Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MODA > Dr Henderson - Cardiovascular and Renal > Flashcards

Dr Henderson - Cardiovascular and Renal Flashcards

0
Q

What is the structure of the Na+ VGCs α subunit?

A

4 homologous domains - each with 6 TM segments

Part of S4 = voltage sensor

Cytoplasmic loop between III and IV is important in inactivation (also S6 in IV andS5/6 linker)

Region between S5 and S6 forms the pore (S6 is the selectivity filter)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

What is the structure of the Na+ VGC?

A

It has three subunits - α, β1 and β2

α1 forms the pore of the channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Which section of the Na+ channel forms the selectivity filter?

A

S6 of the 4 homologous domains of the α subunit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How does local anaesthetics act upon Na+ VGCs?

A

They bind to channel stabilising it in its inactivated state and make it harder for them to reactivate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the structure of a Ca2+ VGC?

A

Has α1, α2, β, γ and δ subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the functions of the different subunits of the Ca2+ VGC?

A

α1 = the channel

α2δ and β enhance channel trafficking and regulate expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Where do dihyrdopyridines act on Ca2+ channels?

A

Two binding sites - one on the segment S6 of domain 4 and the other is the S5-S5 loop of IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Where do phenylalkylamine bind?

A

Bind to S5/S6 link of domain 4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Where do benzothiazepines bind?

A

They bind to the outside of domain IV (?)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the features of L-types Ca2+ channels?

A 
Need large depolarisation to open
Open for a long time
Responsible for the plateau
Large conductance (22-27Ps)
Sensitive to inactivated channels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the features of T-type Ca2+ channels?

A 
Gated with only a small change in potential
Open transiently
Low conductance (8pS)
No sensitivity to dyhydropyridines
Occur with L-type
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the features of K+ VGCs?

A

S4 segment is voltage sensor

4 channels probably aggregate to form a channel (but one is enough)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the two ways by which K+ VGCs inactivate? explain them both

A

N-type - N terminus forms a ball which is ‘sucked’ into the pore occluding it, as the result of electrostatic changes associated with depolarisation

C-type - Is slower and seems to be the result of movement of residues near the extracellular surface of the pore

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the role of inward rectifying K+ channels?

A

Prevent excessive loss of K+ from depolarised cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is effect does parasympathetic activity have on the heart?

A

Stimulation of M2 receptors by ACh reduces the activity of adenylyl cyclase = activation of HGIRK1 (Kir 3.1)

This is a inward rectifying K+ cell and hyperpolarises the pacemaker cells = reduced excitability and reduced HR

Produces the current called I(K-ACh)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are ATP-sensitive Kir channels?

A

Produces the current I(K-ATP)
These channels open in the presence of low intracellular ATP, but close as intracellular ATP rises

In pancreatic beta cells their closure leads to insulin release
In the heart they act to protect against hypoxic conditions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

I(Na)

A

The current produced by Na+VGCs = depolarising phase of the AP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

I(Ca-L)

A

Produced by L-type Ca2+ channels

The main current during the plateau

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

I(Ca-T)

A

Produced by T-type Ca2+ channels and present in nodal and conductive tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

I(Na-Ca)

A

The current that is the result of the electrogenic activity of the Na+/Ca2+ exchanger

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

I(TO1) & I(TO2)

A

Produced by K+ VGCs of a rather unusual nature

Activate rapidly in Phase 0 and then inactivate rapidly

Responsible for the small ‘notch’ of the AP that constitues Phase 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

I(Ks)

A

Delayed rectifier

Contributes outward current during the plateau and control timing of depolarisation (in Phase 3)

Is the result of two different K+ channels KCNE1 and KLQT2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

I(Kr)

A

Another delayed rectifier

Kv11.1 channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

I(Kur)

A

The third delayed rectifier

Probably due to a channel called Kv1.5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

I(Kp)/I(Cl)

A

I(Kp):-
Caused by a plateau K+ channel that shows no rectification of voltage sensitivity
Produced by TWIK channels

I(Cl):-
Chloride current from CFTR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

I(K1)

A

Inward-rectifier stabilising the resting potential and prevent K+ loss
(I(K-ACh) and I(K-ATP) produce the same sort of current

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

I(f)

A

Pacemaker current

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the structure of Kir channels? What contributes to their inward rectifying nature?

