Foundations 1 Test Misc Week 3-4 Flashcards
when is beta-oxidation triggered?
fasting, exercise, after a fat rich meal
What is ketogensis? where does it occur? when does it occur?
production of ketone bodies that occurs in the liver when there are high levels of acetyl-CoA
which type of epithelium can be ciliated?
pseudostratified (located in airways)
which type of epithelium can contain micro-villi?
simple columnar (located in GI tract)
eccrine sweat glands are what type of gland?
simple coiled tubular gland
mucous secretions of intestinal glands are what type of gland?
simple tubular glands (multicellular), also contain unicellular goblet cells
the exocrine pancreas is what type of gland?
compound acinar
which type of medical imaging gives you the best tissue contrast?
MRI
which medical imaging technique(s) us X-rays?
radiography and CT
which medical imaging technique gives the worst resolution
Nuclear medicine (used to view anatomy and physiology in real time with gamma rays)
which imaging technique has many artifacts?
Ultra sound
which imaging technique uses radiofrequency waves
MRI
what is ECM composed of?
Ground substance (glycoproteins, glycoaminoglycans) and protein fibers (collagen)
what are the layers of integument from keratin to muscle?
keratin–>epidermis (stratified squamous)–>dermis (connective tissue)–>hypodermis/subQ/superficial fascia (fat, blood, nerves)–>deep fascia–>muscle
incidence vs prevelence
incidence: number of new cases
prevalence: total number of cases
P=I*D
what is incidence rate?
IR=incidence/sum of DISEASE FREE person time
what are the essential AA?
PVT TIM HLL
Phe, Val, Tyr, Thre, Ile, Met, His, Lys, Leu
A positive nitrogen balance is seen in what two cases?
Pregnancy and growth
what is PKU? cause? signs?
A decrease in Tyr production due to Phe hydroxylase defici (Phe–>Tyr) or lack of Phe Hydroxylase cofactor (tetrahydrobiopterin). Tyr becomes essential and neuro-toxic Phe metabolites accumulate. Mental retardation, musty body odor
Cachexia: cause? seen in? treatment?
excessive protein and AA (Gln) degradation (negative nitrogen balance). seen in cancer and burns. Treatment: steroids, Gln supplement
Protein Quality
Complete: maintain growth and life
Partially Complete: maintain life not growth
Incomplete: not maintain life
what is the sparing effect?
some nutrients can spare other nutrients from being used. Carbs spare protein use, Tyr spares Phe use, Cys spares Met use
Homocystinuria: what is it? causes?
accumulation of homocysteine due to a mutation in cystathionine synthase (homocysteine–>cystathionine).Homocysteine disrupts collagen cross-linking causing strokes and heart attacks, Cys becomes essential
Note: Met–>homocysteine–>cystathionine–>cys
Acute Lymphatic Leukemia: cause? treatment?
Asn-synthase deficiency in WBCs (Asp-x->Asn). L-Asparaginase (Asn–>Asp) is used to treat and starve these cells of dietary Asn
what does the biological value of a protein tell you?
how much dietary protein is retained in the body (accounts for protein lost in urine and feces)
what is the best measure of the completeness of a protein?
PDCAAS (protein digestibility corrected AA score): compares the amount of AA in each protein to the requirements for a 2-5 year old
what are the three dietary lipids
(sterols, phospholipids, glycerides)
what is a reason a nutrient (biotin/B7) would not have a RDA? what do you do if this is the case?
insufficient research. go by Adequate intake levels
what is the RDA?
intake of food fro a group (men/women/age) that meets 97.5% of the needs of individuals within that group
what is DRI?
dietary requirements (EAR, tolerable upper level, adequate intake) with a goal of preventing nutrient defficeincies and preventing over-nutrition
Is hip-waist ratio or BMI better for determining risk of heart attacks?
