CSF First Aid/BRS Block 1 Flashcards
what is the clinical name for brittle bone disorder?
what is the most common type of genetic mutation?
which collagen type?
what are the symptoms?
may be confused with?
Osteogenesis Imperfecta
- most common form is autosomal dominant
- collagen type I (bone, skin, tendon, dentin, fascia, cornea, late wound repair)
1. multiple fractures with minimal trauma; may occur during birth process
2. blue sclera due to the translucency of the connective tissue over the choroid
3. hearing loss (abnormal middle ear bones)
4. dental imperfectiosn due to lack of dentin
May be confused with child abuse.
-type II is fatal in etero or the neonatal period. incidence is 1: 10,000
what causes scurvy and why?
clinical symptoms?
vitamin C deficiency because lack of ascorbic acid (from bit c) which acts as a cofactor (for propyl hydroxylase) in collagen production
s/s: swollen gums, bruising, hemarthrosis, anemia, poor wound healing, weakened immune response
what are the essential amino acids? What does that mean?
which are acidic and basic. What is their charge at physiological pH? which is most basic?
Which are required during periods of growth?
-only L form aa are found in proteins
Basic: Shallow HAL had a positive image
Histidine, arginine, lysine—> positive at body pH
Acidic: Hey mate, you’re an asshole
Glutamate, aspartate—> negative at body pH
Histidine and Arginine are required during periods of growth. Arg and lys are increased in histones which bind negatively charged DNA.
Histidine is not charged at physiological pH bc it has a ring and can transfer positive charge. has 2 pkas- 5.8 and 7.8.
essential: PVT TIM HALL/ i like to teach my vets lumbar puncture
Phe, Val, The, Trp, Ile, Met, His, Arg, Leu, Lys
describe protein migration in an electric field
Positively charged proteins are cations and migrate toward the cathode(–).
neg charged proteins are anions and migrate toward the anode (+)
marfans syndrome
Marfan syndrome results from mutations in the gene for the highly a-helical
fibrillary protein fibrillin, which is a major component of microfibrils found in the extracellular matrix. Patients have defective connective tissue, particularly in the ligaments and aorta. They present with excessively long extremities and fingers, arachnodactyly, and a predisposition to dissecting aortic aneurysms and valvular disease.
prion diseases
Prion diseases like Creutzfeldt-Jakob disease (CJD) result from the transmission
of a proteinaceous agent that is capable of altering the normal a-helical arrangement of the prion protein and replacing it with b-pleated sheets and smaller a-helices, similar to the pathogenic form. The resulting misfolded protein is resistant to degradation, with death of the affected neurons. Patients suffer pronounced involuntary jerking movements (startle myoclonus) and rapidly deteriorating dementia.
hoeobox proteins
the family of transcription factors known as homeobox proteins contains
helix-turn-helix motifs. They play a significant role in pattern development during development of the limbs and other body parts. Disruption of protein–DNA interactions in these proteins may result in congenital malformations
misfolded proteins can aggregate to form—
Misfolded proteins can aggregate to form insoluble b-pleated fibrils, or amyloid. These fibrils accumulate in tissue, often resulting in worsening pathology as the amyloid accumulates. See
Table 1-1 for some clinically relevant amyloidopathies.
mutations in patients with a1-antitrypsin (AAT) deficiency result in a misfolded
protein that gets trapped within the cell. Patients with decreased levels of this protease inhibitor manifest with cirrhosis and emphysema.
hungtington disease
Huntington disease results from the expansion of a region of polyglutamine
repeats within the Huntington protein. The protein aggregates and forms intranuclear inclusions, resulting in neuronal cell death. Patients present with progressive movement disorders and dementia.
A24-year-oldmanpresentstoyourclinic with several concerning symptoms. He states that he has uncontrollable movements called chorea, occasional stiffness, slurring of speech, difficulty planning his day and balancing his checkbook, and bouts of anxiety and crying spells. He also professes that this has been noted in some relatives on his mother’s side. What is true about the nature of the molecular mutation of this disorder?
