CV Week 2 Flashcards
_________ is located in the hollow organs of the body and all vasculature except for capillaries and endothelial cells
Smooth muscle
Describe structures that have smooth muscle
trachea and airways, vasculature, bladder, female reproductive organs, epididymis and vas deferences, musculature through GI tract, lymphatic vasculature
True or false - Because smooth muscle is responsible in a diverse group of organs, it requires a diverse range of regulatory mechanisms to perform specific functions
TRUE
In __________, smooth muscle cells all behave independently. Few gap junctions are found in these types of cells because there is no great need to electrically couple.
Multi-unit
In __________, smooth muscles behave as one unit which is accomplished by having many gap junctions interconnecting cells.
Single unit
Describe body structures that contain
a) multiunit smooth muscle cells
b) single unit smooth muscle cells
a) airways, vasculature, neural regulation
b) GI tract
_________ smooth muscle tends to be multiunit, whereas _________ smooth muscle tends to be single-unit
Tonically active, rhythmically active
Describe how ADH regulates smooth muscle
ADH is released by posterior pituitary and causes vasoconstriction of smooth muscle (and increased water reabsorption of the kidney)
_________ cause contraction, proliferation and remodeling of blood vessels
Inflammatory mediators
Nitric oxide is an example of ______________. It is produced in the immediate environment of the muscle and causes vasodilation of the blood vessels.
Humoral or paracrine signaling
Describe key differences between smooth muscle and skeletal muscle
Myofilaments in skeletal muscle are more highly ordered and produce bands whereas actin and myosin filaments are arranged differently. Smooth muscle contains dense bodies. Smooth muscles also contract more slowly than skeletal muscle.
Why do smooth muscle cells contract more slowly than skeletal muscle?
Cross bridge attachment.detachment is much slower thus rate of contraction is much slower.
True/False - although smooth muscle cells contract more slowly than skeletal muscle, smooth muscle cells can achieve equivalent (or greater) peak contractions
true
How does slower cross-bridge cycling in smooth muscle affect energy efficiency?
Since cycling of cross-bridges is slower, energy expenditure decreases. This energy efficiency is particularly important to generate sustained contractions over minutes or hours (ie tone)
Describe the different types of myogenic activity (intrinsic to the musculature)
phasic with tone (anal sphincter), phasic (colon), tonic (some blood vessels)
Describe the steps in activating cross-bridge cycling in smooth muscle.
1) Myosin binds to actin filament and an inorganic phosphate is released
2) Power stroke where actin gets pulled towards middle of sarcomere
3) Rigor (myosin in low energy form). ADP is released and new ATP binds to myosin head.
4) Myosin unbinds from actin. ATP is hydrolyzed.
5) Cocking of myosin head (myosin in high energy form) and ready to bind again.
Describe MLCK’s role in cross-bridge cycling
MLCK phosphorylates MLC20 (myosin) and facilitates its binding to actin. This facilitates cross-bridge cycling.
Describe MLCP’s role in cross-bridge cycling
MLCP dephosphorylates MLC20 and reduces cross-bridge cycling –> muscle relaxation
What is MLCP activity regulated by?
pathways that in effect regulate Ca++ sensitivity of contractile apparatus
What determines the force and duration of contraction?
The balance between myosin phosphorylation and dephosphorylation; therefore, the balance btwn activity of MLCK and MLCP
How does Ca++ vary in when there are a) high MLCK levels; b) high MLCP levels
a) high MLCK - high Ca++; b) high MLCP - low Ca++
_________ (2) are examples of excitatory agonists that cause Ca++ sensitization and thus greater force by inhibiting MLCP
Rho Kinase and PKC
_________ (2) are examples of inhibitory agonists that reduce Ca++ sensitization and thus relax muscle, reducing the force by aggravating MLCP activity
cAMP and cAMP dependent mechanisms
What are three pharmacological agents that are excitatory agonists in regulation of contraction via pharmacochemical coupling?
Ach, norepinhephrine, substance P
What are two pharmacological agents that are inhibitory agonists in regulation of contraction via pharmacochemical coupling?
adenosine, vasoactive inhibitory peptide
How do ROCK and PKC inhibit MLCP activity and thus stimulate contraction?