A

Two membrane spanning domains

Mg2+ and spermine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Draw a graph of I against V for the inward rectifying channels

A

Well done have a cookie

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the stages of a ‘typical’ cardiac AP?

A 
0 - Rapid depolarisation
1 - Notch
2 - Plateau
3 - Repolarisation
4 - Inactivation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What can mutations of K+ VGCs cause?

A

Long QT syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What cause LQT3?

A

A mutation in the loop connecting domains III and IV of the cardiac Na+ VGC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What channels cause I(f)

A

HCN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the structure of HCN channels?

A

S1-6 structure
Voltage sensitive S4 segment
Selectivity pore between S5 and S6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What an important feature of HCN channels? (Adrenergic stimulation)

A

They are directly activated by cAMP as opposed to phosphorylation by PKA

cAMP binds to the C-terminus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

When is the HCN channel open and when is it closed?

A

Opened on hyperpolarisation and closed on depolarisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

How does sympathetic stimulation affect the heart?

A

β1 receptor stimulation results in increase cAMP = increased I(Ca-L) and I(Ca-T) by phosphorylation of the α1subunit

In nodal tissue cAMP directly interacts with the HCN channel increasing I(f)

Also sensitisation of Ryanodine receptors = increase Ca2+ release

Phosphorylation of SERCA2 and phospholamban

Increased calcium sensitisation by phosphorylation of tropinin C

Delayed rectifiers are also enhanced = shorter AP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What effect does parasympathetic have on the heart?

A

ACh acts via the M2 receptor = decreased cAMP (Gi)

The potential at which I9f) is activated is shifted to a more negative level

Ca2+ currents are diminished

I(K-ACh) is stimulated, hyperpolarising the cells, making it more difficult to produce APs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Why are parasympathetic effects more chronotropic that ionotropic?

A

Because the M2 receptors are mainly found in the nodal tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What effect does cholera toxin have on the heart?

A

It mimics β1 stimulation through stimulation of the G-protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What effect does forskolin have on the heart?

A

Mimics sympathetic action though stimulation of adenylyl cyclase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Forskolin?

A

Stimulates adenylyl cyclase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is an ectopic pacemaker?

A

A pacemaker that isn’t the SAN (ectopic focus)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

How can an MI cause dysrhythmias?

A

By damaging the conductive pathway of the heart and slowing the conduction velocity of the tissue = uneven spread of discharge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What is Wolff-Parkinson-White syndrome?

A

Congenital abnormal conducting fibres which accelerate the transmission of impulse from atria to ventricles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What can be the cause of dysrhythmias?

A

Infarct
Congenital abnormality in the conducting fibres (WPW syndrome)
Mutant ion channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What is SADS?

A

Sudden Adult Death Syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Draw a diagram to show the normal conductive pathway through the heart and the two types of dysrhythmias.

A

Normal

Inappropriate dysrhythmias and circus dysrhythmias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is Vaughan Williams classification of anti-dysrhythmic based on?

A

Their effect on the cardiac AP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What are the classes of antidysrhythmic agents?

A

Class 1 - Block Na+ VGCs (subdivided by kinetics)
Class 2 - Sympathetic antagonists
Class 3 - Prolong AP (and thus refractory period)
Class 4 - Ca2+ channel blockers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Class I antidysrhythmic agents

A

Block Na+ VGCs

IA = Increased AP duration, intermediate ass/dis
IB = Decreased AP duration, fast ass/dis
IC = No effect on AP, slow ass/dis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Class II antidyrythmic agents

A

Sympathetic antagonists (beta-blockers)

52
Q

Class III antidysrhythmic agents

A

Prolong AP and this refractory period

53
Q

Class IV

A

Ca2+ channel blockers

54
Q

Quinidine

A

Class IA anti-dysrhythmic agent

Increased AP duration, intermediate dis/ass

55
Q

Procainamide

A

Na+ VGC blocker (use dependence as it is charged)

