FUCK!!! Flashcards
the AV valves between atria and ventricles
tricuspid and mitral valves
chronotropy
rate of depolarization; heart rate
ionotropy
aka contractility; Ca2+ binds troponin
preload
ventricular filling ~ end diastolic volume
blood flows from
high to low pressure
how much of ventricular filling is passive
80%
s3 and s4 heart sounds
s3 can be healthy or pathologic
s4 is pathologic; atria force blood into non compliant ventricle
which ventricle has the higher pressure
Left Ventricle
Aorta is 120/80mmHg so its
the blood pressure value
more force; atria or ventricles
ventricles
ACXVY for at the atria
A wave: atrial contraction (atrial systole)
C wave: tricuspid buldge
X-descent: atrial relax (atrial diastole)
V wave: passive filling (ventricular systol)
y-descent: atria empty into ventricles with open AV valves
dicrotic notch
division between 2 waves in aortic valves; when valve closes (elastic recoil)
Stroke volume
volume ejected with each heart beat
SV=
SV= EDV-ESV
cardiac output
volume ejected each systole x heart rate
–> give o2 and nutrients to tissues
–> equal in left and right ventricles
CO=
CO = SV x HR
ejection fraction
proportion of EDV ejected with each heart beat
–>estimated heart function in heart failure
EF=
EF= SV/ EDV
EF= (EDV-ESV)/ EDV
preload of 1 ventricle depends on ____ of other ventricle
cardiac ouput
treppe effect
accumulate Ca2+ in SR as HR increases (not enough time to remove calcium)
skeletal myocyte excitation- contraction coupling
Ach (nicotinic receptor) –> depolarize –> Na+ VGC open –> Ca2+ VGC open –> t tubules get AP deeper –> Ca2+ binds troponin and open the myosin binding site on actin by moving tropomyosin out of the way –> cross bridge formation
where does most of the calcium come from in skeletal muscle contraction
little bit from Ca2+ VGC
but the main action of Ca2+ VGC is to open ryanodine receptor in SR and the SR is where most of the Ca2+ is from
cardiac myocytes differences from skeletal myocytes
-no tetany bc long refractory period
-synctium; intercalated disks (gap junctions and desmosomes) = coordinated heart contraction
-t tubules less important; rely more on L-type Ca2+ channels
-1 nucleus, lots of mitochondria; ATP, oxidative metabolism with fats
automatic cells 4 phases
phase 4: unstable, funny current (Na+ and K+)
phase 0: depolarize by L-type Ca2+ channels (NOT Na+ VGC)
-no phase 1 or phase 2 plateau
-phase 3: repolarize; K+ efflux
where is there a delay in heart conduction
AV node; give atria time to eject blood to ventricles and time for ventricles to fill
bundle of His (AV bundle) purpose
carry AP along septum to ventricle
purkinje fibers carry AP to…
apex then base = ventricular contraction
fibrous skeleton so
atria and ventricles can only communicate through AV node
Bachman’s bundle
right and left atrium contract simultaneously
4 major types of APs in the heart
- myocyte APs (ventricular and atrial)
- purkinje cell APs (almost same as ventricular but unstable 4 like automatic cell)
- automatic cell APs
automatic cells
-SA and AV node
-depolarize without external stimuli
what cell takes over in complete heart block
purkinje cells give AP because cant go from atria to ventricles with AV node and SA
SA node is
pacemaker; HR = 60-100bpm
4 typical phases of myocyte APs
phase 4- resting membrane potential, leaky K+, Nernst = -84mv
phase 0- rapid depolarization, Na+ VGC open; influx
phase 1- initial repolarization, close Na+ VGC, K+ VGC open= efflux
phase 2- plateau- open L-type Ca2+, influx (Ca2+ and K+ balance out)
phase 3- slow repolarization; close Ca2+, open slow K+ VGCs
calcium spark
1 Ca2+ VGC opens and elicits small Ca2+ release from neighbouring ryanodine receptor on SR –> summation = increase in Ca2+ in cytosol (some contribution from ECF)
3 things remove Ca2+ from cytosol
-SERCA
-Na+ Ca2+ exchanger; 3 Na in, 1 Ca out
-sarcolemma calcium ATPase; Ca out
what is SERCA regulated by
phospholambdin phosphorylation
beta 1 receptors (SNS)
beta 1 –> cAMP –> phospholambdan –> phosphorylate troponin –> L-type Ca2+ VGC –> Ca2+ influx –> enhance contractility and quicker Ca2+ reuptake into SR
ECG measures? what is a little box?
