Module 3 Cardiovascular Flashcards
Contents of superior mediastinum:
Organs: Thymus, trachea, oesophagus, and ligamentum arteriosum.
Arteries: Aortic arch with branches-brachiocephalic trunk, left common carotid artery, left subclavian artery.
Veins and lymphatics: SVC, brachiocephalic veins, arch of azygos, thoracic duct. Nerves – Phrenic, vagus.
Contents of anterior mediastinum:
Sternopericardial ligaments, fat, some lymphatic vessels, lymph nodes and branches of the internal thoracic vessels, and the thymus (in the infants).
Contents of middle mediastinum:
Heart, pericardium, great vessels, trachea, bronchi, oesophagus, and lymph nodes.
Contents of posterior mediastinum:
Descending thoracic aorta, the azygos and the two hemiazygos veins, the vagus and splanchnic nerves, the oesophagus, the thoracic duct, and some lymph glands.
Name some mediastinal tumours
Anterior mediastinum: substernal thyroid goiters, lymphoma, thymoma, and teratoma.
Middle mediastinum: lymphadenopathy, metastatic disease from small cell carcinoma of lungs.
Posterior mediastinum: Neurogenic tumors.
Mediastinitis
inflammation of the tissues in the mediastinum, due to rupture of the organs
Pneumomediastinum
presence of air in the mediastinum, which might lead to pneumothorax, pneumoperitoneum, and pneumopericardium.
What can widened mediastinum indicate?
indicative of several pathologies: Aortic aneurysm or dissection or rupture, hilar lymphadenopathy, oesophageal rupture, cardiac tamponade, mediastinal mass, pericardial effusion.
Pericardial layers
Fibrous outer
parietal layer
serous lining
visceral layer (epicardium)
myocardium
endocardium
pericardial sac attachments
attached to the central tendon of the diaphragm, the sternum, the mediastinal pleurae, and the tunica adventitia (outer layer) of the great vessels (SVC & pulmonary vessels).
Innervation of the pericardium
Nerves supplying the pericardium arise from the vagus nerve [X], the sympathetic trunks, and the phrenic nerves. The phrenic nerve (C3-C5) is responsible for the somatic innervation of the pericardium, as well as providing motor and sensory innervation to the diaphragm.
Blood supply of the pericardium
The pericardium is supplied by branches from the internal thoracic, pericardiacophrenic, musculophrenic, and superior phrenic arteries, and the thoracic aorta. The veins from the pericardium enter the azygos system of veins and the internal thoracic and superior phrenic veins.
What anatomical feature is useful for surgeons in heart surgery
The transverse pericardial sinus separates the heart’s arterial outflow (aorta & pulmonary trunk) from its venous inflow (SVC & pulmonary veins).
Location: Posterior to ascending aorta & pulmonary trunk; anterior to the SVC; superior to left atrium.
Applied anatomy: The transverse pericardial sinus can be used to ligate the arteries of the heart during coronary artery bypass grafting.
Pericarditis
Pericarditis: It is an inflammatory condition of the pericardium. Common causes are viral and bacterial infections, systemic illnesses (e.g., chronic renal failure), and after myocardial infarction.
Pericardial effusion
Pericardial effusion: Usually, only a tiny amount of fluid is present between visceral and parietal layers of the serous pericardium. In certain situations, this space can be filled with excess fluid.
Cardiac tamponade
As fibrous pericardium is a relatively fixed structure that cannot expand easily, a rapid accumulation of fluid within pericardial sac may compress heart, resulting in biventricular failure.
Constrictive pericarditis
Abnormal thickening of the pericardial sac, which usually involves only the parietal pericardium, can compress the heart, impairing heart function and resulting in heart failure
Heart surfaces
The base of the heart is quadrilateral and directed posteriorly. It consists of the left atrium, a small portion of the right atrium, and the proximal parts of the great veins
The right margin is the small section of the right atrium that extends between the superior and inferior vena cavae. The left margin is formed by the left ventricle and left auricle. The superior margin is formed by both the atria and their auricles. The Inferior margin is marked by the right ventricle.
The anterior surface faces anteriorly and consists mostly of the right ventricle, with some of the right atrium on the right and some of the left ventricle on the left.
The heart in the anatomical position rests on the diaphragmatic surface, which consists of the left ventricle and a small portion of the right ventricle
What is the cardiac skeleton
The cardiac skeleton is a collection of dense, fibrous connective tissue in the form of four rings (anulus fibrosus) between the atria and the ventricles, which surround the two atrioventricular orifices, the aortic orifice and opening of the pulmonary trunk.
The fibrous skeleton of the heart separates the atria from the ventricles and gives attachment to the cusps of the atrio-ventricular valves (mitral and tricuspid) valves to the myocardium.
Describe the anatomy of the different AV valves in the heart
Right AV/tricuspid valve has three cusps: anterior, septal & posterior.
The left AV/bicuspid/mitral valve has two cusps: anterior/aortic and posterior/mural.
Backward prolapse of the cusps is prevented by the chordae tendineae that connect the papillary muscles of the ventricular wall to the AV valves, that cause tension to better hold the valve, and prevent backflow of the blood from the ventricles to the atria.
The papillary muscles & chordae tendineae together are known as subvalvular apparatus, that keeps the valves from prolapsing into the atria when they close. AV valves are formed by the flap-like cusps that are anchored to the ventricular wall by tendinous filaments.
What can cause heart tremors
Papillary muscles damage can lead to valve incompetence and cardiac murmurs.
Describe Aortic semilunar valves
left, posterior, right cusps with semilunar valves prevent backflow of blood from these arteries into the ventricles. Unlike the AV valves, these valves do not have chordae tendineae and are like the valves in the veins.
Right and left coronary arteries begin in the right and left aortic sinuses found in each cusp
Describe pulmonary semilunar valves
left, anterior, right cusps with semilunar valves prevent backflow of blood from these arteries into the ventricles. Unlike the AV valves, these valves do not have chordae tendineae and are like the valves in the veins.
How to auscultate the heart valves
Aortic - 2nd R ICS medial
Pulmonary - 2nd L ICS medial
Tricuspid - 4/5th L ICS medial
Mitral 5th L I CS mid clavicular line
Interior of the right atrium
Presence of R atrio-ventricular orifice.
Presence of crista terminalis.
Openings of SVC, IVC, coronary sinus.
Coronary sinus receives blood from the coronary veins, and it opens in between IVC and the right AV orifice.
Interatrial septum - a solid muscular wall that separates right and left atria.
Fossa ovalis in the septal wall with its prominent margin, limbus fossa ovalis.
Openings of the smallest cardiac veins
interior of the right ventricle
Presence of right atrio-ventricular orifice, guarded by tricuspid valve.
Presence of trabeculae carneae, papillary muscles, and the chordae tendineae in the right ventricle.
interior of left atrium and left ventricle
Presence of trabeculae carnae, anterior and posterior papillary muscles in LV.
Presence of the mitral valve guarding the left atrio-ventricular orifice.
Presence of the interatrial and IV septa.
What can occur at the Right auricular appendage
Site for thrombi - PE
Often excised in pulmonary bypass
Triangle of Koch
Landmark for AV node
Just above coronary sinus
sites of arrhythmia genesis
crista terminalis and atrial septum
What is the inferior vena caval opening used for?
sending catheters into
Right Coronary Artery anatomy and supplies
RCA arises from right aortic sinus; anastomoses with the left circumflex artery, a branch of LCA.
