Final Flashcards
(354 cards)
1
Q
What are phasic contractions and where do we see them?
A
periodic contractions followed by relaxation
esophagus, stomach (antrum), small intestine
2
Q
What are tonic contractions and where do we see them?
A
maintain a constant level of contraction without regular periods of relaxation
stomach (orad), lower esophageal sphincter, ileocecal sphincter, internal anal sphincter
3
Q
What do we call depolarization and depolarization of the membrane potential in the GI smooth muscle?
A
slow waves
4
Q
When do action potentials occur in the GI smooth muscle?
A
when depolarization does the membrane to or above threshold
5
Q
What modulates generation of APs and strength of contractions?
A
neural activity and hormonal activity
6
Q
What do we call weak contractions produced by subs threshold depolarization?
A
basal contractions
7
Q
What effects do parasympathetics have on slow waves and via what chemical?
A
increases amplitude and # of APs
ACh
8
Q
What effects do sympathetics have on slow waves and via what chemical?
A
hyperpolarization- decreases amplitude of slow waves
NE
9
Q
What are the pacemakers for GI smooth muscle?
A
interstitial cells of cajal
10
Q
What phase of swallowing is voluntary? What about involuntary?
A
oral is voluntary
involuntary- pharyngeal and esophageal
11
Q
What all happens during the pharyngeal phase of swallowing?
A
soft palate is pulled upward -> epiglottis moves -> UES relaxes -> peristaltic wave of contractions is initiated in pharynx-> food is propelled through open UES
12
Q
What controls the esophageal phase of swallowing?
A
swallowing reflex and ENS
13
Q
What controls the swallowing reflex?
A
medulla
14
Q
Describe the afferent branch of the swallowing reflex
A
food in pharynx -> afferent sensory input via vagus/glossopharyngeal N -> swallowing center (medulla) -> brain stem nuclei -> efferent input to pharynx
15
Q
What is the primary peristaltic wave in the esophageal phase a continuation of?What is it controlled by?
A
pharyngeal peristalsis
medulla (won’t work post vagotomy)
16
Q
Why do we get a secondary peristaltic wave in the esophagus? Who all controls it?
A
if 1 wave fails to empty esophagus or if gastric contents reflux into esophagus
medulla and ENS
occurs even after vagotomy ro without oral and pharyngeal phases
17
Q
What are two problems that result from the esophagus living in the thoracic cavity and being effected by that negative pressure?
A
- keep air out of upper end
- keep acidic gastric contents out of lower end
18
Q
What can cause gastroesophageal reflux?
A
intra-abdominal pressure is increased due to pregnancy or morbid obesity
19
Q
What causes gastroesophageal reflux disease (GERD)?
A
abnormal relaxation of the LES
20
Q
What causes achalasia?
A
lack of VIP or ENS has been knocked out so LES stays closed during swallowing and impaired peristalsis
21
Q
What is receptive relaxation?
A
decrease in pressure and increase in volume in road region of stomach
vagovagal reflex
22
Q
Why does the orad exhibit minimal contractile activity?
A
little mixing of ingested food occurs there
23
Q
What decreases stomach contractions and increases gastric distensibility?
A
CCK
24
Q
What is the maximum frequency of gastric contractions? Where do they occur?
A
3-5waves/min
mid stomach -> pylorus
25
What is retropulsion?
most gastric contents are propelled back into stomach for further mixing and further reduction of particle size
26
What all increase AP and force of gastric contractions?
parasympathetic stimulation, gastrin, motilin
27
What all decreases AP and force of contractions?
sympathetic stimulation, secretin, GIP
28
What four things increase the rate of gastric emptying?
- decrease in distensibility of road
- increased force of peristaltic contractions
- decreased tone of pylorus
- increased diameter and inhibition of segmenting contractions of proximal duodenum
29
following a meal, how long does it take fro gastric emptying?
about 3 hours
30
What inhibit gastric emptying?
- relaxation of orad
- decreased force of peristaltic contractions
- increased ton elf pyloric sphincter
- segmentation contractions in intestine
31
What is the entero-gastric reflex?
negative feedback from duodenum to slow down rate of gastric emptying
32
What all is involved in the enters-gastric reflex?
- acid in D -> secretin released -> inhibit stomach motility via gastrin inhibition
- fats in D -> stimulate CCK and GIP -> inhibit motility
- hypertonicity in D -> (unknown hormone) -> inhibit gastric emptying
33
What is gastroparesis? What causes it?
slow emptying of stomach/paralysis of stomach
| damage to vagus nerve- idiopathic or due to high glucose
34
What causes large particles of undigested residue to get out of the stomach?
migrating myoelectric complexes (MMC)
35
How often do MMCs occur and when? What controls them?
90 min intervals during fasting
| motilin
36
What kind of movements do segmentation contractions generate?
back and forth
| no forward propulsive movement
37
What cause peristaltic contractions?
circular and longitudinal muscles working in opposition of each other's actions
38
In the stomach, slow waves initiate contractions. But in the intestine, what is necessary for muscle contraction? What role do slow waves play here?
```
spike potentials (AP)
slow wave frequency sets max frequency of contractions
```
39
What are the slow wave frequencies of the intestines?
D- 12 cycles/min
J- 10 cycles/min
I- 8 cycles/min
40
What is the neural input for intestine contractions?
peristaltic reflex via ENS
| PNS stimulates, SNS inhibits
41
What hormones stimulate contractions of intestines?
```
serotonin
certain prostaglandins
gastrin
CCK
motilin
insulin
```
42
What hormones inhibit contraction?
epi
secretin
glucagon
43
What coordinates the vomiting reflex? What carries the afferent impulses?
medulla- vomiting center
| vagus and sympathetic afferents
44
What are the events of vomiting?
