exam 1 Flashcards
1
Q
What are the primary circulating fuels of the body and their concentrations?
A
Glucose: 70-115 mg/dl, CHO(carbohydrate) in circulation
Triaclyglycerols: 100-250 mg/dL, bound and packaged in either GI derived chylomicrons or liver and gut derived VLDLs
Free-fatty acids: 20-200 mg/dL, non-esterified and bound to albumin, primary fuel in the fasted state
2
Q
Name steps to converting nutrient into acetyl CoA into another nutrient
A
- breakdown of large macromolecules to simple subunits
- breakdown of simple subunits to acetyl CoA accompanied by production of limited ATP and NADH
- complete oxidation of acetyl CoA to h20 and CO2 involved production of much NADH, which yields much ATP via electron transport
3
Q
What are the secondary circulating fuels?
A
amino acids, glycerol, lactate/pyruvate, ketone bodies
4
Q
How many calories do we ingest every day?
A
9 kilocalories per day +/-
5
Q
How to calculate BMI?
A
weight/(height^2)
kg/m^2
1kg = 2.205 lb
1 in = 2.54 cm
1m = 100 cm
6
Q
obesity epidemic numbers
A
72.9% US adults obese/overweight
35.7% US adults obese
17-20% of children obese (up from 9% in last 20 years)
obese individuals spend $1,800 more each year on healthcare
300K+ annual deaths from obesity
7
Q
Name etiology of obesity
A
genetics metabolic and physiological environment appetite regulation biochemical endocrine neuronal
8
Q
associated risks of obesity
A
hypertension stroke diabetes cancer skin disorders early death
9
Q
Name the classes of obesity and their numbers.
A
BMI 25-29.9 oberweight
30-34.9 obesity I
35-39.9 obesity II
40+ obesity III (morbidly obese)
body composition not accounted for in BMI
10
Q
when does risk for mortality goes up in females for obesity regarding BMI?
A
once body fat percentages go below 12-14% for females, risk for mortality is as high as obese class I because hormone levels get completely disregulated in ameteria(loss of menses because body cannot support life)
11
Q
normal adipocyte number vs obesity
A
25-40x10^9 adipocyte normal
obese > 160x10^9 adipocytes
obeses adults shrink adipocyte cells but cannot lose them —Cellular apoptosis doesn’t occur until prolonged starvation because body resists cell breakdown despite lipid shrinking in adipose cells
12
Q
what is the difference in amount of calories in maintaining obesity in normal adults vs natural obese adults?
A
requires 2x amount of calories in normal individuals to maintain obesity but natural ones require 1/2 as many calories to maintain obesity
13
Q
normal body percentages
A
male: 10-25%, female: 18-32%
14
Q
Why do we need fat to live?
A
fuel for energy source, insulator to protect form the environment and amintain core body tmeperature, protection around soft tissues and hard tissues, myelin sheaths protects electrical current from moving beyond the acon for nueromusculasr communication, women need for pregnacy
15
Q
fruit shpae vs type of obesity
A
pear > gynoid
apple > andoid (associated with disease like diabetes type II, high BP, cancer etc. Visceral stress)
16
Q
Least invasive to most invasive measurements of body composition
A
BMI waist to hip ratio waist to height ratio hydrodensitometry* gold standard bioelectrical impedance
17
Q
Difference between Victoza and Saxenda?
A
Saxenda is marketed obesity drug, Victoza as diabetes type II drug; that’s why Saxenda is 4x more expensive (vanity drug)
Both are the same, Liraglutide
18
Q
What is Saxenda an agonist for?
A
GLP-1 rececptor agonist
19
Q
What is the BMI and conditions of the individuals who use Saxenda?
A
BMI >30 individuals OR
BMI>27 overweight and at least 1 weight-related condition (hypertension, type II diabetes)
20
Q
What is the dosage needed for Saxenda (Liraglutide)?
A
0.6 mg per day for 1 week, increasing 9.6 mg/day in weekly intervals until 3 mg/day dose is achieved
MUST walk up to this dose because side effect profile is too strong and patient cannot tolerate(will vomit and be nauseous)
21
Q
What is the dosage of Liraglutide in Saxenda versus Victoza?
A
Saxenda – 3mg/day
Victoza – 1.8 mg/day
22
Q
What is weight loss expected in Saxenda?