Branches: SA nodal branch supplies the SA node
Its right marginal branch supplies apex of heart.
A branch to AV node before giving off its final branch, the posterior interventricular branch.
RCA supplies the right atrium, majority of right ventricle, SA & AV nodes, interatrial septum, a portion of left atrium & left ventricle, postero inferior one third of interventricular septum.
Left Coronary artery anatomy
LCA arises from left aortic sinus, and branches into left anterior descending & left circumflex.
Being larger than RCA, the LCA supplies most of left atrium and left ventricle, most of the IV septum, the AV bundle and its branches.
What does right dominant coronary artery
The posterior descending branch arises from the RCA and supplies major portion of the diaphragmatic surface of the LV.
L Circumflex artery is relatively small
What does left dominant coronary artery mean?
The posterior descending branch arises from an enlarged circumflex branch
Clinical examples of pathology in the coronary arteries
Narrowing of coronary arteries is caused by atherosclerosis or arteriosclerosis. It results from plaques deposits of cholesterol, resulting in coronary artery disease or ischemic heart disease.
Stable angina is the chest pain on exertion that improves with rest. Unstable angina is chest pain that occurs at rest, feels more severe and last longer than stable angina.
A heart attack results from a sudden plaque rupture and formation of a thrombus that blocks blood flow to a portion of the heart leading to tissue necrosis and death (infarct).
CAD can also result in heart failure or arrhythmias. Heart failure is caused by chronic oxygen deprivation due to reduced blood flow. Arrhythmias are caused by inadequate blood supply to the heart that interferes with heart’s electric impulse.
Spontaneous coronary artery dissection is a rare condition, in which the wall of one of the coronary arteries tears, causing severe pain. Unlike CAD, it tends to occur in younger individuals.
Coronary venous routes
Great: apex - anterior IV sulcus - coronary sulcus - sinus
middle: apex - posterior interventricular sulcus - sinus
Small: Coronary sulcus - sinus
Posterior: posterior surface of LV - sinus or great cardiac vein
Cardiac conduction route
SA node - AV node - bundle of his - L and R bundle - purkinje fibres
Intrinsic HR?
100bpm
Cardiac innervation
The heart is autorhythmic – without any neural input the heart will still beat.
Stimulation of the parasympathetic system decreases the heart rate, reduces force of contraction, & constricts coronary arteries.
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Preganglionic parasympathetic fibers reach heart as cardiac branches from right and left vagus CNX.
Stimulation of the sympathetic system increases heart rate and increases the force of contraction.
Sympathetic fibers reach cardiac plexus through the cardiac nerves from the sympathetic trunk.
Preganglionic sympathetic fibers from the upper four or five segments of the thoracic spinal cord enter and move through the sympathetic trunk.
They synapse in the cervical and upper thoracic sympathetic ganglia, and postganglionic fibers proceed as bilateral branches from sympathetic trunk to the cardiac plexus.
Describe cardiac plexus anatomy
This plexus consists of a superficial part, inferior to the aortic arch and between it and the pulmonary trunk, and a deep part , between the aortic arch and the tracheal bifurcation. From the cardiac plexus, small branches that are mixed nerves containing both sympathetic and parasympathetic fibers supply the heart. These branches affect nodal tissue and other components of the conduction system, coronary blood vessels, and atrial and ventricular musculature.
From medial to lateral, list the main vessels
Common carotid artery, internal jugular vein, subclavian artery, subclavian vein
Five dilations appear during the growth of heart tube
Truncus arteriosus
Bulbus cordis
Primitive (left) ventricle
Primitive atrium
Left and right horns of sinus venosus
What do the components of the primitive heart tube become?
Sinus venosus horns: become the posterior walls of the true atria
Primitive atrium: forms the anterior walls and muscular parts of both atria (auricles)
Primitive ventricle: forms most of the left ventricle
Inferior end of the bulbus cordis (conus arteriosus) forms the right ventricle
Truncus arteriosus forms the ventricular outflow tracts (aorta and pulmonary trunk)
Folding of the primitive heart tube
Heart tube simultaneously elongates and begins to loop at end of week 3
Primitive atrium moves posteriorly & superiorly
Primitive ventricle moves to the left
Bulbus cordis (right ventricle) moves inferiorly, anteriorly and towards the right side
Folding is complete by end of week 4
Process of atria septation
Septation begins at the end of week 4 with a crescent-shaped outgrowth from the posterior wall – septum primum
Septum primum grows anteriorly and shrinks the opening between the left and right sides of the primitive atrium - the foramen (ostium) primum
Endocardial cushions develop around the periphery of the atrioventricular canal
Dorsal and ventral cushions fuse to form the septum intermedium (dividing the atrioventricular canal into right and left)
Septum primum fuses with the septum intermedium (closing the foramen primum)
Before the foramen primum closes, a new foramen opens near the superior edge of the septum primum due to cell death – foramen secundum
While septum primum is growing the septum secundum appears on ceiling of right atrium (next to the septum primum)
Grows posteroinferiorly and stops before reaching the septum intermedium
Leaves an opening near the floor of the right atrium – the foramen ovale
Septation of the ventricles
Heart undergoes remodelling to bring the future atria and ventricles into their correct positions
Ventricles align with their respective outflow tracts
Muscular interventricular septum forms at the end of week 4 and grows toward the endocardial cushion, leaving interventricular foramen
Membranous part of interventricular septum grows inferiorly from the endocardial cushion to close the foramen
Septation of the ventricles and outflow tract
During weeks 7 and 8 the truncus arteriosus undergoes a process of septation & division to convert it into the ascending aorta and a separate pulmonary trunk
Conotruncal ridges divide truncus arteriosus into two channels and fuse with interventricular septum
Process occurs helically – right ventricle connects to pulmonary trunk and left ventricle to aorta as a result of spiral fusion process
During this process, swellings within the truncus arteriosus give rise to the semilunar valves of the aorta and pulmonary trunk
Key Pharyngeal arch arteries
3rd pharyngeal arch arteries form common carotid and internal carotid arteries
4th pharyngeal arch arteries form right subclavian artery and part of aortic arch on the left
Left 6th arch artery forms ductus arteriosus (fetal shunt)
Right 6th arch artery degenerates to allow passage of right recurrent laryngeal nerve
What is Coarctation of the aorta
Congenital constriction of aorta
Surgical repair needed soon after birth if severe
Ductus arteriosus may still be patent
Most common occurrence is distal to the left subclavian artery, directly opposite the opening for the ductus arteriosus
Circulatory changes after birth
Loss of umbilical circulation causes the ductus venosus to degenerate – forms ligamentum venosum in adult
More blood enters pulmonary arteries
Blood returning from the lungs increases pressure in left atrium and septum primum is pushed against septum secundum to close foramen ovale – fossa ovalis in adult
Constriction of the ductus arteriosus - ligamentum arteriosum in adult
Atrial septal defects (ASDs)
Incomplete septation of atrium
E.g. ostium secundum defect – defect in middle of septum
Patent foramen ovale
Not a true septal defect but similar
Incompetence of fossa ovalis valve, may be probe-patent
~25% of the population
Reverse flow from left to right atrium
Non-cyanotic – may not be identified until adulthood
Ventricular septal defects (VSDs)
Incomplete septation of ventricles
Most common congenital cardiac abnormality in children
Commonly due to incomplete closure of the membranous part of the interventricular septum (80% of VSDs)
Reverse flow from left to right ventricle
Non-cyanotic, but if large may lead to pulmonary hypertension and increased risk of arrhythmias
Patent ductus arteriosus
Ductus arteriosus connects pulmonary trunk to aorta
Blood bypasses lungs in fetal circulation
Normally closes after birth due to reversed flow and withdrawal of placental prostaglandins
Failure to close = blood flow from aorta to pulmonary circulation
Non-cyanotic, but lead to pulmonary hypertension long-term
Persistent truncus arteriosus
Incomplete septation of truncus arteriosus
Aorta and pulmonary trunk fail to develop separately, remaining as one single vessel
Ventricular septal defect present
Cyanotic
Transposition of the great arteries
Aorta arising from the right ventricle (dextro-transposition)
Pulmonary trunk arising from the left ventricle
Pulmonary and systemic circulations are not continuous, therefore oxygenated blood not pumped around body
Cyanotic
Dependent on ductus arteriosus to deliver oxygenated blood to the aorta – can be encouraged using prostaglandin E1
Tetralogy of Fallot
Four defining features:
Pulmonary valve stenosis
Ventricular septal defect
Over-riding aorta
Right ventricular hypertrophy
(also cyanosis – ‘tet spells’)
Is cardiac muscle striated?
