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Flashcards in Biochem to Immuno, plus Pathophys Deck (35)
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Short pt with disproportionately short limbs and large head? Mutation? Inheritance?

Achondroplasia - most cases occur sporadically, but autosomal dominant

Mutation in fibroblast growth factor receptor 3 (FGFR3), which inhibits chondrocyte proliferation and differentiation leading to impaired cartilage maturation and thus impaired endochondral/cartilage-mediated ossification (found in the epiphyseal growth plates of long bones)

Intramembranous/non-cartilage-mediated ossification is normal.


Pt with muscle weakness - difficulty rising from chairs and combing hair, MHC I overexpression on sarcolemma and CD8 infiltration on muscle biopsy?

symmetric progressive proximal muscle weakness


What is fibrillin and where is it found? What disorder is it defective in? Inheritance?

extracellular glycoprotein
major component of microfibrils that forms a sheath around elastin fibers
Fibrin in the extracellular space acts as a scaffold for deposition of elastin extruded from connective tissue cells.

microfibrils present in blood vessels/aortic media, periosteum, and suspensory ligaments of the lens

Marfan syndrome
Defective fibrillin-1 gene
Autosomal dominant


34yo pt with mild urethritis that resolves spontaneously, negative for gonococcal infection - weeks later, acute conjuctivitis, right knee pain, vesicular rash on palms and soles?

Reactive arthritis

will also likely have sacroiliitis


Case fatality rate for an infection - how calculated?

number of fatal cases divided by the total number of people with the disease


Pt with tiredness and a mediastinal mass on imaging? What disease and mechanism?

Myasthenia gravis
circulating antibodies against cell surface ACh receptor results in binding and complement-mediated destruction, producing weakness (most commonly in extraocular muscles)

Associated with thymoma or thymic hyperplasia


Are specificity and sensitivity influenced by disease prevalence? What about PPV and NPV? What relationship?

Specificity and sensitivity are NOT influenced by disease prevalence

PPV varies DIRECTLY with prevalence and pretest probability
(high prevalence/pretest prob. = high PPV)

NPV varies INDIRECTLY with prevalence and pretest probability
(high prevalence/pretest prob. = low NPV)


Pt taking TMP-SMX with joint pain, itchy rash, and fibrinoid necrosis and neutrophil infiltration in arteries and small arterioles?

Serum sickness - Type III hypersensitivity

circulating antigen-IgG complexes activate complement to attract neutrophils which release lysosomal enzymes (tissue damage)

Would find hypocomplementemia 5-10 days after antigen exposure


What is heteroplasmy?

coexistence of both mutated and WT versions of mitochondrial genomes in an individual cell


Pt with neuromuscular lesions, lactic acidosis, and ragged red skeletal muscle fibers? What is the defect? Inheritence?

Mitochondrial myopathies
failure of oxidative phosphorylation leads to myopathy, lactic acidosis, and CNS disease

Muscle biopsy = "ragged red fibers"

Mitochondrial inheritance - variable expression due to heteroplasmy (coexistence of both mutated and WT mtDNA in a cell)


Pt with history of joint pain, swelling, stiffness, and subcutaneous nodules at elbow? What serum findings?

Rheumatoid arthritis
anti-IgG antibody (IgM)


Calcium, phosphate, and PTH levels in pts with osteoporosis? Common fracture that results? What are the two types?

NORMAL lab values and normal bone mineralization
Vertebral crush fractures often occur as a results (back pain, loss of height, kyphosis)

Type I: postmenopausal (increased bone reabsorption due to low estrogen)
Type II: senile (men and women over 70yo)


Describe the steps of collagen synthesis - which steps occur outside the cell? Name three diseases that result from defects in collagen production and the relevant step.

1. Synthesis (collagen alpha chains: Gly-X-Y)
2. Hydroxylation (OH on proline and lysine) **Vitamin C/scurvy
3. Glycosylation & Triple Helix formation (sugar on OH-lysine and triple helix formation via H and disulfide bonds) **Osteogenesis imperfecta
4. Exocytosis (into ECM)
---outside of cell---
5. Proteolytic processing (N and C terminal regions cleaved to form insoluble tropocollagen)
6. Cross-linking (covalent Lys-LysOH cross-linkage by lysyl oxidase forming collagen fibrils) **Ehlers-Danlos

VitC - problem with hydroxylation
Osteogenesis imperfecta - problem with triple helix formation
Ehlers-Danlos - problem with cross-linking tropocollagen into collagen fibrils


What are osteoblasts derived from? What are osteoclasts derived from?

