Week 2 Flashcards
1
Q
If there is an issue in the urea cycle, and the ammonia is not able to be cleared from the body, what could happen?
A
Ammonia could build up in the brain and cause brain damage
2
Q
What is the committed step of bile acid synthesis?
A
Cholesterol to 7(alpha) hydroxycholesterol with the enzyme 7(alpha) hydroxylase
3
Q
What does the presence of bile acids do to the synthesis of bile acid?
A
Negative feedback; it inhibits it
4
Q
What is the function of non-absorbable bile acid binding resins, like cholestyramine?
A
LARGE increase in bile acid excretion
causes a lowering of cholesterol because bile acid synthesis is induced
5
Q
The induction of _____________ causes the rate of bile acid synthesis to increase
A
7(alpha) hydroxylase
6
Q
What are gallstones made out of?
A
Bile that is supersaturated with cholesterol
7
Q
__________ is the insufficient secretion of bile salts or phospholipids into the gall bladder or excess cholesterol secretion into the bile
A
cholelithiasis
8
Q
What happens in the event of a chronic disturbance in the bile salt mechanisms?
A
malabsorption syndromes and deficiency in fat soluble vitamins
9
Q
Describe the phases involved in the inactivation and detoxification of xenobiotics
A
Phase 1 increases the polarity and is catalyzed by cytochrome P450 enzymes
Phase 2 takes the primary metabolites to secondary metabolites
10
Q
Describe a cytochrome P450
Who is her family? What is she made of? Where does she live? Who are her best friends? (what does she co-localize with?) How does she work (operate)
A
She’s apart of the CYP superfamily
She has heme containing proteins in her
She is present in the ER
Her bestie is NADPH cytochrome P450 reductase
Use the ETC to get their work done
11
Q
What do CYPs do?
A
detoxify pharmacological agents
12
Q
Agents that inhibit CYP will _______ drug levels in plasma
A
increase
13
Q
Agents that stimulate CYP will cause ______ in drug levels in plasma
A
Decrease
14
Q
If a patient takes statins with grapefruit juice, what will happen to the statin levels in the plasma?
A
There will be an increase in the statin levels. Citrus juices act as an inhibitor of CYP, which is what allows for the statins to be metabolized. Without the CYP being utilized, statins cannot be broken down which means that they are active in the plasma and they lower the cholesterol that is in the blood too much
15
Q
If a patient drinks caffeine but is also taking ciprofloxacin, why are their caffeine levels elevated for a longer period of time after consuming the caffeine?
A
The cipro inhibits the CYP1A2 and causes a slower metabolism of the caffeine and causes an increase in the caffeine levels because of the lack of metabolism
16
Q
Describe personalized medications. How do they work?
A
Everyone has variations of CYPS; so you can genotype for them and treat accordingly
17
Q
How is tylenol removed from the body?
A
Tylenol conjugates with the glucuronic acid or sulfate and then are excreted via the kidney
18
Q
Describe what happens in a tylenol overdose
A
Tylenol is conjugated in the kidney by CYP3A4 to NABQ1 which needs to be detoxified by glutathione
If there is a tylenol overdose, the system becomes overwhelmed and the glutathione is not able to detoxify the NABQ1, which is toxic to the liver and causes hepatic failure and death
19
Q
Why is NABQ1 toxic to the liver?
A
causes free radical mediated per oxidation of membrane lids and damages hepatocytes
20
Q
A patient comes in with a suspected tylenol overdose, what do you give the patient?
A
N-acetyle cysteine
21
Q
What are the major changes that occurs with diseases of the liver?
A
Normal leaky membrane that is between endothelial cells is filled with a high density membrane of fibrillar collagen
increased stiffness in the vascular channels leads to portal hypertension
IMPAIRED free exchange of the material between the hepatocytes and blood
22
Q
What are the labs used to assess liver function on a metabolic panel (list them)
A
Albumin Transaminases Alkaline phosphatase Prothrombin time (PT) Bilirubin Urea (BUN) Glucose TAGs Cholesterol
23
Q
If a person has a liver disease, what would you expect the ALT and AST levels to be?
