test 2 key Flashcards
what are the 2 things that the force of a cardiomycote depends on with each systole
- ionotropy (contractility)
- optimal overlap between myosin and actin in diastole
what is ionotropy and what is it increased by
contractility from calcium binding troponin
increased by SNS, HR, cortisol, thyroid homrone
what is the optimal overlap between actin and myosin in diastole length? what’s it determined by?
(1.95-2.25)
Determined by preload (ventricular filling- end diastolic volume)
afterload
(pressure to overcome to eject blood into great arteries).
Tension the ventricles need to open aortic valve
what increases afterload
Increased by aortic stenosis, elevated BP
increasing afterload has what effect on stroke volume and ejection fraction
Increasing afterload decreases stroke volume and ejection fraction
if ionotropy decreases then what happens to ejection fraction and stroke volume
decreased ejection fraction lower stroke volume
chronotropy
Rate of depolarization aka heart rate
how much of ventricular filling is passive
80%
which side of heart has lower pressure
right ventricle bc left ventricle goes into systemic
Atrial pressure curve
- A Wave – Atrial contraction (atrial systole)
- C Wave – Bulging of tricuspid
- X Wave – Atrial relaxation (atrial diastole)
- V Wave – Passive filling of the atria (ventricular systole)
- Y Wave – Emptying of atria into the ventricles with the opening of AV valves (early diastole).
what is the dicrotic notch
2nd wave after aortic valve closes (elastic recoil)
s3 and s4 ok?
- S3 in healthy people unless new emergence (MI)
- S4 pathologic (non compliant ventricle)
what part of the heart has the highest pressure and is what causes our 120/80 blood pressure
aorta
what corresponds to preload
end diastolic volume
what is end diastolic volume
the volume in the ventricle at the end of diastole
what is end systolic volume
the volume in the ventricle at the end of systole
what is stroke volume
the volume ejected with each heartbeat
formula for stroke volume
SV = EDV – ESV
what is stroke volume impacted by
- Preload
- Contractility (inotropy)
- Afterload
increasing afterload does what to stroke volume and ejection fraction
decreases stroke volume and ejection fraction (higher oxygen demand in hypertension)
cardiac ouput
is the volume ejected by each systole X heart rate
cardiac output formula
CO = SV X HR
what determines oxygen and nutrient delivery to tissues
cardiac ouput
what is cardiac output increased by
catecholamine, stretching of ventricles, increased HR and contractility, increased central blood volume, increased systolic BP, increased preload and venous return
what is the SNS trope effect and how does it increase cardiac output
accumulate Ca2+ in SR as HR increases; not enough time to remove Ca2+
what decreased cardiac ouput
PNS
why does cardiac output need to be equal in the left and right ventricle
ventricle to prevent pulmonary congestion and systemic hypoperfusion
what is ejection fraction
is the proportion of EDV that is ejected each beat
what is an estimate of heart function in heart failure
ejection fraction
what is a normal ejection fraction
> 50%
ejection fraction formula
▪ EF = SV/EDV = (EDV – ESV)/EDV
preload of one ventricles depends on ____ of the other
cardiac output
SERCA (Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase)
- Reuptake Ca2+ into SR after contraction
what happens if SERCA activity decreases
prolonged muscle relaxation (diastolic dysfunction), reduced Ca2+ release for contraction and weaker heartbeats (negative ionotropy)
Skeletal myocyte excitation contraction coupling
- Ach on nicotinic receptor initial depolarization
- Na+ VGC open depolarize sarcolemma (AP) open Ca2+ VGC
- L type Ca2+ VGC opens ryanodine receptor in SR (T tubules get AP deeper into myocyte)
a. Most Ca2+ that enters cytoplasm if from SR - Increased cytosolic Ca2+ binds troponin open myosin binding site on actin (move tropomyosin out of way) cross bridge formed and force generation
- Ca2+ decrease when AP stop; pump Ca2+ into ECF or SR
- When Ca2+ decrease the tropomyosin covers myosin binding sites again sarcomeres relax
what acts on nicotinic receptor to start excitation contraction coupling (in skeletal muscle)
Ach
what gets AP deeper into myocyte in skeletal muscles
t tubules
most of the Ca2+ that enters the cytoplasm is from the (in skeletal muscle)
SR
cross bridge cycle
- ADP + Pi on myosin head, allosterically inhibited by tropomyosin so cant bind actin
- Ca2+ binds troponin C so myosin can bind actin rigor state detach when ATP binds myosin head and is hydrolyzed
sarcomere
- Thick (myosin) and thin (actin) filaments overlap for contraction and cross bridge
similarities in skeletal and cardiac myocutes
- Striated, involve actin: myosin overlap
- Parabolic isometric length: tension relationship
- Peak isometric forces matches optimum passive resting length
- T-tubules exist in both (get AP deeper into muscle fibers)
- Ca2+ ATPase pumps to remove Ca2+ into SR
what is in cardiac myocytes that’s not in skeletal
no tetany in cardiac
have a syncytium
why no tetanic contraction in cardiac myocytes?
due to long electrical refractory period (extracellular calcium triggers intracellular calcium release)
syncytium in cardiac myocytes
cardiac myocytes are interconnected via branches and intercalated disks (gap junctions and desmosomes)
t tubules in cardiac myocytes
T tubules play a less important to the excitation- contraction coupling of cardiac cells; they are larger but fewer
cardiac cells; how many nuclei and mitochondria ? what form of metabolism?
cells have 1 single nucleus and LOTS of mitochondria
Oxidative metabolism (use fats), little glycogen stores
4 APs in the heart
myocyte:
1. atrial
2. ventricular
- purkinje
- automatic cell
4 phases of myocyte APs
- Phase 4= resting membrane potential (RMP)
- Phase 0= rapid depolarization (upstroke)
- Phase 1 and 2= prolonged depolarization/plateau
- Phase 3= repolarization
what’s shorter; atrial or ventricular APs?