electrical activity
-little box is 0.1mV high and 0.04 seconds wide
P wave
atrial depolarization via SA node
PR interval
impulse from SA node through atria and AV node to ventricles (AV node delay for ventricular filling)
AP from SA –> AV node
QRS complex
ventricular depolarization (via bundle of His and Purkinje)
ST segment
ventricles fully depolarized, before they depolarize
T wave
ventricular repolarization
QRS interval
AP from end of AV node to throughout ventricles
QT interval
ventricle depolarize and repolarize
3 layers of blood vessels
tunica intima
tunica media
tunica externa/adventitia
tunica intimia is made of
simple squamous endothelium
tunica media is made of
muscle cells
which layer is thickest in arteries
tunica media
which layer is thickest in veins
tunica externa/adventitia
tunica externa/adventitia components
vasa vosaorum (blood vessels), fibroelastic CT
4 types of arteries
elastic arteries/conducting
muscular arteries/distributing
arterioles
metaarterioles
elastic arterioles/ conducting
i.e. aorta, pulmonary trunk
elastic fibers for high pressure near heart, major pressure reservoirs
muscular arteries/ distributing
i.e. brachial and femoral arteries
smooth muscle, most abundant in body
most common artery in body
muscular arteries/ distributing
arterioles
constrict and dilate, control systemic BP
metaarterioles
regulate flow into capillaries via pre capillary sphincters
3 types of capillaries
continuous capillaries
fenestrate capillaries
sinusoidal capillaires
which are the majority of capillary in the body
continuous capillaries
what is least permeable and most permeable capillary
least- continuous capillary
most- sinusoidal capillary
continuous capillaries
least permeable, majority, intercellular junctions for water soluble substances to pass
exception: BBB, BtestesB –> tight junctions (Claudius and occluding)
caveolae (caves): endocytosis of macromolecules
intracellular cleft; for small (albumin cant go through)
coalesces and make vesicular channels –> pinocytosis and endocytose ECF –> increase in inflammation to transport antibodies and nutrients
3 types of veins
large
medium
small (venules)
large veins
vena cava, portal vein, pulmonary veins
thick tunica advanetitia with dense CT, collagen, elastic fibers, vasa vasorum
medium veins
femoral, renal and brachial veins
valves to prevent back flow to limbs
small veins (venules)
post capillary and collecting venules
collect blood from capillaries
valves formed via
reflection of tunica intima
lumen bigger in vein or artery
vein
2/3 blood in
systemic vein
veins can somewhat constrict via
catecholamines
poiselles law vs Reynolds #
poiselles; laminar flow
Reynolds; turbulent flow (i.e. atherosclerosis, hypotension)
–> likely if increased blood velocity, decreased or irregular diameter and decreased viscosity (faster)
pressure and velocity in arteries, capillaries and veins
arteries- high pressure, fast velocity
capillaries- low pressure, slow velocity
veins- low pressure, moderate velocity
basement membrane of capillaries
type IV collagen
series circulation vs parallel circulation
series- higher resistance
parallel- majority, reduce resistance even though small radius i.e. capillaries
lower resistance in parallel or series circulation
parallel
compliance
amount of pressure need to change volume
high compliance
small amount of pressure= large change in volume
what are more complaint; veins or arteries
veins; blood resevoir
arteries have low compliance to maintain high BP
mean arterial pressure MAP
MAP= DP + 1/3 (SP-DP)
1/3 of cardiac cycle in systole
edema
too much movement across capillary walls
albumin keeps H2O in capillary
glycosaminoglycans absorb H2O and reduce edema
what reduces edema
albumin and glycosaminoglycans
2 ways capillary blood flow is regulated
- autoregulation
2.myogenic regulation
autoregulation of capillaries
capillary bed regulates flow via local tissue factors
h2o, o2, co2, [lactate, K+, adenosine= exercise] all vasodilate
myogenic regulation of capillaries
constant flow despite changes in MAP because if pressure drops then dilate and if pressure increases then constrict
Increased Blood Pressure (Stretch):
When blood pressure increases, it causes the walls of arterioles (the small arteries leading to capillaries) to stretch.