A
ALT And AST levels would be increased because these are released from eh damaged hepatocytes
24
Q
T/F: ALT is more sensitive because it is cytosolic
A
TRUE
25
If a person has an issue with Vitamin A storage in the liver, which cells are likely affected?
Stellate cells
26
If someone is dehydrated, what will happen in regards to salivary gland innervation: include mechanistic steps
The parasympathetics will be inhibited, Ach will not be released from CN VII and CN IX and is not able to bind to the mCHAR on the acinar and ductal cells
IP3 and CA2+ are NOT increased
27
What is the effect of ADH And aldosterone on the saliva?
Decreases Na composition (absorbs it) and increases K+ concentration (secretes it)
28
What is the function of HCl
initiates protein digestion
pepsinogen to pepsin
kills a large number of bacteria
29
What is the function of mucus
protects the gastric lining from damage by neutralizing acid
30
What is intrinsic factor?
Helps with the absorption of B12
31
What is released from the parietal cells?
Intrinsic factor and HCL
32
What is released from chief cells?
pepsinogen (in response to a low pH)
33
What is released from G cells
Gastrin
34
What effect does Atropine have on the parasympathetic nervous system?
Does not allow the Act to bind to the mACHR
35
How does omeprazole help to lower the gastric acid in the stomach?
IT inhibits the K/H pump that is in the lumen of the parietal cells
Cl does not follow H+ out because H+ isn't getting out, so there is not any secretion of HCl which will increase the pH in the stomach
36
As the pH of the gastric acid decreases, what happens to the gastrin release?
It is inhibited so that the HCl is not secreted as much
37
T/F Atropine will block both the direct and indirect pathway of vagal stimulation on the parietal cells
False it will only inhibit the direct pathway
Atropine will not have any affect on the gastric secretion
38
________ acts on G cells to inhibit gastrin release
Somatostatin
39
_________ potentates the actions of ACH and gastrin
Histamine
40
What do antagonists of H2 (cimetidine) receptors do to histamine, Ach, and gastrin?
it messes with the H2 receptor and histamine cannot bind, therefore decreasing the abilities of Ach and gastrin
41
What does an antagonist of an mACHR (atropine) do to histamine, Ach, and gastrin?
the effects of ACH will be blocked, which will decreased the Ach-potentiated effects of histamine and gastrin
42
What is cimetidine used to treat, and why? (MOA)
Used to treat duodenal and gastric ulcers as well as GERD because it inhibits the H2 receptors
Normally histamine will cause an increase in gastric function and in turn, an increase in the acidity of the stomach: blocking this will neutralize things and ease the sx
43
Chewing, swallowing, smell, and test are the stimuli that cause acid secretion during the _______ phase
cephalic
44
Distention of the abdomen will cause the acid secretion during the ________ phase
gastric
45
Digested proteins will cause the acid secretion during the ______ phase
intestinal phase
46
Which phase of gastric acid release will be "abolished" if a vagotomy occurs
Cephalic phase
47
True/False
| Coffee (caffeinated and decaf) stimulate gastrin secretion
True
48
_____ _______ stimulation is the most important stimulus for pepsinogen secretion
Vagus nerve
49
True or false: Pepsin does not convert pepsinogen to pepsin, only trypsin can do that
False
| pepsin do too
50
Failure to secrete IF is associated with ________ & with absence of parietal cells
achlorhydria
51
If the body does not produce or secrete enough intrinsic factor, what kind of anemia will result and why?
Pernicious anemia because of the lack of B12
52
Atrophic gastritis and autoimmune metaplastic atrophic gastritis are common causes of ________ ________
pernicious anemia
53
What is atrophic gastritis?