Cardiac Muscle is STRIATED
Contraction of Striated Muscle:
The shortening of striated muscle is brought about by the thick filaments pulling the thin filaments towards the centre of the sarcomere, thereby making the H zone and I bands shorter
What is the contraction of cardiac muscle dependent on?
Contraction is calcium and ATP dependent
Describe cardio myocytes
Small cells with a single nucleus (usually)
T-tubule and sarcoplasmic recticulum systems less well developed than skeletal muscle (IC Ca+ increase (from SR release) facilitated by EC Ca+ entering through Ca+ channels)
Mitochondria take up 30-40% of cell volume (much higher than any skeletal muscle cells) as continued contraction required so no capacity for oxygen debt
Branched cells linked together by intercalated disks
Acts as a functional (but not structural) syncytium
What are intercaleted discs in cardiac muscle
Act as electrically boundaries between cardiac muscle cells with ‘leaky’ gap junctions
What are connexons?
Adjacent plasma membranes of neighbouring muscle cells communicate rapidly through transmembrane protein channels called connexons
These are charged aqueous pores which allow small ions to move freely from one cell to another changing the electrical activity of the neighbouring cell
Action potential in SA node vs other cardiac cells
SA NODE – Needed as trigger and not to generate contraction force
OTHER CELLS – Na+ initially then Ca+ induced plateau phase to maintain (200ms) depolarisation and contraction
Autonomic control of the heart
Higher centres > cardiac accelerator nerves (s) > NA on B1
> Vagus nerves (ps) > ACh on musc
The heart contains 2 types of specialized cardiac muscle cells:
- Contractile cells or Cardiomyocytes (99%) – Mechanical work
2. Autorhythmic or pacemaker cells – Initiate and conduct action potentials for contractile cells
Sinoatrial (SA) node
Small, specialized region in the right atrial wall near the opening of the superior vena cava
Atrioventricular (AV) node:
Small bundle of specialized cardiac muscle cells located at the base of the right atrium, near the septum, just above the atria-ventricular junction
Bundle of His (AV bundle):
Tract of specialized cells that originates at the AV node and enters the interventricular septum. At the septum, it divides to form the right and left bundle branches that travel down the septum, curve around the tip of the ventricles, and travel back toward the atria along the outer walls
Purkinje fibers
Small, terminal fibers that extend from the Bundle of His and spread throughout the ventricular myocardium, like twigs of a tree branch
Two areas of myocardium
SubENDOcardial section
Fibres run away from midwall towards the endocardial surface
SubEPIcardial section
Fibres run away from midwall towards the epicardial surface
How does an ECG relate to the areas of the myocardium
ECG = ENDO - EPI
ENDO cells are activated slightly quicker:
Phases of the cardiac cycle:
Atrial systole, Isovolumetric Contraction, Rapid Ejection, Reduced Ejection, Isovolumetric Relaxation, Rapid Ventricular Filling, Diastasis
Atrial systole:
Last phase of diastole
ECG P to R-wave.
Depolarisation of the atria leads to atrial contraction (see the ‘a’ wave on the atrial pressure curve).
A tiny amount of ‘topping off’ completely fills the ventricle.
Affected by AF (atrial stasis)
Rarely, a 4th heart sound (atrial “jet” or LV stiffness).
Isovolumetric Contraction:
First phase of systole.
Begins at the peak of the R-wave of the ECG.
No real change in the volume of the ventricles during this phase.
First heart sound (‘lub’) caused by closing of the A-V valves and associated blood turbulence when ventricular pressure exceeds atrial pressure.
Rapid Ejection:
During ST segment.
When ventricular pressure exceeds that in the aorta or the pulmonary artery, semilunar valves open and rapid ejection (2/3) from the ventricles starts.
‘c’ wave in the atrial pressure curve is caused by slight (due to papillary muscles) distension of the A-V valves into the atria (normally not measurable).
Reduced Ejection:
Final phase of systole.
Coincides with the T-wave of the ECG (ventricular repolarisation).
Blood flow out of the ventricles continues, but happens more slowly (reduced ejection).
Eventually, pressure in the ventricle falls below that in the arteries. Semilunar valves close.
Isovolumetric Relaxation
First phase of diastole.
Atria have been filling with blood (atop the closed A-V valves) and atrial pressure has been rising gradually.
Blood flow out of the ventricles stops (hopefully the ventricles are sufficiently empty).
The 2nd heart sound (‘dup’) occurs when the semilunar valves close.
Rapid Ventricular Filling:
When ventricular pressure falls below atrial pressure, the A-V valves open.
This allows blood to flow from the atria into the ventricles.
A third heart sound may be heard in children, who have thinner chest walls, but in adults this is usually a clear sign of cardiac problems, such as congestive heart failure (atrial press. too high
Diastasis
Filling of the ventricles continues more slowly, as atrial and ventricular pressures rise.
This continues until the ventricles are almost full (at 120mL), when the whole thing starts over again!
Mitral stenosis
Incomplete opening of the mitral (bicuspid, left AV) valve can lead to backup of blood into the left atrium and inadequate filling of the ventricle.
Aortic stenosis
Incomplete opening of the aortic valve – can lead to inadequate ventricular emptying.
Mitral regurgitation
Either the mitral valve closes, but cannot fully prevent backflow of blood into the left atrium during ventricular contraction, or it does not close properly.
Children gross motor skills milestones
Social smile 4-6 weeks
Holds head up when sat 3 months
Rolling over 5 months
Sitting without support 6-7 months
Crawling 8-9 months
Cruises 10 months
Fine motor skills children milestones
Holds small objects 3-4 months
Reaches for toys 5 months
Transfers from one hand to other 6-7 months
Grips with fingers 8-9 months
Pincer grip 10 months
Children speech and language milestones
Cooing 3 months
Dada-Mama 10 months
2-3 words 12 months
Name 3 body parts 18 months
2-3 word sentences 2 years
Full sentences 2.5 years
Children receptive language milestones
By 1 year
Pointing
Understands simple commands
By 18 months
Simple two step commands
By 2-3 years
Understands up to 300-900 words
Understands complex commands
Social skills in children
Social smile 4-6 weeks
Finger feeds 6-8 months
Peek-a-boo 6-9 monts
Waves bye-bye 10 months
Drinks from a cup 12 months
Helps undress 18 months
Warning signs to spot in child development
No smile by 8 weeks
No eye contact by 3 months
Not reaching for objects by 5 months
Not sitting at 9 months
Not walking at 18 months
No speech at 18 months
No 2-3 word sentences at 2½
Order for assessing children development
primitive reflexes, gross motor, vision, fine motor, hearing, speech and language.