- Atrial APs shorter than ventricular, allowing for faster contraction cycles
purkinje fibers have an unstable phase _
unstable phase 4; can spontaneously generate APs in abnormal conditions
automatic cells are :
pacemaker cells (SA and AV nodes)
automatic cells have an unstable phase _ and depolarize via __________
unstable phase 4 to spontaneously depolarize via funny currents (If)
which node sets the HR
SA node
where is SA node located
SA nodes in right atrium close to entrance of superior vena cava
phase 4; what is open? memebrane potential?
resting membrane potential
o (leaky K+ channels are open)
o Nernst= -84mV
phase 0; what opens?
rapid depolarization
o open VGC Na+; Na+ influx
phase 1
initial rapid repolarization
o close Na+ VGC
o open fast K+ VGC allowing K+ efflux
o membrane potential close to 0
phase 2
plateau
o open L-type Ca2+ channels that allow Ca2+ to influx
o No summation is possible due to the prolonged depolarization of the myocyte, no further action potential can be delivered to the cardiac myocyte
o Plateau bc Ca2+ channels (in) and slow K+ channels (out) cancel each other out
phase 3
: slow repolarization
o Close Ca2+ channels
o open slow K+ VGCs
calcium spark
1 Ca2+ VGC opens and elicits small amount of Ca2+ release from neighbouring ryanodine receptor on SR summation of these to increase cytosolic Ca2+
how to get ca2+ into SR? regulated by?
- SERCA get Ca2+ into SR
Regulated by phospholamban (phosphorylate to increase activity)
how is calcium removed from cytoplasm
Calcium sequestered by sarcolemma calcium ATPase (ca2+ out) and sodium-calcium exchanger (3 Na in, 1 Ca out; depolarize)
activation of SNS has what effect on contractility
- Active SNS (Beta 1 receptors) increase cAMP phosphorylate phospholamban and troponin and l-type Ca2+ VGC
SNS
- Increases cytosolic calcium release with each AP greater force of contraction
- Increase relaxation after reduced troponin affinity and increased SERCA activity
- Net: quick, forceful contraction and quicker relaxation
atria vs ventricular myocyte AP
- Atria don’t need to generate as much force
- RMP (phase 4) is slightly more depolarized (reduced K+)
- Lower plateau (phase 2) (lack of Ca2+ channels)
what are the pacemakers
- SA node, AV node, Purkinje fibers: generate APs spontaneously (no external stimuli)
primary pacemaker? bpm? backup?
a. SA node= primary pacemaker (60-100bpm)
i. AV node as backup
ii. Purkinje in pathologic states
heart rate is determined by
which cell depolarizes most frequently - SA node
phase 4 RMP in automatic cells
not stable; funny current from gNa+ and gK+ open during hyperpolarization and closed in depolarization
which phases are missing in automatic cells
phase 1 and 2
which phases are in automatic cell APs
phase 4, 0, 3
phase 0 and phase 3 in automatic cells
- Depolarization in phase 0 if from L type Ca2+ channels NOT Na+ VGC (closed)
- Phase 3: Ca2+ VGC close, K+ open (efflux = more negative)
PNS impacts on automatic cell AP
- Increase K+ = hyperpolarize
- Decrease Ca2+ influx= slow depolarization
- Increased atrial refractory period= decrease HR and decrease cardiac output
negative and positive ionotropy
- Positive ionotropy (contractility) = SNS increases rate of depolarization, RMP more +
- Negative ionotropy= PNS decrease rate of depolarization, RMP more –
where in the conduction system is there a delay
- Delay at AV node: time for atria to eject blood into ventricle prior to ventricular contraction
what carries the AP along the septum of the heart
- Bundle of His (AV bundles)
where do purkinje fibers carry AP to
to apex and base of heart ventricles contract
fibrous skeleton of heart purpose
isolates atria and ventricles and prevents direct conduction (so that only communication is via AV node)
Bachman’s bundle
allows for rapid conduction from right to left atrium = simultaneous atrial contraction
ECGs measure what
electrical differences across the heart
baseline in an ECG
= whole heart is either repolarized or depolarized
wave in an ECG
different electrical state in 2 separate areas of the heart
little box in an ECG
0.1mV high x 0.04 seconds wide
(big box= 0.5 mV x 0.2 seconds)
P wave
atrial depolarization (via SA node)
PR interval
time it takes for impulse to travel from SA node through atria and AV node to ventricles
QRS complex
ventricular depolarization (conduction pathway via Bundle of His and Purkinje fibers)
ST segment
when ventricles are fully depolarized, before they repolarize
T wave
ventricular repolarization
QRS interval
time it takes for AP to travel from end of AV node and throughout ventricles
QT interval
ventricular depolarization and repolarization
heart failure
- Contractility is significantly impaired resulting in reduced ejection fraction (how much is pumped out versus how much remains in the ventricle)
cardiac arrest
- Heart suddenly and unexpectedly stops pumping, often caused by ventricular arrhythmia’s, such as ventricular fibrillation or ventricular tachycardia
angina
- Pain brought on by ischemia, that doesn’t result in permanent heart damage
tachyarrhythmia
Abnormal heart rhythm (arrhythmia) with a heartbeat of >100 beats per minute (tachycardia)
3 layers of walls of veins and arteries (in to out)
tunica intima
tunica media
tunica externa/adventitia
what’s in the tunica intima
a. Simple squamous endothelium, subendothelial CT, internal elastic lamina
what’s in the tunica media
a. Thickest layer in arteries
b. Smooth muscle cells and fibroelastric CT, external elastic lamina
what’s in the tunica advnetitia/externa
a. Outermost layer
b. Thickest layer in veins
c. Dense irregular CT
d. Houses vasa vasorum (blood vessels to supply tunica adventitia and media)
which layer is thickest in veins? in arteries?
