GI Lecture 4-6 Flashcards
1
Q
What can you find in the liver lobule?
A
Portal venules, arteriole of hepatic artery, bile duct.
2
Q
What kind of capillaries are found in the liver? Why?
A
Sinusoidal ( this is to allow proteins and large solutes to enter the blood)
3
Q
What are the functions of the liver?
A
- Carbohydrate metabolism (gluconeogenesis, glycolysis)
- Amino acid and protein metabolism (synthesis of plasma proteins)
- Lipid Metabolism ((fatty acids 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
4
Q
What are the components the liver produces that is part of the plasma protein?
A
◦ Albumins
◦ Lipoproteins:
‣ VLDLs
‣ LDLs
‣ HDLs
◦ Glycoproteins: haptoglobin, transferrin
◦ Prothrombin and fibrinogen
◦ Non-immune alfa- and beta-globulins
5
Q
What are VLDLs and what do they do?
A
Lipoproteins: They transport triglycerides from liver to the other organs.
6
Q
What are LDLs and what do they do?
A
Lipoproteins: They transport cholesterol esters from liver to the peripheral tissues. (bad cholesterol)
7
Q
What are HDL’s and what do they do?
A
Lipoproteins: They remove cholesterol from the peripheral tissues and transports it to the liver. (good cholesterol)
8
Q
What hormones are synthesized in the liver? What are they?
A
- Angiotensinogen -> Prohormone
- Thrombopoetin -> Hormone (Growth factor)
- IGF (Insulin-like growth factors) -> IGF 1 and 2
- Hepcidin -> Small peptide hormone (iron homeostasis)
9
Q
What is biotransformation?
A
• Group of reactions involved in the conversion of toxic molecules in non-toxic, water soluble and more excretable substances.
10
Q
What is important about most drugs that we can give to patients?
A
• Most drugs are liposoluble (and would, therefore, stay long in the body). Biotransformation is essential for the termination of their action and their elimination from the body
11
Q
What is the largest site for biotransformation?
A
The liver
12
Q
What are the enzymes involved in biotransformation in the liver?
A
Cytochrome P450 enzymes
13
Q
TRUE or FALSE: Drug Metabolism leads to increased polarity
A
True
14
Q
What does increased polarity mean in terms of drug metabolism?
A
makes drugs and their metabolites more water soluble
15
Q
How many phases are involved in biotransformation?
A
2
16
Q
What occurs in phase one of biotransformation?
A
Phase I - (oxidation+ Hydroxylation (adding -OH group) + Carboxylation (adding -COOH group) to a foreign compound. This is performed in the sER and the mitochondria (reactions with proteins called cytochrome P450)
17
Q
What occurs in phase two of biotransformation?
A
Phase II- called conjugation, addition of glucuronic acid, glycine or taurine to the target substance. Makes the product of phase one more water soluble so it can easily be eliminated.
18
Q
Where is bile produced?
A
The bile is produced in the hepatocytes and is modified in epithelial cells of the gallbladder.
19
Q
What is the role of the Gall bladder?
A
Gallbladder: Storage and concentration through electrolyte and water resorption.
20
Q
What is synthesized to make bile acid?
A
Bile acids are synthesized from cholesterol and conjugated with amino acids ( glycine, taurine)
21
Q
What is bile acids, and where are they secreted?
A
Bile acids are amphipathic molecules and most important component of bile. They are secreted into the duodenum where they emulsify fat droplets in small intestine.
22
Q
When bile acids are secreted into the duodenum and emulsify fat droplets in the small intestine, what is formed?
A
Forming mixed micelles
23
Q
What is the path of bile in the liver?
A
Bile is excreted into bile canaliculi ( small canals between hepatocytes). Bile canaliculi gradually feed into larger canals and then into common bile duct (ductus choledochu)
24
Q
What is the muscle that prevents bile from leaking into the duodenum?
A
• Sphincter of Oddi (smooth muscle)
25
When there is no digestion, where is bile stored?
gallbladder.
26
What causes oddi's sphincter to relax and release bile?