A
upward 8-10%
23
Q
What is the goal of weight management and treatment?
A
primary goal is to prevent further weight gain because diet and exercise are effective in preventing further gain once obesity is reached, but isa means of maintenance not treatment once an individual is obese
Reduce ->maintain->track in children
24
Q
what is the weight loss goals?
A
down 10% from weight baseline with moderate caloric deficit . (500-1000 kcal/day)
redcuce 1lb of body fat per week, which is essener
25
most metabolic pathways have a rate-limiting step. Why?
AKA committed step, to control metabolic flux, nonbidirectional processes to control the movement of substances in enzymatic sequences in regulation. typically expends the most energy in first enzymatic step to know you have enough energy to finish the rest of the sequence
26
what are the satiation signals?
CCK and serotonin (5-HT), peptide YY, GLP-1
accumulation of chemical inhibitory signals that eventually causes satiety within the meal for meal termination, largely arising form the GI tract. Meal initiation is primarily the result of an absence of satiating signals.
27
the gustatory system is postulated to be essential in what?
distinguishing palatable foods from non-palatable foods
28
What is the sham feeding paradigm?
Rats can treat sucrose solutions and beverages accurately while humans cannot. they calorically compensate even if the sucrose concentration changes. they consume more with open fistula because the GI tract is responsible for those satiation signals. Without it, they continue to drink.
29
what is responsible for the discrete balance of caloric consumption?
CNS, vagus nerve -- a conduit of communication between brain and peripheral organs
nucleus tractus solitarus -- first nucleus in brain that receives the communication signals
30
What is CCK and what does it do?
CCK is a satiety signal primarily derived from the GI tract and reduces the size of a meal acutely. Singularly only that meal. physiologically required for meal size control satiation signal. injections daily do not work because of chronic problems like pancreatitis and gallbladder stones, and tachyphylaxis (drug resistance) and toxicity
31
The OLETF and LETO rats difference?
OLETF rat lacks functional CCK1 receptor expression and the control rats LETO have the CCK receptor, but CCK does not alter feeding in the OLETF rat
32
Tie together CCK, GLP1 and PPG
CCK made from I cells in small intestine, PPG and GLP1 made from L cells
PPG and CCK make GLP1
33
What are the the GLP receptor agonists as a pharmacological treatment for obesity?
```
Exendin-4 (half ife 2.5 hours)
and Liraglutide (half life 13 hours)
```
because unlike CCK, there are nonlife-threatening side effects
34
Why are Exendin-4 and Liraglutide FDA-approved?
approved for treating type II diabetes because resistant to enzyme degradation and reduced renal excretion, negligible risk of life-threatening adverse events
Incretin effects
35
L cell to incoming glucose load steps
L cells sense macronutrients and secrete GLP1, which on pancreatic beta cells and into circulation, which causes release of insulin secretion, body proactively causing release to deal with incoming glucose load
36
how often do you take exendin-4 and liaglutide?
exendin-4 -- twice daily
liraglutide -- once daily
both produce comparable and pronounced suppressions in food intake and body weight
37
Does exendin-4 treat obesity?
no, it treats diabetes and improves co-morbidity at least a bit
38
difference in weight loss of liraglutide and exendin?
lirgalutide only drug approved to treat obesity, exendin treats diabetes
liraglutide meets 5-10% sustained weight loss but exendin does not. *liraglutide meets it but plateaus
39
what is leptin
protein product of ob/ob gene found in animals
-controls appetite, body weight and obesity
acts in multiple nuclei within the brain to regulate energy balance
interacts with almost all neuropeptides known to be involved in energy balance and food intake
40
how is leptin released into circulation?
Leptin is released into the circulation form adipocytes in proportion to the amount of energy (fat) storage; it acts as a catabolic hormone by decreasing appetite and increasing expenditure
41
Leptin and obesity and CSF relation?
Ratio of leptin in CSF to serum leptin is decrease in obese individuals
resistant leptin penetration in brain, CSF concentration of leptin is saturated, no longer responding in same magnitude but leptin causes suppressed food intake and body weight ONLY in lean individuals
42
Name the drugs that are approved for long term use in treating obesity.
