Exam 2 Flashcards
What drives blood flow?
Pressure gradient
Pulmonary wedge pressure
Measure of pressure in L atrium
How is stroke volume calculated?
End-diastolic volume minus end-systolic volume
How is ejection fraction calculated?
EF = SV / EDV
Why does the right ventricle have a shorter isovolumetric contraction than the left ventricle?
The RV doesn’t require as much pressure to open the pulmonary semilunar valve
More time spent in systole or diastole?
Diastole
L vs R ventricle: pressure and flow
Both sides eject same vol, (same CO and flow), but pressure and therefore velocity are higher from L side
How is left ventricular ejection fraction calculated?
Ejection fraction = stroke vol / end diastolic vol
What does the S1 heart sound indicate?
Closure of the tricuspid and bicuspid valves in response to ventricular contraction.
Which valve (tricuspid or bicuspid) closes first?
Bicuspid closes just before tricuspid
Why does the pulmonary valve open before the aortic valve?
Lower pressure required to open pulmonary valve than aortic valve. Therefore, R ventricle has shorter period of isovolumetric contraction.
Why does the aortic valve close before the pulmonary valve?
Greater pressure in the systemic circuit than the pulmonary circuit, which forces valve closed sooner.
What does the S2 heart sound indicate?
Closure of the aortic and pulmonary semilunar valves.
Which heart sound can have a normal physiologic split?
S2
Effect of inspiration on R heart
Increased negative intrathoracic pressure results in greater venous return to R atrium and ventricle, increased EDV, and greater R ventricular ejection volume. This delays closure of pulmonary valve (P2), increasing the splitting of S2.
Effect of inspiration on L heart
Increased negative intrathoracic pressure results in retention of blood in pulmonary vv, causing reduced venous return to L atrium/ventricle. This decreases EDV and ejection volume of L ventricle, reducing the duration of L ventricular ejection and accelerating closure of aortic valve (A2), which enhances split of S2.
What are the features of an S3 heart sound?
Occurs early in diastole, after S2
Called protodiastolic gallop
During rapid ventricular filling
Normal in younger people
May indicate ventricular enlargement or decreased compliance
What are the features of an S4 heart sound?
Occurs in late diastole, just before S1
Associated w/ unusually strong atrial contraction
Indicative of pathology
Presystolic gallop
Structural issues that can cause turbulence in heart
Thickening of valve leaflets
Narrowing (stenosis) of valve openings
Holes in chamber walls or septae between chambers
Characteristics of Mitral Insufficiency
Systolic murmur
Results in abnormally high L atrial pressure during ventricular contraction
Characteristics of Mitral Stenosis
Diastolic murmur
L atrial pressure is higher than normal because blood doesn’t move to L ventricle as easily
Characteristics of Aortic Stenosis
Systolic murmur
Much higher L ventricular pressure to overcome stenotic valve
Characteristics of Aortic Insufficiency
Diastolic murmur
Aortic pressure drops below normal level due to regurg of valve
Is valve opening/closing active or passive?
Passive
What is the dicrotic notch?
Pressure wave created in the aorta due to the closure of the aortic semilunar valve
Jugular venous pulse waves
A wave: atrial contraction pressure
C wave: pressure from ventricular contraction causing AV valve to bulge into atrium
V wave: increased atrial pressure de to passive filling with AV valve closed
What are large a waves indicative of?
Tricuspid stenosis
R heart failure
What are cannon a waves indicative of?
3º heart block
What does an absence of a waves indicate?
Atrial fibrillation
What does a large v wave indicate?
