Cardiovascular Flashcards
How long do RBCs live?
120 days
Main hormone for driving RBC production?
Erythropoetin
Haemoglobin made up of…
2 alpha polypeptide chains and 2 beta polypeptide chains
RBC size
7-8 x 2-2.5um
WBC size
7-30um
Where are RBCs and WBCs developed?
RBC - Bone marrow
WBC - Thymus (T-Cells)
Bone Marrow (B-Cells)
Humoral Immunity
B cells come into contact and divide by clonal expansion forming Memory B Cells and Plasma Cells (secrete antibodies against pathogens)
Cell-Mediated Immunity
Antigens engulfed and displayed by phagocytes triggering clonal expansion of T(helper) cells into B cells, memory T(helper) cells and T(cytotoxic) cells
Defends against infected cells, cancers and transplant tissues
Define Haemocrit
Ratio of volume of RBCs to total volume
Proportion of T and B lymphocytes in blood
80% T
20% B
Main hormone for driving WBC production
Granulocyte-macrophage colony stimulating factor (GM-CSF) (will only stimulate production of myeloblastic WBCs and not lymphoid cells)
Main hormone driving platelet production
Thromboprotein (TPO)
(Leads to increased megakaryocyte production)
Neutrophils (Granulocyte)
Most abundant WBC, phagocytic and release cytokines to reduce inflammation
Monocytes (Granulocyte)
Mature into either macrophages or dendritic cells (both antigen presenting)
Eosinophils (Granulocyte)
Fights parasites
Platelet lifespan and size
7-10 days
2-5um
How are platelets formed from megakaryocytes?
Exocytosis of megakaryocytes
Secretory granules in platelets (4 types)
Alpha granules (e.g-plasminogen)
Dense granules (e.g-serotonin)
Lysosome
Peroxisome
Platelet function
Endothelial injury so platelets change shape to adhere to the cut. Excessive granular release results in aggregation of platelets
The coagulation cascade can then occur from the platelets’ surfaces
Blood serum
Plasma without clotting factors
3 options for treating low clotting factor production
Fresh Frozen Plasma (FFP)
Cryoprecipitate
Fibrinogen Concentrate
Antigens on red cells
Millions on their surface (several hundred are blood group antigens)
Antigens and antibodies present on RBCs of each blood group
Grp A - A antigen, anti-b antibodies
Grp B - B antigen, anti-A antibodies
Grp AB - A and B antigens, no antibodies
Grp O - No antigens, anti-A and anti-B antibodies
Rhesus antigens
Over 45 different Rh antigens
Most important is Rh D (coded by RHD gene)
Highly immunogenic antigen and a high proportion of D neg people form anti-D if exposed to D pos blood
Blood donation types
-Whole blood
-Apheresis - blood removed and separated externally and components not needed are returned
Separation of blood donation
Centrifugation separates blood into RBC layer, WBC and platelet layer, plasma layer
Plasma only kept from male donors (female plasma more likely to contain antibodies that could cause a serious reaction)
Storage and shelf life of each blood constituent
RBCs - 4degreesC, 35 days
Platelets - 22degreesC (with continuous agitation to prevent clumping), 7 days
Cryoprecipitate
FFP thawed to 4degreesC and a fibrinogen rich layer is skimmed off
IVIg
Made from large pools of plasma
Can have normal IVIg - contains antibodies to viruses common in population
Or specific IVIg - contains known high antibody levels to a particular condition (anti-D Ig in pregnancy)
Typical ECG Settings
Speed = 25mm/sec
Voltage = 10mm/mV
ECG - 1 small square is 0.04 seconds, 1 big square (5 small squares) is 0.2 seconds
1 big square in the other direction is 0.5mV
On ECG graph:
Positive deflection (above baseline) shows…
Negative deflection (below baseline) shows…
Net current flow towards lead
Net current flow away from lead
What does each part of ECG show?
P?
