GI - Physiology - Exocrine Pancreas; Liver; Digestion & Absorption Flashcards
1
Q
What are the two main goals of pancreatic exocrine secretions?
A
Neutralize acidic chyme (via HCO3-);
promote digestion (via zymogens)
2
Q
Make the diagnosis.
A
Acute pancreatitis
3
Q
What are the two main cell types of the exocrine pancreas?
A
Acinar;
ductal
4
Q
Via what intracellular messenger do vagal stimulation and cholecystokinin cause increased pancreatic enzyme exocytosis?
A
Increased [Ca2+]
5
Q
What intestinal hormone causes increased pancreatic HCO3- secretion?
What intestinal hormone causes increased pancreatic enzyme secretion?
A
Secretin;
cholecystokinin
6
Q
An increase in intracellular [Ca2+] in the pancreatic acinar cells will cause what results?
A
Increased enzyme secretion;
increased Na+, Cl-, and H2O secretion
7
Q
Which portion of the exocrine pancreas secretes enzymes, NaCl, and H2O?
Which portion of the exocrine pancreas secretes HCO3-?
A
Acinar cells;
ductal cells
8
Q
Pancreatic acinar cells secrete ______________ in response to _______________ stimulation.
Pancreatic duct cells secrete ______________ in response to _______________ stimulation.
A
Enzymes, NaCl, H2O;
cholecystokinin, vagal stimulation
HCO3-;
secretin
9
Q
What channel allows for Cl- return to the pancreatic lumen after it is exchanged for HCO3- and enters ductal cells?
A
The CFTR channel
10
Q
What percentage of pancreatic fluid is made up of acinar secretions (enzymes, H2O, NaCl)?
What percentage of pancreatic fluid is made up of ductal secretions (HCO3-, H2O)?
A
25%
75%
11
Q
An increase in pancreatic fluid flow rate has what effect on HCO3- and Cl- levels in the fluid?
A
More [HCO3-];
less [Cl-]
12
Q
Name some of the digestive enzymes secreted by pancreatic acinar cells.
A
α-amylase;
pancreatic Lipase;
various proteases (pepsin, trypsin, chymotrypsin, carboxypeptidases, elastase)
13
Q
Describe the activation of pancreatic zymogen proteases.
A
Enteropeptidase (enterokinase) on duodenal brush border –>
activates trypsin –>
activates the others
14
Q
How is auto-activation of trypsin within the pancreatic acinar cells avoided?
A
- Pancreatic enzymes exist as zymogens while in the pancreas
- Trypsin inhibitors can block any existing activity within the pancreas
(e. g. trypsin inhibitory peptide and α-1 antitrypsin)
15
Q
What is the stimulating factor that increases secretin secretion by S cells of the duodenum?
What is the stimulating factor that increases cholecytokinin secretion by I cells of the duodenum?
A
Gastric acid in the duodenum;
fatty acid and amino acids in the duodenum
16
Q
How are secretin and cholecystokinin secretion potentiated?
A
Vagal stimulation
17
Q
______ cells secrete secretin.
______ cells secrete cholecystokinin.
______ cells secrete glucose-dependent insulinotropic peptide.
A
S
I
K
18
Q
What are the three stimulatory phases of pancreatic exocrine secretion?
A
Cephalic (minor role - vagus);
gastric (minor role - vagus/gastrin);
intestinal (vagus/secretin/cholecystokinin)
19
Q
Name the two most common causes of acute pancreatitis.
For what percentage does each account?
A
Alcohol abuse (40%);
gallstones (40%) (often associated with hyperlipidemia);
genetic diseases (e.g. cystic fibrosis);
hyperparathyroidism
20
Q
What bloodwork will you find in a paient with acute pancreatitis?
A
Elevated serum α-amylase and lipase;
decreased total cholesterol, HDL, and LDL
21
Q
What three organs are very commonly affected in patients with cystic fibrosis?
A
Lungs,
liver,
pancreas
22
Q
What digestive complications do patients with cystic fibrosis face?
