trigger 3 - hypertrophic cardiomyopathy Flashcards

1
Q

bundles of what make up cardiac myocytes

A

myofibrils

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2
Q

sarcomeres

A

repeating units making up myofilaments
region between two Z-lines
composed of thick and thin filaments

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3
Q

myosin ATPase

A

enzyme that hydrolyses ATP required for actin and myosin cross-bridge formation

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4
Q

3 proteins that make up thin filaments

A

actin
tropomyosin
troponin

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5
Q

troponin complex

A

attached to tropomyosin

contains troponin C - binding site for calcium

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6
Q

when calcium binds to troponin C…

A

conformational change in troponin complex

myosin head exposed

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7
Q

length-dependent activation

A

stretching the sarcomere increases the affinity of Troponin-C (TNC) for Ca2+

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8
Q

types of cardiac action potential

A

non-pacemaker A.P. - fast response

pacemaker A.P. - slow response

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9
Q

where are pacemaker action potentials found

A

sinoatrial node

atrioventricuar node

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10
Q

compare length of duration of between neural/skeletal APs and cardiac APs

A
neural = 1 ms
skeletal = 2-5 ms

cardiac = 200-400 ms

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11
Q

compare role of Calcium in depolarization of neural/skeletal APs to cardiac APs

A

depolarisation of:

neural/skeletal: - caused by opening of Na+ channels

non-pacemaker cardiac: - caused by opening of Na channels, Ca influx prolongs duration of AP causing plateau phase

pacemaker cardiac: - Ca2+ involved in initial depolarisation

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12
Q

3 examples of non-pacemaker action potentials in the heart

A

purkinje cells
atrial myocytes
ventricular myocytes

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13
Q

phase 4

non-pacemaker AP

A

resting membrane potential = -90mV
K+ channels are open - K+ leaves cell making it more negative inside
both fast Na channels and slow L-type Na channels are closed

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14
Q

phase 0

non-pacemaker AP

A
rapid depolarisation (by AP in adjacent cell)
-70mV
Na+ influx through fast Na+ channels
K+ channels close
membrane potential gets more positive
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15
Q

phase 1

non-pacemaker AP

A

(small rapid dip after peak on graph)

initial re-polarisation
opening of special/transient K+ channels
short-lived outward K+ hyperpolarisation

however, Ca influx through slow channels delays this repolarisation

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16
Q

phase 2

non-pacemaker

A

plateau phase

Ca2+ influx through long-lasting L-type channels
open when membrane depolarises to -40mV

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17
Q

phase 3

non-pacemaker

A

repolarisation

K+ efflux
Ca2+ channels inactivation

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18
Q

maintenance of resting membrane potential in cardiac

A

K+ channels open - K+ leaves cell making it more -ve

Na+ and Ca2+ channels closed, cannot enter cell

-90mV

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19
Q

antiarrythmic drugs

A

alter fast-response action potentials
alter (ERP) - effective refractory period
block specific ion channels

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20
Q

effective refractory period (ERP)

A

stimulation of cell cannot initiate action potential
during phases 0, 1, 2, 3, and early 4

fast Na channels close and stay inactivated after phase 1

protects the heart by preventing multiple APs
at a high HR, the rate would be unable to properly fill and ventricular ejection would reduce

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21
Q

non-pacemaker cells to pacemaker cells

A

they can transform under certain conditions

e.g. hypoxia, membrane depolarisation, fast Na channels close
Ca2+ still influxing - same as pacemaker

