Physiology Flashcards
(64 cards)
1
Q
What is the function of the CV system?
A
facilitate exchange of
- gases (O2 + CO2)
- electrolytes
- fluid
- large molecules
- heat
- heart: hormonal synthesis (ANP)
–> make sure adequate blood flow is delivered to organs
2
Q
What determines organ blood flow?
A
(Pa - Pv)/SVR
3
Q
What determines vascular resistance?
A
- length and diameter of blood vessels
- anatomical arrangement of vascular network
- blood viscosity
4
Q
What are inotropic changes?
A
changes in contraction resulting from altered Ca++ handling and myosin ATPase activity
5
Q
How is inotropy modulated on a cellular level?
A
- Ca++ entry through L-tvpe channels
- Ca++ release from sarcoplasmatic reticulum
- Ca++ binding to cTnC
- Myosin phosphorylation
- SERCA activity
- Ca++ eflux across sarcolemam
6
Q
What regulates the amount of Ca++ entrry into the myocyte?
A
phospharylation of the L-type Ca++ channel
7
Q
What increases binding of Ca++ to TnC?
A
- increase in free intracellular Ca++
- binding affinity of TnC for Ca++
8
Q
Why does acidosis cause decreased muscle contraction?
A
Decreases the affinity of TnC for Ca++
9
Q
How does increase in preload increased cardiac contraction on a cellular level?
A
increases binding affinity of TnC for Ca++
10
Q
How does hypoxia affect cardicac contraction on a cellular level?
A
- Sequesterin of Ca++ into SR is ATP dependent (SERCA pump) –> decreased ATP diminishes SERCA activity –> reduction of subsequent Ca++ release by SR –> decreased inotropy
- decreased Na+K+ATPase activity –>increased intracellular Ca++
- decreased Ca++ATPS activity –>increased intracellular Ca++
Latter two do not increase inotropy because lack of ATP decreases myosin ATPase activity
11
Q
What does lusitropy depend on?
A
ability to rapidly reduce intracellular Ca++
12
Q
What decreases lusitropy on a cellular level?
A
- increase premeability of sarcolemma to Ca++ –> increases intracellular Ca++ concentration –> inhibits relaxation
- Inhibition of Ca++ATPS and Na+/Ca++ ATPase –> increases intracellular Ca++
- Impairment of SERCA pump activity
- increased TnC affinity for Ca++ (drug related)
13
Q
How long can myocytes contract in the absence of O2?
A
1min
–> have only limited anaerobic capacity for ATP generation
14
Q
What substrates can cardiac myocytes use for aerobic ATP generation?
A
- carbohydrates (glucose)
- lactate
- amino acids
- ketones
- fatty acids
15
Q
Why does epinephrine cause smooth muscle relaxation at lower concentrations?
A
B2 receptors have higher affinity for Epinephrine than Alpha1 + 2 –> B2 receptor activation increase intracellular cAMP –> inhibition of MLCK –> inhibition of actin-myosin interaction
16
Q
Name 4 functions of endothelial cells
A
- barrier for exchange of fluid, electrolytes, macromolecules between IV and EV space
- regulation of smooth muscle function through synthesis of vasoactive substances
- Modulation of platelet aggreagation
- Modulation of leukocyte adhesion and transendothelial migration
- Endothelin-1 synthesis
17
Q
What are the main vasoactive substances synthetized by endothilial cells?
A
- NO
- PGI2
- Endothelin-1
18
Q
How do endothelial cells modulate platelet aggregation?
A
Through biosynthesis of NO and PGI2
19
Q
How do endothelial cells modulate leukocyte adhesion?
A
Through biosynthesis of NO and expression of surface adhesion molecules
20
Q
What increases endothelial NO production?
A
- acetylcholin binding to M3 receptor
- bradykinin binding to B2 receptor
- increased shearing forces
- cytokines (TNF, Interleukines)
21
Q
What are the main functions of NO?
