First Aid for the USMLE Step 1 2022 - A Student-to-Student Guide

713 Pages·2022·241.312 MB·English

by  Tao Le, Vikas Bhushan, Matthew Sochat, Caroline Coleman, Connie Qu

Contents
Contributing Authors vii General Acknowledgments xiii
Associate Authors viii How to Contribute xv
Faculty Advisors ix How to Use This Book xvii
Preface xi Selected USMLE Laboratory Values xviii
Special Acknowledgments xii First Aid Checklist for the USMLE Step 1 xx
` SECTION I GUIDE TO EFFICIENT EXAM PREPARATION 1
Introduction 2 Test-Taking Strategies 19
USMLE Step 1—The Basics 2 Clinical Vignette Strategies 21
Learning Strategies 11 If You Think You Failed 22
Timeline for Study 14 Testing Agencies 22
Study Materials 18 References 23
` SECTION I SUPPLEMENT SPECIAL SITUATIONS 25
` SECTION II HIGH-YIELD GENERAL PRINCIPLES 27
How to Use the Database 28 Pathology 203
Biochemistry 31 Pharmacology 229
Immunology 93 Public Health Sciences 257
Microbiology 121
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` SECTION III HIGH-YIELD ORGAN SYSTEMS 281
Approaching the Organ Systems 282 Neurology and Special Senses 503
Cardiovascular 285 Psychiatry 575
Endocrine 331 Renal 601
Gastrointestinal 365 Reproductive 635
Hematology and Oncology 411 Respiratory 683
Musculoskeletal, Skin, and Connective Tissue 453 Rapid Review 713
` SECTION IV TOP-RATED REVIEW RESOURCES 737
How to Use the Database 738 Biochemistry 742
Question Banks 740 Cell Biology and Histology 742
Web and Mobile Apps 740 Microbiology and Immunology 742
Comprehensive 741 Pathology 743
Anatomy, Embryology, and Neuroscience 741 Pharmacology 743
Behavioral Science 742 Physiology 744
` 
Abbreviations and Symbols 745 Index 771
Image Acknowledgments 753 About the Editors 828
vi
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HIGH-YIELD GENERAL PRINCIPLES
H I G H - Y I E L D P R I N C I P L E S I N
Biochemistry
“The nitrogen in our DNA, the calcium in our teeth, the iron in our blood, ` Molecular 32
the carbon in our apple pies were made in the interiors of collapsing stars.
We are made of starstuff.” ` Cellular 44
—Carl Sagan
` Laboratory Techniques 50
“Biochemistry is the study of carbon compounds that crawl.”
—Mike Adams ` Genetics 54
“We think we have found the basic mechanism by which life comes from ` Nutrition 63
life.”
—Francis H. C. Crick ` Metabolism 71
DNA was the first three-dimensional Xerox machine.
—Kenneth Ewart Boulding
This high-yield material includes molecular biology, genetics, cell
biology, and principles of metabolism (especially vitamins, cofactors,
minerals, and single-enzyme-deficiency diseases). When studying
metabolic pathways, emphasize important regulatory steps and enzyme
deficiencies that result in disease, as well as reactions targeted by
pharmacologic interventions. For example, understanding the defect
in Lesch-Nyhan syndrome and its clinical consequences is higher yield
than memorizing every intermediate in the purine salvage pathway.
Do not spend time learning details of organic chemistry, mechanisms, or
physical chemistry. Detailed chemical structures are infrequently tested;
however, many structures have been included here to help students
learn reactions and the important enzymes involved. Familiarity with
the biochemical techniques that have medical relevance—such as
ELISA, immunoelectrophoresis, Southern blotting, and PCR—is
useful. Review the related biochemistry when studying pharmacology or
genetic diseases as a way to reinforce and integrate the material.
