USMLE Step 1: Biochemistry & other
Biochemistry
Biochemistry
Dermatitis herpetiformis strongly associated with what?
Celiac disease
Monoclonal lymphocyte proliferation is a strong evidence of what?
Malignancy
Most common renal malignancy
- clear cell ca
- arises from renal tubular cells
- high glycogen & lipid accumulation
abnormal bleeding in patient with uremia due to qualitative platelet disorder
- PTT?
- Platelet count?
- aPTT
- normal
- normal
- normal
Lacunar infarcts
most often due to hypertensive arteriolosclerosis of small, penetrating arterioles
Rupture of apical subpleural blebs
most common cause of primary spontaneous pneumothorax
Extended consumption (>3 mo) of appetite suppressants is associated with what?
increased incidence of pulm. hypertension
vWF disease
most common inherited bleeding disorder
Treatment of hemophilia A
Desmopressin: releases vWF & factor VIII from the endothelium
Synaptophysin: stain for what?
CNS tumors
GFAP: stain for what?
Glia tumors
PCOS: increased risk for which malignancy?
increased risk for endometrial adeno-ca
NSAID-associated chronic renal injury: histologic
papillary necrosis & chronic interstitial nephritis
Opsoclonus-myoclonus
paraneoplastic snyndrome associated with neuroblastoma (increased nr. of copies of the N-myc)
Causes of dilated cardiomyopathy (6)
- viral myocarditis (Coxsackie B)
- Peripartum cardiomyopathy
- Alcohol abuse
- chronic supraventricular tachycardias
- cardiotoxic drugs (e.g. doxorubicin)
- thiamine deficiency (wet beriberi)
Burkitt-lymphoma
C-myc = transcription activator
AL amyloidosis is associated with which malignancy?
Multiple myeloma
Prinzmetal angina: what can provoke spasms?
Ergonovine can provoke coronary spasms
MS
Clinical features
brain tumor in kids
- most likely medulloblastoma or pilocytic astrocytoma
- brain imaging:
- medulloblastoma: only solid
- pilocytic astrocytoma: cystic & solid components
Chromatin structure
- negative DNA loops twice around positively charged histone octamer, which then forms the nucleosome core (H2A, H2B, H3, H4)
- H1 ties beads together
- Heterochromatin
- Euchromatin
- condensed, inactive, inaccessible
- less condensed, active, accessible
- Methylation
- Hypermethylation
- Acetylation
- C-G base pairs on the template strand are methylated –> allows mismatch repair enzymes to distinguish between old & new strands
- inactivates transcription of DNA
- relaxes DNA coiling –> transcription
- Purines
- Pyrimidines
- Bonds
- 2 rings
- Adenosine
- Guanine: has a ketone
- Amino acides necessary for purine synthesis: glycine, aspartate, glutamine
- 1 rings
- Thymine: has a methyl; in DNA
- Cytosine: becomes uracil when deaminated
- Uracil: in RNA
- Bonds
- G-C bond stronger (3H)
- A-T bond (2H)
- Nucleoside
- Nucleotide
- Base + ribose
- Base + ribose + phosphate
De novo pyrimidine and purine synthesis
- Purines:
- start with sugar + phosphate (PRPP)
- add base
- Pyrimidines:
- make temporary base (orotic acid)
- add sugar + phosphate (PRPP)
- modify base
Antineoplastic and antibiotic drugs interfering with nucleotide synthesis (5)
- Hydroxyurea: inhibits ribonucleotide reductase
- 6-mercaptopurine: blocks de novo purine synthesis
- 5-fluorouracil: inhibits thymidylate synthase (dTMP decreased)
- Methotrexate: inhibits dihydrofolate reductase (dTMP decreased)
- Trimethoprim: inhibits bacterial dihydrofolate reductase (dTMP decreased)
Orotic aciduria
- Definition
- Findings (4)
- Treatment
- Inability to convert orotic acid to UMP
- due to defect in either orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase
- autosomal recessive
- Findings
- increased orotic acid in urine
- megaloblastic anemia
- failure to thrive
- No hyperammonemia
- Treament: oral uridine administration
Purine salvage & salvage deficiencies
- Adenosine deaminase deficiency
- excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase –> prevents DNA synthesis and thus decreases lymphocyte count –> SCID (severe comined immunodeficiency disease)
- Lesch-Nyhan syndrome
- absence of HGPRT –> excess of uric acid production & de novo purine synthesis
- findings: retardation, self-mutilation aggression, hyperuricemia, gout, choreoathetosis
- x-linked recessive
Mutations in DNA (4)
- Silent: same aa, often base change in 3rd position of codon
- Missense: changed aa (conservative - new aa is similar in chemical structure)
- Nonsense: change resulting in early stop codon (UAA, UGA, UAG)