Tricuspid regurgitation
Effect of Skeletal Muscle “Pump” on Lower Extremity Venous Pressure
Standing: pooling of blood in lower extremity veins causes increased venous pressure in foot
Walking: mm contraction + valves promotes venous return to heart and decreases venous pressure in foot
Equation for work performed by the heart
Work = aortic pressure x change in volume
W = p · ΔV
Tension heat
Consumes the most energy in the heart
Results from splitting of ATP during isovolumetric contraction
No “work” being done because there is no movement
Major determinant of ventricular wall tension
Afterload
Major determinants of myocardial O2 demand
Wall tension
Heart rate
Contractility (inotropic state)
Key factors impacting stroke volume
Preload
Afterload
Contractility
Preload
Effectively synonymous with end diastolic volume
Directly proportional to stroke volume (increased preload = increased SV)
Afterload
A measure of the amount of force the ventricle needs to generate to overcome the pressure keeping the semilunar valves closed
Good indirect measure: MAP
Increased afterload results in decreased stroke volume
Contractility (Inotropy)
Measure of force generation independent of preload
Increased inotropy will result in lower end systolic volume and therefore increased stroke volume
How are wall tension, pressure, radius, and thickness related?
Wall tension is proportional to systolic pressure and radius of the chamber
Wall tension is inversely proportional to wall thickness
What is the Frank-Starling law?
The stroke volume of the heart increases in response to an increase in the volume of blood filling the heart (the end diastolic volume) when all other factors remain constant.
Active tension in heart
Dramatic increase in active tension with increasing sarcomere length.
How does heart failure affect the Frank-Starling relationship?
Failing heart will result in a shallower curve, since the chamber(s) become less able to pump the blood filling them
How are cardiac output and venous return related?
Venous return must equal cardiac output
Mean systemic filling pressure
Pressure exerted by the volume of blood itself on the system
X-intercept on venous return curve.
Depends upon the blood volume and compliance of vascular system.
Molecular mimicry
Microbial epitope is similar enough to a self epitope that, when activated against the microbe, TH1 cells will react to self as well
Epitope spreading
Local tissue damage leads to release of self Ag from tissues. These are picked up by APCs that further activate lymphocytes, leading eventually to further release of self-Ag.
Bystander activation
Non-specific activation of self-reactive lymphocytes because factors necessary for activation happen to be present.
Cryptic antigen model
Self-Ags that have been taken up by DCs are differentially processed. This uncovers epitopes that would otherwise be hidden. These epitopes activate self-reactive TH1 cells, leading to more damage.
Group A Streptococcus
Gram-pos cocci
Beta hemolytic (uses heme as food source)
M protein
Found in mucoid strains of strep (heavily encapsulated)
Can interact with the Vβ region of TCRs, making it a superantigen
Can result in polyclonal T cell expansion and cytokine storm
How are Jones critera for ARF used?
Diagnosis requires two major manifestations or one major and two minor manifestations along with evidence of preceding S. pyogenes infection.
Major manifestations of ARF
Carditis
Polyarthritis
Chorea
Erythema marginatum
Subcutaneous nodules
Minor manifestations of ARF
Arthralgia
Fever
Elevated ESR or CRP
EKG evidence of prolonged PR
Polyarthritis in ARF
Common finding, probability increases w/ reinfection
Occurs symmetrically in large joints
Synovial fluid is sterile but w/ high WBC
Tx: ASA and corticosteriods
Contributing virulence factor: hyaluronic acid capuse of microbe
Carditis in ARF
Occurrence about 3 wks post infection
Pancarditis (involvement of whole heart)
Cardiomegaly
New onset of murmurs, most commonly apical systolic, and involving mitral valve
Contributing virulence factor: M protein
Arthritis vs Arthralgia
Arthritis: painful joint, tender to touch, swollen
Arthralgia: painful joint w/o tenderness or swelling
Types of receptor modulators
Full agonist
Partial agonist
Neutral agonist
Inverse agonist
Full agonist
Fully mimics endogenous ligand
Partial agonist
Does not fully induce endogenous response
May be a lower amplitude response, or only induce one of multiple effects of endogenous ligand
Inverse agonist
Blocks or reduces constitutive activity
Also called competitive antagonists
What is the NT used by all preganglionic ANS neurons?
ACh; cholinergic neurons
What type of receptors are found in postganglionic receptors of the parasympathetic nervous system?
nAChR (primary type)
mAChR
M2 subtype of mAChR
Found in heart and lungs
Is a GPCR that has Gαi/o domain
Inhibits adenylate cyclase pathway
M3 subtype of mAChR
Found in lungs
Is a GPCR with a Gαq domain
Works in the PLC pathway to generate IP3 and DAG
Nicotinic vs Muscarinic receptors
Nicotinic are ionotropic
Muscarinic are metabotropic (GPCRs)
Major difference between cholinergic and adrenergic signal transduction
Cholinergic transduction terminated by enzymatic degradation (AchE)
Adrenergic signal transduction terminated by reuptake of NT
What is the precursor for all catecholamines?
Tyrosine
Are adrenergic receptors metabotropic or ionotropic?
Metabotropic
There are NO ionotropic adrenergic receptors
Pathway of catecholamine synthesis
- Tyrosine is pumped into cell
- Tyrosine converted to Dopa in cell cytoplasm
- Dopa converted into Dopamine in cell cytoplasm
- Dopamine pumped into vesicle
- Dopamine converted into norepinephrine
- Norepinephrine converted to epinephrine (mainly in adrenal medulla)
Na+-dependent tyrosine transporter
Transports tyrosine into nerve terminal
Vesicular monoamine transporter (VMAT-2)
Transports Norepi, Epi, dopamine, and serotonin into vesicles
Norepi transporter (NET)
Imports norepi into nerve terminal
Metabolism of catecholamines
Modify catecholamines after reuptake
Monoamine oxidase (MAO)
Catechol-O-methyltransferase (COMT)
What is the signaling pathway of α1 receptors?
Phospholipase C pathway
Cleaves PIP2 into IP3 and DAG, eventually activating PKC
What is the signaling pathway of α2 receptors?
Gαi pathway
Inhibits adenylyl cyclase from forming cAMP
What is the signaling pathway of the β receptors?
All work through Gαs to stimulate adenylyl cyclase to produce cAMP
Rule of thumb for α1 receptors
stimulate contraction of all smooth muscle
Ex: causes vasoconstriction via contraction of vascular smooth muscle
Rule of thumb for muscarinic receptors
Stimulate contraction of smooth muscle (different pathway than that of α1 receptors)
Rule of thumb for β2 receptors
Relax smooth muscle
Ex: result in vasodilation
How does sympathetic nervous system increase HR?
Norepi effects on β1 agonists results in:
Increased If (increased steepness of phase 4)
Increased ICa (increases slow depolarization rate and lowers threshold)
Decreased IK (increases steepness of phase 4)
Net result: faster depolarization to threshold, which increases HR
How does parasympathetic nervous system decrease HR?
Agonistic ACh effects on M2
Decreased If (decreases slow depolarization rate)
Decreased ICa (decreased slow depolarization rate, increases threshold so it takes longer to get there)
Increased IK (decreases max diastolic potential)
Net effect: longer time for depolarization to reach threshold, decreases HR
Factors that can promote increased EDV
Increased central venous pressure
Decreased HR
Increased ventricular compliance
Increased atrial contractility
Increased aortic pressure
Pathological conditions
Factors that may reduce EDV
Decreased filling pressure
Increased HR
Decreased atrial contractility
Decreased afterload
Diastolic failure from decreased ventricular compliance
Mitral or tricuspid valve stenosis
5 Positive Inotropic Agents
β1 adrenergic antagonists
Cardiac glycosides (digitalis derivatives)
Decreased ECF [Na+]
Increased ECF [Ca++]
Increased HR
5 Negative Inotropic Agents (decreased contractility)
M2 muscarinic agonists
Decreased ECF [Ca++]
Ca++ channel blockers
Increased ECF [Na+]
Decreased affinity of troponin for Ca++ (ex. acidosis)
What controls short term regulation of blood pressure?
Neural control
What controls long term regulation of blood pressure?
Endocrine/paracrine control