What is the small blip in arterial pressure called and what causes it
There is a small ‘blip’ in the pressure profile when the aortic valve closes; this is known as the ‘incisure’ or the ‘dichrotic notch’
How is mean arterial pressure calculated?
MAP = DBP + ⅓PP
=DBP + ⅓ (SBP-DBP)
The Milieu Interieur:
homeostasis
What percentage of blood is found in venous circulation?
afferent vessels act as conduits and reservoirs. About 70% of blood volume is in the venous circulation (capacitance)
Four Parameters affecting arterial blood pressure:
Circulatory volume (and hence stroke volume)
Force of ventricular contraction
Elasticity of arteries
Peripheral resistance
Describe the factors affecting resistance to steady, streamlined flow through a rigid cylindrical tube
R = 8ηL/πr4
resistance R, viscosity η, length L, radius r
Baroreceptor reflex
Pressure receptors (baroreceptors) exist in the wall of the arch of the aorta and in the carotid sinus
These specialised nerve endings send information to the CNS about MAP
If MAP decreases, the receptors decrease input which results in activation of the SNS and inactivation of the PNS
The overall effect is to increase MAP by increasing HR and SV, and increasing TPR by constricting blood vessels
Aldosterone
Released from the adrenal cortex; increases salt and water retention by the kidneys
Antidiuretic hormone (vasopressin)
Released from the posterior pituitary; constricts blood vessels and increases water retention by the kidneys
Atrial natriuretic peptide
Released from the atria when stretched; increases salt and water excretion by the kidneys
Cortisol
Released from the adrenal cortex; increases the actions of the sympathetic nervous system on its target cells
Erythropoietin
released from the kidney; increases production of erythrocytes (increasing blood viscosity)
Describe how angiotensin II is formed (RAAS)
Renin is released from cells near the glomeruli in the kidney in response to lowered kidney perfusion pressures caused by (amongst other things) lowered BP
Renin acts on a protein called angiotensinogen (gen– erates angiotensin) and cleaves this precursor at specific sites to form angiotensin I (inactive)
Angiotensin I is converted to angiotensin II by the action of angiotensin converting enzyme (ACE; lung capillaries and endothelial cells of blood vessels). Angiotensin II is the active form of the peptide
Physiological Actions of Angiotensin II:
Angiotensin II constricts blood vessels; hence it can increase TPR and raise MAP
Angiotensin II also stimulates thirst and promotes the release of ADH; increasing circulating blood volume, CO and MAP
Angiotensin II also stimulates the release of aldosterone from the adrenal cortex; increasing circulating blood volume, CO and MAP by this route also (salt & water retention)
How does atrial stretch regulate MAP
When venous return is raised (e.g. in the case of increased circulatory volume):
Atrial myocytes release atrial natriuretic peptide (ANP), which is a vasodilator and:
Promotes Na+ excretion – H2O follows
Inhibits secretion of ADH (antidiuretic
hormone or “vasopressin”)
Cardiac accelerator nerves send signals to:
c. Increase heart rate and ventricular contractility
Sympathetic vasomotor nerves cause … in BP responses
vasoconstriction
Layers of blood vessel
Lumen
Tunica intima; Endothelial cells & basement membrane, Supporting connective tissue
Internal elastic lamina
Tunica media; Smooth muscle and elastin
External elastic lamina
Tunica adventitia; Supporting connective tissue (fibres with some vessels & nerves)
Tunica media in arteries and veins
Large tunica media in arteries for strength
Role of arterioles in resistance & blood pressure
Reduced blood flow leads to improper perfusion of tissues and lack of nutrients (ischaemia) which can lead to cell death
Too much flow damages delicate tissue structure.
Arterioles control this by varying their diameter
What are metarterioles?
pre-capillary sphincters
Capillaries features
Thin walled vessels to facilitate exchange of nutrients with the tissue
Endothelial cells (1 cell thick) & basement membrane & some collagen fibrils
Occasional pericyte – contractile cells
Diameter is approx. 5-8 µm (RBC is 7 µm)
Endothelial cells: joined by tight junctions and contain many vesicles
Transport across endothelial cells
Diffusion (gases and ions)
Transcytosis via pinocytotic vesicles (proteins and lipids)
Via the intercellular space (cells)
Where do you find the following capillaries: Continuous
Fenestrated
Sinusoidal
Continuous - most common, everywhere
Fenestrated - in tissues with high fluid transport e.g. intestinal villi
Sinusoidal - liver, spleen, lymphoid, bone marrow
What causes varicose veins
Incorrect functioning of valves leads to the formation of varicose veins
How does the venous system help to blood flow against gravity
Valves and the muscle pump synchronously
Types of blood flow
Endothelium is a smooth, non-stick surface which facilitates laminar flow
Turbulent flow occurs where vessels branch and when blood pressure is raised
Thrombus
Solid mass of blood constituents formed within the vascular system in life
Atherosclerosis
fatty deposits in the tunica intima harden the walls and narrow the lumen - arteries
Arteriolosclerosis
wall thickening and hardening affecting small arteries and arterioles
Definition of hypertension
That level of BP above which treatment does more good than harm
Hypertension >140/>90
Hypertension classifications
Hypertension is either:
Primary (Idiopathic) or
Secondary (to a different disease)
And either:
Benign = stable elevation in BP
Malignant = dramatic rise over a short period of time
Why does Blood pressure drop upon standing?
When standing from a sitting or lying position, gravity causes blood to collect in capacitance vessels below the level of the heart.
Blood pressure drops because there’s less blood flowing back to the heart.
When detected by baroreceptors, the CNS promotes an increase in MAP by increasing HR and SV, and TPR by constricting blood vessels
Primary hypertension pathogenesis
Pathogenesis unknown but likely factors are:
Kidneys role in regulation of ECF volume through Na and water regulation
SNS hyper-reactivity (vessel wall tone and peripheral resistance)
RAAS activity (Na homeostasis and vasoconstriction)
Intracellular Na and Ca levels
How can kidney issues lead to secondary hypertension?