arteries- tunica media
veins- tunica externa/adventitia
elastic arteries
have most elastic membranes (for high pressure blood flow from heart)
a. Aorta, pulmonary arteries, common carotid arteries, subclavian arteries, common iliac arteries
muscular arteries
have more smooth muscle (in tunica media) for regulating blood flow
a. Radial artery, femoral artery, brachial artery, coronary arteries, popliteal artery
arterioles
control flow into capillary beds and regulate BP through constriction or dilation
metarterioles
are transitional vessels between arterioles and capillaries (via precapillary sphincters to regulate blood flow)
what regulated blood flow to capillaries
pre capillary sphincter
3 types of capillaries
continuous
fenestrated
sinusoidal
what type of capillary is the majority
continuous capillaries
which capillary is the least permeable
continous capillarie
which capillary is the most permeabel
sinusoidal capillaries
continuous capillaries
- Least permeable, majority of capillaries
- Intercellular junction for flow of water-soluble substances
fenestrated capillaires
- Moderately permeable (filtration and absorption organs i.e. kidneys, endocrine glands)
kidneys, endocrine, pancreas, intestines are which type of capillary
fenestrated
sinusoidal capillaries
- Highly permeable to large particles (i.e proteins), in specialized organs (liver, spleen, etc)
- Discontinuous basal lamina, big gap junctionsw
what type of capillaries are CT, muscle, neural, brain
continuous capillaries
what type of capillaries are bone marrow, spleen, lymph
sinusoidal capillaries
large veins
- i.e. vena cava, pulmonary veins, portal vein
- tunica intima has prominent subendothelial layer
- tunica media is thin with few muscle cells
- tunica adventitia is thickest layer with dense CT, collagen, elastic fibers, vasa vasorum
function of large veins
return deoxygenated blood to heart from systemic
medium veins
- i.e. femoral vein, renal vein, brachial vein
- tunica intima is think subendothelial layer
- tunica media is thin and scattered smooth muscle cells
- tunica adventitia is thickest layer with collagen and elastic fibers
what do medium veins have to prevent back flow
- valves in limbs to prevent backflow of blood due to low pressure
function of medium veins
drain blood from organs and limbs using valves to direct blood flow towards heart
small veins (venules)
i.e. postcapillary venules, collecting venules
- tunica intima: thin basal lamina
- tunica media: few layers of smooth muscle or absent
- tunica adventitia: thin layer of CT
function of small veins (venules)
collect blood from capillaries and begin process of returning it to larger veins
how are valves made in medium and large veins
via reflections in tunica intima (esp lower extremities)
how much of the body blood volume is in systemic veins and why
- lumen of veins is larger (and don’t constrict much) than arteries; 2/3 of body’s blood volume is in systemic veins
a. can restrict via catecholamines
poiseuilles law for blood Flow through a tube
effect of radius, length, viscosity
a. smaller radius= higher resistance and decreased flow
b. increased length and viscosity= higher resistance (i.e. dehydration)
c. only applicable in laminar flow (not turbulent)
turbulent flow is increased by
turbulent flow at high velocities or area with bifurcations and atherosclerotic plaques (sharp changes in vessel diameter)
a. use Reynolds number for turbulent flow
b. pathologies increasing turbulent flow: atherosclerosis, stenosis, hypertension, aneurysm, valvular heart disease
Bernoulli principle
pressure is constant in a system, regardless of velocity
two types of circulation
series and parallel
series circulation
one vessel to another; less common (ie. heart to aorta)
a. total resistance= sum of resistances of each individual vessel= higher overall resistance and less efficient blood flow
what is the more common arrangement of circulation in body; series or parallel
parallel
parallel circulation
blood flow through multiple vessels simultaneous; majority arrangement in body (i.e. capillary beds)
a. total resistance is less, each additional pathway provides alternative rout for blood flow; more efficient
b. capillaries have higher resistance due to small radius but in parallel it decreases it
total blood volume in body? when is it?
- total =5 L
a. 80% systemic circulation 60% systemic veins and 20% small arteries and capillaries
veins are ____ and easily distend to hold lots of blood
floppy
compliance
- How much pressure is required to change the diameter (volume) of blood vessel
high compliance
small amount of pressure large change in volume
what is more compliant; veins or arteries
- Veins more compliant than arteries (less muscle, more floppy) “blood reservoir”
a. Arteries stiffer, esp. atherosclerosis, calcify
low compliance in
in arteries; don’t stretch easily bc of muscle and elastic fibers to help maintain high BP and efficient flow of blood
a. Compliant, yet elastic arteries decrease cardiac work
central blood volume (25%). (most is systemic
- Vena cavae, heart, pulmonary circulation
- Determines preload
upright posture; how to get blood back to heart
- Valves in leg veins of lower body
- Skeletal muscles contract when standing and surround leg veins
- Inhale decreases intrathoracic pressure and draws blood up
mean arterial pressure
- Average of systolic and diastolic
- 1/3 of cardiac cycle is in systole
- MAP= DP + 1/3(SP-DP)
how much of cardiac cycle is spent in systole
1/3
microcirculation
- Distributing artery (branches) when go to organ further branching into arterioles (regulate blood flow, resistance, BP) metarterioles (discontinuous muscle) (pre-capillary sphincters to regulate blood flow) capillaries (site of nutrient and gas exchange) (type IV collagen in basement membrane)
basement membrane in capillaries
type Iv collagen
continuous capillaries allow for
least permeable) are leaky and allow free movement of small, water-soluble substances across
exception for continuous capillaries
blood brain barrier and blood testes barrier
what is in the blood brain barrier and blood testes barrier that reduces permeability
i. Tight junctions from occludins and claudins
pinocytosis
endocytose extracellular fluid vesicles that allow for regulated exchange of substances between bloodstream and tissue; even if tight junctions
pinocytic vesicles can coalesce and form
vesicular channels
what increases pinocytosis
i. Increased pinocytosis and permeability in inflammation to transport immune cells to affect area
caveolae “small caves” in continuous capillaries of
i. Endocytosis and transcytosis of macromolecules
ii. Intercellular clefs for small molecules (albumin wont get through- albumin keeps water in capillary)
starling forces; oncotic pressure and hydrostatic pressure
i. Hydrostatic pressure pushes fluids out
ii. Oncotic pressure pulls fluids in
too much movement across capillaries
edema
how to reduce edema
i. Reduced by glycosaminoglycans (absorb water) and lymphatics
auto regulation; caused by what?