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22
Q

no true resting membrane potential

A

pacemaker action potentials

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23
Q

why is depolarisation slow in pacemaker cells

A

no fast Na+ channels

depolarisation current carried by slow Ca2+ influx

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24
Q

3 phases of SA node action potentials

A

0, 3, 4

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25
phase 4 | pacemaker
spontaneous depolarisation | triggers action potential once threshold potential is reached (-30/-40mV)
26
phase 0 | pacemaker
depolarisation phase | incline on graph
27
phase 3 | pacemaker
repolarisation (decline on graph) complete repolarisation = around -60mV
28
phase 3 to phase 4 | pacemaker
when -60mV (repolarisation) has been reached slow Na+ channels open creating 'funny current' and Na+ influx cause membrane to spontaneously depolarise and initiate phase 4
29
T-type (transient) Ca2+ channel | pacemaker
opens when membrane potential reaches -50mV during depolariation influx of Ca2+ causes more depolarisation of membrane to -40mV causes L-Type Ca2+ channels to open more Ca2+ influx causes membrane to reach threshold potential (-30/-40mV)
30
what kind of state is necessary for pacemaker cells to become activated
hyperpolarised -ve voltage needed at end of phase 3
31
cause of phase 0 depolarisation | pacemaker
mainly by increased conductance of Ca2+ through L-type Ca2+ channels that open near the end of phase 4
32
what happens to 'funny' and T-type Ca2+ channels near the end of phase 4 (initial depolarisation of pacemaker)
funny currents decline - Na channels close Ca2+ currents through T-type channels decline - channels close
33
penetrance
probability that a person carrying a disease-associated genotype will develop the disease within a given time period
34
penetrance calculation
number of individuals displaying symptoms, divided by the number of individuals with a disease causing mutation x 100
35
incomplete penetrance
when thenumber of individuals who display clinical features of the condition is less than those who carry the mutation.
36
complete penetrance
if a person carrying a disease-associated genotype always develops the conditon
37
expressivity
measures the extent to which a given genotype is expressed at the phenotypic level
38
physical symptoms of cardiomyopathy
``` fatigue dizzyness - reduced O2 to the brain breathlessness - fluid build up around lungs chest pains - reduced O2 to the heart unusual heart beat - palpatations ```
39
hypertrophic cardiomyopathy
ventricle walls become thicker (mainly left and septum) muscle cells are in disarray - disorganised stiffness make it harder to relax and fill with blood and contract and pump blood out
40
HOCM
hypertrophic obstructive cardiomyopathy if the thickening of the heart muscle obstructs blood flow out of the heart
41
causes of HCM
single genetic mutation
42
inheritance pattern of HCM
autosomal dominant | mutated gene is found on a non-sex chromosome
43
beta-blockers and HCM
can prevent arrhythmias | reduce symptoms of obstruction
44
ICD
Implantable Cardioverter Defibrillator detect and correct any dangerous arrhythmias - could cause cardiac arrest
45
ARVC - Arrhythmogenic Right Ventricular Cardiomyopathy
disorder of the myocardium (heart muscle wall) parts of myocardium break down over time - increase risk of abnormal heart beat proteins that make up desmosomes affected
46
autosomal dominant with variable penetrance
the child of an affected parent will have 50% chance of inheriting the abnormal gene, but will not then necessarily go on to have the condition
47
MRI
magnetic resonance imaging
48
why may MRI need to be used instead of ECG for diagnosis of ARVC
signs on an echocardiogram can be very subtle in the early stages of the condition
49
ablation
if medication doesnt seem to work, the part of the heart causing palpations is targeted and cauterised using wires passing through the heart
50
mechanism to prevent sudden cardiac death
implantable cardiac defribrillator (ICD)
51
describe the contractions of vascular smooth muscle (VSM)
slow, sustained and tonic (maintained for a few mins)
52
describe cardiac muscle contractions
rapid and short duration
53
MLCK
myosin light chain kinase enzyme that phosphorylates myosin light chains in the presence of ATP (leads to cross-bridge formation between myosin heads and actin)
54
noradrenaline from sympathetic nerve binds to which receptors in the heart?
beta-1 and beta-2
55
acetylcholine from parasympathetic nerve binds to which receptor type in the hearT?
M2
56
P wave on ECG (first small hump)
atrial depolarisation | trigger for heart contraction
57
QRS complex
ventricle depolarisation
58
bradychardia
slow HR
59
why is efficiency so important in economic evaluation (why are health heed and effectiveness not enough?)
scarcity of resources
60
3 main types of economic evaluation
1. cost-effective analysis (CEA) 2. Cost-utiltiy analysis (CUA) 3. Cost-benefit analysis (CBA)
61
cost-effective analysis
effectiveness measured in natural units | e.g. £ per case detected
62
cost-utility analysis
effectiveness measured in preference-based units £ per Quality-Adjusted Life-Year (QALY)
63
cost benefit analysis
effectiveness also measured and valued in £ net benefit in £
64
QALY
quality adjusted life year measure of diseased burden on quality and quantity of life
65
morbidity
quality of life
66
what should you state to make a good economic evaluation
the perspective of the analysis e.g. patient, patient's family, primary care, health system, society
67
sensitivity analysis
to see if the results are sensitive to different assumptions | vary input variables or assumptions
68
why might false-positives occur?
sample contamination
69
advantage of direct detection methods
good for multicoloured labelling - less prone to non-specific background labelling fewer steps
70
limitation of direct detection
lower sensitivity requires primary antibody to be specifically labelled
71
advantage of indirect detection
higher sensitivity more versatile
72
immunoglobulin
antibody e.g. IgG
73
antigens
proteins or polysacchardies within or on the surface of cells
74
what makes immunnohistochemistry so precise
antibodies bind specifically to the antigen that triggered the antibody's pr
75
direct detection method
antibody attached directly to indicator molecule e.g. fluorescent molecules or HRP enzyme excess added washed away substrate added to localise reaction
76
indirect method
primary antibody added first e.g. IgG - binds to and recognises antigen of interest excess antibody washes away a linking antibody added to mixture - recognises the primary antibody - retains one antigen binding site substrate added to localise reaction
77
why is PCR important in diagnosis
early stages of processing DNA for sequencing do detecting the presence or absence of a gene to help identify pathogens during infection
78
3 steps of PCR
1. denaturing - break H-bonds in double-helix 2. annealing - lower the temp to enable primers to attach by H-bonds to template DNA 3. extension - raise temp and new DNA is made- taq DNA polymerase enzyme
79
why is electrophoresis used after PCR
to check the quantity and size of DNA fragments produced
80
Taq DNA polymerase enzyme
adds DNA bases to the template strand in 5' to 3' direction taken from thermophilic bacteria - thermus aquaticus stable at high tempertures optimum temp = 72
81
5 steps of traditional cloning methods
1. vector preparation 2. insert preparation 3. ligation 4. transformation 5. colony screening
82
vector preparation
restriction enzymes digested by vector (plasmid) dephosphorylation of vector prevents self-ligation 'sticky ends' - more compatible purification of desired fragments recommended for successful ligation
83
insert preparation
restriction digestion blunt end creation purification