P - Atrial contraction (depolarisation)
(atrial repolarisation then occurs but isn’t displayed on ECG)
QRS - Ventricular depolarisation
T - Ventricular repolarisation
Normal PR Interval
120-200ms
Normal QRS Width
Less than 120ms
Prolonged QRS caused by bundle branch block (right bundle or 1 of the 2 left bundles) causing them to work slower
Normal QT interval
Men: 350-440ms
Women: 350-460ms
ECG Electrodes vs Leads
Electrode - Physical connection to patient in order to measure the potential at that point (10 electrodes record a 12 lead ECG)
Lead - Graphical representation of electrical activity in a particular vector
Bipolar vs unipolar ECG leads
Bipolar - Measures pd between 2 electrodes (one designated +ve, one designated -ve)
Unipolar - Measure pd between an electrode and a reference electrode (set as 0)
The Bipolar Limb Leads
I) Pos L arm, Neg R arm (current flowing to L arm shows +ve deflection) (0 degrees)
II) Pos L leg, Neg R arm (current flowing to R arm shows -ve deflection) (60 degrees)
III) Pos L leg, Neg L arm (current flowing to L leg shows +ve deflection) (120 degrees)
Which bipolar limb lead gives most positive deflection?
Lead II as it’s at 60degrees and the heart is slanted at 60degrees (normal cardiac axis of conduction if maximal conduction is between -30 and 90degrees)
Unipolar Limb leads
aVL - from -ve reference to +ve L arm (-30 degrees)
aVR - from -ve reference to + R arm (-150 degrees)
aVF - from -ve reference to + L leg (90 degrees)
6 Unipolar Chest Leads
V1 and V2 look at septum of LV (LAD and Right coronary artery)
V3 and V4 look at anterior wall (left anterior descending artery)
V5 and V6 look at lateral wall (circumflex artery)
Blood flow through organs
Liver 27%
Kidneys 22%
Muscle 15%
Brain 14%
Skin 6%
Bone 5%
Heart 4%
Other 3.5%
Bronchi 2%
Thyroid 1%
Adrenal 0.5%
Blood flow through organs
Liver 27%
Kidneys 22%
Muscle 15%
Brain 14%
Skin 6%
Bone 5%
Heart 4%
Other 3.5%
Bronchi 2%
Thyroid 1%
Adrenal 0.5%
Myogenic tone
Offers a resting level vascular smooth muscle contractile activity so muscle in arteries is never fully relaxed
Capacitance vessels
Blood vessels that contain most of the blood (the veins)
What 2 factors move blood through veins
-Contraction of skeletal muscle on veins
-Sympathetic Nervous System mediated vasoconstriction
Where do lymphatics empty into the venous system
Via thoracic duct into the left subclavian vein
Cardiac Output (CO) =
Heart Rate (HR) x Stroke Volume (SV)
Blood Pressure =
CO x Total Peripheral Resistance (TPR)
Pulse Pressure (PP) =
Systolic - Diastolic Pressure
Mean Arterial Pressure (MAP) =
Diastolic pressure + 1/3 PP (between Diastolic and Systolic)
Frank-Starling Mechanism
Says the lower the Left Ventricle End Diastolic Pressure (LVEDP), the lesser the stroke volume in systole (as less blood is flows back into the LV)
Typical artery for taking blood pressure
Brachial artery (big artery, located on the arm and level with the heart)
Taking blood pressure
Pressure cuff strapped around upper arm (pressure above systolic)
Then a heartbeat can be heard as pressure drops in the range between systolic and diastolic and then disappears below diastolic (stethoscope placed over brachial artery below the cuff)
Autoregulation of arterioles allows for consistent flow despite pressure changes
This is excellent in the…
Moderate in the…
Poor in the…
Renal/Cerebral/Coronary
Skeletal Muscle / Splanchnic
Cutaneous (to act as a capacitance)
A Humoral Factor Vasoconstrictor
Endothelin-1 (responsible for myogenic contraction)
Humoral Factor Vasodilators
Hypoxia
Adenosine
Bradykinin
NO
K+, CO2
Drop in pH
Tissue breakdown products
Vasodilators and vasoconstrictors produced by the endothelium
NO and prostacyclin (vasodilators)
Endothelin (vasoconstrictor)
Hormonal Vasoconstrictors
Epinephrine (at the skin)
Angiotensin II
Vasopressin (ADH)
Hormonal Vasodilators
Epinephrine (at the muscle)
Atrial Natriuretic Peptide
How is epinephrine (hormone) a vasoconstrictor and vasodilator?