- reverse peristalsis of Si
- stomach and pylorus relaxation
- forced inspiration to increase abdominal pressure
- movement of the larynx
- LES relaxation
- glottis closes
- forceful expulsion
45
What causes relaxation of the ileocecal sphincter? What about contraction?
distention of ileum
| distention of colon
46
What makes up the longitudinal muscle layer of the large intestine?
taeniae coli
| run from cecum to rectum
47
What does sympathetic innervation of large intestine?
T10-L2
superior mesenteric ganglion- proximal regions
inferior mesenteric ganglion- distal region
hypogastric plexus- distal rectum and anal canal
48
What nerves control the external anal sphincter?
somatic pudendal nerves
49
What is the rectosphincteric reflex?
rectum fills and smooth muscle wall contracts
| internal anal sphincter relaxes
50
What pathways do you have to destroy to cause a loss of voluntary control of defecation?
pathways within spinal cord that lead to cerebral cortex
sensory of rectal distention
voluntary control of external sphincter
51
What causes Hirschsprung disease?
ganglion cells absent from segment of colon
52
What is the result of the absence of the ganglion cells from a segment of colon in Hirschsprung disease?
VIP levels low -> SM constriction/loss of coordinated movement -> colon contents accumulate
53
What is the gastroileal reflex?
gastric distention relaxes ileocecal sphincter
54
What are the gastro and duodena-colic reflexes?What transmits them?
distention of stomach/duodenum initiates mass movements in colon
ANS
55
who supplies sympathetics to GI tract
greater, lesser, least splanchnic nn
56
who supplies parasympathetics to the GI tract
vagus, pelvic splanchnics
57
how much of vagus n is sensory
75%
58
how much of vagus n is motor
25%
59
what do we call it when a stimulus and reflex both travel along the vagus n
vagovagal reflex
60
whats the name of the sensory nuclei in the medulla where the vagus sends its afferent info
nucleus of tracts solitaries (NTS)
61
D cells of the GI mucosa release __ when there is acid in the lumen
somatostatin
62
what does somatostatin do
inhibits gastric acid secretion
63
ECL cells in the gastric glands store and secrete ___ to increase acid production by parietal cells
histamine
64
the pancreas releases more insulin after oral ingestion of glucose than IV injection of a similar plasma concentration -- what do we call this
the incretin effect
65
the incretin effect (more insulin released after eating glucose verus injecting it in an IV) occurs for what reason
oral glucose induces GIP secretion, IV injection of glucose does not do this
66
when the stomach is distended or stimulated by vagus n, G cells release ___ which stimulates mucosal growth
gastrin
67
gastrin secreting tumor called ___ causes more acid production in stomach and thus hypertrophy of mucosa, ulcers, or steatorrhea
zollinger ellison syndrome
68
i cells in the duodenum and jejunum secrete ___ when protein or FA is present
CCK
69
I cells in what regions secrete CCK?
duodenum and jejunum
70
what hormone causes gallbladder contraction and inhibits gastric emptying
CCK
71
S cells that secrete secretin are found in what region of the GI tract
duodenum
72
duodenal S cells secrete __ when FA or acid enters duodenum to increase the pH
secretin
73
this hormone is secreted in duodenum and jejunum and functions to increase insulin secretion from the pancreas and decrease gastric acid secretion
GIP
74
What innervates the striated muscle in the upper 1/3 of the esophagus
Vagus n
75
What is the fluid secreted from the parotid gland composed of and how much of the daily output of saliva is it?
water, ions, enzymes (amylase)
| 25%
76
What is the fluid secreted from the submaxillary and sublingual glands composed of and how much of the daily output of saliva is it?
aqueous fluid and mucin glycoprotein for lubrication
| 75%
77
What cells contract to eject saliva into the mouth?
myoepithelial cells
78
What is the saliva in the intercalated duct like compared to plasma?
similar ionic composition
79
What are striated ducts lined by?
columnar epithelial cells ( ductal cells)
80
How do ductal cells modify the initial saliva? What's an important feature of them?
make it hypotonic
| impermeable to water
81
What are the electrolytes of saliva like compared to plasma?
increased K and HCO3
| decreased NaCl
82
Is there net absorption or secretion of solutes in salivary secretion? What is secreted?
net absorption
| KHCO3
83
Where do the presynaptic parasympathetic nerves that innervate the salivary glands originate? What about postsynaptic?
facial and glossopharyngeal nerves
| autonomic ganglia
84
Where do the preganglionic sympathetic nerves that innervate the salivary glands originate? How do the postganglionic fibers get tot he glands?
cervical ganglion
| periarterial spaces
85
How do vasopressin and aldosterone modify the composition of saliva?
decrease Na concentration
| increase K concentration
86
How do parasympathetics activate salivary glands?
CN VII and IX
release ACh on mAChR
IP3, Ca increases
87
How do sympathetics activate salivary glands?
T1-T3
release NE on BAR
cAMP
88
What is exclusively in control of salivary secretion?
ANS
89
What are the main components of gastric juice?
```
Hal
pepsinogen
mucus
intrinsic factor
H2O
```
90
What is the function of HCl in gastric juice?
pepsinogen -> pepsin
with pepsin = protein digestion
kills bacteria
91
What neutralizes acid and maintains the surface of the mucosa at a neutral pH?
mucus and HCO3
92
What is intrinsic factor required for? Where is it released?
vitamin B12 absorption in ileum
| stomach
93
What kind of glands does the body of the stomach contain? What are the two main cells found in these glands?
oxyntic glands
| parietal cells and chief cells
94
What do parietal cells produce? What do chief cells produce? In what glands and where do you find these cells?
parietal- HCl and intrinsic factor
chief- pepsinogen
oxyntic glands in body of stomach
95
What kind of glands does the antrum of the stomach have? What cells are found here?
pyloric glands
G cells
mucous neck cells
96
What do G cells produce?What do mucous neck cells produce? In what glands and where do you find these cells?
