Usmle Step 1: High Yield

Front 1

How to treat cyanide poisoning?

Back 1

Methemoglobin is the oxidized form of hemoglobin (ferric, Fe3+) which does NOT bind 02 as readily but binds and has high affinity for cyanide.

To treat cyanide poisoning, use NITRITES to oxidize hemoglobin to methemoglobin (which has the high affinity for cyanide) then use THIOSULFATE to bind this cyanide-methemoglobin complex which is renally exrected.

Nitroprusside: IV antihypertensive agent with quick onset of action of 30 seconds. Side effect: cyanide toxicity b/c initially metabolized to release cyanide and NO. Cyanide is then metabolized to thiocyanate and excreted in kidney

Signs of cyanide toxicity:
1. altered mental status
2. lactic acidosis

Treatment: sodium thiosulfate (works by donating additional sulfur to the enzyme that normally metabolizes cyanide to thiocyanate) which can then be excreted.

USMLE: 56 yr old male admitted to ER with severe chest pain. BP 240/130 and HR 100. BB and nitroprusside is started. Several hours later, he seems confused and disoriented. You notice nitroprusside infusion is higher than recommended. Supplying which of the following elements would reverse this patients condtion? Sulfur

Fact:
Cyanide, Rotenone, antimcyin A and carbon monoxide are all electron transport inhibitors of ETC which directly inhibit electron transport causing a decrease in proton gradient and block of ATP synthesis.

Front 2

Muscles used for inspiration and expiration during exercise?

Back 2

InSpiration: external intercostals, Scalene muscles, Sternomastoids

Expiration: rectus abdominis, internal oblique, external oblique, transversus abdominis, internal intercostals

source: pg 504

Front 3

Name the 3 pneumoconioses and which part of lung each affects, pathogenesis?

Back 3

1. COAL MINERS: associated with coal mines. Can result in cor pulmonale, Caplan's syndrome. AFFECTS UPPER LOBES
S/S: exertional dyspnea and nodular intersitial opacities on CXR


2. SILICOSIS: Associated with foundries, sandblasting and mines. Macrophages respond to this and release fibrogenic factors, leading to fibrosis. Thought that this may also disrupt phagolysosomes and impair macrophages and thus INCREASING susceptibility to TB (macrophages cant wall it off).

-AFFECTS UPPER LOBES (The ONLY pneumoconiosis that produces "Egg shell calcification of hilar lymph nodes"-hilar lymphadenopathy and birefringent particles surrounded by fibrous tissue on histologic exam-USMLE!)

3. ASBESTOSIS: associated with shipbuildings, roofing and plumbing. Results in "ivory white" calcified pleural plaques. Asscociated with increased incidence of bronchogenic carcinoma and mesothelioma. AFFECTS LOWER LOBES. (Abestos bodies: golden brown fusiform rods resembling dumbbells, located inside macrophages. Will see Ferruginous bodies (abestos bodies with Prussian blue iron stain) in the lung. Inhaled asbestos fibers are injested by macrophages.
HALLMARK: fibrocalcified parietal pleura plaques over diaphram and posterolateral lung

RECAP:

1. Silicosis INCREASES risk to TB b/c impairs macrophages

2. Asbestosis is the ONLY one which affects LOWER LOBES and consists of golden brown fusiform rods resembling dumbbells, located inside macrophages.

3. All 3 can result in a restrictive lung pattern (decreased all lung volumes. PFT normal or >80%)


Source: pg 511

Front 4

List the 2 types of Adenocarcinoma of lung (peripherally located)?

Back 4

1. Bronchial: develops in sites of prior pulmonary inflammation or injury (most common lung cancer in non smokers and females)

2. Bronchioalveolar (USMLE): grows along airways. Arises from alveolar epithelium composed of tall columnar cells that line alveolar septae without evidence of vascular or stroma invasion. Can present as peripheral mass or LIKE PNEUMONIA-Imaging: pneumonia like consolidation.

S/S of lung cancer: cough, hemoptysis, bronchial obstruction, wheezing, pneumonic "COIN" lesion of xray or noncalcified nodule on CT

Front 5

Physical findings between pleural effusion and pneumonia (lobar)?

Back 5

1. PLEURAL EFFUSION: decreased breath sounds over effusion, dull resonance, DECREASED fremitus

2. Pneumonia (lobar): may have bronchial breath sounds over lesion, dull resonance, INCREASED fremitus

Front 6

Pymalion effect?

Back 6

occurs when a researchers belief in the efficacy of a treatment changes the outcome of that treatment

Front 7

What is it called when subjects in different groups are not treated the same; more attention is paid to treatment group, stimulating greater compliance? (Behavioral Science)

Back 7

Procedure bias

Front 8

Hawthrone effect?

Back 8

occurs when the group being studied changes its behavior due to the fact they know they are being studied

Front 9

What is the formula for relative risk and what does it mean?

Back 9

Relative risk:

relative probability of GETTING a disease in exposed group compared to unexposed groups. (for chohort studies-looks in future/prospective)

RR= TP/TP+FP divided by FN/FN+TN

vs

Odds ratio:

Odds of HAVING a disease in exposed group divided by odds of having disease in unexposed group. (for case control studies-looks in past/retrospective)

Front 10

Absolute risk reduction? How do you calculate number needed to treat?

Back 10

Absolute risk reduction:


The reduction in risk associated with a treatment as compared to placebo.



Number needed to treat: 1/abosulte risk reduction

Front 11

Standard error of the mean?

Back 11

Standard error of the mean= Standard deviation/square root of sample size

**Increase sample size=decrease standard error**

1 STD=68%

2 STD= 95%

3 STD=99.7%

Front 12

What is difference between type 1 error (alpha) and type 2 error (beta)?

Back 12

Type 1 error (alpha):

Stating there IS AN EFFECT or difference when none exists (aka to mistakenly accept the expermental hypothesis and reject the null hypothesis--rejecting your null hypothesis)

AKA you saw a difference that DID NOT EXIST (convicting a innoncent man)


Type 2 error (beta)

Stating there IS NOT AN EFFECT or difference when one exists (fail to reject the null hypothesis when in fact null hypothesis is actually false)

AKA you did not see a difference that does exist (setting a guilty man free)


POWER= 1-beta

Front 13

How do you calculate confidence interval? Including sample mean, size and Z number?

Back 13

CI= sample mean +/- Z (sample deviation/square root of sample size)



Ex:

100 patients scored 110 average on IQ test with standard deviation of 20. What is the best estimate of the 95% confidence interval?

CI= 110+2* (20/10)= 110+/- 4====106-114



*(b/c 95%=1.96)

Front 14

Explain what things decrease incidence and prevalance?

Back 14

What things DECREASE incidence (NEW cases in a population/total population at risk-does NOT include people currently with the disease or previosuly positive for it)

1. Primary disease prevention: New vaccines, condoms, etc (HPV vaccine)
2. Decreased risk factors

Things that DO NOT affect incidence?

1. Early detection (makes for more effective treatment thou)
2. Access to hospital services (this reduces prevalence)


What things DECREASE prevalance (total cases in population/total population)?

1. Access to hospitals=more treatments (does NOT affect incidence thou)
2. New vaccines
3. Increased death from disease
4 Decreased risk factors
5. Increased recovery

What things INCREASE prevalence?

1. Increased survival
2. Improved quality of care-this scenario is typical for USMLE!

**Primary disease prevention (HPV vaccines) will result in decreased incidence and therefore decreased mortality**-Kaplan

As the prevalance of a disease increases, the positive predictive value increases. Similarly, as the prevalance of disease decreases, PPV decreases and NPV increases-KAPLAN! Sensitivity and Specificity DO NOT change with prevalance--USMLE!

Front 15

How do you calculate number needed to treat?

Back 15

NNT= 1/absolute risk reduction

ARR= event rate in placebo group-event rate in treatment group


event rate in treatment: TP/total

event rate in placebo: FP/total

Front 16

Hartnup disease?

Back 16

AR disease characterized by defective neutral amino acid transporter on renal and instestinal epithelial cells.

Causes tryptophan excretion in urine and decrease absorption from gut

Leads to PELLAGRA-def of niacin (decrease trptophan=decrease niacin (requires B6)=pellagra)

Pellagra:
1. Dermatitis (episodic erythematous and pruitic skin lesions)
2. Dementia
3. Diarrhea (loose stools)

Causes def of niacin:

1. Isonasid for treatment of TB (b/c decreases B6 and you need B6 for conversion of tryptophan to niacin)
2. Malignant carcinoid syndrome (causes increase in tryptophan metabolism)
3. Hartnup disease (cant absorb tryptophan=no niacin)

Front 17

Maks SnRNPs (small nuclear ribsomal proteins)?

Back 17

RNA polymerase II makes mRNA and SnRNPS.

This enzyme is inhibitd by alpha amantin (found in mushrooms)-causes liver failure if injested

Eukaroytes Transcription (DNA-->RNA)
RNA Poly 1: rRNA (occurs in nucloeus)
RNA Poly II: mRNA and SnRNPs
RNA Poly III: tRNA

*No proofreeading

Prokaryotic Transcription (DNA-->RNA)
1 RNA Poly (multisubunit)-makes all 3 kinds of RNA

Front 18

Excessive injestion of avidin (found in egg whites) leads to what?

Back 18

Biotin defiency (also caused by excessive antibotic use)

Biotin: serves as CO2 carrier for carboxylase enzymes:

1. Pyruvate to OAA in gluoconeogenesis (leads to increased pyruvate-->conversion to lactate-->metabolic acidosis
2. Acetyl Coa carboxylse to malonyl Coa (fatty acid synthesis rate limiting step which occurs in cytoplasm)
3. Propionyl-coa to methymalyonyl coa (leads to increased propionyl and increased fatty acids)

Front 19

Name the 4 reactions that require vitamin B1 thiamine?

Back 19

1. Pyruvate dehydrogenase (glycosis--cytoplasm)
2. A-ketogluturate dehydrogenase (TCA-mitochondria)
3. Transketolase (HMP-cytoplasm)
4. Branched chain AA dehydrogenase--> maple urine syrup disease)


Requires 5 enzymes
1. PDH
2. A-ketogluturate (TCA)
3. A-keto dehydrogenase (Branched chain amino acid)

5 enzymes
1. Riboflavin (Vitamin B2) for FAD+
2. Niacin (Vitamin B3) for NAD+
3. Lipoic acid (inhibited by arsenic---> vomiting, rice water stools, garlic breath)
4. Coenzyme A
5. Thiamine (vitamin b1)

Front 20

Cortisol upregulates what processes?

Back 20

Cortisol upregulates what processes?

1. Increases gluconeogenesis (while epi and glucagon increase glycogenolysis)
2. Increases PNMT enzyme in adrenal (adrenal: 80% epi, 20% nor-epi--most of nor epi and dopamine created by PNS and SNS) which upregulates conversion from nor-epi to ep and the epi maintains blood pressure (alpha 1 receptors)


Cortisol decreases:
1. bone formation
2. inflammation
3. immune fxn

Front 21

What are the 3 post translational modifications?

Back 21

1. Trimming: removal of N or C terminal propeptides from zymogens to generate mature proteins

2. Covalent alterations: Phosphorylation, glycosylation and hydroxylation

3. Proteasomal degradation: Attachment of ubiquitin to defective proteins to tag them for breakdown

Front 22

labile and stable cells? Give examples?