disease (parenchymal or vascular)
Renal artery stenosis → renal failure
Atherosclerotic disease of renal blood vessels causes reduced renal blood flow, RAAS activation, vasoconstriction, Na and H2O retention, hypertension
Acute kidney disorders:
Majority cause decreased urine formation and increased retention of Na and H2O = hypertension
Chronic kidney disorders: Hypertension is common
Non kidney causes of secondary hypertension
Endocrine disorders- hyperthyroidism, Cushings, adrenal hyperplasia, hyperaldosteronism
Tumours: pheochromocytoma, adrenal adenocarcinoma
Cardiovascular disorders e.g. coarctation of aorta
Drugs: cocaine, amphetamines, EPO, liquorice, sympathomimetic drugs e.g. decongestants, oral contraceptives
Often can be cured by surgery or treatment
Complications of Hypertension in the heart
Left ventricular hypertrophy
Remodelling of heart due to increased pressure/volume
Hypertrophy - Increase in cell size due to increase in content of subcellular components
Coronary heart disease
Atherosclerosis in arteries supplying blood to heart muscle
Angina
Pain due to reduced blood flow to the heart muscles
Heart failure
Heart weakens/stiffens and cannot pump effectively
Sclerosis
thickening and hardening
Arteriosclerosis
thickening and hardening of vessel walls
Arteriolosclerosis
thickening and hardening of arteriole walls
Atherosclerosis
thickening and hardening of artery walls due to an atheroma
Four recognisable stages of atheroma
Fatty streak (barely visible)
Lipid plaque (smooth, yellow, raised)
FIBROLIPID plaque (hard, white)
Complicated ATHEROMA
Stages of atheroma
Damage to endothelium > accumulation of oxidised LDL in macrophages > disruption of elastic lamina, collagen deposition, free lipid accumulation > fibrolipid plaque, fibrous cap, necrotic core
Complications of atheroma
Expansion of intima -> reduction of size of lumen -> reduced blood flow & hence oxygenation of tissue: ischaemia
Coronary arteries -> angina
Leg arteries -> intermittent claudication
Mesenteric arteries -> ischaemic colitis
Cerebral and vertebral arteries -> cerebral ischaemic events
Severe ischaemia from partially occluded vessels can cause infarction
Risk factors for atheroma
A Arterial hypertension
T Tobacco
H Hereditary (familial hypercholesterolaemia)
E Endocrine (diabetes, hypothyroidism, postmenopausal oestrogen deficiency)
R Reduced physical activity
O Obesity
M Male gender
A Age
Aortic dissection
Blood enters the media causing a split in the vessel wall (unusual in atherosclerotic arteries)
Can rupture into adventitia causing haemorrhage into surrounding area or pericardium
Aneurysm
Abnormal, permanent focal dilatation of an artery.
Enlarging intimal atheroma plaque leads to atrophy of media
Muscle and elastic fibres in media replaced by collagen
Collagen strong but neither contractile nor capable of elastic recoil i.e. loss of elasticity
With each systolic pulse, wall of artery stretches and thins, PARTICULARLY WHEN BLOOD PRESSURE IS ELEVATED
Cerebrovascular disease due to hypertension
Stroke or TIA result of haemorrhage or infarction due to atherosclerosis, thrombus, aneurysm etc.
Hypertension leads to small vessel damage
This results in:
Rupture: intracerebral haemorrhage due to microaneurysm (Charcot-Bouchard aneurysm)
Microinfarcts due to thrombo-embolic events: hypertensive lacunae (common). Can cause vascular dementia due to loss of white matter
Hypertensive retinopathy
retinal arterioles
Primary benign hypertension:
Silver wiring
Arteriovenous nipping
Malignant hypertension
Flame haemorrhages
Cotton wool spots
Papilledema
Order of hypertension drugs to give
ACE (<55yrs) or Ca blockers
A+ C
A + C + diuretic
+ further diuretic, a blocker, B blocker
What is a lipoprotein?
Protein-lipid complexes
Hydrophobic lipids (triglycerides, cholesterol) in core
Hydrophilic lipids on surface
What are triglycerides?
Used for Energy Storage
More caloric value than carbohydrates
Typically 20% of body weight
Made of three linked fatty acids
Note these are very hydrophobic
Thus separate out of plasma samples
What is cholesterol?
All carbons in cholesterol are derived from acetate
What does cholesterol do?
Lipid constituent of cell membranes
(highest concentration in cytoplasmic membranes)
Precursor of steroid hormones
Precursor of vitamin D (cholecalciferol)
Precursor of bile acids
Main components of Chylomicron, LDL and HDL
CM, LDL: triglycerides
HDL: cholesteryl ester
What do lipoproteins do? Take what from where to where
Chylomicron
TG - gut > tissues
VLDL
TG, Chol - liver > tissues
HDL
Chol - tissue > liver
LDL
Chol - remaining in circulation
Examples of common genetic defects affecting lipoprotein transport
LDL receptor deficiency (1:500 autosomal dominant) - Can’t take up LDL
Over production of apoB100 (1:50 autosomal dominant) - More VLDL produced= more LDL made
Mutant form of apoE (1:5000 autosomal recessive) - Can’t take up remnants (IDL, etc) more LDL
Dyslipidaemia
A disorder of lipoprotein metabolism, including lipoprotein overproduction or deficiency.
Elevation of the total cholesterol, the “bad” low-density lipoprotein (LDL) cholesterol and the triglyceride concentrations, and a decrease in the “good” high-density lipoprotein (HDL) cholesterol concentration in the blood.
Desirable lipid profile
Total C: <5.2
LDL: <2.6
HDL: >1.6
TG: <1.7
allostatic load
amount of wear and tear throughout a persons life
cumulative inequality
long term effect of living under poor conditions
ECG Deflections
Depolarisation moving towards a unipolar electrode, or + pole of bipolar lead = positive deflection
Full depolarisation is represented on an ECG during the:
ST segment
ECG electrode placement
V1 – 4th intercostal space and sternum (R)
V2 – 4th intercostal space and sternum (L)
V3 – Midway between V2 and V4
V4 – 5th intercostal space and mid clavicle (L)
V5 – 5th intercostal space and axilla beginning
V6 – 5th intercostal space and mid axilla
R arm, L arm, L leg
R leg - neutral
ECG heart regions
aVL -Upper left side of heart
Lead I -Travels toward aVL creating a 2nd high lateral head
aVF - Inferior wall of heart
Lead II - Travels toward aVR to become 2nd inferior lead
Lead III - Travels toward aVF to become 3rd inferior lead
V2,3,4 - Anterior face of the heart
V1 - Changes in V1 & V2 only = “septal leads”
V5 & V6 - Left side of the heart – “lateral leads”
ECG - P wave
Depolarisation of atria
Right atrial activation begins first
Relatively little muscle
Small amplitude
P - R Interval
Time for conduction through AV node; Time from onset of atrial depolarisation to onset of ventricular depolarisation
Measured from start of P wave to 1st deflection of QRS complex (irrespective of whether the QRS complex begins with a Q wave or an R wave)
Duration 0.12 – 0.20 s (120 – 200 ms)
QRS Complex
Ventricular Depolarisation
Large muscle mass of LV results in
QRS predominantly representing LV
QRS Duration: < 120 ms (0.12 s)
R wave height variable
S wave depth < 30 mm
Q Waves
Normal Q waves can be found in leads facing the left ventricle (I, II, aVL, V5, V6 )
Occasionally occur in lead III
< 2 mm in depth (two small squares)
< 40 ms in duration (one small square)
ST Segment
ST Segment: J Point to start of T Wave
End of ventricular depolarisation to beginning of repolarisation. Muscle is depolarised and is contracting - isoelectric ≠ inactive!