- Frame shift: change resulting in misreading of all nucleotides downstream, usually resulting in a truncated, nonfunctional protein
- Helicase
- DNA topoisomerases
- Primase
- DNA polymerase I
- DNA polymerase III
- DNA ligase
- Telomerase
- Unwinds DNA template at replication fork
- Create a nick in the helix to relieve supercoils created during replication
- Makes an RNA primer on which DNA ppolymerase III can initiate replication
- Prokaryotic only. Degrades RNA primer and fills in the gap with DNA
- Prokaryotic only. Has 5' –> 30 synthesis and proofreads with 3' –> 5' exonuclease
- Seals
- Enzyme adds DNA to 3' ends of chromosomes to avoid loss of genetic material with every duplication
Single strand DNA repair (3)
- Nucleotide exicision repair: mutated in xeroderma pigmentosum
- specific endonucleases release the oligonucleotide-containing damaged bases
- DNA polymerase and ligase fill and reseal the gap, respectively
- Base excision repair:
- specific glycosylases recognize and remove damaged bases
- AP endonuclease cuts DNA at apyrimidinic site
- empty sugar is removed
- gap is filled and resealed
- Mismatch repair: mutated in HNPCC
- Unmethylated, newly synthesized string is recognized
- mismatched nucleotides are removed
- gap is filled and resealed
Double strand DNA repair
- Nonhomologous end joining: mutated in ataxia telangiectasia
- brings together 2 ends of DNA fragments
- no requirements for homology
- mRNA start codons
- mRNA stop codons
- AUG
- Eukaryotes: codes for methionine
- Prokaryotes: codes for formyl-methionine
- UGA, UAG, UAA
RNA polymerases
- Eukaryotes
- Prokaryotes
- Eukaryotes
- RNA polymerase I makes rRNA
- RNA polymerase II makes mRNA (opens DNA at promoter site); alpha-amanitin (death cap mushrooms) inhibits RNA polymerase II –> liver failure
- RNA polymerase III makes tRNA
- No proofreading function, but can initiate chains
- Prokaryotes
- 1 RNA polymerase (multisubunit complex) makes all 3 kinds of RNA
RNA processing (eukaryotes)
- Capping on 5' end (addition of 7-methylguanosine occurs in cytosol)
- Polyadenylation on 3' end (ca. 200 A's)
- Splicing out of introns
= mRNA
Disease in which antibodies against spliceosomal snRNPs are found
Lupus
Lac operon
when active, E. coli can metabolize lactose
- Lactose inhibits the repressor
- Glucose inhibits the activator
tRNA
- Structure
- Charging
- Structure
- 75-90 nucleotides
- secondary structure, cloverleaf form
- anticodon end is opposite 3' aminoacyl end
- all tRNAs have CCA at 3' end
- aa is covalently bound to the 3' end of the tRNA
- Charging
- Aminoacly-tRNA synthetase (1 per aa, uses ATP)
- aa-tRNA bond has energy for formation of peptide bond
- a mischarged tRNA reads usual codon but inserts wrong amino acid
Tetracyclines bind 30S subunit, preventing attachment of aminoacyl-tRNA
Protein synthesis
- Initiation
- Elongation
- Termination
- Initiation
- Activated by GTP hydrolysis
- initiation factors help assemble the 40S ribosomal subunit with the initiator tRNA
- Ribosom: eukaryotes (40S + 60S –> 80S), prokaryotes (30S + 50S –> 70S)
- ATP –> charging of tRNA; GTP –> tRNA gripping
- Elongation
- Aminoacyl-tRNA binds to A site
- Ribosomal rRNA catalyzes peptide bond formation, transfers growing polypeptide to amino acid in A site
- Ribosome advances 3 nucleotides toward 3' end of RNA, moving peptidyl RNA to P site
- Termination
- Stop codon ist recognized by release factor, and completed protein is released from ribosome
-
- 1 / 288
-
Lernkarten
P450 microsomal oxidase system
- role
- what poisoning causes it to produces free radicals?
- important for detoxification
- carbon tetrachloride poisoning
Reactive arthritis: what marker?
HLA-B27 spondyloarthropathy
Guillan-Barré syndrome
An immune-mediated acute demyelination of the peripheral nerves
Necrotizing enterocolitis
- one of the most GI emergencies affecting newborns
- associated with prematurity & initiation of enteral feeding
- abdominal x-ray: pneumatosis intestinalis
WBC casts: pathognomonic for what?
Acute pyelonephritis when accompanied by systemic manifestations of febrile illnes
Patent ductus arteriosus: cyanosis?
cyanosis of the lower body
Medullary cancer of the thyroidea
extracellular deposits of amyloid formed by calcitonin secreted from neoplastic parafollicular c-cells
Red neuron
- a neuron responding to an irreversible injury
- 12-24h after injury:
- cell body shrinkage
- eosinophilia of cytoplasma
- pyknosis of the nucleus
- loss of Nissl substance
Hepatic angiosarcoma associated with exposure to what?