When running, vasoconstricts at skin and vasodilates at muscle (so greater O2 supply to muscle)
Where are baroreceptors located?
Primary - Arch of aorta and carotid sinus (found at bifurcation point of common carotid artery)
Secondary - In veins, myocardium, pulmonary vessels
Afferent and efferents of baroreceptors
Afferent - Glossopharyngeal (IX)
Efferents - sympathetic and Vagus (X) (carry info to effectors)
Baroreceptors response to increased blood pressure (vice versa for pressure decrease)
Increase firing = increased parasympathetic (Vagus) or decreased sympathetic = reduced CO and TPR = reduced BP
If arterial BP deviates from norm for more than a few days, what effect does this have on baroreceptors?
They adapt and reset to a new baseline pressure to be regulated (like in hypertension)
ANP effect on cardiopulmonary baroreceptors (in atria, ventricles and PA)
When atria, PA and ventricles stretch, ANP is secreted
This reduces the vasoconstrictor centre in medulla, reduces BP and reduces angiotensin, aldosterone and ADH release (alters blood volume)
Chemoreceptors (present in the medulla) role in control of blood pressure
Raised PaCO2 (and acidosis)= vasoconstriction (through increased TPR)
Reduced PaCO2 (and alkalosis)= reduced medullary tonic activity (lower BP)
PaO2 less effect on medulla but a decrease will result in some vasoconstriction
Fainting Mechanism
Heat, standing and dehydration lead to decreased venous return = decreased CO = decreased perfusion to brain = faint
Blood loss results in…
Decreased venous return so heart compensates by increasing HR to maintain constant BP (constant BP with increased HR is a tell tale sign)
Pale skin is a sign as vessels vasoconstrict
Left ventricular ejection off each gender (as % of the volume)
Female - 65%
Male - 55%
What causes S1 and S2?
S1 - Mitral valve closing
S2 - Aortic valve closing
S3
Third heart sound occurs at the beginning of diastole (in the rapid diastolic filling period of the ventricles)
It’s benign if seen in youth but problematic if it is present later in life
Preload and afterload of the ventricles
Preload - load present before LV contraction starts
Afterload - load after ventricles have started to contract (BMI increase results in increase number of small vessels in body = Higher BP resulting in a higher afterload putting more strain on the LV)
Define Gastrulation
Mass movement and invagination of the blastula to form 3 layers (ectoderm, mesoderm, endoderm)
What comes from the ectoderm?
Skin, nervous system, neural crest (which contributes to cardiac flow, coronary arteries)
What comes from the mesoderm?
Predominant layer that gives rise to the CV system (a little bit comes from the ectoderm)
It also gives rise to muscle, kidneys, blood, bone
What comes from the endoderm?
GI Tract (including pancreas and liver but not smooth muscle), endocrine organs
In the formation of the primitive heart tube, the bulbus cordis forms…
Most of RV and parts of the outflow tracts for aorta and pulmonary trunk
In the formation of the primitive heart tube, primitive ventricle forms…
Most of the LV
In the formation of the primitive heart tube, primitive atrium forms…
Anterior parts of LA and RA
In the formation of the primitive heart tube, the sinus venosus forms…
SVC and part of RA
Before cardiac septation, what is the name of the internal opening between the atrium and the ventricle
The atrioventricular canal
Role of endocardial cushions in cardiac septation
2 masses of tissue: the superior and inferior endocardial cushions. They grow and move the atrioventricular canal to the right and eventually the cushions fuse forming a L and R atrioventricular canal
Through what does blood leave the ventricle when there is only only ventricle and one atrium?