G- gastrin
mucous neck- mucus, HCO3, pepsinogen
pyloric glands in antrum of stomach
97
where do G cells release gastrin?
into the circulation
98
What is the net result of parietal cells working?
secrete HCl
| absorb HCO3
99
What does omeprazole do?
inhibits H/K ATPase in treatment of ulcers to reduce H secretion from parietal cells
100
What does cimetidine do?
antagonist of H2 receptors to treat duodenal and gastric ulcers and GERD
101
What do H2 receptors in parietal cells normally bind to? What's the result of this?
histamine -> cAMP -> stimulates H/K ATPase to secrete H+
102
What is the passive feedback mechanism that regulates HCl secretion?
pH falls -> gastrin release is inhibited -> decrease in HCl secretion
103
What does gastrin bind to in parietal cells?What's the result of this?
CCKB receptor -> Gq -> IP3/Ca -> stimulate H/K ATPase
104
How does the vagus nerve directly stimulate HCl secretion? What can block this?
releases ACh to stimulate parietal cells
| atropine
105
How does the vagus nerve indirectly stimulate HCl secretion?
releases GRP to stimulate G cells which produce gastrin which stimulate parietal cells
106
What does potentiation require?
separate receptors on the target cell for each stimulant
107
What does histamine potentiate the actions of when it comes to secretion of HCl?
ACh and gastrin
108
Due to potentiation, antagonists of H2 receptors (cimetidine) block what else other than histamine?
effects of Ach and gastrin
109
Due to potentiation, what else do antagonists of mAChRs (atropine) block the effects of other than ACh?
Ach-Potentiated effects of histamine and gastrin
110
What are the stimuli for the cephalic phase of HCl secretion and what are the mechanisms of this phase?
smelling and tasting, chewing, swallowing
vagus nerve activates parietal cells via Ach
vagus nerves activate G cells via GRP to release gastrin which activate parietal cells
111
What stimulates the gastric phase of HCl secretion? What are the mechanisms this works?
distention of stomach, presence of amino acids and peptides
activates vagus nerve (parietal cells and G cells)
local reflex -> G cells -> gastrin -> parietal cell
AAs -> G cell -> gastrin -> parietal cell
112
What do we take in that can stimulate G cells to produce gastrin?
coffee and alcohol
113
What stimulates the intestinal phase of HCl production and what are the mechanisms?
products of protein breakdown activate intestinal G cells
114
What make up the non parietal component of gastric juice?
NaCl, K at same concentration as plasma, HCO3-
alkalne
115
What is the osmolarity of parietal component of gastric juice? What happens as the secretion rate increases?
hyperosmotic
| concentrations approach those of pure parietal cell secretion
116
How does somatostatin directly inhibit HCl secretion?
binds to receptors on parietal cells coupled to adenylyl cyclase via Gi protein
antagonizes histamine effect
117
How does somatostatin indirectly inhibit HCl secretion?
inhibits release of histamine from ECL cells and gastrin from G cells
118
What inhibits somatostatin from being released?
vagus nerve releasing Ach on to D cells
119
What cells in what glands secrete pepsinogen?
chief cells and mucus cells in oxyntic glands
120
What two things stimulate the secretion of pepsinogen?
```
vagal stimulation (most important)
H+ triggers local reflexes to stimulate chief cells
```
121
Other than protein breakdown, what's another function of pepsin? Whats the optimal pH?
converts pepsinogen to pepsin
| 1.8-3.5
122
When is pepsin reversibly and irreversibly inactivated?
reversibly >5.0
| irreversibly >7-8
123
If develops pernicious anemia, what are they lacking and what should you suspect has been destroyed?
intrinsic factor to bind to vitamin B12
| gastric parietal cells (atrophic gastritis)
124
How does the stomach protect itself from the super acidic stuff in it?
mucous neck cells secrete mucus
| gastric epithelial cells secrete HCO3- to neutralize acids or inactivate pepsin
125
if you suspect a patient has a gastrinoma what test do you perform and how does it work?
secretin stimulation test
| inject secretin there will be increase in gastrin release
126
What are the peptic ulcer diseases a result of?
- loss of protective mucosal barrier
- excessive H+ and pepsin secretions
- combo of the two above
127
What enzyme does H pylori have that allows it to live in the stomach? What does this enzyme produce?
urease converts urea to NH3 which alkalinizes the environment so it can attach to gastric mucosa
128
What is the difference between gastric and duodenal ulcers for diagnosis?
duodenal ulcers have an increase in H+ secretion
129
Why do duodenal ulcers have an increase in H+ secretion?
h pylori inhibits somatostatin secretion from D cells
130
Other than inhibiting somatostatin secretion, how else does h pylori lead to an acidic duodenum?
inhibits duodenal HCO3- secretion
131
Why do patients with Zollinger-Ellison syndrome have steatorrhea?
low duodenal pH inactivates pancreatic lipase
132
Why are H+ secretory rates so high in Zollinger-Ellison syndrome?
tumor (in pancreas usually) secretes large quantities of gastrin
133
So how does Zollinger-Ellison syndrome lead to an ulcer in the duodenum?
excessive H+ arrives to duodenum and overwhelms buffer capacity of HCO3- in pancreatic juice
134
How do you treat ZE syndrome?
cimetidine (inhibits histamine), omeprazole (inhibits H/K ATPase), surgical removal of tumor
135
What does pancreatic juice contain?