- arsenic, thorotrast, polyvinyl chloride
- tumor cells express CD31 (endothelial cell marker)
- ARPRD
- ADPRD
- at birth
- 40-50y
Meconium ileus
quite specific for CF
Acanthosis nigricans: resistance to what?
Insulin
Asbestosis causes most commonly which malignancies?
Bronchogenic Ca followed by mesothelioma
familial chylomicronemia: clinical presentation
presents in childhood with recurrent episodes of acute pancreatitis
high levels dietary aflatoxin exposure associated with what?
G:C –> T:A transversion in codon 249 of the p53 gene –> increased risk HCC
Mitral valve prolapse: regarding endocarditis
most common cardiac abormality predisposing to native vavle bacterial endocarditis
Neurologic damage associated with Vit B12 deficiency
- subacute, combined degeneration of the posterior & lateral spinal columns
- Diagnosis of Vit B12 deficiency: increased serum level of methylmalonic acid
Most common cause of recurrent lobar hemorrhage?
Cerebral amyloid angiopathy
most likely cause of fatigue & new-onset cardiac murmur in young adults?
- bacterial endocarditis
- acute diffuse, proliferative glomerulonephritis secondary to circulating immune complexes –> can result in acute renal failure
Left atrial enlargement can impinge what?
N. laryngeus recurrens sinister
Reye syndrome
- occurs in children with febrile illness treated with aspirin
- hepatic failure + encephalopathy
- histologic: microvesicular steatosis of hepatocytes without inflammation, and cerebral edema
Markers:
- Cytokeratin
- CD20
- CD3
- Myeloperoxidase
- Chromgranin A & neuron-specific enolase
- epithelial origin
- B-lymphocytes
- T-lymphocytes
- Myeloid cells
- mesenchymal origin
- neuroendocrine tumors
HER2/neu oncogene
- 185 kD transmembrane glycoprotein
- has intracellular tyrosine kinase activity –> accelerates cell proliferation
- increases the risk of breast & ovarian cancer
Dactylitis is the most common presentation of what disease in young children?
- in sickle cell disease
- in case of hemolysis, haptoglobin levels decrease by binding to free hemoglobin, and the complex is hepatically cleared
Most common defect in achondroplasia?
activating mutation of FGF receptor-3
Multiple sclerosis: plaques
- within plaques: loss of myelin sheaths & depletion of oligodendrocytes
- cerebrospinal fluid: oligoclonal bands of IgG may be detected
- oligodendrocyte depletion is also senn in progressive multifocal leukencephalopathy
Kussmaul sign
paradoxical rise in jugular venous pressure on inspiration –> indicative of limited right ventricular filling due to right heart failure
Normal pressure hydrocephalus: triad?
- ataxic gait
- urinary incontinence
- dementia
- symptoms are explained by distortion of periventricular white matter
- is a communicating hydrocephalus
- occurs due to a diminished reabsorptive capacity of the arachnoid villi
Cluster headaches
- severe, episodic, unilateral periorbital & temporal oain associated with lacrimation, nasal congestion & ptosis
- usually occur at same time each day
- more common in males
Thrombangiits obliterans
- semental thrombosing vasculitis –> extends into contiguous veins & nerves, encasing them in fibrous tissue
- heavy smokers with onset before 35
- associated with hypersensitivity to intradermal injections of tobacco extracts
aneurysmal compression of the oculomotorious
- early: dilated pupil & loss of accomodation
- late: ptosis & ophthalmoplegia
Diabetic ophthalmoplegia
- "down & out" position
- normal-sized, reactive pupil
- ptosis
Sarcoidosis: macrophages produce what?
activated macrophages –> extrarenal formation of 1,25-dihydroxy vit D
preterm infants: increased risk to develop what?
- hemorrhagic disease
- need supplemation of Vit K
neurofibrillary tangles & amyloid plaques are classic for what?
Alzheimer's
What antibody inhibits T-lymphocytes?
- anti-CD3
- useful in treatment of acute rejection in patients with kidney, heart & liver transplants
N. gonorrhoeae have the ability to do what?
ability of modifying their outer membrane proteins by the process of antigenic variation
IL-8
- produced by macrophages
- induces chemotaxis & phagocytosis in neutrophils
Wiskott-Aldrich syndrome: triad
- eczema
- thrombocytopenia
- combined B- & T-lymphocyte deficiency
- typical:
- onset early in life:
- thrombocytopenia at birth
- eczema & repeated infections (particularly by encapsulated organisms) following at 6-12 months of age
- onset early in life:
IL-4
produced by TH2 –> facilitates growth of B-cells & TH2-lymphocytes and stimulates antibody isotype switching, particularly to IgE
