PHSL3061 Exam 3

cardiac action potential (AP)

1. atrial depolarization; get P wave
2. PR interval: time taken for dep. to go through atria and atria contracting
3. QRS: ventricular depolarization
4. ST: plateau
5. T wave: ventricular repolarization

phase 4 of cardiac AP

depolarization opens voltage gated Na channels

phase 0 of the cardiac AP

1. Na enters cell (down potential gradient)
2. rapid increase of RMP
3. reversal potential (voltage at which they begin to close)

phase 1 of cardiac AP

1. Na channel closes
2. K+ channels open (goes out of cell)
3. causes partial repolarization
4. membrane potential begins to decrease

phase 2 of cardiac AP

1. opening of L type calcium channel (caused by Na depolarizing cell)
2. Ca2+ moves out of cell (slow rate)
3. plateau phase (ca2+ coming in and K+ is going out)
3. calcium channel begins to close

phase 3 of cardiac AP

1. outward current (more K is going out)
2. repolarizes membrane; brings it back to original state
2. Na+/ K+ATPase, Na / Ca exchanger and Na / H exchanger establish conc gradient and reset myocyte

ECG

summation of currents in an individual heartbeat

How ECG is recorded

1. Currents generated by the heart create an electrical signal that can be measured.
2. Placement of the leads dictates shape of signal.

A-Fib

ventricular arrhythmias (Long QT syndrome)

* Caused by delayed depolarization
* 16 known genes that encode different channels
* Can also be acquired (drug induced; why drugs don't make to the third trial)
* Low K and Mg raise RMP (Lead to early after depolarization and delayed after depolarization)

ECC (excitation contraction coupling)

How we turn electrical signals in the heart into a mechanical force that can push a lot around the body

Sequence of ECC step 1

Action potential is generated

Sequence of ECC step 2

Action potential travels along the sarcolema (cell membrane)

Sequence of ECC step 3

Travel down T- tubules (triggers opening)

Sequence of ECC step 4

Fast sodium channels open (Na rushes in and depolarizes membrane)

Sequence of ECC step 5

Calcium channel opens (calcium enters)

Sequence of ECC step 6

Hits ryanodine receptors
* Gets calcium release from the SR through the ryanodine receptors
* Calcium binds to troponin complex (Cal troponin C)

Sequence of ECC step 7

Binding causes conformational change in troponin complex expose actin
* Myosin heads binds to actin, hydrolyzes ATP (contraction)
* System gets a reset (Ca gets pumped back to SR)

Myosin

thick filament

Actin

thin filaments

Titin

Anchors thick filaments
* Acts as a shock absorber (Crucial for setting the passive tension of the sarcomere)

Tropomyosin

Regulate ability / inability of myosin to bind to actin

Troponin complex (C, T, I)

* Facilitates cross bridge cycling
* Can alter the position of tropomyosin and where it moves tropomyosin (allowing contraction to occur)

systole: isovolumetric contraction

Mitral and aortic valves closed . Muscle force without shortening

systole: ventricular ejection

Ventricular pressure decreases when aortic pressure is high. Aortic ventricle opens, ventricular walls contract, blood is ejected.

diastole: Isovolumetric relaxation

Mitral and Aortic valves are closed (letting relaxation to begin)

diastole: Ventricular filling

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

diastole: atrial contraction

Aortic valve and atria mitral valve on the left side, pulmonary valve and the tricuspid valve on the right side are closed.
* QRS is fired and muscle begins to contract
* Muscle force generation without shortening, pressure is building up

Equation governing MAP

MAP = CO X TPR

Cardiac Output (CO)

Volume of blood pumped / time (Could regulate arterial pressure and volume)

CO equation

CO = HR x SV

What controls arteriole resistance

Vasodilation and vasoconstriction

Baroreceptors

Bring about changes in pressure in minute to minute status (homeostasis)

Baroreceptors : short term regulation of MAP

1. Baroreceptors sense pressure and send electrical signals to the brain
2. Brain senses and responses accordingly
3. Increase signal (increase pressure will activate parasympathetic and decrease sympathetic)
4. Decrease signal (decrease pressure with activate sympathetic and decrease parasympathetic)

Blood volume : Long term regulation of MAP

1. When baroreceptors are continually activated, they reset themselves
2. Hypertension becomes your new normal
3. Involves coordination of the circulatory and renal systems.

systolic pressure

Maximal arterial pressure during ventricular ejection

diastolic pressure

Minimal arterial pressure just prior to ventricular ejection

pulse pressure

difference between systolic and diastolic pressure

mean arterial pressure

Average arterial pressure through the cardiac cycle
MAP = diastolic pressure + 1/3 pulse pressure

General Principles

1. Flow is proportional to pressure
2. Flow is inversely proportional to resistance

Describe how arteriolar resistance determines MAP

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vasodilation

Relaxation of the smooth muscle to allow the vessel to open, so that flow can proceed through the vessel. Decreases pressure

vasoconstriction

Ability of the smooth muscle to contract, to reduce the lumen size

Active Hyperemia (Local control of Vascular Tone 1)

Response of the local vasculature to change in metabolism

Steps to vasodilation

1. Decrease in local concentration of O2
2. Increased CO2
3. Increase concentration of H+ ions
4. Adenosine being produced from ATP metabolism
5. Increase K+
6. Eicosanoids: Class of oxidatively metabolized fatty acid (prostaglandin)
7. Osmotically active substances produced by metabolism
8. Bradykinin (Locally produced peptide)
9. Nitric Oxide (NO)

active hyperemia is well developed in

Skeletal and cardiac muscle and glandular tissue

flow autoregulation (local control of vascular tone 2)

1. Change in blood flow are regulated by changes in pressure (rather than metabolites)
2. Change in resistance to regulate blood flow (vasodilation vs vasoconstriction)

Mechanism of flow autoregulation

1. Regulation by local production of vasoactive metabolites
2. Regulation by myogenic response (Smooth muscles when stretched it contracts, when relaxed its relaxed)

vasodilation mechanism

1. decrease in pressure
2. decrease stretch

vasoconstriction mechanism

1. Increase in pressure
2. increase stretch

reactive hyperemia

Restoration of flow (results to profound in flow)

response to injury

causes release of local vasoactive substances

Sympathetic neurons (Extrinsic control of vascular tone)

1. Alpha 1 adrenergic receptors
2. Low epi = Beta 2 (vasodilation)
3. High epi = Alpha 1 (Vasoconstriction)

Parasympathetic neurons

NO PARASYMPATHETIC INNERVATION IN OUR SYSTEMIC VASCULATURE

Noncholinergic, Nonadrenergic, Autonomic Neurons

Immediate release of NO (nitric oxide). Causes vasodilation in gut

Epinephrine

1. Released by the adrenal glands (NOT FOUND IN SYMPATHETIC NERVE TERMINALS)
2. Can activate B2 adrenergic receptors in skeletal muscle and induce vasodilation
3. Can bind and activate adrenergic receptors (Alpha 1 & 2 and Beta)

Epinephrine is a hormone that

can do vasodilation and vasoconstriction. Depends on the affinity of the receptors and concentration of agonist

Angiotensin

1. RAAS system
2. Vasoconstriction ; binds to angiotensin receptors in smooth muscle cells and induces vasoconstriction

Vasopressin (ADH)

Maintain blood volume. Keeps pressure up

ANF (atrial natriuretic factor)

1. Made in atria. Causes diuresis and reduced blood volume.
2. Decrease load in heart failure

continuous capillary

1. Do Not readily diffuse
2. No fenestration between
3. Basis for blood brain barrier

fenestrated capillary

1. Have fenestrations or pores
2. Found in skeletal muscles

sinusoidal capillary

1. Large fenestration
2. Found in liver (toxin filter)

Capillaries

Thin wall tubule of endothelial cells (NO SMOOTH MUSCLE OR ELASTIC TISSUE)

intercellular clefts

Water filled spaces between cells

Metarterioles

link arterioles to capillaries (regulating opening and closing of capillaries)

Basic mechanisms allow exchange between plasma and interstitial fluid

1. Diffusion
2. Vesicular transport
3. Bulk flow

Diffusion

Primary mechanism in which nutrients like CO2 and glucose are exchanged

Lipid soluble molecules

O2, CO2 freely diffuse through the capillary wall

polar molecule

1. Flow through intercellular clefts
2. Molecules with a charge (Na+ , K+, Cl-)
3. Pore size is a big determinant of permeability

O2

1. O2 concentration on the proximal end of the capillary is higher than in the interstitial fluid and muscle cells
2. Concentration gradient allows diffusion of O2 out of the capillary (As blood flows through, the concentration
decreases at the distal end

CO2

1. Produced by cellular respiration, increases CO2 concentration above levels in the plasma
2. Drives CO2 diffusion into the capillary (As blood flows through, CO2 in the plasma increases, decreasing the gradient)

Glucose

1. Continuous uptake from the interstitial fluid into muscle cell
2. Produces concentration gradient allowing glucose to diffuse through intercellular clefts
3. Active hyperemia will increase flow, thereby increasing delivery

interstitial fluid

Acts as a reservoir that interacts with the plasma transporting fluid back and forth

bulk flow of protein free plasma

1. Maintain the distribution of extracellular fluid volume

Principle of bulk flow

1. Capillary wall is highly permeable to water
2. Ultrafiltration / filtration : Hydrostatic pressure causes the capillary wall to act as a filter
3. Plasma (NOT PROTEINS) can move between the two compartments

High capillary pressure

Favors fluid movement out of the capillaries

Osmotic pressure in the capillaries

is high favoring fluid movement into capillaries

capillary hydrostatic pressure

push out

interstitial fluid hydrostatic pressure

Push in

osmotic force due to plasma protein concentration

Pull in

venous blood

Flow is moved by pressure differences

venous blood flow

1. Pressure driven system between peripheral veins and right atrium
2. Facilitated because veins are low resistance
3. Valve in peripheral system prevent backwards flow

venous pressure

1. Flow moved by pressure difference
2. Controlled by volume of blood and vessel compliance
3. Compliance and resistance are inversely related (Increase in compliance = decrease in resistance)

Veins regulated by sympathetic neurons

Induce venous constriction (Regulate venous return, ultimately ending diastolic volume and CO through Starling Law

lymphatic system

1. Lymph vessels carry lymphatic fluids to the lymph nodes
2. Lymphatic fluid from interstitial fluid is returned into circulation
3. Lymphatic system picks up everything including protein
4. Extra water is ultimately dumped back into the RA

hypertrophy

Increase in volume of an organ or tissue due the enlargement of its cells

Remodeling

Structural and functional changes that occur (accompany any type of response to stress)

physiologic hypertrophy

Increase in heart size with sustained or elevated function (good)

pathologic hypertrophy

increase in heart size with declining function (bad)

concentric remodeling

-wall thickening
-decrease in ventricular volume
-myocyte thickening
-no increase in heart size
-seen with pressure overload

eccentric hypertrophy

-Increased ventricular volume
-Wall thinning remains constant
-Contractile function is declining
- Seen with volume overload (MI)

concentric hypertrophy

-Proportional increase in wall thickness and ventricular volume
- Myocyte thickening
-Seen with pressure overload (Hypertension)

myocyte remodeling

1. Myocyte shape change
2. Concentric hypertrophy ; Myocytes get thicker. sarcomeres are added in parallel
3. Eccentric hypertrophy ; gets longer. sarcomeres are added in series

fibrotic remodeling

1. Important aspect of remodeling in heart failure
2. Beneficial: Required for scar formation (essential in wound healing)
3. Detrimental: Increase passive stiffness and decrease diastolic function

Perivascular

Wraps around coronary arteries

interstitial

Wraps around cardiac myocytes (Not localized to one area, Makes ventricles stiff)

replacement

1. Dead cardiac myocytes are chewed up by immune system and replaced by fibroblasts(don't contract)
2. Decrease systolic function

myocardial infarction

1. Blockage of the coronary artery
2. Downstream myocytes don't get oxygenated (Wound healing response
3. Cardiac rapture (NO OCCURENCE of wound healing response)

Key changes in function when exercising

1. CO : Increase from 5 L/min to 10
2. Change in blood flow distribution (toward skeletal muscle, heart, and skin (arterial vasodilator) . Away from kidney and gut (Arterial vasoconstriction)
3. Drop in peripheral resistance: Vasodilation in skeletal muscle
4. Mean Arterial Pressure (MAP): Increases slightly (CO increases more than the drop in peripheral resistance)
5. Systolic pressure increases quite a bit (Increased adrenergic stimulation, Increasing contractility of our muscle
6. CO is increased by increased sympathetic activity (B-Ars increase HR, B-Ars increase contractility - direct effect on SV. Small increase in EDV (Starling Law)
7. Increase venous return
(Increased activity in skeletal muscle squeezes blood through. Increased respiration, sympathetic drive increases venous tone. Great blood flow through skeletal muscle arterioles