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SECTION II BIOCHEmISTRY ` BIOCHEMISTRY—MOlECUlAR BIOCHEmISTR Y ` BIOCHEMISTRY—MOlECUl AR
` BIOCHEMISTRY—MOlECUlAR
Chromatin structure DNA exists in the condensed, chromatin form to
fit into the nucleus. DNA loops twice around a
histone octamer to form a nucleosome (“beads
DNAdouble-helix on a string”). H1 binds to the nucleosome
and to “linker DNA,” thereby stabilizing the
chromatin fiber.
H1 histone
DNA has ⊝ charge from phosphate groups.
(linker)
DNA Histones are large and have ⊕ charge from
lysine and arginine.
In mitosis, DNA condenses to form
chromosomes. DNA and histone synthesis
Nucleosome Euchromatin Supercoiled
(H2A, H2B, structure occurs during S phase.
H3, H4) 2
Heterochromatin Mitochondria have their own DNA, which is
circular and does not utilize histones.
Metaphase
chromosome
Heterochromatin Condensed, appears darker on EM (labeled H Heterochromatin = highly condensed.
in A; Nu, nucleolus). Sterically inaccessible, Barr bodies (inactive X chromosomes) may be
A
E thus transcriptionally inactive.  methylation, visible on the periphery of nucleus.
 acetylation.
H
Nu
Euchromatin Less condensed, appears lighter on EM (labeled Eu = true, “truly transcribed.”
E in A). Transcriptionally active, sterically Euchromatin is expressed.
accessible.
DNA methylation Changes the expression of a DNA segment DNA is methylated in imprinting.
without changing the sequence. Involved with Methylation within gene promoter (CpG islands)
aging, carcinogenesis, genomic imprinting, typically represses (silences) gene transcription.
transposable element repression, and X CpG methylation makes DNA mute.
chromosome inactivation (lyonization). Dysregulated DNA methylation is implicated in
Fragile X syndrome.
Histone methylation Usually causes reversible transcriptional Histone methylation mostly makes DNA mute.
suppression, but can also cause activation Lysine and arginine residues of histones can be
depending on location of methyl groups. methylated.
Histone acetylation Removal of histone’s ⊕ charge Ž relaxed DNA Thyroid hormone receptors alter thyroid
coiling Ž  transcription. hormone synthesis by acetylation.
Histone acetylation makes DNA active.
Histone deacetylation Removal of acetyl groups Ž tightened DNA Histone deacetylation may be responsible for the
coiling Ž  transcription. altered gene expression in Huntington disease.
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BIOCHEmISTR Y ` BIOCHEMISTRY—MOlECUl AR BIOCHEmISTRY ` BIOCHEMISTRY—MOlECUlAR SECTION II
Nucleotides Nucleoside = base + (deoxy)ribose (sugar).
Nucleotide = base + (deoxy)ribose + phosphate; 5′ end of incoming nucleotide bears the
linked by 3′-5′ phosphodiester bond. triphosphate (energy source for the bond).
α-Phosphate is target of 3′ hydroxyl attack.
Purines (A,G)—2 rings. Pure As Gold.
Pyrimidines (C,U,T)—1 ring. CUT the pyramid.
Thymine has a methyl.
Deamination reactions: C-G bond (3 H bonds) stronger than A-T bond
Cytosine Ž uracil (2 H bonds).  C-G content Ž  melting
Adenine Ž hypoxanthine temperature of DNA. “C-G bonds are like
Guanine Ž xanthine Crazy Glue.”