Usually level ± 1 mm from baseline - may slope slightly upwards
QT interval
Total time for depolarisation
& repolarisation of the ventricles
T & U waves
T Wave
Ventricular repolarisation
Asymmetrical
Rarely exceeds 10 mm
U Wave
Small deflection after T Wave
Many ECGs have no discernable U Wave
The ECG trace: calibration measurements
1 square = 0.2 seconds
2 square = 10mm
Normal amplitude is 10 mm per millivolt
Normal speed is 25 mm per second
Three predisposing situations to thrombus formation
changes in the internal surface of the vessel
changes in the pattern of blood flow
changes in the blood constituents
Platelet activation factors
ADP (released by ruptured endothelial cells / erythrocytes)
Platelet activating factor (released from exposed vessel wall)
Collagen (vessel ECM)
Epinephrine (trauma)
Thrombin (a clotting factor)
Immune complexes (infection)
High physical shear force (force applied by blood flow)
von Willebrand Factor (vWF)
von Willebrand Factor (vWF) forms bridge between:
platelet GpIb and exposed subendothelial collagen
GpIIb/IIIa expressed by other platelets forming aggregates
Vascular defects - clotting
Reduced production of collagen (defective clotting)
Vitamin C deficiency
Corticosteroid excess
Genetic defects in collagen production (Ehlers-Danlos syndrome)
Nitric oxide, nitrates:
increased production of NO (increased vasodilation)
Platelet defects
Genetic defects in:
platelet GPIb-IX (Bernard-Soulier syndrome)
platelet GPIIb-IIIa (Glanzmann’s thrombasthaenia)
Also, conditions impairing bone marrow function
Platelet activation pathway
Adhesion > conformational change > release vasoconstrictors and coag factors > further recruitment = haemostatic plug
Intrinsic coagulation cascade pathway
12 > 11 > 9 > 8 > 10
extrinsic coagulation cascade pathway
7 > 10
Common coagulation cascade pathway
10 > 10a + 5 > Pro -> thombin > fibrinogen -> fibrin
coagulation cascade pathway positive feedback
Thrombin exerts positive feedback on common and intrinsic pathways as well as fibrin cross-linking
Creating an amplification loop – once started, rapid chain reaction
coagulation cascade pathway negative feedback
Thrombin binding thrombomodulin -> activates Protein C, which inhibits factor VIIIa and Va
Coagulation factor post-translational modification in hepatocytes
Factors IX, X, VII, II and Protein C, protein S require carboxylation by gamma glutamyl carboxylase
How to test for clotting factor defects?
aPTT
Activated Partial thromboplastin time
Tests intrinsic pathway
PT
Prothrombin time
Tests extrinsic pathway
Genes affecting clotting factors
Common mutations
Factor V gene
Prothrombin gene
Rare mutations
Serpin Family C Member 1 - Antithrombin deficiency
Protein C, Inactivator Of Coagulation Factors Va And VIIIa - Protein C deficiency
Very rare (hereditary or acquired)
Congenital dysfibrinogenaemia
Increased levels of:
factor VIII
factor IX
factor XI
fibrinogen
Genes affecting fibrinolysis
a2-antiplasmin (another plasmin inhibitor)
PAI-1 (plasminogen activator inhibitor type 1)
Describe fibrinolysis
Plasminogen binds lysine on fibrin strand
Tissues plasminogen activator converts plasminogen to plasmin (inhibitor of this: plasminogen activator inhibitor I, II)
Plasmin breaks down plasmin (inhibitor of this: a2-anti-plasmin and a2-macroglobulin)
Systematic approach to reading ECGs
Name – correct patient and ECG?
Is there any electrical activity?
What is the ventricular (QRS) rate/ heart rate?
Is the QRS rhythm regular or irregular?
What is the axis of the heart?
Is the QRS duration normal or prolonged?
Is atrial activity present?
How is the atrial activity related to the ventricular activity?
Is the ST segment raised or depressed in specific leads?
Are there Q waves present in specific leads?
Sinus Bradycardia
Normal sinus rhythm- slowed down, Normal conduction
R-R intervals constant and regular
All waveforms present and one P-wave to each QRS complex
The rate is <60 bpm, but not usually <40 bpm
Patients are asymptomatic and no treatment is required
Often caused by beta-blockers/ calcium channel blockers
May also be seen in athletes and occur during sleep
Sinus Tachycardia
Normal sinus rhythm- faster than 100 bpm, Normal conduction
R-R intervals constant and regular
All waveforms present and one P-wave to each QRS complex
The rate is >100 bpm, but not usually >130 bpm at rest
Patients are normally asymptomatic
Often occurs in response to stress/ exercise
May be caused by hypovolaemia/ underlying medical conditions
Two types of Tachycardia
Supraventricular in which the pacemaker site is above the AV node
Ventricular Tachycardia (also called wide complex tachycardia’s) in which the pacemaker lies below the AV node
Ventricular Tachycardia
Ventricular Tachycardia (also called wide complex tachycardia’s)
tachycardia’s in which the pacemaker lies below the AV node
QRS width is prolonged (over 0.12 seconds or 3 small boxes)
Supraventricular tachycardia
Supraventricular in which the pacemaker site is above the AV node
QRS width is normal (under 0.12 seconds or 3 small boxes)
Paroxysmal supraventricular tachycardia (comes and goes)
Supraventricular tachycardia (sustained)
Atrial flutter (a characteristic type of sustained SVT)
Sinus Arrhythmia
Regularly irregular” variation on sinus rhythm, Normal conduction
P-P interval varies by more than 10%
Can be naturally occurring or due to heart damage
Respiratory – where the P-P interval lengthens with expiration and shortens with inspiration
Non-respiratory sometimes seems in association with complete Heart Block/ heart disease
Atrial Fibrillation
“Irregularly irregular” rhythm
No P waves, Absence of isoelectric baseline
Variable AV conduction – untreated ventricular response is usually rapid
May cause no symptoms but is often associated with palpitations, fainting or chest pain
Often becomes persistent/permanent (versus paroxysmal, or pAF)
Usually associated with COPD, CHF or other heart disorders
Atrial Flutter
Saw-tooth pattern
Atrial rate 300bpm
Seen with a variable ventriculat rate. E.g. Flutter with 2:1 block with give a HR of 150bpm
Premature ventricular contractions
ventricle contracts on its own, without receiving a signal from the SA node. These are classified as follows:
1) UNIFOCALoriginating from the same site in the ventricle – therefore all PVC’s look exactly alike
2) MULTIFOCAL
originating from different sites in the ventricle - such that the PVC’s have different morphologies
3) PVC labels: BIGEMINY - one normal beat alternating with a PVC; TRIGEMINY - two normal beats followed by a PVC etc.
Junctional Beats
lack of a P-wave in the junctional escape beat
This signifies a lack of atrial depolarization associated with this beat
This beat originated at or just above the AV node because the QRS width is normal but there is no P-wave
Premature atrial contactions
when a pacemaker in the atria other than the SA node initiates an impulse
This results in 2 possible phenomenon:
A QRS complex is produced by the PAC
A QRS complex is not produced by the PAC
In either case there is usually some pause in the rhythm following the PAC as the ventricle is in its refractory phase when the ‘extra’ P-wave is created so cannot produce a QRS complex
Susceptibility to Ventricular Arrhythmias
Acute coronary syndromes and LV ischaemia
Plasma K+ levels
LV dysfunction (heart failure) and LVH predispose to ectopic activity
Prolonged QT interval (>500 msecs)
QTc duration Pro-arrhythmic effects of drugs
Genetic predisposition – ‘channelopathies’
1st Degree Heart (AV) Block
P-R Interval longer than 0.20 seconds (constantly)
Most common conduction disturbance (7%)
May be found in athletes
Usually asymptomatic
Does not normally require treatment if asymptomatic, esp. in young
May want to check U&E’s if metabolic disturbance suspected
Increases risk of AF, pacemaker use and all-cause mortality
2nd Degree Heart (AV) Block - Mobitz Type I (Wenckeback)
P-R Interval is progressively longer until one P wave is blocked
Cycle begins again after the blocked P wave
Occurs in the AV node, above the bundle of His
2nd Degree Heart (AV) Block - Mobitz Type II
P-R Interval is constant
May see a fixed ratio but not always e.g. 2:1 (2 P-waves for every QRS), 3:1, 4:1 block
Some P waves are not conducted to the ventricles
Occurs in below the bundle of His
More serious than Mobitz I
Often leads to 3rd degree (complete) heart block
External pacing may be required depending on the clinical context
3rd Degree Heart (AV) Block - Complete:
All impulses from the atria are blocked by the AV node
Heart rate
40-60 bpm if escape rhythm is junctional (AV node)
20-40 bpm if escape rhythm is ventricular
Requires subsidiary pacemakers in ventricles to act
PR interval is random
No relationship between P wave and QRS complex
External pacing is common treatment
Channels involved in ventricular action potentials
Upstroke: Voltage gated Sodium channels
Plateau: L type calcium channels
Repolarisation: Delayed rectifier potassium channels
Channels involved in SA Node action potential
Pacemaker : HCN, GIRK
Upstroke: T-type calcium channels
Repolarisation: Delayed rectifier potassium channels
Classification of anti-arrhythmic drugs
Class I Inhibition of voltage-gated sodium channels
Class II Beta adrenergic receptor antagonists
Class III Amiodarone and similar drugs
Class IV Calcium channel blockers (cardiac selective)
Unclassified
(sometimes called class V) Adenosine, digoxin.
