Week 3 Flashcards
(144 cards)
1
Q
What leads should you not see Q waves?
A
Right side leads, V1-V3
2
Q
What do changes in ST segment indicate?
A
Myocardial infarction
3
Q
What is the difference between mutation and polymorphism
A
- Mutation: rare change in the NT sequence, usually but not always a disease-causing attribute (<1% freq)
- Polymorphism: A variation in the DNA sequence that occurs in a population with a frequency of 1& or higher
4
Q
What is the difference between genome and chromosome mutation?
A
- Genome mutation: chromosome missegregation
- Chromosome mutation: chromosome rearrangement, ie. translocation
5
Q
Which is the most common:
Chromosome mutation
Gene mutation
Genome mutation
A
- Genome mutation is the most common due to for example chromosome missegregation
6
Q
Transition and Transversion are both type of genetic base substitution. Differentiate the two:
A
- Transition: exchange base pair that is still in the same class, i.e. purine for purine or pyrimidine for pyrimidine
- Transversion: opposite, purine for pyrimidine
7
Q
What is STEMI?
What is it associated with?
A
- ST Elevation
- Associated with coronary vessel total occlusion = MI
8
Q
What does NSTEMI indicate?
A
non-ST elevation with ST depression or T inversion = partial coronary vessel occlusion
9
Q
Hyperkalemia can induce what type of heart rhythms
A
- Arrhythmias: V tac, V fib, Asystole
10
Q
Describe EKG changes in hyperkalemia
A
- Peaked T wave rather than rounded in precordial leads
- Flattening or absence of P wave & prolongation of PR interval
- Widening of QRS complex: more so in extremely elevated levels
11
Q
Describe the appearance of EKG in hypokalemia
A
- QT prolongation
- U waves present
- Shallow, non prominent T wave
- ST Segment depression
12
Q
What is Wolff-Parkinson-White syndrome?
What does the EKG look like?
A
- Ventricular pre-excitation syndrome
- Conduction pathway bypasses the rate-slowing AV node
- Delta wave appearing resulting in widened QRS complex and shortened PR interval
- can also transmit electrical impulses abnormally from the ventricles back to the atria
13
Q
What is the most common arrhythmia associated with Wolff-Parkinson-White syndrome?
A
Paroxysmal Supraventricular Tachycardia
14
Q
Describe visual EKG characteristics of A. fib
A
- No P waves
- Irregularly spaced QRS complex
15
Q
Describe visual EKG characteristics of Atrial Flutter
A
- Sawtooth P wave pattern due to back-to-back atrial depolarization waves
16
Q
What are the EKG characteristics of First Degree AV Block:
A
- Prolonged P-R segment
- Benign, > 0.2 sec
17
Q
Which type of heart block has two types?
What are they?
A
Second degree heart block has 2 types of
- Type I AKA Mobitz I AKA Wenckebach
- Type II AKA Mobitz II
18
Q
Describe EKG characteristics of Wenckebach AV block?
What type of block is this?
A
Wenkebach is Second degree AV block Type I
- Progressive elongation of PR interval
- Intermittent dropped beat (dropped QRS complex)
- variable R-R interval
19
Q
Describe EKG characteristics of Wenckebach AV block?
What type of block is this?
A
Wenkebach is Second degree AV block Type I
- Progressive elongation of PR interval
20
Q
Describe EKG characteristics of Mobitz Type II AV Block
A
- Dropped QRS complex, not preceded by increasing PR interval
21
Q
Describe the EKG characteristics of Third degree AV block
A
- Atria & ventricles beat independently of each other
- P waves & QRS complex not rhythmically associated with one another
- Atrial rate > Ventricular rate such that there are more P waves than QRS complexes
22
Q
When is EKG flat line considered Asystole?
A
When the flatline is > 6 seconds
23
Q
What is a normal PR interval?
A
Between 0.12-0.2 secons
24
Q
What is a normal QRS interval?
A
0.06-0.11 seconds
25
What are the EKG characteristics of A Fib?
- No P waves
- R-R interval is irregular
26
What is the regular QT interval on EKG?
0.36-0.44 seconds
27
When differentiating L & R heart axis deviation, what leads are being observed?
How to determine?
