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Disease, Diagnostics and Therapeutics > Hypertrophic Cardiomyopathy > Flashcards

Hypertrophic Cardiomyopathy Flashcards

1
Q

T wave

A

Ventricular repolarisation

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2
Q

What is needed for pacemaker cells to become activated

A

hyperpolarised

-ve voltage needed at end of phase 3

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3
Q

What are the 5 steps in traditional cloning

A
  • vector preparation
  • insert preparation
  • ligation
  • transformation
  • colony screening
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4
Q

What is the difference generally between smooth and cardiac muscle contractions

A

VSM undergoes slow, sustained, tonic contractions, whereas cardiac muscle contractions are rapid and of short duration.

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5
Q

Give an example of a technology used for recombinant DNA

A

CRISPR

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6
Q

How common is HCM

A

1 in 500

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7
Q

What type of mutation are the HCM mutations normally

A

usually point or missense, bur can be indels

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8
Q

What is the function of myosin ATPase

A

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

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9
Q

What type of genetic dominance/recessiveness is HCM

A

autosomal dominance

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10
Q

Describe sarcomeres

A

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

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11
Q

What is the effective refractory period (ERP)

A

stimulation of cell cannot initiate action potential

fast Na channels close and stay inactivated after phase 1

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12
Q

Intercalated discs contain three different types of cell-cell junction. What are these?

A
  • Fascia adherens junctions
  • Expanded desmosomes
  • Gap Junctions
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13
Q

What is a conjugated protein

A

a protein bound to something else.

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14
Q

What is faulty in ARVC

A

Desmosomes

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15
Q

What does the calcium-calmodulin complex activate

A

myosin light chain kinase

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16
Q

bundles of what make up cardiac myocytes

A

myofibrils

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17
Q

What is an ECG

A

A trace showing the rhythm of the heartbeat, where abnormalities can be detected.

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18
Q

What do indels cause in a genetic sequence

A

frame shift

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19
Q

QT interval

A

Time taken for ventricular depolarisation and repolarisation

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20
Q

What is HCM

A

overgrowth of the septum of the heart into the left ventricle, causing outflow tract obstruction so blood cannot flow out of the aortic valve.

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21
Q

P wave

A

Atrial depolarisation

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22
Q

What gene is most commonly affected in HCM

A

42% cardiac MyBP-C

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23
Q

What are the ‘funny’ channels gated by

A

Hyperpolarisation activated cyclic nucleotide gated channels

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24
Q

What is the function of the Hyperpolarisation activated cyclic nucleotide gated channels

A

They keep generating Aps.

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25
Q

On an ECG trace, how would you work out HR using squares

A

HR= 1500/number of small squares in RR interval
Or
HR= 300/number of large squares in RR interval

26
Q

True or false: HCM is frequently asymptomatic until sudden cardiac death

A

True

27
Q

Why is depolarisation slower in pacemaker cells

A

no fast Na+ channels

depolarisation current carried by slow Ca2+ influx

28
Q

What is ARVC

A

This is an enlargement of the right ventricle, loss of myocytes, and a fibrotic, fatty heart

29
Q

When does VSM relaxation occur

A

when there is reduced phosphorylation of MLC

30
Q

What is CRISPR cas-9

A

a CRISPR-associated protein containing two nuclease domains, programmed by small RNAs to cleave DNA

31
Q

How is the resting membrane potential maintained

A

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

Na+ and Ca2+ channels closed, cannot enter cell

-90mV

32
Q

Explain the steps of a non-pacemaker cardiac action potential

A
  • Rapid depolarisation due to opening of fast Na+ channels (0)
  • Initial repolarisation caused by opening of K+ channel (1)
  • Inward Ca2+ movement through L-type channels (slow) which open when membrane reaches -40mV. Plateau phase due to delayed repolarisation. (2)
  • Repolarisation occurs when K+ channels open, and closure of Ca2+ channels (3)
  • True resting membrane potential (stable). Closed Na+ and Ca2+ channels, open K+ channels. (4)
33
Q

What are gap junctions

A

o Provide direct contact between the cardiac cells
o Facilitate electrical communication, so that waves of depolarisation spread rapidly over the entire heart, by passing from cell to cell
o connexin subunits make pores

34
Q

Q wave

A

Left to right interventricular septum depolarisation

35
Q

What are fascia adherens junctions

A

o Actin filaments attach to thin filaments in the muscle sarcomeres to the sarcolemma
o So, they all contract together in a functional syncytium

36
Q

What does MLC phosphorylation lead too

A

cross-bridge formation between the myosin heads and the actin filaments, and smooth muscle contraction.

