CVS Flashcards
What is gastrulation?
Mass movement and invagination of the blastula to form the ectoderm, mesoderm and endoderm
What is a gene?
DNA which when expressed is transcribed into RNA which is translated into protein with a function
What is a transcription factor?
A type of protein which when expressed ‘turns on’ other gene expression
What is the definition of contractility?
The state of the heart which enables it to increase its contraction velocity, to achieve higher pressure, when contractility is increased (independent of load) it is the end-systolic pressure volume relationship
What is elasticity?
It is the myocardial ability to recover its normal shape after removal of systolic stress
What is compliance?
It is the relationship between the change in stress and the resultant strain. It is reflected at the end-diastolic pressure-volume relationship
What is diastolic distensibility?
It is the pressure required to fill the ventricle to the same diastolic volume
What are the constituents of blood?
45% cellular: mainly RBC but there are also WBC and platelets 55% plasma The haematocrit is 0.45
What are red blood cells?
They are simple cells with no nucleus or mitochondria. There is a membrane to enclose HB because alone it would cause renal failure. It carries the enzymes of glycolysis
What is haemoglobin?
A tetramer of 2 alpha and 2 beta chains. It consists of protein, heme and Fe2+ ion
What does haemoglobin do?
It allows oxygen to bind reversibly with Fe2+ in aqueous solution. It carries oxygen from lungs to tissues. The normal level is 12.5-15.5g/dL
How are white blood cells produced?
They are produced from immature precursor cells in the bone marrow derived from stem cells. The rate of production is under hormonal control by a series of growth factors. Mature cells circulate in the blood
What stimulates cells to proliferate and differentiate?
Hormonal growth factors: Epo = RBC, G-CSF = WBC Tpo = platelets
How long do blood cells last?
RBC last 120 days Platelets last 7-10 days WBC last 6 hours
What are primitive cells?
Most primitive cells are stem cells and the are normally in the bone marrow. They are pluripotent, they proliferate and differentiate into mature RBC, WBC and platelets. Precursor cells are not found in blood
What are platelets?
Small cytoplasmic anucleate cells that block up holes in blood vessels. The longer the bleeding time the worse the platelet function. They are made in bone marrow from megakaryocytes, polyploid cells, cytoplasm buds off to become platelets
What do platelets do?
They circulate in an inactive state. They bind to damaged blood vessels and adhere, change shape and degranulate and aggregate into a platelet plug. The normal levels is 149-499
What are neutrophils?
The most numerous WBC, lasts 10 hours. A lack of number or function results in recurrent bacterial infection
What do neutrophils do?
They phagocytose and kill bacteria. They release chemotaxins and cytokines, which are an inflammatory response
What are coagulation proteins?
A series of proteins (enzymes) that circulate in an inactive form that make blood clot. They convert soluble fibrinogen into insoluble fibrin polymer
What are plasma proteins?
They are soluble and in plasma component; carrier proteins for nutrients and hormones; immunoglobulins (antibodies); coagulation proteins and albumin
What is albumin?
A major protein in the plasma. They are produced in the liver so in liver disease not enough albumin is produced. It determines oncotic pressure so keeps intravascular fluid in the right space so lack of albumin results in oedema
What are immunoglobulins?
They are produced by plasma cells in response to non-self protein antigens. There are several classes: IgG, IgM, IgA, IgE
What keeps blood fluid?
Coagulation proteins and platelets circulate in inactive form so the blood doesn’t clot. Endothelial cells, anticoagulant & fibrinolytic pathways actively keep it fluid. It is a balance between keeping blood in vessels fluid and out of it clotted
What is the coagulation cascade?
It is a series of 13 proteolytic enzymes that circulate in an inactive state and are sequentially activated in a cascade. The key enzyme is thrombin that cleaves fibrinogen, creating fibrin polymerisation, which is a clot.
Why does the coagulation cascade have lots of steps?
Multiple steps allow for biological amplification and regulation, not an all or nothing response so it can be graduated in response to severity of stimulation
What is the structure of arteries?
They contain mainly elastic, collagen, smooth muscle & mucopolysaccharide ground substance. There is an intima, media and adventitia. There are two elastic laminae, one either side of the media
What is in the intima of an artery?
