All Usmle

Front 1

Case-Control Study
Definition and variable measured:

Back 1

1. A retrospective comparison of two groups -- a control group and a disease group -- searching for the existence of a risk factor or factors.| - i.e. smoking histories are compared in a group of women with breast cancer to those in a group of women without breast cancer.||2. Odds ratio -- i.e., that one group will have it, vs. odds that the other will have it.| - Women with breast cancer are twice as likely to have smoked in the past than women without it.

Front 2

BAX
(1) Function
(2)Path

Back 2

(1) This enzyme of the intrinsic pathway to apoptosis functions to segregate BCL-2, permitting cytochrome C to escape from the mitochondrial membrane and activate caspases.

BAX is upregulated by p53.

Hint 2

(2) When p53 is knocked out by mutation, BAX cannot be stimulated, and BCL-2 protects the cell from apoptosis indefinitely, resulting in cell immortality.

Front 3

(1) What are the proportions of lipid-subtypes in the cell membrane?

(2) How does cholesterol effect the structure of a lipid membrane?

Back 3

(1)
50% phospholipids

50% cholesterol

Traces of others

Hint 3

(2)
Cholesterol stiffens and weakens the bilipid membrane because it interferes with the fluid interaction of phospholipids.

Front 4

Cohort study|Variable measured:

Back 4

Relative risk (RR).| - i.e., our cohort study of two groups of patients, smokers and non-smokers, revealed a 5-fold risk of developing lung cancer.| - Answers the question: "what will happen?"

Front 5

BCL-2
(1) Function:
(2) Path:

Back 5

Function:
This anti-apoptotic enzyme functions to prevent cytochrome C from escaping the mitochondria and causing caspase activation.

Hint 5

Path:
The t(14:16) translocation moves the BCL-2 gene so that it's adjacent to and co-expressed with the Ig heavy chain gene.

Result: lots and lots of BCL-2, no apoptosis, and therefore follicular lymphomas (ALL).

Front 6

Location of Vimentin

Back 6

Intermediate filament found in connective tissue

Front 7

Phase 1 of clinical trials|Design and objectives:

Back 7

Prospective study with control group using a **small number of healthy subjects.**| - Objective: determine the toxicity, safety, and pharmacokinetics of the drug.

Front 8

What are the 2 extrinsic pathways to apoptosis?

Back 8

(1) Ligand-receptor interactions:

Fas ligand binds to Fas [CD95] on cell surface, triggering caspase activation.

Hint 8

(2) Cytotoxic T-cell pathway:

1. CD8+ T cells recognize tumor or viral antigen and secrete perforin to punch holes through the problematic cell

2. CD8+ T cells then secrete granzyme, which enters through those holes and activates caspases

Front 9

Location of Desmin

Back 9

Intermediate filament found in muscle

Front 10

Phase 2 of clinical trials|Design and objectives

Back 10

Prospective study with control group using a small number of sick patients.| - Objective: determine efficacy, optimal dosing, and adverse effects.

Front 11

What types of hypoxic cellular injury are (1) reversible, and (2) irreversible?

Back 11

(1) Reversible hypoxic injury ~ membrane swelling.

1. ATP production slows d/t lack of O2 to run the ETC. Intracellular hyperosmolality and swelling occur as a result of:
--a. Na/K ATPase slows down
--b. Calcium ATPase slows down
--c. Lactic acid fermentation results in increased H+ in the cell (and lactic acidosis, more globally)

2. Blebbing occurs when swelling pulls plasma membrane away from the cytoskeleton.
--Results in microvilli effacement, just as inflating a surgical glove results in shrinking of the fingers.

3. RER swelling occurs for the same reasons, resulting in ribosome detachment and decreased protein synthesis
--B/c ribosomes are attached by weak, non-covalent bonds to the RER.

Hint 11

(2) Irreversible damage
Inner mitochondrial membrane damage
--releases cytochrome C. There's no recovering from this.
1. Plasma membrane damage
--this is why troponin is a good indicator of irreversible damage (infarct!)

3. Lysozomal membrane rupture releases proteases, etc., that autodigest the cell.

Front 12

Location of Cytokeratin

Back 12

Intermediate filament found in epithelial cells

Front 13

Phase 3 of clinical trials|Design and objectives:

Back 13

Prospective study using a large number of healthy patients, randomly assigned to the test and control groups.| - Objective: compare new treatment to current standard of care.| - Control group can be given a different, established treatment or a placebo.

Front 14

What nuclear changes do we see in (1) reversible hypoxic injury and (2) irreversible hypoxic injury?

Back 14

(1) this injury is accompanied by reversible clumping of chromatin.

Hint 14

(2) This injury is accompanied by (in order):

1. Pyknosis: irreversible chromatin condensation
2. Karyorrhexis: blebbing of nucleus into vacuoles in the cytoplasm
3. Karyolysis: dissolution of chromatin in dying cells resulting in the characteristic finding of coagulation necrosis: no nuclei and diffuse pink staining.

Front 15

Location of GFAP

Back 15

Intermediate filament found in found in Neuroglia

Front 16

Phase 4 of clinical trials|Design and objectives:

Back 16

Postmarketing surveillance trial of patients after approval of drug.| - Detects rare or long-term adverse effects.

Front 17

Which part of the colon is most susceptible to hypoxic injury?

Back 17

Splenic flexure of the Large Intestine, b/c it is the watershed region supplied by the terminal superior and inferior mesenteric circulations.

Front 18

Location of Neurofilaments

Back 18

Intermediate filament found in neurons.

Front 19

How does knowing the 5 intermediate filaments help us?

Back 19

Because they're very large and abundant cytoskeletal structures, a stain specific for one of them will light up the tissue it lives in.

Front 20

Formula for sensitivity

Back 20

True positives / (true positives + false negatives)||True positives / Total positives

Front 21

What organs undergo (1) red/hemorrhagic infarct, and (2) pale infarct?

Back 21

(1) Soft organs supplied by dual circulation:
-- Lungs, Liver, Intestine
-- Or any organ that is reperfused after infarct.

Hint 21

(2) Solid tissues with a single blood supply, i.e.:
-- Heart, Kidneys, Spleen

Front 22

Ouabain
Mech:

Back 22

This toxin is found in leaves and bark in Africa and was used to poison arrow and spear-tips.

It blocks the K+ side of Na/K ATPase.

Front 23

Formula for specificity

Back 23

True Negatives / (true negatives + false positives)||True negatives / Total negatives

Front 24

Give an example of each of the 2 kinds of shock.

Back 24

(1) Low output failure: can be due to:
-- Hypovolemia, i.e. in dehydration
-- Cardiogenic, i.e. in dilated cardiomyopathy.
-- accompanied by cold extremities, low TPR

(2) Hi output failure: can be due to:
-- early sepsis: tachycardia
-- accompanied by warm extremities, decreased TPR, lots of volume lost to interstitial space.

Front 25

Cardiac glycosides
Mech:

Back 25

Directly inhibit Na/K ATPase (slightly), decreasing the cells ability to pump out Ca2+.

Result: increased intracellular Ca2+ = increased cardiac contractility!

Front 26

Formula for PPV

Back 26

True Positives / (True positives + False positives)||True positives / Total positive test results|| = the probability that a positive test result is correct.

Front 27

Clinical symptoms of inflammation:

Back 27

Rubor
Dolor
Calor
Tumor
functio laesa (loss of function)

Front 28

Where are types II and III collagen found?

Back 28

Type II collagen: found in cartilage.

Type III collagen: found in blood vessels, lymph nodes, dermis, and early wound healing. AKA reticulin

Front 29

Formula for NPV

Back 29

True negatives / (True negatives + False negatives)||True negatives / Total negatives|| = the probability that a negative test result is correct.

Front 30

Molecular components of "Rolling" in leukocyte extravasation

Back 30

On leukocytes: Sialyl Lewis (glycoprotein)
On Endothelium: E- and P-Selectins

Front 31

Ehler Danlos?
Path & Presentation:

Back 31

Path: Type III collagen is defective d/t alpha chain mutation.

Hint 31

Presentation: joint hypermobility, hyperelastic skin, heart valve issues

Front 32

In chronic disease, which is greater: prevalence or incidence?

Back 32

In chronic disease, prevalence is greater than incidence because a low rate of new diseases can still result in a relatively hi prevalence.

Front 33

In the "Tight Binding" stage of leukocyte extravasation, what molecular components are interacting?

Back 33

Leukocyte: LFA-1 (integrin)
Endothelium: ICAM-1

Front 34

Types of Collagen disorders:

Back 34

Type I: Osteogenesis imperfecta, scurvy

Type III: Ehler Danlos

Type IV: Alport's (defective) & Goodpastures (auto-antigenic)

Front 35

Difference between Odds Ratio and Relative Risk

Back 35

Odds ratio refers to the relative odds that a patient with a risk factor for a disease will also have that disease *right now*.| - It is determined via Case-Control study.||Relative risk refers to the risk that this patient will contract that disease in the future.| - It is determined by Cohort study.

Front 36

In the Diapedesis stage of leukocyte extravasation, what molecular components are at work?

Back 36

PECAM-1 proteins on both leukocytes and endothelium are interacting, here...

Front 37

Describe Collagen Structure:

Back 37

Triple helix made of Gly-X-Y repeats!

X and Y can be proline, hydroxyproline, or hydroxylysine!

The Glycine residues line up axially, stabilizing the structure by their hydrophobic interactions.

Front 38

Define "Number needed to harm"

Back 38

1 / Attributable Risk

Front 39

After successful extravasation from the blood vessel, how is the leukocyte directed to its target?

Back 39

CILK:

C5a
IL-8
Leukotriene B4
Kallikrein (protease that converts HMW kininogen to bradykinin)

Front 40

Steps of Collagen Synthesis:

Back 40

(1) Intracellular steps:
1. Translation of Gly-X-Y polypeptide.
[preprocollagen]

2. Hydroxylation of lysin and proline residues
(requires vitamin C)

3. Glycosylation of hydroxylysine residues

Hint 40

(2) Extracellular steps:

4. Proteolytic processing: cleavage of terminal regions of procollagen
[Tropocollagen, the basic monomer]

5. Tropocollagen strands link to eachother via lysine-hydroxylysine crosslinkages for enhanced strength.
[Collagen fibril]

Front 41

Recall bias

Back 41

Occurs when the patient's knowledge that he has a disease alters his answers to study questions.

Front 42

What phase of drug metabolism is sometimes responsible for the production of toxic compounds?

Back 42

Phase I drug metabolism occurs in the liver and is carried out by CYP450 enzymes, NADPH, and oxygen.

Phase I are *non-synthetic* reactions, including oxidation, reduction, hydrolysis, cyclization and decyclization reactions.

They can sometimes toxify otherwise harmless substances.

Hint 42

Contrast with Phase II *conjugation* reactions, which are usually detoxifying in nature.

These reactions include:
-- methylation by methyltransferases
-- acetylation by acetyltransferases
-- glycosyluronidation
-- etc.

Front 43

Steps of Collagen Synthesis:

Back 43

(1) Intracellular steps:
1. Translation of Gly-X-Y polypeptide.
[preprocollagen]

2. Hydroxylation of lysin and proline residues
(requires vitamin C)

3. Glycosylation of hydroxylysine residues

Hint 43

(2) Extracellular steps:

4. Proteolytic processing: cleavage of terminal regions of procollagen
[Tropocollagen, the basic monomer]

5. Tropocollagen strands link to eachother via lysine-hydroxylysine crosslinkages for enhanced strength.
[Collagen fibril]

Front 44

Late-look bias

Back 44

Occurs when patients who have passed away from an illness are therefore excluded from a study of that illness.