Back 22

1 labile: never go to GO (divide rapidly with a short G1)
-Regenerate from stem cells

Ex: 1. bone marrow
2. gut
3. epithelium
4. skin and hair follicles

2. Stable (quiescent): enter G1 from GO when stimulated

1. Hepatocytes
2. Lymphocytes

Front 23

COPI vs COPII? What are the functions of the golgi?

Back 23

Normally proteins made in RER exit and head to golgi. From golgi, the proteins head to:

1. plasma membrane
2. lysosomes
3. Secretory vesicles

COP1: retrograde from golgi back to ER

COPII: anterograde from RER to cis golgi (A has 2 in it like fetus has 2 umbilical arteries)

Clathrin: trans-golgi--->lysosomes, plasma membrane--->endosomes (receptor mediated endocytosis)



Functions of the golgi apparatus

1. Distrubution center of proteins and lipids from ER to
A. Plasma membrane
B. Lysosomes
C. Secretory vesicles

2. Modifies N-oligosaccharides on asparagine (RER initially did N-linked oligosaccharide additon to may proteins)

3. Adds O oligosaccharides to serine and threonine residues

4. Adds mannose 6 phosphate to specific proteins targed to lysosomes

5. Proteoglycan assebly from core proteins

6. Sulfation of sugars in proteoglycans and of selected tyrosine on proteins

Kaplan:

An investigator is conducting a study on albumin synthesis. She wants to characterize the carbohydrate chains that will be eventually transferred to the protein component of albumin. Which of the following molecules functions as a substrate for the synthesis of these carbohydrate chains? Dolichol

In the synthesis of glycoproteins (most proteins with some attached sugars), the very long, phosphated lipid, DOLICHOL serves as the substrate for forming the branched carbohydrate trees that are then transferrd to proteins.
-This process occurs on the RER (N-linked oligosaccharide additon to many proteins) and the resulting glycoproteins are then transferred to the golgi complex for further processing before:
1. incorporation into plasma membrane
2. Transfer to lysosomes
3. Release as secreted proteins

RECAP:
-N-linked carbohydrate chains that will be transferrd to the protein component of albumin are assembled in the RER and attached to dolichol phosphate
-They are subsequently transferred to the nitrogen or asparagine to form glycoproteins that are secreted (albumin), retained in plasma membrane (insulin receptor) or targeted to lysosomes (hexosaminidase A)

Front 24

Vimentin is a immunohistochemical stain for what? Desmin?

Back 24

1. Vimentin: connective tissue/mesenchymal tissue (Sarcomas)

2. Desmin: muscle-Rhabdomyosarcoma (neoplasm of striated skeletal muscle----one of the most neoplasms of childhood often shows some skeletal MUSCLE differention)-Kaplan!)
-Most common site is head and neck region, followed by genitourinary region

3. Cytokeratin: epithelial cells-USMLE!

4. GFAP: neoplasms of glial origin (neuroglia,GBM, astryocytomas, ependymomas, oligodendrogliomas)

5. Neurofilaments: neurons (Neuroblastomas, pheochromocytomas, Merkel cell tumors, Paragangliomas)

6. Synaptophysin: CNS tumors of neuronal origin (A transmembrane glycoprotein found in presynaptic vesicles of neurons, neuroectodermal and neuroendocrine cells. These are rare and compose less than 1% of CNS tumors-USMLE!

7. Chromogranin A and neuron specific enolase-markers for neuroendocrine tumors

Front 25

Used to profile gene expression level of thousands of genes simulatenously to study certain diseases and treatments?

Back 25

Microarrays:

thousands of nucleic acid sequences are arranged in grids on glass or silicon. DNA or RNA probes are hydridized to the chip, and a scanner detects the relative amounts of complementary binding.

Able to detect single nucleotide polymorphisms (SNPs) for a variety of applications including genotyping, foresenic analysis (FINGER PRINTING AT CRIME SCENE), predispostion to disease, cancer mutations, etc.

Front 26

Used for specific localization of genes and direct visulization of anomalies (microdeletions) at molecular level (when deletion is too small to be visulized by karyotype)?

Back 26

FISH (Fluorescence in situ hybridization)

Fluroescence= gene is present
No fluroescence= gene has been deleted.

VS

Microarrays:

thousands of nucleic acid sequences are arranged in grids on glass or silicon. DNA or RNA probes are hydridized to the chip, and a scanner detects the relative amounts of complementary binding.

Able to detect single nucleotide polymorphisms (SNPs) for a variety of applications including genotyping, foresenic analysis (FINGER PRINTING AT CRIME SCENE), predispostion to disease, cancer mutations, etc.

Front 27

1. loss of heterozygosity?

2. locus heterogeneity?

3. Pleiotrophy?

4. Dominant negative mutation?

5. Germ line mosaic?

6. Uniambiguous?

7. Degenerate/Redundant?

8. Genetic linkage?

9. Penetrance?

10. Polyploidy?

11. Allelic heterogenity?

Back 27

1. loss of heterozygosity:-USMLEsim!

If a pt inherits or develops a mutation in a tumor supressor gene, the complementary allele must be deleted/mutated before cancer develops. This is NOT true of oncogenes (Ex: retinoblastoma)

2. locus heterogeneity:

mutations at different loci can produce same phenotype (EX: Marfans syndrome, MEN 2B and homocystinuria--->all produce marfanoid habitus)

3. Pleiotropy: 1 mutation leads to multiple phenotypic abnormalities (EX: A mutation in 1 gene for Hunningtons disease causes triad of movement disorder (chorea), behavioral abnormalities (agressivness, apathy, depression) and dementia)

4. Dominant negative mutation:
-Exerts a dominant effect
-A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning
-Ex: mutation of Tx factor in its allosteric site. Nonfunctioning mutant can still bind DNA, preventing wild type Tx factor from binding

5. Germ line mosaic-NMBE!, USMLEsimX2!
-Produce disease that is not carried by parents somatic cells

6. Uniambiguous
-Each codon specifies only 1 amino acid

7. Degenerate/Redundant
-More than 1 codon may code for the same amino acid

8. Genetic linkage
-describes alleles that tend to be inherited jointly, usually b/c they are located near one another on same strand of DNA

9. Penetrance
-proportion of individuals with a given genotype that express the associated phenotype

10. Polyploidy-occurs when more than 2 complete sets of homogous chromosomes exist within a cell or organism. Ex: 69XXX or 69XXY in partial hydatiform mole

11. Allelic heterogenity
-Different mutations in the SAME genetic locus cause similar phenotypes
-More than one type of mutation is possible in a given gene and different mutations can cause alterations in or loss of protein function resulting in disease

Ex: Both Duchenne and Beckers muscular dystrophy result from mutations in dystropin gene (which resides on short arm of X chromosome) but they present differently b/c the mutation causing duchenne dystrophy causes complete loss of dystrophin function while the mutation causing Beckers results in a structurally abnormal but partially functional dystrophon gene product

Front 28

heteroplasmy? Unipaternal disomy?

Back 28

heteroplasmy:

presence of both normal and mutated mitochondrial DNA, resulting in variable expression in mitochondrial inherited dieases (Mitochondrial inheritances-Transmitted ONLY through mother--distingush from AD where you will see transmission from father in some generations whereas in mitochondrial, you will only see coming from mother: 1. Lebers herediatry optic neuropathy, 2. Myoclonic epilepsy with ragged red fibers (MERRF), 3. Mitochondrial encephalopahthy with stroke like epispodes and lactic acidosis (MELAS)

***Blotchy red muscle fibers on Gomori trichome stain are characteristic of mitochondrial myopathies***

Unipaternal disomy:

offspring recieves 2 copies of chromosome from 1 parent and no copies from other (EX: Complete hydatiform mole)

Front 29

Features of Von Recklinghausen?

Back 29

NF-1 (aka Von Recklinghausens disease)-chromosome 17, autosomal dominant

1. Cafe-au-lait spots

2. Neurofibromas- benign rubbery cutaneous tumors on skin. Rarely undergo malignant transformation
-tumors of Schwann cells which are dervived from neural crest-USMLE!
- Rubbery texture that exhibit pathognomonic "buttonholing"-these buttonhole down through the skin with gentle pressure

3. Lisch nodules-pigmented iris harartomas-can see on slit lamp exam

4. Skeletal disorders-scoliosis

5. Optic pathway gliomas

Front 30

Name 4 trinucleotide repeat expansion diseases?

Back 30

1. Huntingtons disease (CAG on chromosome 4)-depression, dementia, choreiform movements. ENLARGEMENT OF LATERAL VENTRICLES-Kaplan!..........The CAG repeats in the abnormal HD gene rapidly increase during spermatogenesis. Thus, pts who recieve an abnormal gene from their fathers tend to develop the disease earlier in life. (the number of trinucleotide repeats on HD gene remains the same during maternal transmission)

Kaplan
-43 yr old man presented with 6 month history of progressive memory loss and personality changes. His wife says that his brother has similar symptoms. PE shows abnormal writhing movements of limbs and hyperreactive patellar reflexes. Causes: expanded trinucleotide tandem repeat


2. Myotonic dystrophy (CTG)-abnormal slow relaxation of muscles, weakness and gait disturbances, cataracts, frontal baldness and gonadal atrophy, atrophy of type I fibers-SIR-USMLE!

3. Fragile X syndrome (CGG)-enlarged testes, long face/large jaw, large ears, mitral valve prolapse
-Increased repeats lead to familial mental retardation gene-1 (FMR1) inactivation by hypermethylation-USME-normally it is required for normal neural development. Fragile X is NOT associated with increased chromosomal instability or breakage!!!!!!!! Named b/c when lymphocytes from affected individuals are cultured in a folate and thymidine depleted medium, the resulting karyotype is analyzed and the region of x chromosome appears constriced and thin/fragile. Increased chromosomal instability seen in xeroderma pigmentosum, ataxia telangiectasia, fanconi anemia, blooms syndrome)

4. Friedrichs ataxia (GAA)-dysfuntion in mitochondrial-->staggering gait, nystagmus, hypertrophic cardiomyopathy-USMLE! (cause of death along with bulbar dysfunction-unable to protect airway), kyphoscolosis (presents in childhood with this)

-The dorsal root ganglia degenerate, causing trans-synaptic degeneration in the ipsilateral gracile and cuneate nuclei

*All exhibit anticipation (disease severity increase and age of onset decrease in successive generations)

Front 31

Functions of vitamin C? Def leads to?

Back 31

Functions

1. antioxidant
2. Faciliates iron absorption by keeping iron in Fe2+ state (sometimes given to pts with iron defieincy anemia to help with/improve oral absorption)
3. Hydroxylation of proline and lysine in collagen synthesis
4. For dopamine b-hydroxylase (converts dopamine to NE)

Def leads to:

1. Scurvy-swollen gums, bruising, hemarthrosis (bleeding into joints), anemia, poor wound healing, weakend immune response.

Front 32

Rate limiting step of? TCA? Gluconeogenesis? Fatty acid synthesis?

Back 32

1. TCA: Isocitrate dehydrogenase
2. Gluconeogenesis: fructose 1, 6 bisphosphatase
3. Fatty acid synthesis: Acety-CoA carboxylase (ACC)

Front 33

Increase ETC membrane permeability causing a decrease proton gradient and increase O2 consumption. ATP synthesis stops, but the electron transport continues and produces heat?