Class IA anti dysrhythmic agent
Intermediate ass/dis, increases AP duration

56
Q

Lidocaine

A

Na+ VGC blocker
Local anaesthetic

Class IB antidysrhythmic agent
Fast ass/dis, decreased AP duration

57
Q

Flecainamide

A

Na+ VGC blocker

Class IC antidysrhythmic agent
Very slow ass/dis, no effect on AP

58
Q

Amlodarone

A

Class III antidysrhythmic agent
Unknown mechanism
Prolongs AP and thus refractory period

59
Q

How do β-blockers work as antidysrhythmics?

A

In ischaemic heart disease cells are partly depolarised and therefore liable to inappropriate excitation

Beta blockers prevent their discharge by lowering their excitability

60
Q

What limits the used of Class IV antidysrhythmic agents?

A

Ca2+ channel blockage can compromise the excitation-contraction coupling process

61
Q

What are the main cause of heart failure?

A 
MI
Beta haemolytic streptococci
Protozoal infection
Dysrhythmias
Systemic/pulmonary hypertension
Heart valve insufficiencies
Diabetes mellitus
Anaemia
Vitamin B1 deficiency
62
Q

What are the four class of dyspnoea

A

Class I - Minimal dyspnoea
Class II - dyspnoea while walking on the flat
Class II - dyspnoea on getting in/out of bed
Class IV - dyspnoea whilst lying in bed

63
Q

What are the drug types used to treat hypertension?

A 
Diuretics
ACE inhibitors
Betablockers
Alpha 1 antagonists
Ca2+ chennel openers
KCOs
Centrally acting alpha a2/II agonists
Other
64
Q

How do cardiac glycosides work?

A

Inhibit the Na+/K+ ATPase thus reducing the activity of Na+/Ca2+ exchanger therefore increasing [Ca2+]i

65
Q

Why are β-blockers used in the treatment of heart failure? Which beta blockers are used?

A

Because chronic adrenergic stimulation of the myocardium leads to desensitization making heart failure worse

Also sympathetic activity decreases hearts efficiency

β1 selective blockers eg bisoprolol and carvedol

66
Q

What is the ratio of adrenoceptors in a normal heart? what is it in heart failure?

A

β1 β2 α1
Normal 70:20:10
Heart failure 50:25:25

67
Q

Bisoprolol?

A

β1 selective agonist used in the treatment of chronic heart failure

68
Q

Carvedilol?

A

β1 selective agonist used in the treatment of chronic heart failure

69
Q

What effect does chronic sympathetic stimulation have on the heart?

A

Alters ratio of adrenoceptors through desensitization

Enhances apoptosis in cardiomyocytes

70
Q

What are inodilators?

A

Phosphodiesterase inhibitors - therefore raise [cAMP]i and thus mimics the effects of beta adrenoceptors stimulation

Used in the treatment of heart failure

71
Q

What is the property of PDE I and what is its inhibitor?

A

Ca2+/calmodulin dependent

Phenothiazines

72
Q

What is the property of PDE II and what is its inhibitor?

A

cGMP-stimulated

No inhibitor

73
Q

What is the property of PDE III and what is its inhibitor?

A

cGMP-inhibited

milrinone

74
Q

What is the property of PDE IV and what is its inhibitor?

A

cAMP-specific

Rolipram

75
Q

What is the property of PDE V and what is its inhibitor?

A

cGMP-specific

Dyhyrdopyridamole and sildenafil

76
Q

Milrinone?

A

PDE type II inhibitor used in the treatment of heart failure

Inhibition of PDE leads to an increase in cAMP and vasodilation (decreases the afterload of the heart)

77
Q

Dipyridamole?

A

PDE type V inhibitor

78
Q

Methylxanthines

A

Eg caffiene

Non-selective PDE inhibitors and A1/2 antagonists
This leads to positive iontropic and chronotropic effects (and increased tendency to give dyrhythmias)

79
Q

Levosimendan?

