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DDT > Cardiomyopathy > Flashcards

Cardiomyopathy Flashcards

1
Q

What is visceral smooth muscle?

A

Smooth muscle located in the GI tract, bladder, uterus

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2
Q

Number and position of nuclei in

  • cardiac muscle
  • skeletal muscle
  • smooth muscle
A

Cardiac muscle: 1-4, located centrally
Skeletal muscle: Many nuclei, located on outer edge
Smooth muscle: One nucleus, located centrally

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3
Q

Which types of troponin are present in

  • cardiac muscle
  • skeletal muscle
  • smooth muscle
A

Cardiac muscle: I, T and C
Skeletal muscle: C
Smooth muscle: None

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4
Q

Where would you find a diad and a triad?

A

Diad in cardiac muscle: One t-tubule to one SR

Triad in skeletal muscle: One t-tubule to two SRs

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5
Q

Where is the t-tubule located in cardiac muscle?

A

Z disc

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6
Q

Where is the t-tubule located in skeletal muscle?

A

A-I junction

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7
Q

What causes smooth muscle contraction?

A

Calcium forms a complex with calmodulin
Complex activates MLCK
MLCK phosphorylates regulatory light chains
Causes contraction

MLCP removes phosphates from regulatory chains
Causes relaxation

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8
Q

What effect does Gs subunit receptors have on smooth muscle contraction?

A 
Increase in adenylate cyclase
Increase in cAMP
cAMP inhibits MLCK
No phosphorylation of light chains
No contraction
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9
Q

What effect does Gi subunit receptors have on smooth muscle contraction?

A 
Decrease in adenylate cyclase
Decrease in cAMP
No inhibition of MLCK
Phosphorylation of light chains
Contraction
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10
Q

What effect does Gq subunit receptors have on smooth muscle contraction?

A 
Hydrolyses PIP2 into IP3 and DAG
IP3 releases Calcium from SR
Calcium binds calmodulin
Complex activates MLCK
Phosphorylation of light chains 
Contraction

Also causes activation of Rho-Kinase
Rho-kinase inhibits MLCP

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11
Q

What is the function of DAG?

A

DAG remains within the membrane

Activates Protein kinase C

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12
Q

How does NO mediate smooth muscle contraction?

A 
NO activates guanyl cyclase
Increase in cGMP
cGMP activates MLCP
Removes phosphates from light chains
Relaxation
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13
Q

Which receptors are present on vascular smooth muscle for control of vasoconstriction/contraction?

A

a1 - contraction
a2 - contraction
AT1 - contraction
V1 - contraction

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14
Q

What G-protein subunit are AT1 and V1 receptors coupled to?

A

Gq

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15
Q

How is vasodilation initiated?

A

Parasympathetic NS releases Ach, binds to muscarinic Ach receptors

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16
Q

How does immunohistochemistry work?

A

Used to detect presence (or lack of presence) of specific proteins in a tissue slice
Antigens are labelled with fluorophores which emit light upon excitation

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17
Q

What can immunohistochemistry be used to diagnose?

A

Can diagnose ARVC (after death) by staining a myocardial biopsy for desmosomal proteins

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18
Q

What are the steps of immunohistochemistry?

A

Tissue slice fixed on formalin to expose proteins
Block non-specific binding sites with serum
Wash away anything unbound with saline tween
Incubate with antibodies
Reaction to visualise

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19
Q

What are the advantages of direct immunohistochemistry?

A

More specific
Fewer steps
Just primary antibodies used

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20
Q

What are the advantages of indirect immunohistochemistry?

A

More sensitive
Allows for amplification of the protein when it is in low abundance
Involves using secondary antibodies, producing by injecting another species with IgG antibodies

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21
Q

What is the cause of ARVC?

A

Autosomal dominant mutation
Mutation in desmosomal proteins
Less adherence of cardiomyocytes - separate and die during contraction
Replaced with scar and fat tissue which does not conduct as well
Right ventricle wall thins and ventricle enlarges

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22
Q

What are the phases of a pacemaker action potential (just numbers)?

A

4, 0, 3, 4

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23
Q

What happens during the ‘4’ phase of a pacemaker action potential?

A

At -60mV, HCN (slow sodium) channels open
Allows influx of the ‘funny current’ causing depolarisation
Depolarisation causes opening of T-type and L-type calcium channels

24
Q

What happens during the ‘0’ phase of a pacemaker action potential?

A

The action potential threshold is at -40mV

T-type calcium channels close but L-type channels remain open allowing rapid depolarisation

25
Q

What happens during the ‘3’ phase of a pacemaker action potential?