• After meal gallbladder is emptied:
◦ increased amino acids and fatty acids in duodenum-\> Increased CCK -\> contraction of smooth muscle and relaxation of Oddi's sphincter.
27
What is the refractory mechanism that affects the circulation of bile?
Refectory -\> increased Ach -\> contraction of the smooth muscle.
28
What is the components of bile?
Bile acids, Bile pigment, phospholipids, cholesterine, Na+, K+, Ca++, Cl-, HCO3-
29
What is the pH of bile?
8.2
30
What is the general steps of synthesis and circulation of bile acids?
Cholesterol within hepatocytes interact with bile acids, this then goes through transporters that transport the bile into the bile caniculi, where the bile is then fed into the bile duct and eventually is released into the duodenum. The bile acids are reabsorbed through the intestinal lumen in the ileum through a sodium transporter, and 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.
31
What percentage of bile is made each time we eat? How much is recirculated?
95 % is recirculated, 5% is what is made de novo in the liver.
32
What are the two tissues that compose the pancreas and what do they each secrete?
• Pancreas is composed of two functionally separate types of glandular tissues, the endocrine (secretion of hormones) and the exocrine pancreas (secretion of digestive enzymes)
33
What is the exocrine pancreas?
The exocrine pancreas is an acinar gland connected by arborizing system of ducts.
◦ Structure of exocrine pancreas resembles the salivary gland
34
What is the secretion in the acinus of the exocrine pancreas made of?
• Secretion in acinus resembles the primary saliva (i.e Cl- channel apical; Na+/K+/2Cl- cotransporter basolateral);
35
In the exocrine pancreas, where does the addition of HCO3- occur?
In the ducts.
36
What are zygomens?
Inactive forms of proteases which are not going to harm the pancreatic cells.
37
What digestive enzymes are produced in the pancreas?
‣ Peptidases (produced in inactive form): Trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidase A and B.
‣ Nucleases: Ribonuclease, desoxyribonuclease
‣ Amylases: alpha- amylase
‣ Lipases
38
What receptors do pancreatic cells have?
• Pancreatic cells have receptors for acetylcholine, CCK, and secretin
39
How can diet effect the concentration of specific digestive enzymes?
◦ increased starch -----\> Increased amylase
◦ Increased fat and protein ----\> Increased lipases and peptidases.
40
What are the phases of regulation for the exocrine pancreas?
Regulation:
◦ Cephalic phase (site, smell, imagination)
◦ Gastric Phase (dilation of the stomach)
◦ Intestinal Phase
41
What occurs in the intestinal phase of regulation of the exocrine pancreas?
‣ decrease in pH --\> increase secretin) (this is to balance the ph and keep it from becoming too acidic and damage the intestines)
‣ Increase in AA, FF ----\> increase in CCK
42
What are two examples of impairment of pancreas secretion?
- Pancreatic insufficiency
- Pancreatitis
43
What is pancreatic insufficiency? What is the clinical signs?
◦ Insufficient production of digestive enzymes by the exocrine pancreas; mal digestion;
◦ Clinical signs: Greasy/oily stools (steatorrhea), polyphagia, rapid weight loss
44
What is pancreatitis? What is the clinical signs?
◦ In dogs relatively frequent (middle to old age, obese dogs); acini destroyed and replaced by connective tissues because of auto-digestion Increased risk when eating too much fat, human food or garbage
45
What does secretin stimulate?
Production of a bicarbonate rich secretion
46
What does acetylcholine and CCK stimulate?
Secretion of an enzyme and chloride rich fluid.
47
What is the active form of trypsinogen?
Trypsin
48
What does it mean to be amphipathic?
One side of compound hydrophilic, one side hydrophobic.
49
When does the reflectory response within the bile duct occur?
can occur just before eating.
50
What is the pathway of bile acids?
Bile acids within the bile in the gallbladder is released into the small intestine via the bile duct. The bile acids are absorbed via the intestinal lumen and then will be absorbed into blood stream where it is returned to the liver through the hepatic portal vein.
