Musculoskeletal UWorld Flashcards
Which sarcomere bands remain the same and which change over the course of muscle contraction?
The A-band (myosin filaments) stays the same.
The H-band (area where myosin does not overlap actin) and I-band (area where actin does not overlap myosin) decrease during contraction. “An Interesting Zoo Must Have Mammals” = Actin in the I-band attaches to the Z-line. Myosin in the H-band attaches to the M-line.
Sensitivity
Probability a diseased person will test positive
TP / (TP + FN)
Specificity
Probability a non-diseased person will test negative
TN / (TN + FP)
Positive predictive value
Probability disease is present given a positive result
TP / (TP +FP)
*affected by prevalence and pre-test probability
Negative predictive value
Probability disease is absent given a negative result
TN / (TN + FN)
*affected by prevalence and pre-test probability
Positive likelihood ratio
Likelihood of having the disease given a positive result
Sensitivity / (1 - Specificity)
Negative likelihood ratio
Likelihood of not having the disease given a negative result
(1 - Specificity) / Sensitivity
A child is born with flaccid leg paralysis, dorsiflexed foot contractures and urinary incontinence. Physical exam reveals anal atresia. What condition did the mother likely have during pregnancy?
Poorly controlled maternal diabetes can result in caudal regression syndrome.
Sensorimotor innervation of the peroneal nerve
Superficial: sensation to dorsum of foot and innervation to lateral compartment (eversion)
Deep: sensation to 1st webbed space and motor to anterior compartment (dorsiflexion)
Numbness/pain on sole of foot vs medial foot.
Sole = tarsal tunnel compression of tibial nerve.
Medial foot = compression of saphenous nerve
HLA class II antigens
DR, DP and DQ
Rotator cuff muscle origins, insertions, innervation and function
Supraspinatus: originates at supraspinous fossa, inserts at greater tuberosity, innervated by suprascapular nerve, abducts arm.
Infraspinatous: originates at infraspinous fossa, inserts at greater tuberosity, innervated by suprascapular nerve, externally rotates arm.
Teres minor: originates at lateral border of scapula, inserts at greater tuberosity, innervated by axillary nerve, externally rotates arm.
Subscapularis: originates at sub scapular fossa, inserts at lesser tuberosity, innervated by upper and lower subscapular nerves, adducts and internally rotates arm.
Function of free ribosomes
Synthesis of proteins in the cytosol, nucleosol, peroxisome matrix and nuclear-encoded mitochondrial proteins.
Function of rER ribosomes
Synthesis of secretory proteins, membrane proteins and proteins within the rER, golgi and lysosomes.
How do ribosomes end up on the rER?
The 60S subunit binds translocon on the rER.
In which organelle does steroid hormone synthesis take place?
sER
What is responsible for skin wrinkling as people age?
Reduced collagen fibril production leads to a net decrease in dermal collagen
What histones make up the nucleosome core?
H2A, H2B, H3 and H4. H1 is located outside of the core and binds to DNA of adjacent nucleosomes, resulting in more efficient DNA packing.
Epigenetic process involved in genomic imprinting
DNA methylation by DNA methyltransferases
B. anthracis toxins
Edema factor: acts as adenylate cyclase, increases cAMP, increasing edema and causing phagocyte dysfunction.
Lethal factor: zinc-dependent protease that inhibits MAP-K signaling, resulting in apoptosis
Protective antigen: gets LF and EF intracellular
B. pertussis toxins
Pertussis toxin: Gi ribosylation results in disinhibition of adenylate cyclase -> increased cAMP, edema and phagocyte dysfunction.
Adenylate cyclase toxin: functions as adenylate cyclase, increasing cAMP, edema and phagocyte dysfunction.
C. botulinum toxin
Blocks pre-synaptic release of ACh
C. difficile toxin
A: recruits and activates PMNs
B: induces actin depolymerization leading to cell death, necrosis and pseudomembrane formation.
S. dysenteriae toxin
Shiga toxin: disables 60S subunit, reducing protein synthesis and inducing cell death
S. pyogenes toxins
Pyrogenic exotoxin: superantigen, scarlet fever
Streptolysin O & S: damages erythrocyte membranes
Viral DNA/RNA recombination mechanism
Genetic exchange via crossing over on homologous regions
Viral DNA/RNA reassortment mechanism
2 segmented viruses exchange whole genome segments (“BOAR”: bunyavirus, orthomyxovirus, arenavirus, reovirus”
Viral phenotypic mixing mechanism
Co-infection of a host cell and incorporation into DNA results in a capsid from one virus and genome from the other virus
Why is there reduced complement levels in patients with SLE?
Immune-complex deposition results in complement activation.
What determines to natural progression of leprosy in patients infected by M. leprae?
Tuberculoid: least severe, skin hypopigmentation, plaques and decreased sensation due to intact cell-mediated immune response (Th1)
Lepromatous: most severe, weak cell mediated response (Th2) results in disseminated disease,
How does vitamin B6 result in a microcytic hypochromic anemia? Pellagra? Hypercoaguability?
A) It is necessary for the enzyme ALA synthase to function in generation of porphyrins for heme synthesis, deficiency = sideroblastic anemia.
B) B6 is needed in the synthesis of niacin. Also needed to synthesize DA, histamine, 5-HT and GABA.
C) Needed for cystathione synthase conversion to cysteine. Absence = homocysteinemia.
Southern blot
Northern blot
Western blot
Southwestern blot
Southern = DNA Northern = mRNA Western = protein Southwestern = DNA-bound protein
Structures contained within the carpal tunnel
FDP, FDS, median nerve and FPL
Common meds to avoid in older adults (Beers criteria)
Anticholinergics Alpha-blockers (orthostasis) TCAs (sedation) Sulfonylureas (hypoglycemia) Muscle relaxants (sedation)
1st line drug for acute gout flare
NSAIDs. PMNs phagocytose crystals and release inflammatory mediators that recruit more PMNs, resulting in a vicious cycle that can be broken by NSAID-mediated inhibition of prostaglandin synthesis and reduced PMN activation.
Preferred therapy for gout prophylaxis
Xanthine oxidase inhibitors: allopurinol or febuxostat. Probenecid would be second line
Bisphosphonate mechanism of action
Pyrophosphate analogue that attaches to hydroxyapatite binding sites on bone. Osteoclast uptake of bisphosphonates prevents further bone resorption, induce osteoclast apoptosis and reduce osteoclast recruitment and activation.
Second line drugs for osteoporosis in patients who cannot tolerate bisphosphonates?
Raloxifen (SERM)
Teripartide (rPTH)
Denosumab (RANK-L monoclonal antibody)
Characteristics of drugs that largely undergo hepatic metabolism prior to renal excretion
Highly lipophilic drugs (lipophilic drugs escape renal tubules easily) with a high volume of distribution.
Drug efficacy
Maximum pharmacodynamic effect achievable with a given drug (loops are always more efficacious than thiazides, regardless of dose)
Drug potency
Dose of drug required for desired effect. Drugs with better potency penetrate to target tissue well and have high affinity for the target receptor.
Water soluble vitamin functions and signs of deficiency
B1 - decarboxylates alpha-keto acids in carbohydrate metabolism (pyruvate -> acetyl CoA and alpha-ketoglutarate -> succinyl CoA). Deficiency = beriberi (CHF, neuropathy) and Wernicke-Korsakoff syndrome.
B2 (riboflavin) - carries H+ in mitochondria (FAD, FMN). Deficiency = angular chelosis, stomatitis, glossitis and normocytic anemia
B3 (niacin) - H+ acceptor (NAD+). Deficiency = pellagra
B6 (pyridoxine) - transamination, decarboxylation and deamination of amino acids in amino acid synthesis. Deficiency = cheilosis, stomatitis, glossitis, seborrheic dermatitis, neuropathy.
B7 (biotin) - cofactor for all 4 carboxylase enzymes
B9 - hydroxymethyl/formyl carrier in purine and thymine synthesis. Deficiency = megaloblastic anemia and neural tube defects.
B12 - isomerase and methyltransferase cofactor in DNA and methionine synthesis. Deficiency = megaloblastic anemia and neurologic side effects
Ascorbic acid - hydroxylation of proline and lysine residues in collagen synthesis. Deficiency = scurvy.