Subclasses of sodium channel blockers
Class IA e.g. disopyramide - slows rate of depolarization
Class IB e.g. lidocaine - fast association and dissociation prevents premature beat
- blocks when cells are depolarised.
Class IC e.g. flecainide, propafenone - slows rate of depolarization
Expected cardiac output athletes vs non athletes
Untrained = 70 bpm x 71 ml = 5000 ml
Trained = 50 bpm x 100 ml = 5000 ml (resting bradycardia
Four factors that determine SV:
The volume of venous blood returned to the heart (pre-load)
Ventricular distensibility (stiffness)
Ventricular contractility (inotropy)
Aortic or pulmonary artery pressure (afterload)
Frank-Starling Mechanism
an increased volume of blood enters the ventricle (preload; EDV), causing it to stretch, and consequently it contracts with more force
Due to activity of:
The muscle pump:
Respiratory pump: chest pressure decreases
on inspiration and abdominal increases; pushes blood into thorax
Venoconstriction: reflex sympathetic actions
Length-tension relationship of cardiac muscle
Increases in length only effective up to a certain point…Lo
Coronary Blood Flow during cardiac cycle
Three-quarters of left coronary blood flow occurs during diastole
Because during systole the blood vessels within the myocardium are compressed
How is coronary blood flow increased during exercise?
Coronary resistance vessels (arterioles) are surrounded by cardiac muscle cells
Exposed to chemicals released from the cardiac myocytes on activity (akin to ‘autoregulation’)
Adenosine, vasodilatory prostaglandins, H+, CO2, decreased O2 and nitric oxide (NO) all play an important role in coronary vasodilation
Smaller arterioles also have β-adrenoceptors that mediate vasodilation in response to sympathetic activation (e.g. release of NE/E)
Relationship Between Exercise Workload and HR
When workload is constant, HR increases rapidly until it reaches a plateau (i.e., steady state)
For each increase in workload, HR will increase to a new steady-state value in 2-3 minutes
Exercise training decreases steady-state heart rate for a given submaximal workload
Continued increase in heart rate during exercise due to:
Temperature increases (prolonged exercise)
Feedback from proprioceptors (e.g. muscle spindle)
Accumulation of metabolites or changes in partial pressures of gases (e.g. chemoreceptors)
- Increased supply of catecholamines
- Further sympathetic output to SA node/ ventricles
Exercise and Stoke Volume relationship
SV, like HR, also increases with increasing work rate
Unlike HR, SV usually plateaus at ~40-60% of VO2max
Not so in trained athletes who have lower RHR due to increased vagal tone and dramatically increased LV capacity
How does Blood “know” Where to Go during exercise?
Increased muscle flow is offset by centrally mediated generalized sympathetic arteriolar constriction
circulating E/ “spillover” of NE causes
- arteriolar constriction in most tissues
(i.e. those expressing α receptors; e.g. in viscera)
- arteriolar dilation in some tissues
(i.e. those expressing β receptors; e.g. in skeletal muscle)
Mechanism behind afterload reduction
Decreased total peripheral resistance (TPR) (afterload) is due to increased vasodilatation (active hyperaemia) in arterioles and capillaries supplying active muscles
What Purpose does Increased Blood Flow Serve?
Delivery of fuel substrates and O2 (and removal of waste!) Increased arterio-venous oxygen difference with increased work intensity: (Fick Equation: VO2 = Q x a-v O2 difference)
Active hyperaemia
the increase in local blood flow that occurs in response to exercise (or other reasons of increased metabolic demand). Can be mediated by neural, hormonal, autocrine and metabolic factors.
Autoregulation of blood flow
regulation of local blood flow over a range of perfusion pressures, independent of neuronal and hormonal influences (e.g. in heart, kidney, brain).
Reactive hyperaemia
the increase in local blood flow that occurs following occlusion of the blood supply to a tissue (e.g. during coronary vasospasm/occlusion cuffs etc). Occlusion leads to build-up of the by-products of cellular respiration and vasodilatory chemicals. A hyperaemic response is seen when blood supply is restored.