A

L-type calcium channels close and potassium channels open, allowing potassium efflux and repolarisation

26
Q

What are the phases of a cardiomyocyte action potential (just numbers)?

A

0, 1, 2, 3, 4

27
Q

What happens during the ‘0’ phase of a cardiomyocyte action potential?

A

Action potential arrives initiating opening of fast sodium channels, allowing rapid depolarisation

28
Q

What happens during the ‘1’ phase of a cardiomyocyte action potential?

A

The action potential peaks at +20mv

Sodium channels close and potassium channels open allowing slight K+ efflux, and slight repolarisation

29
Q

What happens during the ‘2’ phase of a cardiomyocyte action potential?

A

L-type calcium channels open allowing calcium influx

The balance of calcium influx and potassium efflux leads to a plateau

30
Q

What happens during the ‘3’ phase of a cardiomyocyte action potential?

A

L-type calcium channels close

Potassium efflux continues, causing repolarisation

31
Q

What happens during the ‘4’ phase of a cardiomyocyte action potential?

A

Resting potential reached at -90mV

32
Q

What is an intercalated disc?

A

The point where two cardiomyocytes join

33
Q

What proteins are present connecting cardiomyocytes transversley?

A

Adherens junctions and desmosomes

34
Q

What proteins are present connecting cardiomyocytes longitudinally?

A

Gap junctions

35
Q

What is the function of desmosomes?

A

Tight adherence of cardiomyocytes
Attaches to the intermediate filaments
Provides mechanical strength to the heart

36
Q

What is the function of gap junctions?

A

Ion channel called connexins
Allow ion flow between cardiomyocytes
Allows for electric coupling

37
Q

What is the function of adherens junctions?

A

Contains catenin and cadherin
Cadherin joins intracellular action of sarcomere to sarcolemma
Links actin of adjacent cells

38
Q

How is heart rate increased through sympathetic nervous system activity?

A 
NA binds to B1 and B2 receptors
Increase adenylate cyclase
Increase cAMP
cAMP activates HCN sodium channels
cAMP also activates PKA
39
Q

What effects does protein kinase A have in regulation of heart rate?

A

Phosphorylation of…

  • L-type calcium channels
  • PLM on Na+/K+ exchanger, faster sodium removal creates concentration gradient for NCX Na+/Ca2+ exchanger, faster calcium removal
  • PLB on SERCA
  • Ryanodine receptors
40
Q

What receptors are present on the heart?

A

B1 and B2

41
Q

How is calcium removed from cardiomyocytes?

A

Ca2+ reuptaken into SR by ATPase powered SERCA
Na+/K+ exchanger re-establishes membrane potential by pumping Na+ out. Creates Na+ concentration gradient used by NCX Na+/Ca2+ exchanger to remove calcium

42
Q

What is the cause of hypertrophic cardiomyopathy?

A

Autosomal dominant mutation affecting genes related to sarcomere
Leads to myocardial disarray
Part of heart becomes hardened/thickened due to overgrowth

43
Q

What are the two most common mutations leading to hypertrophic cardiomyopathy?

A

42% caused by mutation in MYBPC3 gene, codes for myosin binding protein C which has role in sarcomere organisation

40% caused by mutation in MHY7 gene, codes for beta-myosin heavy chain

44
Q

On an ECG, how much time is 1 square equivalent to?

A

0.04 seconds

45
Q

What is length dependent activation?

A

As the sarcomere stretches further, the affinity of troponin C for calcium increases

46
Q

How do anti-arrhymthia drugs work?

A

Block specific ion channels to extend the effective refractory period
Usually potassium channel blocks or sodium channel blockers

47
Q

What is the effective refractory period?

A

Phases 0, 1, 2 and partly 3 of the cardiomyocyte action potential
Stimulation does not result in a new action potential as the sodium channels are not reactivated

48
Q

What is penetrance?

A

Proportion of people with a disease who will express symptoms of it?

49
Q

What does the p wave indicate?

A

Atrial depolarisation

50
Q

What does the Q wave indicate?

A

Left to right interventricular depolarisation

51
Q

What does the R wave indicate?

A

Ventricular depolarisation

52
Q

What does the S wave indicate?

A

Purkinje fibre depolarisation

53
Q

What does the T wave indicate?

A

Ventricle repolarisation

54
Q

How is heart rate calculated?

A

1500/number of small squares in R-R interval?

55
Q

What does HCN channel stand for?

A

Hyperpolarisation-activated cyclic nucleotide-gated channels

DDT (10 decks)

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