hip-waist ratio had a stronger correlation
what are the hormones that regulate appetite? Role? produced? short or long-term
Decrease appetite:
Leptin: adipocytes, long term, increase energy utilization
PYY: intestines, short-term, slows gastric emptying
Increase Appetite:
Orexin: lateral hypothalamus, supppress REM, increase wakefulness
Ghrelin: stomach, short term when you think about food
what is metabolic syndrome
cluster of conditions (increases visceral obesity, increasesd bp, increased cholesterol) that increases the risk for CVD and diabetes
impact of insulin on TG of adipocytes
Promotes LPL (storage of FFAs into TGs)
Inhibits HSL (release of FFAs)
what are adipokines? what is the relationship between adipokine levels and visceral obesity?
adipokines are the hormones produced by adipocytes; as obesity increases, adipokine levels increase (except adiponectin)
what is the role of adiponectin?
anti-atherosclerotic effects, enhance insulin sensitivity, increase glucose uptake
Obestiy is…
a crhonic low grade inflammatory state due to increase size of adipocytes and increased macrophages
how does increased adipocyte size/number increase insulin resistance?
Adipocytes enlarge and produce more IL-6, leptin that recruits tissue macrophages and increases FFAs. Increased FFAs and TNF-alpha (released by macrophages) produces insulin resistance
what is RQ of fats, proteins, carbs
Carbs 1.0
Fats: .7
protein: .8
describe the energy source over a a 2 hour intense workout
0-10 min: only glycogen within smooth muscle
10-20: muscle glycogen and liver glycogen
> 20 min: muscle, liver, and FAs
> 2hours: FAs with near glycogen depletion in muscle and liver
what percent of our total energy goes into basal metabolic rate?
50-70%
B1 defic: moderate, severe
moderate: Wernickes-Korsakoff (chronic alcoholic)
Severe: beriberi
vitamin(s) defic that results in sores at corner of mouth (cheilosis) and tongue issues (Glossitis)
B2 and B6 deficiency
B5 AKA
Pantothenate
B6 AKA
Pyridoxine
B12 deficiency
Megaloblastic and pernicious anemia
what are the only 2 vitamins not rich in plants?
B12 and D
Niacin is made from…
Trp
what is the fetal origins hypothesis? what was the kidney example?
fetal experiences “program” future disease. embryo kidney functional capacity was limited by some insult (malnutrition, lack protein, increased glucocoritcoids) and the embryo adapted by slowing kidney growth (decreased nephrons). once the baby was born the kidney had to work harder which led to the death of more kidney. this lead to an increased BP and poor kidney fxn. Adaptions of fetus of fetus to insult became maladaptive later in life
compare the mid brain and front brain: which develops faster? what are their roles?
Mid brain: develops quickly, controls emotions (amygdala)
front brain: develops gradually, keeps impulses of mid brain at bay (has trouble keeping up with mid brain early in development and in the teens)
what is the role of the hypothalamus and hippocampus? how do they interact
hypothalamus: maintains homeostasis, activates stress response
hippocampus: memory center
hippocampus terminates stress response of the hypothalamus
describe brain growth over the life-span
0-3: rapid growth
3-25 moldable brain where 1/2 of the neurons are pruned away
what did the dutch famine experiment show?
increased disease seen in (adult) children of malnourished mothers
what did the Carolina Abecedarian study show?
high quality pre-school (health care, nutrition, cognitive stimulation) had long lasting positive impact on kids (better graded, better health)
what are the four US probe types? what are their general roles?
- Linear: superficial
- Phased Array: abdomen and cardiac
- Curvilinear: abdomen
- Endoluminal: vaginal, rectal, oral
what is the attenuation of air? what does that mean?
- it means that little US signal will return after passing through air (all the waves are absorbed)
what is the most abundant AA in circulation; this is also used to treat cachexia
Gln (non-essential made from Glu+ ammonia, but it can become depleted). Nitrogen shuttle!
how much extra kcal/day should a lactating mother consume?