Front 45

List the causes of free radical damage other than UV radiation exposure.

Back 45

1. Drug metabolism (Phase I)
2. Nitric oxide
3. Redox reactions
4. Transition metals
5. Leukocyte oxidative burst

Front 46

How does intracellular collagen differ from extracellular collagen? Why must we finish making this stuff outside the cells?

Back 46

As pro- and preprocollagen, the molecule is still soluble.

Once the hydrophilic end segments are cleaved in the RER lumen, the molecule becomes insoluble, and would be lethal to cells.

Front 47

Pygmalion effect:

Back 47

Occurs when a researcher's beliefs regarding the efficacy of a treatment effect the outcome of that treatment| - i.e., the researcher gives more attention to patients who are getting the treatment than to the placebo group.| - compare to Hawthorne effect, in which the subjects are the source of the bias.

Front 48

List the 4 enzymes that reduce free radical damage.

Back 48

1. Catalase:
- found in peroxisomes, generates H2O2 used to neutralize free radicals
- also a virulence factor found in bacteria.

2. Superoxide dismutase & Myeloperoxidase:
- Macrophages use these to generate the H2O2 and CLO- radicals of the oxidative burst, which allows them to digest what they've eaten.

3. Glutathione peroxidase
- found in liver, exhausted Tylenol overdose.

Front 49

What are the most common and most deadly forms of osteogenesis imperfecta? How do they differ?

Back 49

Osteogenesis Imperfecta Type I:
Mildest form
Autosomal dominant

Osteogenesis Imperfecta Type II:
autosomal recessive
Lethal, perinatally

Front 50

Define "Power".

Back 50

Power is the probability that when a study claims its findings differ from the null hypothesis, they actually do.

It can also be phrased as the probability of rejecting the null hypothesis when it is in fact false.

= 1 - beta, or 1 - type II error

Front 51

What prominent symptom of several different lysozomal storage disorders is caused by free radical damage?

Back 51

Retinopathy of prematurity: a retinopathy that can be accompanied by excessive O2 therapy in premature infants with too little surfactant.

Often accompanied by ARDS.

Front 52

Steps of PCR:

Back 52

1. Denaturation:
Add lots of mRNA primers, dNTPs, and heat-stabile DNA Polymerase from geyser bacterium to your sample, and heat to denature it.

2. Reanneal: cool enough for RNA primers to anneal, and for special DNA-P to do its work.

Repeat, repeat, repeat

Hint 52

Concept: we use RNA primers that we know to be flanking the gene we want to amplify.

After several cycles, we'll have tons of DNA from that gene only.

Front 53

Define Type I Error in clinical studies.

Back 53

This error occurs when the researcher claims that there is a significant difference between the experimental hypothesis and null hypothesis, but there is not one.

Front 54

Mechanism of leukocyte burst?
In what cells does it occur?

Back 54

1. NADPH + O2 --NADPH Oxidase--> NADP + O2- [superoxide!]

2. O2- --Superoxide dismutase--> H2O2

3a. H2O2 --Myeloperoxidase--> CLO- [hypochlorite = bleach; very powerful!]
-- this is the leukocyte burst

3b. H2O2 + GSH ---> H2O + GSST (inactive metabolite of used-up glutathione).
-- this is the protective mechanism by which we get rid free radicals (esp in liver)

Hint 54

This process is used to kill phagocytized materials in neutrophils and monocytes *only*. *Not* macrophages.

Front 55

How do we visualize our PCR results?

Back 55

This lab test is visualized using gel electrophoresis on agarose gel.

Shorter pieces of DNA travel further.

We then compare the gel against a DNA ladder.

Front 56

Define Type II error

Back 56

Occurs when the researcher claims there was no difference between the experimental hypothesis and the null hypothesis.

Front 57

What pathology is associated with inheritance of a defective Glucose-6-phosphate dehydrogenase gene (G6PD)?

Back 57

This genetic deficiency results in inability to renew spent NADP+ to NADPH by reducing it with Glucose-6-Phosphate.

Result: Hemolytic anemia aggravated by antimalarial drugs and any other source of radical damage.
-- Because G6PD is the only source of NADPH in RBCs, this deficiency causes them to be particularly susceptible to free radical damage.
-- No G6PD ==> no NADPH ==> no GSH

Front 58

Which Blotting Technique does what?

Back 58

SNoW
DRoP

Southern Blot: used to separate DNA

Northern Blot: used to separate RNA

Western Blot: used to separate Protein

Front 59

Define Gaussian

Back 59

The type of distribution in which mean = median = mode

Front 60

What is the biochemical mechanism of reperfusion injury?

Back 60

Free radical injury

Front 61

Materials for a Laboratory Blot:

Back 61

1. DNA/RNA/Protein is electrophoresed on agarose gel, then transferred to a filter.

2. Denaturant is applied and radiolabeled primers are added
[nucleic acid primers for Noorthern and Southern blots, and antibody primers for Western blot]

3. Read by exposing to film

Front 62

Define positive skew

Back 62

Mean > median > mode
- Distribution in which there is a tail on the positive side of the curve.

Front 63

What are the causes of transudates and exudates, respectively?

Back 63

Transudates: hi hydrostatic pressure, low oncotic pressure in the serum compartment. (low osmolarity in the interstitium)

Exudates: blocked lymphatics or inflammation (hyperosmotic interstitium)

Front 64

Laboratory Blot Techniques:

Back 64

1. DNA/RNA/Protein is electrophoresed on agarose gel, then transferred to a filter.

2. Denaturant is applied and radiolabeled primers are added
[nucleic acid primers for Noorthern and Southern blots, and antibody primers for Western blot]

3. Read by exposing to film

Front 65

Which measurement of central tendency changes the least as skew increases?

Back 65

Mode changes the least, b/c the value that corresponds to the greatest number of subjects doesn't really move much.

Front 66

How does microarray work?

Back 66

We immobilize thousands of DNA fragments from known genes on a chip, then add radiolabeled primers from our patient sample.

I have no idea how we get radiolabeled primers from a patients blood/CSF/urine sample, but we do.

Front 67

What information do we get from standard deviation and standard error?

Back 67

The former tells us how widely a population varies.||The latter gives us an estimate of the quality of the sample.

Front 68

List the granulomatous diseases.

Back 68

1. TB
2. Crohn's
3. Treponema Pallidum (syphilis)
4. Histoplasmosis (and other fungal infections)
5. M. leprae (leprosy
6. Bartonella henselae (cat scratch fever)
7. Sarcoidosis
8. Berylliosis
9. Takayasu arteritis (large vessel, i.e. aortic arch)
10. Giant Cell Arteritis (temporal and ophthalmic arteries)
11. Wegener's granulomatosis (medium-sized vessel: lung and renal)

Front 69

How do ELISA's work?

Back 69

If we're testing for the presence of an antibody in the patient's serum, add its antigen with peroxidases specially attached.

If we're testing for presence of an antigen in the patient's serum, add specific antibodies with peroxidases attached to the sample.

Either way, if the patient is sero-positive, there'll be an intense color reaction.

Front 70

Standard deviations for the 95th and 99th percentiles?

Back 70

95th percentile = 2.standard deviations|99.7th percentile = 3 standard deviations

Front 71

Biochemistry of granulomatous inflammation:

Back 71

1. Th1 cells at the site secrete INF-gamma, causing macrophage chemotaxis.

2. Macrophages at the site secrete TNF-alpha, inducing and maintaining granuloma formation.

3. Multinucleate giant cells form.

Front 72

Pleiotropy

Back 72

1 gene has more than 1 effect on an individual's phenotype.

i.e. PKU: it's a monogenic disorder, but causes MR, hair and skin changes, and a bunch of other seemingly unrelated problems.

Front 73

What percentage of a population fits within 1 standard deviation of the mean?

Back 73

68% of the population falls within 1 standard deviation of the mean.

Front 74

What is erythrocyte sedimentation rate, and what does it tell us?

Back 74

This serological datum measures the amount of time it takes for RBCs to coagulate and precipitate out within a test tube.

Products of inflammation bind to RBCs, causing aggregation and increasing ESR.

Front 75

Loss of heterozygosity

Back 75

The 2nd hit of the 2-hit hypothesis.

Front 76

Which statistical test would we use to compare the means of two different populations? How about 3 different populations?

Back 76

For the former, we use a t-test|For the latter, we use ANOVA (Analysis of Variance)

Front 77

What are the consequences of elevated / decreased ESR?

Back 77

Elevated ESR:
-- Infections
-- Temporal arteritis
-- Cancer
-- Pregnancy
-- SLE

In inflammatory states, hi presence of fibrinogen causes clotting/sedimentation rate to increase

Hint 77

Decreased ESR:
-- Sickle cell (altered shape)
-- Polycythemia (too many)
-- CHF (unknown)

Front 78

Dominant negative mutation
Give an example

Back 78

When a heterozygote produces 1 mutant allele that doesn't only fail to work, but also interferes with the function of the other, normal allele.

Hint 78

Example: a mutation of a Transcription factor allele in its allosteric site: allele can still bind its target, blocking out the good copy of the TF from acting!

Front 79

Equation for Power

Back 79

1 - beta||Beta = probability that null hypothesis was confirmed mistakenly by results of research.

Front 80

What form of poisoning is a common cause of free radical damage?

Back 80

Iron poisoning is one of the most common causes of poison-induced fatality in children.

the free radical burden it causes damages membranes.

Front 81

Lyonization

Back 81

Random X inaction in females, resulting in one normal X chromosome and one Barr body.

Perfectly normal, but it means that any mutations on the normal X chromosome will be dominant.

Front 82

Equation for Confidence Interval

Back 82

Saying that C.I. = 95% is the same as saying that we expect 95% of the population to fall within 2 standard error measurements of the mean in either direction.||CI = [mean - Z(SEM)] through [mean + Z(SEM)]||SEM = Standard deviation / (square root of n)

Front 83

How do we identify amyloid deposits in diagnostic testing?

Back 83

These deposits display apple-green birefringence of Congo Red stain under polarized light.

Front 84

Locus heterogeneity

Back 84

When mutations at two different loci cause the same phenotype.

Hint 84

Occurs in Marfan's, MEN 2B, and homocystinuria, all of which result in clinical marfan's syndrome.

Front 85

How do we use the chi-square test?

Back 85

The chi-square test is used to check the differences between 2 or more percentages or proportions of categorical outcomes.| - i.e., tests the difference between proportions of pt's with bodyweight > 140 between groups A, B, and C at a given time.

Front 86

Bence Jones
(1) Protein & its source:
(2) Associated pathology:

Back 86

Protein making up deposits: AL
Derived from: Ig light chains

Hint 86

Amyloidosis seen in multiple myeloma

Front 87

Heteroplasma

Back 87

Inheritance of both normal and mutant mitochondrial DNA (mtDNA), resulting in variable expression of mitochondrial disease.

Hint 87

Depends upon which mitochondria were inherited by the lucky germ cell!

Front 88

What are the degrees of disease prevention?

Back 88

PDR:
1st degree: Prevention, i.e. via lifestyle changes
2nd degree: Early diagnosis, i.e. by pap smear
3rd degree: Reduction of disability, i.e. by cytoxin treatment!

Front 89

Achondroplasia
Etiology and biochem
Inheritance pattern

Back 89

FGFR3 (fibroblast growth factor 3) defect resulting in dwarfism, short limbs, but head and trunk are normal size.