It is composed of an inner surface lining of endothelial cells and very little collagen and ground substance
What is the adventitia made of?
Mainly collagenous connective tissue with blood vessels and some nerves
What are capillaries?
Comprise of tubes of endothelial cells bound to a basement membrane with co-existing pericytes, which have muscle fibres & may regulate blood flow.
What are sinusoids?
The vessels that connect arterioles and venules are sinusoids, allowing blood to percolate between tissue compartments
What are lymphatics?
Very similar to capillaries, but often a large diameter & less regular cross-section profile. They are endothelial lined with a basement membrane, that progressively merge to form larger vessels with some collagen in the background
Where are lymphatics?
Present in virtually all tissues, except the cornea, joint cartilage, CNS and bone marrow. Valves are found within some lymphatics, mainly in the legs
What is the structure of arterioles?
They may have an obvious media and adventitia. However, smaller arterioles show only a few medial cells with poorly defined elastic lamellae. A thin adventitia and normal intima also exist.
Where are semilunar valves?
Between the ventricles and outgoing arteries
What is the structure of semilunar valves?
They have three layers between epithelium on both sides: (1) Fibrosa: dense fibrous tissue (2) Spongiosa: loose connective tissue - proteoglycans (3) Ventricularis: collagenous tissue with elastic.
What is the cardiac conduction system?
These specialised groups of cells act to modulate & control cardiac contraction (SAN, AVN, His bundle & bundle branches)
What does the cardiac conduction system do?
They allow the 2-stage cardiac contraction with rapid ventricular contraction allowing pressure to be applied to the blood within the chambers & thereby blood flow
What is a resting membrane potential?
Normally only permeable to K+. Only the ions that can cross the membrane affect the resting potential. K+ ions diffuse outwards. Anions cannot follow. There is an excess of anions inside the cell, which generates a negative potential inside the cell
What are the chordea tendinae?
Fan-like bands of dense collagenised tissue that interface with the ventricular wall & the edge/underside of the cardiac valve
What is the Nernst equation and what does it do?
It determines the potential associated with ionic concentration gradients. E = 60log([outside][inside])
How do voltage gated K+ channels work in skeletal muscle?
There is an increase in permeability to K+ after sodium influx, which causes almost immediate repolarisation
How do Voltage Gated K+ channels work in cardiac cells?
There is a decrease in permeability to K+ after Na+ influx so the return to resting state isn’t rapid. Decreases K+ exiting the cell during plateau, which prolongs plateau phase. The increased permeability to K+ only after slow Ca2+ channels close & this causes repolarisation
How do the fast voltage gated Na+ channels?
The conformational shape is determined by the voltage of the cell, changes as cell loosed negativity. The activation gate closed in resting state, they suddenly open between -50mV to -70mV & Na+ floods through the gate. It closes after a short period of time after activation gate opens, which stops the influx
What are the voltage gated Ca2+ channels?
They are slower than fast Na+ channels and remain open for longer. Some Na+ does pass through but it is mainly Ca2+. It is responsible for the plateau portion of action potential. It is particular to hearty muscle cells.
What is excitation-contraction coupling?
The action potential is spread from the membrane to the transverse tubule to the sarcoplasmic reticulum. The Ca2+ is released from T tubules & from the sarcoplasmic reticulum. It diffuses into myofibrils & promotes the sliding of actin & myosin filaments, which cause muscle contraction
What are the myocyte membrane pumps?
K+ is pumped in and Na+ and Ca2+ is pumped out, these are both against the electrical & concentration gradients, so they require active transport & ATP
How is action potential propagated?
The action potential spreads over the cell membrane. The Na+ affects adjacent cells & causes depolarisation. Newly depolarised cells also cause depolarisation. Ions can travel directly via gap junctions
What does the AVN do?
Transmits cardiac impulses between atria and ventricles. It delays the impulses which: allows the atria to empty blood into ventricles because it has less gap junctions so the AV fibres are smaller than atrial fibres
What does the His-Purkinje system do?
It transfers impulses from the AV mode to ventricles. It has rapid conduction to allow coordinated ventricular contraction, this is caused by very large fibres & it has high permeability at gap junctions
How is sympathetic cardiac stimulation controlled ?
It is controlled by adrenaline, noradrenaline & type 1 beta adrenoreceptors. It increases adenyl cyclase & cAMP.