intrinsic ability of capillaries to regulate blood flow via local tissue factors
a. Metabolic factors: CO2, O2, H+, lactate, adenosine, K+ = vasodilate
myogenic regulation of blood flow in capillaries
a. Constant rate of tissue flow despite changes in mean arterial pressure (via dilate or constrict)
myogenic regualtion vs autoregulation
myogenic- dilate or constrict
auto regulation- local tissue factors to regulate blood flow (i.e. CO2, K+)
nitric oxide is made by? and released by? to vasodilate
- Made by endothelial cells and released by shear stress (force on blood vessel)
steps of nitric oxide vasodilation
- NO guanylyl cyclase cGMP PK G relax smooth muscle
what causes vasodilation
- Histamine: vasodilate arterioles, constrict venules edema
- Bradykinin: via inflammatory signals
- Prostaglandin E2 and I2
- Epinephrine and norepinephrine via beta 2 receptors
what cause vasoconstriction
- Epinephrine and norepinephrine via alpha 1 receptor
- Serotonin via tissue damage
- Thromboxane A2 and prostaglandin F
- Angiotensin II
- ADH
- Reaction to damage (platelet plug formation)
for NE and E which receptors do vasodilate and which do vasoconstrict
beta2= vasodilate
alpha1= vasoconstrict
which metabolic factors override the ANS in exercise
- Lactate: anerobic; increase blood flow and oxygen delivery
- K+: vasodilate and increase blood flow
- Adenosine: result of ATP breakdown; vasodilate
cerebral blood flow regulated by
pH and adenosine
Cushing reflex in brain
increased intracranial pressure decreases perfusion
pulmonary circulation is controlled by
- Controlled by O2
a. Decreased= constrict
b. OPPOSITE TO MOST VASCULAR BED which dilate in low oxygen
c. This allows for gas exchange efficiency
effect of oxygen on pulmonary (opposite to most other vascular beds)
vasoconstrict
which receptors in skin to constrict? purpose?
- SNS alpha 1 receptors = constrict regulate body temperature
coronary - mechanical compression during systole doses what to blood flow
decrease
stimulating hemorrhage via lower body negativee pressure
Lower Body Negative Pressure (LBNP) simulates hemorrhage by redistributing blood into the lower extremities.
- Key Concept: Mimics central hypovolemia without physical blood loss
5 causes of edema
increased blood hydrostatic pressure (push water out of vessel)
drop in oncotic pressure (pull water into vessel)
increased vascular permeability
blocked lymphatic drainage
sodium and water retention
increased hydrostatic pressure causing edema causes?
- Increased blood hydrostatic pressure (pushing force to move water out of vessel into tissue)
a. i.e. malignant hypertension, cushings (increase aldoterone)
drop in blood oncotic pressure causing edema- causes?
- drop in blood oncotic pressure (pulling force to draw water into blood vessel)
a. albumin for oncotic pressure
b. nephrotic syndrome= leak albumin from glomerulus
c. hepatic failure,
transudate
low protein, low cellular content from pressure imbalances
exudate
high protein, high cellular content caused by inflammation and vessel damage
transudate vs exudate in edema
- Transudate= low protein, low cellular content from pressure imbalances
- Exudate= high protein, high cellular content caused by inflammation and vessel damage
angioedema
edema in deep layers of skin esp seen in face
anasarca
= edema in many body parts
anasarca vs angioedema
- Anasarca= edema in many body parts
- Angioedema= edema in deep layers of skin esp seen in face
arterial vs venous side; which has greater oncotic or hydrostatic pressure
- Arterial side: hydrostatic pressure > oncotic pressure (fluid into interstitum)
- Venous side: hydrostatic pressure < oncotic pressure (filtered fluid is recaptured by osmosis)
hyperemia and congestion are both caused by
increased blood volume
hyperemia
arteriolar dilation leads to increased blood flow
a. Erythema
b. i.e. blood flow returns when warm after being out in cold
congestion
passive process = reduced outflow of blood from a tissue (passive hyperemia)
a. systemic (heart failure) or local (venous obstruction)
hemosiderin in congestion how?