ROCK phosphorylates MYPT1 subunit of MLCP and PKC via Ca++ and PLC-b mechanism phosphorylates CPI-17,(inhibitory proteins)
Smooth muscle cells contains transport proteins and organelle membranes that set and regulate membrane potential, generate excitable events and ___________________
Ca++ entry into and removal from the cytoplasm
Like other excitable cells, the PM has some level of permeability of each ion species present. The dominant membrane permeability in smooth muscle is due to ______________
K+ channels
RMP is smooth muscle is usually _________ mV
-40 to -80
_________ couple smooth muscle cells into an electrical syncytium and provide low electrical resistance pathways between cells
Gap junctions
Describe the structure of a gap junction.
Gap junction is contains numerous CONNEXONS which are channels assembled by six connexin proteins each that form the pore.
Glucose, glutamine, ADP, adenosine, and cAMP all have same ________ through connexins
permeability
What happens to connexons when they are attached to a damaged cell?
They close, can be regulated somewhat by Ca++ and pH
Name 4 types of K+ channels found in smooth muscle cells
voltage-dependent K+ channels (Kv), Ca++ activated K+ channels (BK), 1 transmembrane pore formign loop (Kit, Katp), and 2 transmembrane forming loops (K2p)
Ca++ entry (excitation) tends to be controlled by __________.
K+ channels, due to their importance in regulating membrane potential
________ are voltage-independent channels that are important for resting or basal K+ conductance. They contribute to the resting potential of the smooth muscle cells.
2 pore K+ channels (K2p)
High expression of _________ can reduce the tendency for smooth muscle cells to generate action potentials, making the muscle less excitable
Voltage-activated K+ channels
High abundance of ____________ can lead to rhythmic patterns of activity. These channels are also important for large amplitude hyperpolarizations produced by some inhibitory neurotransmitter as well as some other agonists.
Ca++ activated K+ channels (ekg BK)
____________ are active in negative voltage range and therefore also contribute to a more hyperpolarized cell. They also mediate responses to some inhibitory agonists.
Inward rectifiers (Kir)
Ca++ entry is controlled by _______ because these channels set or regulate membrane potential that determines Ca++ entry via __________
K+ channels, voltage dependent Ca++ channels
Depolarization induced activation of ____________ lead to Ca++ entry and contraction of smooth muscle
L-type Ca++ channels
________ is a Ca++ channel blocker. When added, the muscle relaxes because the __________ have been shut down.
Nifedipine, L-type Ca++ channels
Describe the two ways which Ca++ stimulates cell to depolarize
Ca++ activates Cl- to leave the cell –> depolarization and Ca++ activates non-selective cation channels –> depolarization
Describe how Ca++ causes hyperpolarization of the cell
Activates BK to transport Ca++ out
Describe Ca++’s role in CICR
Ca++ enters cell and stimulates Ca++ induced Ca++ release in sarcoplasmic reticulum
Describe how depolarization leads to contraction via Ca++ channels
depolarization causes an increase in Cav channels opening which increases Ca++ entry
Describe how hyperpolarization leads to decreased contraction via Ca++ channels
Decrease in open Cav channels which leads to decreased Ca++ entry and therefore decreased contraction
There are three major mechanisms that reduce Ca++ and that relaxation of smooth muscle depends on. What are they?
ATP-driven SR Ca++ pump, AT driven PM Ca++ pump, and Na/Ca exchange (NCX, uses Na+ gradient).
The more minor mechanisms are Ca++ binding molecules in cytoplasm and active Ca++ transport in mitochondria.
_______ is a short-acting gas and free radical whose unpaired electrons cause this chemical to be highly chemically reactive
Nitric Oxide
The biological actions of nitric oxide are rapidly terminated due to what? This makes this compound short-acting. It must be synthesized on demand.
Spontaneous oxidation to NO2 and NO3 resulting in a bio half life of around 3-5 seconds.
Nitric oxide is highly ______ so its post-junctional effector proteins are typically within the cell.
lipophilic
True or false: NO can be synthesized by variety of different cell types
True
The highest levels of nitric oxide in the body are found in the _______
neurons
Describe how nitric oxide inhibits smooth muscle contraction.
Vasodilator binds receptor on endothelial cell which activates NOs. NO is produced from Arginine. NO rapidly diffuses across membranes to a smooth muscle cell. It binds guanylyl cyclase which increases cGMP concentration and leads to relaxation of the smooth muscle cell.