What controls parasympathetic cardiac stimulation?
It is controlled by acetylcholine & M2 receptors, which inhibit adenyl cyclase & reduce cAMP
What is the absolute refractory period?
The Na+ and Ca2+ channels closed to stop further stimulation during the action potential. It has less time for atria than ventricles. It prevents excessively frequent contractions, which allows time for the heart to fill.
What is the relative refractory period?
It is after the absolute refractory period. It is when some Na+ channels are inactivated but some aren’t. Only strong stimuli can cause action potential. It is effected by heart rate
What does the SAN do?
It normally determines the heart rate at a higher resting potential of -55 to -60 mV. It gradually drifts towards the threshold for discharge. The steeper the drift, the faster the pacemaker. It is driven by slow Ca2+ channels.
Where in the cardiac cells has the highest automacity?
SAN cells have the highest automacity & the spontaneous discharge of the heart muscle cells decreases down the heart.
What causes platelet shape change?
Activation of platelets lead to change from smooth discoid shape to spiculated forms with pseuodopodia, increasing surface area & possibility for cell-to-cell interactions
What is the voltage of a resting potential?
It is -90mV and is maintained by the Na/K pump. K+ is inside the cell and Na+ is outside the cell
What is the glycoprotein IIb/IIIa receptor for?
Platelet activation. There are 50,000-100,000 copies on the resting platelet surface, this increases with platelet activation.
What does platelet activation do?
Platelet activation increases the affinity of the receptor for fibrinogen, which acts as a cross bridge linking platelets together into aggregates from one receptor to another.
What stimulates platelet activation?
When there is a rupture, collagen gets exposed and it has von Willebrand factor, which activates platelets
What platelet surface receptors are there?
Glycoprotein IIb/IIIa is the main receptor. Adhesive Luganda and soluble agonists.
How do adhesive ligands act as platelet surface receptors?
Adhesive ligands in the subendothelium allow platelets to adhere to damaged vessel walls via receptors for collagen as well as GP IIb/IIIa, which bind to von Willebrand factor attached to collagen
How to soluble agonists act as platelet surface receptors?
Soluble agonists are released by forming thrombus, which bind to platelet surface receptors & amplify platelet activation
How do platelet activation mechanisms work?
There are lots of receptors that all link via various secondary messenger systems to platelet activation. They cause GP IIb/IIIa to get expressed more, which links more platelets together and causes a larger activation. It is positive feedback.
What does cyclooxygenase do?
It is made when membrane phospholipids are broken down. Cyclooxygenase 1 is used in platelet aggregation and renal function. Cyclooxygenase 2 is used in bone formation, renal function, mitogenesis and growth.
What platelet P2 receptors are there?
P2Y1, P2Y12, P2X1
What does the P2Y1 platelet receptor do?
It is activated by ADP and is linked to Gq paired receptors, which causes Ca2+ release & initiation of platelet aggregation (shape change)
What does the P2X1 platelet receptor do?
It is stimulated by ATP and causes calcium release and aggregation of platelets
What does the P2Y12 platelet receptor do?
It is activated by ADP. It is linked to a G-alpha-i paired receptor, which is linked to a cycloAMP (cAMP), which amplifies the platelet aggregation. There is an amplification of granule release & procoagulant activity
What is the fibrinolytic system?
It breaks down fibrin and tiny blood clots. Plasminogen is broken down to plasmin by tPA. The plasmin breaks down fibrin into fibrin degradation products (FDP)
What does the platelet alpha granule?
This is the chemical reservoir of the platelet. It contains lots of WBC regulations. It is expressed on the outside of the platelet & it binds to a WBC so the WBC gets covered by platelets.
Name some chemicals in the platelet alpha granule?
P-selectin: pro-inflammatory leukocyte interaction PAI-1: inhibition of thrombolysis
What is gastrulation?
Mass movement & invagination of the blastula to form three layers: - Ectoderm: skin, nervous system, cardiac outflow - Mesoderm: all muscle, most systems, kidneys, blood - Endoderm: GI tract & endocrine
Where is the CVS embryologically derived from?
Most of the CVS is derived from mesoderm cells but there is some contribution from the cardiac neural crest cells from the ectoderm
Name some cardiac transcription factors?