500-700 kcal/day for milk.
compare the diet of infants to the diet of adults
Infants: higher kcal/kg of body weight, higher fat, lower protein
adults; more carbs and proteins
what is the single most common nutrient deficiency in the US?
iron
what is koilonychia
spoon shaped nails due to iron deficiency
what age group do we see individuals become picky eaters
toddler (1-3)
what type of cell jxn are intermediate filaments found in?
desmosomes
what are the four classes of intermediate filaments
Vimentin: connective tissue and muscle
neurofilaments: nerve cells
keratins: in all epithelial cells
nuclear lamins: progeria!!
what are the uses of taxol, colchicine, and vinblastine?
all anti-cancer drugs that prevent cell division.
taxol: stabilizes MT
vinblastine/colchicine: prevent MT polymerization
what is congenital myopathy? cause
muscle weakness caused by a lack of muscle-specific actin
GLUT4 vs GLUT2
GLUT4: the only insulin sensitive glucose transporter. seen in membranes of muscle, liver and adipose cells
GLUT2: found in beta-cells of pancreas, detects rising glucose levels
what is the structure of pre-proinsulin?
signal peptide–B–C–A
how is insulin stored
in vesicles around w/ 3 (ab/ab insulin dimers) around a Zn ion
GLUT4 is released via..
receptor mediated endocytsosis (Insulin>RTK>IRS-1>PI-3K>GLUT4 exocytosed
what is myotonic dystrophy? what can it lead to?
muscle wasting/weakness that can lead to diabetes
HLA status and type II diabetes
HLA gene complex codes for the antigens presented by cells. the DR locus has correlations to T1DM.
DR3: increase risk for T1DM (antibodies produced against beta cells)
DR4: increase risk for T1DM (antibodies produced against insulin)
DR2: protective role associated with T1DM
we discussed two genes found through the GWA study that were thought to play a role in increased risk for type II diabetes, what were they
TCF7L2: codes for TF in Wnt pathway (proglucagon synthesis), homozygous carriers 2x increased risk for T2DM
FTO gene: set of genes associated with obesity (methylation of RNA that preferentially produce fat); secondary risk of diabetes
MODY disorders affect what type of cell?
beta cells!
what is meant when diabetes is called a complex disease?
influenced by biological, behavioral and environmental factors
by the time of T2DM diagnosis how would you describe the function of beta cells?
their function is already 50% impaired
values for normal, and diabetic fasting glucose
normal: 70-100 mg/dL
diabetes: >125 mg/dL
between=IFG, pre-diabetes
when should you begin screening of diabetes?
- BMI>25 w/ an additional risk factor
2. over 45 yo
total cholestrol should be below? LDL cholesterol?
total: below 200mg/dL
LDL: below 100 mg/dL
how does sulfonurea work?
increases intracellular calcium and promotes insulin release from beta cells (effective monotherapy for MODY T2DM)
how does metformin work?
decreases gluconeogenesis of the liver and reduces insulin resistance (very effective monotherapy for T2DM)
how do SGLT2 inhibitors work?
prevent glucose reabsorption in the kidneys
how do TZD (pioglitazone) work?
decrease insulin resistance of skeletal muscle and fat
what are the diabetes ABCs?
complications associated with diabetes (increased A1C, increased BP, increased cholesterol)
what effect do catecholamines have on the liver
Increase: glycogen degradation, gluconeogensis
decrease: FA synthesis, glycogen production, glycolysis
what effects do catecholamines have on skeletal muscle?
Increase: glycolysis, gycogen breakdown, TG utilization
Decrease: glycogen production
what effect do catecholamines have on adipose?
Increase: lipolysis
decrease: storage of FAs (TG production)
what explains the alternate responses of liver and skeletal muscle to catecholamines?
Same signaling pathway (E/NE–>GPCR–>Adenyl cyclase–>cAMP–>PKA–>phosphoryaltes F-2,6-BPase AKA PFK-2.
however phosphorylation of PFK-2 in liver deactivates it (creates less F-2,6-BP and thus less glycolysis)
phosphorylation of PFK-2 in skeletal muscle acitavates it (creates F-2,6-BP and promotes glycolysis)
what are the effects of cortiosol (glucocorticoids) on the liver?
Increase: glycogen production, gluconeogensis
what are the effects of cortisol in skeletal muscle?