In the NO pathway, cGMP activates _____________ which then goes on to phosphorylate several proteins important in promoting vasodilation
cGMP dependent protein kinase (PKG)
How do proteins phosphorylated by PKG promote vasodilation? (3 ways)
Proteins inhibit Ca++ release from IP3 receptors; proteins inhibit activation of L-type Ca++ channels; proteins increase Ca++ uptake by SR. These three mechanisms all lead to more highly activated MLCP (Ca++ desensitization)
What are the lateral leads?
I, V5, V6, AVL
What are the inferior leads?
Lead II, Lead III, avF
What are the anterior or septal leads?
V1-V4
How would you determine that rhythm is in normal sinus?
Upright P wave in inferior leads (lead II, lead III, aVF) [biphasic wave in lead VI - in textbooks]
How would you determine if there is a left axis deviation?
R wave in lead I is pointing upward (+) and R wave in lead II is pointing downward (-) (left each other)
How would you determine if there is right axis deviation?
R wave in lead I is pointing downward (-) and R wave in lead II is pointing upward (+) (right at each other)
How long is a normal PR interval?
less than 200 msec or 1 big box
How long is a normal QRS?
less than 120 msec or 3 little boxes
How long is a normal QTc?
Corrected for heart rate, should be 1/2 of R-R interval, <450 msec or 2.5 big boxes
If there is no correlation between the P wave and QRS and PR interval varies BUT P-P intervals and R-R intervals are consistent, what condition does this indicate?
3rd degree heart block
If the PR interval gets progressively longer until a QRS is dropped, what condition does this indicate?
2nd degree heart block, mobitz type I
If the PR interval is consistently longer than 200 msec (one big box), what condition does this indicate?
1st degree heart block
If the PR interval is consistent but a QRS is dropped randomly, what condition does this indicate?
2nd degree heart block, mobitz type II
The ____ is ALWAYS the first downward deflection in the QRS complex. If there is no downward deflection, then it doesn’t exist
Q wave
Why is a prolonged QTc medically significant?
If ventricles attempt to depolarize or contract on top of a Q wave, this leads to serious dysrhythmias such as V-fib and V-tach
What happens in right atrial enlargement?
right atrial depolarization lasts longer than normal and its waveform extends to end of left atrial depolarization (uneven double hump with taller 1st hump). P wave is taller than normal although width remains unchanged.
What happens in left atrial enlargement?
left atrial depolarization lasts longer. Amplitude is unchanged. Height remains same but duration is longer than 120 msec (3 little boxes). NOTCHED WAVE (“p mitrale”) near peak in lead II
What does an inverted T wave indicate?
ischemia
What does a spiked T wave indicate?
hyperkalemia
_______ are wide, random QRS complexes that usually come in early and can be unifocal or multifocal
Premature ventricular complexes
In _______ every other beat is a PVC whereas in _______ every 3rd beat is a PVC
bigeminy, trigeminy
What varies in a sinus arrhythmia?
R-R intervals
In a ____________ the heart beat happens sooner than expected. P waves are present and QRS complex is no different than baseline.
premature atrial complexes
In _________ there is an irregularly irregular rhythm and ___________ vary without any pattern. There is also an absence of _______ . Atrial HR can run 400-500 bpm.
atrial fibrillation, R-R intervals, P waves
In a _________, P wave is often inverted (esp in lead II) but may be under or after QRS and the heart rate is slow.
junctional rhythm
What differentiates between high junctional rhythm (stable) and low junctional rhythm (unstable)
Narrow QRS suggests stable (high) whereas wide QRS suggests unstable (low)
In __________ there is a narrow QRS (less than 120 ms or 3 small boxes) and heart rate of over 100 bpm. If there is a wide QRS, what is this called?
supraventricular tachycardia; SVT with aberrancy (typical in younger patients)
_________ is a wide complex tachycardia that is typically in older patients with previous myocardial infarction
ventricular tachycardia
In __________, there are no QRS complexes. This represents a chaotic and mechanical cardiac arrest.
ventricular fibrillation
A ___________ is can be seen in leads I, II, AVL, V1-V6 and represents a previous MI. In which leads does this deflection not represent pathology?
pathological Q wave, not pathology in leads III and AVR.
______________ is a reentry tachyarrhythmia via accessory pathway.
Wolf-Parkinson White
What accessory pathway is usually seen in WPW?
“Bundle of Kent” located between atria and ventricle on side. This electrical signal goes through without delay in AV node and meets the normal signal in ventricular purkinje.
What is diagnostic for WPW?