Hand, MEF2, GATA, Fog-1, Tbx, Pitx2 Transcription factors are expressed is a tissue specific manner
How does gene duplication cause evolution?
As organisms evolve, gene duplication occurs sporadically. Each copy of each gene can then evolve separately into different but related genes. This accounts for increasing complexity of development
What are the stages of embryological cardiac formation?
(1) day 19, formation of the primitive heart tube (2) day 22, cardiac looping, the node secretes nodal, which circulates left due to cilia (3) cardiac septation: there is one common atrium and ventricle
How does the arterial system vary?
Elastic arteries are the major distribution vessels (aorta, etc.) increase efficiency. Muscular arteries are the main distributing branches & control distribution. Arterioles are the terminal branches
What do cardiopulmonary baroreceptors do?
Stimulation leads to inhibition of vasoconstrictor centre in the medulla, which inhibits the release of angiotensin, aldosterone and vasopressin (ADH) leading to fluid loss and a fall in BP. It plays an important role in blood volume regulation
What type of atrial baroreceptors are there?
Atrial A: responds to tension during atrial systole Atrial B: responds to tension during atrial filling
What do atrial baroreceptors do?
They send vagal afferents to medulla when stimulated. Stimulation reduces sympathetic outflow to kidney (increased renal blood flow and urine) but increased outflow to the SA node (increased heart rate)
What is vasculogenesis?
Angioblasts (from splanchnopleuric mesoderm) coalesce to form angioplasties cords throughout the embryonic disc. They migrate to form the aorta.
What is angiogenesis?
It adds to vasculogenesis and is driven by growth factors and takes place via proliferation and sprouting
What are blood islands?
They form outside the embryo in the extraembryonic mesoderm. They are a core of hemoblasts surrounded by endothelial cells, they go on to form the vessels in the embryo. They migrate between day 17-21 & vascularise the yolk sac, chorionic villus and stalk
What are the main components of myocardium?
Contractile tissues, connective tissue, a fibrous frame and a specialised conduction system
What is myosin?
It is 2 heavy chains (head), 4 light chains. There are alpha myosin and beta myosin. The heads are perpendicular on the thick filament at rest, and bend towards the centre of the sarcomere during contraction
What is actin?
It is a globular protein and a a double-stranded macromolecular helix (G-actin). Both together form the F-actin.
What is tropomyosin?
It is an elongated molecule, made of two helical peptide chains. It occupies each of the longitudinal grooves between the two actin strands and regulates the interaction between the other 3
What are the key features of a working myocardial cell?
It is filled with cross-striated myofibrils. It has mitochondria in it that create ATP through aerobic metabolism and oxidative phosphorylation. The heart relies on free fatty acids and oxygen to produce energy
What does the myocardial membrane do?
It regulates excitation-contraction coupling and relaxation. The plasma membrane is full of pumps. It separates the cytosol from extracellular space and sarcoplasmic reticulum
What happens during cardiac muscle contraction?
Sliding of actin over myosin by ATP hydrolysis through the action of ATPase in the head of the myosin molecule. These heads form the cross bridges that interact with actin
What are the types of troponin?
TnI: with tropomyosin inhibit actin & myosin interaction TnT: binds troponin complex to tropomyosin TnC: has a high affinity with calcium binding sites, signalling contraction, binds to actin when not bound to Ca2+
What does TnC do?
The TnC bond with Ca2+ drives TnI away from actin, allowing the actin to interact with myosin. Ca2+ in unbound using ATP as energy
What are the phases of the cardiac cycle?
Left ventricle contraction: - isovolumic contraction and maximal ejection. Left ventricle relaxation: - start of relaxation and reduced ejection, isovolumic relaxation, rapid ventricle filling and ventricle suction, slow ventricle filling and atrial booster
What are the heart sounds?
- Closure of the mitral valve 2. Closure of the aortic valve 3. The jittering of the ventricular valve when the blood enters the ventricle. Only heard in people under 25 4. Jittering of the ventricular valves due to atrial contraction (not healthy)
What controls the contractile cycle?
Calcium ions, troponin phosphorylation, myosin ATPase
What happens during ventricular systole?