The smooth muscle cells in the walls of these arterioles respond to this stretch by contracting (a phenomenon known as the myogenic response). This constriction reduces the diameter of the arteriole, thereby decreasing the flow of blood into the capillaries.
This is a protective mechanism to prevent overdistention of the capillaries and potential damage to delicate capillary walls.
Decreased Blood Pressure (Reduced Stretch):
When blood pressure decreases, the walls of the arterioles are less stretched. In response, the smooth muscle cells in the arteriole walls relax, causing the arterioles to dilate.
This dilation helps maintain blood flow through the capillary network by preventing the pressure in the capillaries from becoming too low, ensuring adequate perfusion to tissues.
NO effect and pathway
vasodilate via shear stress
NO –> guanylyl cyclase –> cGMP –> PKG –> dephosphorylate myosin and relax
vasodialtors of capillaries
histamine
bradykinin
prostaglandin E2 and I2
NE, E via beta 2 receptors
vasoconstriction of capillaries
NE, E alpha 1 receptors
serotonin
ADH
AT II
thromboxane A2 and prostaglandin F
NE and E 2 receptors
beta 2= vasodilate
alpha 1= vasoconstrict
cerebral blood flow is regulated by
ph and adenosine
cushing reflex in the cerebrum
increased intracranial pressure will decrease perfusion
pulmonary capillaries are unique- low oxygen causes
vasoconstriction; for efficient gas exhange
skin receptors
SNS alpha 1, body temperature
coronary capillaries regulated by
oxygen and adenosine
causes of edema
increased hydrostatic pressure (from increased arterial pressure i.e. malignant hypertension, decrease venous drainage)
decreased oncotic pressure (albumin, i.e. nephrotic syndrome and hepatic filature)
increased vascular permeability
blocked lymph (malignancies, surgeries)
increase Na+ and H20 retention via ADH and aldosterone
damaged endothelium
transudate vs exudate in edema
transudate- low protein and cell content from pressure imbalances
exudate- high protein and cell content from inflammation and vessel damage
arterial and venous; is hydrostatic or oncotic pressure greater
arterial: H > O
venous: O > H
anasarca and angioedema
anasarca- generalized edema in body
angioedema- in deep layers of face
what is most severe edema
pulmonary and brain
hyperemia and congestion are both from
local increase in blood volume
hyperemia
arteriol dilation increases blood flow; erythema i.e. blood flow when warmed up after being in cold outside
causes local increase in blood flow
congestion
passive hyperemia; decreased blood outflow from a tissue; cyanosis because of red blood cell stasis
can be systemic or local
RBC breakdown and get hemosiderin= hemoglobin degrade in macrophage
local increase in blood volume
long standing congestion
hypoxia, apoptosis, fibrosis, hemosderin laden macrophages
pulmonary vs hepatic congestion causes
pulmonary- left heart failure
hepatic- right heart failure
nutmeg liver from
hepatic congestion
infarct
tissue death from ischemia
white vs red infarct
white= organs with single blood supply (kidney or spleen)
red= dual blood supply (lung, intestine, testis)
arterial or venous occlusion for white and red infarcts
white infarct= arterial occlusion (cause white appearance; abrupt and severe damage since cut off only blood supply)
red infarct= venous occlusion (blood pools and causes red/blue colour, slow process because dual blood supply)
shock
inadequate blood flow to organs
types of shock
cardiogenic- MI, myocarditis, cardiac tamponande, pulmonary embolus
hypovolemic- hemorrhage, diarrhea, dehydration
septic- infection
distributive (too much dilation; not enough pressure= anaphylactic and neurogenic)
anaphylactic; type 1 hypersensitivity
neurogenic- brain damage or spinal cord injury
in shock the myocardial pump fails causing
decreased blood volume, vasodilation, increased vascular permeability
(inadequate blood flow to organs)
