2. Anatomy & Physiology of the Cardiovascular System Flashcards
Myocardial structure - macro-anatomy
- Left ventricle is thicker to pump blood at a higher pressure around the body
- Valves prevent backflow to increase efficiency of blood pumping through the heart
- Spinal arrangement of heart muscle squeezes blood up the apex
- In a healthy heart 60% of the volume of the heart chamber is squeezed out in each heartbeat – ejection fraction
- Cardiac muscle cells contract ~20% due to shortening & bulging of the muscle cells
Intercalated discs contain
- Gap junctions for cell-to-cell ion movement (rapid spread of electrical signals)
- Desmosomes transfer force from cell-to-cell (end to end)
Cardiomyocyte sarcomere components
- Myosin – thick filaments
- Actin – thin filaments
- Titin – spring which relaxes the muscle after contraction
Cardiomyocyte length-tension relationship
- Frank-Starling Law states that the stroke volume of the left ventricle will increase as the left ventricular volume increases due to the myocyte stretch causing a more forceful systolic contraction
- Force development proportional to myofilament (actin & myosin) overlap
Cardiomyocyte ultrastructure
- ~30% of the energy is used for regulation of contraction
- Depolarisation triggers calcium induced calcium release from the sarcoplasmic reticulum
Cardiac excitation-contraction coupling
- Ca enters cell during action potential plateau
- Triggers release of more Ca from sarcoplasmic reticulum
- Ca binds to myofilaments (troponin-C)
- Activates cross-bridge cycling
- Cell shortens
- Most Ca pumped back in SR
- Some Ca exits cell by Na-Ca exchanger & sarcolemmal Ca pump
Myofilament Ca2+ sensitivity & movement
- Ca2+ binds to Troponin-C (TnC)
- TnC changes conformation
- Tnl moves away from actin-myosin binding site
- Actin binds to myosin & contraction occurs
- As [Ca2+]I falls, Ca2+ dissociates from TnC
- Tnl again blocks actin-myosin binding site
- Relaxation occurs
Phosphorylation of Tnl (i.e. by beta-adrenergic signalling) promotes dissociation of Ca2+ from TnC & myocyte relaxation
Cardiac cycle - left vs right
- Pressure is greater in the left side vs right side due to pumping blood further away from the heart
- Ventricular volume is the same in both sides
Measuring cardiac function - echocardiography
- Systolic function can be assessed by looking at a cross-sectional view of the heart (parasternal short axis)
- Diastolic function can be assessed by looking at a longitudinal view of the heart (apical 4 chamber view)
Diastolic function - doppler flow (mitral inflow)
Measures blood flow velocity through mitral valve:
- E wave – blood flowing into the ventricle by passive filling (due to pressure gradient)
- A wave – blood flowing from atrium into the ventricle by active filling (due to atrial contraction)
Normal: E/A > 1
Impaired relaxation E/A < 1
Diastolic function - tissue doppler (mitral valve movement)
Measures velocity of tissue movement at mitral valve
- E’ wave – passive LV filling
- A’ wave – filling due to atrial contraction
Diastolic function – E/e’
E/e’ ratio increases with the severity of heart failure, correlates well with heart failure biomarkers (e.g. NT pro BNP values), & declines when heart failure improves
Electrical activation of the myocardium
- Depolarise atria
- Depolarise septum (left to right)
- Depolarise ventricular walls towards apex & up towards base
Biomarkers of heart damage
- During onset of myocardial infarction plasma membranes of necrotic myocytes becomes leaky
- Molecules e.g. CK-MB, myoglobin, troponin I leak out of the cell into circulation
- These molecules can be used as biomarkers for diagnosis of myocardial infarction
Vascular tree
- Arterial side is thicker than the venous side due to pressure difference
- Valves are present in the venous side to help blood return to the heart
- Movement such as walking/running helps blood flow back to the heart
Cardiac output distribution
- Vascular ‘tree’ perfused in series
- Organ ‘beds’ perfused in parallel
- At rest, highest flow to gut & kidney ‘reconditioning’ organs
- Flow through each ‘bed’ controlled at arterioles by local & central signals
Capillary exchange
Comprised of hydrostatic fluid & osmotic pressure that drive interstitial fluid out of capillary (net filtration) & into capillary (net absorption)
Capillary exchange & lymph formation
- Network of blind-ending lymph capillaries lying near blood capillaries – permeable to protein & fluid
- The lymphatic vessels contain excess interstitial fluid, white blood cells (immune cells), also transports fats from gut
- Lymph flow is slow – aided by smooth muscle contractions around the lymph vessels – also used valves to aid flow
- Lymph is directed through lymph nodes before returning to blood
Enters blood via:
- Lymphatic duct (right side)
- Thoracic duct (left side)
Both ducts empty into subclavian veins
Lymph nodes are important in the adaptive immune response
- Macrophages phagocytose microbes at the site of infection, then travel to the lymph nodes to trigger the immune response (via lymphocyte activation)
Oedema
Accumulation of interstitial fluid
Increase in venous pressure:
- E.g. Congestive heart failure leads to venous pooling which results in fluid accumulation in the lungs
Increase in interstitial pressure
- E.g. Lymph vessel blockage due to a parasitic infection results in gross oedema of the limbs (i.e. elephantiasis)
- Note – caused by poor lymph drainage rather than capillary dysfunction
Blood pressure
- The driving force to push blood through the circulation
- Pressure is related to resistance of the vessels
- Resistance (systemic)»_space; Resistance (pulmonary)
- Biggest pressure drop in arterioles
- Largest overall resistance in arterioles
Mean arterial pressure (MAP)
MAP = DP + 1/3 PP PP = SP-DP
Regulation of blood flow
- Vasoconstriction – smooth muscle cells contract & increase the resistance of the vessels
- Vasodilation – smooth muscle cells relax & decrease the resistance of the vessel
- Blood flow decreases with increased resistance & increases with increased pressure gradient
CO = HR x SV BP = CO X TPR
Determinants of arteriolar blood flow
Systemic pressure maintenance:
- Neural: Sympathetic tone autonomic nervous system (Adrenaline & Noradrenaline)
- Circulating hormones (constrict): Angiotensin II, endothelin, adrenaline
Tissue flow protection:
- Locally produced mediators (dilate): Nitric oxide (‘EDRF’), bradykinin, prostaglandins, histamine
- Locally produced metabolites (dilate): CO2, adenosine, H+ (decrease pH), K+, temp, osmolarity, low O2
Determinants of vessel blood flow – sympathetic NS activation
- Noradrenaline constricts blood vessels
- Adrenaline dilates blood vessels
Both act on smooth muscle cells
Baroreflex regulation of blood pressure
Act on baroreceptors which are located in the carotid sinus & aortic arch