Osteoblasts - differentiate from mesenchymal stem cells in periosteum

Osteoclasts - differentiate from monocytes/macrophages


Describe the pathway of osteoclast differentiation/maturation.

RANK-ligand expressed on surface of osteoblasts binds RANK receptor on osteoclasts to activate and induce differentiation.
OPG (soluble decoy receptor) also made by blasts - the more OPG, the less clast activation.
increased bone turnover with high RANK-L and low OPG by blasts

# of RANK receptors on clasts also affects turnover ratio - more receptors, more bone resorption (as in hypoestrogenism)


Why are ALP levels increased in Paget's?

alkaline phosphatase levels increase during active bone formation
ALP is a byproduct of osteoblast activity!


Describe osteoclasts - how would you identify them on biopsy?

Multinucleated (normal: 2-5 nuclei)
Foamy cytoplasm
Ruffled border at contact with bone
+ for tartrate-resistant alkaline phosphatase (TRAP-positive)

In Paget's: larger and more nucleated (up to 100)


Describe the extrinsic pathway of apoptosis. What is the consequence of mutations of the Fas receptor or Fas ligand?

FasL binding of Fas receptors allows for trimerization of Fas receptors.
Cytoplasmic "death domains" of Fas receptors form a binding site for Fas-associated death domain (FADD) adapter protein, which stimulates the activation of initiator caspases.

Fas-FasL interaction necessary for negative selection in thymic medulla.
Mutations of FasL or Fas receptor can prevent apoptosis of autoreactive lymphocytes, increasing risk of autoimmune disease (basis of autoimmune disorders!).


What is the normal mechanism of vaccine protection against bacteria? What is the mechanism for C. tetani?

Most bacteria: Circulating antibodies bind to microbial cells to signal both macrophage phagocytosis and complement fixation to cause bacterial death.

Tetanus: Humoral immunity specific for the tetanus toxin (tetanospasmin protein toxin that can travel via retrograde axonal transport into the CNS)
Neutralization of the toxin with antitoxin antibodies


Mechanism of C. tetani exotoxin tetanospasmin?

travels retrograde to the CNS

blocks release of inhibitory neurotransmitters from inhibitory motor interneurons in the CNS (loss of inhibition = sustained contraction)


1yo male with recurrent, indolent skin infections and gingivitis, plus delayed separation of umbilical cord after birth? Inheritance?

LAF-1 integrin (CD18) defect
Leukocyte Adhesion Deficiency (type 1)

Autosomal recessive

Skin infections would be WITHOUT pus formation


What type of hypersensitivity disorder is myasthenia gravis? Hypersensitivity pneumonitis? Contact dermatitis?

MG = Type II

HP = Type III or Type IV

CD = Type IV


What is Goodpasture syndrome?

autoantibodies formed against noncollagenous domain of alpha-3 chain of collagen IV (anti-glomerular basement membrane/anti-GM antibodies)
Type II hypersensitivity

cause inflammatory destruction of BM in renal glomeruli and lung alveoli


Pt with sacral agenesis with lower extremity paralysis -- risk factor?

Caudal regression syndrome

Associated with poorly controlled maternal diabetes


Pt stung by bee with edeamtous and erythematous plaque with evanescent borders and mild central pallor - what hypersensitivity type? What Ig type characteristic? What released?

Type I
IgE crosslinked by antigen in allergic response (also anaphylaxis)
Degranulation of mast cells and basophils - release histamine and heparain, forms the wheal described above


Which cytokine responsible for class switching of B cells?

produced by Th2 cells
facilitates growth of B cells and Th2 differentiation
also antibody isotype switching to IgE and IgG


Male pt with 2mo. lower back pain and morning stiffness - limited anterior flexion of spine and inflammation/early fusion of sacroiliac joint?

Ankylosing spondylitis


What are the seronegative spondyloarthropathies? Genetic association?

Psoriatic arthritis
Ankylosing spondylitis
Inflammatory bowel disease
Reactive arthritis

Strong association with HLA-B27 (codes for HLA MHC class I)


What is the most specific serum autoantibody for rheumatoid arthritis?

anti-cyclic citrullinated peptide antibody
(more specific than anti-IgG antibody)


2yo pt with urine sample turned black - deficiency? Inheritance?

Alkaptonuira / ochronosis
Congenital deficiency of homogentisate oxidase in degradation pathway of tyrosine to fumarate

Autosomal recessive, benign but arthralgias may occur (homogentistic acid toxic to cartilage)