```
Orlistat (alli),
Qsymia (phentermine/topiramate)
Lorcaserin (Belviq)
Saxenda (Liraglutide)
Contrave (Naltrexone/bupropion)
```
43
What is the over the counter FDA obesity drug that is only drug that doesn't affect the CNS?
Orlistat (Alli)
Gi lipase inhibitor and binds and inhibits function. Digests lips, specifically triglycerides because to absorb fats, you must break down into triglycerides first.
44
What does ORLISTAT do?
prevents digestion of ingested fats, which goes into feces since digestion is repressed (malabsorption)
1/3 is in feces
5% weight loss at 6 months
45
Orlistat side effects?
PRIMARILY GASTROINTESTINAL
--mild to moderate--
decreased absorption of fat-soluble vitamins
anal leakage common because fats are slippery
-oily spotting
-fatty/oily stool
-increased defecation
-flatus with discharge
You shart
occurs within 3 months of therapy
46
What is lorcaserin (belviq)?
serotonin receptor agonist to act in CNS as appetite suppressant -->activation of hypothalamic POMC neurons
5-6% weight loss
not a strong drug in treating obesity
47
Lorcaserin side effects (Belviq)?
headache, upper resp./sinus infections, nausea
48
Is lorcaserin a strong drug to treat obesity?
no, weight loss lasts six months but then weight comes back
49
What is Qsymia (phentermine /topiramate)?
appetite suppressant
Off target effects:
Phentermine through amphetamine
phenethylamine as psychostimulant
topiramate -- as anticonvulsant and anti-addiction by activating GABA systme
14-15% weight loss
50
What is Qsymia (phentermine /topiramate) side effects?
SEVERE
```
seizures
hallucinations
hostility
bizarre behavior
mood changes
numbness
nausea/diarrhea
```
51
What is Contrave (Naltrexone/bupropion)?
opioid receptor anatagonist and re-uptake inhibitor of dopamine and noradrenaline
52
side effects of Contrave (naltrexone/bupropion)?
```
suicidal thoughts/actions
depression
anxiety
panic attacks
insomnia
fatigue
```
53
Is contrave popular?
no, weight loss percentage not high over a year, just 5%
54
weight loss by obesity drug percentages
Orlistat -- 5% at 6months
Lorcaserin -- 5-6% at 6 months but weight comes back (not strong drug)
Qysmia -- 14-15% weight loss but severe side effects
Contrave -- 5% weight loss over a year (not effective)
Liraglutide (Saxenda) -- 8-10% safest and most popular FDA drug
55
when to use obesity drug treatment?
only those at medical risk
BMI >30, >27 with co-morbidity
56
whehn should weight loss surgery be used?
should be reserved for those patients who have failed in other attempts to lsoe weight and are suffering from the complications
less severely obese patients may be considered with at high risk with other co-morbid conditions
Produces the longest period of sustained weight loss
57
What is Roux-en-Y gastric bypass surgery?
duodenum and jejunum surgically connected with new small stomach pouch with stomach left in peritoneal cavity , stomach almost completely bypassed from GI nutrient flow but left in peritoneal cavity
58
Why is stomach left in peritoneal cavity in roux-en-y gastric bypass surgery?
endocrine hormones produced
| intrinsic factors made in stomach, and without it you cannot absorb vitamin b12
59
complications of roux-en-y gastric bypass surgery?
```
severe nausea/vomiting
dumping syndrome
malabsorption of vitamin b12, folate, calcium, iron
dehydration
infection
behavioral/psychological changes
overabundance of GOp1, abundance of satiation signal
14-15 small meals per day
```
60
other surgeries not used?
vertical banded and adjustable gastric band
61
how does surgery work for metabolic physiology?
changes body but patietns can regain 75-100% of weight in about 3-5 years and overcome surgery options
62
difference between type I and type II?
type I -- insulin dependent diabetes, failure to produce insulin
autoimmune destruction of beta cells/absence of insulin because receptors are not there and body identifies cells as non-self (IDIOPATHIC UNKNOWN CAUSE), genetic predisposition +idiopathic virus(?) --->beta cell injury (autoimmune) and insulin dependent
type II -- non insulin dependent
failure of receptors to regulate the hormone of signalling cascase
impairment, resistance, NOT AN ABSENCE
inadequate exercise +excessive food intake + genetic predisposition -> obesity -> insulin resistance
63
characterizations of diabetes?