A
Malabsorption,
acute pancreatitis,
obstruction,
etc.
23
Q
Does gastrin potentiate pancreatic acinar secretions (via CCK) or ductal secretions (via secretin)?
A
Acinar
(to digest the proteins the stomach has sensed and responded to by secreting gastrin)
24
Q
Presence of fatty acids in the duodenum causes increased ___________ (hormone) secretion.
Presence of gastric acid in the duodenum causes increased ___________ (hormone) secretion.
A
Cholecystokinin;
secretin
25
What test can you use to help confirm a diagnosis of acute pancreatitis?
Blood work --\> elevated serum α-amylase and lipase
26
What test can you use to help confirm a diagnosis of cystic fibrosis?
Sweat test
27
What is the likely diagnosis?
What is the primary cause?
Cholecystitis;
gallstones
28
What percentage of hepatic circulation comes from the portal vein?
What percentage of hepatic circulation comes from the hepatic artery?
75%
25%
29
What is a hepatic lobule?
The hepatocytes around a central vein and several associated portal triads
30
**True/False**.
Hepatocytes are a single layer of epithelial cells.
What type of junctions connect them?
True;
tight junctions
31
Describe the bile cannaliculi and apical / basolateral sides of a hepatocyte.
Cannaliculi and apical sides = between cells
Basolateral sides = sides facing space of Disse
32
What are the main components of bile?
Water (82%),
bile acids (12%),
phospholipids (4%),
cholesterol (1%)
bilirubin (\<1%)
33
What cell is here described:
## Footnote
*change fluid in bile duct lumen to make bile*
Cholangiocytes
34
Describe the function of cholangiocytes.
35
Describe the changes in pH and electrolytes from hepatic bile to gallbladder bile.
**Increase:**
Sodium
Bile acid (pH decreases initially until Cl-/HCO3- exchange catches up)
**Decrease:**
Bicarbonate (pH decreases until Cl-/HCO3- exchange catches up)
Chloride
36
How are bilirubin and cholesterol excreted?
Through bile
37
What are the purposes of bile?
Fat emulsification
Antibacterial
Neutralize gastric acid
38
**True/False**.
Bile acids are amphipathic and form chylomicrons.
**False**.
Bile acids are amphipathic and form _micelles_.
39
Bile acids are the end product of __________ metabolism.
What enzyme is responsible for cholesterol synthesis?
What enzyme is responsible as the rate-limiting step of bile acid synthesis?
Cholesterol;
HMG-CoA reductase,
7α-hydroxylase
40
Why can statins cause cramps and neurological symptoms?
Changes in myelin (due to decreased cholesterol synthesis)
41
Primary bile acids are formed in the \_\_\_\_\_\_\_.
Secondary bile acids are formed in the \_\_\_\_\_\_\_.
Liver;
colon
42
Secondary bile acids (formed in the colon) are conjugated with:
Glycine or taurine
43
How are secondary bile acids reabsorbed by the colon?
Na+-dependent cotransport
44
Describe bile acid circulation.
45
What sphincter is relaxed by CCK?
The sphincter of Oddi
46
What substances are released secondary to CCK action at the gallbladder and common bile duct?
VIP and NO (relaxation of Oddi);
ACh (further gallbladder contraction)
47
\_\_\_\_\_\_ ________ turns heme into iron and bilirubin.
Heme oxygenase
48
Unconjugated bilirubin is transported in the blood via \_\_\_\_\_\_\_\_.
Albumin
49
Which sex is at a greater risk of gallbladder disease?
Why?
Women;
oral contraceptives, estrogen
(effects on cholesterol, I think)
50
What surface has the largest surface area of the body in potential direct contact with immunogenic/toxic substance?
The GI tract
51
\_\_\_% of Ig-secreting cells are in the GI tract.
80%
52
Describe the GALT.
53
**True/False**.
The enteric NS has the same number of neurons as the spinal cord (100,000,000)
True.
54
Describe the function of histamine and somatostatin as paracrine factors.