b. cyanosis from red cell stasis eventually extravasate/ breakdown and cause hemosiderin (degradation product of hemoglobin found in macrophages)
long standing/ chronic passive congestion
a. hypoxia, cell death, fibrosis, congestion, hemorrhage, phagocytose and catabolise debris accumulate hemosiderin-laden macrophage
pulmonary congestion acute vs chronic
a. acute: alveolar capillaries engorged with blood, nutmeg appearance
b. chronic: septa become thickened and fibrotic and have hemosiderin laden macrophages
hepatic congestion
a. acute: hepatocytes degenerate, sinusoids and venules are distended with blood hypoxia and fatty change
infarct
tissue necrosis from lack of blood supply, oxygen, ischemia
white infarct
organs with only a single blood supply (i..e kidney or spleen)
red infarct
organs with dual blood supply (i.,e. lung, intestine)
what causes a red and white infarct
red= venous occlusion
white= arterial occlusion
pulmonary infarct
complication of pulmonary embolus in congestive heart failure
- cant provide oxygen to larger lung structures necrosis and hemorrhage
shock is from
- from trauma, MI, hemorrhage, PE, sepsis…
hemodynamic and metabolic disturbances in shock
circulatory system fails to supply adequate microcirculation to perfuse vital organs
distributive shock
anaphylactic and neurogenic shock
myocardial pump failure in schock
decrease blood volume, increase vasodilation, increase vascular permeability
types of shock
cardiogenic (i.e MI)
hypovolemic (i.e. hemorrhage)
septic
anaphylactic
neurogenic
septic shock
- high levels of pro-inflammatory cytokines. Leukocytes, activate coagulation and complement cascades
- dysregulated vascular reflexes
- warm skin
distributive shock
too many vessels dilated, not enough blood to keep the pressure up
symptoms in hypovolemic and cardiogenic shock
- hypotension, weak rapid pulse, tachypnea, cool clammy cyanotic skin
2 stages of shock
I- compensated
II- decompensated
compensated stage of shock
a. tachycardia, but BP normal (compensatory mechanisms to increase HR and peripheral vasoconstriction)
decompensated stage of shock
a. tachycardia and hypotension
decompensated vs compensated stages of shock
compensated has tachycardia but normal BP
decompensated is tachycardia and hypotension
ishcemic heart disease
- inadequate blood supply to myocardium
most common cause of ishcemic heart disease
atherosclerosis of coronary arteries
stable angina
when lumen on large artery reduced 50-75% and IHD symptoms increase during activity
i. occlusion from plaque or thrombosis
unstable angina
lumen reduced 80-90%, symptoms at rest
i. from thrombus that forms and is broken down
unstable vs stable agina
stable= only symptoms at activity
unstable= symptoms at rest and thrombus broke down
what exacerbates ishcmeic heart disease
increase metabolic demand ie. a. increase HR, wall tension, contractility
what are the 2 components to acute coronary syndrome
unstable angina and MI
Prinzmetal angina (vasospastic or variant angina)
- unstable angina, but with better prognosis
- caused by coronary artery spasm
- occurs in morning, unrelated to exertion
- responds well to vasodilators
adaptations to chronic heart ischemia
- hypertrophy and changes in contraction
- develop coronary collateral circulation
acute infarction
- heart only gets oxygenated blood during diastole
what type of angina is more likley to cause myocardial infarction/heart attack
unstable angina
symptoms of MI
chest pain, heartburn, interscapular pain, dyspnea…
time course of MI
- first few minutes: cells and mitochondria swell, lose glycogen
- 30-60 minutes: irreversible ischemia myocyte injury
- Day 2-3: neutrophils enter necrotic tissue, edema, hemorrhage
- Day 5-7: neutrophils replaced by macrophages, myofibroblasts deposit collagen (scar tissue)
- Week 1 >: collagen depositions
- Week 3: scar tissue remodel
vessels most often involved in MI
- Anterior descending branch of left coronary artery (50%)
- Right coronary artery (30-40%)
- Left circumflex artery (15-20%)
which artery is most often involved in MI
- Anterior descending branch of left coronary artery
reperfusion injury in MI
damaged cardiomyocytes after blood flow is restored to ischemic tissue
what happens to contraction band in reperfusion injury (MI)
- Contraction band necrosis (along Z disk, disorganized sarcomeres) from Ca2+ flooding sarcolemma and ROS damaging mitochondria
2 types of MI
STEMI (st elevation)
NSTEMI (non-st elevation)
STEMi vs NSTEMI
STEMI: - Permanent occlusion/ complete blockage of coronary artery
NSTEMI: - Partial blockage of coronary atery
- Global hypoxia, small vessels occluded, transient occlusion
what’s worse STEMI or NSTEMI
STEMI is generally worse than NSTEMI due to the complete blockage of a coronary artery and the larger area of heart muscle affected.
ischemicc heart disease symptoms
- Asymptomatic
- Chest pain- angina pectoris (refer to left arm, scapular, sternal etc) crushing/sqeueezing pain
- Dyspnea, fatigue, palpitations, diaphoresis (sweat)
- Complication : MI
acute ischemic heat disease
- Stable or unstable angina, MI, sudden cardiac death
a. Stable angina: chest or arm pain, reproduced with exertion or stress, relieved with rest and nitroglycerine
b. Unstable angina: chest or arm pain, occurs and not relieved at rest
c. Cardiac death: from dysrhythmia
ischemic heart disease diagnosis
- ECG : ST elevations…
- Cardiac enzymes ; troponin, CK-MB (creatine kinase) (most reliable)
- Angiogram
- Echocardiogram
- Nuclear medicine imagine
what is the most reliable blood marker for ishemic heart disease
creatine kinase MB (CK-MB)
ishcemic heart disease treatment
- Treat causes of imbalance of energy supply and demadn to myocardium
a. ASA aspirin (antiplatelet agent), antihypertensives, beta blockers, calcium channel blockers, nitroglycerine, blood glucose control…
different treatment for STEMI vs NSTEMI
- NSTEMI: no clot busting drugs (bc partial blockage)
- STEMI: clot busting drugs, thrombolytic drugs
- For both; revascularization (angioplasty or stent), resuscitation
2 characteristics of a normal ventricles
compliant (diastolic filling at low atrial pressure), strong (ventricles generate enough force)
cardiomyopathies
damaged myocardium- decreased compliance and contractility
reasons for heart failure
- Increased afterload (ventricles hypertrophic and decrease contractility)
- Impaired oxygen; ischemic heart disease
- Cant relax/ reduced compliance bc fibrosis
- Cardiomyopathies= damaged myocardium- decreased compliance and contractility
risk for heart failure
- Hypertension, MI, valve disease, diabetes…
2 types of heart failure
HFrEF (systolic dysfunction)
HFpEF (diastolic dysfunction)
HFrEF (heart failure with reduced ejection fraction)
AKA systolic disfunction
b. Impaired contractility reliance on elevated preload for adequate cardiac output
HFpEF (heart failure with preserved ejection fraction)
AKA diastolic dysfunction
b. Elevated diastolic pressures; good contractility, maybe impaired EDV
c. Impaired compliance
impaired diastolic function — meaning the heart is unable to relax and fill with blood properly.