5-methylcytosine Ž thymine
Amino acids necessary for purine synthesis (cats
Uracil found in RNA; thymine in DNA. purr until they GAG):
Methylation of uracil makes thymine. Glycine
Aspartate
Glutamine
Purine (A, G) Pyrimidine (C, U, T)
Nucleoside
CO
2 Carbamoyl Aspartate
Aspartate Glycine phosphate
C N C
Phosphate
N C N C
C N10–Formyl- O-
C C tetrahydrofolate C C O P O-
N O
N N N
N10–Formyl- Glutamine Nitrogenous base CH₂
tetrahydrofolate
Deoxyribose sugar
Nucleotide
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SECTION II BIOCHEmISTRY ` BIOCHEMISTRY—MOlECUlAR BIOCHEmISTR Y ` BIOCHEMISTRY—MOlECUl AR
De novo pyrimidine Various immunosuppressive, antineoplastic, and antibiotic drugs function by interfering with
and purine synthesis nucleotide synthesis:
Pyrimidine synthesis:
Pyrimidine base production Purine base production or
(requires aspartate) Ribose 5-P reuse from salvage pathway ƒ Leflunomide: inhibits dihydroorotate
(de novo requires aspartate, dehydrogenase
Glutamine + CO glycine, glutamine, and THF)
2 ƒ 5-fluorouracil (5-FU) and its prodrug
2 ATP CPS2 (carbamoyl
phosphate capecitabine: form 5-F-dUMP, which inhibits
2G lAuDtaPm +a Ptei + synthetase II) PpyRrPoPp (hpohsopshpahtoe)r isbyonstyhle tase thymidylate synthase ( dTMP)
Purine synthesis:
Carbamoyl ƒ 6-mercaptopurine (6-MP) and its prodrug
phosphate
Aspartate azathioprine: inhibit de novo purine
Leflunomide
synthesis; azathioprine is metabolized via
PRPP 6-MP,
Orotic azathioprine purine degradation pathway and can lead to
acid
immunosuppression when administered with
UMP synthase UMP Mycophenolate, xanthine oxidase inhibitor
(impaired in IMP ribavirin
Hydorrooxtyicu raecaiduriaRi)bonuclreeodtiudctease UDP AMP GMP Puƒ rimMnyeocn aoonppdhh eponsyporhilmaattieed dainneehd y srdyibrnoatgvheiernisnai:ss e:inhibit inosine
dUDP CTP ƒ Hydroxyurea: inhibits ribonucleotide
reductase
THF Nm5eNth10y-lene THFDHF dUMhymidylate Psynthase 5ca-FpUe,citabine ƒ arMendedut hpcotyatrsrimee x(eat thdeae (omMxiTynXteh):,y imtnrihimdibienitteh d omihpoyrnidmorop (fhTooMlasptPeh) ,a te
Dihydrofolate T
reductase dTMP [dTMP]) in humans (methotrexate),
bacteria (trimethoprim), and protozoa
MTX, TMP,
(pyrimethamine)
pyrimethamine
CPS1 = m1tochondria, urea cycle, found in liver
and kidney cells
CPS2 = cytwosol, pyrimidine synthesis, found in
most cells
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BIOCHEmISTR Y ` BIOCHEMISTRY—MOlECUl AR BIOCHEmISTRY ` BIOCHEMISTRY—MOlECUlAR SECTION II
Purine salvage deficiencies
Nucleic acids Ribose 5-phosphate Nucleic acids
PRPP synthetase De novo synthesis
Nucleotides GMP IMP AMP
Cladribine, pentostatin
Lesch-Nyhan
syndrome
ADA
HGPRT APRT
Nucleosides Guanosine Inosine Adenosine
SCID
PRPP
Free bases Guanine PRPP Hypoxanthine Adenine
XO
Allopurinol
Xanthine
Febuxostat Degradation and salvage
XO
Uric acid
Urate oxidase (rasburicase)
Allantoin
Excretion
ADA, adenosine deaminase; APRT, adenine phosphoribosyltransferase; HGPRT, hypoxanthine guanine phosphoribosyltransferase, XO, xanthine
oxidase; SCID, severe combined immune deficiency (autosomal recessive inheritance)
Adenosine deaminase ADA is required for degradation of adenosine One of the major causes of autosomal recessive
deficiency and deoxyadenosine.  ADA Ž  dATP SCID.
Ž  ribonucleotide reductase activity
Ž  DNA precursors in cells Ž  lymphocytes.
