Cardiomyopathy Flashcards Preview

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Flashcards in Cardiomyopathy Deck (55):
1

What is visceral smooth muscle?

Smooth muscle located in the GI tract, bladder, uterus

2

Number and position of nuclei in
- cardiac muscle
- skeletal muscle
- smooth muscle

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

3

Which types of troponin are present in
- cardiac muscle
- skeletal muscle
- smooth muscle

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

4

Where would you find a diad and a triad?

Diad in cardiac muscle: One t-tubule to one SR
Triad in skeletal muscle: One t-tubule to two SRs

5

Where is the t-tubule located in cardiac muscle?

Z disc

6

Where is the t-tubule located in skeletal muscle?

A-I junction

7

What causes smooth muscle contraction?

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

MLCP removes phosphates from regulatory chains
Causes relaxation

8

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

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

9

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

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

10

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

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

11

What is the function of DAG?

DAG remains within the membrane
Activates Protein kinase C

12

How does NO mediate smooth muscle contraction?

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

13

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

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

14

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

Gq

15

How is vasodilation initiated?

Parasympathetic NS releases Ach, binds to muscarinic Ach receptors

16

How does immunohistochemistry work?

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

17

What can immunohistochemistry be used to diagnose?

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

18

What are the steps of immunohistochemistry?

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

19

What are the advantages of direct immunohistochemistry?

More specific
Fewer steps
Just primary antibodies used

20

What are the advantages of indirect immunohistochemistry?

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

21

What is the cause of ARVC?

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

22

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

4, 0, 3, 4

23

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

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

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

The action potential threshold is at -40mV
T-type calcium channels close but L-type channels remain open allowing rapid depolarisation

25

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

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

26

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

0, 1, 2, 3, 4

27

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

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

28

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

The action potential peaks at +20mv
Sodium channels close and potassium channels open allowing slight K+ efflux, and slight repolarisation

29

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

L-type calcium channels open allowing calcium influx
The balance of calcium influx and potassium efflux leads to a plateau

30

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

L-type calcium channels close
Potassium efflux continues, causing repolarisation

31

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

Resting potential reached at -90mV

32

What is an intercalated disc?

The point where two cardiomyocytes join

33

What proteins are present connecting cardiomyocytes transversley?

Adherens junctions and desmosomes

34

What proteins are present connecting cardiomyocytes longitudinally?

Gap junctions

35

What is the function of desmosomes?

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

36

What is the function of gap junctions?

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

37

What is the function of adherens junctions?

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

38

How is heart rate increased through sympathetic nervous system activity?

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

39

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

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

What receptors are present on the heart?

B1 and B2

41

How is calcium removed from cardiomyocytes?

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

What is the cause of hypertrophic cardiomyopathy?

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

43

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

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

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

0.04 seconds

45

What is length dependent activation?

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

46

How do anti-arrhymthia drugs work?

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

47

What is the effective refractory period?

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

What is penetrance?

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

49

What does the p wave indicate?

Atrial depolarisation

50

What does the Q wave indicate?

Left to right interventricular depolarisation

51

What does the R wave indicate?

Ventricular depolarisation

52

What does the S wave indicate?

Purkinje fibre depolarisation

53

What does the T wave indicate?

Ventricle repolarisation

54

How is heart rate calculated?

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

55

What does HCN channel stand for?

Hyperpolarisation-activated cyclic nucleotide-gated channels