- Use Leads I & Lead II
- Using class method: Lead I is L thumb, Lead II is right thumb
- If Lead I has **POSITIVE** QRS & Lead II _negative_ QRS = Left axis deviation
- If Lead II has **POSITIVE** QRS & Lead I has _negative_ QRS = Right axis deviation
28
What does it indicate if looking Lead I & Lead II and both have negative QRS?
What could cause this?
- Extreme axis deviation
- Caused by misplaced limb electrone
- V tach if QRS is wide
- Rare
29
What conditions can cause L axis deviation?
- Hypertrophy of L ventricle
- HTN
- Aortic stenosis
- Aortic regurgitation
30
___________ axis deviation is normal in newborns.
Right axis deviation is normal in newborns
31
What conditions can cause R axis deviation?
- Pulmonary HTN
- Pulmonary Valve stenosis
- Interventricular septal defect
- Situs invertus
- L posterior fasiscular block
32
What is the vertebrae level of highest point of the iliac crest
L4
33
What vertebrae level is PSIS?
S2
34
Sidebending comes from the ___________ spine while Flexion/Extension comes from _____________ spine.
- Sidebending: Thoracic
- F/E: Lumbar
35
Where is Ligamentum flavum?
Between laminae on the posterior surface of the vertebral canal
36
What thoracic vertebrae are the spine at the same level as their transverse process?
T1-T3 & T12
37
What thoracic vertebrae are the spinous process 1/2 level below the transverse processes?
T4-T6 & T11
38
What thoracic vertebrae are 1 whole level below their transverse process?
T7-T9 & T10
39
________________ contraction of the Rotatores muscles = Extension
Bilateral contraction of the Rotatores = Extension
40
What is the significance of the posterior longitudinal ligament in the thoracic vertebrae?
Prevents central disc herniation which is worse than 1 sided disc herniation
41
_________________ Contraction of the Rotatores muscles = rotation to the opposite side
Unilateral
42
Type I dysfunction can be attributed to what thoracic muscles?
Erector spinae
43
What is “BUL”
Orientation of thoracic superior facet
Backward, Upward, Lateral
44
Compare the articulation of rib to vertebrae vs vertebrae to rib
- Rib: transverse process and body of the same # vertebrae, the body of the vertebrae above
- Vertebrae: the same # rib & the rib below
45
T/F: Rib one is the only exception to rib articulation rules. Such that Rib 1 articulates only with T1
False, while Rib 1 only articulates with T1
Ribs 10-12 articulate with only same vertebrae
Ribs 11-12 do not articulate with transverse process
46
Where do Anterior and Middle scalene attach?
What is their purpose?
Ant & Middle attach to Rib 1 & lift ribs up for respiration
47
Where does posterior scalene muscle attach? What is its action?
Attaches to second rib
Elevation of rib for respiration
48
Which type of ribs are pump handle ribs?
What is pump handle movement?
1. True ribs that attach to the sternum
2. Open and close ribs anterior and posterior
49
What ribs are bucket handle ribs?
What is the purpose of this motion?
- Opens ribs laterally on the transverse axis
- All ribs have pump and bucket, lower than rib 7 more and more
50
What is exhalation dysfunction
- Anterior of the rib is stuck downward = inhalation restriction
- Posterior of rib is stuck up
51
Describe inhaled dysfunction
Stuck up in anterior
Down in posterior
Exhale restriction
52
Ribs 11 & 12 rib dysfunction are most related to:
- Little to do with respiration
- Moreso quadratus lumborum & postural
53
Describe the movement of Rib 11 & 12
Backwards and forwards
54
What is REX BITE LIN
- R ribs = Exhaled
- Bottom Rib = Inhaled
- Top rib = Exhaled
- L rib = inhaled
55
In inhalation rib dysfunction, which rib is the “key” rib?
- Inhalation dysfunction, anterior stuck upwards
- Bottom rib is “key” rib
56
In exhalation dysfunction, which rib is the “key” rib?
- Exhalation dysfunction, anterior stuck downwards
- Top rib is the “key” rib
57
Describe EKG characteristics of SVT
- Regular Rhythm
- HR b/t 150-200
- P wave merged with T wave
- PR interval normal if seen
- QRS complex normal
58
What are common organ targets for in vivo gene therapy?
Eye
Brain
Liver
Skeletal muscle
59
What are some common cell types that are used in Ex Vivo gene therapy?