51
What causes the conversion of trypsinogen to Trypsin? Where is it activated?
enteropepsidase. In the duodenum
52
During an episode of pancreatitis what occurs to the zymogens that causes local damage of pancreatic cells?
During pancreatitis, the zymogen granules and lysosomes can fuse, and their contents can mix together in intracellular vacuoles, leading to premature, increased, intracellular activation of zygomens. Such abnormal activation leads to local damage of pancreatic cells
53
What can occur in pancreatitis when trypsinogen, trypsin, and zymogens are prematurely activated?
Additionally, if there is premature intracellular activation of trypsinogen, trypsin, and zymogens, this causes additional activation of other zymogens, thus leading to additional pancreatic damage.
54
What inflammatory mediators are released during an episode of pancreatitis?
Many inflammatory mediators are also released, including TNF-alpha, IL-1, IL-2, IL-6, IL-8, IL- 10, IFN-alpha, IFN-gamma, and platelet activating factor
55
What can the release of inflammatory mediators cause in a patient with pancreatitis?
This can lead to shock, disseminated intravascular coagulation (DIC), and death
56
What usually activates zymogens?
They are activated by cleavage of the amino-terminal polypeptide chain. Zymogens are normally not activated until they reach the small intestine.
57
What is the treatment of pancreatitis?
Stabilization of patients with fluid/electrolyte therapy is recommended. Additionally, analgesics and antibiotics are often recommended. Both parenteral and enteral feeding, after vomiting ceases, have been recommended
58
What is the prognosis of a patient with pancreatitis? What causes it? Who is more susceptible?
Overweight dogs are more susceptible. There is no known/ definitive cause. Prognosis varies, depending on cause, severity, and chronicity of disease.
59
What are the functions of carbohydrates in the body?
Functions:
- Energy source
- Storage form of energy
- Cell membrane component (communication)
- Structural component (cell wall of bacteria)
60
What are carbohydrates made from?
All carbohydrates are made from monosaccharides
61
Monosacharides are categorized based on what?
Monosaccharides (simple sugars) are categorized according to the number of carbons
62
TRUE OR FALSE: Carbohydrates are the most abundant organic molecules in nature.
TRUE
63
What are disaccharides?
Monosaccharides linked by glycosidic bonds
64
What are oligosaccharides?
3-10 Monosaccharides
65
What are polysaccharides?
\> 10 monosaccharides (up to a hundred!)
66
What is the name of the product?
Lactose
67
In humans and pigs, where does digestion of carbohydrates begin, and what helps to digest them?
Digestion begins in the mouth with alfa-amylase in salivary glands
68
What are major dietary carbohydrates?
starch, glycogen, saccharose, lactose
69
After digestion begins in the mouth, how does further digestion occur for carbohydrates?
- Further digestion of carbohydrates is achieved by pancreatic enzymes
- Digestion is finished by enzymes synthesized by the intestinal mucosa
70
Where does absorption of carbohydrates occur? What is it mediated by and where is that mediator located? What facilitates this action?
Absorption of carbohydrates takes place in the duodenum and upper jejunum and is mediated by a Na+-dependent transport mechanism (SGLT1) present at the apical membrane, and by facilitated transport mechanisms present at both the apical (GLUT5) and the basolateral membrane (GLUT2)
71
Where are proteins denatured?
In the stomach
72
What partially hydrolyzes protiens in the stomach?
Pepsin
73
Where does the final digestion of protiens take place?
In the small intestine
74
What are lipids used for?
o Prostaglandins
o Steroid hormones
o Phospholipids
o Platelet-activating factor (PAF)
o Sphingomyelin: component of myelin in nerve fibers
75
Fat has amphiphatic character, what does this mean?
It has a hydrophillic side and a hydrophobic side of the compound
76
Where does emulsification occur? What is the goal of emulsification?
Emulsification occurs in the duodenum and aims to reduce the surface area of the hydrophobic lipid droplets (crucial for lipase function which binds at the interface droplet/aqueous solution)
77
What do bile acids consist of (Chemical composition)?