A

Calcium sensitiser used in the treatment of heart failure

Binds to tropinin 3 leading to more efficient binding

80
Q

Draw the Intrinsic Pathway for clot formation

A

XII —> XIIa
XI —> XIa
IX —> IXa
\/ Xa
\/ Thrombin
Fibrinogen —> Fibrin
\/ <— XIII

81
Q

Draw the extrinsic pathway for clot formation

A 
VIIIa ---> VII
            X ---> Xa
                        \/  Thrombin
                Fibrinogen ---> Fibrin
                                             \/ <---XIII
82
Q

What is the pathway of clot lysis?

A

Plasminogen —–> Plasmin ——> Fibrinogen
\/ \/
————–> Fibrin

83
Q

Streptokinase?

A

47kDa protein formed by haemolytic streptococci

Binds to plasminogen activator and causes generation of plasmin

Leads to degeneration of fibrin in clots (and breakdown of factor II, V and VII)

84
Q

Anistreplase?

A

Clot lysis
Combination of plasminogen and anisoylated streptokinase
Streptokinase is inactive until the anisoyl groups is removed in the blood

More prolong activity that streptokinase

85
Q

Alteplase?

A

Single chain human tissue plasminogen activator

Have greater activity bound to fibrin - localises their activity

86
Q

Duteplase

A

Double chain human tissue plasminogen activator

Have greater activity bound to fibrin - localises their activity

87
Q

Reteplase?

A

Human tissue plasminogen activator

Have greater activity bound to fibrin - localises their activity

88
Q

Clopidogrel

A

Inhibits platelet aggregation by inhibiting binding of ADP to its receptor on platelets

Used with low dose aspirin

89
Q

Eptifibatide

A

Cyclic heptapeptide inhibitor of glycoprotein IIb/IIIa receptor (aIII/b3 antagonist)

(receptor required for the fibrinogen bridging between platelets that causes aggregation)

90
Q

Tirofaban

A

Non-peptide inhibitor of glycoprotein IIb/IIIa receptor (aIII/b3 antagonist)

(receptor required for the fibrinogen bridging between platelets that causes aggregation)

Used to prevent MI in patients with unstable angina

91
Q

Abciximab

A

Monoclonal antibody that acts as an inhibitor of glycoprotein IIb/IIIa receptor (aIII/b3 antagonist)

Also binds to vitronectin (involved in cell adhesion)

(receptor required for the fibrinogen bridging between platelets that causes aggregation)

92
Q

Heparin

A

Naturally occuring anticoagulant from basophils and mast cells

Binds to enzyme inhibitor antithrombin III (AT-III) causing a conformational change that exposes its active site

AT-III inactivates thrombin

Used in unstable angina, after MI and as a prophylactic to prevent DVT

93
Q

Warfarin

A

Inhibits clotting

Inhibits the synthesis of clotting factors II, VII, IX and X and proteins C, S and Z

Dosing of warfarin is complicated as it interacts with many commonly used drug and chemicals

94
Q

Dabigatran

A

Thrombin inhibitor

Used for patients with AF and one additional risk factor for stroke

95
Q

Rivaroxaban

A

The first Xa inhibitor

96
Q

Aminocaproic acid

A

Competitively inhibits plasminogen activation

97
Q

Tranexamic acid

A

Analogue of aminocaproic acid

Competitively inhibits plasminogen activation

98
Q

What is the role of the macula densa?

A

Detects levels of Na+ and Cl- and secretes local hormones to maintain GFR = auto-regulation

99
Q

Where does renin come from? and what is its role?

A

Juxtaglomerular cells and leads to the production of angiotensin II

100
Q

What happens to the arterioles if there is a fall in GFR?

A

Afferent dilates

PGI2 leads to constriction of efferent (and increased angiotensin II)

101
Q

What does an increase in GFR lead to?

A

Increased Na+ in macula densa
Adenosine release
A1 receptor stimultion at afferent arteriole and juxtaglomerular cells
Decreased cAMP
Constriction of afferent arteriole and inhibition of renin

102
Q

How do Loop diuretics work?

A

Act on Loop of Henle

Block Na+/K+/2Cl- co-transport in the luminal membrane in the thick ascending limb = increased Na+ excretion

103
Q

Furosemide?