Inflammation of the stomach mucosa that leads to the loss of parietal cells
54
What is autoimmune metaplastic atrophic gastritis?
The immune system attacks the intrinsic factor protein or gastric parietal cells
55
What are common causes of an issue with the absorption of vitamin B12
Gastrectomy and a gastric bypass
56
What are the protective factors of gastroduodenal mucosa
HCO3 and mucus (protects from the acid)
Prostaglandins
Mucosal blood flow (increased blood flow typically protect)
Growth factors
57
What are the damaging factors to the gastroduodenal mucosa?
```
H+ and pepsin
H pylori
NSAIDs
Stress
Smoking
Alcohol
```
58
In Zollinger Ellison syndrome there is a duodenal or pancreatic neuroendocrine tumor: what does this typically cause?
Increased H+ secretion
Increased parietal cell mass
Increased H+ secretory rates
Inhibition of the absorption of sodium and water by the small intestine (secretory diarrhea)
59
What happens when there is excess H+ in the duodenum?
overwhelms the buffer capacity of HCO3 in the pancreatic juice and will create an ulcer
60
If there is a low pH in the intestinal contents, what will occur physiologically?
Inactivates the pancreatic enzymes
Interferes with the emulsification of fat by bile acids
Damages intestinal epithelial cells and villi
Leads to maldigestion and malabsorption
61
Describe the secretin stimulation test. What is secretin expected to do in a normal person. What is it expected to do with someone who has a gastrinoma?
Normal: secretin will cause an inhibition of gastrin release
Gastrinomas: secretin will cause an increase of gastric release
62
When I say gastrinoma, you say
Zollinger Ellison syndrome
63
Helicobacter pylori and the use of NSAIDS are common causes of ______ ________ _______
peptic ulcer disease (ulcers)
64
If there is a loss of the protective mucosal barrier or an increase in H+ and pepsin secretions or a combination of the two (from NSAIDs, or bacteria), what is a common outcome of this?
Peptic ulcer disease
65
There are two common types of peptic ulcer disease disease
Gastric ulcers
Duodenal ulcers
66
_________ releases cytotoxins that breakdown the mucosal barrier and underlying cells
H. Pylori
67
The enzyme ______ allows the bacteria to colonize the gastric mucosa in an H. pylori infection. How dies this enzyme work? ie what is the mechanism of action?
urease
Urease converts the urea to ammonia to alkalize the environment creating ammonium which is cytotoxic
68
What does ammonium do to the cell?
Damages the epithelial cells and breaks the mucosal barrier
69
how is H. pylori diagnosed?
By administering a test of urease activity
70
______ _______ form on the lining of the stomach and occur because there is a defect in the gastric mucosal barrier
Gastric ulcers
71
_____ _______ form on the lining of the duodenum; are the most common, an do not become malignant: H+ secretion rates are increased
Duodenal ulcers
72
In cystic fibrosis, the _____ is one of the first organs to fail
pancreas
Cl is not able to get out of the cell and be cotransported with HCO3
73
The phases of the pancreas are the same as the stomach: cephalic, gastric, and intestinal: which two produce only enzymatic secretions, and which one secretes enzymatic and aqueous secretions?
Cephalic and gastric only secrete enzymatic
Intestinal secretes aqueous and enzymatic
74
How is C-peptide used as a diagnostic tool for diabetes?
C-peptide is secreted when proinsulin is cleaved into insulin, if there are low levels of c-peptide, then you can assume that the patient has type 1 diabetes
75
What would you expect the c-peptide levels to be in type 2 diabetes?
Since the insulin is able to get out, but it is an issue in the receptor causing the pathology, then you would expect the insulin to be higher because it is not able to reach the receptor
C-peptide has a higher half life than insulin
76
Type 1 or Type 2 DM?
Destruction of B cells
Type 1
77
Type 1 or Type 2 DM?
Insulin resistance
Type 2
78
Type 1 or Type 2 DM?