Increase: protein degradation
what are the effects of cortisol in skeletal muscle:
increase: Lipolysis (increase FFAs, insulin resistance)
ethanol consumption activates which pathways? what is the result?
actiavtes ADH pathway (cytosol of liver) when at low levels and MEOS pathway when at excessively high levels (ER of liver). Produces an abundance of NADH, and acetyl-CoA, and ATP
Effects:
- hypoglycemia (no need to produce glucose at liver, inhibited glycolysis)
- lactic acidosis: high NADH/NAD+ drives lactate production
- Hyperlipidemia: FA oxidation cannot occur without NAD+
T2DM is characterized by hyperglycemia; what can cause hyperglycemia? 5
- decreased insulin (progressive B-cell dysfunction)
- impaired insulin signaling (insulin resistance)
- accelerated gastric emptying
- elevated glucagon
- impaired incretin effect
how quickly are incretins degraded?
very quickly; half-life is in minutes. would not expect increased levels over an hour after a meal (degraded by DPP-4)
GLP-1: found? produced? role?
produced by Gut-L cells of distal ileum and colon. increase insulin, decrease glucagon, increase insulin sensitivity, increase beta cell size, slow gastric emptying, cardio/neuro protection
Exenatide and Liraglutide are type of…
GLP-1 mimics used to treat T2DM. Require daily SubQ injections and cause weight loss
vildaliptin and sitaglipitn are types of…
DPP-4 inhibitors used to treat T2DM. daily pills that are weight neutral
what are teh CRH? what are their normal sequence of activation?
Glucagon–>Catecholamines (short-acting)–>Glucocorticoids and GH (long acting)
what is hypoglycemia induced autonomic failure
- T1DM over 5 years has lost ability to secrete glucagon
- recurring hypoglycemic events result in progressive desensitization NE/E receptors. this results in the body becoming “numb” to the effects of NE/E
what causes DKA?
most common in T1DM:
hyperglycemia occurs but because of lack of insulin the cells cannot uptake glucose–>the body thinks it needs more glucose so it releases CRH that increase glycogen degradation and gluconeogenesis–> when this fails the cells break down FAs (poorly)–>this results in the accumulation of ketone bodies. Hyperglycemia and ketonemia increases the fluid lost in the urine. Severe dehydration occurs, tachycardia, respiratory distress, coma
a patient has been diagnosed with polycistic ovary syndrome… how should you advise them?
increased risk of insulin resistance (diabetes)
early in T2DM progression what will be elevated?
insulin (hyperinsulimeia) to try and compensate for increased glucose. beta cells will eventually fail to compensate
what are two endocrine disorders associated with diabetes? how?
Cushing’s syndrome: increased cortisol leads to chronic hyperglycemia and beta cell dysfunction
Acromegaly: increased GH, induces hyperglycemia–>B cells will eventually fail to keep up
According to the diabetes prevention program, what is the best way to prevent pre-diabetes from turning into T2DM
exercise! legacy effect (16% reduction in risk for every kg lost)
Primary Ciliary Dyskinesia: cause? effects?
an autosomal recessive disease affecting motile cilia due to a loss of dynein (NOT primary cilia). results in impaired mucocilary elevator, infertility in males (flagella), situs inversus
autosomal dominant polysystic kidney disease: cause?
large cytsic kidneys formed due to lack of polycystin (important in primary cilia/non-motile cilia)
what are the two cellular adhesion molecules we discussed
Cadherins (Ca dependent, lateral domain)
integrins (basal domain)
what are the four juncitons found in the lateral domain of epithelial cells; from most apical to most basal
- Zonula occludins (tight jxn)
- Zonula adherins (intermediate jxn)
- Macula adherins (desmosomes)
- Gap junctions
Zonula occludens: role and important proteins
separates the apical and basal surfaces. Occludin and claudin
zonula adherins: role and important proteins
connects adjacent cells. cadherins, actin, catenins
macula adherins: role and important proteins
spot welds adjacent cells to resist shear force. Desmo-, plakoglobins, keratin
Gap junctions important proteins
Connexin, connexon
two types of junctions seen in the basal surface of epithelial cells
focal adhesions
hemidesmosomes
focal adhesions: role and important proteins
attach cell to BM, communication form ECM to cell
Integrin, fibronectin, collagen, laminin
Hemidesmosomes: role and important proteins
Role: connect cell to ECM
protein: BP230, Collagen XVII, collagen VII, integrins
Pemphigus Vulgaris: cause? blister type? nikolsky?