Bile acids (liver) consist of a sterol ring with a side chain of amino acid (taurine or glycin)
78
What are the main dietary lipids?
Cholesterol esters, phospholipids, triglycerides
79
Where do lipids digestion start?
Partially in the stomach (gastric lipase)
Bile acids emulsify the large fat drops
Emulsified fat droplets are still too large to enter the spaces between microvilli
80
What is the role of pancreatic lipases ?
Pancreas lipases hydrolize triglycerides into monoglycerides and free fatty acids
81
What will form mixed micelles?
Monoglycerides, FFA, cholesterol, and liposoluble vitamines will form mixed micelles
82
How are mixed micelles absorbed?
Mixed micelles approache the brush border membrane of enterocytes where they will be absorbed
83
Do short chain fatty acids form mixed micelles? Why or Why not?
Short chain FA do not form mixed micelles (can directly be absorbed)
84
Once absorbed, what is the path of the mixed LCFA?
LCFA go into the endoplasmic
reticulum for re-esterification
(re-synthesis) of more complex
lipids as follows:
MAG + free fatty acids ---\> TAG
85
What is the pathway of chylomicrons?
Chylomicrons are released by exocytosis into the lymphatic vessels -\> thoracic duct -\>
-\> left subclavian vein -\> blood
86
Which segment of the small intestine or proximal large intestines has the highest permeability through its tight junctions?
Jejunum
87
Which segment of the small intestine or proximal large intestines has the lowest permeability through its tight junctions?
Colon
88
Which segment of the small intestine or proximal large intestines has the highest resistance through its tight junctions?
colon
89
Which segment of the small intestine or proximal large intestines has the lowest resistance through its tight junctions?
Jejunum
90
Where does the water absorption take place in the gastrointestinal tract?
85% of water absorption intestine
takes place in the small intestine (55% in duodenum
and jejunum and 30% in ileum); about 14% is absorbed in the large
intestine
91
What is required for efficient absorption of water?
- Increasing resorption surface
- Mucosa uptake mechanisms
- High blood perfusion
- Permeability
92
How are the monovalent ions absorbed?
Na+ transport is very efficient since it represents the driving force for most transport processes Chloride is absorbed by carriers as well as passice through the paracellular pathway K+ is mainly absorbed in the small intestine through the paracellular pathway
93
94
List in order of lowest to highest permeability the sections of intestine.
Colon -\> Ileum -\> Jejunum
95
List in order of lowest to highest resistance the sections of the intestines.
Jejunum-\> Ileum -\> Colon
96
What does calcitriol do?
Increases apical Ca++ channels Increases calbindin synthesis Increase Ca++ ATPase
97
Where is Ma++ absorbed?
Through Mg++ channels and paracellularly
98
How is Phosphate absorbed?
Through Na+/Phosphate symporter.
99
Where is viatmin D produced? What influences its synthesis?
Produced in the kidneys. Synthesis is under the influence of PTH
100
What is calcium absorption modulated by?
Modulated by vitamin D in intestine
101
What is calcitriol and what will it stimulate?
Calcitriol is active vitamin D hormone. It will stimulate building/ opening of calcium channels at apical membrane.
102
What occurs to the diameter of the intestine as we move from oral to aboral?
Diameter decreases as we move through GI tract.
103
What is haptocorrin and what does it do?
Transcobalamin I. This protects B12 from stomach acid.
104
What releases B12 from Haptocorrin?
Trypsin
105
Where is B12 absorbed?
Ileum
106
Where is iron absorbed ?
Small intestines
107
What breaks down Fe3+ to Fe2+?
Ferriductase
108
What is iron important for ?
The development of RBC/ B12
109
Why is iron oxidized?
So it could be bound to protien (apotransferrin) which is converted to transferrin.
110
What are the energy poor end products of catabolites?
CO2, H2O, NH3
111
What are the precursor molecules of complex molecules that are anabolites?
Some amino acids, Sugars, fatty acids, nitrogenous bases.
112
What are some energy sources in living organisms?
Glucose, Fatty acids, amino acids, ketone bodies, volatile fatty acids.