3 phases of wound healing
Inflammation: PMNs in 1st day, macrophages in 2-3 days for phagocytosis of necrotic debris
Proliferative: fibroblasts and endothelial vascular cells form granulation tissue with new vessels from days 3-5.
Maturation: fibroblasts synthesize collagen and elastin to form a scar by 6-8 weeks that increases in tensile strength (initially ~30%) over months
What drug could you give a patient to augment the anti-inflammatory effects of azathioprine?
Xanthine oxidase inhibitor (allopurinol). This results in blockade of the inactivating pathway of azathioprine metabolism. Metabolized azathioprine instead goes the HGPRT route and serum levels of 6-TG increase, increasing its effects without increasing the dose.
A mother notes that the urine in the toilet from her 2-year old turned black after sitting there for a while. He also has a bluish-black coloring to his ears, nose and cheeks. What enzyme deficiency could be causing his condition?
Homogentistic acid dioxygenase.
Amino acids elevated in MSUD
Leu, Ile and Val
Amino acid change associated with sickle cell anemia
Glu -> Val substitution
What links osteocyte to osteocyte in mature bone?
Canaliculus. This is a gap junction and an extension of their plasma membranes that allow for signal transduction, solute absorption and solute excretion.
Cyclosporine mechanism of action
Inhibits NFAT from entering the nucleus and impairs the production and release of IL-2
Why use calcipotriol for psoriasis?
It activates the vitamin D receptor, which promotes keratinocyte differentiation and limits proliferation.
Biologics used in treatment of psoriasis
Etanercept (anti-TNF-alpha) and ustekinumab (anti-IL-12 and IL-23, limits proliferation of CD4+ T-cells and Th17 cells)
How does PTH stimulate bone resorption
It binds to osteoblasts, causes them to release RANK-L and M-CSF, which activates osteoclasts and increases production of osteoclasts.
It also reduces production of OPG, which competitively inhibits RANK-L binding to the osteoclastic receptor. Note that estrogen increases OPG levels, decreasing osteoclast activation.
Hypothesized pathogenesis of SLE
Normally T-cells express a Fas receptor and undergo apoptosis in the presence of constant stimulation by self antigens. Normally Fas-L binds Fas-R -> initiator caspase activation (8 & 10) -> executioner caspase activation (3 & 6) -> karyorrhexis, organelle autophagy and membrane blebbing. Any disruption in this process can result in accumulation of excess T-cells that respond to self.
Costimulatory molecules necessary for T-cell activation
CD28 on T-cell
B7 and APC
Costimulatory molecules necessary for B-cell class switching to occur
CD40 on activated B-cell
CD40L on activated T-cell with subsequent cytokine release
Viruses with segmented genomes
Orthomyxoviruses and rotavirues
Universal start codon
AUG -> methionine
Stop codons
UAG, UGA and UAA stimulate releasing factor binding to ribosome and release of the amino acid chain
Oocyte progression through puberty and menstruation
By 5 months gestation, the full store of oocysts are determined and are arrested in prophase of meiosis I as primary oocytes (46, 4N) until puberty.
At puberty, FSH causes a handful of oocytes to complete meiosis I and become secondary oocytes (23, 2N) and polar bodies. The polar body degenerates and the secondary oocyte progresses to metaphase of meiosis II.
At fertilization, meiosis II completes with the paternal DNA and the second polar body degenerates.
How does S. aureus avoid opsonization and phagocytosis?
Protein A binds IgG at the complement binding site in the Fc region, preventing production of C3b necessary for opsonization.
Why are COX-2 inhibitors associated with higher likelihood of stroke/MI?
They block production of PGI2, which normally causes vasodilation and inhibits platelet aggregation. COX-1 activity is also preserved with increased Tx-A2 activity, vasoconstriction and platelet aggregation.