A
- smooth musle relaxation
- inhibition of platelet aggregation
- inhibition of early inflammatory response via inhibition of adhesion molecules mediating leukocyte attachment to endothelial surfaces
22
Q
What stimulates and inhibits Endothelin-1 synthesis by endothelial cells?
A
Stimulation:
1. Angiotensin II
2. Vasopressin
3. Thrombin
4. Cytokines
5. shearing forces
Inhibition:
1. NO
2. PGI2
23
Q
What is the resting membrane potential of ventricular myocytes?
A
-90mV
24
Q
What determines the resting membran potential?
A
- concentrations of positively and negatively charged ions across the cell membrane
- relative permeability of the membrane to these ions
- ion pumps
25
What ion is most important for determining resting membran potential?
K+
26
What is the equilibrium potential?
Potential difference acrtoss the membrane required to maintain the concentration gradient across the membrane
--> for K+ it represents the elctrical potential necessary to keep K+ from diffisind down its concentration gradient out of the cell
27
What is the Nernst potential?
Equilibrium potential for K+
28
How can you calculate the Nernst potential?
Ek = -61log (K+inside)/(K+outside) = -96mV
29
Why does K+ slowly leak out of the cell?
It's equilibrium potential is -96mV and the resting membrane potential is -90mV --> +6mV drives K+ slowly out of cell (but there is a finite permeability for K+)
30
What is the Nernst potential for Na+?
+52 mV
31
The electrochemical force acting on sodium is -142 (-90 -(+52) = -142mV --> this force pulls sodium into the cell. Why does it not leak?
At rest the permeability of the membrane for Na+ is low. This also applies for Ca++.
32
Why is the resting membran potential so close to Ek, but so far away from Na+ and Ca++?
Membrane is much more permeable to K+ at resting state
33
What is the primary determinant of changes in membrane potential?
changes in ionic conductances
34
What maintaints the ionic gradients?
1. Na+K+ATPase (3Na+ out and 2K+ in)
2. Na+/Ca++ exchanges (3Na+ in and 1C++ out)
3. Ca++ ATPase (Ca++ out)
35
What two types of ion channels exist?
1. Voltage gated ion channels (opens and closes in response to changes in menbran potentials)
2. receptor-gated ion channels (opens and closes in response to chemical signals operating on receptors)
36
How does increased SNS activity mediated by an increase in norepinephrine B1 stimulation increase HR in the SA node?
Increase in slope 4 via increase in funny current (Na+) and T and L-type Ca2+ channels
--> decrease in action potential duration
37
What increases SA node firing rate?
* sympathetic stimulation
* muscarinic receptor antagonist
* B-adrenoceptor agonist
* circulating catecholamines
* Hypokalemia
* Hyperthyroidism
* Hyperthermia
38
What decreases SA node firing?
* parasympathetic stimulation
* Muscarinic receptor agonist
* B-blocker
* Ischemia/hypoxia
* Hyperkalemia
* Sodium channel blockers
* Calcium channel blockers
* Hypothermia
39
What leads to abnormal automaticity? What happens on a celllular level? What does the action potential look like?
* pharmacological blockage of fast Na+ channels in phase 0
* Inactivation of fast Na+ channels by depolarization caused by hypoxia
--> ischemic cells develop slow spontaneous automaticity due inward Na+ and Ca2+ currents depolarizing the cell
40
What happens in "triggered activity" on a cellular level?
Early afterdepolarization: slow inward Ca2+ current during late phase 2 or phase 3
Delayed afterdepolarization: incward Ca2+ and Na+ current
--> possibly linked to increased intracellular Ca2+ concenstration during ischemia, digoxin toxicity and excessive catecholamine stimulation
41
What extrinsic factors increase conduction velocitiy within the heart?
1. Sympathetic stimulation
2. Muscarinic recptor antagonist
3. B-adrenoceptor agonists
4. Circulating catecholamines
5. Hyperthyroidism
42
What extrinsic factors decrease conduction velocitiy within the heart?