Lesch-Nyhan Defective purine salvage due to absent HGPRT, HGPRT:
syndrome which converts hypoxanthine to IMP and Hyperuricemia
guanine to GMP. Compensatory  in purine Gout
synthesis ( PRPP amidotransferase activity) Pissed off (aggression, self-mutilation)
Ž excess uric acid production. X-linked Red/orange crystals in urine
recessive. Tense muscles (dystonia)
Findings: intellectual disability, self-mutilation, Treatment: allopurinol, febuxostat.
aggression, hyperuricemia (red/orange “sand”
[sodium urate crystals] in diaper), gout,
dystonia, macrocytosis.
Genetic code features
Unambiguous Each codon specifies only 1 amino acid.
Degenerate/ Most amino acids are coded by multiple codons. Exceptions: methionine (AUG) and tryptophan
redundant (UGG) encoded by only 1 codon.
Wobble—codons that differ in 3rd (“wobble”)
position may code for the same tRNA/amino
acid. Specific base pairing is usually required
only in the first 2 nucleotide positions of
mRNA codon.
Commaless, Read from a fixed starting point as a continuous Exceptions: some viruses.
nonoverlapping sequence of bases.
Universal Genetic code is conserved throughout Exception in humans: mitochondria.
evolution.
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SECTION II BIOCHEmISTRY ` BIOCHEMISTRY—MOlECUlAR BIOCHEmISTR Y ` BIOCHEMISTRY—MOlECUl AR
DNA replication Occurs in 5′ Ž 3′ direction (“5ynth3sis”) in continuous and discontinuous (Okazaki fragment) fashion.
Semiconservative. More complex in eukaryotes than in prokaryotes, but shares analogous enzymes.
Origin of Particular consensus sequence in genome AT-rich sequences (such as TATA box regions)
replication A where DNA replication begins. May be single are found in promoters and origins of
(prokaryotes) or multiple (eukaryotes). replication.
Replication fork B Y-shaped region along DNA template where
leading and lagging strands are synthesized.
Helicase C Unwinds DNA template at replication fork. Helicase halves DNA.
Deficient in Bloom syndrome (BLM gene
mutation).
Single-stranded Prevent strands from reannealing or degradation
binding proteins D by nucleases.
DNA Creates a single- (topoisomerase I) or double- In eukaryotes: irinotecan/topotecan inhibit
topoisomerases E (topoisomerase II) stranded break in the helix topoisomerase (TOP) I, etoposide/teniposide
to add or remove supercoils (as needed due to inhibit TOP II.
underwinding or overwinding of DNA). In prokaryotes: fluoroquinolones inhibit TOP II
(DNA gyrase) and TOP IV.
Primase F Makes an RNA primer on which DNA
polymerase III can initiate replication.
DNA polymerase III G Prokaryotes only. Elongates leading strand DNA polymerase III has 5′ Ž 3′ synthesis and
by adding deoxynucleotides to the 3′ end. proofreads with 3′ Ž 5′ exonuclease.
Elongates lagging strand until it reaches Drugs blocking DNA replication often have a
primer of preceding fragment. modified 3′ OH, thereby preventing addition of
the next nucleotide (“chain termination”).
DNA polymerase I H Prokaryotes only. Degrades RNA primer; Same functions as DNA polymerase III, also
replaces it with DNA. excises RNA primer with 5′ Ž 3′ exonuclease.
DNA ligase  I Catalyzes the formation of a phosphodiester Joins Okazaki fragments.
bond within a strand of double-stranded DNA. Ligase links DNA.
Telomerase Eukaryotes only. A reverse transcriptase (RNA- Upregulated in progenitor cells and also often in
dependent DNA polymerase) that adds DNA cancer; downregulated in aging and progeria.
(TTAGGG) to 3′ ends of chromosomes to avoid Telomerase TAGs for Greatness and Glory.
loss of genetic material with every duplication.
G 3'
E
Topoisomerase DNA polymerase III 5'
C A
Helicase Origin of replication
Leading strand
B
Replication fork Lagging strand 3'
Okazaki fragment
D 5'
A
Area of interest Single-stranded RNA primer
Origin of replication
binding protein
Leading strand Lagging strand I
F DNA ligase
Primase
Fork Fork
movement movement
G
DNA polymerase III
Lagging strand Leading strand H
DNA polymerase I
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