- Stem cells
- B cells
- T cells
- Natural killer cells
60
For blood related genetic disorders, what is the preferred therapy?
Ex-vivo gene therapy
61
List 3 types of vectors that deliver therapeutic genes to the body
Overall, what do these vectors do?
1. RNA viruses (Retrovirus)
2. DNA Viruses
3. Non-viral vectors
They deliver wild type genes to the body
62
List 3 types of RNA viruses used in gene therapy
1. γ-Retrovirus (Murine leukemia virus)
2. Lentivirus (LVV)
3. Human T-cells lymphotropic viruses
63
List 3 types of DNA viruses that are used to deliver gene therapy
1. Adenovirues
2. Adeno-associated viruses (AAV)
3. Herpes simplex virus (HSV)
64
Why are non-viral vectors _not_ often used to deliver therapeutic genes?
They are not very powerful
65
One disadvantage of retroviruses is that their ability to infect cells can be limited, explain
1. Gamma-retrovirus can only infect **dividing** cells
2. Lentivirus (LVV) can only infect d + **nondividing** cells
66
How are retroviruses used?
Are they in vivo or ex vivo use?
- Viruses insert their RNA, in the form of reverse-transcribed DNA, into the chromosomes of cells
- Retroviruses can transverse nuclear membranes
- Use in ex-vivo due to risk of oncogenesis in in vivo use
67
List 2 advantages of retroviruses & 1 disadvantage
1A. Wide host range
2A. Long term expression of transgene so only needs to be injected once
1D. Cannot be used for large sized genes
68
What cell types are adenoviruses best used for in gene therapy? Why?
- Adenoviruses are used in neurons & muscle cells
- Adenoviruses can invade cells that are _not dividing_
69
Contrast Retroviruses and DNA viruses use to deliver theraputic genes
- Retroviruses insert into the chromosomes and thus do not need repeat injections
- Adenoviruses do not insert their DNA into host & thus requires repeat injections
- Adenoviruses can be used in vivo
- Retroviruses are used ex-vivo
70
T/F: Adenoviruses can be modified to disallow an immune response due to requiring repeated injections. This is because they do not insert their DNA in to the host DNA, so the inserted gene is lost
- 1/2 False, they do invoke immune response
-The remaining is true
71
What are Adeno-associated viruses?
- A type of ss DNA virus that is dependent on helper viruses
- The vectors integrate stably into the host’s DNA, and they are known to cause disease in humans
72
What are the advantages of Adeno-associated viruses ( AAV) location integration
- stable integration into genome in _CHROMOSOME 19_ only which makes it predictable for use and allowable use in vivo
73
List advantages and disadvantages of Adeno-Associated viruses (AAV)
- Not assoc. w/disease
- can obtain high titer virus stocks
- small genome easy to manipulate
- infects both dividing and non-dividing cells
- Disadvantage: can only insert a small DNA sequence
74
What is LVV?
Lentivirus which is a type of DNA virus
75
What are some characteristics of retinitis pigmentosa (RP)?
- Night blindness
- Tunnel vision (due to loss of peripheral vision)
- Latticework vision
76
What is the cause of Retinitis pigmentosa?
- Mutation in gene coding for enzyme in visual pathway
- RPE65 coding for an enzyme that converts all-trans-retinyl esters to 11-cis-retinol
77
What is the name of the gene therapy used in retinitis pigmentosa (RP)?
What is the mechanism of action?
1. Luxturna
2. Use Adeno-associated viruses (AAV) to carry normal copy of target gene (RPE65) and inject AAV into retinal pigment epithelium
78
Briefly describe the generation and production of recombinant adeno-associated viruses and what disorder it can be used in
- AAV production cells with 3 plasmids
1. AAV2 containing plasmid with gene of interest
2. AAV2 plasmid carrying Rep-Cap
3. Plasmid w/helper genes isolated from adenovirus
- Used in TX of Retinitis pigmentosa
79
List side effects of Luxtruna & describe why it can be reliably found on chromosome 19
- SA: Floaters, eye pain, swelling, redness, increased intraocular P
- It is an AAV which always insert on chromsome 19
80
What type of gene therapy is ADSTILADRIN?
What conditions is it used for?