HCO3-
| enzymes to digest carbs, proteins, lipids
136
What part of the pancreatic glands secrete enzymes?
acing cells
137
What part of the pancreatic glands release the aqueous solution? What does it contain?
ductal cells
| HCO3-
138
What enzymes secreted by the pancreas are active?
amylases and lipases
139
What is the net result of pancreatic ductal cells doing their job?
secrete HCO3-
| absorb H+
140
What stimulates the cephalic phase of pancreatic secretion? What is it mediated by and what does it produce?
smell, taste, conditioning
vagus n
enzymatic secretion
141
What initiates the gastric phase of pancreatic secretion? What is it mediated by and what does it produce?
distention of stomach
vagus n
enzymatic secretion
142
What accounts for 80% of pancreatic secretion? What does it produce?
intestinal phase
| enzymatic and aqueous
143
How does the sympathetic nervous system innervate the pancreas and what effect does it have?
postganglionic nerves from celiac and superior mesenteric plexuses
inhibit secretions
144
How does the parasympathetic nervous system innervate the pancreas and what effects does it have?
pre ganglionic synapse in ENS
postganglionics synapse on exocrine pancreas
stimulates secretion
145
How is pancreatic secretion from acinar cells regulated during the intestinal phase?
Phe, Met, Try activate I cells -> CCK -> CCKA receptors on acinar cells -> IP3, Ca -> enzymes
Vagovagal reflex -> Ach -> mAChR on acinar cells -> enzymes
146
How is pancreatic secretion from ductal cells regulated during intestinal phase?
acid activates S cells -> secretin -> cAMP in ductal cells -> aqueous solution (HCO3-)
also ductal cells respond to Ach and CCK
147
What are the two types of digestive activity?
cavital (luminal) and membrane (contact)
148
What is cavital (luminal) digestion?
results form action of enzymes secreted by salivary glands, stomach, pancreas
149
What is membrane (contact) digestion?
hydrolysis by enzymes synthesized by epithelial cells
150
What re the longitudinal folds in the small intestine called?
folds of Kerckring
151
Where are villi the longest and shortest in small intestine?
long in duodenum
| short in terminal ileum
152
What's the turnover rate for enterocytes? What are they susceptible to because of this?
3-6 days
| irradiation and chemotherapy
153
What is the major mechanism for uptake of protein in enterocytes?
pinocytosis
154
What are the barriers a solute must move through during transmural movement for absorption?
- unstirred layer of fluid
- glycocalyx
- apical membrane
- cytoplasm of cell
- basolateral membrane
- basement membrane
- wall of capillary or lymphatic vessel
155
What are the three end products of carbohydrate digestion?
glucose, galactose, fructose
156
What are the only things absorbed by enterocytes? What does this mean?
monosaccharides
| majority of ingested carbs have to be digested to monos
157
What transporter brings in glucose and galactose on the apical border of enterocytes? What is transported with them?
SGLT1
| Na
158
What transporter sends glucose, galactose, and fructose out of the basolateral side of enterocytes? By what mechanism?
GLUT 2
| facilitated diffusion
159
What transporter brings fructose in on the apical side of the enterocytes? By what mechanism?
GLUT5
| facilitated diffusion
160
What test is used to measure the absorptive capacity of the proximal small intestine? What is a positive result?
d-xylose test
| less than 4g of d-xylose excreted in 5 hours
161
What does starch get broken down into? With what enzymes?
a-amylase to a-dextrins, maltose, maltotriose
| a-dextrinase, maltase, sucrase breaks them down to glucose
162
What does lactose get broken down into and by what enzyme?
glucose and galactose
| lactase
163
What does sucrose get broken down into and by what enzyme?
glucose and fructose
| sucrase
164
What enzyme activates trypsinogen? Where does this take place?
enterokinase
| small intestine
165
What are the five pancreatic enzymes (activated)?
trypsin
chymotrypsin
elastase
carboxy-pptidase A and B
166
Which enzymes are endopeptidases and what does this mean?
trypsin
chymotrypsin
elastase
hydrolyze interior peptide bonds
167
Which enzymes are exopeptidase and what does that mean?
carboxypeptidases A and B
| hydrolyze one amino acids t a time from the C-termial ends of proteins and peptides
168
Why is it that if you don't have trypsin it appears you don't have any pancreatic enzymes?
trypsin activates everyone including trypsin itself (autocatalysis)
169
What do pancreatic proteases do when they run out of ingested proteins to digest?
digest themselves and each other
170
Who breaks oligopeptides down into amino acids, dipeptide, tripeptide? Where?
peptidases
| brush border
171
What transporters bring in amino acids and with what?
four separate ones for neutral, acidic, basic, iminio
| Na
172
What are dipeptides and tripeptides brought into enterocytes with? How do they exit?
H+
| peptidases break them down to amino acids and they facilitated diffuse out
173
Chronic pancreatitis and cystic fibrosis have what effect on digestion?
deficiency of pancreatic enzymes
| won't absorb proteins
174
What transporter is missing in cystinuria? What amino acids will you excrete?
Na/di-basic aa transporter
| cystine lysine arginine ornithine
175
What amino acids do you excrete with Hartnup disease?What do the symptoms resemble?