The truncus arteriosus
Platelet shape change when activated
Smooth discoid -> Spiculated (increased SA to increase cell-cell interactions)
Number of receptors on surface increases increasing the platelets affinity for fibrinogen (which links and binds platelets together)
Surface receptor expressed by platelets
Glycoprotein IIb/IIIa (50k-100k copies resting on surface)
Platelet adhesion to an atherosclerotic rupture
Collagen receptors on platelet bind to subendothelial collagen (which is exposed)
GP IIb/IIIa also binds to von Willebrand Factor (VWF) (secreted from endothelial cells) which is attached to collagen
GPVI receptor also binds to collagen which activates the platelet
Platelet activation
Shape change
GP IIb/IIIa receptor converted to a receptor that will bind fibrinogen (for cross-linking)
As GPVI binds to collagen, the platelet synthesises and releases Thromboxane A2 which binds to the TPa receptor on the platelet (further activating platelet)
Conversion of Arachidonic Acid in endothelial cells
Arachidonic acid converted by Cyclooxygenase 1 and 2 (COX-1 and COX-2) into Prostaglandin H2 -> Prostacyclin (inhibits platelet aggregation and inhibits vasoconstriction)
Conversion of Arachidonic Acid in platelets
Arachidonic acid converted by COX-1 into Prostaglandin H2 -> Thromboxane A2 (results in platelet aggregation and vasoconstriction of the vessel wall)
Low dose aspirin effect on platelet aggregation
Low dose aspirin inhibits COX-1 so less Thromboxane A2 is released from platelets than Prostacyclin from endothelial cells (higher dose aspirin inhibits both COX-1 and COX-2)
What happens when ADP binds to P2Y12 receptor on a platelet?
Gi protein inactivates adenylate cyclase so cAMP can’t be formed
Gi protein activates PI3 kinase
These responses amplify platelet activation
What happens when ADP binds to P2Y1 receptor on a platelet?
Gq protein activates Phospholipase C which produces Protein kinase C and Ca2+
These initiate aggregation and shape change
Interaction between platelets and leukocytes
P-selectin on platelet binds to PSGL-1 on leukocyte triggering secretion of a-granules from platelet (containing inflammatory mediators)
Also triggers secretion of cytokines, proteolytic enzymes and pro-thrombotic factors from the leukocyte
Every cell in our body needs to be bathed in fluid and within ….. of a source of circulation
2mm
Muscular vs elastic arteries
Elastic - major distribution vessels (aorta, brachiocephalic, carotids, etc)
Muscular - main distributing branches
General structure of artery/vein from inside out
Tunica Intima (endothelial cells resting on a BM)
Tunica Media (vascular smooth muscle cells)
Internal Elastic Lamina
Adventitia (Fibroblasts) (vasa vasorum present - smaller blood vessels within)
What do the 1st and 2nd aortic arches become?
Minor head vessels
1st - Small part of maxillary
2nd - Artery to stapedius
What do the 3rd aortic arches become?
The carotid arteries
What do the 4th aortic arches become?
R side lose connection with aorta and becomes part of artery which goes down to the arm
Left side becomes part of the arch of the aorta
What do the 6th aortic arches become?
R arch Pulmonary Trunk
L arch ductus arteriosus
Sarcomere Ultrastructre
Basic contractile unit of a muscle fibre
Consists of half an I (light) band, then an A (dark) band, then half an I band
I bands consist of just actin
A bands consist of both actin and myosin during contraction and just myosin during relaxation
Z lines bisect each I band
2 actin helices above and below a myosin filament
Chemical Mechanism of Relaxation of a Cardiac Myocyte
Energy from hydrolysis of ATP breaks the bond between Ca2+ and Troponin C and Ca2+ is actively transported back into the sarcoplasmic reticulum and the troponin complex rebinds to actin as troponin I is no longer inhibited by Ca2+
Chemical mechanism of contraction of cardiac myocyte
Ca2+ move massively into cytosol by protein channels when the sarcolemma is depolarized (Ca2+ is stored in the sarcoplasmic reticulum)
Ca2+ then binds with Troponin C exposing the myosin binding sites on actin
Nodes on the myosin then bind to actin
Hydrolysis of ATP (using ATPase) in the myosin head moves myosin heads towards the M-line dragging the actin with it
What is the sarcolemma?
The membrane of a cardiac myocyte
What are T-tubules of a cardiac myocyte?
Invaginations in the sarcolemma that allow Ca2+ to get closer to the centre of the cell quicker
T-tubule membranes are consistent with the sarcolemma
What separates adjacent cardiac muscle cells?