stage 1 (compensated) vs stage 2 (decompensated) shock
compensated= tachycardia with normal BP
decompensated= tachycardia and hypotension
symptoms in ischemic heart disease
asymptomatic or chest pain, dyspnea, fatigue, palpitations
what is the mechanism in ischemic heart disease
blood flow to the myocardium is inadequate
main cause of ischemic heart disease (90%)
atherosclerosis
what makes ischemic heart disease worse
things that increase heart metabolic demands; HR, Ca2+ contractility, wall tension
stable angina
IHD symptoms during activity, 50-75% of lumen decreases, Bette with rest and worse with exercise, fixed with nitrgoclycerine
unstable angina
IHD symptoms at rest, 80-90% of lumen decreased, not better with rest or nitroglycerine
thrombus breaks down
acute coronary syndrome
unstable angina + MI
acute IHD
-stable or unstable angina
-MI
-sudden cardiac death (dysrhythmia)
chronic IHD can lead to
heart failure
IHD diagnosis
ECG
cardiac enzymes; CK-MB, troponin T and I
angiogram
echocardiogram
IHD treatment
ASA antiplatelet agent (decrease thrombus)
antihypertensive
beta blocker
nitroglycerine (decrease preload and afterload; vasodilate)
Ca2+ channel blocker (decrease contractility)
IHD complications
MI
chronic IHD can lead to
congestive heart failure
pritizmetal angina (vasospastic or variant angina) cause
coronary artery spasm
pritizmetal angina (vasospastic or variant angina) symptoms
at rest in the morning
respond to Ca2+ blockers and nitroglycerine
adaptations in chronic ischemia of the heart
hypertrophy and collateral circualtion
MI symptoms
pain could be in scapula, heart burn, dyspnea, fatigue- not typical presentation always
cells in MI
cells and mitochondria swell and lose glycogen
what opens in MI
MPTP (mitoahcondria pore) opens from an increase in Ca2+ –> please H+, no ATP, more Ca2+ in cytosol
time frame in MI
30-60 min: irreversible, coagulative necrosis (Ca2+ accumulate, ROS, decrease ATP, open MPTP)
2-3 days: neutrophils in necrotic tissue, edema, hemorrhage
5-7 days: scar tissue, replace neutrophils with macrophages, myofibroblasts deposit collagen
reperfusion injury after MI
damage cardiomyocytes if restore blood to quick after ischemia
contraction band necrosis
transmural infarcts/ STEMI
blocked coronary artery
use clot busting drugs
non-transmural infarct/ NSTEMI
partially blocked coronary artery; transient occlusion
what to do in STEMI and NSTEMI
revascularize- angiopalsty or stent
MI most common vessel effected
anterior descending branch of left coronary artery (50%)
diagnose heart failure
ECG
BNP
HFrEF, decreased ejection fraction <40%
HFpEF, EF >50%, left ventricle hypertrophy
2 most common cause of heart failure
- chronic IHD (HFrEF)
- hypertension (concentric LV hypertrophy)
mechanisms of heart failure
-increased afterload –> hypertrophic ventricles
-chronic ischemia from low oxygen
-decreased compliance (cant relax)
-cardiomyopathy- damaged myocardium impairs compliance and contractility
2 types of heart failure
systolic dysfunction/ HFrEF
diastolic dysfunction/ HFpEF
HFrEF (heart failure with reduced ejection fraction)/ systolic dysfunction
impaired contraction, rely on increased preload
HFpEF (heart failure with preserved ejection fraction)/ diastolic dysfunction
impaired EDV (compliance), elevated diastolic pressure, but contraction OK
forward flow vs backward flow problem in heart failure
forward= impaired cardiac output
backward= congestion
what is first to fail in heart failure
left ventricle because greatest afterload
what is it called when the right ventricle fails first in heart failure
cor pulmonale (COPD, OSA, pulmonary hypertension)
pulmonary microcircualtion
constrict if low O2
concentric vs eccentric hypertrophy usually happens 1st
concentric
concentric hypertrophy
ventricular wall thickens, no increase in chamber size
eccentric hypertrophy
myocytes increase length and the chamber enlarges