A

Loop diuretic (blocks Na+/K+/Cl- co-transport)

Also causes venodilation and thus reduces atrial filling pressure

Can lead to hypokalaemia, metabolic alkalosis, Ca2+ and Mg2+ loss and a reduction in uric acid excretion

104
Q

How do thiazide diuretic work?

A

Block Na+/Cl- cotransporter in the thick ascending limb or distal tubule

Bind to Cl- site

105
Q

Hydrocholorothiazide

A

Thiazide diuretic

Blocks Na+/Cl- cotransporter in the thick ascending limb or distal tubule

Binds to Cl- site

Also vasodilator effect

106
Q

Bendroflumethiazide

A

Thiazide diuretic

Blocks Na+/Cl- cotransporter in the thick ascending limb or distal tubule

Binds to Cl- site

Also vasodilator effect

107
Q

What are the side effects of thiazide diuretics?

A

Hypokaleamia
Metabolic acidosis
Increase Mg2+ secretion but decrease that of Ca2+
Uric acid excretion is also decreased

108
Q

How do carbonic anhydrase inhibitors work?

A

Inhibit carbonic anhydrase
Net effect of CA is reabsorption of both Na+ and HCO3-
Therefore this is stopped by inhibition (no HCO3- for the Na+/HCO3- exchanger)
Needs 99% block to be effective

109
Q

Acetazolamide?

A

Carbonic anhydrase inhibitor

Used to be a diuretic, now used to treat glaucoma

110
Q

How do potassium sparring diuretics work?

A

They have different mechanisms but all interfere with Na+ absorption in the late distal tubule

111
Q

Amiloride

A

Potassium sparring diuretic that prevents Na+ reabsorption by blocking apical Na+ channels

112
Q

Triamterene

A

Potassium sparring diuretic that prevents Na+ reabsorption by blocking apical Na+ channels

113
Q

Spironolactone?

A

Potassium sparring diuretic

Acts as an antagonist of the action of aldosterone

114
Q

Canrenone

A

Potassium sparring diuretic

Acts as an antagonist of the action of aldosterone

115
Q

Mannitol?

A

Osmotic diuretic
Filtered at the glomerulus and then not reabsorbed

Rapidly reduces intracranial pressure so is useful in cerebral oedema

116
Q

What causes renin release? What acts to reduce it?

A

Reduction in the perfusion pressure at the kidney and by sympathetic nerve stimulation as the result of increased [cAMP]i

Adenosine, AMP and by negative feedback by angiotensin

117
Q

How do ACE inhibitors work?

A

Prevents production of angiotensin II = no aldosterone secretion (no Na+/water retention)

118
Q

Saralasin?

A

Angiotensin II peptide partial agonist

119
Q

Losartan?

A

AT1 angiotensin II receptor antagonist (non peptide)

120
Q

What is the role of AT2 receptors?

A

Vasodilation
Inhibition of cell proliferation
Present in the brain and during fetal development

121
Q

Captopril

A

ACE inhibitor

122
Q

Aliskiren?

A

Renin inhibitor

123
Q

Enalapril?

A

ACE inhibitor

124
Q

Which enzyme catalyses the conversion of angiotensin II to III

A

Aminopeptidase A

125
Q

What are AT4 receptors?

A

Angiotensin IV receptors that are widely located

They are actually enzymes - insulin regulated aminopeptidases

126
Q

Bradykinin?

A

Natriuretic agent and renal vasodilator

127
Q

How is bradykinin involved in diuresis?

A

If high Na+ reaches the distal tubule then kallikrein is released to convert kinogen into bradykinin

Inhibits Na+ reabsorption (via B2 receptors in the collecting duct)

128
Q

How does ANP work?

A

Released from the heart in response to atrial stretch

Acts via membrane bound GC to form cGMP

Leads to reduciton in BP by...
Vasodilation
Inhibition of noradrenaline secretion
Stimulates diuresis and natriuresis by increasing GFR and inhibition of Na+ absorption
Inhibits renin release

MODA (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions