Muscular Dystrophy

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-Genetic DIsease

-1/3500 males

-Progressive muscle degeneration(cardiac &skel)

-Due to absence of COSTAMERES

[Poor balance, diff. walking, freq falls,droopy eyes]

Multiple Sclerosis

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-Autoimmune Disease attacks myelin sheath around nerves

-3x more common in women

-less prevalent in tropical than temperate climates

[muscle weakness/spasms,difficulty moving]

Myasthenia Gravis

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-AUtoimmune disorder (1/7500 Americans)

-flattened post junctional folds

-damage to postsynaptic membrane

[facial weakness & difficulty chewing, limb weakness,repiratory difficulty]

Malignant Hyperthermia

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-RAre genetic disorder

-mutated RYANODINE RECEPTOR

-treat with Dantrolene IV

[massive muscle conrtraction, rapid rise in body temperature]

Underlying pathologies of

HTN

-alterations of flow

-atherosclerosis

-hyperlipidemia

3 complications of 

HTN

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-Increased wrk of heart [HF, Arrythmias]

-Dec. flow to kidneys [renal failure]

-Dec. flow to brain [dementia, stroke]

CV-Renal drugs acoount for

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29/100 most prescribed drugs

[ex: lisinopril,valsartan, metoprolol, amlodipine, HCTZ]

Cv provides flow to tissues. Tissues need flow for delivery

FLOW is

1. directly related to

2. inversely related to 

1. Blood Pressure on the input (arterial) side

2. Resistance to flow (WITHIN THE TISSUE,based on arteriole constriction)

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1. Dilation 

2. Constriction

BP = CO x TPR

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CO = HR x SV   (Controlled by ANS)

[image]

CO (Cardiac Output)= ???

[depends on contraction,relaxation]

CO = HR x SV   (Controlled by ANS)

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Work increases

[against art. press.]

1. inc radius

2. inc P (in artery)

3. decrease R (arterial)

Arterial pressure

{Delta}P = Q(output) x R(resistance)

Arterial resistance R =

[larger radius = less resistance]

[image]

Vein (compliance/floppiness)

eq?

[image]

C = {delta}V/{delta}P

compliance = volume/ pressure

Flow to Kidney 

Q = {delta}P/R

To inc flow 

inc P in artery or dec R in arteriole

[image]

If R to 1 organ inc then flow to that organ _______

Flow to other organs _____________

1. decreases

2. increases 

(inc R to GI=dec flow to GI=inc BP=inc Flow to brain) 

[Flow to tissue = BP/R]

Firing Rates

SA:, AV:, Purkinje:

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SA:60-100/min [-50 to-60mV resting]

AV: 50-60/min

Purkinje:30-40/min [-90mV resting]

What do we call Cells outside SA(sinoatrial node)?

[image]

Latent pacemakers

GENERATE ESCAPE(AV node or purkinje fibers)

OR ECTOPIC BEATS (ventricular walls)

Internodal pathway:

Bachmann bundle:

AV: 

Bundle of his:

Bundle branches:

Purkinje fibers:

Internodal pathway:SA to AV

Bachmann bundle:SA to LA

AV:delays, secondary pacemaker

Bundle of his:large fibers

Bundle branches:in septum

Purkinje fibers:impulse spreads rapidly over ventricles

Whats happening?

[image]

4: beginning resting potential [Na+ leak into cell]

0: Beginning of action potential [Ca2+ in]

3: K+ efflux (out)

NA CA K

What's Happening?

Ventricular Muscle Phases

[image]

0: Na+ entry triggers depolarization

1: Transient K+ efflux (TMP to 0mV)

2: Na+ causes K+ out (plateau)

large amount Ca2+ in [L-TYPE!!!!Ca2+ channels open long time]

3: K+ efflux more than outgoing Na+

4: Back to rest [Na+ & Ca2+ close, Open K+]

Funny Channels (If) are

[SA node]

I=conductance

f=funny

-non slelective ion channels(all voltage gated)

-constantly open (leaky) to cations at RMP

-Ca2+ open at threshold

-K+ open when fully depolarized

Ventricular muscle Channels

[both channels must be open to wrk]

-all voltage gated

-L-type Ca channels open at depolarized membrane pot.

-A # of K+ channels make up Kto and Kdr

-Kdr opening causes cell repolarization(heart refills w/ blood)

Heart Contraction

[image]

phase 0 depolarize

Phase 2 inc P Ca2+ 

Triggers Ca2+ release from SR [binding site on ryanodine receptor]

inc free Ca2+

Heart relaxation

[image]

Repolarize phase 3 

P K+ efflux [hyperpolarizing to -90mV agn]

3Na+/2K+ pump

Na+/Ca+exchange (Ca out Na in)

1. Na+

2.Ca2+

PLB  (Phospholamban) is the main way we rid calcium to restore relaxation of Cardiac muscle and is....

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-Protein stuck to ATPase [inhibits act. of Ca2+ pump]

-Dissociates & inc act of SERCA which restores Ca2+ in SR [RELAXATION]

the Sarcoplasmic Reticulum (SR)

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What effects SV (Stroke volume)?

[3]

1. Preload

2. Afterload

3. Contractility

HR frequency change via ___and ____

Strngth of Contrction controlled via

PNS & SNS

SNS [local effect via initial stretch]

Sympathetic nerves = Nor and Epi

Parasymp nerves = Acetylcholine

[PNS and SNS wrk together on heart]

INC & SPEED up SA and AV activity 

DEC and SLOW dwn SA and AV activity 

Vagal effect = Brake

[Dec HR]

-Pronounced Dec in Pacemaker Pot.

-Dec prob of open If and Ca2+ channels

-Inc prob of open K+

Vagal effect makes cells start at a ____________membrane pot. [<-60]

[inc threshold & dec slope]

lower

[cells more hyperpolarized]

[inc pain = inc vagal tone & can cause syncope]

[Causes bradycardia]

Sympathetic EFFECT = inc HR

[dec threshold inc slope]

-Inc probability of OPEN If (funny=leaky) channels

-inc probability of Ca2+ channels

-Tachycardia

ex: HR of 60-70 bpm can go to 140-160bpm

SA node firing

[every P wave results in QRS complex in normal heart]

Na+ or Ca2+ influx _______________

while

Efflux of K+ ______________cells

Depolarizes

Repolarizes (HYPERPOLARIZES)

Gap junctions

[Ca2+ stored in SR in cardiac myocites]

Gap junctions

[Ca2+ stored in SR in cardiac myocites]

[image]

SA node [Right atrium] = blood returns to heart from inf. &sup ven. Cav

to

AV node = [set by SA node]

to

Purkinje fibers = between atrium and ventr. [large myocites]

1. WHere do escape beats occur?

2. where do ectopic beats occur?

[image]

1. Av node or purkinje fibers

2. Ventricular walls (left or right)

Proteins letting out K+

[K+ delayed & rectifying/repolarizing]

The refractory phase is important for 

[image]

The refractory phase is important for 

[image]

What is SERCA/ what does it do?

-Smooth endoplasmic reticukum Calcium ATPase pump

[restores Ca2+]

What is SERCA/ what does it do?

-Smooth endoplasmic reticukum Calcium ATPase pump

[restores Ca2+]

Changes in blood volume affect venous return

examples...

-more intake or retention

-loss w/ sweat or hemmorrage

Changes in blood volume affect venous return

examples...

-more intake or retention

-loss w/ sweat or hemmorrage

-P and QRS

-Dec PR interval

-Dec RR interval

-Dec AV node delay

-Dec SA node firing rate

-Inc AV node delay[slower conduction throughout ATRIA]

-Inc RR and PR interval

Exercise inc ______ and _____

and dec. PNS and RR interval

-SNS/SA node firing

-HR

Release of Ca2+ = Phase ____

Restorage [repolarization] = Phase ___

Phase 2

Phase 3

Release of Ca2+ = Phase ____

Restorage [repolarization] = Phase ___

Phase 2

Phase 3

-SA node 

&

-Ventricles

1. L-Type Ca2+ channels [Ca2+ entry]

2. Ryanodine Receptor [Ca2+ induced Ca2+ release from SR]

3. Troponin [Cross bridge formation]

The Frank-Starling Mechanism

[INTRINSIC EFFECT OF myocardium]

Out flow matches inflow

inc volume enters heart during Diastole

-Out flow matches inflow

-inc volume enters heart during Diastole

-INC. Venous return, EDV, Stretch of fibers, SV

-Inc volume at end of beat due to pressure aortic valve

-INC. BP, ESV, EDV, Stretch of fibers, SV

-Change in  blood volume.

-inc in intake or retention

-loss w/ sweating, hemorrhage

Change in compliance

-SNS dec compliance(alpha 1 rec)

-Muscl activity

-Inc wall stress during contraction w/ inc P or r of ventricle

-inc BP

-Aortic Stenosis

-Inc chamber size [dilation]

-Chronically inc afterload [Hypertension] 

-Chronically inc SNS

-Chronically inc Preload (volume overload)

Time of Ventricular depolarization & repolarization

{used clinically]

[Normal is QTc = 440-460msec] corrected QT

Atrial depolarization

[Depolarization means contraction]

Ventricular Depolarization

[Depolarization means contraction]

Ventricular Depolarization

[Depolarization means contraction]

Ventricular Repolarization

[beginning of ventricular relaxation]

Effect of K+

1. Inc plasma K+=less negative RMP (more Na+)...

2. Decrease in Plasma K+ = more neg RMP (Na+ If channels available

[image]

1. BRADYCARDIA =  Repolarization impaired [less excitable]

2. Tachycardia = Repolarization period faster [more excitable]

-Abnormal location takes over as pacemaker

-Ischemia/apoptosis causes leaky cells

-Hyperkalemia/calcemia inc. cells excitability

Afterdepolarization

-Excitation during relativerefractory period [stage 3 or 4]

LEADS TO TACHYCARDIA

1. premature ventricular contraction

2. Ventricular Tachycardia

3. Torsades de Pointes

inadequate blood to organs

(especially heart or from heart to periphery)

Re-entry

[image]

-Always irregular tachycardias

-recurrent pathways produced by ischemia

1. ATRIAL FLUTTER-regular P waves (mostly looks regular)

2. ATRIAL FIBRILLATION-irregular P waves 

3. VENTRICULAR FIBRILLATION- DEATH, very fast irregular QRS, need defibrillator to revive, NO cardiac out put

ATRIAL FLUTTER

[image]

regular P waves (mostly looks regular)

[image]

ATRIAL FIBRILLATION

[image]

irregular P waves 

[image]

 VENTRICULAR FIBRILLATION

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 DEATH, very fast irregular QRS, need defibrillator to revive, NO cardiac out put

[image]

BUNDLE BRANCH BLOCK

[image]

Are characterized by QRS shape change

[can happen in left or right]

-Beta blockade [too much beta blockers]

-vagal stimulation [slowing of HR]

-hypokalemia [lowers RMP]hyperpolarizes cell

-digitalis(drug effect)

-hypoxic or ischemic damage or scarring

1st degree nodal Block

[image]

slow A to V conduction [inc P-R interval]

2nd degree Nodal Block

[image]

not all A contraction causes V contraction

[multiple P waves]

slower than 1st degree

3rd degree nodal block

[image]

-A, V dissociated

-PR intervals are variable

-SOOOOO slow that Ventricles take over own firing

Arrhythmias

[image]

1. SINUS: inc or dec of rate

2. NODAL: SLowing [block]

3. Conduction Pathway: Blocks, abnormal pathways, re-entry

4. Abnormal impulses = ectopic foci-cells outside acting as pace

[triggered activity] 

1. SA node rate changes.....

2. AV node rate changes or block.....

1. change HR w/o chnging ECG shape

2. alter relation of P to QRS w/o chnging QRS shape

4 valves

APTM

A & P

CLOSED DURING FILLING [DIASTOLE]

M & T

CLOSED DURING CONTRACTION [SYSTOLE]

2 NORMAL HEART SOUNDS 

1. 1st sound at strt of V contract. [M & T closing]

2. 2nd sound at strt of diastolic filling [A & P close]

During Systole what happens?

[image]

-Ventricles contract

-A & P valves open

-Ventric. press. gets greater than aortic p

What happens during Diastole?

[image]

-A and P Valves close

-Ventricles relax

-ventricular pressure falls below Aortic

Mitral valve prolapse [minor form, can be asymptomatic]

Mitral valve regurgitation [more severe, backflow]

Mitral Valve Prolapse

[especially in woman]

-enlarged leaflets or chordinae tendinae too long

-backflow of blood into atria during ventricular systole[intermittent]

Mitral Valve Prolapse Sx (MVP)

[10-15% women]

-can be asymptomatic, no regurgitation & normal cardiac func

-can cause midsystolic clicks or late systolic murmur

-pt's have chest palpitations (arrythmias)

Progress to regurgitation

rupture of chord [sudden regurgitation]

infective endocarditis

microthrombus formation- emboli

atrial or ventricular arrhthmias

Mitral regurgitation{SYSTOLIC}

[image]

rupture of chordaae tendinae[acute]

-structural abnormality or damage to valve [chronically occurs]

{from endocarditis, ischemic heart disease CAD, structural abnormality of structural abnormality of valves or papillary muscles, LV enlargement, calcification}

Mitral Regurgitation Sx {SYSTOLIC}

holosystolic or pansystolic murmur (all of systole S1 to S2)

-backflow into LA leads to inc LA pressure (pronounced when acute and severe)

-pressure overload in atrium

{left atrial enlargmnt, atrial arrythmias,thrombus formation 20%, pulmonary edema & possible right heart failure}

-pressure overload in atrium

{left atrial enlargmnt, atrial arrythmias,thrombus formation 20%, pulmonary edema & possible right heart failure}

-normal opening = no sound

- S3 and S4 due to flow of blood into large heart

Stiff valve not completely opening

Reduces flow throu valve

Valve does not completely close

backflow or regurgitation

[regurge is floppier]

1/3 systole

2/3 diastole

{heart sounds = valve closure}

thickning/calcification of valve

thickening & shortening of chordae tendina [due to rheumatic fever, strep infection]

Mitral stenosis Sx {DIASTOLIC}

[image]

-loud S1 (closure) possible snap & diastolic rumble

-rdeuced outflow into LV casue in P in LA

-Pressure overload in atrium 

-LA enlargement

-Atrial arrythmias

-thrombus formation (20%)

-pulmonary edema (possible right heart failure)

Aortic stenosis {SYSTOLIC}

[image]

-rigid valve bc calcify/fibrosis

{rheumatic heart disease}

-senile calcification

-congenital deformed

-valve with deposits of Ca2+

-late systolic ejection murmur[S4 sound]

-Reduced Outflow into aorta

[leads to dec aortic P, inc LV P]

-Pressure ovrload in ventricle

{chest pain, syncope,fatigue,left heart failure, dizziness w/ exercise, fatigue,dyspnea,cyanosis}

Aortic Regurgitation {DIASTOLIC}

[image]

dialated/hypertrophied left ventricle

-rheumatic disease

-cingenital valve defect

-endocarditis

-aortic root dilation[marfan syndrome, aneurysm, syphilis]

-Hypertension

early diastolic murmur

[valves should be closing during diastole]

-backflow into LV leads to abnormal aortic P

-acute(rupture): LV P wave increase fast

-Volume overload of ventricle (risk)

-LV dilation Ventricular arrythmias

-fatigue, exercise intolerance, angina

-pulmonary edema, dyspnea w/ progression

Atrial septic Defect [end of diastole but beginning of systole]

-incomplete closure of atrial septum

(req mor wrk fromright heart)

-opening between left and right atrium [did not close after fetal time]

-blood in RA seeps into LA

-Causes murmur 

-Inc risk of pneumonia, clots and stroke

Ejection fraction =

[measures myocardial performance]

Ejection Fraction = SV/EDV

[sv=amount pumped per beat

EDV = volume available to be pumped]

EDV 

venous return

(intrrinsic mech. of muscle stretch with filling)

Response to P or volume overload

wall tension = P x radius/2

aortic regurgitation

volume loading heart failure

myocardial infarction

Aldosterone OR COrtisol 

(meralcorticoid receptor blockers)

-Renin-Angiotensin system (AT2RBs and ACE inhib.s)

ISCHEMIA 

Pulmonary Edema

Heart Failure

Angina

Arrythmias

[larger heart to inc. stroke volume]

Hypertropic Cardiomyopathy

-ABnormal diastolic RELAXATION

-thickening of tissue in wall with abnormal fiber struct 

[image]

Inc or normal contractility

decreased relaxation

increseased diastolic P

[ischemia,angina,mor muscle mass]

Hypertropic Cardiomyopothy Sx

(hard to fill heart)

s3,s4 sounds

diastolic murmur if mitral obstruct

ventricular arrythmias

hypotension (fatigue if aortic valve obstructed)

Ventricular dilations

alcohol, anticancer drugs

Impaired systolic

dec SV, dec EF

Dilated Cardiomyopathy Sx (systolic)

[image]

S3 sounds

Murmur(mitral regurg)

Arrythmia=Afib,Vtach

Edema= congestive heart failure

[faatigue,weak,syncoope]

Restrictive Cardiomyopathy

[rigid ventr wall]

dec diastolic relaxation

dec filling 

inc diastollic filling P

inc veinous P

palpitations and syncope

weakness

Arryhtimias-   afib, vfib

Edema, HF

inability to pump to meet demands of CO

EF low(sytolic failure)

<35%

dilated cardiomyopathy

valve disease- aortic stenosis/regurg

long standing HTN

cardiac ischemia

increasing Ca2+ release from SR

[norep and angiotensin II]

inc Ca2+ storage in SR

[inc K+ efflux-hyperpolarize cell(makes lessexcitable)]

[NO,lactic acid,prostacyclin,adenosine]

hemmorhage

burns

diahrrea

vomitting

[low volume]

Myocardial failure, acute valve defect , MI

[Low CO]

allergic reaction to bite drug 

food

[vasodilation]

infection reaches bloodstream and causes inflammation

[vasodilation]

too much NO produced

reflex response to traumatic injury

[loss of vascular tone]

ddec urine prod [to keep fluids]

tiredness or fatigue

rapid/irregular heart beat[heart tries to inc blood sent to body]

congestsion

weakness,fatigue

more co2

heart beats harder and faster[palpitations]

edema in peripheral [lowere extremeties]

weight gain

inc urination(at night)