ventricular remodelling in heart failure via
increased TGF b
2 main pathways in CHF
RAAS and SNS
angiotensin II in CHF
AT II increases when cardiac output to kidneys decrease
causes vasoconstriction, edema, increased BP
SNS in CHF
beta adrenergic
endothelin 1 in CHF
vasoconstriction
JNK and MAPK in CHF
inflammation and apoptosis
Ca2+ in CHF
less released for contraction, inhibited uptake (increased in diastole and decreased in systole)
IGF1 and PI3K in CHF
hypertrophy
ANP and BNP in CHF
become resistant to them and no longer lead to Na+ and H2O loss
signs in CHF
pitting edema
increased JVP
s3,s4
crackle, wheeze
hepatosplenomegaly
3 causes/ mechanisms in atherosclerosis
-diabetes (AGEs)
-dislipidemia (LDL)
-Lp(a)- increased endothelial damage via immune cells and plaque formation also inhibits clot breakdown
lp(a) mechanism
increased endothelial damage via immune cells and plaque formation also inhibits clot breakdown
medications for CHF and angina
-beta blocker (SNS- NE)
-cardiac glycosides (digoxin): inhibit Na/K+ pump which decreases Na+ Ca2+ exchangers = increased Ca2+ in systole
-diuretics: increase water and sodium loss
angina medications
-Ca2+ channel blockers
–> dihydropyridine: vasodilate
–> nondihydropyrine: slow AV conduction (HR) and contractility
-nitrates (NO): vasodilate
medications for dyslipidemia
-HMG CoA reductase inhibitors (statins); decrease hepatocyte cholesterol production
-PCSK9 inhibitors: block the degradation of LDL receptors
-ezetimibe: decrease cholesterol absorption
-niacin B3: inhibit lipolysis
valve pathologies
stenosis (narrow)
regurgitation (backflow)
–> incompetence: valve doesnt close
–> prolapse: valve into proximal chamber
aortic stenosis/sclerosis
very common, >65yrs
from congenital bicuspid aortic valves
calcific aortic stenosis: myofibroblast become osteoblast like –> valve calcifies which increases afterload and causes concentric hypertrophy
aortic regurgitation
related to aortic stenosis, ankylosing spondylitis, rheumatic heart disease, infective endocarditis
can cause shock
most common valve pathology
mitral valve prolapse
mitral valve prolpase
go back into left atrium
enlarged annulus and chord tendinae, myxomatous CT, proteoglycans, redundant leaflets
cadherin deficit, CT problem
mitral valve regurgitation
from chronic mitral valve prolapse
papillary or chordae tendinae rupture
rheumatic fever cause
autoimmune from group A strep (strep thoat or strep skin)
M protein
rheumatic heart disease (group A strep)
affect all cardiac layers (Endo, myo, peri)
2-3 weeks after infection
inflammation –> valvular stenosis
= mitral (chordae tendinae)
=aortic stenosis (bicuspid)
most common
most common valve pathologies from rheumatic heart disease
= mitral (chordae tendinae)
=aortic stenosis (bicuspid)
3 types of cardiomyopathies
- dilated cardiomyopathy
- hypertrophic cardiomyopathy
- restrictive cardiomyopathy
most common cardiomyopathy
dilated
HF_EF in the cardiomyopathies
dilated= HFrEF
hypertrophic= HFpEF (can delve into HFrEF)
restrictive= HFpEF
dilated cardiomyopathy causes
genetic sarcomere, infection, inflammation, toxic (alcohol, catecholamines, sarcoidosis, x linked)
what happens in dilated cardiomyopathy
heart muscle enlarges and weakens; LV enlarges most- mitral regurgitation
what valve issue in dilated cardiomyopathy
mitral regurgitation (LV enlarged most)
symptoms of dilated cardiomyopathy
hypertrophy and fibrosis of cells
asymptomatic –> heart failure (fatigue, dyspnea), palpitate, syncope
hypertrophic cardiomyopathy cause
-genetic deficit in sarcomere (gain of function)
mechanism in hypertrophic cardiomyopathy
overgrown septum; obstruct outflow of LV to aorta
symptoms in hypertrophic cardiomyopathy
asymptomatic, syncope (lose consciousness bc cerebral hypoperfusion)
least common cardiomyopathy
restrictive cardiomyopathy
causes of restrictive cardiomyopathy
deposits of ECM, amyloidosis (accumulate protein), hemochromatosis (iron), sarcoidosis (granuloma infiltrate), autosomal dominant
