Exam 3 Cardio-physiology

What generates the AP in the heart?

The SA node

Intraventricular Septum

The portion of the heart that separates the two ventricles

Purkinje Fibers

Fibers in the ventricles that transmit impulses to the right and left ventricles, causing them to contract

- NOT nerve fibers, but rather specialized cardiac myocytes

Right / Left Bundle Branch

Extends toward the apex and then radiate across the inner surfaces of both ventricles

Bundle of HIS

A bundle of modified heart muscle that transmits the cardiac impulse from the atrioventricular node to the ventricles causing them to contract

P-Wave

Depolarization of the RA and LA

P-R Interval

The conduction delay through the AV node which allows atrial contraction to complete before ventricular contraction starts

QRS Complex

Ventricular depolarization and atrial repolarization

T-Wave

Repolarization of the ventricles

U-Wave

Not always present; a late repolarization

What is the difference between a segment and an interval?

A segment is a flat line, an interval is a flat line + deflection

Bradycardia

A slow heart rhythm, < 60 BPM

Tachycardia

A fast heart rhythm, > 120 BPM

How do you treat tachycardia?

Catheter oblation, K+ blocker, Ca2+ blocker, Beta blocker and blood thinners

Premature Atrial Contractions

Caused by ectopic pacemaker activity

Ecotopic

When the ventricles start producing their own AP's

Wandering Atrial Pacemaker

Pacemaker shifts between SA node, atrium, and AV node

Atrial Tachycardia

Multifocal pacemaker potentials outside the SA node, HR exceeds 100 -- a type of supraventricular tachycardia (SVT)

Atrial Flutter

An inconsistent fast heart rate -- can lead to AFib

Atrial Fibrillation

Uncoordinated electrical activity, with no rhythmic activity in the atria

- Short circuit in the atria

- Irregular HR

- Increased risk of V-Fib / V-Tac

- Risk of stroke (Blood stasis --> Clots)

Long-QT Syndrome

A condition in which there is a delayed repolarization, such that the QT interval > 450 ms

-Can be genetic or acquired

- #1 reason why cardiovascular drugs fail in clinical trials

Ventricular Tachycardia

The AV node is driving a higher than normal firing rate, superseding SA node input

Ventricular Fibrillation

Uncoordinated electrical activity; no rhythmic action

1st Degree Heart Block

Increased P-R interval (> 100-200 ms)

2nd Degree Heart Block (Mobitz vs Wenckebach)

1. Mobitz -- A consistent P-R interval with a dropped QRS

2. Wenckebach -- A variable P-R interval

What is the saying for 1st Degree Heart Block?

If R is far from p, you have 1st Degree!

What is the saying for both 2nd Degree Heart Blocks?

1. Mobitz -- If some P's don't get through you have Mobitz II

2. Wenckebach -- Longer, longer, longer then drop, then you have Wenckebach

3rd Degree Heart Block

P and Q waves are asynchronous

What is the saying for 3rd Degree Heart Block?

If the P's and Q's don't agree then you have type III

Myosin

Thick filament

Actin

Thin filament

Titin

Anchors thick filament

Tropomyosin

A protein of muscle that forms a complex with troponin regulating the interaction of actin and myosin in muscular contraction

Troponin Complex (C, T, I)

Facilitates cross-bridge cycling

5 Stages of ECC:

1. Ca-Binding / Actin exposed

2. Myosin binding

3. Power stroke

4. ATP binding

5. ATP hydrolysis

cTnT

Tropomyosin-binding subunit--it regulates the interaction of troponin complex w/ thin filaments

cTnI

Inhibits ATPase activity of actin-myosin

cTnC

A Ca-binding subunit, playing the main role in Ca-dependent regulation of muscle contraction

- When cTnC binds to Ca, it moves cTnI to expose Actin to Myosin

Serum cTnI

Released following muscle injury & is used as a diagnostic tool to detect MI's

What are the 2 phases of systole?

1. Isovolumetric Contraction

2. Ventricular Ejection

Isovolumetric Contraction

Muscle force w/o shortening

- Mitral and aortic valves closed

Ventricular Ejection

Ventricular pressure increases and when > aortic pressure, AoV opens, ventricular walls contracts, and blood is ejected

What are the 2 phases of diastole?

1. Isovolumetric Ventricular Relaxation

2. Ventricular Filling

Isovolumetric Ventricular Relaxation

Early part of diastole in which the mitral and aortic valves are closed

Ventricular Filling

Ventricular pressure rapidly drops below atrial, mitral valve opens, blood flows rapidly into the ventricle

Stroke Volume

The amount of blood pumped out of the heart during one beat

- Not 100%

How is the majority of the blood delivered to the ventricle?

Just through passive flow; atrial contraction does very little to pump blood through to the ventricles

What are some key differences between the right and left heart?

1. Pressure changes in the right heart are qualitatively similar to left heart, but absolute pressures are lower

2. Right ventricle systolic pressures ~25 mmHg, diastolic pressure ~0 mmHg

3. Stroke volume essentially the same

4. RH is essentially a low pressure high volume system

Preload

The initial stretching of the cardiac myocytes prior to contraction

- Determined by venous return and ventricular filling

Afterload

The force or load against which the heart contracts to eject blood

Contractility

The tension developed and velocity of shortening of myocardial fibers at a given pre and afterload

- Represents a unique and intrinsic ability of cardiac muscles to generate a force independent of any load or stretch applied

End Systolic Pressure Volume Replationship

The measure of systolic fxn

- Describes the maximal pressure generated at a given LV volume (systolic fxn)

- The slope of the ESPVR is an index of contractility

- Increased slope: increased contractility

End Diastolic Pressure Volume Relationship

The measure of diastolic fxn

- Describes the passive filling curve for the ventricle

- Slope inversely related to ventricular compliance (stiffer ventricle)

What is cardiac output?

Heart rate x stroke volume

Cardiac Contractility

The strength of a cardiac contraction

How does the parasympathetic nervous system affect the heart?

1. Regulated by vagus nerve

2. Innervates the SA node

3. Reduces HR

4. Reduces the Na current, therefore slowing the rate of depolarization

How does the sympathetic nervous system affect the heart?

1. Post ganglionic nerve fibers innervate the SA and AV node and the LV

2. These nerves release NE, increase HR

3. Circulating epi from the adrenal cortex can also increase HR

4. Increases the Na current, therefore increasing the rate of depolarization

Frank-Starling Relationship

Greater EDV (preload) leads to greater stretching of the sarcomere and a greater force of contraction

Sympathetic Regulation of Contractility

1. Sympathetic stimulation increases force of contraction: contractility

2. The Frank-Starling law does not apply to contractility

All vessels have what kind of layer?

An endothelial layer

Arteries

A thick layer of smooth muscle and connective tissue

- Elastic, so provides high conductance

Arterioles

A layer of smooth muscle

- Regulates contraction / relaxation -- overall resistance

Capillaries

Endothelial layer

- Facilitates oxygen / nutrient transfer

Venules / Veins

Increasing amount of connective tissue w/ vessel size, little smooth muscle -- accounts for low resistance

What are the 9 fxns of endothelial cells?

1. Physical barrier

2. A permeability barrier

3. Secretion of paracrine agents that act on smooth muscle

4. Angiogenesis

5. Regulates ECF

6. Regulates smooth muscle proliferation

7. Produce growth factors in response to injury

8. Regulates platelet clotting

9. Hormone synthesis

Arties are high elastic:

- Allows arteries to fxn as high flow, low resistance tubes

- Arteries also act as a pressure reservoir that allows continuous flow during diastole

Compliance

Change in vol / Change in pressure

Velocity

Distance / time

Systolic Pressure

The maximum arterial pressure during ventricular ejection

Diastolic Pressure

The minimum arterial pressure just prior to ventricular ejection

What are standard systolic / diastolic pressure values?

Systolic--120 mmHg

Diastolic--80 mmHg

Pulse Pressure

Systolic Pressure - Diastolic pressure

What are 3 determinants of the pulse pressure?

1. Stroke volume

- Greater stroke volume = greater pulse pressure

2. Speed of blood flow

- Faster blood flow = greater pulse pressure

3. Arterial compliance

- Decreased compliance (associated w/ disease) = greater pulse pressure

Mean Arterial Pressure (MAP)

The average arterial pressure through the cardiac cycle

- Diastole is about 2x as long as systole, so equation is MAP = DP + (1/3)*PP

Does systolic, diastolic, and MAP change as you age?

Systolic goes up, Diastolic goes down, but MAP stays about the same

What are the 2 major functions of the arterioles?

1. Responsible for determining relative blood flow to individual organs

2. Major factor in determining mean arterial pressure (MAP)

What is the equation that governs flow?

Flow = delta(P) / Resistance

What is the major source of resistance in the vasculature?

Arterioles

What is the equation for the flow through an organ?

Forgan = MAP / Resistance

MAP is essentially _____ systemically, so flow is regulated by changes in resistance which is controlled by:

Equal;

1. Vasodilation

2. Vasoconstriction

3. All vascular smooth muscle has intrinsic mechanics

Active Hyperemia

A local production of vasoactive mediators as a result of increased metabolism, which causes vasodilation

- Very well developed in skeletal and cardiac muscle and glandular tissue

What metabolites affect active hyperemia?

- Decreased O2

- Increased CO2

- H+

- Adenosine

- K+

- Eicosanoids

- Osmotically active substances produced by metabolism

- Bradykinin

- NO

Flow Autoregulation

A response to a change in blood flow due to a change in MAP

- A lowering in pressure induces vasodilation to maintain flow and an increase in pressure induces vasoconstriction to lower flow

What are the 4 ways you can locally control your arteriole vascular tone?

1. Active Hyperemia

2. Flow Autoregulation

3. Reactive hyperemia

4. Response to injury

What are the mechanisms by which flow autoregulation occur?

1. Regulation by local production of vasoactive metabolites

2. Regulation by 'myogenic response'

- Increased pressure, increased stretching, vasoconstriction

- Decreased pressure, decreased stretching, vasodilation

Reactive Hyperemia

Following occlusion, it is the reestablishing of flow that results in transient and profound increase in flow

- Basis of ischemic injury

Response to Injury

Causes release of local vasoactive substances

Extrinsic Control of Vascular Tone

1. Sympathetic neurons (Alpha-1 AR)

2. There is no parasympathetic innervation!

3. Noncholinergic, noradrenergic, autonomic neurons

4. Hormones

Neural Controls

1. Vasoconstrictors -- Sympathetic nerves that release NE

2. Vasodilators -- Neurons that release NO

Hormonal Controls

1. Vasoconstrictors -- Epi (Alpha-1 AR), angiotensin II, Vasopressin

2. Vasodilators -- Epi (Beta-2 AR), ANF

Local Controls

1. Vasoconstrictors -- Internal blood pressure (myogenic response), endothelin-1

2. Vasodilators -- Decreased O2, K+, CO2, H+, Osmolarity, Adenosine, Substances released during injury, NO

Intercellular Clefts

Water-filled spaces between cells

What accounts for the slower capillary velocity?

The greater total cross-sectional area

- Governed by the equation A1V1 = A2V2

The 3 basic mechanisms of exchange:

1. Diffusion

2. Vesicular transport

3. Bulk flow

How do lipid soluble molecules travel?

O2, CO2, freely diffuse through the capillary wall

How do polar molecules flow?

Through intercellular clefts (water-filled pores between endothelial cells)

- Pore size is a big determinant of permeability

- The brain has very tight junctions

Transcytosis

The movement of secretory vesicles through endothelial cells

- Only does a small level of transport

What does interstitial fluid function as?

A reservoir that interacts w/ the plasma, transporting fluid back and forth

Bulk flow of protein-free plasma:

- Maintains the distribution of ECF volume

- Not!!!!!! the exchange of metabolites

Ultrafiltration

Hydrostatic pressure causes the capillary wall to act as a filter -- plasma (but not protein) can move between the 2 compartments