Wave of depolarisation arrives and opens the L-calcium tubule. Ca2+ arrive at the contractile proteins. The LVp>LAp so the mitral valve closes & the LVp rises above Aop because of isovolumic contraction. The aortic valve opens and ejection starts.
What is isovolumic contraction?
When the muscle wall contracts, so tension and pressure increase
What happens during ventricular diastole?
LVp peaks then decreases. Due to the influence of phosphorylated phospholambdian, cytosolic Ca2+ is taken up by the SR. There is a phase of reduced ejection. The LVp<aop></aop>
What is ventricular filling?
The LVp<lap></lap>
What is preload?
The load (blood) present before LV contraction has started
What is afterload?
The load (blood) after the ventricle starts to contract
How are blood types decided?
RBCs carry many different proteins on their surface membrane, which differ between individuals. These are the red cell antigens and they are inherited.
What are the red blood cell systems?
There are over 400 different systems of red cell antigens. There are only 2 very important systems: ABO and Rhesus
How many blood groups are in the ABO blood group system?
There are 4 blood groups: A, B, AB or O. O is 45% A is 40% B is 12% AB is 3%
What are ABO antigens?
They are carbohydrate antigens, not proteins. They are naturally occurring antibodies from age 6 months. You can find out blood type using antibodies anti-A and anti-B. Type O reacts with nether. Can check blood cells & serum
What is Starling’s law?
Within physiological limits, the larger the volume of the heart, the greater the energy of its contraction and the amount of chemical change at each contraction
Can plasma be transfused?
The plasma is frozen within 6 hours of collection. It contains all the coagulation proteins and inhibitors. It is only used if it is a massive transfusions or dilution all coagulopathy, in liver disease and DIC
What is cryoprecipitate?
It is rich in fibrinogen. It is used in DIC and massive transfusion if specific lack of fibrinogen.
What is the goal of circulation control?
To maintain systemic arterial pressure
What is mean arterial pressure?
MAP = cardiac output X total peripheral resistance = diastolic pressure + 1/3(systolic pressure-diastolic pressure)
What are the regulators of circulation?
-Blood vessels: vasodilation and vasoconstriction: affects resistance -Heart: rate and contractility: CO = HR x stroke volume -Kidney: fluid balance: longer term control
What are the key pathways in circulation?
- Local mechanisms - CNS - Peripheral neural pathways - Vascular reflexes - Humoral factors
How do blood vessels change circulation?
Smooth muscle in the vessel wall (media) allows changes in vessel calibre in response to the mechanisms. The main effector vessels are the resistance vessels (smaller arteries and arterioles)
How are blood vessels innervated?
Most arteries & veins are innervated solely by sympathetic NS, which exerts tonic contractile effect. Parasympathetic NS innervated some vessels in certain viscera & pelvic organs; activation reduces vascular tone & resistance
What is aortic distensibility?
The ability of the artery to stretch. It maintains the aortic flow.
What does myogenic mean?
Originating from muscle fibres
What does transmural mean?
Existing or occurring across the whole wal of an organ or blood vessel
What myogenically affects blood vessels?
Increased transmural pressure can stimulate vasoconstriction and vice versa
How do local metabolic factors affect blood vessels?
When the oxygen supply is decreased, vasodilator metabolites accumulate, increasing local blood flow. Mediators include K+, O2, adenosine, phosphate and osmolarity
Where is the depressor region of the cardiovascular centre?
It is the caudal ventral part of the medulla. It directly inhibits the spine, the pressor region, also exhibits tonic and rhythmic activity
Where is the pressor region in the cardiovascular centre?
It is in the dorsal lateral medulla. It stimulates vasoconstriction, cardiac acceleration, increased myocardial contractility, the region is tonically active with rhythmic changes related to respiration
What does tonically active mean?
A low level of activity all the time
Where are arterial baroreceptors?
They are stretch receptors in the carotid sinus (more sensitive) and aortic arch (less sensitive).
How is blood pressure regulated?
Short term blood pressure is regulated by the arterial baroreceptors. Long term blood pressure is blood volume. If the pressure deviates from normal for a while a new baseline is set
Where do arterial baroreceptors project to?
The central projection is the nucleus of the tract solitarius of the medulla in response to pulsatile changes in BP.
What does stimulation of the arterial baroreceptors do?