mechanism in restrictive cardiomyopathy
restricted ventricular filling, decreased diastolic volume, normal systole
where is Lp(a) made and in response to
made in liver bc increased IL6, cytokines (inflammation)
what is a key feature in lp(a)
kringel units
what does lp(a) look like
LDL - both contain apo(b)
what is the pathogenic factor of lp(a)
transports oxidized phospholipids
unstable plaques
what degrades collagen and makes the cap weaker
-rupture and release pro-coagulant molecules
weaker cap: macrophages make metalloproteinases to degrade collagen
more stable cap
increase collagen via growth factors
hallucination
sensory perception
formed (voice commands), unformed (non specific sounds)
with insight (aware) or without insight (think is real)
schizophrenia DSM5
> 2 symptoms for 6 months or 1 month active symptoms (1-4), need 1 of the 1st 3
- delusion
- hallucination
- disorganized speech
- disorganized or catatonic behaviour
- negative symptoms
cause of schizophrenia
dysregulated dopaminergic system- hyperactive tonic firing and reduced GABA in hippocampus
2 things that back up schizophrenia and dopamine hypothesis
- antipsychotics block D2 receptors
- drugs that increase dopamine (l-dopa, amphetamines) increase psychosis
GABA interneurons
inhibit dopamine in schizo- develop last and are damaged by ROS
monoamines in the dopaminergic system
NE, serotonin, dopamine
what part of the brain releases dopamine
midbrain- VTA and substantial nigra
reward/motivation for dopamine
VTA –> nucleus accumbens and ventral striatum
motor for dopamine
substantia nigra –> striatum
executive function in dopamine
VTA and substantia nigra –> many cortical areas
tonic firing for dopamine
slow, at rest, pacemaker via ventral palladium
slower by GABA
phasic firing in dopamine system
RAS: glutamate release onto dopamine –> AP
in response to stimuli
phasic firing changes
stronger via hippocampus if new stimuli
weaker phasic and tonic firing via amygdala in chronic stress
schziophrenia and inflammation
-kyurenic acid blocks NMDA receptor= psychosis
activate microglial cells - prune synapses
what causes pain in migraine
trdigemiocervical complex (TCC) –> thalamus –> cortex
things that cause pain in migraine
serotonin and CGRP (vasodilate)
medication for migraine
5HT-1 receptors for serotonin are blocked by “-triptans”
block CGRP (vasodilate)
cause of migraine
spreading depression wave (excitability) through cortex and activate TCC
central sensitization in migraine
central sensitization: cytokines –> release nerve growth factor from mast cells –> BDNF in C fibers –> pro pain
c fibers release CGRP and substance P
c fibers release (in migraines)
c fibers release CGRP (vasodilate) and substance P (edema, vasodilate, mast cell degranulation)
stomach microbiome and migraines
-h pylori triggers CGRP release
IBS increase serotonin
gut permeability –> LPS –> infalmmatory cytokines
POTS (Postural orthostatic tachycardia syndrome)
lying to standing; HR increases > 30bpm with no hypotension or drop in blood pressure
or HR >120bpm
if from lying to standing and HR increases and BP drops what is it
orthostatic hypotension
symptoms of POTS
light headed, blurry vision, weak, nausea, palpitations
who does POTS effect more
women > men
test for POTS
tilt table test
3 types of POTS
neuropathic POTS
hypovolemic POTS
hyperadrenergic POTS
neuropathic POTS
lower limb blood pool because of less NE in the limbs
hypovolemic POTS
decrease blood volume
-elevated renin and AT II
-inadequate aldosterone
-deconditioning
hyperadrenergic POTS
increase NE
beta 1 and 2 autoantibodies
4 heart sounds in order from right to left top to bottom
APTM
location of SA, AV and purkinje
SA node: superior right atrium- sends signal to both atria
AV node: inferior RA- connect atria and ventricles
AV bundle of HIS sends signal to ventricles
Purkinje in ventricles