Back 33

Uncoupling agents:

1. 2, 4-DNP
2. ASA (fevers often occur after ASA overdose)
3. Thermogenin in brown fat (USMLE)


Oligomyin:

ATPase inhibitor
-Directly inhibits mitochondrial ATPase causing increase in protein gradient. No ATP is produced b/c electron transport stops

Front 34

Leads to hemolytic anemia in G6PD pts?

Back 34

1. Oxidizing agents:

A. fava beans
B. sulfonamides
C. primaquine
D. Anti-TB drugs
E. Dapsone-USMLE!
2. Infection
-Can ppt hemolysis (free radicals generated via inflammatory response can diffuse into RBCs and cause oxidative damage)

Findings:

1. Heinz bodies: oxidized hemoglobin precipitated within RBCs
2. Bite cells: result from phagocytoic removal of Heinz bodies by macrophages

Front 35

Cells that lack sorbitol dehydrogenase have increased risk of what?

Back 35

Excess GLUCOSE---aldose reductase--->SORBITOL--sorbitol dehydrogenase--->FRUCTOSE (USMLE)

Tissues lacking sorbitol dehydrogenase (only have aldose reductase):

1. Schwann cells--->peripheral neuropathy
2. Lens--->cataracts
3. Retina-->retinopathy
4. Kindeys

*These cells will have INCREASED sorbitol (causes osmotic damage)


*Liver, ovaries, seminal vesicles have both enzymes

Front 36

Fabrys disease? S/S? Enzyme deficient?

Back 36

Fabrys disease (along with Hunters syndrome only ones with X-linked recessive inheritance!!-USMLE)


S/S: peripheral neuropathy of hands/feet (episodic burning pain of hands, feet and proximal extremeties precipatated by exercise, fatigue, fever called acroparesthesia), angiokeratomas (small, punctate and dark red to blue-black, dont blanch with pressure and increase in size and number with age), cardiovascular/renal disease (may have elevated BUN/CREAT). Without enzyme replacement, progressive renal insuffiency occurs leading to renal failure and death-USMLE!


Deficient enzyme: a-galactosidase A which leads to accumulation of ceramide trihexoside

USMLE: Pt presented for evaluation of skin lesions (angiokeratomas) on his lower abdomen. A sample of his fibroblasts is obtained and found to fail to metabolize ceramide trihexoside. The pt is greatest risk for developing? renal failure

Front 37

Gauchers disease?

Back 37

Gauchers disease (most common lysosomal disease):


Hepatospenomegaly, aseptic necrosis of femur bone crises and macrophages that look like crumpled tissue paper?


1. Gauchers cells (macrophages that look like crumpled tissue paper
2. Only lysosomal storage disease that spares brain. Only affects liver


Enzyme deficient: B-glucocerebrosidase which results in accumulation of glucocerebroside

Front 38

How do you distinguish between Niemann Picks disease and Tay Sachs (both AR lysosomal storage diseases)?

Back 38

Niemann-Pick (AR)

1. Progessive neurodegeneration-->motor neuropathy-->areflexia and hypotonia
2. cherry red spot on macula
3. foam cells
4. hepatosplenomegaly

Enzyme deficient: Sphinogomyelinase which results in accumulation of Sphinogmyelin

KAPLAN: 15 month old boy with history of mental retardation, failure to thrive and progessive neurologic deterioration is brought for exam. PE shows hepatospenomegaly and funduscopic show retinal pallor sparing (cherry red spot) in left eye.

VS

Tay-Sachs

1. Progresive neurodeneration
2. Developmental delay
3. Cherry red spot on macula
4. LYSOSOMES WITH ONION SKIN
4. NO HEPATOSPENOMEGALY (vs Niemann-Pick)

Enzyme defiecient: Hexosaminidase A which results in accumulation of GM2 ganglioside in neurons (ballooned neurons)-NMBE!

Front 39

Hunters vs Hurlers disease? Enzyme deficient?

Back 39

Hurlers syndrome (A mucopolysaccharidoses)


1. Developmental delay
2. gargoylism
3. aiway obstruction
4. corneal clouding

Enzyme deficient: a-L-iduronidase which leads to accumulation of heparan sulfate and dermatan sulfate

VS

Hunters syndrome:


1. Mild Hurlers
2. Agressive behavior
3. NO corneal clouding

Enzyme deficient: Iduronate sulfatase which leads to acucmulation of heparan sulfate and dermatan sulfate

*The ONLY X-linked recessive (along with Fabrys disease: peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease which has deficient A-GALACTOSIDASE enzyme which leads to accumulation of CERAMIDE TRIHEXOSIDE)

NBME: 18 month old with MR, coarse facial features and hepatosplenomegaly, joint stifness, increased dermatan sulfate and heparan sulfate

Front 40

The umbilical arteries arise from the internal iliac arteries in utero. What will they become once they obliterate? What will umbilical vein become?

Back 40

1. Umbilical arteries--->Medial umbilical ligaments

vs

MediaN umbilical ligamnet=remnant of urachus (aka allaNtois)- a structure that connected bladder to umbilicus

Failure of urachus to obliterate
1. Patent UrachUs=Urine discharge from umbilicus
2. Vesicourachal diverticulum-outpouching of bladder

If you get mixed up, think the bladder (median) is more in middle than medial (umbilical arteries which come off lateral from internal iliac)



2. Umbilical vein--->ligamentum teres (connects liver to anterior abd wall and divides the anatomic left and right lobes of liver. Can be seen on CT as a dark structure b/c contains some fat)

Front 41

Name the embryonic structure that it came from?

1. Ascending aorta and pulmonary trunk?

2. Right ventricle and smooth parts (outflow tracts) of left and right ventricle?

3. Portion of left ventricle?

4. Trabeculated left and right atrium?

5. Coronary sinus?

6. Smooth part of right atrium?

7. SVC?

Back 41

1. Truncus arteriosus

2. Bulbus cordis

3. Primitive ventricle

4. Primitive atria

5. Left horn of sinus venosus (SV)

6. Right horn of sinus venosus (SV)-KAPLAN!

7. Right common cardinal vein and right anterior cardial vein


RECAP:

Smooth part of atrium: sinus venosus

Trabeculated part of atrium: primitive atrium

Front 42

Answer the hem/onc question?

1. Causes of target cells?

2. Cause of basophilic stippling?

3. Name 4 histologic features of benign lymph nodes?

4. Causes of aplastic anemia?

5. Aklyating agents that cross BBB and can be used for brain tumors such as GBM?

Back 42

1. Target cells: HALT

H: Hbc disease
A: asplenia
L: liver disease
T: thalassemia

The hunter said "HALT" to his target

Target cells
-red cells with a peripherally dense rim of hemoglobin enclosing a zone of pallor, often with a darker central punctum.
-They appear as a result of increase in area of red cell membrane and or decrease in hemoglobin.

Kaplan:

Examination of peripheral smear from a pt with HCT of 30% shows large numbers of target cells. The pt will most likley further show? abnormal hemoglobin synthesis (read: thalessemia)

2. Basophilic stippling: Baste the ox TAIL

Thalassemia
Anemia of chronic disease
Iron defieincy
Lead poisoning (inhibits rRNA degradation causes basophilic stippling from the aggregation of ribosomes)

*These are blue ribosomal precipitates
*Reticulocytes are also have bluish cytoplasm and reticular precipatates of residual ribosomal RNA-USMLE!
-Slightly larger and bluer than a mature RBC
-Lacks a nucleus but retains a basophillic reticular network of residual rRNA

3.
A. Multiple large germinal centers
B. Recognizable light and dark zones
C. Frequent mitoses
D. Tingle body macrophages: macrophages containing debris from ingested lymphocytes

*Remember lymph nodes would be tender!!

4. Failure or destruction of myeloid stem cells due to:

A. Radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites)
B. Viral agents (parovirus b19, EBV, HIV, HCV)
C. Fanconi anemia (inherited defect in DNA repair)
D. Idiopathic (immune mediated, primary stem cell defect)-may follow acute hepatitis!!!

Bone marrow: hypocellular with fatty infiltrate-USMLE!


5. Nitrosoureas
A. Carmustine
B. Lomustine
C. Semustine
D. Streptozocin

*Require bioactivation
*Side effects: CNS toxicity (dizziness and ataxia)

Front 43

What is the difference between malformation and deformation?

Between agenesis and aplasia?

Back 43

Malformation: INTRINSIC distruption which occurs during embyronic period (weeks 3-8)
EX: Holoprosencephaly-results form failure of forebrain cleavage into cerebral hemispheres which normally occurs during 5th week of development. Associated with trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) or fetal alcohol syndrome. A primary abnormality in a development process-USMLE! (Other examples: congenital heart disease, anencephaly, polydactyl, syndactyl)
VS

Deformation: EXTRINSIC disruption which occurs AFTER embryonic period (>8 weeks)
EX: Uterine constraint on a fetus in breech position can cause congenital dislocation of the hip or clubbed feet

Agenesis: Absent organ due to ABSENT primordial tissue

VS

Aplasia: Absent organ with primordial tissue PRESENT

Disruption: secondary destruction of a previosuly well formed tissue or organ. EX: Amniotic band syndrome

Front 44

Explain atrial septum formation?

Back 44

1. Endocardial cushions (which require migration on neural crest cells) grow upward and close the canal between atria and ventricles (AV canal). This endocardial cushion also helps form parts of membranous ventricular septum.

2. A membrane called SEPTUM PRIMUM grows down toward endocardial cushions but leaves a small hole called FORAMEN PRIMIUM aka OSTIUM PRIMUM.
-Failure of this to close occurs when the septum primum dosent go all the way down towards endocardial cushion and leaves a hole.

3. Another hole in top of SEPTUM PRIMUM is formed and called FORAMEN SECUNDUM-allows right to left shift of blood as spetum secundum begins to grow

4. A membrane comes down called the SEPTUM SECUNDUM and forms FORAMEN OVALE

5. Foramen ovale usually closes after birth b/c increase LA pressure

Front 45

Difference between gastroshisis and omphalocele?

Back 45

Gastroshisis: failure of LATERAL FOLDS to completely close and fuse.
-Extrusion of abdominal contents through abdominal folds that are NOT covered by periotenum
-INCREASED AFP

Omphalocele: persistence of herniation of abdominal contents into umbilical cord but COVERED by periotoneum
-Midgut herniates through umbilical ring during 6th week and returns to abdominal cavity while rotating around SMA in 10th week

Front 46

1. What type of amyloid may be depositied in a pt with chronic inflammation such as 10 years of Rheumatoid Arhtirits?

2. What type of amyloid would be present in a pt with type II DM?

3. What type of amyloid would be present in a pt with medullary carcinoma of thyroid?

Back 46

1. Secondary amyloidosis leads to AA amyloid protein (derived from serum amyloid associated protein-chronic inflammatory diease)

-Pt with 12 yr history of RA presented with SOB on exertion and bilateral rales. XRAY showed cardiomegaly. Micro showed infilfration of muscle with homogenous pink material.