polyuria,polydipsia (excessive thirst) glucose concentraiton after at least 8 hours of fasting .126 mg/dL, and plasma glucose concentration >200 mg/dL 2 hours after oral glucose 75g intake (oral glucose tolerance test) and unexplained weight loss
genetic, metabolic, and acquired conditions that result in hyperglycemia
64
alpha and beta cell difference? IMPORTANT
alpha -- makes hormone glucagon is there is low blood glucose by breaking down stored glucose through glycolysis in liver into blood 70-155 mg/dL
beta-- makes hormone insulin
65
details about insulin's functions
hormone produced by beta cells of pancreas to regulate blood glucose level in body
signal for the conversion of free glucose to glycogen and stores it in liver
promotes for glycogensis, lipogenesis, proteogenesis, nucleid acid synthesis
66
beta cells in pancreas responsible for production of what hormone?
insulin
67
insulin is required for glucose enter from where?
bloodstream because both have GLUT4 glucose receptor in cell and only way to get glucose in cell
68
what is bad? refined or complex carbs?
refined
69
how many people have diabetes?
5% Type I, 95% type II
| 7 million undiagnosed
70
what makes Type I diabetes markered despite being idiopathic?
triggering event and beta cells go from injured to dead and cannot be re-expressed or replicated
71
type II diabetes onset
stomach changes food into glucose ->glucose enters bloodstream -> pancreas makes insulin -> insulin enters bloodstream -> glucose can't get into the cells up the body and build up in the blood vessels
72
normal level of A1 C hemoglobin in individuals is what?
4-6%
73
is A1C a diagnosable test?
no, it's a measure of blood glucose and tests chronic state of blood glucose
74
how to explain unexplained weight loss in type ii diabetes lack of insulin?
Body becomes a state of mobilizing stored fuels because body think its doesn’t have any fuels and breaks down the fat
Further exacerbation of the problem
75
Cause of insulin inaction?
decreased receptors on cells!!!!!
Cells become saturated with glucose
other causes: abnormal b-cell secretory product, circulatory anti-insulin antibodies occurring years down that road and body targets cells for destruction
76
When the Glut 4 glucose transporter cannot fuse with membrane, what happens?
low glucose flow into cell and then there are decreased receptors on cell
77
Insulin dependent diabetes occurs how vs noninsulindependent
Type I
genetic predisposition + idiopathic virus? ->beta cell injury autoimmune destruction ->insulin dependent
less than 10% beta cells is diagnosis
TRIGGERING EVENT
Type II
Inadequate exercise + excess food intake + genetic predisposition -> Obesity ->Insulin resistance
78
What mutation in what genes causes autoimmune diseases?
system that judges similarity of tissues is the Human Leukocyte Antigen (HLA)!!!!!
destruction of b-cell by immune system
proteins on cell surface display normality to immune system as a way to distinguish 'self' and 'nonself', where nonself antigens are targeted for destruction by killer T-cells
MUTATIONS IN proteins in CLASS II genes (HLA-DR and HLa-DQ regions) ASSOCIATED WITH TYPE I DIABETES AND OTHER AI DISEASES
79
What are the two regions in class II genese with mutated proteins that put cell at risk of being identified as non self?
HLA-DR and HLA-DQ
80
What causes the non self identification to occur?
Antigen changing shape slightly from single point mutations (lock and key example), where antibodies are created for it once macrophage notices this, which is why you can never re-express beta cells
Mutation in DQ and/or DR region will trigger autoimmune destruction of B-cells
81
what is relationship between lipids and macrovascular disease?
proliferation of smooth muscle cells form lip filled plaques that migrate to do arterial occlusion
Fat builds up in arteries and palsma over the years for increased risk of CVD
LDL bad lipoprotein
HDL good lipoprotein
82
what is the relationship between membrane structure and microvascular diseases?