K+ goes out of the cells and there is a lack of insulin effect on the Na/K ATPase
Type 1 DM
79
Type 1 or Type 2 DM?
A patient comes in with an increased blood glucose, increased blood amino acid concentration, polyuria, polydipsia
Type 1
80
Type 1 or Type 2 DM?
A patient comes in with hyperkalemia?
Type 1 DM
the body secretes potassium in order to try to get insulin to be released, because potassium is a stimulating factor
81
What will happen to blood sugar levels during exercise?
Blood sugar will decrease because AMPK is activated and GLUT4 is taken to the membrane so that glucose is able to supply the muscles
82
What effect does fasting have on insulin and glucagon?
Inhibits insulin release
Stimulates glucagon release
83
Describe incretin
Intestinal derived hormone that is secreted in response to GI glucose and fat
stimulates insulin secretion and inhibits glucagon secretion; slowing gastric emptying
84
Describe what happens to the muscular system when there is an insulin deficiency or an insulin resistance
There is a decreased tissue glucose utilization which leads to increased amino acid catabolism
There will be an increased blood level of amino acids in the blood in t1DM
These are then able to go to the liver and aid gluconeogeneis which leads to hyperglycemia, which causes the kidney to excrete more urine, resulting in a urine depletion which then causes polydipsia
85
Describe what happens to adipose tissue when there is an insulin deficiency or resistance
There is increased lipolysis which leads to polyphagia, and ketogenesis in the liver
This can lead to an increase in ketoacidosis causing a diabetic coma or causing the kidney to release more urine, resulting in volume depletion and polydipsia
86
If there is a decreased GLUT 4 uptake, decreased ability of insulin to repress hepatic glucose production, and the inability of insulin to repress adipose tissue uptake and lipolysis, which is likely being described?
Obesity induced insulin resistance
87
Autoimmune thyroid disease, celiac disease, and addisons disease are all associated conditions of _______
T1DM
88
Obesity, lipid abnormalities, PCOS and NAFLD are associated conditions of ______
T2DM
89
Why is IgA commonly used by the GI system immunologically?
does NOT activate complement
does not activate phagocytes
resistant to proteolysis by the peptidases in the stomach, small intestine, and the pancreas
90
Undigested dietary carbohydrates produce_____
SCFAs: acetate, propionate, and butyrate
91
Differentiate between a non-immune mediated and an immune-mediated reaction
non-mediated is more of a food intolerance
immune mediated is a food allergy
92
________ _______ _______ is a chronic condition that can cause cramping, constipation, and diarrhea
IBS
93
_______ ________ is caused by toxins such as bacteria in spoiled food can cause severe digestive symptoms.
food poisoning
94
______ _______ is a chronic digestive condition that is triggered by eating gluten
Celiac disease
95
Describe an IgE food allergy in terms of
| 1. first exposure
The allergen is ingested
B cells interact with the allergen and create a plasma cell that releases IgE to the mast cells
IgE binds to the mast cell
96
Describe an IgE food allergy in terms of
| 2. Second exposure
Allergen is ingested
cross links to the mast cell in the tissues
releases vasoactive amines, cytokines, and lipids
97
What is the role of Treg cells in control of food allergies?
To inhibit the mast cell reactivity, reduce IgE synthesis, and increase IgG and IgA synthesis
Also inhibit Th1, Th2, and Th17 cells from creating an inflammatory response
98
Vitamin D, Vitamin A, and folate ______ inflammatory responses
suppress
99
Describe the non-IgE mediated allergic reaction to peanuts
Peanuts can cause a production of C3a
c3A will stimulate the macrophages, basophils, and mast cells
PAF and histamine increases the vascular permeability and smooth muscle contractility
100
If a patient ingests a peanut and there is an increase in the amount of IgG1 that is present in the cell, what will likely happen after that?