2. Amylin amyloid derived from AE protein (AE=Endocrine)

3. A-CAL dervived from calcitonin (A-CAL=CALcitonin)

*Amyloid has apple-green birefringence on congo red stain under polarized red light*

Front 47

Tuberous sclerosis (autosomal dominant)? Findings?

Back 47

1. facial lesions (adenoma sebaceum)
2. hypopigmented "ash leaf spots" on skin
3. Cortical (brain) and retinal hamartomas
4. Seizures
5. Mental retardation
6. Renal cysts
7. Renal angiomyolipomas (benign tumor composed of blood vessels, muscle and fat-can be diagnosed with abdominal CT b/c density of fat is less than water. -USMLE!!
8. Cardiac rhabdomyomas!!!!-Cardiac tumor in kids (vs Atrial myoxoma in adults)-can present with valvular obstruction and arrythmias
9. Subependymal giant cell astrocytoma: can grow and lead to increased size of ventricles. Family member may have similar findings b/c Autosomal dominant-NBME!!)

Front 48

Name the paraneoplastic cells found in?

1. Renal cell carcinoma

2. Small cell carcinoma

3. Hepatocellular carcinoma?

Back 48

1. Ectopic EPO, ACTH, PTH, Prolactin


2. ACTH, ADH, antibodies to presynaptic calcium channel (Lambert Eaton)

3. Epo

Front 49

What conditions will you see Psammoma bodies (dystrophic calcification)?

Back 49

1. Papillary adenocarcinoma of thyroid

2. Serous papillary cystadenocarcinoma of ovary

3. Meningioma

4. Malignant mesthelioma

Front 50

Explain phase I and phase II metabolism?

Back 50

Phase 1: (ROH)-Reduction, oxidation, hydroylsis
-usually yields polar, water soluble metabolites (often still active)
-Cytochrome p450

Phase II: (GAS)-Glucuronidation, acetylation, sulfation
-Usually yields very polar, INACTIVE metabolies (renally excreted)
-Conjugation

*Geriatrics loose phase I first

Front 51

What is unique about S.Pneumoniae, H.Influenzae and Neisseria and their bacterial virulence factors?

Back 51

All have IgA protease and exhibit competence

IgA protease: enzyme that cleaves IgA and allows attacthment to respiratory mucosa. Destroys the IgA antibody that would normally prevent attachment and pentration of the bacteria (USMLE)

Competence-AKA transformation: can take up DNA from the environment. If you see any question about DNA transfer and one of these organisms, its chromosomal fragment uptake from enviroment/media.

Front 52

1. Name the live attenuated vaccines?

2. Name the killed vaccines?

3. Name the recombinant vaccines

Back 52

1. Live:
A. Small pox
B. Yellow fever
C. Chickenpox (VZV)
D. Sabin polo virus
E. MMR
F. Rotavirus
7. Influenza (intra nasal)

*Induces humoral and cell mediated immunity and NO booster needed but dangerous to give to immunocomprised or to their close contacts. Promotes more prolonged synthesis and secretion of mucosal IgA than killed vaccine. This increase in mucosal IgA offers immune protection at the normal site of viral entry. USMLE!

2. Killed:

A. Rabies
B. Influenza (shot)
C. Salk Poli (salK=Killed)
D. HAV

*Induces ONLY humoral immunity

3. Recombinant:

A. HBV
B. HPV


ACTIVE VS PASSIVE IMMUNITY

1. Active: Kaplan!
-give pt the shot and they make their own antibodies
-Induced after long exposure to foregin antigens
-Slow onset
-Long lasting protection (memory)
-Ex: DTap vaccine

2. Passive
-Give pt preformed antibodies from another host (Botulism toxin, HBV, Tetanus, Rabies)
- Rapid onset
-Short life span of antibodies (half life-3 weeks)
-Example: IgA in breast milk

Front 53

Micro Quick Recap bacterial:

1. All bacteria have polysaccharide capsules (protects against phagocytosis) except?

2. Name the gram positive rods (bacillus)? Gram negative rods ("coccobacillary")?

3. Why cant you gram stain Chlamydia?

4. What is the stain for acid fast organisms? B. Pertussis? Cryptococcus neoformans?

5. Gram positive rod with metachromatic (blue and red) granules that grows on cysteine-tellurite agar?

6. What 5 genes are encoded in a lysogenic (speciliazed transduction) bacteriophage?

Back 53

1. Bacillus anthracis (contains D-glutamate capsule)-USMLE!

2. Gram + Rods
A. Clostridrum
B. Cornebacterium (Diphteria)
C. Bacillus
D. Listeria (monocytogenes)
E. Mycobacterium (acid fast)

Gram - Rods
A. Haemophilius influenza
B. Pasteurella (animal bites)
C. Brucella (brucellosis)
D. Bordetella Petussis

3. Its an intracellular parasite and lacks MURAMIC ACID (one of the components in peptidoglycan cell wall) in cell wall. Diagnose by cytoplasmic inclusions seen on Giemsa or fluroescent antibody stained smear.

Has a cell wall but lacks peptidogylcan. It produces PBPs (penicillin binding proteins) and also has genes for peptidoglycan synthesis however, peptidoglycan has not been found within the cell wall of this organism. This is called chlamydial anomaly.

Both C. Trachomatis and U. urealyticum (another cause of nongonococcal urethritis) lack peptidoglycan within the cell wall (UU lacks a cell wall all together) so you CANT use antibotics targeting cell wall synthesis or cell wall stability b/c they wont be effective. You need to use antiribosomal agents like macrolides (Azithromycin) or tetracyclines (doxcycline)-USMLE!


4.
A. Ziehl-Neelson

B. Pertussis: Bordet-Gengou (potato) agar (The pertussis toxin causes increase in lymphocytes (lymphocytosis) and alters hormonal activity with cAMP and increases insulin secretion=HYPOGLYCEMIA-Kaplan!!)-Treatment: erythomycin.

C. Mucicarmine stain (USMLE) and india ink.
-Cryptococcus neoformans-from pigeons and affects immunocompromised pts (kidney transplant pts, etc) and is transmitted by resp route. May cause pulmonary disease/pneumonia like symptoms, meningitis. It is the only pathogenic fungus that has a polysaccharide capsule. The capsule appears red on mucicarmine stain and clear unstained zone with india ink.

5. Corynebacterium Diphteria (ADP ribosylation of EF-2)-looks like chinese characters. Gram positive, catalase positive rod that will grow on cysteine-tellurite agar as dark black, slightly iridescent colonies. It can also be cultured in Lofflers medium where it will develop cytoplasmic metachromatic granules (visualizable after staining with an aniline dye such as methylene blue on microscopy)-USMLE!

6. ABCDE (USMLE)

shigA like toxin
Botulinum toxin
Cholera toxin
Diptheria toxin-USMLE, NBME, KAPLAN
Erythogenic toxin of GAS (Scarlet fever)-KAPLAN!

Front 54

Ixodes tick causes what 3 diseases?

Back 54

1. Lymes disease -caused by Borrelia Burgdorferi

Treat with doxcycline or cefrixaone-USMLE!

2. Babesia- fever and hemolytic anemia most in NE US (Connecticut)
-Babesia microti: intraerythrocytic protozoan parasite
-Causes hemolytic anemia that is severe in splenectomized pts
-Several cases have been transmitted by blood transfusions

-Blood smear: no RBC pigment, appears as MALTESE cross

Treat: Quinine, Clindamycin


Kaplan:
A 50 yr old woman develops fever, HA, chills, fatigue 1 week after returning from a trip to the woods. A blood smear shows small rings in the RBCs. The vector of this dease can also transmit which of the following organisms? Borrelia Burgodorferi

3. Granulocytic ehrlichisosis
-Caused by Ehrlichia phagocytophila
-Pathognomonic feature: presence of morulae (berry like clusters of organisms inside the patients granulocytes
-Similar to Rocky mountain spotted fever but NO rash

Kaplan:
16 yr old boy brought to ER b/c fever, joint and muscle pain, photophobia, malaise. He says he felt well until 4 days ago but now has HA and has been vomiting. Temp 104. PE shows no rash, ulceration or petechiae. Labs show thrombocytopenia, absolute leukopenia, increased serum transaminases. Peripheral blood smear shows granulocytes that contain berry like clusters of intraceullar organisms. The vector for this caustive agent is the same for what organism?
A. Borrelia burgdoferi

All transmitted by Ixodes tick bite that lives on deer and mice!!

vs

Rocky mountain spotted fever
-Caused by Rickettia Rickettsii
-Rash on palms and sole that then migrate to wrist, ankles and trunk
-Edemic to East coast (Tenennsee, SC, NC, Atlantic ocean)
-S/S: fever, N/V, abd pain then 1-5 days later get the rash starting on hands and sole of foot
-Also, thrombocytopenia, DIC, increase LFTs, ARF, ARDS

Treat: Tetracycline, Chloraphmicol, or Doxycline

Front 55

Quick Recap Virus:

1. Name the characteristics common to all DNA viruses (with exceptions)?

2. Name the negative strand RNA viruses?

3. Name the segmented RNA viruses?

4. Neoplasms associated with HIV?

5. A. Cause of pneumonia in a pt post viral infection?

B. Cause of bronchitis in smokers?

C. Cause of lobar pneumonia in diabetic or alcoholic?

6. Hearing loss, seizures, petechial rash in neonate?

7. Painful genital ucler with inguinal adenopathy?

8. Low grade fevers, cough, hepatospenomegly and oval organisms within macrophages in a HIV pt?

Back 55

1.
A. all are double stranded (except parvo-single stranded-aplastic crisis in SCA-USMLE!, B19)
B. All are linear (except papilloma (HPV-circular) and polyoma (JC virus-circular) and hepadana-Hep B-circular))
C. All are icosahedral (except pox-brick shaped-KAPLAN! (Side note: Largest DNA virus)
D. All replicate in nucleus (except pox-carries its own dna-dependent RNA pol-small pox and molluscum contagiosum)-KAPLAN!

Kaplan:
A previously healthy 3 yr old boy is brought to the dr by his mother b/c of a rash that appeared 2 days ago. PE shows multiple umbilicated, flesh colored papules on the trunk. Characteristic of the organism? replicates in cytoplasm

-Molluscum contagiosum, caused by pox virus
-Can be transmitted sexually or through direct nonsexual contact
-Replicates in cytoplasm and produces eosinophillic intracytoplasmic inclusion bodies
-Pts with advanced HIV may develop severe, generalized and persistent eruption, often involving face and upper body
-Common in wresting teams

RECAP:
Flesh colored dome lesions with central dimple=molluscum contagiosum. NBMEx2

2. Negative strand-must transcribe negative strand to positive strand before replicating its RNA

1. Arenaviruses (lassa fever encephaltiis-spread by mice)
2. Bunyaviruses (aseptic encephalitis)
3. Paramyxovirus (Parainfluenza (causes croup), RSV (bronchiolitis in infants), Rubeola-Measles (Cough, coryza, conjunctivitis, koplik spots then maculopapular rash starting from head/face and moving down to trunk-includes hands and feet vs truncal rash in rubella), Mumps (causes bilateral parotitis, orchitis, pancreatitis-KAPLAN)-all contain surface F (fusion) protein which causes respiratory epithelial cells to fuse and form multinucleated cells. PALIVIZUMAB is a monoclonal antibody used in RSV to neutralize F protein. This prevents infection of the host cell. NBME, KAPLAN!!