37
Q

What are the symptoms of ARVC

A

palpitations, lightheadedness, and fainting. ARVC can also cause shortness of breath and abnormal swelling in the legs or abdomen.

38
Q

What can reduce phosphorylation of MLC

A
  1. reduced release of calcium by the SR or reduced calcium entry into the cell
  2. inhibition of MLCK by increased intracellular concentration of cAMP
  3. phosphatase-activated MLC dephosphorylation.
39
Q

What is faulty in HCM

A

sarcomere

40
Q

What is the purpose of the effective refractory period

A

protects the heart by preventing multiple APs

at a high HR, the rate would be unable to properly fill and ventricular ejection would reduce

41
Q

What is the purpose of the intercalated discs of the heart

A

connect cardiomyocytes to work as a single functional organ/syncytium

42
Q

What is the name for the invagination of the sarcolemma

A

Transverse (t) tubule

43
Q

An increase in which ion stimulates VSM contraction

A

calcium

44
Q

Compare the role of Calcium in depolarization of neural/skeletal APs to cardiac APs

A

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

45
Q

Explain the steps of a pacemaker cardiac action potential

A
  • Spontaneous depolarisation (pacemaker potential) caused by funny currents. T-type Ca2+ open; further depolarisation. L-type Ca2+ opens. K+ channels close (4)
  • Depolarisation of the AP, caused by increased Ca2+ conductance through L-Type channels. T-type channels close. (0)
  • Repolarisation of the AP as K+ channels open and Ca2+ close. Hyperpolarisation reached. Na+ ion channels open, initiating phase 4- also called funny currents or If. (3)
46
Q

what happens to ‘funny’ and T-type Ca2+ channels near the end of phase 4 (initial depolarisation of pacemaker)

A

funny currents decline - Na channels close

Ca2+ currents through T-type channels decline - channels close

47
Q

S wave

A

Interval between ventricular depolarisation and repolarisation

48
Q

What is the length-dependent activation of the sarcomere

A

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

49
Q

In VSM what does free calcium bind to initatially

A

Calmodulin

50
Q

How to calculate penetrance

A

number of individuals displaying symptoms, divided by the number of individuals with a disease causing mutation x 100

51
Q

Define penetrance

A

probability that a person carrying a disease-associated genotype will develop the disease within a given time period

52
Q

What happens when calcium binds to troponin C

A

conformational change in troponin complex

myosin head exposed

53
Q

ST segment

A

Interval between ventricular depolarisation and repolarisation

54
Q

What causes phase 0 depolarisation of pacemaker cells

A

mainly by increased conductance of Ca2+ through L-type Ca2+ channels that open near the end of phase 4

55
Q

Define recombinant DNA technology

A

the joining of DNA from two different species, that are inserted into host organisms to produce new genetic combinations

56
Q

What is unusual about the cardiac pacemaker AP

A

There is no resting phase or RMP & Ca2+ (instead of Na+) is responsible for main depolarisation.

57
Q

What are the two types of cardiac action potential

A

non-pacemaker A.P. - fast response

pacemaker A.P. - slow response

58
Q

Describe smooth muscle

A

non-striated, single celled (mononuclear) and is found in organs such as the bladder, GI tract and blood vessels.

59
Q

What are expanded desmosomes

A

o strong adhesion between cells
o link to the intermediate filament of the cytoskeleton
o structural integrity

60
Q

R wave

A

Early ventricular depolarisation

61
Q

What 3 proteins make up the thin filament

A

actin
tropomyosin
troponin

Disease, Diagnostics and Therapeutics (14 decks)

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