Autosomal-dominant

Hint 89

Autosomal Dominant

Front 90

What is a "living will"?

Back 90

This term designates a written advanced directive specifying what sorts of treatments and procedures we are to receive or not receive in the event that the patient becomes incapacitated and cannot speak for himself.

Front 91

Secondary Amyloidosis
(1) Protein and it's source:
(2) Associated pathology

Back 91

Protein: AA
Derived from: Serum amyloid-associated protein

Hint 91

Amyloidosis found in chronic inflammatory disease

Front 92

Autosomal Dominant Polycystic Kidney Disease (ADPKD)
[the adult form]
Etiology:

Back 92

Always bilateral, massive enlargement of kidneys d/t multiple large cysts.

Presents with flank pain, flank swelling, hematuria.

Hint 92

Autosomal dominant

**Associated with berry aneurisms
An infantile recessive form exists that's much worse.

Front 93

How much should we tell a curious child about her illness?

Back 93

In this situation, the parents make the determination, not us.

Front 94

Transthyretin deposits
Pathology & its precursor:

Back 94

Found in senile cardiac amyloidosis

Derived from: AF protein [Old *Fogies]

Front 95

Familial Hypercholesterolemia

Back 95

Elevated LDL d/t defective or absent LDL receptor.

Presents with MI, very hi cholesterol. Homozygotes are rare and don't live long.

Hint 95

Autosomal Dominant

Front 96

What are the parameters of an Apgar assessment?

Back 96

This assessment of newborns is made at 1 and 5 minutes after birth. It scores the child's health based on:
1. Appearance
- coloration of body and extremities, signifying quality of ventilation
2. Pulse
3. Grimace (reflex irritability):
- poke child on foot, 1 point for a grimace, 2 for withdrawal of foot
4. Activity (muscle tone)
- no motion, weak motion, strong kicking
5. Respiration
- no breathing, weak/slow breathing, rapid breathing & crying.

Front 97

Amylin deposits
Pathology & its precursor:

Back 97

Found in amyloidosis in DM2

Derived from: AE [*Endocrine]

Front 98

Familial Adenomatous Polyposis

Back 98

Colon becomes covered in polyps. Colorectal cancer is inevitable.

APC mutation on chromosome 5.
[5 letters in polyp]

Hint 98

Autosomal Dominant

Front 99

How is an Apgar assessment interpreted?

Back 99

The APGAR assessment, given once at 1 minute and once at 5 minutes, each time gives us a score between 1 and 10 for a newborn child.||Interpretation of results:| - 10-7 is normal| - 4-6 = "assist and stimulate"| - Less than 4 indicates imminent danger of death.

Front 100

A-CAL

Back 100

Found in amyloidosis secondary to Medullary Carcinoma of the Thyroid

Derived from: Calcitonin

Front 101

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
Etiology:
Pattern of Inheritance:

Back 101

Inherited disorder of blood vessels. Findings include telangiectasia, recurrent epistaxis, arteriovenous malformations.

Presents with purpura, nosebleeds, telangiectasia on tongue.

Hint 101

Autosomal Dominant

Front 102

Moro reflex

Back 102

When startled, the child extends arms and legs. This reflex disappears by 3-4 months of age.

Front 103

beta-amyloid

Back 103

Found in amyloidosis in Alzheimer's Disease.

Derived from amyloid precursor protein (APP)

Front 104

Hereditary spherocytosis
Etiology:
Pattern of Inheritance:

Back 104

Spheroid eryhthrocytes d/t ankyrin or spectrin defect.

Presents with hemolytic anemia, increased MCHC.

This is the disorder in which the wire mesh of the normal spleen is responsible for your hemolysis.

Hint 104

Autosomal Dominant

Front 105

Milestones of early development
0-3 months:

Back 105

1. Rooting reflex
2. Moro reflex disappears
3. Can hold head up

Front 106

β2-microglobulin

Back 106

Found in dialysis-associated amyloidosis.

Derived from MHC class I proteins.

Front 107

Marfan's Syndrome
Etiology:
Pattern of Inheritance:

Back 107

Fibrillin gene mutation resulting in connective tissue abnormalities.

Hint 107

Autosomal Dominant

Front 108

At what ages do children typically begin to experience stranger anxiety?

Back 108

7-9 months.

Front 109

Cause of metaplasia?

Back 109

Cell change usually environmental exposure.

Front 110

MEN
Etiology:
Pattern of Inheritance:

Back 110

Familial tumors of the endocrine glands.

Types 2A and 2B are caused by RET mutation.

Hint 110

All 3 syndromes are autosomal dominant

Front 111

At what ages do children typically lose the Moro reflex?

Back 111

At 3-4 months, children cease to reflexively extend arms and legs when startled.

Front 112

Define desmoplasia.

Back 112

Defined as fibrous tissue formation in response to neoplasm. Seen in many tissue types, i.e. breast and pancreas.

Front 113

Neurofibromatisis type 1
Etiology:
Pattern of Inheritance:

Back 113

Cafe Au lait spots
neural tumors
blindness

Lisch nodules are ubiquitous

Mutation on long arm of chromosome 17

Hint 113

Autosomal Dominant

Front 114

At what ages do children typically lose the rooting reflex?

Back 114

At 3-4 months, children cease to reflexively turn their head in the direction of a stroke on the cheek. This reflex serves to bring them to the nipple.

Front 115

Difference between grading and staging:

Back 115

Grading is based upon degree of dedifferentiation of the neoplastic cells, and is recorded as I-IV.

Staging is based upon degree of localization/spread, i.e. bloodborne mets = Stage 4.

Staging is more prognostic of outcomes.

Front 116

Neurofibromatosis type 2

Back 116

Bilateral acoustic schwannomas
Juvenile cataracts
NF2 on Chromosome 22

[2's disease: Type 2 on chrom. 22]

Hint 116

Autosomal dominant

Front 117

At what ages do children typically begin to show a social smile?

Back 117

At about 3 months of age, children begin to smile.

Front 118

What staging system is most commonly used at present? How is it used?

Back 118

TNM staging is currently the most commonly used staging scale in diagnosis of neoplasms.

T: describes primary Tumor; it's degree of dedifferentiation, etc.

N: degree of spread to regional lymph Nodes

M: Presence of Mets

Hint 118

The method of TNM staging varies for each different type of cancer, but in general it is supposed to tell us about the primary tumor, any regional spread, and any distal metastases.

Front 119

Tuberous sclerosis

Back 119

Facial lesions
Hamartomatous masses in cortex and retina
Increased incidence of astrocytomas

Hint 119

Autosomal dominant

Front 120

At what age does a child become able to transfer toys from hand-to-hand?

Back 120

At about 7-9 months of age, children begin to show more complex motor behaviors such as this.

Front 121

What distinguishes an invasive carcinoma from a carcinoma in situ?

Back 121

The invasive carcinoma must make collagenases and/or hydrolases (metalloproteinases) in order to burrow through the basement membrane underlying the epithelium.

Front 122

von Hippel-Lindau disease

Back 122

Hemangioblastomas of retina/cerebellum/medulla.

Half of these individuals also develop renal cell carcinoma.

Familial form is caused by VHL gene mutation on p arm of chromosome 3.

Hint 122

Autosomal dominant

There is also a sporadic form caused by loss of p arm of chromosome 3.

Front 123

At what age does a child begin to walk?

Back 123

Children develop this ability at about 12-15 months of age.

Front 124

Define cachexia. What are its chemical mediators?

Back 124

Loss of weight, muscle atrophy, and fatigue that occur in chronic disease.

Mediated chemically by:
-- TNF-alpha (AKA cachectin)
-- INF-gamma
-- IL-6

Front 125

VHL
(1) Genetics & biomolecular changes
(2) Path

Back 125

(1)
Gene located on 3p. Can be lost d/t del(3p) or mutation to the VHL gene on 3p.

VHL normally degrades the transcription factor HIF-1α, preventing it from triggering PDGF and VEG-2F expression.

Hint 125

Disease consists of medulloblastomas, hemangiomas of the retina/cerebellum/medulla.

Half of these individuals also will get renal cell carcinoma.

Bottom line: when VHL is knocked out, we'll see cancerous expansion of many small blood vessels.

Front 126

At what age do children begin to manifest separation anxiety?

Back 126

Children begin to manifest this emotional response at 12-15 months of age.

Front 127

What neoplasm(s) are associated with Down's Syndrome?

Back 127

1. ALL (we ALL fall DOWN)

2. AML

Front 128

Cystic Fibrosis
Normal vs. pathological pulmonary biochem:

Back 128

Normal Lungs:

CFTR is a Cl- channel that actively secretes chloride in lungs

CFTR regulates ENaC, preventing excessive Na+ absorption by the lung epithelium.

Hint 128

Lungs in CF:

1. Cl- channel is absent or defective, so less Cl- is secreted from lung epithelium.

2. Cl- channel cannot, under these circumstances, downregulate ENaC activity, and Na+ is reabsorbed into lung epithelium too vigorously

3. H2O follows Na+ out of the airways and into the epithelium

4. Result: thick, stagnant mucous in airways that forms plugs and invites bacterial colonization.

so it can't regulate ENaC, and lots of Na+ (and therefore H2O) is reabsorbed.

Front 129

At what age do children begin to develop their core gender identity?

Back 129

Children begin to develop their core gender identity at 24-36 months of age.

Front 130

What neoplasm(s) are associated with Xeroderma Pigmentosum?

Back 130

*1. Squamous cell carcinoma (most of all)

2. Melanoma

3. Basal cell carcinoma

Front 131

Genetics of CF & Location of Cystic Fibrosis gene

Back 131

CFTR is located on the long arm of Chromosome 7

Autosomal recessive inheritance pattern

Front 132

At what age do children typically begcome capable of riding a tricycle?

Back 132

At 3 y/o, children typically become able to participate in this more complex form of play.

Front 133

What neoplasm(s) are associated with Chronic atrophic gastritis, pernicious anemia, and postsurgical gastric remnants?

Back 133

Gastroadenocarcinoma

Front 134

Complications of Cystic Fibrosis

Back 134

Lung:
1. recurrent infections by pseudomonas and staph aureaus
2. chronic bronchitis, bronchiectasis

GI: pancreatic insufficiency

Front 135

How many words does a 3 y/o's vocabulary typically contain?

Back 135

At this age, a child can speak about 900 words and can make complete sentences.

Front 136

What is tuberous sclerosis and what are its complications?

Back 136

Syndrome characterized by facial angiofibroma, large hamartomas in the cortical matter, seizures, and MR?

Seizures are the result of mass effects from these big growths.

Hint 136

1. Astrocytoma
2. Angiomyolipoma
3. Cardiac rhabdomyosarcoma

Front 137

Compare CF pathophys in skin vs. lung

Back 137

In lung, CF is caused by defect in a Cl- channel that normally actively SECRETES Cl-.

In the skin, CF is caused by defect in a Cl- channel that actively REABSORBS Cl-

In both cases, pathological buildup of Cl- is mirrored by pathological buildup of Na+ and H2O, because CFTR regulates ENaC.

Front 138

How many words does a child's vocabulary typically have between 12 and 24 months of age?

Back 138

At this age, a child typically can speak about 200 words.

Front 139

What neoplasm(s) are associated with actinic keratosis?