There will be an increase in allergen-Ab complexes and macrophage activation that will release PAF
101
The ______ and _______ are molecules that are a predisposing factor for celiac disease
HLA-DQ2 and HLA-DQ8
immune response against gluten peptides
102
A patient with celiac disease, typically has serum antibodies against an enzyme, _____ _________ ___
Tissue transglutaminase 2`
103
This proline rich protein is poorly digested in the small intestinal tract and is rich inglutamine resides
Gluten
104
Describe what happens when a person with celiac disease is exposed to gluten
The antibodies that the patient has to TG2 will not allow the gluten to be broken down into glutamate and broken down. Instead it will cause an inflammatory T cell mediated response against the bowels leading to malabsorption
105
What is the preferred screening method of celiac disease?
tTG-IgA test
106
What ethnic groups are most at risk of developing T2DM?
African americans
Native americans
Hispanic
107
Which genes are involved in T1DM
HLADQ2 and DQ8
108
_____ expression and presentation of insulin in thymus to developing T cells in critical to protecting against development of T1DM.
AIRE
109
True/False: Decreased breast feeding does not have an effect on T1DM
False
Decreased breast feeding is linked to diabetes because cows milk has less insulin, so the baby isn't getting as much exposure
110
```
A patient comes in and has increased
M1 macrophages
mast cells
B2 cells
CD8 T cells
IFNy and Th1
in the tissues, would you expect them to have T1DM or T2DM?
```
T2DM: inflammatory processes in the adipose tissues is a common sign of obese adipocytes, which are associated with T2DM
111
True/False: The presences of 2+ antibodies is highly predictive of future T1DM
True
112
_______ is when liver cells are damaged and replaced by scar tissue. Excessive alcohol intake is a common cause
Cirrhosis
113
______ _______ can be caused by cirrhosis
Portal hypertension
114
______ ______ are swollen connection between systemic and portal systems at inferior end of esophagus
Esophageal varices
115
______ _____ swollen connections between systemic and portal systems around umbilicus
Caput medusae
116
If there are elevated aminotransferases, there is likely what pathology present?
Hepatocyte injury; liver injury
117
If there is an elevation in the alkaline phosphate of the serum, what is likely the pathology that is present?
Bile duct injury- cholestasis
118
________ measures the livers ability to detoxify metabolites and transport organic anions into the bile
Bilirubin
119
When the function of the liver declines, what will happen to the level of albumin?
It will decline as well. Albumin is made in the liver
120
What does prothrombin show?
Reflects the degree of hepatic synthetic dysfunction
it increases as the ability of a cirrhotic liver to synthesize clotting factor diminishes
121
_______ _______ is caused by increased conjugated bilirubin in the first week of postnatal and is caused by the breakdown of erythrocytes and low activity of UDP glucuronyl transferase
Physiological jaundice
122
What kind of bilirubin is produced in hemolytic anemia?
Increased unconjugated bilirubin
123
This is a defect in the ability of the hepatocytes to secrete conjugated bilirubin into the bile
Dubin-Johnson syndrome
124
What is mutated in Dubin-Johnson syndrome?
MRP2
125
What are some of the sx of Dubin Johnson syndrome?
Mild jaundice throughout life that is worsened by alcohol, BCPs, infection, and pregnancy
BLACK liver
126
Describe Gilberts disease
Mutation in the gene that codes for UDP glucuronyltransferase
causes hyperbilirubinemia when stressed
increased unconjugated bilirubin in the blood
127
_____ _______ syndrome is the mutation in the gene that codes for UDP glucuronyltransferase and can occur in two types
Crigler Najjar syndrome
128
Describe type 1 Crigler Najjar syndrome
noticed early in life
UDP glucuronyltransferase is not functional
characterized by CP, Sensorineural hearing loss, and eye gaze issues
damages neurons, astrocytes, and microglia (kernicterus)
129
Describe type 2 Crigler-Najjar syndrome
Diagnosed later in life, less function of the UDP glucuronlytransferase
survive
130
List the treatments that are sometimes used in Crigler-Najjar syndrome
```
Phototherapy: bilirubin lights
Blood transfusions
Oral calcium phosphate and carbonate
Liver transplant
phenobarbital
```
131
_____ ______ is the buildup of conjugated and unconjugated bilirubin due to mutations in OATP1B1
Rotor syndrome
132
What does OATP1B1 do?