PR less than 125 ms (3 small boxes) and at least one delta wave.
How does WPW cause tachyarrhythmia (2 ways)
Narrow complex - the abnormal signal returns and depolarizes AV node, causing it to fire before the SA node.
Wide complex - abnormal signal hits AV node during its refractory period. Will pass through all the way around and come back to AV node in retrograde fashion.
What are common symptoms of WPW?
unexplained syncope and palpitations infrequently. Normal risk not high except if there’s abnormal pathways.
Drugs such as digoxin, Beta-blockers, verapanil, and adenosine will make WPW worse. Why?
Work mainly on AV node not on accessory pathway
What drug and surgical treatments are used for WPW?
Procanamide and Amiodarone. Surgical catheter ablation to damage accessory pathway.
What are the most common congenital defects?
Heart followed by genital/urinary tract
Describe the pathway of cardiac progenitor cells to the mesoderm
Cardiac progenitor cells form in epiblast then migrate in cranial –> caudal order through the primitive streak to the SPHLANCNIC LATERAL PLATE MESODERM
Where do prospective myoblasts and hemangioblats reside?
in the SPHLANCNIC MESODERM in front of the neural plate and on each side of th emebryo
In formation of the heart tube, angiogenic cell clusters initially coalesce to form ______________
right and left endocardial tubes [ endothelial heart tubes ]
After the embryo folds ________ and __________, the endocardial tubes fuse via ________ to form the heart tube
cardiocaudally, laterally, programmed cell death
Describe the four layers of the primitive heart from inside to outside
endocardium, cardiac jelly, myocardium, epicardium (outside covering of the tube)
The cardiac jelly is a thick, acellular material made by ____________
myocardium
In the epicardium, _______ migrates from the septum transversum to form the ____________
mesothelium, coronary arteries
On day 18, the endocardial tubes and dorsal aortae are formed between what two layers?
endoderm and sphlancnic mesoderm
On day 22, the embryo is in the __________ and fusion occurs only the ______ region of the horseshoe shaped heart tube
8 somite stage, caudal
What structures rise from the crescent portion of the horseshoe shaped heart tube?
outflow tract and most of ventricular region
In 22-day embryo, _____________ drain the yolk sac
vitelline veins
In 22-day embryo, __________ carry O2 from the placenta
umbilical veins
In 22-day embryo, _______________ drain body wall and head
common cardinal vein
True or false: The inflow and outflow tracts are connected to the heart tube before any cardiac folding takes place
True
Around day 23, the _______ begins to form from a series of expansions, constrictions and fold
cardiac loop
What are the four initial dilations of the heart tube?
sinus venosus, primitive atrium, primitive ventricle, bulbus cordis
What two features of the heart does the cardiac loop create?
1) normal position of heart chambers; 2) changes a single circuit system into an asymmetrical circuit system with pulmonary and systemic circulations
At day 24, remodeling of the _______ begins with a shift to the right of venous return
sinus venosus
What does the right vitelline vein give rise to?
inferior vena cava
What does the right anterior cardinal vein give rise to?
superior vena cava
What does the left sinus horn give rise to?
coronary sinus and oblique vein of the left atrium
The right sinus horn blends into the right posterior wall of the right atrium to become the smooth area _____________
sinus venarum
What three vessels open into sinus venarum?
THINK RIGHT ATRIUM. Inferior vena cava, superior vena cava, coronary sinus
The sinus venarum contains the ___________ which act as conducting fiber tract from SA node to AV node
crista terminalis
_________ are found in the cardiac jelly where they are described as “swellings”
endocardial cushions
What germ tissue are endocardial cushions derived from?
sphlancnic mesoderm
The sphlancnic mesoderm (endocardial cushions) and __________ in the conotruncal area play a role in formation of the _____________
neural crest cells, septa and valves
Endocardial cushions are important because they play a role in __________
cardiac defects
The primitive atrium is partitioned between the right and left _________
endocardial cushions
During partitioning of the primitive atrium, a thin membranous septum called the __________ because the right and left endocardial cushions
septum primum
After the formation of the septum primum, programmed cell death forms the ________
ostium secundium
What is the role of the ostium secundium?
Maintains the right to left shunt bypassing the pulmonary circulation
What thick muscular septum forms to the right of the septum primum?
Septum secundum
The ________ forms in the septum secundum which maintains the right to left shunt
Foramen ovale
When does the foramen ovale close?
immediately after birth
At birth, closure of the foramen ovale is functiona. Describe what this means in terms of atrial pressure.