Back 139

Squamous cell carcinoma

Front 140

Cystic fibrosis
Normal vs. pathological biochem in skin:

Back 140

Normal Skin:

1. CFTR is a Cl- transporter that actively *reabsorbs* Cl- from sweat

2. CFTR upregulates ENaC activity, and therefore Na+ reabsorption.

Hint 140

Skin in CF:

1. CFRT is absent or defective, so less Cl- is reabsorbed by the skin.

2. Cl- channel cannot regulate ENaC, so Na+ isn't reabsorbed either.

3. Lots of NaCl is lost in sweat.

Front 141

At what point does grieving become considered pathological?

Back 141

more than 2 months.

Front 142

What is Plummer-Vinson syndrome?

What neoplasm(s) are associated with Plummer-Vinson syndrome?

Back 142

atrophic glossitis, esophageal webs, associated with anemia. Pathophys unknown.

Hint 142

benign but associated with development of squamous cell carcinoma of the esophagus.

Front 143

Treatment of CF

Back 143

Palliative:
1. Give N-Acetylcysteine to loosen mucous plugs
2. Give lots of electrolytes. LOTS!

Gene modification therapy is in the works but not yet ready.

Front 144

In what age group is suicide most common?

Back 144

Males age 65-74 have the highest rate of suicide in the U.S.

Front 145

What neoplasm(s) are associated with Cirrhosis?

Back 145

Hepatocellular carcinoma

Front 146

List the X-Linked Recessive disorders

Back 146

B W F G O L D H H
(Be Wise, Fool's GOLD Heeds Silly Hopes)

Bruton's aggamaglobulinemia
Wiskott-Aldrich syndrome
Fabry's Disease
G6PD Deficiency
Ocular Albinism
Lesch-Nyhan syndrome
Duchenne's muscular dystrophy
Hunter's Syndrome
Hemophilia A and B

Front 147

Define BMI, and its normal ranges.

Back 147

1. kg / m^2|2. Ranges:|18.5 > underweight|18.5 - 24.9 = normal|25 - 29.9 = overweight|30 - 39.9 = Obese|40 < Morbid obesity

Front 148

What neoplasm(s) are associated with Ulcerative Colitis?

Back 148

Colonic adenocarcinoma

Front 149

Duchenne's Muscular dystrophy
Genetics & Biochem

Back 149

(1)
X-linked Recessive

Deletion/frameshift mutations in Dystrophin protein

Hint 149

(2) Biochem:

Dystrophin connects Actin of cytoskeleton to sarcolemmal membrane of myocytes.

Result of deletion: force of muscle fiber contraction is not transferred to cell membrane; the cell doesn't contract, only its organelle does.

Front 150

What are the brain waves corresponding with each stage of sleep?

Back 150

beta waves: REM & Awake

alpha waves: Awake with eyes closed

theta waves: Stage 1

Sleep spindles and bruxism: Stage 2

delta waves: Stage 3

Front 151

What neoplasm(s) are associated with Paget's disease of the bone?

Back 151

1. Secondary osteosarcoma
2. Secondary fibrosarcoma

Front 152

Becker's Muscular Dystrophy
Genetics & Biochem

Back 152

(1)
X-linked recessive

Missense/nonsense Mutation (*NOT* frameshift/deletion) to dystrophin gene.

Hint 152

(2) Biochem:

Some dystrophin is made, but it's abnormal to a greater or lesser degree.

The result is a disorder that's less severe and has a later onset than in Duchenne's.

Front 153

What is the principle neurotransmitter in REM sleep, and where is it acting?

Back 153

ACh is the principle neurotransmitter in this form of sleep.|ACh hyperactivity is seen in the reticular formation.

Front 154

What neoplasm(s) are associated with immunodeficiency states?

Back 154

Malignant lymphomas

Front 155

Muscular dystrophies
Presentation & Diagnostics

Back 155

These disorders are inherited and present at anytime from childhood to early adulthood wiht progressive muscle wasting and myocyte degredation.

Histological abnormalities include:
Muscle tissue can become replaced with fat.
Muscle fibers will vary in size and diameter.

Hint 155

Diagnose via increased serum Creatinine Kinase and muscle biopsy.

Front 156

What is the most common pathological sleep symptom in depressed patients?

Back 156

Early waking is the most common sleep symptom in these patients.

Front 157

What neoplasm(s) are associated with AIDS?

Back 157

1. Aggressive malignant lymphomas (non-Hodgkins)
2. Kapoi's sarcoma

Front 158

Fragile X
Path & Presentation

Back 158

X-linked defect in methylation and expression of the FMRI gene.

Results in trinucleotide expansion repeat of CGG

Hint 158

Second most common cause of MR!

X-linked, X-tra long gene, Xtra large testes, jaw, and ears!!

Front 159

Activity in what brain center is responsible for eye activity during REM sleep?

Back 159

Hyperactivity in the PPRF is associated with the eye movements characteristic of REM.

Front 160

What neoplasm(s) are associated with autoimmune diseases, i.e. Hashimoto's, thyroiditis, and myasthenia gravis?

Back 160

Lymphoma

Thymomas are common in MG and Lambert-Eaton's (and are a type of lymphoma)

Front 161

List the trinucleotide repeat diseases and their repeated sequences.

Back 161

1. Fragile X: CCG
2. Friedrich's ataxia: GAA
3. Huntington's Disease: CAG
4. Myotonic Dystrophy: CTG

Front 162

How does depression affect REM sleep?

Back 162

Depression decreases REM latency, while increasing total time spent in REM sleep in these patients. It also increases the amount of time spent in REM early in the sleep cycle.| - *REM latency is the amount of time it takes for the patient to enter REM after falling asleep.

Front 163

What neoplasm(s) are associated with Acanthosis nigricans?

Back 163

Underlying visceral malignancies, i.e. stomach, lung, and uterus.

Front 164

What disorder is often associated with duodenal atresia?

Back 164

Down's Syndrome.

Front 165

Which brain center is responsible for circadian rhythms?

Back 165

The Suprachiasmatic nucleus of the hypothalamus is responsible for this function.

Front 166

What neoplasm(s) are associated with radiation exposure?
(not sun -- i.e. irradiated water)

Back 166

Sarcoma
Papillary thyroid cancer

Front 167

List the trisomies and their associated syndromes.

Back 167

1. Down's Syndrome: trisomy 21

2. Edward's Syndrome: trisomy 18

3. Patau's Syndrome: trisomy 13

Hint 167

Remember:

Down's = Drinking age (21)

Edward's = Election age (18)

Patau's = Puberty (13)

Front 168

Bulemia symptoms:

Back 168

Eroded tooth enamel
25% present with enlarged parotid glands
Irregular menses

Front 169

What gene mutation and defective product is associated with CML?

Back 169

ABL ==> BCR-ABL t(9,22) -- The Philadelphia Chromosome translocation!

Together, these genes form a constitutively expressed tyrosine kinase

Treatable with imatinib.

Front 170

Screening for Down's in Pregnancy

Back 170

1. Decreased α-fetoprotein
2. Increased β-hCG
3. Decreased estriol,
4. normal inhibin A

Front 171

What psychiatric complications of childbirth are common, and in what time frames?

Back 171

Maternity Blues: more than half of women, resolves within 10 days.

Hint 171

Post-partem depression: 10-20% of women, occurs anywhere from 2 weeks to 1 year post-partem.

Front 172

What gene mutation is associated with Burkitt's lymphoma?

Back 172

C-MYC mutation on Chromosome 8

Results in constitutive transcription factor expression for HAT's

Front 173

Screening for Edward's syndrome in pregnancy

Back 173

1. Decreased α-fetoprotein
2. Decreased β-hCG
3. Decreased estriol
4. Normal inhibin A

Front 174

When is it OK to discuss patient information with the patient's spouse? Is it always OK?

Back 174

Only when he is incapacitated.

Front 175

What gene mutation is associated with follicular and undifferentiated lymphomas?

Back 175

BCL-2 mutation

Results in constitutive protection from apoptosis

Front 176

Screening for Patau's syndrome in pregnancy

Back 176

1. Normal α-fetoprotein
2. Normal β-hCG
3. Normal estriol
4. Normal inhibin

Front 177

What gene mutation is associated with breast, ovarian, and gastric carcinomas?

Back 177

erb-B2 mutation.

Results in constitutive activation of a tyrosine kinase

Front 178

Contrast presentations of the three trisomies.

Back 178

1. Down's: flat facies, epicanthal folds, simian crease

2. Edward's: micrognathia, lowset ears, clenched hands

3. Patau's: cleft lip/palate, holoprosencephaly, polydactyly

Front 179

What gene mutations are associated with colon carcinoma?

Back 179

1. Ras mutation results in constitutive action of a GTPase, and therefore of a G protein.

2. APC (in FAP)

3. DCC (Deleted in Colon Carcinoma)

Front 180

List the chromosomes commonly involved in Robertsonian translocation.

Back 180

Chromosomes 13, 14, 15, 21, 22

Results in loss of short, 'p' arms of chromosomes, and a giant chromosome

Front 181

What gene mutation is associated with lung tumors?

Back 181

L-myc mutation

Results in constitutive action of a transcription factor for growth factors.

Front 182

Cri-du-chat syndrome
Presentation and Genetics:

Back 182

Presentation:

Microcephaly
Moderate to severe MR
Hi pitched, cat-like scream
Congenital VSD

Hint 182

Congenital microdeletion of short arm of chromosome 5 (46, XX/Xy, 5p-)

Front 183

What gene mutation is associated with neuroblastoma?

Back 183

N-myc mutation

Results in constitutive action of a transcription factor for growth factors.

Front 184

Williams Syndrome
Presentation and Genetics:

Back 184

Presentation:

Long, "elfin" facies, MR, hypercalcemia, very friendly and with good verbal skills

Hint 184

Microdeletion of long arm of chromosome 7. Deleted region includes elastin gene.

Front 185

What gene mutation is associated with MEN types IIA and IIB? (and papillary thyroid carcinoma?)

Back 185

ret mutation

Results in constitutive action of a tyrosine kinase.

Front 186

22q11 deletion of syndromes
Presentation and Genetics:

Back 186

Variable presentation including:
Cleft palate
Abnormal facies
Thymic aplasia
Cardiac defects
Hypocalcemia

CATCH-22

Hint 186

Due to microdeletion at 22q11

CATCH-22

Front 187

What gene mutation is associated with GIST?

Back 187

c-kit mutation

Constitutive activation of a cytokine receptor.

Treatable with imatinib

Front 188

Vitamin A
3 active forms
Generation in body

Back 188

(1)
3 active forms are:
retinal
retinol
retinoic acid

Hint 188

(2)
1. Eaten as β-carotenes in green veggies.

2. Esterified in liver to retinol esters.

3. Retinol is secreted from liver and binds to RBP, traveling together to target tissues

4. Retinol is taken up in tissues and irreversibly converted to retinoic acid.

5. Retinoic acid activates gene transcription of protein products.

Front 189

What gene mutation is associated with Retinoblastoma and osteosarcoma?

Back 189

Rb knockout.

Normally, Rb prevents G1-->S cycling

Front 190

Physiological Functions of Vitamin A

Back 190

**Antioxidant!

1. Component of visual pigments.
2. Important in normal cell differentiation; prevents squamous metaplasia
3. Bone and tooth development.

Front 191

What gene mutation is associated with Li-Fraumeni snydrome?

Back 191

p53 knockout mutation.

p53 is the Guardian of the Genome. It prevents G1-->S cycling.

Front 192

Vitamin A
Deficiency & Excess

Back 192

Deficiency results in night blindness, dry skin

Hint 192

Excess results in:

Arthralgias, fatigue, HA, skin changes, sore throat, alopecia.

Front 193

What gene mutation is associated with Breast and ovarian cancer? What type of gene product is affected?

Back 193

BRCA1 knockout mutation

BRCA1 is a DNA repair protein.

Front 194

Di George Syndrome
Presentation & Path:

Back 194

Pt. will be an infant sick with chronic infections from birth.

Congenital heart defects, esp tetralogy of Fallot, are commonly associated.

Abnormal facies

Hypocalcemia d/t absence of parathyroid glands.

Hint 194

AKA thymic dysplasia, passed on via autosomal dominant inheritance.

Causative mutation results in abnormal development of the 3rd and 4th branchial pouch, so it's often associated with congenital abnormalities and hypoparathyroidism.

Diagnosed by severely decreased T cell count.

Occurs in 50% of patients with 22q11 deletion syndromes.

Front 195

What gene mutation is associated with breast cancer but not ovarian cancer?

Back 195

BRCA2 knockout mutation.

BRCA2 is a DNA repair protein.

Front 196

Velocardiofacial syndrome
Presentation & Path

Back 196

Presents with palate, facial, and cardiac defects.

Hint 196

Caused by 22q11 mutation. Like DiGeorge's, the branchial arches are affected but unlike DiGeorge's, immunodeficiency is uncommon in these patients.

Front 197

What gene mutation is associated with melanoma?

Back 197

p16 knockout mutation.

Front 198

Vitamin B1
MoA

Back 198

AKA thiamine or thiamine pyrophosphate (TTP), this nutrient acts as a cofactor in several reactions:

1. Decarboxylation of pyruvate dehydrogenase in glycolysis

2. Decarboxylation of α-ketoglutarate dehydrogenase in the TCA cycle.

3. Transketolase in the HMP shunt

4. Branched-chain AA dehydrogenase.

Front 199

What gene mutation is associated with colorectal cancer secondary to FAP?

Back 199

APC gene knockout.

Front 200

Vitamin B1
Deficiency & Excess

Back 200

1. Deficiency results in Impaired glucose breakdown and ATP depletion. Highly aerobic tissues like brain and heart are affected first.

2. Wernicke-Korsakoff syndrome
3. Beriberi

Hint 200

No B1 excess syndromes are known.

Front 201

What gene mutation is associated with Wilms' tumor?

Back 201

WT1 gene knockout.

**Causes an anaplastic renal sarcoma in kids
**Most common renal tumor in kids

Front 202

Wernicke-Korsakoff syndrome
Presentation &
Path & Etiology:

Back 202

Wernicke-Korsakoff:

Classic triad of confusion, ophtalmoplegia, ataxia

Also lying, personality change, and memory loss

Hint 202

Caused by thiamine (B1) deficiency

Absence of cofactor for glycolytic, TCA, and HMP reactions decreases aerobic production of ATP.

Highly aerobic tissues are injured first.

Common causes of thiamine deficiency are alcoholism and malnutrition.

Front 203

What gene mutation is associated with Neurofibromatosis type 1?

Back 203

NF1 gene knockout

Front 204

Wet vs. Dry beriberi
Presentations
Path & Etiologies

Back 204

(1)
Wet beriberi: high-output cardiac failure, dilated cardiomyopathy, edema. Hi BP

Dry beriberi: polyneuritis, symmetrical muscle wasting

Hint 204

(2)
Both are caused by thiamine (B1) deficiency.

Common causes of B1 deficiency are alcoholism and malnutrition.

Front 205

What gene mutation is associated with neurofibromatosis type 2?

Back 205

NF2 gene knockout

Front 206

Vitamin B2
MoA
Deficiency

Back 206

Riboflavin is the precursor to 2 coenzymes in oxidation and reduction reactions: FAD and FMN

Hint 206

Deficiency results in:
1.
Glossitis
Stomatitis
Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth)

2.
Corneal vascularization

Front 207

What gene mutation is associated with pancreatic cancer?

Back 207

DPC gene knockout

"Deleted in Pancreatic Cancer" -- think of DCC in colorectal cancer.

Front 208

Vitamin B3
Derivatives
MoA

Back 208

Derived from tryptophan

Synthesis requires B6

Hint 208

Constituent of NAD+ and NADP+

**Remember: Niacin is the layman's nickname for Nicotinamide. NAD = Nicotinamide Adenine Diphosphate.

Niacin is made into NAD!

Front 209

What gene mutation is associated with colon cancer?

Back 209

DCC gene knockout mutation

(*Deletion causes Colon Cancer)

Front 210

Vitamin B3
Deficiency & Excess

Back 210

Deficiency: 3 D's of B3

Diarrhea, Dermatitis, and Dementia

We call B3 deficiency Pellagra, but it usually specifically refers to the "pearl necklace" of niacin deficiency

Hint 210

Excess: facial flusing

Front 211

PSA

Back 211

Prostate-specific antigen.

Elevated in BPH, prostatitis, and most importantly, prostate carcinoma.

Used for screening, confirmation, and monitoring for recurrence only. *Not initial diagnosis.

Front 212

Deficiencies of Vitamin B2 vs. B3:

Back 212

Riboflavin: 2 C's of B2 (plus stomatitis!)

1. Cheilosis (inflammation and scaling of the lips, stomatitis & glossitis)

2. Corneal vascularization

Hint 212

Niacin: 3 D's of B3

Diarrhea
Dermatitis
Dementia

Front 213

Prostatic acid phosphatase

Back 213

Marker for prostate carcinoma

Front 214

Vitamin B5
(1) MoA
(2) Deficiency

Back 214

Pantothenate

Essential component of:
1. CoA
2. Fatty acid synthase

**We can't make anything without it!

Hint 214

Deficiency uncommon.

Dermatitis
Enteritis
Alopecia
Adrenal insufficiency

**Rapidly-dividing epithelial cells are injured first!

Front 215

CEA

Back 215

Carcinoembryonic antigen.

Marker found in ~70% of:

1. Colorectal cancers

2. Pancreatic cancers.

Non-specific b/c also found in gastric, breast, and thyroid medullary cancers.

Front 216

Vitamin B6
MoA
What do we need it to make?

Back 216

Pyridoxine

Converted to a cofactor in:

1. Transaminations (AST & ALT)

2. Decarboxylation reactions

3. Glycogenolysis (glycogen phosphorylase)

Hint 216

We need pyridoxine to make:

1. Histamine
2. Pyruvate from serine in gluconeogenesis
3. Niacin from tryptophan
4. Heme

Front 217

α-fetoprotein

Back 217

Normally found in fetus. Elevated in:

1. Hepatocellular carcinomas

2. Yolk Sac Tumor

Front 218

Hartnup disease

Back 218

Decreased intestinal absorption and renal reabsorption of neutral amino acids.

Results in low tryptophan

Excess tryptophan is normally converted into niacin, therefore low tryptophan = low niacin

Pellagra and B3 deficiency result.

Front 219

β-hCG

Back 219

Elevated in:

1. Chorionic carcinoma (non-seminomatous germ cell tumor)

2. Mole pregnancy

Front 220

Causes of B3 deficiency:

Back 220

Deficiency caused by:

1. Malnutrition

2. Hartnup's disease: inability to absorb B3 in intestine and to reabsorb it in urine.

3. Carcinoid Syndrome: b/c its precursor, tryptophan, is instead being made into serotonin!

Front 221

CA-125

Back 221

Elevated in malignancies of the ovarian surface epithelium

Front 222

Vitamin B6 deficiency
Effects:
Causes

Back 222

1. Sideroblastic anemia
2. Convulsions
3. Peripheral neuropathy

Hint 222

Deficiency can be caused by:

1. Isoniazid
2. Unfortified goat milk.

Front 223

S-100

Back 223

Elevated in:

1. Melanoma
2. Neural tumors
3. Astrocytomas

Hint 223

Highly sensitive for melanocyte dedifferentiation indicating meloma
Also produced by neural crest-derived cells, so it'll be elevated in neural/glial tumors.

Front 224

B12
(1) MoA
(2) Deficiency

Back 224

Accepts methyl groups from both N5-methyl-TH4 and homocysteine, activating TH4 and deactivating homocysteine!

Therefore, it is necessary for:
1. reducing serum levels of homocysteine, which helps prevent arterial disease.
2. Methylation of dUMP to dTMP.

Hint 224

Cobalamin deficiency results in:

1. Macrocytic, megaloblastic anemia d/t dTTP shortage

2. Atherosclerotic disease d/t homocysteinemia

3.
Neurologic symptoms d/t abnormal myelin

Front 225

Alkaline phosphatase
(bone variant)

Back 225

Elevated in:

1. Mets to bone
2. Obstructive biliary disease
3. Paget's disease of bone

Hint 225

Alk-phos is made by the liver. It is also made by and tethered to osteoblasts.

Alk-phos is therefore a good indicator of osteoblastic activity. If elevated, consider:
1. osteoblastic-osteoclastic stage of Paget's disease
2. osteoblastic bone mets

Front 226

Where do we get our B12?

Back 226

We get it from animal products, but it is only made by microorganisms.

Most people have a several year storage pool in the liver.

Front 227

Pt. presents with elevated serum Bombesin.
DDx:

Back 227

Elevated in:

1. Neuroblastoma
2. Lung cancer
3. Gastric cancer

Hint 227

AKA GRP (Gastrin-Releasing Peptide), Bombesin is a GI neurocrine, made by the neurons of the gastric mucosa. It will be increased in gastric hyperplasia/tumor.

Front 228

Causes of B12 Deficiency:

Back 228

1. Malabsorption, i.e.:
Celiac sprue
Enteritis
Diphyllobothrium latum

2. Lack of intrinsic factor, i.e.:
pernicious anenia
gastric bypass
absence of terminal ileum in Crohn's

Front 229

TRAP

Back 229

Tartrate-resistant acid phosphatase

Elevated in:

*Hairy* cell leukemia, the pre-plasma cell, B cell malignancy

Catch that "Hairy" animal in the "TRAP"

Front 230

Distinguishing folic acid deficiency from B12 deficiency

Back 230

The syndromes are distinct in that there are no neurological symptoms in folic acid deficiency, but many in B12 deficiency.

Front 231

CA-19-9

Back 231

Elevated in pancreatic adenocarcinoma

Front 232

Causes of folate deficiency:

Back 232

Most common vitamin deficiency in the U.S.

Usually caused by pregnancy or alcoholism.

Malabsorption disorders
Tapeworm
Chronic pancreatitis

Drugs:
Phenytoin
Sulfonamides
MTX

Front 233

Calcitonin

Back 233

Elevated in thyroid medullary carcinoma

Front 234

Biotin
(1) MoA
(2) Deficiency

Back 234

This nutrient is a cofactor for carboxylation reactions.

Cofactor in the following reactions:

1. Pyruvate carboxylase
2. A.CoA carboxylase
3. Propionyl CoA carboxylase

Hint 234

Dermatitis
Alopecia
Enteritis
Adrenal Insufficiency

**Same as B5, which, not incidentally, also is involved in A.CoA synthesis!

Front 235

Which neoplasms may secrete ACTH?

Back 235

Small cell carcinoma may secrete ACTH or ACTH-like peptide

Result: Cushing's syndrome

Front 236

3 Functions of Vitamin C

Back 236

1. Hydroxylation of Collagen
deficiency = scurvy]

2. Absorption of iron (by reducing it in the gut; Fe3+ can't be absorbed)
[deficiency = microcytic anemia]

3. Necessary for DA beta-hydroxylase to convert DA to NE.
[depression]

Front 237

Which neoplasms may secrete ADH?