HFrEF vs HFpEF
HFrEF is primarily a systolic dysfunction with a reduced ejection fraction, leading to significant heart muscle damage and worse prognosis without treatment.
HFpEF is a diastolic dysfunction with preserved ejection fraction, where the heart struggles to fill properly due to stiffening or thickening of the heart muscle, often seen in older adults or those with chronic hypertension or metabolic conditions. impaired diastolic function — meaning the heart is unable to relax and fill with blood properly
forward flow vs backward flow problem in chronic heart failure
Forward flow problems in chronic heart failure involve inadequate perfusion to the body’s organs and tissues, leading to fatigue, dizziness, and organ dysfunction.
Backward flow problems occur when blood backs up into the lungs or body due to the heart’s inability to pump blood effectively, leading to symptoms like shortness of breath, edema, and organ congestion.
what part of the heart is usually first to fail in chronic heart failure
usually left ventricle because greatest afterload
then pulmonary congestion icreases and the right ventricle will faail
when the right ventricle fails first what happens
o Cor pulmonale: pulmonary hypertension from COPD, OSA
o Lung disease causes hypoxia and pulmonary vasoconstriction
cor pulmonale
pulmonary hypertension from COPD, OSA
right ventricle problem
Cor Pulmonale refers to right-sided heart failure that occurs as a result of chronic lung disease or pulmonary conditions that cause increased pressure in the pulmonary arteries (pulmonary hypertension).
low oxygen concentrations in pulmnonary microcirculation causes
constriction
- Different than other vascular beds; help redirect blood flow to regions with higher oxygen; optimize gas exchange
concentric vs eccentric hypertrophy
Concentric hypertrophy is a response to pressure overload, resulting in thickened ventricular walls with preserved or reduced chamber size. This type of hypertrophy is often seen in diastolic heart failure (HFpEF) and can lead to diastolic dysfunction.
Eccentric hypertrophy results from volume overload, leading to dilated heart chambers with thinned walls. This type of hypertrophy is typically associated with systolic heart failure (HFrEF), where the heart becomes less efficient at pumping blood.
concentric hypertrophy
thicken ventricular wall; increased afterload
eccentric hypertrophhy
dilate or thin ventricular wall; volume overload
ventricular remodelling in chronic heart failreu
o Myosin use more ATP
o Increase TGF beta
o Myocytes enlarge and less
in chronic heart failure what happens to angiotensin II
- Angiotensin II increases as cardiac output to kidneys decrease
o AT II binds myocytes and causes hypertrophy and CT deposits
o Increase volume and vasoconstriction = edema and afterload
what happens to beta adrenergic receptors in chronic heart failure
downregulated
o Hypertrophy and fibrosis of myocytes
o SNS in short term improves cardiac but long term bad
inflammatory cytokines in chronic heart failure
o JNK and MAPK – remodel and apoptosis
calcium changes in chronic ehart failure
o Release less Ca2+ per AP
o SERCA Ca2+ uptake is limited
o Elevated diastolic Ca2+ and impair Ca2+ spikes in contraction
whicvh pathway for chronic heart failure is good for healthy hypertrophy
o Activate IGF-1 and PI3K
impacts of SNS and RAAS in chronic heart failure
- Activate SNS and RAAS
o Increase HR, BP, contractility
o Retention of Na+ and water
Increase preload and cardiac output - Over time bad… excessive vasoconstriction and volume retention
o Baroreceptors that increase pressure, decrease PNS
o Increase ADH= increase volume
o Excess SNS= decreased renal perfusion = chronically elevated renin and AT II to maintain kidney blood flow
in chronic heart failure which 2 things aren’t released by stretched ventricles to protect against fluid overload
- Protection against fluid overload: ANP and BNP (released by stretched ventricles)
o In heart failure, become resistance to BNP and ANP
o No longer leads to Na+ and water loss
chronic heart failure symtpoms
- Fatigue
- Left side: orthopnea, dyspnea, angina, impaired cognitive function
- Right side: edema, RUQ pain
chronic heart failure signs
- Pitting edema
- Hepatosplenomegaly
- Elevated JVP (Right sided heart problem)
- S3 or S4
- Crackles, wheezing, pleural effusion
class I to class IV chronic heart fialure
class II- good at rest but physcical activityh causes fatigue, palpitations, dysnpenea, angina
classs IV- heart failure and aging at rest and worse with activity
heart failure diagnosis
- BNP
- Echocardiography
- Chest x-ray: cardiomegaly and pulmonary edema
HFrEF and HFpEF %
- HFrEF: reduced ejection fraction; <50 %
- HFpEF- normal (>50%) but left ventricle hypertrophy, atrial enlargement
what is the most common cause of heart failure?
- Chronic IHD (coronary artery disease)
second most common cause of chronic heart filaure? what does it present as HF_EF?