**Histamine** – secreted by _ECL cells_ and stimulates HCl release
**Somatostatin** – secreted by D _cells_ in response to decreased GI luminal pH
55
The action of histamine at H2-receptors in the stomach is blocked by what endogenous hormone?
Secretin
56
2.
57
Gastrin is secreted by what type of cell?
CCK is secreted by what type of cell?
Secretin is secreted by what type of cell?
Glucode-dependent insulinotropic peptide is secreted by what type of cell?
G cells;
I cells (duodenum and jejunum);
S cells (duodenum);
K cells (duodenum and jejunum)
58
What are the stimuli for secretion of gastrin?
What are the stimuli for secretion of CCK?
What are the stimuli for secretion of secretin?
What are the stimuli for secretion of glucose-dependent insulinotropic peptide?
Amino acids, distention, vagal stimulation;
lipids and amino acids;
gastric acid and fatty acids;
oral glucose, fatty acids, and amino acids
59
What are three substances that directly inhibit gastric acid secretion?
Somatostatin;
secretin;
glucose-dependent insulinotropic peptide (aka gastric inhibitory peptide)
60
Gastrin is directly blocked by:
Secretin
61
Gastrin causes increased secretion of:
CCK causes increased secretion of:
Secretin causes increased secretion of:
Glucose-dependent insulinotropic peptide causes increased secretion of:
HCl;
pancreatic enzymes, pancreatic HCO3-;
pancreatic HCO3-; biliary HCO3-;
insulin
62
Gastrin's non-secretory effects include:
CCK's non-secretory effects include:
Secretin's non-secretory effects include:
Glucose-dependent insulinotropic peptide's non-secretory effects include:
Growth of gastric and intestinal mucosa, increased gastric motility;
gallbladder contraction, sphincter of Oddi relaxation, growth of pancreas and gallbladder, slowed gastric emptying;
inhibits gastrin/histamine, slowed gastric emptying;
inhibits glucagon, slowed gastric emptying
63
Describe the vessels found within a single intestinal villus.
64
What structural feature of the GI tract lends the highest increase in surface area to the tract (plicae circularis, villi, crypts of Lieberkuhn, microvilli)?
Microvilli
| (600x increase)
65
**True/False**.
GI stem cells are mostly found between the microvilli.
**True/False**.
GI stem cells are mostly found at the bottom of the crypts of Lieberkuhn.
66
Describe the histological differences between the small intestine and large intestine.
67
Describe the differences in breakdown and absorption between protein, carbohydrates, and lipids.
**Proteins**: broken down into oligopeptides or amino acids --\> oligopeptides then digested within enterocytes
**Carbohydrates**: broken down into monomers
**Lipids**: broken down into fatty acids --\> resynthesized into triglycerides in the enterocytes
68
What is the main carbohydrate we eat?
What is the main carbohydrate of dietary fiber?
Amylopectin (plant starch);
cellulose
69
Describe how a branched carbohydrate is broken down in the GI tract.
1. α-amylase cuts branched structures (such as amylopectin) into monomers
2. Disaccharides and limit-dextrans are then cut down by further brush border hydrolases (isomaltase, sucrase, lactase, etc.)
70
What transporter allows for apical glucose uptake in the GI tract?
What transporter allows for apical fructose uptake in the GI tract?
SGLT1
GLUT5
71
What transporter allows for basolateral glucose uptake in the GI tract?
What transporter allows for basolateral fructose uptake in the GI tract?
GLUT2
GLUT2
72
Is protein uptake in the GI tract sodium-dependent at either the apical or basolateral sides?
Apical only
| (secondary active transport)
73
What type of diarrhea can a lactase deficiency cause?
Why is there excess gas production?
Osmotic diarrhea;
the bacteria turn the excess sugar into H2 and CO2
74
What is Hartnup disease?
To what disorder does it lead?
A disorder (renal and intestinal) of oligopeptide and tryptophan absorption;
**pellagra** (niacin defiiency leading to dermatitis + diarrhea + dementia)
75
What is cystinuria?
What is the common result?
Improper gut cysteine absorption;
renal stones
76
B.