Back 237

SIADH, and hypervolumemia may result from ADH secretion by:

1. Small cell lung carcinomas
2. Intracranial neoplasms

Front 238

In what forms do we take in vitamin D from (1) plants and (2) milk?

What other forms exist in human physiology?

Back 238

D2 = ergocalciferol, which is ingested from plants

D3 = cholecalciferol

Hint 238

Monohydroxy D3 (25-OH D3): storage form of calciferol

Dihydroxy D3 (1,25-OH D3): active form.

Front 239

There are 3 neoplasms that may secrete either PTH-related peptide, TGF-β, TNF-α, or IL-1, and are known for causing *humoral hypercalcemia of malignancy*. List them.

Back 239

While some malignancies cause hypercalcemia because they are directly osteolytic, others are associated with humoral hypercalcemia of malignancy. These include:

1. Squamous cell cancer of the lung
2. Renal cell carcinoma
3. Breast carcinoma

Front 240

Distinguish mechanisms for conversion to active Vitamin D in endogenous vs. ingested Vitamin D.

Back 240

Endogenous:

D3 --> 25-OH D3 (liver) --> 1,25-OH D3 (kidney)

Hint 240

Exogenous:

dehydrocholesterol --> Vitamin D3 (photoconversion in skin) --> 25-OH D3 (liver) --> 1,25-OH D3 (kidney)

Front 241

Which neoplasm may cause erythropoietin oversecretion?

Which neoplasms may result?

Back 241

Tumors that cause elevated erythropoietin:

1) Renal cell carcinoma
2) Hepatocellular carcinoma

**Both are derived from cells that normally make EPO

Hint 241

Elevated erythropoietin, resulting in polycythemia, may be associated with (though not necessarily caused by):

1. Hemangioblastoma
2. Pheochromocytoma

Front 242

Vitamin E
Function & Deficiency

Back 242

Function: Anti-oxidant

Hint 242

Deficiency:

1. Hemolytic anemia d/t radical damage

Front 243

(1) Which neoplasm may secrete antibodies against Ca2+ channels at the neuromuscular junction?

(2) Presentation

Back 243

Anti-Ca2+ channel antibodies are sometimes secreted by:

1. Small cell lung carcinoma (most common cause)
2. Thymoma

Hint 243

Lambert-Eaton Syndrome:
1. Weakness that improves as the day goes on
2. Most pronounced in the proximal muscles.

Front 244

Vitamin K
MoA:
Deficiency:

Back 244

Gamma-Carboxylation, i.e. of the coagulation factors!

Hint 244

Increased PT/INR *and* aPTT!!

Front 245

Excess nucleic acid turnover (and subsequent gout and urate nephropathies) may result from which kinds of neoplasms?

Back 245

Leukemias and lymphomas.

Front 246

Vitamin K is necessary for the synthesis of which proteins in the coagulation cascade?

Back 246

This vitamin is necessary for synthesis of

Clotting factors: 2, 7, 9, 10

Clotting cofactors: Protein C and Protein S

Front 247

Paraneoplastic causes of Cushing's Syndrome:

Back 247

1. Small cell lung carcinoma
2. Pancreatic carcinoma
3. Neural tumors

*All 3 are causing a Cushing's Disease by secreting ACTH

Front 248

Zinc deficiency:

Back 248

Deficiency of this nutrient results in delayed wound healing, hypogonadism, decreased growth of adult hair, anosmia and dysgeusia.

Front 249

Paraneoplastic causes of inappropriate antidiuretic secretion:

Back 249

1. Small-cell carcinoma of the lung
2. Intracranial neoplasms

May secrete either ADH or natriuretic hormones.

Front 250

Which deficiency/excess of which nutrient causes anosmia and dysgeusia?

Back 250

Zinc deficiency causes anosmia (lack of smell) and dysgeusia (aberrant sense of taste -- i.e. metallic taste on back of mouth)

Front 251

Paraneoplastic causes of Hypercalcemia:

Back 251

1. Squamous cell carcinoma of the lung
2. Breast carcinoma
3. Renal carcinoma
4. Adult T-cell leukemia/lymphoma

**These tumors can secrete either PTHRP, TGF-alpha, TNF, or IL-1.

Front 252

Mechanism of ethanol metabolism:

Back 252

Ethanol --ethanol dehydrogenase--> acetaldehyde --acetaldehyde dehydrogenase--> Acetate

Front 253

Paraneoplastic causes of hypoglycemia:

Back 253

1. Ovarian carcinoma
2. Fibrocarcinoma (breast cancer)
3. Other mesenchymal sarcomas

**These tumors secrete insulin or insulin-like substance.

Front 254

Disulfiram
MoA:

Back 254

Inhibits acetaldehyde dehydrogenase, increasing acetaldehyde buildup.

Acetaldehyde causes hangover symptoms!

Hint 254

**This drug induces hangover by interrupting the last phase of ethanol breakdown to acetate!

Front 255

Paraneoplastic causes of carcinoid syndrome:

Back 255

1. Hepatocellular carcinoma
2. Bronchial adenoma
3. Pancreatic carcinoma

**These tumors secrete Serotonin or bradykinin.

Front 256

Fomepizole
MoA:

Back 256

Inhibits alcohol dehydrogenase and is an antidote for methanol or ethylene glycol poisoning.

Front 257

Paraneoplastic causes of polycythemia:

Back 257

1. Renal cell carcinoma
2. Hepatocellular carcinoma

**Both secrete EPO

Front 258

How does ethanol consumption alter normal glucose metabolism?

Back 258

Ethanol metabolism causes NADH to build up in the liver. To restore NAD+, we have to reverse 2 major pathways:

Pyruvate ---> Lactate instead of A.CoA

Oxaloacetate ---> malate instead of citrate!

Hint 258

Result:

1. Depletion of pyruvate to make new NAD+ results in decreased gluconeogenesis ---> hypoglycemia!

2. Downregulation of TCA d/t depletion of oxaloacetate

Front 259

Paraneoplastic causes of myasthenia:

Back 259

**1. Thymoma/thymic hyperplasia
2. Small cell Lung cancer

**It's believed that MG is caused by B cells in the thymus secreting anti-AChR antibodies!!

Front 260

Define marasmus

Back 260

Energy malnutrition resulting in tissue and muscle wasting, loss of subcutaenous fat, and variable edema.

Front 261

Paraneoplastic causes of disorders of the central and peripheral nervous system

Back 261

Breast carcinoma

Front 262

What metabolic processes occur in the mitochondria?

What processes occur in the cytoplasm?

Back 262

1. TCA
2. ETC
3. Fatty acid oxidation
4. A.CoA production

Hint 262

1. Glycolysis
2. Fatty acid synthesis
3. HMP Shunt
4. Protein synthesis (RER)
5. Steroid synthesis (SER)

Front 263

Rate-limiting step of Glycolysis

Back 263

Fructose-6-phosphate --PFK-1--> Fructose-1,6-phosphate

Front 264

Rate-limiting step of Gluconeogenesis:

Back 264

Fructose-1,6-bisphosphonate

Front 265

Rate-limiting step of TCA cycle:

Back 265

Isocitrate dehydrogenase

Front 266

Rate-limiting step of glycogen synthesis

Back 266

Glycogen synthase

Front 267

Rate-limiting step of glycogenolysis

Back 267

Glycogen phosphorylase

Front 268

Rate-limiting step of HMP shunt

Back 268

G6PD

Front 269

Rate-limiting step of de novo pyrimidine synthesis:

Back 269

Carbamoyl phosphate synthetase II

Front 270

Rate-limiting step of de novo purine synthesis:

Back 270

Glutamine-PRPP amidotransferase

Front 271

Rate-limiting step of Urea cycle

Back 271

Carbamoyl phosphate synthetase I

Front 272

Rate-limiting step of Fatty acid synthesis

Back 272

Acetyl-CoA carboxylase

Front 273

Rate-limiting step of Fatty acid oxidation

Back 273

Carnitine acyltransferase I

Front 274

What's the difference between the actions of biotin and folic acid?

Back 274

Biotin is a cofactor in carboxylation reactions -- it adds CO2

THF is methyl group donor -- it adds CH3

Front 275

What is the difference between the activity of NADH and NADPH?

Back 275

NADH is usually involved in catabolic processes, i.e. Glycolysis and the TCA

NADPH is usually involved in anabolic processes, like steroid and fatty acid synthesis.

Front 276

HMP Shunt:

(1) What does it do?
(2) Describe the most prominent associated pathology.

Back 276

NADPH is made by the HMP shunt, AKA the pentose-5-phosphate pathway.

A small fraction of the Glucose-6P that's made in the first step of glycolysis gets shunted off to this pathway to restore NADP+ to NADPH.

Hint 276

G6PD is the rate-limiting step of the shunt. When it is defective, NADPH deficiency occurs which is minor in most tissues, but not in the erythrocytes, where the shunt is the only source of NADPH.

Result: oxidative/radical damage to RBCs and hemolytic anemia.

Front 277

How do hexokinase and glucokinase differ?
(1) General description
(2) Kinetics

Back 277

Both of these enzymes phosphorylate glucose as part of the first step of glycolysis.

Hexokinase is found in all cells and specializes in operating in a low glucose environment to provide a small amount of glucose for each cell's needs.

Glucokinase is found in the liver, and specializes in working in a hi glucose environment to rapidly phosphorylate lots of glucose, providing glycogen storage for the whole body.

and is inhibited by the presence of glucose 6-P. This allows individual cells to burn only as much glucose as they need.

Glucokinase is found in the liver, and is not; this allows the organ to function as a glycolytic machine for the rest of the body.

Hint 277

Hexokinase has a hi affinity for glucose and a LOW K_m, so it can operate in low glucose environments.

It also has a low V_m, so that regardless of the environment, it doesn't make a lot

Glucokinase has a LOW substrate affinity and a HI K_m, but a very hi V_max, so it works best where there's lots of glucose, and makes stuff for the whole body.

Front 278

(1) What is the rate-limiting step of glycolysis, and (2) how is it regulated?

Back 278

Fructose-6P + ATP --PFK-1--> Fructose-1,6-bisphosphate

Hint 278

As the rate-limiting enzyme, PFK-1 is:

Downregulated by ATP, Citrate

Upregulated by AMP, fructose-2,6-BP

Front 279

Which two steps of glycolysis consume ATP?

Back 279

Glucose --Gluco/Hexokinase--> G-6P

Fructose-6P --PFK-1--> Fructose-1,6-bisphosphate

Front 280

In which two steps does glycolysis produce ATP?

Back 280

#1: yields 2 ATP

1,3-bisphosphoglycerate --phosphoglycerate kinase--> 3-phosphoglycerate

#2: also yields 2 ATP

Phosphoenolpyruvate--Pyruvate kinase--> Pyruvate

Front 281

How do blood sugar levels interact with the rate-limiting step of glycolysis?
(main idea)

Back 281

Background:

2 enzymes act on the substrate of hte rate-limiting reaction: PFK-1 and PFK-2

PFK-1 is responsible for the main substrate.

**In the presence of insulin, PFK-2 is activated.
**PFK2's activity effectively induces PFK-1 (and therefore glycolysis).

Front 282

(1) What is the mechanism by which insulin interacts with the rate of glycolysis?

(2) How about glucagon?

Back 282

Hi blood sugar --> hi insulin --> decreased cAMP --> dephosphorylation of PFK-2 gives it a kinase activity --> increased production of Fructose-2,6-bisphospate --> increased PFK activity --> increased glycolysis.