- Second most common cause is chronic hypertension
o Myocardial hypertrophy and fibrosis
o Presents as HFrEF
concentric or eccentric LV hypertrophy in chronic hypertension leading to heart failure
concentric (can process to eccentric)
atherosclerosis pathophysiology
- Fatty streak deposit oxidized LDL activate macrophages calcify, accumulate cholesterol, foam cells, fibrous cap w necrotic tissue, stenosis of lumen
risks for atherosclerosis
smoking, high BP (hypertension), oxidative stress
o Lp(a)
-diabetes and dyslipidemia (LDL and AGES)
Lp(a)
increase endothelial damage via immune cell recruitment and plaque formation
Also inhibits clot breakdowns
which receptor do beta blockers work in for congestive heart failure
beta 1 receptors to block NE and SNS
effect that beta blockers have on heart
(beta 1/NE – block SNS, NE)
o IHD: reduce cardiac oxygen demand
o CHF: reduce and reverse cardiac remodeling
cardiac glycoside (digoxin) is a medication fro CHF and does what
o Inhibit Na+/K+ pump
o Increase cytosolic Ca2+ Increase contractility
Via Na+/Ca2+ exchanger
diuretics for CHF
o Reduce blood volume- increase water and Na+ loss
Loop and thiazide diuretics
Spironolactone
ACE inhibitors
2 types of calcium channel blockers for CHF
o Dihydropyridine = cause vasodilation
o Nondihydropyridine= slow AV conduction (HR) and decrease contractility
nitrates medication for CHF
o NO = vasodilate
o Decrease preload and afterload and vasodilate
HMG CoA reductase inhibitors (statins) do what
o Reduce hepatocytes ability to produce cholesterol upregulate LDL receptor and increase its clearance
Decrease circulating TG, reduce oxidative stress
PCSK9 is a medication to do what in CHF
o Block PCSK9 protease in hepatocytes
o This protease degrades LDL receptor
o More LDL receptors available to clear LDL
ezetimibe medication for CHF
o Reduce absorption of dietary and bilary cholesterol
niacin for CHF
o Inhibit lipolysis in adipose tissue; less FFA release so less VLDL and LDL production
damage to valves from?
- Congenital disorders, wear and tear, inflammation, ishcemia, aortic dissection, idiopathic
stenosis of a valve
narrowed valvve= impair outflow
regurgitation in a vlave
backflow across valve
how does regurgitation effect EDV and preload and outflow
backflow across the valve results in
- Increased EDV and preload and impair outflow
2 types of regurgitation
incompetence
prolapse
incompetence in valve
valve doesn’t close completely
prolapse in valve
backwards valve movement into proximal chamber
most common valve pathology
mitral valve prolapse
mitral valve prolapse goes into which part of the heart
left atrium
-Enlarged valve leaflets and redundant and billow into LA systole
rheumatic heart disease from what
group A strept infection
PAGE 34-35 FOR CHARTS
3 types of cardiomyopathies
- restritcive
- hypertrophic
- dilated
most and lease common form of cardiomyopathy
most common= dilated
least common= restrictive
restrictive cardiomyopathy
The heart muscle becomes stiff and less flexible, making it difficult to fill with blood between heartbeats. This is the least common type of cardiomyopathy, but it can occur at any age.
hypertrophic caardiomyopathy
The heart muscle thickens, making it harder for the heart to work. This condition can start at any age, but it mostly affects the heart’s main pumping chamber.
dilated cardiomyopathy
The heart’s chambers thin and stretch, causing the heart to grow larger. This condition usually starts in the heart’s main pumping chamber, making it difficult for the heart to pump blood to the rest of the body. It can affect people of all ages.
what happens to septum in hypertrophic cardiomyopathy ? how is outflow impacted?
Septum overgrown; outflow obstruction in left ventricle (i.e. entry to aorta blocked)
causes of hypertrophic cardiomyopathy
Autosomal dominant; common
Genetic deficits in sarcomere proteins
Gain of function mutation in sarcomere proteins
clinical features of hypertrophic cardiomyopathy
Asymptomatic
-athletes heart (sudden cardiac death from dysrhythmias)
-with aging; angina, dyspnea, syncope (sudden loss of consciousness from impaired cerebral hypoperfusion)
is hypertrophic cardiomyopathie HFpEF or HFrEF
HFpEF (can develop into HFrEF)
hypertrophic, dilated and restrictive cardiomyopahty are
HFpEF or HFrEF
hyper- HFpEF (can progress to HFrEF)
dilated- HFrEF
restrictive- HFpEF
mortality rate for restrictive cardiomyopthy
High mortality rate bc heart failure
which cardiomyopathy has high mortality
restrictive cardiomyopathy
severity for dilated cardiomyopthy?
Can reverse damage if eliminate initial insult (i.e. alcohol use)
not as good if genetic…
ir restrictiva cardiomyopthy HFpEF or HFrEF
isolated diastolic dysfunction, HFpEF picture – stroke volume is normal in most cases
causes of dilated cardiomyopathy
SO MANY! that’s why its most common
Genetic deficits in sarcomere proteins or infection, inflame, toxic
toxicities (i.e. alcohol, catecholamine, cancer therapy)
-peripartum
-genetics
-inflammatory (infection, sarcoidosis)
is dilated cardiomyopathy HFrEF or HFpEF
HFrEF
symptoms of dilated cardiomyopathy
Asymptomatic –> heart failure symptoms (fatigue, exercise intolerance, dyspnea, dependent edema)
-mitral regurgitation
-palpitations/syncopal episodes from dysrhythmias
microscopy of dilated cardiomyopthy
Microscopy can alternate between hypertrophy and atrophic/fibrotic sections of myocardial cells
what does heart look like in dilated cardiomyopthy
Heart is massive (2-3x size)
-ventricles dilated more than atria
-heart wall appears flabby
-regurgitation of AV valves
restrictive caridomuopthy
Characterized by restricted ventricular filling, reduced diastolic volume in one or both ventricles, and normal or near-normal ventricular systolic function and wall thickness
causes of restrictive cardiomyopathy
Some are autosomal dominant mutations
Most secondary causes from outside the heart:
-amyloidosis (accumulate abnormal proteins in various tissues; i.e kidneys) form beta pleated sheets from liver or antibody fragments proteins deposit extracellularly
-hemochromatosis (accumulate iron in cardiomyocytes)
-sarcoidosis (granuloma disease infiltrate wall of ventricle)
where is Lp(a) made
in the liver
what does Lp(a) look like?