transports bilirubin and other components from the blood to the liver
133
________ are caused by too much absorption of water from bile, too much absorption of bile acids from bile, too much cholesterol in bile, inflammation of the epithelium
Gall stones
134
Where do most of the gallstones form?
In the body of the gallbladder; usually asymptomatic
135
_______ is the inflammation of the gallbladder from obstruction of the cystic duct from a stone
Cholecystitis
136
Gallstones that are occluding the common bile duct are called __________
choledocholithiasis
jaundice and conjugated hyperbilirubinemia
137
______ is the infection of the bile duct
Cholangitis
138
What are the symptoms that are seen with a leptin or a leptin receptor gene deficiency?
Early onset severe obesity, infertility, hyrerphagia, infections
139
What are the symptoms of melanocortin 4 receptor gene mutation
Early onset severe obesity, increased linear growth, hyrerphagia, hyperinsulinemia
140
What are the symptoms of Prader will syndrome?
Neonatal hypotonia, slow infant growth, small hands and feet, mental retardation, hypogonadism, hyrerphagia, leading to severe obesity, elevated gherkin
141
What are the symptoms of a POMC deficiency
obesity, red hard, adrenal insufficiency due to ACTH, hyperproinsulinemia, hyrerphagia, pale skin, cholestatic jaundice
142
If the vagal activity is blocked, then the amount of material that is in the stomach no longer influences _____ ______
meal size
143
What is the lateral hypothalamic area involved in?
It is the hunger center
144
The satiety center is the ______ _______ ______
ventromedial hypothalamic nucleus
145
What stimulates the orexigenic pathway?
hunger, and it makes you want to eat more
146
What are the orexigenic hormones?
Ghrelin
147
What is the anorexigenic pathway hormones?
Insulin
CCK
PPY
Leptin
148
______ is secreted in the stomach by endocrine cells, bind to growth hormone receptors and stimulate the neurons that release NPY
Ghrelin
149
What are the actions of Ghrelin?
```
Increased appetite
Increased gastric motility
Increased gastric acid secretion
Increased adipogenesis
Decreased insulin secretion
```
150
______ binds to receptors in the POMC And the NPY systems to inhibit NPY and stimulate POMC
Insulin
151
What are the actions of insulin?
Increased appetite
| Increased metabolism
152
______ is released by I cells in the duodenum and allows for satiety
CCK
153
_____ is released by the L cells of the ileum and binds to Y2R in the hypothalamus to inhibit NPY and stimulate (released inhibition) of POMC
PYY
154
Leptin is secreted by _____ cells and inhibits the NPY system and stimulates the POMC system
adipose
155
What does the appetite suppressing hormone do?
Decreases appetite, increases metabolism, and decreases gherkin release
156
Describe glucagon like peptide GLP1
proglucagon derived peptide
secreted with PYY From L cells in the ileum
incretin
levels will rise after a meal and fall during fasting
reduces food intake, suppresses glucagon secretion, and delays gastric emptying
157
________ is released from the L cells in response to ingested food in proportion of the caloric intake
Oxyntomodulin
158
_______ _______ is secreted from the islet of Langerhans, it decreases the food intake through the Y4R in the brainstem and hypothalamus
Pancreatic peptide
159
Anorexia nervosa causes several hormonal changes. List some of these
Polymorphisms in the genes that are involved in eating attitudes, regulation of eating behavior and reward mechanisms
Leptin is released
Ghrelin becomes resistant
PYY is elevated
160
What two genes help with protection from T1DM?
DR2 and DQ6