Hint 282

Low blood sugar --> hi glucagon --> hi cAMP in cells --> PFK-2 is phosphorylated and given a phosphatase activity --> PFK-2 reconverts Fructose-2,6-bisphosphate to fructose-6P --> Fructose-2,6-Bisphosphate levels decrease and PFK-1 is downregulated --> Glycolysis stops.

Front 283

What cofactors are required for pyruvate processing enzymes to function?

Back 283

1. Pyrophosphate (Thamine/TTP)
2. FAD (B2, riboflavin)
3. NAD (B3, niacin)
4. CoA (B5, pantothenate)
5. Lipoic Acid

Hint 283

We treat the enzyme complex responsible for pyruvate processing as though it were a single enzyme, pyruvate dehydrogenase, but obviously it's 3 enzymes. Don't worry about them.

Front 284

Pyruvate Dehydrogenase Deficiency
Etiology & Presentation

Back 284

Causes:
1. Genetic deficiency
2. Cofactor deficiency (i.e. B1 def in alcoholism)

Hint 284

Presentation:

Neurological defects

Front 285

So we've made pyruvate from glucose. What are the 4 things we can do with it?

Back 285

Can be made into:

1. A.Coa for the TCA

2. Lactic acid fermentation

3. Oxaloacetate for either Gluconeogenesis or TCA

4. We can package waste NH3 from the periphery into it, turning it into alanine.
[This is then shipped back to the liver for entry into the Urea Cycle.]

Front 286

What are the products of one turn of the TCA Cycle?

Back 286

For each turn of the cycle, we burn 1 A.CoA. The net output is:

3 NADH
1 FADH2

1 GTP
2 CO2

= 12 ATP

Front 287

What are the enzymes of the TCA cycle?

Back 287

Citrate Is Krebs Starting Substrate For Making Oxaloacetate!!

Citrate
Isocitrate
α-ketoglutarate
Succinyl CoA
Succinate
Fumarate
Malate
Oxaloacetate

Front 288

Where and how is α-ketoglutarate metabolized?

Back 288

α-ketoglutarate is a metabolite of the TCA cycle:

α-KG --α-KG dehydrogenase--> Succinyl CoA

Hint 288

α-ketoglutarate dehydrogenase is interesting because it is just like pyruvate dehydrogenase!

It's a complex of 3 enzymes with the same 5 cofactors: B1, B2, B3, B5, lipoic acid.

Front 289

How does arsenic affect cellular metabolism?

Back 289

Arsenic inhibits lipoic acid from acting as a cofactor in pyruvate dehydrogenase.

The result is neurological problems, lactic acidosis

Front 290

Arsenic poisoning
Presentation:

Back 290

This type of toxicity presents with vomitting, rice-water stools, and garlic breath.

Front 291

How does NADH made in the cytoplasm during glycolysis get restored to NAD+, so glycolysis can continue?

Back 291

NAD+ and NADH CANNOT cross the inner mitochondrial membrane!

Instead, oxaloacetate is converted to a non-TCA substrate -- aspartate -- which crosses through a channel.

Hint 291

1. Oxaloacetate --> Aspartate
2. Aspartate crosses opposite glutamine
3. Aspartate is reconverted to oxaloacetate in the cytoplasm
4. OAA accepts H:- from NADH, becoming malate
5. Malate crosses back into matrix to be reused by TCA

Front 292

List the basic amino acids.

Back 292

Lysine
Arginine
Histidine

(all positively charged in serum)

Front 293

List the acidic amino acids.

Back 293

Aspartate
Glutamate
(both negatively charged in serum)

Front 294

Histone Structure

Back 294

Tetramers of H2A, H2B, H3, and H4 proteins form nucleosome core.

DNA wraps twice around each core.

H1 proteins are not in the nucleosome core, but rather tie the nucleosome beads together.

Front 295

What are the two functions of methylation DNA methylation?

Back 295

(1) Template strand cytosine and adenine residues are methylated, indicating to DNA polymerase which strand is the template for repairs.

(2) Hypermethylation: CpG islands of DNA tend to become hypermethylated, inactivating transcription.
-- CpG islands are associated with the promoters for housekeeping genes that we want to express at low basal rates.

Front 296

Role of acetylation in gene expression.

Back 296

This modification, performed by histone acetyltransferases (HATs), loosens DNA from heterochromatin to euchromatin, increasing transcription.

Front 297

Distinct characteristics of the 5 nucleotides:

Back 297

Cytosine: ammonia group
Uracil: ketone
Thymine: methylated

Adenine: ammonia group
Guanine: ketone + ammonia group

Front 298

What simple pyrimidine modification is frequently responsible for mutations, and how is it repaired?

Back 298

Cytosine deaminates to uracil spontaneously and at a constant rate.
-- C ==> U, resulting in an AT mismatch
-- Repaired by BER

Front 299

How do healthy cells combat skin cancers?

Back 299

This mutation is combated with Nucleotide Excision Repair.

1. In NER, excision endonuclease detects the dimer b/c the shape is distorted, and nicks the damaged strand on both sides of the lesion, perhaps several bases down.

2. Exonucleases remove the fragment

3. DNA Polymerase I replaces the missing fragment, and DNA Ligase ligates it into the strand.

Hint 299

Thymidine dimer formation is the most common cause of skin cancers, i.e.:
-- Melanoma
-- Basal cell carcinoma
-- Squamous cell carcinoma

Front 300

What simple purine modification is responsible for mutations, and how does it happen?

Back 300

Methylation of Guanine by alkylating agents, i.e. cytoxan, results in it's mismatch with thymine.

-- G-->C
-- met-G-->T

Front 301

State Mechanism of de novo purine synthesis. Note requirements for production of both bases.

Back 301

1. Ribose 5-phosphate --PRPP Synthetase--> PRPP

2. PRPP + NH3 from glutamine ---> 5-Phosphoribosylamine -->-->--> Inosine monophosphate (IMP)

3a. IMP + aspartate & GTP ---> AMP
3b. IMP + NAD & ATP --> GMP

Hint 301

**Guanosine requires ATP and NAD+ for its generation.

**Adenosine requires GTP for its generation.

Front 302

What is the committed step of de novo purine synthesis?

Back 302

PRPP + NH3 from glutamate ---> 5-ribosylamine + PPi

Front 303

What is the rate-limiting step in de novo purine synthesis?

Back 303

Ribose-5-phosphate ---PRPP Synthetase--> PRPP

Front 304

What is the major difference between purine and pyrimidine synthesis?

Back 304

In purine synthesis we start with a ribose backbone and build a base to it.
-- *Inosine*

In pyrimidine synthesis we make a temporary base and add the backbone to it, then modify the base.
-- **Orotic Acid**

Front 305

What is the major difference between purine and pyrimidine synthesis?

Back 305

In purine synthesis we start with a ribose backbone and build a base to it.
-- *Inosine*

In pyrimidine synthesis we make a temporary base and add the backbone to it, then modify the base.
-- **Orotic Acid**

Front 306

Hydroxyurea
MoA & Indications

Back 306

Inhibits thymine production by inhibiting ribonucleotide reductase

Hint 306

Indications:

Chemotherapeutic agent used to keep white count low in AML.

Front 307

Hydroxyurea
MoA & Indications

Back 307

Inhibits thymine production by inhibiting ribonucleotide reductase

Hint 307

Indications:

Chemotherapeutic agent used to keep white count low in AML.

Front 308

6-mercaptopurine
MoA and Ind

Back 308

A false purine analogue that both:

(1) inhibits production of real purines via feedback inhibition

(2) gets incorporated into DNA, terminating DNA synthesis.

Hint 308

Maintenance therapy for children with ALL.
Often given as azothioprine, a precursor.

Front 309

6-mercaptopurine
MoA and Ind

Back 309

A false purine analogue that both:

(1) inhibits production of real purines via feedback inhibition

(2) gets incorporated into DNA, terminating DNA synthesis.

Hint 309

Maintenance therapy for children with ALL.
Often given as azothioprine, a precursor.

Front 310

5-fluorouracil
MoA & Ind

Back 310

Tumor cells convert it to a false fdUMP, which irreversibly inhibits thymidylate synthase.

This blocks thymidine synthesis, resulting in a thymidine-less death.

Front 311

Mechanism of Pyrimidine Synthesis:

Back 311

1a. As with purine synthesis, we make PRPP from Ribose-5-phosphate.

1b. CO2 + Gln + ATP ---CPT II---> Carbamoyl Phosphate

2. Carbamoyl Phosphate -->-->--> Orotic Acid

3. Orotic Acid + PRPP ---> UMP

4a. UMP ---> dUMP (or fdUMP in chemo)

4b. UMP ---ribonucleotide reductase---> CTP

5a. dUMP ---Thymidylate synthase + met-THF---> dTMP

Front 312

Causes of orotic aciduria.

Back 312

(1) Inability to convert orotic acid to UMP caused by autosomal recessive deficiency in either:
-- orotic acid phosphoribosyltransferase
-- orotidine 5'-phosphate decarboxylase

Front 313

Presentation of orotic aciduria

Back 313

Symptoms seen in infancy:

1. Increased orotic acid in urine
2. Megaloblastic anemia
3. Failure to thrive

Front 314

Clinical findings in orotic aciduria:

Back 314

Symptoms seen in infancy:

1. Increased orotic acid in urine
2. Megaloblastic anemia
3. Failure to thrive

Front 315

What is the committed step of pyrimidine synthesis?

Back 315

Gln + CO2 + 2ATP ---CPT II---> Carbamoyl phosphate

The production of carbamoyl phosphate is the committed and rate-limiting step of pyrimidine synthesis.

Front 316

2 Purine Breakdown Pathways:

Back 316

(1)
1. AMP ---AMP deaminase---> IMP
2. IMP ---> Inosine
3. Inosine ---> Hypoxanthine
4. Hypoxanthine ---Xanthine oxidase---> Xanthine
5. Xanthine ---Xanthine oxidase---> Uric Acid

(2)
1. AMP ---> Adenosine
2. Adenosine ---Adenosine Deaminase---> Inosine
3, 4, 5: same as above

Front 317

SCID
Path & Presentation:

Back 317

Adenosine deaminase (ADA) deficiency results in:

1) Buildup of ATP b/c we can't break it down. ATP buildup downregulates ribonucleotide reductase, resulting in decreased DNA synthesis.

2) inability to break down adenosine into inosine. Buildup of adenosine is toxic to B and T lymphocytes.

Hint 317

Presentation: Bubble boy

Front 318

Lesch-Nyhan syndrome
Path & Presentation:

Back 318

Path:
Caused by X-linked Recessive deficiency of HGPRT, which converts both hypoxanthine and guanine to IMP.

Results:
(1) Hypoxanthine buildup ---> excess uric acid production
(2) Guanine buildup ---> excess uric acid production.

Hint 318

Presentation:
MR, aggression, self-mutilation, choreoathetosis, hyperuricemia and gout.

Front 319

DNA Polymerase I

Back 319

Prokaryotic only. Degrades RNA primer and fills gaps.

Front 320

DNA Polymerase III

Back 320

*Prokaryotes only*. Elongates leading strand by adding deoxynucleotides until it reaches primer of preceding fragment, then falls off.

Front 321

What pathology results from loss of nonhomologous end joining?

Back 321

Ataxia telangiectasia: disease consisting of cerebellar ataxia, dilation of blood vessels in skin and eyes, and immunodeficiency of T and B cell origin.

Front 322

Which carbon on an incoming nucleotide bears the triphosphate?