LDL
what do Lp(a) and LDL both contain
apo(b)
what is Lp(a) made of
kringle units
what makes lp(a) pathogenic
- Transports oxidized phospholipids
what does Lp(a) do
- causes coagultation, unstable plaques, activates monocytes, pro inflammatory cytokines (IL-6)
what is an unstable plaque
unstable fibrous cap thats prone to rupture
how to increase stability in a plaques cap
via collagen
o activated platelets release growth factor for collagen deposition
what breaks down a fibrous cap on a plaque
- activated macrophages produce metalloproteinases that degraded collagen
delusion
belief despite evidence against
hallucination
with or without?
formed vs unformed?
sensory perception in absence of stimuli
- with insight (aware) or without insight (thinks is real)
- formed (i.e. voice making command) or unformed (i.e. non specific sound)
DSM criteria for schizophrenia
- need 2+ symptoms, 1 month active symptoms and 6 months of signs
- delusion OR hallucination OR disorganized speech (must be one of these)
- disorganized or catatonic (psychomotor) behaviour
- negative symptoms (decreased function ie.. limited speech and emotion)
which 1/3 symptoms must be in shcizeophrenai
- delusion OR hallucination OR disorganized speech
speech issues in schizophrenia
derailment: loose association
poverty of speech
tangentiality: go off topic
lack of logic
perseveration: repetitive thoughts or speech
neologism: made up word
thought blocking: stop abrupt in middle of speaking
clanging: rhyme or alliteration
echolalia: repeat or mirror words
behavioural issues in schizophrenia
incoherent or erratic behaviour
inappropriate emotional responses
difficulty planning or sequencing
motor immobility
stupor: unresponsive
rigidity: muscle stiffness
strange postures: catalepsy
excessive motor activity
echopraxia: imitate or mirror movements
what system is dyregulated//hyperresponsive in schizophrenia
dopaminergic system
which monoamines in dopaminergic syste
dopamine, NE, serotonin
antipsychotic drugs block what receprot
D2 dopamine receptor
drugs that increase dopamine increase
psychosis
what is the last interneuron to be incorporated into the developing brain and is therefore vulnerable to insults like oxidative stress
GABA
dopaminergic system- which areas of the brain release dopamine
- Neuronal cell bodies that release dopamine are in midbrain
o Ventral tegmental area (VTA) and substantia nigra
which dopamine area of the brain for reward and motivation and projects where
VTA –>nucleus accumbens and ventral striatum (of basal ganglia)
which dopamine area of the brain for motor and projects where
substantia nigra –> striatum (of basal ganglia
which dopamine area of the brain for executive function and projects where
VTA and dorsal substantia nigra –> many cortical areas
which type of firing is at rest in dopamine system
tonic firing
tonic firing
dopamine neuron fire in slow pacemaker fashion at rest
what slows down the tonic firing of dopamine system
o Ventral pallidum release GABA and slows it down
o Hyperfunctioning tonic firing in hippocampus in schizophrenia and reduced GABA
o Stress in early childhood reduces GABA and overactivates amaygdala
phasic firing in dopamine system is caused by?
RAS detects stimulus glutamate release onto dopamine neurons rapid action potentials
what increases phasic firing in the dopamine ssytem
- Stronger phasic firing in response to new or stressful stimulus: activate hippocampus (subiculum) to enhance tonic firing
chronic stress impact on the firing of dopamine system
- Decrease tonic and phasic firing in chronic stress –> activate amygdala
pro infallmatory cytokines involved in psychosis in schizophrenia
TNF alpha, IL6, IL1beta
what do profinlmatory cytokines produce that causes psychosis
TNF alpha, IL6, IL1beta –> kyureneic acid production –> block NMDA receptor –> psychosis
microglial cells and schizophnreia
cogntiive dysfunction
migraine has pain from what input
trigeminovascular input
pathophysiology of migraine
- Pain from trigeminovascular input
- Meningeal vessels trigeminal ganglion syanpses on second order neurons in trigeminocervical complex in brainstem thalamus cortex
what modulates pain in migraine and causes vasoconstrict or dilate in migraines
- Modulate pain by midbrain nuclei (dorsal raphe nucleus, locus coeruleus, nucleus raphe magnus)
which medications act on pain pathway in migraines
o 5-HT1 receptors: bind serotonin in trigeminal nucleus
o CGRP; vasodilate to modulate pain on efferents
neuromuscular theory of migraines
o Primary neural dysfunction= wave of spreading depression (slowly travelling wave of neural excitability) throughout cortex, activates trigeminal complex
pro inflammatory cytokines in migraines
- Pro-inflammatory cytokines release nerve growth factor (NGF) from mast cells increase BDNF from C fibers = pro-pain in dorsal horn
pain pathway in migraines
o Orthodromic (periphery to SC)
o Antidromic (SC to periphery)
c fibers release what in migraines
o C fibers release substance P (mast cell, edema, vasodilate) and CGRP (vasodilate) –> inflammation
migraines and microbiome?
o H pylori
o IBS- visceral hypersensitivity; food intolerances, high serotonin
o Dysbiosis permeability LPS leak pro inflame cytokines