-Paramyxoviruses spread from cell to cell by synctia formation. This protects them from exposure to substances that exist extraceullary (antibodies) and makes cell mediated immunity an absolutely essential event for recovery and cure.
-This is why MMR vaccine must be live-attenuated, to stimulate strong cell mediated immunity

KAPLAN:
-A 27 yr old man develops fever of 102. PE shows bilateral parotid gland swelling and orchitis. Antibodies against the most likley causal agent are ineffective due to? Syncytia formation

4. Orthomyxoviruses (Influenza)
5. Filovirus (Ebola/Marburg hemorrhagic fever-fatal!!)
6. Rhabdovirus (rabies)-skunks, bats, racoons---> hypersalvation, hydrophobia, agitation, photophobia, paralysis. We have a killed virus for this. Negri bodies (cytoplasmic inclusions in neurons commonly in purkinje cells of cerebellum)

*Always bring polyermase or fail replication*

3.
A. Bunyavirus
B. Orthomyxoviruses (Influenza)
C. Arenavirus
D. Reovirus (Rotavirus)-KAPLAN!-----ALL RNA viruses are SS except reoviridae and Rotavirus which are DS

*These segments can undergo high frequency recombination via reassortment, causing antigenic shifts/GENETIC SHIFT that lead to worldwide pandemics of the flu


4.
A. Kaposi sarcoma (HHV-8)
B. Invasive cervical carcinoma (HPV)
C. Primary CNS Lymphoma (B-lymphocyte origin (CD20+ and CD79a+) with diffuse large B cell lymphoma most common subtype and associted with EBV-USMLE!...appear as dense, ceullar aggregates of uniform, atypical lymphoid cells.
D. Non-Hodgkins lymphoma


5.
A. Staphylococcus and H.Influenza

Think Staph in a pt with flu like symptoms (post viral) and then cavitary pneumonia!!

Kaplan:
67 yr old woman develops flu like symptoms and then several days later, she has high fever, dyspnea, cough with mental status changes. Xray shows cavitary lesion. Agent? Gram positive, catalase positive, coagulase positive, beta hemoyltic (complete hemolysis) and grows on mannitol salt agar (salt tolerant)=Staph Aureus


B.
1. Haemophilius influenza-encapsulated gram negative rod
2. Legionella-dosent gram stain well. Use silver stain and charcoal yeast extract with iron and cysteine
3. Moraxella-gram negative coccus

KAPLAN
-50 yr old man presents to physician b/c of chronic cough. He has smoked 1 pack of cigs for 30 yrs. Crackles and wheezes are heard on ausculation of the chest. A CXR show no abnormalities. Gram stain shows gram negative coccobaccilli. Organism? H. Influenza

C. Klebsiella
-Intestinal flora that causes lobar pneumonia in alcoholics and diabetics when aspirated
-Red currant jelly sputum
-Gram negative, oxidase negative, lactose fermenter (with E.coli)

*Also causes nosocomial UTIs

Kaplan
58 yr old male presents to ER after being found in streets. Rectal temp 101.8 and smells of wine. His coughing produces thick, bloody sputum.(currant jelly) PE shows dullness to percussion, increased vocal fremitis, decreased breath sounds (all point to lobar pneumonia vs pleural effusion have decreased fremitis) and wet crackles over right lung field. Xray shows consolidation of right upper lobe. Most likley organism?

Gram negative, oxidase negative bacillus=Klebsilla

6. CMV torch infection (most common infection in neonate in US)-can cause cholecystitis!!!

7. Chancroid from Haemophilus ducreyi

Genital herpes: also PAINFUL penile, vulvar or cervical vesicle with ulcer.
-Can cause systemic symtpoms such as fever, HA, myalgia

8. Histoplasma Capsulatum (causes ONLY pulmonary symptoms in immunocompetent hosts called fungus flu, which may present as an acute pneumonia with flu like symptomatology)-Oval yeast cells in macrophages
-Does NOT spread from person to person b/c: is intracellular-KAPLAN!
-In Ohio, Mississipppi and Missouri river valleys of central US
-Small intraceullar organism with NO true capsule (depsite its name)
-Would see calcifying lesions in the lung

Kaplan: A 35 yr old man who lives in central US develops fever, chest pain and dry cough. CXR shows opacities consistent with calcified masses. Results of PPD are negative. a CT guided biopsy will show? small intraceullar yeast with a thin cell wall but no true capsule

Front 56

Name the mechanism of resistance?

1. Aminoglycosides?

2. Vancomycin?

3. Tetracycline?

4. Macrolides?

5. Chloramphenicol?

6. Acyclovir?

7. Foscarnet?

8. Isonazid?

9. Azoles?

10. Rifampin?

11. Tumor/Cancer cells?

12. Ciprofloxacin?

13. Pseudomonas?

Back 56

1. Transferase enzymes that inactivate the drug by acetylation, phosphorylation or adenylation-USMLE (also Sulfonamides and Chloramphenicol)
-Aminoglycosides are syndergistic with beta lactam antibotics (PCNs) and block 30s subunit (tetracycline also blocks 30s)-USMLE

USMLE: Enterococci isolated from a pt with severe urinary tract infection are shown to produce an enzyme at the surface of the cytoplasmic membrane that is involved in acetyl group transfer to exogenous substances. The bacteria are most likely resistant to which of the following antibotics? Gentamycin

-The enterococci has acquired resistance to multiple antibotics including: PCN, aminoglycosides, TMP-SMX, and Vancomycin. Each resistance occurs by different mechanisms.
-Aminoglycosides: plasmid mediated or transposons
1. Gentamycin
2. Neomycin
3. Amikacin
4. Tobramycin
5. Streptomycin

2. Occurs with amino acid change of D-ala D-ala to D-ala D-LAC (Vs Penicillins which confer resistance by altered PBP)
Vanc (can cause red man syndrome: diffuse flushing-NOT an allergic rxn or contraindication to use-Slow infusion or pre-treat with anti-histamine

3. Decreased uptake into cells or increased efflux out of cells by PLASMID encoded transport pumps
Tetracycline- drugs ability to accumulate intracellulary makes it very effective against Rickettsia and Chlamydia.
-Contraindicated in pregnacy-discoloration of teeth-USMLE

4. Include Azithromycin, Clarithromycin and Erythromycin
-Methylation of 23s rRNA binding site of 50S subunit
Side effect: prolonged QT interval (esp erythromycin)
-P450 inhibitor (except Azithromycin)=increase levels of warfarin, theophyllines

5. Plasmid encoded acetyltransferase that inactivates drug
Side effects: aplastic anemia (decrease wbcs, decrease rbcs, decrease plts)-USMLE

6. Lack of viral thymidine kinase



7. Foscarnet-

-USE: CMV retinitis when ganciclovir fails
-Does NOT require activation by viral kinase (Also Cidofovir does NOT require viral kinase-is already monophosphorylated-USMLE!
-Resistance: mutated DNA polymerase
-Side effects: Nephrotoxic-decrease Mg2+, decrease Ca2+-USMLE

VS

Ganciclovir:

USE: CMV
Requries viral kinase
Side effects: neutropenia, leukopenia, thrombocytopenia, renal toxicity
Resistance: Mutated CMV DNA polymerase or lack of viral kinase


8. Isoniazid
-Decrease synthesis of mycolic acids
-Needs bacteria catalase peroxidase to convert it into an active metabolite)

Resistance occurs by 2 selective gene mutations-USMLE!
1. Decrease in bacterial expression of catalse peroxidase enzyme=no activation of isoniazid once the drug enters the bacterial cell
2. Modification of the protein target binding site for isoniazid.

Use of monotherapy isoniazid leads to rapid resistance.
You can only use monotherapy isoniazid for pts with positive PPD but have a negavite CXR (no evidence of disease)

Know:
1. INH (Injuries neurons and hepatocytes-peripheral neuropathy and hepatoxicity
2. HIPS (lupus like symptoms)
3. Will have different half lifes in fast vs slow ACETYLATORS-USMLE!


9. Azoles
-bind to ergosterol in CELL MEMBRANE and forms pores that allow leakage of electrolytes

Resistance:
Decrease of the cell membrane ergosterol content

10. Rifampin
-inhibits DNA dependent RNA polymerase

Resistance: modification of the rifampin binding site on the bacterial DNA dependent RNA polymerase-USMLE!

11. Tumor cells

Tumor cells can resist chemo via human multidrug resistance (MDR1) gene
-The product of this gene is P-glycoprotein, a transmembrane protein that functions as an ATP dependent efflux pump-USMLE!
-P-glycoprotein: normally expressed in intestinal, CNS blood brain barrier and renal tubular epithelial cells and functions to eliminate foregin compounds from the body.
-In tumor cells, this ATP powered transmembrane pump protein actively removes chemotherapeutic agents, particularly hydrophobic agents like antrhacyclines, preventing the action of chemo drugs

12. Ciprofloxacin (flouroquinolones)
-CHROMOSOME encoded mutation in DNA gyrase-KAPLAN!
-Gram positive cocci (staph saprophyticus) causes UTIs in sexually active people and cipro is used to treat it

13. Pseudomonas
-chromosomally mediated mutation to a porin protein that restricts the flow of many antibotics into the cell
-Causes
1. Opportunistic infections in burn pts
2. Cysitis in pts with urinary cathethers-USMLE!
3. Pneumonia in pts with cystic fibrosis-USMLE!
4. Malignant otitis externa-KAPLAN, NMBE!
5. Sepsis (black lesions on skin)
6. Osteomyletis (in diabetics)
7. Hot tube folliculitis

-Pseduomonas
-Produces blue green pigment
-Inactivates EF-2 (similar to diptheria)-USMLE!
-Produces endotoxin (fever and shock)
-NBME: Many studies have concluded that PYOCYANIN has a derogatory effect in cystic fibrosis which enables P. aeruginosa to persist in the cystic fibrosis lung; it is often detected in the sputum from cystic fibrosis patients. Pyocyanin in vitro has the ability to interfere with functions such as ciliary beating and therefore cause epithelial dysfunction as the ciliary are needed to sweep mucus up the throat.

Front 57

What the bacteria, virus and parasite organisms that can undergo antigen variation?

Back 57

1. Bacteria:

A. Salmonella-has 2 flagellar variants
B. Borrelia-relapsing fever
C. Neisseria gonorrhoeae: pilus protein (uses to attach)-USMLEx2

2. Virus:

A. Influenza: (shift-major, drift-minor)

3. Parasites

A. Trypanosomes (programmed rearrangment)

*This is the reason why we dont have vaccines for these organisms

Front 58

Name the Type IV hypersensitivty disorders?

Back 58

1. Type I DM
2. MS
3. Guillane barre (campylobacter)
4. Hashimoto thyroditis
5. Graft vs host disease
6. PPD
7. Contact dermatitis (poion ivy, nickel allergy) VS actopic dermatitis

Type IV
-NO antibodies involved
-IL-12 induces differentiation of T cells into TH1 which activates macrophages and leads to damage
-IL-10 from TH2 inhibits TH1 and therefore TYPE IV hypersensitity response

Front 59

What are the normal pressures in the heart? Explain the PCWP?