```
neutral amino acids
tryptophan
pellagra (deficiency of niacin)
```
176
What channel gets messed up in CF? What is the pancreas not able to secrete?
regulated Cl- channel in apical surface of the ductal cell
| loss of HCO3- secretion
177
What enzymes break triglycerides down into monoglycerids and 2 FAs?
lingual, gastric, pancreatic lipase
178
Cholesterol ester is broken down into what by what?
cholesterol and 1 FA
| cholesterol ester hydrolsae
179
Phospholipid is broken down into what by what?
lysolecithin and 1 FA
| phospholipase A2
180
What is in the core of the micelle and what is on the exterior?
core has products of lipid digestion
| lined by bile salts
181
What emulsifies the lipid droplets in the stomach?
dietary proteins
182
What is the important role of CCK in lipid digestion? What stimulates its release?
slows rate of gastric emptying
| dietary lipids appearing in small intestine
183
What solves the problem of bile salts displacing pancreatic lipase off of the lipid-water interface of emulsified lipid droplets?
collapse (activated by trypsin)
| binds to lipase, displaces bile salts
184
Who hydrolyzes triglycerides to produce glycerol? What is another job of this enzyme?
cholesterol ester hydrolase
| catalyzes production of cholesterol
185
What is the optimum pH for pancreatic lipase?
6
186
What are the steps for absorbing lipids?
1. solubilization of micelles- bile salts are amphipathic
2. diffusion of micellar content across apical membrane
3. reesterifcation
4. chylomicron formation (with apoproteins)
5. exocytosis of chylomicron
187
If you have a failure to synthesize Apo B (B-lipoprotein) what does this result in?
abetaliproteinemia
| unable to absorb chylomicrons so unable to absorb dietary lipids
188
What changes in intestinal function can result in steatorrhea?
- reduction in rate of production of pancreatic lipase
- decrease in HCO3- production
- any reduction in surface area
189
Regulation of what is critical for the integrity of pancreatic enzyme function? Who does this job?
acidity of duodenal content
| pancreas by secreting HCO3-
190
What are three ways the pancreas can be messed up that leads to too much acid in the duodenum?
pancreatic insufficiency- failure to secrete adequate amount of pancreatic enzymes
pancreatitis- impaired HCO3- and enzymes secretion
Zollinger-Ellison syndrome: gastrin-secreting tumor
191
What does a deficiency of bile salts interfere with? What are two things that can cause this?
formation of micelles
ill resection
small intestinal bacterial overgrowth
192
Why does an overgrowth of small intestinal bacteria cause a deficiency of bile salts? What causes this overgrowth?
deconjugate bile salts, can damage mucosa
| two causes: decreased gastric acid secretion, small intestine dysmotility
193
What is tropical sprue? What is a symptom of it?
decreased # of intestinal epithelial cells
| steatorrhea, diarrhea
194
How do you treat tropical sprue?
tetracycline and folate
195
What causes celiac sprue? What does this result in?
autoimmune disorder
antibodies develop against gliadin
destroy small intestine villi
hyperplasia of intestinal crypts
196
What malabsorption do you see in celiac sprue patients?
folate
iron
calcium
vitamins A, B12, D
197
What are unique symptoms of celiac sprue?
```
tingling/numbness of hands or feet
itchy skin with a rash
fatigue
seizures
easy bruising
bone fractures
```
198
What are the fat-soluble vitamins and how are they absorbed?
A, D, E, K
| same as lipids
199
What are the water-soluble vitamins? How are they absorbed?
B1, B2, B3, B12, C, biotin, folic acid, nicotinic acid, pantothenic acid
most with Na-depenednt cotransport mechanism in small bowel
200
What are all the proteins Vitamin B12 (cobalamin) forms complexes with in order to be absorbed?
R proteins (salivary juices)
IF
Transcobalamin II
201
Why would patients with celiac disease have a lot of bruising?
impaired absorption of vitamin K
202
What are two jobs vitamin B12 has as a hydrogen acceptor coenzyme?
reducing ribonuleotides to deoxyribonucleotides (replication of genes)
co-factor in folate coenzyme recycling and nerve myelination
203
Why does a deficiency of vitamin B12 lead to pernicious anemia?
it's important in DNA synthesis in RBCs
204
Why would a gastrectomy or gastric bypass lead to deficiency of vitamin B12?
loss of parietal cells (source of IF)
205
Let's say a patient still has their stomach but they develop pernicious anemia. What are possible diagnosis?
atrophic gastritis - loss of parietal cells
| autoimmune metaplastic atrophic gastritis- immune system attacks IF protein or parietal cells
206
What test do we do to see if a patient has pernicious anemia?
schilling test
207
If we can't get the (vitamin) D what happens?
inadequate Ca absorption -> rickets or osteomalacia
208
Who binds free iron in the duodenum? What does he bind to to form what?
apotransferrin
| hemoglobin and free iron
209
Who binds to receptors in membranes of intestinal epithelial cells to get absorbed via pinocytosis and then released into the blood? We're talking iron absorption.
transferrin
210
Where does most of the integration signaling regulating food intake and energy expenditure happen?
arcuate nucleus
211
What is the anorexigenic pathway and where is it occurring?
POMC neurons release a-MSH
a-MSH binds to MCR-4 in second-order neurons
arcuate nucleus
212
What ist he orexigenic pathway and where does it occur?
unger singlas stimulate release of NPY
NPY binds to Y1R
agouti-related peptide (AGRP) is released (antagonist of MCR-4)
213
Mutations in POMC and MCR-4 genes can lead to what
obesity
214
Who does the vagus afferents signal to? What's the next step?
NTS nucleus of the tractus solitarius
| hypothalamus
215
Who secretes ghrelin? What does it bind to? What does it stimulate?
endocrine cells in stomach
growth hormone secretagogue receptors (GHSR)
neurons that release NPY
216
What actions does ghrelin have?
increase appetite, gastric motility, gastric acid secretion, adipogenesis
decrease insulin secretion
217
What effect does insulin have on the NPY and POMC pathways? What are its actions?
inhibits NPY
stimulates POMC
decrease appetite
increase metabolism
218
Why do patients with DM type 1 have an increase in food intake?
decrease in insulin
219
How does CCK elicit satiety?
- acts on vagal -> NTS -> hypothalamus. decrease gherkin
| - decrease gastric emptying to increase gastric distention
220
What cells release CCK?
i cells in duodenum
221
What cells release PYY
L cells of ileum and colon following a meal
222
What does PYY bind to? What is its function?
Y2R in hypothalamus
inhibits NPY neurons
releases inhibition of POMC neurons
223
What cells secrete leptin? What does it bind to?
cells in adipose tissue
binds to receptors in POMC and NPY systems
inhibits NPY
stimulates POMC
224
What effects does leptin have?
decrease appetite
increase metabolism
decrease ghrelin release
225
How can obese humans have high leptin levels but still be overweight?
failure to respond to leptin
226
Who secretes glucagon-like peptide-1 (GLP-1)? What is its job?
co-secreted with PYY from L cells in intestine
| reduces food intake, suppresses glucagon secret, delays gastric emptying
227
When do you see high levels of glucagon-like peptide-1 (GLP-1)?
after meals
228
Other than GLP-1 and PYY, what is another hormone released by L cells of the intestine in response to ingested food? It has an anorectic effect.
oxyntomodulin
229
What effect does pancreatic peptide (PP) have on food intake and how?
decreases food intake through Y4R in brainstem and hypothalamus
secreted from cells in pancreatic islets of langerhans
230
Who secretes glucagon and what does it do?
a cells of pancreatic islets
increases blood glucose levels and insulin secretion
reduces food intake
231
What is amylin stored and released with and what effect does it have?
insulin in response to food intake
| inhibits NPY release
232
What hormones do we see an increase in following gastric bypass?
GLP-1 and PYY
233
what supplies the liver with blood
portal vein - 75%
| hepatic artery - 25%
234
blood supply from what vessel provides the liver with oxygen?
hepatic artery
235
blood supply from what vessel provides the liver with nutrients?
hepatic portal vein
236
what is the name of the structure that receives blood from both the hepatic artery and portal vein
hepatic sinusoid
237
how does blood leave the liver and return to heart
hepatic veins --> IVC
238
blood supplying the liver enters the hepatic sinusoids. due to gaps in the endothelial cells lining the sinusoids, the blood is allowed to come into contact with what other cell type
hepatocytes
| these are the primary functional cell of the liver
239
running in the opposite direction, but parallel to the hepatic sinusoids are what?
bile canaliculi
240
What is the transporter on enterocytes that absorbs bile salts?
apical sodium dependent bile acid transporter (ASBT)
241
stellate cells are another functional cell type present in the liver. what is significant about stellate cells
the liver is very contractile; the stellate cells are largely responsible for the liver's resting contractility
stellate cells are also responsible for the storage of lipids and vitamin A
242
there is a class of cells in the liver that are responsible for protecting the liver against viruses and tumor cells. these cells are similar to (or maybe they're just a specific type of) NK cells. what is the name of these cells
Pit cells
243
a big function of the liver that Zaidi stressed is what
primary distribution center - liver is the hub, gets nutrients and toxins and decides what to do with them.
also glucostasis - keeps glucose levels constant
244
the liver is the only organ with all of the enzymes to carry out what biochemical cycle
urea cycle
245
several structural adaptations exist that allow the liver to be in prolonged contact with blood. basically blood flow is slow through the liver. what are these structural adaptations
lack of tight junctions between endothelial cells
lack of basement membrane between endothelial cells and hepatocytes
fenestrations in endothelial cells
low portal blood pressure
246
hepatocytes take in metabolites from the blood. nutritional stuff is converted to a useful form and used in the way the body most needs it. what happens to the bad shit
into the bile canaliculi to eventually become part of bile
247
isoprenoids are made of how many carbons
5
248
acetyl CoA is generated in what organelle
mitochondria
249
what is the shuttle system used to get acetyl CoA from the mitchondria to the cytoplasm?
citrate shuttle
250
what are the pathways that yield acetyl CoA
oxidative decarboxylation of pyruvate (carbohydrate metabolism)
beta-oxidation of fatty acids (fatty acid metabolism)
breakdown of amino acids (amino acid metabolism)
point here is that we have a bunch of different sources of acetyl CoA
251
the backbone of all steroid hormones is a tetracyclic ring structure called what
sterane ring
252
cholesterol is allicyclic what does allicyclic mean
it means it displays characteristics of both cyclic and linear molecules
253
What causes rotor syndrome?
nonfunctional OATP1B1 and OATP1B3 proteins
| can't transport bilirubin into liver
254
in terms of the fate of synthesized cholesterol it must either be excreted or absorbed what percentage of our ingested cholesterol is designated for each of these fates
5% excreted
| 95% re-absorbed
255
the primary regulation of cholesterol biosynthesis is what
dietary intake; synthesis is inversely proportional to dietary intake
more intake means less synthesis
256
in the first phase of cholesterol synthesis, 2 acetyl groups come together to form a product, then a third acetyl group is added to form what important intermediate
HMG CoA
257
the rate limiting enzyme of cholesterol biosynthesis is what enzyme
HMG CoA reductase
258
Where are the primary bile acids synthesized and what are they?
hepatocytes
| chalice acid and chenodeoxycholic acid
259
What are the secondary bile acids and where are they synthesized? Who converts primary to secondary?
deoxycholic and lithocholic acids
| 7a-dehydroxylase intestinal bacteria
260
What are the bile salts and where are they made?
conjugated in liver
glyco/taurodeoxycholic acid
glyco/taurolithocholic acid
261
What happens to bile salts in the gallbladder?
stored and concentrated (absorption of ions and H2O)
262
Canalicular bile is secreted by ductule cells in response to?
osmotic effects of anion transport
263
What two systems are in charge of uptake of bile salts on the basolateral membrane of hepatocytes?
sodium taurocholate cotransporting polypeptide (NTCP)
| organic anion transport proteins (sodium independent)
264
What two transporters are in charge of sending bile salts out of hepatocytes?
bile salt excretory pump (bsep)
| multidrug resistance protein 2 (mrp2)
265
What is the transporter on enterocytes that absorbs bile salts?
apical sodium dependent bile acid transporter (ASBT)
266
What keeps the liver from making a shiat ton of bile when we already have enough?
bile salts inhibit cholesterol 7a-hydroxylase
| the ol negative feedback
267
What is the majority of bile formation driven by? What is a smaller portion stimulated by?
bile acids secretion
| secretin
268
What effect does secretin have on bile secretion?
stimulates secretion of HCO3- and H2O from ductile cells resulting in
increase in bile volume, [HCO3-], and pH
decrease in [bile salts]
269
What enzyme is in charge of conjugating bilirubin?
UDP glucuronyl transferase
270
Why do we get jaundice with hemolytic anemia?
overwhelm liver's capacity to produce conjugated bilirubin
271
What is the syndrome that has am ild amount of increased levels of unconjugated bilirubin in the blood, pt may have episodes of hyperbilirubinemia due to physiologic stress, mutation in gene for UDP glucuronyltransferase, 30% have no s/s.
gilbert syndrome
272
the addition of what functional group to cholesterol is necessary in order to convert cholesterol to 7-alpha hydroxycholesterol, a direct precursor to bile acids
second OH group
| remember there is already an OH group on the third carbon of the cholesterol tetracyclic backbone
273
what enzyme is responsible for the addition of a hydroxyl group to cholesterol in order to form 7-alpha hydroxycholesterol, a direct precursor to bile acids
7-alpha hydroxylase
274
What are ways to treat crigler-najjar syndroem
phototherapy for up to 4years
blood transfusions
oral calcium phosphate and carbonate (form complexes with bilirubin in gut)
liver transplant (for type 1)
phenobarbital (type 2 only) can help conjugate
275
name the syndrome:
increased conjugated bilirubin w/o elevation of liver enzymes
mild jaundice
black liver
dubin-johnson
276
What causes dubin-johnson syndrome?
mutations in multidrug restiance protein 2 (MRP2) so can't transport bilirubin out of liver cells and into bile
277
Name the syndrome
build up of both unconjugated and conjugated bilirubin but more conjugated
liver isn't pigmented
rotor syndrome
278
What causes rotor syndrome?
nonfunctional OATP1B1 and OATP1B3 proteins
| can't transport bilirubin into liver
279
statins target this enzyme
HMG CoA reductase
280
the first phase of cholesterol biosynthesis ends in the formation of what product?
from what intermediate is this product formed?
IPP
| mevalonate
281
Any babies with what level of serum bilirubin should get phototherapy
>21mg/dL
282
What are causes of gallstones
- too much absorption of water from bile
- too much absorption of bile acids from bile
- too much cholesterol in bile
- inflammation of epithelium
283
Where does a gall stone have to be stuck in order to cause jaundice, biliary-type pain, risk of cholangitis and pancreatitis?
beyond joining of common bile duct and pancreatic duct
284
The majority of gallstones are where? How do they present?
stay in gallbladder
asymptomatic
75%
285
elevated aminotransferases?
primarily result of hepatocyte injury
286
elevated alkaline phosphates?
cholestasis
287
increased PT?
increases as ability of cirrhotic liver to synthesize clotting factors decreases
288
During phase I of drug metabolism, what happens?
drugs are processed via cytochrome P450 enzymes
289
During phase II of drug metabolism, what happens?
conjugation with glucoronide, sulfate, AAs, glutathione
290
in phase II of cholesterol biosynthesis, 6 IPP molecules come together to form what?
squalene
291
in phase II of cholesterol biosynthesis, squalene is converted to what
lanosterol
292
in the final step of cholesterol biosynthesis, lanosterol is converted to cholesterol. this step is blocked in fungi by a class of antifungals called what? name of the drug family
azoles
293
explain how statins work
strong competitive inhibitors of HMG CoA reductase
much higher affinity for the enzyme
increased SREBP maturation
294
explain SREBP and its role in cholesterol biosynthesis
maturation of this binding protein leads to increased expression of LDL receptor. this increased expression allows enhanced clearance of cholesterol by allowing more cholesterol to leave the blood via endocytosis
295
explain the myotoxic side effects of statins
decreased ubiquinone present (this means Inhibited ATP synthesis and carbohydrate metabolism) and decreased levels of prenylated proteins, which attach proteins to the plasma membrane
296
what does the skin do with cholesterol
synthesize vitamin D
297
what does the liver do with cholesterol
make VLDL
298
what do the adrenals and the gonads do with cholesterol
make steroid hormones
299
explain how insulin and glucagon regulate the activity of HMG CoA reductase
enzyme is reversibly phosphorylated
insulin and glucagon can influence whether the enzyme is more present in the phosphorylated/dephosphorylated state in order to modulate its activity
300
antifungal drugs (azoles) work by inhibiting the formation of what cholesterol derivative
ergosterol
301
antifungal drugs (azoles), in high concentrations, can inhibit what mammalian enzyme
the one that converts lanosterol to cholesterol
302
ketoconazole inhibits what enzyme; what pathway is blocked as a result?
7-alpha-hydroxylase
| conversion of cholesterol to bile acids
303
antiestrogens prevent the conversion of what to cholesterol
desmosterol
304
antiepileptic agents inhibit what reaction in cholesterol biosynthesis
conversion of squaliene to lanosterol
305
what enzyme can degrade sterane ring of cholesterol
NO ENZYME CAN DEGRADE STERANE RING OF CHOLESTEROL
306
the addition of what functional group to cholesterol is necessary in order to convert cholesterol to bile acids
second OH group
| remember there is already an OH group on the third carbon of the cholesterol tetracyclic backbone
307
what enzyme is responsible for the addition of a hydroxyl group to cholesterol in order to form bile acids
7-alpha hydroxylase
308
7-alpha hydroxylase is dependent upon what other substance that works as a cofactor
cytochrome P450
309
after a bile acid is created it must be
conjugated
310
what can bile acids be conjugated to
taurine or glycine
311
bile is reabsorbed where
ileum
312
absorption occurs in epithelial cells in the ___ of the intestines
villi
313
secretion occurs in epithelial cells in the ___ of the intestines
crypts
314
the secretion process begins when NaKCl cotransport brings these in from the blood and then ___ flows across the apical side and into the intestinal lumen
Cl which is followed by Na which is followed by H2O
315
Cl- channels in the apical membrane of intestinal crypt epithelial cells (where secretion occurs) are normally closed. what opens them?
ACh or VIP
316
what substance causes the G protein mechanism of secretory intestinal crypt epithelial cells to remain "on" all the time leading to loss of electrolyte and fluid in the form of diarrhea
cholera toxin
317
tight junctions are leaky in the ___ but are not leaky in the __
small intestine, colon
318
what is the net solute movement occurring in the jejunum
Na-HCO3 is being absorbed
319
what is the net solute movement occurring in the ileum
NaCl is being absorbed
320
the epithelial cells in colon villi (absorption occurs here) perform the same solute movement as what other cell in the body
principal cells of the kidney (absorb Na, secrete K)
321
synthesis of Na channels in the colon villi epithelium is dependent on what hormone
aldosterone
322
what commonly consumed substance is known to cause osmotic diarrhea
lactose
323
why does lactose cause osmotic diarrhea
no lactase means we can't break down or absorb lactose-- it remains in the gut lumen and retains water with it
324
how does gut bacteria factor in to lactose intolerance
gut bacteria breaks lactose into particles that are even more osmotically active making the problem worse
325
cholera toxin crosses apical membrane of intestinal epithelial cell and through action on a G protein, it keeps the ___ open at all times
Cl- channel
326
sensing of microbe-associated molecular patterns stimulates what in the intestines
- proliferaiton of intestinal epithelial cells in crypts
| - increased density of panted cells
327
What barrier does our inner mucous layer provide?
high [bactericidal AMPs]
| commensal-specific secretory IgA
328
What innate lymphoid cells respond to microbiota that produce IL-22? What does this stimulate?
lymphoid tissue inducer (Lti)
NK-22 cells
AMP production and promotes epithelial barrier integrity
329
Why kills bacteria that penetrate the enterocyte epithelial layer?
macrophages in lamina propria
330
If bacteria penetrate M cells, what kills them? Do they all die?
macrophages
| small numbers survive for days in DCs
331
What is the benefit of the Ag-loaded DCs from the gut not being able to penetrate farther to reach systemic secondary-lymphoid tissues?
immune responses by live bacteria is confined to mucosa
332
What do MAMPs stimulate IECs to secrete? What do these promote?
```
TSLP
IL-33
IL-25
TGFB
tolerogenic Mo and DCs
```
333
How do DCs induce the development of induced Treg cells?
TGFB
RA
IDO
334
How do iTreg cells and tissue macrophages dampen potential effector responses in the gut?
iTreg produce TGFB and IL-10
| tissue macrophages produce IL-10
335
Epithelial derived ____ and Treg cell derived ____ promote development of IgA+ plasma cells.
TGFB
| BAFF and APRIL
336
How do DCs induce IgA-secreting plasma cells?
RA-dependent mechanisms
337
IBS, food poisoning, psychosomatic diarrhea are all examples of
non immune-mediated ARs
338
IgE-associated food allergies is what type of hypersensitivity?
type I
339
During food allergic reactions, Th2 produce what cytokines?
IL-4
IL-9
IL-13
340
Both local and systemic responses in food allergies are due to what chemicals?
histamine
| platelet activating factor (PAF)
341
What two things does IgG1 lead to?
more IgE
| activates complement -> C3a/C5a -> activates mast cells
342
What effects do PAF and histamine have?
increase vascular permeability and smooth muscle contractility
343
The most important allergens in wheat allergy are?
alpha-amylase inhibitors
germ agglutinin
peroxidase
344
What are the main predisposing factors for celiac disease?
HLA-DQ2 and DQ8
345
Autoantibodies against what are specifically associated with celiac disease?
tissue transglutaminase 2 (TG2)
346
Why is gluten poorly digested in the small intestines?
proline-rich
| lack of prolyl endopeptidases
347
What does transglutaminase 2 (TG2) do?
makes a neutral gleaming charged
| so it modifies gluten
348
Tissue damage from celiac disease is what type of hypersensitivity? Why?
type IV
| self-reactive T cells
349
Why doe we see malabsorption resulting from CD?
T cell-mediated inflammatory response damages mucosa
350
What is gluten presented on after r TG2 makes it a potent immunostimulatory epitope?
HLA-DQ2 or HLA-DQ8 on APCs
351
Once activated by gluten, What do CD4 T cells secrete and what does this induce?
Th1 cytokines like IFNy
| induces release of MMPs by myofibrolasts resulting in villus atrophy
352
What cytokines maintain the Th1 response to gluten in celiac disease?
IL-18
IL-21
IFN-y
353
What cytokine links the adaptive immune system to innate immune responses in CD?
IL-15
354
What tests do you order for CD and in what order?
first: measure IgA to TTG
next: measure total serum IgA (IgA deficiency?)
intestinal biopsy