```
thickened basement membrane and capillary beds
*insulin-associated, not lipid*
angipathies
nephropathies
retinopathies
```
83
the microvascular disease gangrene affected by diabetes how?
loss of nutrients call cell death as a chronic degenerative diseases, irreverisble glycosylation, micro-regional necrosis
84
Altered glucose metabolism caused by hyperglycemia converts glucose to what and why is this a problem?
glucose to polyols
problem because they degrade slowly, which polyol accumulation alters function of peripheral nerves and increased protein glycosylation
85
treatment for diabetes
insulin
hypoglycemic drugs like Metformin, which increases glucose absorption, decreases hypoglycemic risk, and Sulfonyl Ureas (Tolbudimine) that increase Glut II and increase sensitivity to glucose in B-cells
islet cell transplantation but human trials have failed
and exercise
86
type II diabetes incretin hormone do what?
inhibit gastric emptying, reduce food intake and body weight, stimulate insulin response from beta cells in a glucose-dependent manner, inhibits glucagon secretion from alpha cells in a glucose -dependent manner
87
Type II incretin hormones: alpha cells produce what? beta cells produce what?
alpha -- glucagon pancreas
beta -- insulin pancreas
glucose -- liver
88
GLP 1 and DDP-4 roles in glucose homeostasis
Following meal indigestion, incretin hormones GLP1 and GIP released from endocrine cells
Stimulate glucose-dependent insulin cells from pancreatic beta cells
Suppress glucagon release from pancreatic alpha cells
But incretin hormones GLP1 and GIP are degraded by enzyme DPP 4, inhibiting breakdown of incretin hormones and increading their levels to promote glycemic control
89
How is Exendin-4 related to DDP-4?
it is resistant to degradation by the enzyme DPP-4 to enhance GLP1 and GIP incretin hormones
90
What transporter cannot be blocked or no glucose goes into system?
SGLT2 transporter
91
What does Glut 2 do?
increases beta cell sensitivity (insulin)
92
one third rule, which is?
third of meal empties during meal, a third is intermeal interval and a third of meal is in stomach when second meal starts
93
in diabetes, what occurs during gastric emptying?
carbs and hypoglycemia, not absorbed in stomach
94
GERD occurs in what weak sphincter? what are the symptoms and what occurs>
cardiac sphincter location
Gastroesophageal reflux disease causes indigestion, acid regurgitation, sour stomach, chest pain
Stomach acid into esophagus because weak sphincter has less mucus to protect esophagus, acidity causing pain in that location because sensation is near the heart
95
food that make heartburn worse
coffee
citrus products
spicy foods
ibuprofen
96
therapy for heartburn and GERD?
elevation of ehad on bed
smaller meals
eat 3hr prior to sleep
antacids
97
What are the GI diseases?
Crohn's disease, ulcerative colitis, celiac disease
98
What is Inflammatory bowel disease? (AI disease)
inflammatory disorders leading to damage of the GI tract, which casues painful and life-altering symptoms like rectal bleeding, diarrhea and cramping
largely dietary driven and intestinal motility
99
nutritional deficiencies of IBD
mineral and trace element deficiencies, vitamin deficiencies, weight loss and malnutrition
100
cause of IBD
enterocytes, acute attack
HLA Class II single point mutations
triggering event, body displays non-self and targeted for destruction by immune system -- a creation of antibodies for our own enterocytes and possible impaired cytokine secretions by macrophages, critical for inflammatory responses to foreign bacterial agents
101
Where does Crohn's disease occur?
anywhere in GI tract, microscopic inflammation
102
pathology and etiology of Crohns
```
pathology:
malabsorption
abdominal pain
obstruction
abscesses
mucosal thickening
also causes impaired growth in 30% of patients
joint inflammation
skin ulcers
```
Etiology: unknown but suggested AI, genetic, dietary, thought to occur early in life nad have 15-20 year incubation
103
ulcerative colitis
confine to colonic mucosa and 30% to rectum, cured by colectomy
104
difference in location and treatment for ulcerative colitis and crohns
crohns: medication, surgery, nutrition, anywhere in GI tract, skipped areas
Ulcerative colitisL confined to colonic mucosa and 30% confined to rectum, cured by colectomy, only GI bleeding
105
what occurs in both Crohns and ulcerative colitis?
increased risk of colorectal cner, extraintestinal manifestations, diarrhea, chronic relapse and varying degrees of severity
106
short bowel syndrome cause of what?
crohns diseases and is nutritional and metabolic consequence of major resection of small intestine
107
if you lose the ileum you cannot reabsrob what?
bile and b vitamin