A patient presents with:
1) Sensory deficit on medial thigh and inability to adduct the thigh
2) Sensory deficit on anterior thigh and medial leg with poor thigh flexion and leg extension
3) Sensory deficit on lateral leg with poor foot eversion, dorsiflexion and toe extension
4) Sensory deficit on bottom of foot with poor foot inversion, plantar flexion and toe flexion
5)
1) L2-L4 obturator
2) L2-L4 femoral
3) L4-S2 common peroneal
4) L4-S3 tibial
Pathogenesis of acne vulgaris
1) Follicular epidermal hyperplasia with keratin plug that blocks sebum secretion (mechanism of steroid-related acne)
2) Hypertrophy of sebaceous gland (mechanism of steroid-related acne)
3) Gland colonization with propionibacterium acnes
4) Bacteria hydrolyzes TGs in sebum and inflammatory fatty acids are released
Merocrine vs. Holocrine vs. Apocrine glands
Merocrine: exocytosis, salivary, eccrine sweat and apocrine sweat glands
Apocrine: vesicles, mammary glands
Holocrine: cell lysis, sebaceous and meibomian gland
How does the splicesome work?
snRNPs bind to the 5’ donor site and the branch point on the intron. The 5’ end is cleaved and joins the branch point. Finally, the 3’ end is cleaved and the two ends of the exon on joined by a phosphodiester linkage.
Disease with anti-snRNP antibodies
Mixed connective tissue disease
Latissimus dorsi innervation
Thoracodorsal nerve
Enzyme that forms pre-mRNA from DNA template
RNA polymerase II
Post-transcriptional processing of pre-mRNA
7-methyl-guanosine cap is added to the 5’ end
Poly-A polymerase adds poly A tail after the segment AAUAAA
Introns are removed by splicesome
How is collagen able to form a tight triple helix?
It has a simple amino acid sequence of Gly-X-Y that gets repeated and allows for tight coiling. Many of the X and Y’s are Pro because it allows for bending of the helix.
How does allergic contact dermatitis occur?
Lagerhans cells take the antigen to the lymph node and present it to naive CD4+ T-cells. CD4+ T-cells migrate from lymph node to dermis and induce an inflammatory reaction within 24 hours of antigen re-exposure.
Epidermal acanthosis
Expansion of the stratum spinosum
Epidermal hyperparakeratosis
Nucleus remains in apical portion of epithelium, seen in actinic keratosis and psoriasis
Essential cofactor needed for transaminases
B6
Superficial infantile red compressible hemangioma with sharp borders that grows rapidly during the first 1 to 2 years of life and regress by age 5-8.
Strawberry capillary hemangioma
Small bright red cutaneous papules that consist of dilated capillaries in adults
Cherry hemangioma
Anti-histidyl-tRNA synthetase antibodies
Anti-Jo-1 antibodies present in most cases of polymyositis (biopsy will show endomysial inflammation as opposed to perimysial inflammation seen in dermatomyositis)
Largest ion contributing to the resting membrane potential
K+, it has the highest conductance (permeability). Since there is some membrane permeability to Na+, the membrane potential is slightly more positive than the equilibrium potential of K+ by itself.
c-Jun and c-Fos
Nuclear transcription factors coded for by a proto-oncogene that directly bind DNA via the leucine zipper motif.
How to calculate serum drug concentration
Dose / Volume of Distribution
Mechanism of development of wound contractures
MMPs degrade collagen and extracellular matrix. When there is excessive degradation and myofibroblast contraction, wound contractures can occur.
A patient presents with fever, pruritic rash and arthralgias 1 week after receiving monoclonal antibody therapy for AIHA. Skin biopsy reveals small vessel vasculitis with fibrinoid necrosis and PMN infiltrate. What labs would you expect to see?
This patient has serum sickness (type III hypersensitivity). Labs would show decreased C3 secondary to deposition of complement fixing antibodies.
Mechanism of urushiol contact dermatitis
Type IV hypersensitivity.
Langerhans cells phagocytose antigen and take it to regional lymph node and present it to CD4+ and CD8+ T-cells. This causes activation and clonal expansion over 10-14 days. 2-3 days after the second hapten exposure, the CD8+ T-cells that have migrated peripherally and induce apoptosis.
Most common location in bone to see hematogenously seeded osteomyelitis in kids?
Metaphysis of long bones due to slow flowing vasculature through sinusoids. Note that the vertebral body is the most common location in adults.