- ADSTILADRIN is a type of in-vivo gene therapy, more specifically, adenovirus
- Used in TX of superficial/non-muscle invasive bladder cancer
81
Describe the mechanism of action for ADSTILADRIN
- Adenovirus use to deliver interferon α-2b (IDN-α2b) to the bladder
- This binds to interferon-α/β receptor that initiates JAK/STAT pathway resulting in triggering body’s own immune response to eliminate the tumor
82
Why is adenovirus genetic therapy specifically used to treat non-invasive bladder cancer?
- Do not want the gene widespread which makes adenovirus a good candidate since it is DNA virus that does not incorporate into genome
- Must be injected into bladder every few months until cancer resolved
83
What are two conditions that can be treated using ex vivo gene therapy?
1. Beta thalassemia
2. Follicular lymphoma
84
What is the genetic therapy used for Beta thalassemia?
Why not perform regular blood transfusions?
1. Tx: Zynteglo which is a Lentiviral Vector
2. Repeated blood transfusions cause severe problems associated with iron overload
85
What induces follicular lymphoma?
- Cancer that originated from specific type of B-cell division upregulation
- translocation of gene from chromosome 14 to 18 and the gene is now near an enhancer region to induce proliferation of B-cells
86
List 4 types of stem cells
1. Embryonic stem cells
2. Induced pluripotent stem cells
3. Mesenchymal stem cells
4. Hematopoietic stem cells
87
What are iPS cells aka iPSCs?
Is there risk associated with their use?
- Induced pluripotent stem cells
- Pluripotent stem cell that can be generated from adult cells
- Risk: ectopic transcription of 4 genes used to make iPSCs can lead to neoplastic development from cells derived from iPSCs
88
Umbilical cord tissue contain what type of stem cells?
- Hematopoietic stem cells
- Mesenchymal stem cells
89
Other than umbilical cord tissue and blood, where else are mesenchymal stem cells found?
- Developing tooth bud of the mandibular third molar
90
1. Hematopoietic stem cells are found in umbilical cord blood and:
2. What conditions might these cells be used for?
1. Can also be found in bone marrow
2. Combind immunodeficiency (SCID) & Lysosomal storage disease
91
Describe the pathway of Lentivirus
1. Package virus in lab & deliver to stem cells
2. Virus is endocytosed
3. In cytoplasm, use reverse transcriptate to transcribe RNA to DNA
4. Integration to many locations but only use stem cells that have integration in desired spot
92
Gene therapy for beta thalassemia is Zynteglo and involves the use of:
______________ & _____________ to deliver what gene to desired cells?
- Gene therapy for beta thalassemia is Zynteglo and involves the use of hematopoietic stem cells that are engineered ex vivo to use Lentivirus
- This therapy delivers HBB gene to to stem cells that are then transplanted to patient
93
What are some side effects of Zynteglo?
What disorder does this gene therapy aim to treat?
1. SA: Low platelets, low WVBC, pain in arms or legs
2. Use hematopoietic stem cells & lentivirus for longterm treatment of Beta thalassemia
94
What genetic therapy options are available for follicular lymphoma? Give details
- Axicabtagene ciloleucel which is a type of CART T-cell therapy
- Ex vivo (γ-retrovirus or Lentivirus)
95
Describe CAR T-cell therapy
1. Use T cells 2. Ex vivo Tx using γ-retrovirus or LVV 3. Engineered T cells express anti-CD19 CARS that recognize and kill B cells
96
What are adverse effects of gene therapy of Follicular lymphoma?
- Fever, low WBC, Low RBC
97
Describe the resistance between the aorta and L ventricle during ventricular ejection
- At the beginning of systole there is very little resistance since flow is high and pressure difference is subtle to allow blood to flow through
- Towards the end, resistance between the two begins to rise as the ventricular volume is lower and thus pressure is lower compared to systemic vascular resistance = Aorta pressure that is higher
98
S2 marks the closure of semilunar valves, what phase of the ventricular cardiac cycle follows?
Isovolumetric relaxation where _all_ valves are **closed** and the ventricles are relaxing. Pressure begins to drop while volume is already low
99
S1 marks the closure of the AV valves, what phase of the ventricular cardiac cycle follows S1?