At birth, there is a decrease in right atrial P from occlusion of placental circulation and increase in left atrial pressure due to increased pulmonary venous return (USING LUNGS)
When does the anatomical closure of the foramen ovale occur? What two structures fuse?
Occurs at 3 months, septum primum and septum secundum fuse
Incomplete anatomical fusion of septum primum and septum secundum causes ____________. This is present in 25% of the population and clinically usually of no importance.
probe patency of foramen ovale
Defects in the ________ cause the most clinically significant atrial septal defects and are prevalent in females to males in a _____ ratio
ostium secundum, 2:1
The cor triloculare biventriculare is also known as the _______
common atrium
What four heart defects do endocardial cushions play a role in?
atrial septal defect, ventricular septal defect, transposition of the great vessels, tetralogy of fallot
Conotruncial cushions, which also contain neural crest cells, play a role in both heart and _________ defects
craniofacial
During partitioning of the atrioventricular canal, what do the four endocardial cushions form(3)
septum , bicuspid valve, tricuspid valve
During partitioning of the atrioventricular canal, what can go wrong (2)
persistent common atrioventricular canal and abnormal division of the canal
The truncoconal septa form from _________ that migrate from the hindbrain through pharyngeal arches ___, 4, and 6 and then invade the truncus arteriosus to form the septa.
neural crest cells, 3
During the fifth week, _____ ridges/swellings appear and go on to form the ________________ which divides the truncus into the aortic and pulmonary channels
truncal, aorticopulmonary septum
After formation of the truncal swellings, _____ swellings also form which give rise to the _________________
conal, outflow tracts of right and left ventricles
_________ contribute to both swellings to form connective tissue and smooth muscle of aorticopulmonary system
neural crest cells
During partitioning of the truncus arteriosus and the bulbus cordis, _______ lines up the correct outflow tract with the correct ventricle
spiraling
During partitioning of the truncus arteriosus and bulbus cordis, If neural crest cells were to be experimentally removed or blocked during their migration this would lead to ___________
persistent truncus arteriosus
If there is no aorticopulmonary septum formed, then there will be ________
persistent truncus arteriosus
If the aorticopulmonary septum does not spiral there will be ____________
transposition of the great vessels
If the aorticopulmonary septum is misaligned there will be ___________
tetralogy of fallot
Persistent truncus arteriosus is normally accompanied by __________
ventricular septal defect
In persistent truncus arteriosus, which great vessel gets more blood flow and why?
The pulmonary artery section receives more blood flow than the aorta section due to decreased pressure in the lungs compared to systemic circulation.
Describe the basic pathology of persistent truncus arteriosus.
In persistent truncus arteriosus, the great vessels do not separate and there is a VSD. Deoxygenated and oxygenated blood mix and go into body and lungs.
In persistent truncus arteriosus, since the pulmonary artery section receives more blood than aorta, what happens that leads to pulmonary HTN?
Too much blood in the lungs leads to fluid build up which makes it difficult to breathe. Blood vessels to the lungs become damaged. This makes it harder to pump blood into the lungs over time due to pulmonary HTN that develops.
Due to pulmonary HTN, more blood starts to go into the body then the lungs eventually in persistent truncus arteriosus. What occurs as a result?
Cyanosis worsens as blood with lower O2 travels to the body.
How is persistent truncus arteriosus treated?
corrective surgery needed within 6 months of life - closure of VSD and separation of great vessels
Infants with transposition of the great vessels can only survive after birth if they have one of which 3 defects?
patent ductus arteriosus, atrial septal defect, ventral septal defect - allows intermixing of the blood
If these defects are not present, how can they be surgically induced?
Cardiac catheterization (balloon atrial septostomy) may create large hole in the atrial septum or a patent ductus arteriosus can be clinically induced to remain open allowing blood flow btwn pulmonary artery and aorta
Describe the basic pathology of transposition of the great vessels.
The great vessels are switched so the aorta is connected to the right ventricle and the pulmonary trunk is connected to the left ventricle - therefore oxygenated blood going to lungs and deoxygenated blood going to systemic circulation - NOT COMPATIBLE WITH LIFE
During the arterial switch procedure, what remains attached to the aorta?
coronary arteries
Transposition of the great vessels is usually accompanied by an _____________
atrioseptal defect