1. Parasympathetic stimulation
2. Muscarinic recptor agnoist
3. B-blcokers
4. Ischemia/Hypoxia
5. Sodium channel blocker
6. Calcium channel blocker
43
When does "reentry" occur on a cellular level?
When a conducting pathway is stimulated prematurely by a previously conducted action potential --> rapid, cyclical reactivation
44
Explain the effect of ischemia on the myocardium
ischaemia --> decreased O2 delivery + decreased CO2 washout --> cellular hypoxia + acidosis --> decreased. ATP concentration --> reduced activity of various ATP-dependent ion pumps
overall effect:
1. increased extracellular K+ leading to decrease in concentration gradient
2. increased intracellular Ca2+ (--> leads to increased intracellular loss of K+ via actication of K+ channels)
45
How is the action potential of nonpacemaker cells alterend in ischemia?
1. Decreased action potential velocity (flatten phase 0 slope)
2. decreased maximal depolarized voltage (reduced amplitude)
3. Reduction of action potential duration
4. reduction of effective refractory period
--> decreased conduction velocity
46
What ECG changes can be seen in myocardial ischemia?
* arrhythmias
* changes in shape of QRS
* ST segemennt elvation or depression
* T-wave inversion
47
What innervates the heart?
1. Sympathetic efferent fibers
2. Parasympathetic (vagal) efferent fibers
48
What happens during vagal activation of the heart?
* negativ chrtonotropy (reduced HR)
* negative dromotropy (reduced conduction velocity)
* negative inotropy (decreased contractility - moderate in atria but only mild in ventricle)
49
What happens during sympathetic activation of the heart?
* positive chrtonotropy (increased HR)
* positive dromotropy (increased conduction velocity)
* positive inotropy (moderate in atria + ventricle)
50
How are systole and diastole defined?
Systole: Ventricular contraction + ejection
Diastole: Ventricular relaxation and filling
51
Label Wiggers Diagramm
52
How much does atrial contraction contribute to ventricular filling at rest? How does this change with increased HR? What causes this change?
rest: 10%
high HR: up to 40%
1. during tachycardia the diastole is shortened, and therefore als the passive filling of the ventricle.
2. "atrial kick" --> increased SNS activity causes an increase in the force of atrial contraction
53
What causes the 4th heart sound S4?
vibration of the ventricular wall as blood rapidly enters ventricle during atrial contraction
--> can be appreciated with decreased compliance of ventricle (stiffened - e.g. HCM)
54
What causes the 1st heart sound S1?
Sudden closure of AV valves causes oscillation of the blood which causes vibrations
55
Why is the 1st heart sound S1 sometimes split?
MV closure precedes tricuspid closure
56
How does atrial pressure changes during isovolumetric contraction?
increase in pressure due to ongoing venous return + bulging of AV valves in atrium --> cwave on CVP
57
What changes can be seen during the early ejection phase of the ventriclei in the atria?
Decrease in pressure due to pullage of base of atria downards leading to expansion of the atrial chambers = x' descent
58
Why does ejection from the ventricles into the Aorta/PA occur?
Total energy of blood within the ventricles exceeds total energy of blood within aorta/PA = energy gradient
59
What causes the 2nd heart sound? Why is it split?
Closure of aortic and pulmonic valve --> aorta closes slightly before pulmonic
60
What causes the characteristic noth in the aortic and pulmonary artery pressure tracings?
Closure of aortic and pulmonic valve
61
Why does the pressure in the aorta and PA not decline as rapidly as in the ventricles?
1. energy stored in elastic walls
2. SVR AND PVR impede flow of blood into distributing arteries of systemic and pulmonary circulation
62
How much blood of the EDV is normally ejected?
60%
63
How can you calculate the ejection fraction? What is a normal EF?
EF = (EDV-ESV)/EDV = 55%
64
What causes the 3rd heart sound?
tensing of chordae tendinae and AV ring during ventricular filling
--> normal in chliden, but pathological in adults as mostly due to ventricular dilation
