport of cholesterol esters from the liver to other tissues
- Increased in people eating a diet high in saturated fat obese, and/or sedentary (aka bad cholesterol)
What are HDLs and what do they do?
- Lipoprotein
- Remove cholesterol from the peripheral tissue and transport it to the liver
- It is believed that HDLs can absorb cholesterol that are being deposited in the arteries (aka good cholesterol)
What 4 substances does the live secrete that give it an endocrine function?
- Angiotensinogen - a prohormone that will result in angiotensin
- Thrombopoetin - a hormone (growth factor)
- IGF (insulin-like growth factors) - is produced in response to growth hormone (i.e. IGF-1 and 2)
- Hepcidin - is a small peptide hormone (iron homeostasis)
What is biotransformation?
Group of reactions involved in the conversion of toxic molecules in non-toxic, water soluble & more excretable substances
What is important about most drugs that we can give to patients?
- Most drugs are liposoluble (& would, therefore, stay long in the body)
- Biotransformation is essential for the termination of their action & their elimination from the body
What is the largest site for biotransformation?
The liver
What are the enzymes involved in biotransformation in the liver?
Cytochrome P450 enzymes
True or False. Drug metabolism leads to increase polartiy.
True
* Drug metabolism leads to increase polartiy
* Makes drugs & theit metabolites more water soluble
In the liver, where is the bile produced?
Bile is produced in the hepatocytes and modified in epithelial cells of the gallbladder.
What is the function of the gallbladder?
Storage & concentration of the bile through electrolytes (Na+, Cl-, HCO3-) & water reabsorption.
What is synthesized to make bile acid?
Bile acids are synthesized from cholesterol & conjugated w/amino acids (i.e. glycine, taurin)
True or False. Bile acids are amphipathic molecues.
True
What do bile acids secrete?
- Amphipathic molecules
- Secreted into the duodenum where they emulsify fat droplets in the small intestine (formation of mixed micelles)
When bile acids are secreted into the duodenum & emulsify fat droplets in the small intestine, what is formed?
Formation of mixed micelles
What is the path of bile in liver?
- First excreted into the bile canaliculi (small canals btween hepatocytes).
- Bile canaliculi then gradually feed into larger canals & finally into the common bile duct (ductus choledochus).
What is the muscle that prevents bile from leaking into the duodenum?
Sphincter of Oddi
* sphincter of smooth muscle
* guards the entrance of the bile into the duodenum
When there is no digestion, where is bile stored?
Gallbladder
* rats & horses do NOT have a gallbladder
What causes sphincter of Oddi to relax & release bile?
After a meal, the gallbladder is emptied:
* ↑ amino acids & fatty acids in duodenum → ↑ CCK → contraction of smooth m. & relaxation of Oddi’s sphincter
What is the refractory mechanism that affects the circulation of bile?
Reflexive stimulation →↑ Ach → contraction of the smooth m. of the gallbladder
What is the components of bile?
- Bile acids
- Bile pigment
- Phospholipids
- Cholesterine
- Na+
- K+
- Ca+
- Cl-
- HCO3-
What is the pH of bile?
8.2
What is the general steps of synthesis & circulation of bile acids?
- Cholesterol within hepatocytes interact w/bile acids.
- This then goes through transporters that transport the bile into the bile canaliculi
- Where bile is then fed into the bile duct & eventually released into the duodenum.
- The bile acids are reabsorbed through the intestinal lumen in the ileum through a sodium transporter, & then they go through an additional transporter into the bloodstream.
- This then transports back through to the liver where the bile is collected for reuse.
What percentage of bile is made each time we eat? How much is recirculated?
- 95% is recirculated in small intestine and liver
- 5% is what is made de novo in the liver
After fats are digested & absorbed, where does bile acids go?
After fats are digested & absorbed, bile acids go to the ileum, where they are reabsorbed using an active transport process.
Synthesis & enterohepatic circulation of bile acids have been studied for many years. How does it work (type of diffusion)?
- There are primary active transporters that require ATP, to get into bile canaliculi.
- There is recirculation of bile acids w/transporters in the ileum & hepatocytes, carriers are used.
- NO DIFFUSION
What are the two glandular tissues that compose the pancreas & what do they each secrete?
- Endocrine - secrete hormones
- Exocrine - secrete digestive enzymes & electrolytes
What is the exocrine pancreas?
- Is an acinar gland connected by an arborizing system of ducts.
- The structure resembles a salivary gland
What is the secretion in the acinus of the exocrine pancreas made of?
The primary saliva (i.e. Cl- channel apical; Na+/K+/2Cl- cotransporter basolateral)
In the exocrine pancreas, where does the addition of HCO3- occur?
In the ducts
What are zygomens?
- Inactive forms of proteases (protein-digesting enzymes) which are potentially harmful to pancreatic cells.
- “pro” or “ogen” signifes that enzymes are not in active form
What digestive enzymes are produced in the pancreas?
- Peptidases (produced in inactive form) - Trypsinogen, chymotrypsinogen & proelastase (zymogens)
- Nucleases - Ribonuclease & deoxyribonuclease
- Amylases (pancreatic) - α-amylase
- Lipases
What receptors do pancreatic cells have?
- Acetycholine (Ach)
- CCK
- Secretin
How can diet effect the concentration of specific digestive enzymes?
- ↑ starch → ↑ amylase
- ↑ fast & protein → ↑ lipases & peptidases
What are the phases of regulation for the exocrine pancreas?
- Cephalic phase - smell, sight, imagination
- Gastric phase - dilation of the stomach
- Intestinal phase - ↓ pH → ↑ secretin / ↑ AA, FA → ↑ CCK
What occurs in the intestinal phase of regulation of the exocrine pancreas?
- ↓ pH → ↑ secretin (this is to balance the pH & keep it from becoming too acidic & damage the intestines)
- ↑ AA, FA → ↑ CCK
True or False. Ach & CCK both stimuate secretion of an enzyme & chloride-rich fluid.
True
* Ach & CCK both stimuate secretion of an enzyme & chloride-rich fluid.
True or False. CCK stimulates the production of a bicarbonate-rich secretion.
False
* Secretin stimulates the production of a bicarbonate-rich secretion.
What are two examples of impairment of pancreas secretion?
- Pancreatic insufficiency
- Pancreatitis
What is pancreatic insufficiency and the clinical signs?
- Insufficient production of difestive enzymes by the exocrine pancreas; maldigestion
- Clinical Signs: greasy/oily stools (steatorrhea), polyphagia (eats excessive amt of food), rapid weight loss
What is pancreatitis and the clinical signs?
- In dogs relatively frequent (middle to old age, obese dogs)
- Can be very dangerous, there is inflammation of pancreas & enzymes are activated
- Acini destroyed and replaced by connective tissues b/c of autodigestion
- Increase risk when eating too much fat, human food or garbage
- Example - Beagles
What is the active form of trypsinogen?
Trypsin
What does it mean to be amphipathic?
One side of the compound is hydrophilic while the other is hydrophobic
What are the major dietary carbohydrates?
- Starch
- Glycogen
- Saccharose
- Lactose
After digestion begins in the mouth, how does further digestion occur for carbohydrates?
- Further digestion of carbohyrates is achieved by pancreatic enzymes
- Digestion is finished by enzymes synthesized by the intestinal mucosa
Where does absorption of carbohydrates occur? What is it mediated by and where is the mediator located? What facilitates this action?
- Absorption of carbohydrates takes place in the duodenum & upper jejunum
- It is mediated by a Na+ dependent transport mechanism (SGLT1) present at the apical membrane
- This happens by facilitated transport mechanisms present at both the apical (GLUT5) & the basolateral membrane (GLUT2)