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
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Cartes-fiches
Shigella sonnei: pathomechanism
Endocytosis to M cells of Peyer patch in ileum
Nephrotic syndrome
- is a hypercoagulable state
- sudden onset of abdominal or flank pain + hematuria + left-sided variocele –> all this suggests a renal vein thrombosis –> well-known complication of nephrotic syndrome
- loss of anticoagulant factors is responsible –> especially antithrombin III
Myleoperoxidase: role in respiratory infections
- is a heme-containing pigmented molecule
- causes green discoloration of pus or sputum during bacterial infections
- released from neutrophil azurophilic granules
Multiple myeloma in an elderly patient
- easy fatigability
- constipation
- back pain
- azotemia
- biopsy: large eosinophilic casts composed of Bence-Jones proteins
Hemochromatosis
- Mutation of the HFE gene, on the chromosome 6
- Symptoms
- Fatigue
- Malaise
- Joint & bone pain
- liver cirrhosis
- insulin resistance
- erectile dysfunction & hypogonadism –> decreased libido
- congestive heart failure, arrhythmias or pericarditis
- arthritis
- adrenal insufficiency
TNF-alpha
- acute phase protein
- involved in systemic inflammation
- primary role: regulation of immune cells
- can induce fever, apoptotic cell death, cachexia, inflammation and to inhibit carcinogenesis and viral replication and respond to sepsis via IL1 & IL6 producing cells
- A local increase in concentration of TNF will cause the cardinal signs of Inflammation to occur: heat, swelling, redness, pain and loss of function.
- Whereas high concentrations of TNF induce shock-like symptoms, the prolonged exposure to low concentrations of TNF can result in cachexia, a wasting syndrome. This can be found, for example, in cancer patients.
Moderately increased alkaline phosphatase should be followed by what test?
GGT (gamma glutamyl transpeptidase)
Whipple's disease
- caused by bacteria, Tropheryma whipplei
- rare, infectious systemic disease
- causes primarily malabsorption
- common symptoms:
- weight loss
- diarrhoea
- joint pain
- arthritis
- darkening of the skin occurs in half of the patients
Sickle cell patients regarding infections
= are functionally asplenic –> increased risk for infection by encapsulated organisms (St. pneumoniae, Hib)
Gliosis
- nonspecific reactive change of glial cells in response to damage to the cns
- first response to injury: migration of macrophages and local microglia to the injury site = microgliosis (within hours)
- second: oligodendrocyte precursor cells are also recruited to the site and may contribute to remyelination (after 3–5 days)
- Third and final: astrogliosis, the proliferation of surrounding astrocytes, which are the main constituents of the glial scar.
T-cell ALL can cause a mass where?
mediastinal mass that can cause respiratory symptoms, dysphagia or SVCS
Pauci immune glomerulonephritis = ?
ANCA associated rapidly progressive glomerulonephritis (RPGN)
Craniopharyngeoma
- calcified cystic tumor
- remnant of Rathke's pouch
- causes headaches, growth failure, bitemporal hemianopsia
Vit E deficiency
- causes nerve problems
- signs
- neuromuscular problems: e.g. spinocerebellar ataxia, myopathies
- neurological problems: dysarthria, absence of deep tendon reflexes, loss of vibratory sensation and proprioception, positive Babinski sign
- anemia
- retinopathy
- impairment of the immune response
DiGeorge syndrome: deletion of what?
Deletion of long arm chrom. 22
Prior to fertilization, secondary oocytes are arrested in which phase?
Metaphase of meiosis II
consequence of valproate-exposed neonates?
neural tube defects
Phosphatidylcholine (=lecithine) + phosphatidyglycerol
- major constituents of surfactant
- increase sharply after 30 weeks of gestation
- in amniotic fluid
Cleft lip
- failure of proper fusion of the maxillary prominence with the intermaxillary segment
cleft palate
- when palatine shelves of the maxillary prominence fail to properly fuse with one another or with the primary palate
Follicular lymphoma
- t(14;18) –> Bcl-2 overexpression
Early-onset Alzheimer's is associated with 3 gene mutations:
- APP (chrom. 21)
- presenilin 1
- presenilin 2
late-onset Alzheimer's
apolipoprotein E4 genotype
Renal angiomyolipoma
bilateral –> associated with tuberous sclerosis
Hydrocele: what kind of hernia
indirect
CFTR mutation
impairs posttranslational processing of CFTR
What causes enterocysts & Meckel diverticula (=true diverticula)?
failure of obliteration involving the omphalomesenteric duct –> obliterates normally during the 7th week
Ventral & pancreatic bud
- are outgrowths of the duodenum
- join together to form the pancreas
- ventral bud forms the major pancreatic duct
- dorsal bud forms the accessory pancreatic duct
Edward's syndrome (trisomy 18) (4)
- micrognathia
- micropthalmia
- overlapping fingers
- rocker-bottom feet
Kallmann syndrome
- absence of GnRH secretory neurons in the hypothalamus
- clinical findings:
- central hypogonadism
- anosmia
delayed puberty
Patau syndrome (trisomy 13)
- often occurs secondary to nondisjunction during maternal meiosis
- clinical findings:
- cleft lip & palate
- polydactyly, rocker-bottom fett
- holoprosencephaly
Auer rods
AML (M3)
Patent urachus
- leakage of urine through the umbilicus
- 4 anatomical causes:
- urachus cyst
- urachus fistula
- urachus diverticulum
- urachus sinus
Friedreich ataxia
- autosomal recessive
- mutated FXN gene on chrom. 9 with amplified GAA triplets
- associated with:
- hypertrophic cardiomyopathy
- diabetes mellitus
- kyphoscoliosis
- foot deformities
Benign glomus tumor
- appearance
- origin
- can produce a very tender, small red-blue lesion under the nail bed
- originate from the modified smooth muscle cells that control the thermoregulatory functions of dermal glomus bodies
Paraneoplastic cerebellar degeneration
= autoimmune
Cavernous hemangioma
= most common benign liver tumor
Biopsy is contraindicated –> fatal hemorrhage
peptpstreptococcus, prevotella, bacteroides & fusobacterium
- anaerobic bacteria
- normally found in the oral cavity
- most frequent cause of lung abscess
- RF for lung abscess: conditions that increase aspiration risk –> alcoholism, drug abuse, seizure disorders, stroke, dementia
subarachnoid hemorrhage
- cause
- risk after 4-12d
- rupture of saccular aneurysm or arteriovenous malformation
- severe vasospasm after initial insult –> nimodipine can prevent vasospasm
Parvovirus B19
- children
- adults
- erythema infectiosum
- arthritis