Back 59

RA: 5/0 (basically less than 5. could be 0)

RV: 25/0

PA: 25/10- This is the pulmonary capillary wedge pressure.
-This is a good approximation of LA pressure (downstream).
-Normal <25/10= <12 PCWP
-In MV stenosis, PCWP> LV diastolic pressure
-Measured with Swan-Ganz cathether
-This is gold standard for determing cause of acute pulmonary edema
-Also useful in dx mitral stenosis, LV failure

LA: 13/2

LV: 120/0

Aortic: 120/80

Front 60

1. Is present when the effect of the main exposure on the outcome is modified by presence of another variable?

2. What is a Berkson's bias?

Back 60

1. Effect modification
-NOT bias
-A natural phenonomen

2. Refers to selection bias that can be created by selecting hospitalized patients as the control group.
-AKA non random assignment to study group

*Selection/sampling bias is the most common type of bias associated with cohort studies-USMLE

*Volunteers lost to follow up creates a problem for selection bias-USMLE

-Can occur with inappropriate (non random) selection methods or through selective attrition of the study participants. This creates a study population that does not accurately represent the actual population, and can result in erroneous conclusion regarding the exposure-disease relationship.

Front 61

monckeberg arteriosclerosis?

Back 61

-Calcification in MEDIA of arteries
-Especialy radial and ulnar arteries
-Usually found incidentally and benign
-"Pipestem arteries"
-Does NOT obstruct blood flow
-Intima NOT involved

Front 62

Difference between Kaposi sarcoma and Bacillary angiomatosis?

Back 62

Bartonella
-Gram negative rod
-Cats and dogs are reservoir transmitting the organism through bites or scratches
-Causes cat stratch fever (regional lymphadenopahty with or without low grade fever and headaches), bacillary angiomatosis and culture negative endocarditis

Kaplan:
16 yr old girl brought to dr b/c painful enlarged lymph node in right axilla. H/H is normal. Histo exam of biospy of lymph node shows granulomas filled with necrotic debris. Organism? BH



Bacillary angiomatosis: benign capillary skin papules (raised lesions) found in AIDS pts.
-Caused by Bartonella Henselae infections (bacteria)
-Often mistaken for Kaposi sarcoma
-Stain with silver stain and treat with sulfur drug and it goes away-GOLJAN!

*Causes bacillary angiomatosis in immunocomprimised which is vascular proliferation form of infection and can affect any organ system but mostly skin.

vs

Kaposi sarcoma (caused by virus)
-endothelial malignancy of skin associated with HHV-8 and HIV
-Frequently mistaken for bacillary angiomatosis

USMLE:

46 yr old man comes to dr for intermittent, bloody diarrhea and abd pain for past month. He has lost 12 pounds during this time. He was diagnosed with HIV five yrs ago but has been noncompliant with his meds. Labs show CD4 count of 50 and viral load of 650,000. Colonoscopy reveals multiple hemorrhagic polypoidal lesions. Biospy of these lesions reveals spindle cells with surrounding blood vessel proliferation. Dx? Kaposi sarcoma

-Kaposia sarcoma
-vascular malignancy caused by HHV-8
-Skin involvement is characteristic but extracutaneous spread of KS to lungs and GI tract is also common

Front 63

Explain the 3 most important GLUT transporters?

Back 63

1. GLUT-1: brain and RBCs (not insulin responsive)

2. GLUT-2: liver and pancreas (not insulin responsive)

3. GLUT-4: adipose tissue, skeletal muscle (insulin responsive)

Front 64

low serum calcium stimulates secretion of PTH from anterior pituitary, what causes a decreased secretion of PTH?

Back 64

low mageneiusm (diarrhea, aminoglycosides, diuretics). Alcoholism can cause malnutrition leading to severe mg2+ def=causes decrease PTH=decrease in serum calcium secretion=tetany, seizures, tremors, weakness, muscle twitching, trousseau sign, chvostek sign)

Front 65

Which endocrine hormones bind to cytosolic steroid receptors? Nuclear steroid receptors?

Which endocrine hormones use cAMP?

Back 65

Cytosolic steroid receptors: (VET CAP)
1. Vitamin D
2. Estrogen
3. Testosterone (androgen)
4. Cortisol (glucocorticoid)
5. Aldosterone (mineralcorticoid)
6. Progesterone

Nuclear steroid receptors:
1. T3/T4-USMLE!
2. Other hormones that act via nuclear receptors (retinoids, peroxisomal proliferating activated receptors and fatty acids.....
Fat solubule hormones (steroids and thyroxine-T4) cytoplasmic or nuclear receptors which are called zinc-finger receptors. When bound, these undergo conformational change and interact with specific DNA sequences called enhancers to alter transcription. Slow acting thou-USMLE!

Steroid hormones are liphophillic and relatively insoluble in plasma; therefore, they must circulate bound to specific binding globulins, which increase solubility and allow for increased delivery of steroid to target organ. B/c of the need for gene transcription and protein sythesis (to make the binding proteins), the onset of action of these proteins in delayed.

Which endocrine hormones use cAMP:

FLAT CHAMP

FSH
LH
ACTH
TSH

CRH
bHcg
ADH (v2 receptor)
MSH
PTH

Also
1. Calcitonin
2. GHRH
3. Glucagon

Front 66

What endocrine hormones utilize intrinsic tyrosine kinase? Receptor associated tyrosine kinase?

Back 66

*Ligand binding to the extracellular portion of a tyrosine kinase receptor causes dimerization of 2 identical receptor subunits-USMLEsim!
-Each subunit phosphorylates the other causing a conformational change in the intracellular domains of the tyroisne kinase receptor dimer.
-This conformation change exposes subunits catalytic domain and phosphorylation of tyrosine residues on target protein ensues


Tyrosine kinase receptors are transmembrane proteins that have a:
1. ligand binding extraceullar region
2. hydrophobic transmembrane region
3. intracellular (cytoplasmic) domain with inducible tyrosine kinase activity













1. With Intrinsic enzyme activity: receptor tyrosine kinase (MAP kinase pathway-receptor autophosphorylates and trigger phosphorylation of Ras protein)-think growth factors
1. Insulin
2. IGF-2
3. FGF (stimulates angiogenesis with VEGF)-USMLE!
4. PDGF
5. EGF (DOES NOT stimulate angiogenesis) but associated with HER-2: USMLE!


2. Without intrinsic enzyme activity: tyrosine kinase associated receptor (JAK/STAT pathway-receptor activates Janus kinases-JAKs-which phosphorylate STATS-signal transducers and activators of transcription.)
1. GH
2. Prolactin
3. IL-2 (cytokine)
4. cytokines
*Remember these are acidophils (stain pink with eosin) in the pituitary

Front 67

round blue cell malignant tumor and elevated homovanillic acid (HVA) in urine?

Back 67

Neuroblastoma:
most common tumor of adrenal medulla in KIDS
-Can occur anywhere along sympathetic chain (60% occur in abdomen-within adrenals)
-Homovanillic acid (HVA)-breakdown product of dopamine elevated in urine (whereas pheo has elevated VMA (breakdown of nor epi)
-Less likely to deveop HTN (unlike pheochromocytoma which causes epidosic HTN)
-Histo: solid sheets of small cells with dark nuclei and scant cytoplasm (small blue round cells)
-Associated with overexpression of N-myc

S/S:

1. Abd distention or obstruction
2. Bone pain (due to mets)
3. Signs of symphathatetic chain compression---> Horners syndrome (myosis, anhidrosis, ptosis)
4. SVC syndrome (JVD, swelling of upper ext)

Paraneoplastic syndromes:
1. Mets to orbit-->hemorrage and edema ("racoon" or panda like appearance to face)
2. Mets to skin/cutaneous--> nodules that blanch on compression="Blueberry muffin baby"
3. Intractable water diarrhea due to VIP
4. Mets to bone marrow (pancytopenia)
4. Opsoclonus-myoclonus (acute cebellar ataxia with abnormal non rhythmic conjugate movement of eyes)-USMLE!!



USMLE: 2yr old pt found to have spontaneous bursts of non-rhythmic conjugate eye movements in various directions. He also suffers from hypotonia and myoclonus. Exam reveals an abdominal mass (neuroblastoma on adrenals).

Front 68

Name 3 rapid acting insulins?

Back 68

Short acting:
LAG (Lispro, Aspart and Gluigine)-onset of action 15 mins

Long acting:

Glargine (Lantus-once day-lasts 24 hours) and Detemir
Diabetics need 2 types of insulin: basal long acting one (Glargine-Lantus and 1 shot at each meal time=3 shots of Aspart-)

Front 69

Explain what happens when lactose is present and when glucose is present, not present?

Back 69

1. Lactose present:

Lactose binds to REPRESSOR protein which causes a conformation change which prevents the attachement of the repressor protein to the operator region. This then increases transcription of the lac operon structural genes and subsequently increases utilization of lactose for energy.


When the repressor protein cannot bind the operator, transcription of lac operon structural genes will increase, thus increasing the utilization of lactose for energy-USMLE!

Mutations of the repressor protein or its binding site at the operator region will prevent repression of genes of lac operon. This results in constitutive transcription of genes of lac operon, even in presence of glucose (which would normally turn off lac operon b/c lactose=glucose+galactose)



2. No/low glucose:

low glucose=high cAMP

high cAMP binds a protein called catabolite activator protein (CAP) to form cAMP-CAP complex which binds to region upstream from promoter region and acts as positive regulator of lac-operon

High glucose:

=low cAMP=low cAMP-CAP complex=less activation of operon


Take home:

Mechanism of glucose inhibition of lac operon expression is depletion of cAMP-USMLE!

Front 70

Explain how brown pigment stones and cholesterol gallstones are formed?

Back 70

Brown pigment:

Radiopaque stones (seen on xray due to the calcium in them) seen in patients with chronic hemolysis, alcoholic cirrhosis, advanced age and biliary infections.

They arise when injured hepatocytes and bacteria release B-glucuronidase (USMLE)

This enzyme contributes to hydrolysis of bilirubin glucuronides and increaes the amount of unconjugated bilirubin in bile

Infection with E.Coli, Ascaris lumbricoides or the liver fluke Opisthorchis Sinesis significantly elevates the risk of developing brown pigment stones

Chronic hemolysis=increased unconjugated bilirubin precipates in bile as CALCIUM BILIRUBINATE. (sickle cell anemia, B-thalaseemia, hereditary spherocytosis)

KAPLAN: 25 yr old woman with sickle cell anemia is brought to ER b/c of steady pain in right upper quadrant. She states the pain radiates to the right shoulder, especially after large or fatty meal. A diagnosis of cholelithiasis is made. What is the most likely primary composition of the stones? Calcium bilirubinate
-Bilirubin stones can be seen in hepatic cirrhosis, liver fluke infestation also
-The excess bilirubin forms gallbladder stones (calcium bilrubinate) and blocks cystic duct-->pain in upper right abdomen


II. Cholesterol stones: radiolucent (cant see on xray)

Causes:

1. Obesity
2. Chrons disease=no terminal ileum=no absorption of bile acids= increase cholesterol=increase gallstones. ALSO no bile acids=excess lipids in bowel lumen bind to calcium forming soap complexes. Less calcium is able to bind with oxalate=increase oxalate=increase kidney stones. USMLE!
3. Cystic fibrosis
4. Advanced age
5. Clofibrate-to lower TGs...inhibits 7a hydroxlase which reduces conversion of cholesterol into bile acids resulting in increased cholesterol in bile=cholesterol stones
6. Estrogens-increases synthesis of cholesterol by increasing HMG-CoA reductase=increase cholesterol stones
7. Muliparity
8. Rapid weight loss
9. Native american orgin
10. Bile acid resins (cholestyramine)=decrease bile acids=increase cholesterol=increase cholesterol stones
11. Pts on TPN: b/c no stimulation to secrete CCK and gallbladder contraction (b/c food going into IV and not hitting duodneum) and get stasis of bile in gallbladder=gallstones. Give CCK to pts on TPN-USMLE!
12. Liver cirrhosis: decrease synthesis of bile acids=increase cholesterol=cholesterol stones


Fibrates: for decreasing TG

gemifrozil, clofibrate, bezafibrate, fenofibrate: decrease LDL and GREATLY decreases TG while increases HDL.