Back 322

The 5' carbon bears the triphosphate.

The 3' carbon has the hydroxyl group on which the next nucleotide is attached.

Front 323

Stop and Start Codons:

Back 323

Start: AUG (codes for methionine)

End:
UGA U Go Away
UAA U Are Away
UAG U Are Gone

Front 324

What is the role of promoters and enhancers?

Back 324

Promoters are sequences of DNA upstream from that are bound by RNA Polymerase and other TF's.

Enhancers are DNA sequences that bind TFs to enhance transcription.
*They may be upstream, downstream, or IN an INTRON of the gene they enhance!*

Front 325

What enzyme is responsible for transcribing:

Eukaryotic rRNA?
Eukaryotic mRNA?
Eukaryotic tRNA?

Back 325

rRNA: RNA Polymerase I

mRNA: RNA Polymerase II

tRNA: RNA Polymerase III

Front 326

List and describe the various permutations of RNA, IN ORDER, en route to the mature transcript.

Back 326

1) Heterogenous nuclear RNA (hnNRA)
-- completely unprocessed.
-- if it's destined for translation, it's called pre-mRNA

2) mRNA
-- transcript that's been capped, tailed, and spliced *IN THE NUCLEUS*

Front 327

What is the polyadenylation signal?

Back 327

AAUAA

This RNA sequence signals that for the poly-A tail to be attached here by poly-A polymerase.

Front 328

What is the polyadenylation signal?

Back 328

AAUAAA

This RNA sequence signals that for the poly-A tail to be attached here by poly-A polymerase.

Front 329

Splice mechanism, quick and dirty:

Back 329

1. snRNP's bind primary transcript at splicing sites (marked at either end by GU and AG sequences)

2. snRNP's form a spliceosome, there, and fold the intron into a lariat (loop)

3. Splice!

Hint 329

snRNP's = small nuclear ribonucleoproteins.

Front 330

How does lupus interfere with production of mature mRNA?

Back 330

Patients with lupus often make antibodies to spliceosomal snRNP's, disrupting splicing.

Front 331

How do the presence of glucose and lactose affect gene transcription in e. coli?

Back 331

This sugar binds a repressor protein, interfering with its constitutive binding to the promoter sequence of the lac operon.

Hint 331

The presence of this sugar inhibits the activator of the lac operon, the CAP protein, from binding to the lac operon promoter.

It does so indirectly, by downregulating cAMP presence in the cell, which is necessary for CAP's activating behavior.

Front 332

What sequence is at the 3' end of tRNA, and why does this matter?

Back 332

CCA: found at the 3' end of tRNA. The amino acid binds at this end.

CCA: Can Carry Amino acids

Front 333

What drug interferes with the interaction between amino-acyl tRNA and the 30S ribosomal subunit?

Back 333

Tetracyclines attack these proteins specific to bacteria.

Front 334

List the drugs that bind the 30S subunit of bacterial ribosomes to prevent mRNA translation. How do they do so?

Back 334

1) Aminoglycosides bind 30S ribosomal subunit, preventing initiation.

2) Tetracyclines bind the 30S ribosomal subunit, blocking access of charged tRNA's to the ribosomal subunit.

Hint 334

Aminoglycosides: Streptomycin, Amikacin

Tetracyclines: demeclocycline, doxycycline

Front 335

(1) List the toxins that interfere with protein translation in humans. (2) How do they do so?

Back 335

1. Shiga toxin
2. Shiga-like toxin (made by EHEC)
3. Diphtheria toxin

Hint 335

1. This toxin behaves just like tetracycline but in eukaryotes, preventing the binding of charged tRNA to the ribosomal complex.

2. Almost the same toxin is made by enterohemorrhagic E. coli.

3. This toxin inactivates EF-2, preventing the translocation step of protein translation in eukaryotes; the ribosome cannot move down the transcript.

Front 336

What are the major proteins associated with the major steps of protein translation?

Back 336

1. Initiation: IF's

2. Elongation & Translocation: EF's

3. Termination: RF's (release factors)

Front 337

Distinguish Translocation and Elongation in protein translation.

Back 337

Elongation refers to the new peptide bond that's formed.

Translocation refers to the movement of the ribosome down the mRNA transcript to the next codon (in the 3' direction)

Front 338

Ribosomal binding sites:

Back 338

A site: Activation site, where aminoacyl-tRNA first bind

P: site of Peptide elongation

E: Exit site, site of termination

APE

Front 339

List the drugs that bind the 50S ribosomal subunit.

Back 339

Macrolides bind the 50S subunit, preventing ribosomal translocation and halting protein translation.

Clindamycin does the same thing.

Chloramphenicol binds the 50S subunit, but it prevents *elongation.

Hint 339

Macrolides: erythromycin, azithromycin, etc.

Chloramphenicol and Clinda are synthetic antibiotics, and are in their own classes.

Clindamycin causes C diff
Chloramphenicol is cheap!

Front 340

Biochemical role of Mannose-6-phosphate

Back 340

This sugar is added to lysozomal enzymes while still in the Golgi apparatus, marking them for shipment to the lysozomes.

Front 341

List the main vesicular coating compounds and their corresponding destinations.

Back 341

1. COPI: Retrograde transport from Golgi back to ER

2. COPII: anterograde transport from ER to cis-Golgi

3. Clathrin: transport from trans-Golgi to surface membrane

Front 342

I-cell Disease / Mucolipidosis II
Path & Presentation:

Back 342

Lysozomal storage disorder in which inability to add mannose-6-phosphate to lysozomal enzymes results in their being secreted into the extracellular space.

This lysozomal storage disorder looks like MPS but is characterized by inability to transport many different lysozomal enzymes rather than an inability to make a certain lysozomal enzyme.

Hint 342

Presentation: coarse facial features, clouded corneas, restricted joint movement, hi plasma levels of lysozomal enzymes. Often fatal in childhood.

Front 343

List the 5 drugs that act on microtubules.

Back 343

1. Mebendazole/thiabendazole
(antihelminic)

2. Griseofulvin
(antifungal)

3. Vincristine/vinblastine

4. Paclitaxel
(anti-breast cancer)

5. Colchicine
(anti-gout)

Front 344

Kartagener's Syndrome
Path & Presentation

Back 344

Immotile cilia d/t a dynein arm defect.
(dynein arm

Hint 344

Infertility, sinusitis, bronchiectases

Also associated with situs inversus

Front 345

How do cilia move?

Back 345

Made of microtubules with dynein and kinesin arms attaching each to a neighboring microtubule.

Dynein: walks away from the base of the cilia (retrograde)

Kinesin: walks toward center of cilia (anterograde).

Front 346

Chediak-Higashi syndrome
Path & Presentation

Back 346

Recessive mutation to MAP proteins.

MAP proteins stabilize microtubules, preventing "catastrophe".

Simply put, its a defect in microtubular polymerization that results in decreased organelle and granule transportation, especially in:

Neutrophils
Lymphocytes
Melanocytes

Hint 346

A child presents with:

1. oculocutaneous albinism (white hair, red eyes)

2. frequent pyogenic infections.

Front 347

Describe cilia's biochem.

Back 347

9 + 2 microtubule arrangement

9 microtubule doublets form a circle around a central doublet.

Axonemal Dynein links the peripheral doublets together so they move in concert.

Front 348

Galactosemia
Path & Presentation

Back 348

Most common cause: deficiency of Galactose-1-phosphate-uridyltransferase

Less common and less severe:
Galactokinase deficiency

Hint 348

Pt. presents soon after starting breast-feeding with vomiting, lethargy, and failure to thrive.

Left untreated, will result in eye and liver damage.

Front 349

A formerly healthy infant presents at 8 months old who has been losing previously acquired motor function. Hepatosplenomegaly is noted on exam.

Liver biopsy reveals leukocytes with large, sphingomyeloid intracellular inclusions.

Back 349

Niemann-Pick Disease, a lysozomal storage disorder.

Sphingomyelinase deficiency results in accumulation of sphingomyelin in macrophages.

Sphingomyelin deposition in CNS causes neurologic damage.

Hint 349

Histo:

Foamy macrophages/histiocytes in liver and spleen

Front 350

Pt. is a 1.5 y/o presenting with a Gibbus, corneal clouding, coarse facial features (short, upturned nose, wide, upturned nostrils, macrocephaly), claw-hand deformity, and developmental slowness.

Urinalysis shows hi GAGs.

Dx and Path:

Back 350

Hurler syndrome, AKA MPS I, a lysozomal storage disorder.

Mucopolysaccharidosis in which heparan sulfate and dermatan sulfate accumulate d/t deficiency of alpha-L-iduronidase

Front 351

Tay Sachs
Path:

Back 351

Hexosaminidase A deficiency results in lipid accumulation in neurons.

Front 352

Pt. presents in early adolescence with inability to sweat, heat and cold intolerance, and angiokeratomas.

Back 352

Fabry's disease, an X-linked recessive autosomal storage disorder.

Lysozomal storage disorder in which deficiency of alpha-galactosidase A results in buildup of ceramide trihexoside.

Lysozomal byproducts build up especially in highly vascular tissues, resulting in vasculites.

Hint 352

Late stages can present with renal, heart, and lung problems.

Front 353

What is the process and enzyme responsible for the changes of color that we see in a healing bruise?

Back 353

RBC's die in the bruised region, leaving a great deal of Hb at the site of injury that must be recycled.

Heme oxygenase converts this heme to biliverdin in the first step of this reaction.

Biliverdin is a greenish pigment, and that's what we see in bruises.

Front 354

Why does the adrenal gland produce more epinephrine than norepinephrine?

Back 354

In the final step of its synthesis, epinephrine is converted from norepinephrine by phenylethanolamine-N-methyltransferase (PNMT).

Transcription of PNMT is upregulated by cortisol, which the adrenal gland is bathed in.

Front 355

Mechanism of cataract formation in diabetes:

Back 355

1. Chronic hyperglycemia causes too much glucose to be converted into sorbitol in lens cells.

2. Sorbitol builds up too quickly and cannot be converted into fructose by lens cells' modest levels of sorbitol dehydrogenase.

3. Sorbitol is large and cannot leave the cell unless broken down into fructose. Osmotic swelling results.

4. Swelling leads to degeneration and opacification -- cataracts!

Front 356

What is the difference between an endonuclease and an exonuclease?

Back 356

Exonucleases remove nucleotides from the end of a DNA strand, i.e. when DNA Polymerase III corrects its mistakes during DNA synthesis.

Endonucleases remove nucleotides from the middle of a strand, as in NER.

Front 357

How is the proofreading activity of DNA Polymerase I unique among the other DNA Polymerase enzymes?

Back 357

All three of the DNA-P enzymes have a 3'-5' exonuclease capability

DNA Polymerase III synthesizes DNA from 5' to 3' (of course), and proofreads backwards! (from 3' to 5')

Only DNA Polymerase I has a 5' to 3' exonuclease capability.

It uses this to replace RNA primers and damaged base pairs.

Front 358

Deficiency of what enzyme would result in NADH buildup in anaerobic glycolysis?

Back 358

Pyruvate is converted to lactate by pyruvate dehydrogenase.

Without this reaction, we would not be able to produce lactate, which is necessary for replenishing the NAD+ reserve.

Front 359

What is a Nucleolus made of and what does it do?

Back 359

Nucleoli are bundles of proteins and rDNA (DNA that encodes ribosomes), and rRNA.

Nucleoli the sites of ribosome synthesis, from soup to nuts.

Hint 359

Ribosome synthesis is carried out by RNA Polymerase I.