antibodies produced against desmosomes that causes a loss of the lateral domain in epithelial cells. flaccid blisters (easily popped, often just open sores). Nikolsky +. Net-like IF
Bullous Pemphigoid: cause? blister type? nikolsky?
body creates antibodies against BP230 or collagen XVII, loss of hemidesmosomes and basal domain. tense blisters. nikolsky -
Dystrophic Epidermolysis Bullosoa: cause
inherited defect in collagen VII (Hemidesmosomes) that causes skin to fall off and esophageal issues
the smooth ER is important in detox of…
ethanol and barbiturates
drugs metabolized by CYP2C9
phase I metabolism of warfarin (VKORC1, CYP2C9), phenytoin, tolbutamide
drugs metabolized by CYP2D6
antipsychotic, anti-depressant, metprolol, tamoxifen (pro-durg)
what are the 4 metabolizer groups of the many CYP2D6 alleles?
ultrarapid
efficient
intermediate
poor
a person is a UM for a drug, how do you alter their dose? normal drug and pro drug
increase dose of normal drug
decrease for pro-drug
the FDA recommends genetic testing prior to? requires it?
recommends to avoid ADRs: G6PD deficiency, HLA-B1502, HLA-B5701, TPMT deficiency
requires to improve efficacy: trastuzumab (HER2), maravicor (HIV), imatinib (GI tumors)
a person with ____ has an increase risk of ADRs (hemolytic anemia) when taking rasburicase, uricemia, primaquin, dapsone
G6PD defic
a person with ____ has an increased risk of ADRs (steve-johnson syndrome) when taking carbamazepine
HLA-B*1502
a person with ____ has an increased risk of ADRs when taking abacavir
HLA-B*5701
what is the role of TPMT?
phase II inactivation of thiopurines (immunosuppressant).
individuals with _____ have an increased risk of leukopenia when taking azathiorprine
TPMT-deficiency
imatinib is more effective when
treating C-KIT-positive GI tumors
Maravicor is more effective when….
treating CCR5-tropic HIV-1 infection
how do anabolic steroids work
induce muscle hypertrophy by re-inducing fetal geen expression of contractile proteins and increase their synthesis
what is chronic granulomatous disease caused by?
mutation in more than 400 genes in 1 of 5 NADPH oxidase enzymes. frequent life threatening fungal and bacterial infections occur (no HOCl is produced)
what is the role of peroxisome
degradation of VLCFA and branched FA
production of plasmogelens (found in lipid membranes of brain, heart, neutrophils)
AA degradation
production of bile acids (liver)
what are the effects of ADA deficiency?
(converts adenosine to inosine). high dATP levels inhibit ribonucleotide reductase which stops cell division. immune cells are particularly effected by this. causes SEVERE COMBINED IMMUNODEFICIENCY
what causes gout? treatment?
excessive nucleotide (purine) degradation produces an abundance of Uric acid which leads to uric acid crystals in joints; gout. caused by decreased HGPRT activity (guanine–>GMP) or by increased PRPP synthase activity (more nucleotides=more degradation).
allopurinol is used to treat gout because it is a suicide inhibitor of XO.
what is lesch-nyhan syndrome caused by? symptoms?
absent HGPRT (high levels of guanine) lead to very high levels of uric acid. gout-like symptoms AND agressive/self-mutalive behavior
what is the role of ribonucleotide reductase?
converts NDP to dNDP
what is hydroxyurea?
a cancer therapy that inhibits ribonucleotide reductase and therefore stops production of dNTP and halts proliferation
what is the role of thymidylate synthase?
dUMP–>dTMP (only way that dTMP is made)
what is fluorouracil (5-FU)?
blocks thymidylate synthase activity. cancer therapy.
what is the role of DHF reductase?
converts DHF to THF so it can be used to aid thymidylate synthase in the creation of dTMP.
what is methotrexate?
inhibits DHF reductase. cancer therapy