Intercalated discs - Gap junctions that allow conduction across the muscle muscle rather than just in individual cells
Actin structure in a cardiac myocyte
Double stranded helices with tropomyosin attached
Attached to which are complexes of Troponin T, I and C
Troponin C role
Bind to Ca2+ to expose the myosin binding sites on actin (contains high affinity Ca binding sites)
Troponin T role
Binds troponin complex to tropomyosin
Troponin I role
Suppresses contractile activity of actin and myosin
Role of Titin within a sarcomere
Protein that prevents over-stretching of the sarcomere (elasticity)
Without it, stretching of cardiac muscle would result in dilated cardiomyopathy = heart failure
Tropomyosin structure
Made of 2 helical peptide chains
Occupies each of the 2 longitudinal grooves between 2 actin strands
Resting membrane potential of a heart cell
Approx -90mV
Role of Na/K ATPase in restoring resting potential
Pumps 2K+ into cell and 3Na+ out of cell to restore membrane potential to -90mV
K+/Na+ leak channels also allow lots of K+ out of the cell and very small amounts of Na+ into the cell
What causes rapid depolarisation of a cell from -90mV to +20mV?
Opening of voltage gated Na channels so Na+ ions rapidly flow into the cell
What causes the prolonged plateau phase once an action potential has been generated?
Slow Ca channels open causing Ca to enter cell maintaining the depolarised state (the point of this electrical activity is to deliver Ca to the cardiac myocyte cytoplasm)
Delayed rectifier of membrane potential back towards resting potential
Voltage sensitive K channel opens and K+ leaves the cell causing repolarization
Action potential propagation
Local depolarization opens nearby Na+ channels spreading a wave of depolarization across the membrane
What triggers release of Ca2+ from the sarcoplasmic reticulum?
Ca2+ binding to Ryanodine receptors (RyR) on the sarcoplasmic reticulum membrane
Difference between contraction time of skeletal and cardiac muscle
Cardiac muscle contracts up to
15 times longer due to slow Ca channels
Bachmann’s bundle
Found between the L and R atria and conducts electrical impulse from SAN to LA
Effect of sympathetic stimulation in autonomic control
Increases HR (positively chronotropic)
Increases force of contraction (positively inotropic)
These result in increased CO (up to 200% but decreased sympathetic stimulation can drop CO to 30%)
Effect of parasympathetic stimulation in autonomic control
Decreases HR (negatively chronotropic)
Decreases force of contraction (negatively inotropic)
These result in decreased CO
What controls sympathetic stimulation in autonomic control?
Adrenaline, noradrenaline and type 1 beta adrenoreceptors
Increases adenylyl cyclase -> increases cAMP
What controls parasympathetic stimulation in autonomic control?
Acetylcholine
M2 receptors which inhibit adenylyl cyclase -> decreased cAMP
Decreases CO up to 50%
Role of AVN
Fewer gap junctions and AV fibres are smaller than atrial fibres =
-Delayed impulse
-Protects ventricle from
overstimulation
Speed of conduction of:
Atrial and Ventricular muscle fibres?
Purkinje fibres?
0.3-0.5m/s
4m/s
Spontaneous depolarisation of tissue in the heart
SAN is the best at it but if the SAN packs in then the AVN can spontaneously depolarise but more slowly resulting in a slower HR.
The Purkinje fibres can also spontaneously depolarise but even slower than the AVN = even slower HR
Epicardium vs Endocardium repolarisation
Epicardium repolarises slightly later
SAN specialised ion channels
If - Funny current (generated by at channel that leak anions out of the cell)
This increases the membrane potential slowly up to -35mV at which point voltage gated Ca channels open and Ca enters cell depolarising the membrane
What increases the action of the pacemaker (SAN)?
A steeper phase 4 slope (the funny current)
You have a steeper slope when you’re younger due to If channel numbers decreasing with age
Explains why babies have. a higher HR
Refractory Period (approx 0.25 seconds in the ventricle) (less for atria)
Some time after the action potential is generated, the Na+ ion channels are closed and inactivatable
Membrane then returned to resting potential at which point the Na+ channels are closed but activatable
Absolute vs Relative Refractory Period
Absolute - All Na+ channels inactivated
Relative - Comes after and only some Na+ channels are inactivated (so can be activated by a strong stimulus)