Side effects: myositis (risk is increased with concurrent use of statins-which also cause myopathy), hepatotoxicity and cholesterol gallstones

Bile acid resins: cholestyramine, colestipol, colesevelam: decrease bile acid absoporption=increase cholesterol=increase cholesterol stones

Side effects: increases TG, cholesterol stones, decrease absoprtion of fat soluble vitamins

Front 71

Most common benign liver tumor?

Back 71

Cavernous hemangioma
- benign tumor thought to be congenital malformations that consists of blood filled vascular spaces of variable size lined by single epithelial layer
-May be multiple or single and are well circumscribed masses of spongy consitency
-S/S: most are asymptomatic but some may complain of abdominal pain and right upper fullness
-Biopsy of a suspected hemangioma is NOT advisable, as the procedure has been known to cause fatal hemorrhage and is of low diagnostic yield

Front 72

Explain the most important info about each of the Hep viruses?

Back 72

Hep A:
Type: RNA (picornavirus)
Transmission: fecal-oral, oysters (USMLE), shellfish
Incubation: short (30days)
S/S: usually asymptomatic but may have malaise, RUQ pain, hepatomegaly adversion to smoking, fever and dark urine-USMLE!
Disease: acute only. Does NOT progress to chronic hepatitis, cirrhosis, or hepatocelluar carcinoma
Unique: Has vaccine for it (HAV killed vaccine-only humoral immunity)
USMLE: Can be inactivated with water chlorination, bleach, formalin, UV irradiation or boiling to 85degrees for 1 min

Hep B:
Type: DNA (hepadnavirus)
Transmission: parental, sexual, materal-fetal (blood borne) via placenta transfer or during delivery-the presence of HBeAg would indicate HIGH transmitiability-USMLE!
Incubation: long (30-180days)
S/S: initial presention during prodromal period is "serum sickness like" with joint pain, malaise, fever, fatigue, skin rash, pruritis THEN increase in ALT and AST-USMLE! Damage is NOT a direct cytotoxic effect from the virus but from viral antigens on surface of hepatocytes with MHC 1 which activate CD8+ cells which cause all the damage-USMLE!
Disease: acute and chronic (most have subclinical or mild symptoms then self resolve thou >95%-USMLE!)
Unique: have reverse transcriptase which transcribes RNA from DNA template
HBeAG: indicates HIGH transmittibility (e=envelope, you need envelope to send letters/transmit to other people)-USMLE!
Anti-HBeAg: indicates low transmissibility

-Causes several distinctive morphologic changes including:
1. balloning degeneration
2. hepatocyte necrosis
3. portal inflammation
4. The hepatocellular cytoplasm becomes filled with spheres and tubules of HBsAg and the cytoplasm takes on a finey granular, eosinophillic appearance called "ground glass"-USMLE!

-The countries with high rates of Hep B have more than 85% of hepatocellular carcinoma. (produces AFP)
-Most of these people develop HBV infection through vertical transmission at childbirth, which increase their risk of developing HCC by early to mid life 200 fold (READ: the younger you get Hep B, the higher chance you have at getting HCC)
-Universal vaccination of children against HBV would be the one measure that would cause a steep decline in incidence of HCC worldwide-USMLE!



Associated with Polyarteritis nodosa:
-Transmural inflammation of arterial wall with fibrinoid necrosis of medium to small sized arteries
-1/3 of pts can have cutaneous manifestations including livedo reticularis (purplish network of patterned discoloration) and palpable purpura
-Occur in any organ EXCEPT lung-USMLE!


USMLE: 32 YR old male presents with fever, weight loss, myalgias and abd pain. BP is 150/90 and HR 90. If diagnosed with PAN, which of the following arteries will be spared? Pulmonary


-S/S: fever, abd pain, peripheral neuropathy, weakness, weight loss

USMLE: A male presents with fever, weight losss and muscle pain. He visited the ER several weeks ago for dark stools and malaise. Muscle biopsy demonstrates transmural inflammation of arteries with fibrinoid necrosis. Some arteries also show fibrous wall thickening. This pts condition is most likely associated with what? liver infection


Hep C:
Type: RNA (flavivirus)-flava flav!!
Transmission: blood. common cause of post transfusion hepatitis and of hepatitis in IV drug users in US
S/S: mild clinical symptoms but may have malaise, n/v, RUQ pain (Can lead to aplastic anemia-GOLJAN!)

Unique:
1. No proofreeading when replication
2. Has 6 more more genotypes and multiple subgenotypes with variety in antigenic structure of the envelope proteins---> so host antibodies lag behind the production of new mutant strains of HVC and effective immunity is NOT conferred. This is why we dont have vaccine for it-USMLE!
3. Majority of patients (55-85%) develop stable, slowly progressive chronic hepatitis-USMLE!
4. Most remain HCV RNA positive and have persistent elevation of liver enzymes.
5. Due to the genetic diveristy of HCV and its tendency to quickly mutate which allows the virus to evade immune detection and establish chronic infection

Hep D:
Type (Delta agent)
-Defective virus that must be coated by the external coat antigen HBsAg of Hep B

Recap: HbsAg of Hep b virus must coat the HDAg of Hep D virus before it can infect hepatocytes and multiply-USMLE!


Hep E:
Type (RNA hepevirus-KAPLAN!)
Transmission: fecal oral
Unqiue: high mortality in pregnant women

*Hep A and E by fecal oral
*The vowels (A and E) hit your bowels (b/c naked viruses do not rely on an envelope, they are NOT destroyed in gut)

Front 73

External hemorroids vs internal? Which one would present with bright red blood?

Back 73

1. Above dentate/pectinate line
-Internal hemorroids
-NON PAINFUL (b/c lacks pain receptors)
-Present with bright red bleeding
-Become enlarged in portal HTN

-Adenocarcinoma (ENDODERM derivation)
-Artery: superior rectal artery (branch of IMA)
-Vein: superior rectal vein-->drains into inferior mesenteric vein-->portal system


2. Below dentate/pectinate line
-External hemorroids
-PAINFUL (innervated by inferior rectal nerve-branch of pudendal nerve)
-Swelling and irritation-->itching
-Prone to thrombosis

-Squamous cell carcinoma (ECTODERM dervivation)
-Artery: inferior rectal artery (branch of internal pudenal artery)
-Vein: Inferior rectal vein-->drains into internal pudenal vein-->IVC

Front 74

Undiagnosed gastric carcinoma will eventually extend through gastric wall to the serosa and can exhibit what 3 types of mets?

Back 74

1. Virchow's node: involvement of left supraclavicular node by mets from stomach (neck and mediastinal cancers can also spread here)

2. Krukenberg tumor: bilateral mets to ovaries with abundant mucus, signet ring cells-USMLE!

3. Sister Mary Josephs nodule: mets to periumbilical region can result in formation of a subcutaneous mass

In time, extensive perioneal seeding and widespread mets to liver and lungs occurs.

Front 75

Functions of the CCK, VIP and secretion? What happens when these hormones are missing or in excess?

Back 75

Gastrin (phenylalanine and tryptophan are potent stimulators=increase acid secretion. Gastrin also increases growth of gastric mucosa and increase gastric motility. Somatostatin, GIP, prostaglandins and secretin all decrease acid secretion)

1. CCK
-From I cells of duodenum and jejunum when increased fatty acids, amino acids

-FXN:
A. Increase pancreatic secretion-NMBEx2 (acts on neural muscarinic pathways to cause pancreatic secretion)
B. Increase gallbladder contraction
C. Decrease gastric empyting

Defiency (removal of duodenum) leads to:
1. Increase gastric emptying
2. Deceased gallbladder contraction=gallstones

2. Secretion
-From S cells of dudodenum

FXN:
A. Increase pancreatic bicarb (neutralized gastric acid in duodenum, allowing pancreatic enzymes to fxn. Decrease secretin (removal of duodenum)=steatorrhea b/c pancreatic enzymes cant work
B. Decrease gastic secretion
3. Increase bile secretion


Enterokinase/enteropeptidase:
-Also from duodenal mucosa
-Activates trypsinogen into trypsin and then trypsin activates other proenzymes (trypsin, chymotrypsin, elastase, carboxypeptidases) and more trypsinogen-positive feedback loop




3. Vasoactive intestinal peptide (VIP)
-hormone produced by pancreatic islet cells and neurons in GI mucosa
-Causes
1. relaxtion of the GI smooth muscle
2. Inhibiton of gastric acid secretion
3. stimulation of pancreatic bicarb and chloride secretion

VIPoma
-pancreatic islet cell tumor that causes excess VIP secretion resulting in a conditon called pancreatic chlorea or WDHA syndrome (watery diarrhea, hypokalemia and achlorhydia)

Treatment: somatostatin (octreotide) decreases production of all gastrointestinal hormones.

USMLE-Pt presented with persistent diarrhea over last several months. She describes the stool as tea colored and odorless. She denies abd pain, fever or vomiting (rules out inflammtory diarrhea b/c no blood or pus). She reports her diarrhea has persisted despite a trial of lactose free diet (rules out lactose intolerant so suggests a secretory diarrhea.) Sampling of her gastic mucosa reveals lack of gastic acid secretion. Somatostatin treatment relives the diarrhea.

Front 76

Name the 3 types of salivary gland tumors?

Back 76

1. Pleomorphic adenoma:
-Most common tumor!
-Bengin
-Painless (until it invades CN7) movable mass
-High rate of recurrence
-Histo: well differentiated epithelial cells in a chondromyxoid stroma surrounded by a fibrous cap (multiple cell types=pleomorphic). USMLE!
-Can progress to carcinoma--the pt may have mass in jaw for many years and then present with facial paralysis (b/c now has invaded facial nerve inside parotid)

2. Warthins tumor:
-Benign cystic tumor with abudant lymphocytes and germinal center
-Heterotopic salivary gland tissue trapped in lymph node, surrounded by lymphatic tissue
-Non recurring after resection
-Risk factors: smoking and age
-S/S: large painless nodule

3. Mucoepidermoid carcinoma:
-Most common malignant tumor
-Due to genetic translocations
-20-40 yr olds
-Invasive, poorly differentiated cancer composed of mucosal and epidermal cell types (hence mucoepidermoid name)
-Commonly involves facial nerve



Salivary glands
1. Parotid (most serous)
2. Submandibular
3. Sublingual (most mucinous)

*Serous on Sides (parotids)
*Mucinous in Middle (sublingual)

Front 77

Name the diseases associated with Down syndrome?