77
Cystinuria or Hartnup?
Cystinuria
78
Virtually all dietary lipids are __________ (90%).
Triglycerides
79
Name a few luminal substances necessary for proper fat digestion and absorption by the GI tract.
Lipases, bile acids, and phospholipids
80
Children with low sun exposure may be at-risk for what disorder of vitamin D?
Ricketts
81
Name three lipases and a cofactor released into the proximal duodenum.
Glycerol ester hydrolase, cholesterol ester hydrolase, phospholipase A2;
colipase
82
What is colipase?
An amphipathic molecule that anchors lipases to lipid droplets
83
Do micelles contain triglycerides?
No;
free fatty acids
84
How are the fat-soluble vitamins (ADEK) absorped?
They diffuse into micelles and then into enterocytes and then into chylomicrons
85
Which is larger: chylomicrons or micelles?
Which contains triglycerides: chylomicrons or micelles?
Chylomicrons;
chylomicrons
86
Which of the following are formed within enterocytes:
Triglycerides
Cholesterol
Micelles
Chylomicrons
Triglycerides;
chylomicrons
87
Which macromolecules are digested within enterocytes as well as in the GI lumen?
Which macromolecules are reformed within enterocytes after being digested in the GI lumen?
Oligopeptides;
triglycerides
88
Describe the cellular mechanism of calcium absorption in the GI tract.
89
While carbohydrate/protein/lipid absorption happens in each portion of the small intestine, where does the majority occur?
The duodenum (then jejunum, then ileum)
| (Graph A.)
90
In what portion(s) of the small intestine does calcium absorption occur?
All three
| (Graph B.)
91
Where is folate absorbed in the gut?
Duodenum and jejunum
92
Where is iron absorbed in the gut?
The duodenum
93
Where are bile acids absorbed in the gut?
Mostly the ileum
94
The ileum is specifically responsible for the absorption of what two substances?
B12;
bile acids
95
About how much fluid is secreted into the gut every day?
About how much of that fluid is reabsorbed by the small intestine?
About how much of that fluid is reabsorbed by the large intestine?
8. 5 L
6. 5 L
1. 9 L
96
What is the basic mechanism of fluid reabsorption in the gut?
Solute reabsorption
(fluid follows solutes)
97
What two types of junctions are responsible for water reabsorption in the gut?
With what two different tonicities?
**Leaky** junctions --\> **isosmotic** absorption
**Tight** junctions --\> absorption **across** **gradients**
98
The small intestine _absorbs_ net amounts of water and what electrolytes?
The small intestine _secretes_ net amounts of what electrolytes?
Na+, K+, Cl-;
HCO3-
99
The large intestine _absorbs_ net amounts of water and what electrolytes?
The large intestine _secretes_ net amounts of water and what electrolytes?
Na+, Cl-;
K+, HCO3-
100
What causes congenital chloridorrhea?
What pH change is expected?
A deficiency of the gut Cl-/HCO3- exchanger;
metabolic alkalosis (HCO3- retention)
101
What pH effect can secretory diarrhea have?
What pH effect can severe vomiting have?
Metabolic acidosis (HCO3- loss);
metabolic alkalosis (HCl loss)
102
How can diarrhea be classified according to the reason for fluid moving to the vessel lumen?
Osmotic;
secretory
103
**True/False**.
Diarrhea can be caused by _either_ blocking gut solute absorption or increasing gut solute _secretion_.
True.
104
2.
105
4.
106
1.
107
Describe the cellular mechanism of iron absorption in the duodenum.
Specifically, what is the apical transporter and other protein regulating the pathway?
DCT1;
hephaestin
108
In what ways is absorption of glucose and amino acids in the gut similar to reabsorption in the kidneys?
Secondary active transport (Na+-linked) at the apical membrane;
Na+/K+ ATPases at the basolateral membrane
109
Describe post-prandial sodium absorption in the duodenum, jejunum, and ileum.
Na+-linked secondary active transport;
Na+/H+ exchangers
110
Describe sodium absorption during the inter-digestive phase in the ileum and colon.
Na+/H+ and Cl-/HCO3- exchangers;
Na+ leak channels
111
Where does passive Cl- absorption predominate in the GI tract?
Where do Cl-/HCO3- exchangers predominate in the GI tract?
Jejunum, distal colon;
ileum, proximal colon
112
Describe the mechanism of NaCl _secretion_ in the crypts of Lieberkuhn.
CFTR transporters;
paracellular Na+ leakage
113
Describe the changes in K+ absorption and secretion from the small intestine to the large intestine to the distal colon.
114
Describe some of the mechanisms of NaCl absorption and K+ secretion by the **colon**.
Na+-linked cotransporters;
Na+/H+ exchangers;
Cl-/HCO3- exchangers;
K+ leak channels
115
Malfunction/deficiency of the DRA / AE1 channels in this diagram of a colonic cell would result in what effects?
What is the name of this condition?
Alkalosis and osmotic diarrhea
*(due to HCO3- retention and Cl- secretion)*;
congenital chloridorrhea
116
In relative terms, describe the pHs of the following GI tract segments:
## Footnote
**Salivary glands**
**Stomach**
**Biliary tree**
**Pancreas**
**Jejunum**
**Ileum**
**Colon**
Alkaline
Highly acidic
Alkaline
Highly alkaline
Alkaline
Alkaline
Acidic
117
What is the main controlling factor for intestinal ion transport?
Chemical mediators: **absorbtagogues** and **secretagogues**
118
Name some of the secretagogues increasing ion secretion in the intestines.
Acetylcholine,
nitric oxide,
VIP,
histamine,
prostaglandins,
bile acids,
gastrin,
long-chain FAs
119
Name some of the absorbtagogues increasing ion secretion in the intestines.
Opioids,
norepinephrine,
somatostatin
120
What effect do cAMP, cGMP, and Ca2+ have on intestinal **anion** **secretion**?
And **NaCl** **absorption**?
Increase;
inhibition
121
What intracellular mediator(s) increase(s) intestinal **anion** **secretion** and inhibit(s) **NaCl** **absorption**?
cAMP, cGMP, Ca2+
122
What sections of the stomach have parietal cells?
Body + fundus
123
What section of the stomach is the primary location of G cells?
The antrum
124
Which of the three factors that increase gastric acid secretion (histamine, gastrin, acetylcholine) increase intracellular **Ca**2+ in the parietal cells they bind?
Which of the three factors that increase gastric acid secretion (histamine, gastrin, acetylcholine) increase intracellular **cAMP** in the parietal cells they bind?
Gastrin (CCKR), acetylcholine (M3);
histamine (H2)
125
Name that respective intracellular messenger that each of the following utilizes to stimulate increased HCl secretion by parietal cells:
Gastrin
Histamine
Acetylcholine
Ca2+
cAMP
Ca2+
126
Which is more likely to _cause_ ulcer formation, acute or chronic NSAID use?
Acute
| (chronic does increase risk though)
127
How does a urease breath test work?
A patient ingests labeled urea;
labeled CO2 being breathed out is then measured to see if urease is present in the stomach;
if so, this indicates H. pylori infection
128
H. pylori uses urease to turn ________ into \_\_\_\_\_\_\_\_.
Urea;
NH3 + CO2
129
What is the mechanism of H. pylori-induced ulcer formation?
Urease creates ammonia --\> neutralizing HCl so the H. pylori can approach the epithelium;
the H. pylori inhibit somatostatin at the epithelium --\> causing increased HCl production
130
Why can ulcer pain decrease after eating?
Food acts as a buffer
131
**True/False**.
The mucus and unstirred water layers of the stomach contain high concentrations of HCO3-.
True.
132
How is H. pylori infection treated?
Triple therapy:
a PPI (omeprazole)
+ 2 antibiotics
133
What mnemonic can be used to remember the causes of pancreatitis?
I GET SMASHED
**I**diopathic
**G**allstones **E**tOH **T**rauma
**S**teroids **M**alignancy/**M**umps **A**utoimmune **S**corpion sting **H**ypertriglyceridemia/**H**ypercalcemia **E**RCP **D**rugs
134
Use the mnemonic I GET SMASHED to list some major risk factors for pancreatitis.
**I**diopathic
**G**allstones **E**tOH **T**rauma
**S**teroids **M**alignancy/**M**umps **A**utoimmune **S**corpion sting **H**ypertriglyceridemia/**H**ypercalcemia **E**RCP **D**rugs
135
What cofactor does the pancreas secrete to aid lipase in digesting lipids?
What does the pancreas secrete to inhibit trypsin activity?
Why?
Colipase;
trypsin inhibiting protein (TIP),
to prevent pancreatic autodigestion
136
Name two proteins that the duodenum secretes.
One is solely to decrease gastric acid secretion, and one is to aid in protein digestion.
Urogastrone;
pepsinogen
137
What is urogastrone?
A duodenal peptide that inhibits the action of gastrin
138
Where are bile acids reabsorbed in the GI tract?
The ileum
139
Why might a patient present with diarrhea following resection of the terminal ileum?
Secretory diarrhea
(**bile acid**s remain in lumen and Cl- secretion is increased)
140
Which is more soluble, bile salts or bile acids?
Bile salts (better able to emulsify fat)
141
How are bile acids reabsorbed in the ileum?
Where do they go?
Via Na+-linked cotransport;
the portal vein
142
What is chenodeoxycholic acid?
A primary bile acid
| (can be used to dissolve gallstones)
143
What is the rate-limiting enzyme for bile acid production?
7α-hydroxylase
144
What three products does α-amylase produce?
Maltose,
maltotriose,
α-limit dextrans
145
What bonds can α-amylase cleave?
Non-terminal α-1,4 bonds
(forming maltose, maltriose, and α-limit dextrans)
146
Name the substrate each of the following enzymes acts upon:
Isomaltase
Lactase
Sucrase
Maltose, maltotriose, α-limit dextrans;
lactose;
sucrose
147
After α-amylase cleaves amylopectin α-1,4 bonds to produce maltoses, maltrioses, and α-limit dextrans, what enzyme further degrades these products?
What bonds can it cleave?
**Isomaltose**;
α-1,4 (maltose, maltriose) and α-1,6 (α-limit dextrans)
148
How are gut amino acid transporters classified according to their nomenclature?
Upper case letter (e.g. B): Na-dependent
0 Superscript (e.g. B0): neutral amino acids
Lower case letter (e.g. b): Na-independent
+ Superscript (e.g. b+): charged amino acids
149
What type of gut amino acid transporter is missing in Hartnup disease?
Na-dependent for neutral amino acids
| (B0)
150
Are patients protein-deficient in either Hartnup's disease or cystinuria?
No
151
In which locations does most Na-linked cotransport occur in the gut?
Duodenum \> Jejunum \>\> Ileum
152
In which locations does most Na+/H+ exchange occur in the gut?
Jejunum, ileum, proximal colon
153
In which locations does most passive Cl- absorption occur in the gut?
Jejunum, distal colon
154
In which locations does most K+ secretion occur in the gut?
Distal colon
155
In which locations does most Cl-/HCO3- exchange occur in the gut?
Ileum, proximal colon
156
What transporter in the duodenum allows for Fe3+ uptake?
What transporter in the small intestine allows for glucose uptake?
DCT1
SGLT1
157
What transporter in the colon allows for short-chain fatty acid uptake?
What transporter in the colon allows for Cl- (uptake) and HCO3- exchange?
SMCT1
DRA/AE1
158
A deficiency of what transporter in the colon leads to congenital chloridorrhea?
DRA/AE1
| (a Cl-/HCO3- exchanger)
159
**True/False**.
Apical transport of amino acids into the enterocytes is bidirectional.
**False**.
_Basolateral_ transport of amino acids into the enterocytes is bidirectional.
160
What cotransporter allows for glucose uptake in the gut?
What cotransporter allows for glucose uptake in the kidneys?
SGLT1
SGLT2