Isovolumetric contraction where _all_ valves are **closed** but the ventricles are already beginning their contraction which is increasing pressure with no change in volume
100
What is the equation to calculate ejection fraction?
Ejection Fraction = ( Stroke Volume / End Diastolic Volume ) * 100
101
Renin release comes from where?
What does it do?
- Initial part of the Renin-Angiotensin-Aldosterone System
- Renin released by juxtaglomerular cells in kidneys
- Renin converts Angiotensin to Angiotensin I
102
How does ACE-I convert to ACE II?
- _In the lungs_ the enzyme **angiotensin converting enzyme** (ACE) converts Angiotensin I to Angiotensin II
103
Describe the sound of mitral stenosis & where it is heard
- Low pitched diastolic rumble
- Heard at the apex of the heart
104
What decreases mitral stenosis murmur sound?
What makes it worse?
- Decreased intensity with maneuvers that decrease venous return
- Worsened with expiration
105
1. Describe the sound of Mitral valve regurgitation
2. Where is it heard?
1. Holosystolic, high-pitched
- Loudest at apex
- Radiates to axilla
106
1. Describe Tricuspid valve regurgitation sound
2. Where is it heard?
1. Holosystolic, high pitched
2. Loudest at left sternal border 4th ICS
107
1. What worsens mitral valve regurgitation?
2. What worsens tricuspid valve regurgitation?
1. Enhanced by squatting and hand grip
2. Enhanced by inspiration
108
Describe ventricular septal defect sound
- Holosystolic, harsh-sounding murmur
109
Describe Mitral Valve Prolapse Sound
Late systolic crescendo with mid-systolic click
110
Describe how increased sympathetic firing is needed in acute hypovolemia specifically regarding inducing increased venous return & compliance
increased sympathetic tone of the vasculature causes vasoconstriction, which helps to raise blood pressure and increase venous return back to the heart
- this causes _decreased venous compliance_ due to increased pressure
- recall compliance = ΔV / pressure
111
Describe the flow of blood in the umbilical vein during fetal circulation
- Blood travels away from the placenta to the fetus
- The blood is oxygenated from the placenta at 80% O2
112
Describe EKG characteristics of Atrial fibrillation
- Irregularly irregular rhythm
- Narrow QRS
- No organized P waves
113
List three outcomes of acute inflammation
1. Complete resolution
2. Scarring or fibrosis
3. Progression to chronic inflammation
114
What are stimulants of chronic inflammation?
1. Internal Factors: hypersensitivity diseases & autoimmune diseases (presentation of self-antigents)
2. External Factors: non-microbial toxins, microbial
115
Describe autoimmune disorder
Immune system recognizes the normal component of the body as a foreign antigen
116
What is polymorphism?
A variation in the DNA sequence that occurs in a population with a frequency of 1% or higher
117
Differentiate a intrinsic genetic mistake from genetic mistake caused by environmental
1. Intrinsic mutations result when the DNA polymerase makes a mistake
2. Environmental: UV light, nuclear radiation & certain chemicals can alter DNA bases
118
There are two types of mutation that change the identity of a base, describe them
1. Transition: do not alter chemical nature of base, purine for purine or pyrimidine for pyrimidine
2. Transversion: change chemical nature of base, purine for pyrimidine
119
Two types of mutation, transition and transversion can arise from errors during DNA replication including tautomerization & oxidative deamination. Which contributes to which?
1. Tautomerization & oxidative deamination generates _transitions_
2. Oxidation of guanine generates _transversion_
120
Define a silent mutation:
Where does it occur?
- Occurs in the coding region or noncoding region
- Occur when a base pair change in a coding region does not affect the amino acid that is encoded because of the wobble hypothesis.
- The changed codon codes for the same amino acid
121
Define missense mutation:
Where d
- New codon causes insertion of incorrect amino acid into the protein
- The protein function depends on the new amino acid
- Can be okay or bad
122
Define: nonsense mutation
Give an example:
- The new codon causes the protein to prematurely terminate, the product is shortened or not function
- A codon prematurely changed to a STOP codon
- ex: UGG changed to UGA in β-thalassemia or GGA changed to UGA in cystic fibrosis
123
Describe general repercussions of genetic mutation occurring in a regulatory proteins
- Genetic mutation in genes that code for DNA repair enzymes can allow for increased mutation rate for the entire genome
- Genetic mutation in genes coding for transcription factor can cause downstream effects
124
Describe how genetic mutation in Pax-3 gene can cause Klein-Waardenburg syndrome
- Pax 3 gene is a transcription factor
- Genetic mutation in transcription factor can cause widespread downstream effects including congenital deafness & limb abnormalities
125
What might happen if there are mutations in splice sites?
- Genetic mutation in splice site can affect the accuracy of intron removal
- could cause addition of nucleotides to intron
126
What might the spliceosome do if there are mutations in splice sites?
Spliceosome may:
- Leave entire intron unspliced
- Add NT from intron in processed mRNA
- Delete NT from adjacent exon
- Delete an exon from the processed mRNA if next normal splice site is used
127
List 3 disorders that are affected by genetic mutations involving splice sites
- β Thalassemia: splicing defects in HBB gene coding for β globin
- Gaucher's disease: GBA gene
- Tay-Sachs disease
128
Define: frameshift mutation
Loss or gain of 1 to 2 NT resulting in misreading the affected codon and the ones that follow, leading to a different or non-functional protein
129
Define: trinucleotide repeat expansion
- Mutant alleles differ from normal counterparts only in the number of tandem copies of a trinucleotide
- More tandem repeats compared to wild type allele
130
Name 3 diseases induced by trinucleotide repeat expansion
- Huntington disease
- Fragile X syndrome
- Myotonic dystrophy
131
What causes Spinal-bulbar muscular atrophy?
- This form of spinal atrophy is caused by androgen receptor on X chromosome
- CAG trinucleotide repeat has up to 2 times as many repeats as compared to normal
132
Huntington, Spinobulbar Muscular Atrophy, Fragile X syndrome and Myotonic dystrophy are all caused by:
What differentiates them?
- All induced by trinucleotide repeat expansion
- HD & SBMA repeats occur in *coding* region
- Fragile X & Myotonic Dystrophy occur in *untranslated* region
133
What does "g" or "c" mean in genetic mutation nomenclature?
- "g" corresponds to mutation occurring in genomic DNA
- "c" corresponds to mutation occurring in cDNA
134
What is haploinsufficiency?
- Caused by loss-of-function mutation in the heterozygous state in which half normal levels of the gene product result in the phenotypic effects since the remaining copy is unable to make enough product to exhibit normal gene expression
135
Describe how loss of function mutation causes HDR syndrome
- This type of loss of function mutation results in haploinsufficiency
- There are mutations in GATA gene for which the second allele cannot produce enough of the gene's product to maintain normal function
- GATA3 is codes for a transcription factor
136
List 5 characteristics/symptoms of the _____________________ __________________ HDR syndrome.
What causes this disorder?
- HDR syndrome: Hypothyroidism, sensorineural deafness & renal disease caused by loss of function mutation
- Sx: hypocalcemia, tetany, or afebrile convulsions, nephrotic syndrome, cystic kidney, renal dysplasia
137
List the predominant characteristic/symptom of HTT syndrome.
This disorder is caused by ___________________ ___________________ __________________ & is considered a ___________________ _______________________ disorder .
- Hereditary hemorrhagic telangiectasia caused by a loss of function mutation and is considered an autosomal dominant disorder
- Mutation in *ENG* gene that codes for protein Endoglin
- Characterized by vascular dysplasia that occur in mucosal linings of nose & GI
- Arteriovenous malformations in lungs, liver, or brain
138
Describe how ______ of function mutations contribute to Achondroplasia
- Gain of function mutation
- Caused by activating mutation in FGFR3
139
Define hypermorph:
- Hypermorph is related to gain of function mutations
- Increased levels of gene expression
140
Define neomorph:
- Neomorph is related to gain of function mutations
- Development of new function of the gene product
141
Gliomas are caused by what specific type of Gain of function mutation in what gene?
- Gliomas are caused by neomorph mutations in **IDH1** gene
142
What increases severity of gain of function mutations?
What inheritance pattern do they follow?
- Worse if occurring in homozygous state
- Dominantly inherited
143
Nearly all cancers originate from:
Generally and broadly speaking, cancer arises through:
- Nearly all cancers originate from a single cell
- Cancer arises through a series of somatic alteration in DNA in which the alterations involve actual changes in DNA sequences
144