(C) A triplet repeat expansion within a gene
hispatienthasalltheclassicsignsandsymptomsofHuntingtondisease.Hun- tington disease is an autosomal dominant disorder that involves the huntington gene. This gene encodes a sequence of repeating trinucleotides, which gives rise to a polyglutamine stretch in the protein. In certain individuals, those that express Huntington disease, this trinucleotide repeat is greatly expanded, and the stretch of polyglutamine in the protein is enlarged, leading to a dys- functional protein that, over time, leads to altered neuronal function.
Other diseases that result from trinucleotide repeat expansion include spinobulbar muscular atrophy, spinocerebellar ataxia, fragile X syndrome, Friedreich ataxia, and myotonic dystrophy. Huntington disease is not due to a single nucleotide change, a frameshift mutation, or a deletion event within the gene.
A27-year-oldfirefighterisbroughttothe emergency room after being exposed to smoke during a training exercise. He looks ill and has labored breathing. He is clutching his head and exhibits an altered mental status. On examina- tion, you note that he appears red, and his pulse oximetry reads 100%. You suspect carbon monoxide toxicity. What is true of the oxygen saturation curve during carbon monoxide toxicity?
Oxygensaturationcurves relate the saturationofhemoglobinwithoxygen fora given partial pressure of oxygen. If carbon monoxide binds to one of the subunits of hemoglobin, the affinity of the other subunits for oxygen is increased (due to the cooperative nature of oxygen binding to hemoglobin). This shifts the oxygen binding curve to the left. Because the oxygen now has a higher affinity for hemoglobin, it is more difficult for hemoglobin to release oxygen to the
tissues, leading to hypoxia despite oxygen being bound to hemoglobin. Conditions that shift the curve to the right allow oxygen to be released more readily: low pH, increased PCO2, increased temperature, presence of 2,3-bisphosphoglycerate, and absence of carbon monoxide. In other words, hemoglobin will release oxygen in states that allow for normal binding of oxygen and increased oxygen demands by tissues.
A59-year-oldmanpresentswithnephrotic syndrome. Immunoelectrophoresis detects a monoclonal immunoglobulin G (IgG) l subtype in his serum and free l light chains in his urine. A renal biopsy shows amyloidosis. Although several different proteins are precursors to amy- loid deposition, all amyloid fibrils share an identical secondary structure that is which of the following?
Regardlessofthetypeofamyloiddisease,thepathogenesisisrelatedtothe accumulation of b-pleated protein. In the case of multiple myeloma, it is the accumulation of immunoglobulin light chains in the kidney and heart. a-Helical proteins include native fibrillary proteins. The triple helix is a unique structure found in collagen. Helix-turn-helix and leucine zippers are supersecondary structures that are often found in transcription factors, like homeo- box proteins (helix-turn-helix).
Thepatientdescribedinquestion8,whohas multiple myeloma, has not responded to numerous treatments, and his disease is pro- gressing. He sees his oncologist, who wants to start him on the drug bortezomib. Bortezomib inhibits the proteasome from degrading pro- teins. Which class of intracellular proteins will not be specifically degraded as a result of taking this drug?
TheanswerisC. : Polyubiquitinated proteinsTheproteasomenormallydegradesproteinsthathavebeenpolyubiquitinated. As such, in the presence of bortezomib, polyubiquitinlated proteins will accumulate within cells, leading to a selective adverse effect on the cancer cells (myeloma cells) because these are the cells growing most rapidly. Proteins with PEST sequences are rapidly degraded by nonspecific intra- cellular proteases. Although the immunoglobulin light chains are forming the amyloid proteins in this disease, these structures are difficult to degrade, such that inhibiting the proteasome has no effect on the degradation of the amyloid proteins. Immunoglobulin heavy chains are not accu- mulating in this disorder.
Whichaminoacidisamajorneurotransmit- ter in the brain?
glutamate