It inhibits sympathetic mediated vasoconstriction, causing a fall in BP. It increases parasympathetic and decreases sympathetic outflow to the heart
Where are baroreceptors present?
The atria, ventricles, pulmonary artists and the medulla
What are neural influences on medulla?
Baroreceptors (most important) Chemoreceptors Hypothalamus Cerebral cortex Skin Changes in blood concentration of O2 & CO2
What are capillaries?
The functional part of the circulation. Blood flow is regulated by precapillary sphincters. They are between 3-40 microns in diameter.
What are the three types of capillary?
Continuous (most common in brain and muscle); fenestrated (kidney, small intestine, endocrine glands); discontinuous (liver sinusoids)
What are peripheral chemoreceptors?
Small, highly vascular bodies in the aortic arch (aortic bodies) and medial to the carotid sinus (carotid bodies)
What are the functions of peripheral chemoreceptors?
They are stimulated by a fall in PaO2, pH, and rise in PaCO2. They are mainly involved in control of respiration but stimulation also leads to reflex vasoconstriction. They are less important than baroreceptors in circulation control
How does the hypothalamus affect blood pressure?
Stimulation of the anterior hypothalamus leads to a fall in BP and HR, it is the reverse with the posterolateral hypothalamus.
How does the cerebral cortex affect blood pressure ?
It can affect the blood flow and pressure. Stimulation usually leads to vasoconstriction but vasodilation can occur with emotion (blushing). Effects can be mediated via the medulla or directly
What are central chemoreceptors?
Chemosensitive regions in the medulla respond to changes in PaCO2.
How do central chemoreceptors react to a fall in PaCO2?
It decreases medullary tonic activity and BP. It has similar changes in response to the pH
How do central chemoreceptors respond to an increase in PaCO2?
It reacts with a vasoconstriction, increasing peripheral resistance and BP. There is a similar response to a change in pH.
What has intrinsic control of blood flow?
Brain and heart have intrinsic control dominates to maintain blood to vital organs. Skin blood flow is also important in general vasoconstrictor response and in response to temperature
What has extrinsic blood flow?
Skeletal muscle has dual effects: at rest, vasoconstrictor tone is dominant. When exercising, intrinsic mechanisms pre-dominate
How does thrombin activate platelets?
It activates through PAR-1, which increases Ca2+ release from intracellular stores, which releases scramblase, which moves ions from inside the membrane to outside it
How do amino-phospholipids activate platelet coagulation?
They are on the outer platelet membrane. They cause a prothrombin complex which generates thrombin.
What does thrombin do in the platelet procoagulation activity?
Thrombin activates platelets directly but starts the coagulation cascade by creating thrombin through the amino-phospholipid pathway
What is the pericardium?
It comprises a fibrous capsule lining in the heart with the same being reflected around the pericardial cell. The lining cells are mesothelial
What is the heart made of?
It contains mainly cardiac myocytes although the tissue of the valves, pericardium, intrinsic vasculature, nerves and connective tissue need to be considered
What is the lining of the heart?
The inner lining of the heart is endothelial, paralleling blood vessel differentiation. There is a thin layer of connective tissue below this, before it interfaces with cardiac muscle. Nerves and blood vessels course through the epicardium fat & connective tissue
What are cardiac myocytes?
These brick-like cells are the mainstay of the heart. The muscle cell contains abundant myofibrils arranged along the long axis of the cells.
What are in muscle cells?
Myocytes, sarcoplasmic reticulum, abundant mitochondria, moderate amounts of RER and a nucleus that is often central and rounded with a prominent nucleus
Where do baroreceptors send impulses to?
The nucleus tractus solitarius in the medulla
What is the difference between elastic and muscular arteries?
Elastic arteries have multiple elastic lamina in the tunica media.
Muscular arteries have a media almost all composed of smooth muscle
Name 4 vasodilators:
NO, prostacyclin, bradykinin, ANP
Name 4 vasoconstrictors:
Endothelin 1, Angiotensin 2, sympathetic stimualtion,
ADH
Define cardiac output:
Volume of blood ejected by each ventricle per minute
What does a positive reflection on an ECG show?
Depolarisation towards lead
Repolarisation away from the lead
What does a negative reflection on an ECG show?
Depolarisation away from the lead
What is hyperaemia?
Increase in blood flow