Back 77

1. Immunologic: ALL, AML
2. CNS: Alziheimers disease, mental retardation (IQ 20-70)
3. GI: Duodenal atresia, Hirschsprung, Omphalocele, TEF, annular pancreas, imperforate anus
4. Endocardial cushion defects-->persistent AV canal, VSD, ASD, PDA,
5. Endocrine: Hypothroidism, hyperthyrodism, diabetes type I, inferitilty

Front 78

What cancer drugs work on the S phase of cell cycle (DNA replication)?

Back 78

1. Methotrexate (inhibits dihydrofolate reductase)
-Side effects:
A. Myelosuppresion (reversible with leucovorin-USMLE)
B. Macrovesicular fatty change in liver
C. Mucositis
D. Teratogenic

-Clinical use:
A. Leukemia, Lymphomas, Choriocarcinoma, Sarcoma
B. Non neoplastic: abortion, ectopic pregnacy, Rheumatoid Arhritis, Psoriasis

2. 5-Fluorouracil (inhibits thymidylate synthase)
-Side effects:
A. Myelosuppression (NOT reversible with leucovorin but rescuse with thymidine.
B. Photosensitity

-Clinical use:
A. Colon cancer, basal cell carcinoma (topical).
*Synergy with Methotrexate

3. 6-Mercaptopurine (decreases purine synthesis)
Clinical use: Leukemias, Lymphomas (not CLL or Hodgkins)
Side effect:
A. Bone marrow, GI, liver
*Metobolized by xanthine oxidase and thus increase toxicity with allopurinol
*DONT give with allupurinol

4. 6-Thioguanine (decreases purine synthesis)
Clinical use: ALL
Side effects: bone marrow depression, liver
*Can be given with allopurinol

5. Cytarabine (ara-C)
-Pyrimidine antagonist=inhibition of DNA polymerase
Clinical use: AML, ALL, high grade Non hodgkins lymphoma
Side effects: Leukopenia, thrombocytopenia, megaloblastic anemia

6. Hydroxyurea (inhibits ribonucleotide reductase)-used for melanoma, CML and sickle cell anemia

Front 79

What cancer drugs work on the M phase of the cell cycle? (cell division)

Back 79

Mircrotubule inhibitors

1. Vincristine (PREVENT MICROTUBULE FORMATION)
A. neurtoxic-areflexia
B. Peripheral neuropathy-USMLE!
C. Paralytic ileus

USMLE:
A pt with non Hodgkins lymphoma is treated with chemo. He subsequently develops tingling of his hands and feet, symptoms which are suspected to be a drug side effect. What pase of the cell cycle is affected? M


2. Vinblastine
A. Bone marrow suppression (vinBLASTine BLASTS the bone marrow)

*Block polymerization of microtubules so that mitotic spindle cannot form (mitotic spindle inhibitors)

*Clinical use:
A. Hodgkins lymphoma
B. Wilms tumor
C. Choriocarcinoma

3. Palitaxel (hyperstabilizes poylmerized microtubules in M phase so mitotic spindle cant break down. PREVENTS DEPOLYMERIZATION)
-mitotic spindle inhibitor
A. Myelosuppression
B. Hypersensitivity

Clinical use:
A. Ovarian cancer
B. Breast cancer

ADDITIONAL
1. Bleomycin: works on G2 phase (right before M phase where DNA is checked for errors and corrections made if possible.
-induces free radicals which cause breaks in DNA strands

Uses:
1. Testicular cancer
2. Hodgkins lymphoma

Side effects
1. Pulmonary fibrosis
2. Skin changes
3. Minimal myselosuppression

Front 80

Name the appropriate prophalaxtyic drug?

1. Cyclophosphamide?
2. Methothrexate?
3. Cisplatin?
4. IV contrast CT scan in renal insuffiency pt?
5.Doxorubicin?
6. Imipenem?
7. Cyclosporine?

Back 80

1. Cyclophosphamide: use Mesna to prevent hemorragic cysitis-USMLE!

2. Methothrexate: use Leucovorin or folinic acid to recuse-USMLE!

MOA: (inhibits dihydrofolate reductase)

-Side effects:
A. Myelosuppresion (reversible with leucovorin-USMLE)
B. Macrovesicular fatty change in liver
C. Mucositis
D. Teratogenic

3. Cisplatin: use AMIFOSTINE to prevent nephrotoxicty-USMLE!
MOA: cross links DNA.
Side effects: Nephrotoxicity and acoustic nerve damage
Use: Testicular cancer

USMLE:

A 65 yr old female with ovarian cancer is treated with cisplatin based chemo. Which of the following prophylatic measures would be msot likely to limit the toxicity associated with this chemo regimen? AMIFOSTINE

Cisplatin
-side effect of neprhotoxcity
-Causes tubular injury
-Amifostine: cytoprotective free radical scavening agent used to decrease the cumulative nephrotocity associated with platinum containing agents, thereby disallowing rxn with the renal tubules.
-You can also establish chloride diuresis (vis IV normal saline) b/c cisplatin stays in a nonreactive state when in higher chloride conc.


4. IV contrast CT scan in renal insuffiency pt: use N-acetylcysteine to prevent radiocontrast induced nephropathy

5. Doxorubicin-use DEXRAZOXANE to prevent cardiotoxicity

6. Imipenem-use CILASTATIN to decrease inactivation of drug in renal tubules

7. Cyclosporine
-binds to cyclophilins
-Complex blocks the differentiation and activation of T cells by inhibiting calcineurin, thus preventing production of IL-2

Side effects
1. Predisposes to viral infections and lymphoma
2. Neprhotoxic (preventable with mannitol diuresis)

Front 81

Name the antibody to the listed target?

1. CD3?

2. IL-2 receptor?

3. TNF-alpha?

4. Glycoprotein IIb/IIIa?

5. erb-B2?

6. CD20?

Back 81

1. CD3: Muromonab-CD3 (OKT3)
-Prevent acute transplant rejection

2. IL-2: Daclizumab (Kaplan!) and Basiliximab
-Prevent acute rejection of renal transplant
-Side effect: cytokine release syndrome

3. TNF-a: Infliximab and Adalimumab
-Chrons disease, Rheumatoid arthritis, Psoriatic arthritis, Ankylosing spondylitis

4. Glycoprotein IIb/IIIa: Abciximab (USMLE!)
-Prevent cardiac ischemia in unstable angina and in pts treated with percutaneous coronary intervention

5. erb-B2: Trastuzumab (Herceptin)-cardiotoxicity
-HER-2 overexpressing breast cancer

6. CD20: Rituximab (USMLE!
-B cell non Hodgkin lymphoma


SN
1. Sirolimus: inhibits T cell proliferation by binding the serine-threonine kinase, mTOR, which is necessary for cell cycle progression.
-Inhibits T cell proliferation in response to IL-2
-Indicated for kidney transplant rejection prophylaxis
-Side effects:
A. Hyperlipidemia, hypercholesterolemia-KAPALN
B. Thrombocytopenia
C. Leukopenia
*No nephrotoxicity unlike cycosporin

2. Cyclosporine
-binds to cyclophilins
-Complex blocks the differentiation and activation of T cells by inhibiting CALCINEURIN, thus preventing production of IL-2

Side effects
1. Predisposes to viral infections and lymphoma
2. Neprhotoxic (preventable with mannitol diuresis)




3. Tacrolimus (FK506)
-Similar to cycosporine
-Binds to FK binding protein, INHIBITING SECRETION OF IL-2 (this will inhibit T cell proliferation) vs sirolimus which inhibits T cell proliferation in response to IL-2
-Indicated for heart, liver, kidney transplant prophylaxis

Side effects
1. Nephrotoxicity
2. Peripheral neuropathy!!!!!
3. HTN
4. Pleural effusion
5. Hyperglycemia

Kaplan:
35 yr old man with recent liver transplant comes to dr for a follow up exam. Treatment with corticosteroids is begun to prevent rejection of the transplant. Additionally, a drug that reduces the activation of cytotocic T cells by inhibiting IL-2 is given. Drug? Tacrolimus

Front 82

Explain what happens in glomerulus when?

1. Afferent arteriole dilation?

2. Efferent arteriole constriction?

3. Increase plasma conc?

4. Decrease plasma conc?

5. Constriction of ureter?

6. Afferent arteriole constriction?

Back 82

1. Increase RPF, Increase GFR, No change in FF
-Kaplan!

2. Decrease RPF, Increase GFR, Increase FF
-NBME!
-Will increase GFR by increasing glomerular capillary pressure but will also increase renal vascular resistance. This will decreae RPF


3. No change in RPF, decrease GFR, decrease FF
-Will increase colloid osmotic pressure but will decrease GFR by reducing glomerular capillary pressure

4. No change in RPF, increase GFR, increase FF

5. No change in RPF, decrease GFR, decrease FF
-kidney stones, tumor
-USMLE!

6. Decrease RPF, decrease GFR, No change in FF
-Prostaglandins

Front 83

Plasmacytoma?

Back 83

Plasmacytoma (solitary myeloma):

-A localized and isolated soft tissue myeloma/plasma cell proliferation with an M-spike of IgG resembling multiple myeloma but without significant metastatic potential
-Involves soft tissues (lungs, nasopharynx, nasal sinuses)
-Some plasmocytomas involving bone eventually (10-20 yrs) may develop into frank multiple myeloma

KAPLAN:
62 yr old woman undergoes biopsy of a nasopharyngeal mass. Histologic evaluation of the mass shows plasma cells. Serum electrophoresis shows a small monoclonal IgG spike. Bone marrow eval does not demonstrate plasma cell proliferation and no lesions are seen on whole body xray. Dx? Plasmacytoma

Vs

Waldenstrom macroglobulinemia
-malignancy of lymphoplasmacytic cells that secrete IgM
-Monoclonal M spike
-Bone marrow is diffusely rather than focally infiltrated by lymphocytes, plasma cells and hybrid forms
-Hyperviscosity symptoms
-NO lytic bone lesions

Vs

Monoclonal gammopathy of undetermined significance (MGUS)
-monoclonal plasma cell expansion of the elderly without he symptoms of multiple myeloma
-NO lytic lesions, No bence jones proteins, no renal failure, no hypercalcemia
-20% develop one of the above diseases

Front 84

Name the proteins encoded for by the following HIV genes?

1. Env?

2. Gag?

3. Pol?

4. Tat/rev?

5. NEF?

Back 84

1. ENV
-envelope
-gp 120 and gp120
-mutations in this allow escape from host neutralizing antibodies

2. Gag:
-p24: early marker of infection
-indicates exposure to virus
-you make antibodies after this to HIV

3. Pol
-reverse transcriptase
-integrase
-protease

*Mutations in pol gene are responsible for resistance-USMLE!

4. Tat/rev:
-required for viral replication

5. NEF
-decreases expression of MHC 1 on surface of infected cells

Front 85

Difference between actinomyces and Nocardia?

Back 85

Both are gram positive rods forming long branching filaments resembling fungi

1. Actinomyces Isreaelii
-gram positive anaerobe
-Causes oral/facial abscesses that may drain through sinus tracts in skin
-Normal oral flora
-Yellow sulfur granules

2. Nocardia asterioides
-Gram positive
-Weakly acid fast aerobe in soil
-Causes pulmonary infeciton in immunocompromised pts