Describe the location of the main body water compartments
Describe the relative contribution that various body water compartments make to total body water
60% body weight
2/3 ICF 1/3 ECF
80% interstitial 20% plasma
Describe the location of the main body water compartments
Describe the relative contribution that various body water compartments make to total body water
60% body weight
2/3 ICF 1/3 ECF
80% interstitial fluid / 20% plasma
Body Water Electrolytes in and out of cell
Higher sodium in the extracellular fluids
Higher potassium in the intracellular fluid
Higher chloride in the extracellular fluids, and
Higher organic phosphate in the intracellular fluid
Starling Forces
Starling Forces determine how much fluid leaves the plasma and enters the interstitial fluid
BULK FLOW
Passive movement of a large number of ions, molecules or particles in a fluid moving in the same direction down a pressure gradient
Net Filtration Pressure
(capillary hydrostatic pressure + interstitial colloidal pressure)
minus
(blood colloidal pressure + interstitial hydrostatic pressure)
The Balance of these forces is Net Filtration Pressure
Arterial end: NFP = (35 + 1) – (26 + 0) = 10 mmHg out
Venous end: NFP = (16 + 1) – (26 + 0) = 9 mmHg in
Resulting Net Filtration Force = 1 mmHg out
capillary filtration coefficient
gives an indication of the permeability and surface area of the capillaries
OEDEMA
When net fluid movement exceeds lymphatic drainage
EXUDATE
high protein, filters from circulatory system to areas of inflammation
TRANSUDATE
low protein, caused by disturbance of pressures
oedema in In pleural cavity
hydrothorax
oedema In peritoneal cavity
ascites
Localised oedema
Influenced by gravity
‘Dependent’ e.g. congestive heart failure
Diffuse oedema
Severe/ ‘non-dependent’ e.g. renal dysfunction
Extracellular oedema
Lymphatic failure
Obstruction e.g. Cancer; Surgery; Filiaria infection
Can be severe
Abnormal fluid leakage across capillary wall
Many causes e.g. infection,
tissue injury, allergy, heart failure
Intracellular oedema
Cellular pathological consequence
Leads to cellular damage
Will stimulate the inflammatory response
e.g. ischaemia, metabolic depression, inflammation
Increased Capillary Hydrostatic Pressure causing oedema
Excessive renal retention of salt and water (increases blood volume and blood pressure):
congestive heart failure
renal hypoperfusion
excessive salt intake
Impaired venous return (blood pooing in capillaries, esp. in lower limbs):
venous obstruction (e.g. DVT)
failure of the venous pump (e.g. muscle paralysis, immobilization, valve failure)
Arteriolar dilation (more blood flow to capillaries which increases capillary hydrostatic pressure):
heat
neuro-hormonal dysregulation
Decreased Plasma Proteins causing oedema
Loss of proteins in the urine (e.g. Nephrotic syndrome)
Loss of protein from denuded skin:
burns
wounds
Failure to produce proteins:
liver disease (e.g. liver cirrhosis, ascites)
serious protein or calorific malnutrition
Lymphatic Blockage causes by oedema
Inflammatory infections (e.g. Nematodes)
Neoplastic masses
Treatments (e.g. post-surgical, post-irradiation)
Causes for Increased Capillary Permeability causing oedema
Immune reactions (e.g. histamine effect)
Toxins
Bacterial infections
Heart Failure –
Left Hand Side:
The LHS is weakened so pumping blood to the systemic circulation is difficult
Back-up behind the left ventricle causes fluid accumulation in the lungs
Because of this, the pulmonary vascular pressures rises causing pulmonary oedema
Heart Failure –
Right Hand Side:
LHS may be competent so some blood is pumped to the tissues
The RHS is weakened so pumping of blood to the lungs is inefficient
Because of this, venous congestion results in peripheral oedema (pitting oedema)
The LV Ejection Fraction
A common way to quantify the systolic function of a ventricle (usually the LV) is to use the “ejection fraction”
This is merely a way of expressing what proportion of the blood volume in the ventricle at end-diastole is ejected with each heart beat
EF = EDV – ESV
EDV
Most techniques give
a “normal” LVEF as
> 0.5 (or 50%)
New York Heart Association (NYHA) classification
I - No symptoms with normal physical activity; normal functional status
II - Mild symptoms with normal activity, comfortable at rest, slight limitation of functional status
III - Moderate symptoms with less than normal activity, comfortable only at rest; marked limitation of functional status
IV - Severe symptoms with features of HF with minimal physical activity and even at rest; severe limitation of functional status
HFpEF
Heart Failure with a normal LVEF
HFrEF
Heart Failure with a reduced LVEF
pathophysiology of HFpEF and HFrEF
Myocyte hypertrophy, interstitial fibrosis, abnormal Ca handling, Reduced contractility, slowed relaxation, depleted preload reserve
Large ventricle volume in low ef
Small in normal ef
Five basic causes of Heart Failure:
Coronary Artery Disease
Hypertension
Valvular Heart Disease
Cardiomyopathy
Pericardial Disease
Acute and Chronic Heart Failure presentation
Acute Heart Failure – abrupt onset of dyspnoea, orthopnoea and diaphoresis. This is acute pulmonary oedema.
Chronic Heart Failure – patient usually presents with gradual onset of exertional dyspnoea, fatigue and oedema.
However patients can present with an acute decompensation of chronic heart failure (due to pulmonary oedema) that is indistinguishable from new-onset acute heart failure. Various factors can cause such a decompensation.
Inotropy
Inotropy refers to the contractility of the ventricle
Cardiac muscle is unique in that in can alter its intrinsic inotropic state
Changes in inotropy alter the rate of force and pressure development by the ventricle, and therefore change the rate of ejection (and therefore stroke volume)
Cellular mechanisms responsible involve intracellular Calcium flux
Ventricular Remodelling definition
Ventricular remodelling can be defined as any structural change of the ventricle in response to a change in loading conditions – and includes changes in ventricular mass, chamber size and shape
Ventricular remodelling can develop due to:
An increase in afterload (pressure overload)
An increase in preload (volume overload)
Myocardial injury (usually myocardial infarction)
Determinants of LV remodelling after Myocardial Infarction
Infarct location
Infarct size and transmurality
Patency of infarct related coronary artery
Patency of coronary microcirculation
Maladaptive Effects of Epinephrine and Norepinephrine/(Angiotensin II)
Cardiac Myocyte
Hypertrophy
Apoptosis
Necrosis
Increased wall stress
Increased O2 consumption
Impaired relaxation
Fibroblast
Hyperplasia
Collagen synthesis
Fibrosis
Peripheral Artery
Vasoconstriction
Endothelial dysfunction
Hypertrophy
Decreased compliance
Coronary Artery
Vasoconstriction
Endothelial dysfunction
Atherosclerosis
Thrombosis
(Restenosis)
ADH action in heart failure
Increased angiotensin II and S stimulation leads to secretion which worsens things with vasoconstriction and renal fluid absorption
Why do we develop oedema in CHF?
ventricular failure leads to decreased cardiac output. This leads to decreased arterial pressure and a perceived hypovolemic state. The kidneys, adrenals and pituitary all respond by releasing sympathetic hormones, activates the RAAS and releases ADH/vasopressin.
Counter to this, decreased CO leads to increased venous pressure/pulmonary edema and atrial stretch. The body thus is presented with a FLUID OVERLOAD state and responds by releasing ANP to try and decrease the fluid overload.
When is ANP released and what does it do in heart failure?
Increased cardiac chamber stretch induces secretion of ANP and BNP
In heart failure, natriuretic peptides (BNP and NT-pro BNP) are elevated and work antagonistically to RAAS reducing disease progression.
Heart Failure Definition
Heart failure is now thought as a disorder of the circulation, not merely a disease of the heart. Heart failure develops not when the heart is injured but when compensatory hemodynamic and neurohormonal mechanisms are overwhelmed or exhausted.
Which drug class is always avoided when treating heart failure?
Calcium channel antagonists are not used - A reduction in calcium channel action would dangerously reduce contractility.
Are beta blockers used for heart failure?
Yes, Only certain β-blocking agents (carvedilol, nebivolol and bisoprolol) are used for heart failure and are introduced at low doses then gradually increased.
Which natriuretic peptide receptor clears natriuretic peptides from the circulation
NPR-C
What are the natriuretic peptide receptors
NPR-A is found on endothelial surface of large vessels, kidneys and adrenals
NPR-B is found on vascular smooth muscle cells and brain
NPR-C clears natriuretic peptides from the circulation
Sacubitril is combined with ……. to prevent the effects of raised angiotensin II
Valsartan
To reduce Preload and Afterload in a
patient of African ancestry with acute heart failure should be treated with?…
i.v. glyceryl trinitrate + hydralazine
You are trying increase cardiac inotropy in a patient with heart failure, which drug would you use from the following?
milrinone - Milrinone is a phosphodiesterase inhibitor – increases cAMP => force of contraction increases
What patient condition should cause a doctor to take extra care be when administering Digoxin?
hypokalaemia - Digoxin and K+ compete for binding to the Na+/K+ ATPase
If K+ levels are low, the effect of digoxin is increased; ↑ calcium in cell => ↑ force of contraction
Digoxin has a very low therapeutic index anyway, so an increase in the chance of ectopic beats and inducing ventricular tachycardia and fibrillation
What is a surrogate outcome
Disease Orientated Evidence (DOEs)
Outcomes that tend to be defined on the basis of the disease being studied.
e.g.
Reduction in cholesterol levels
Increased bone mineral density
Increase in FEV1
Patient Orientated Evidence that Matters (POEMs)
Outcomes that matter to the patient and their carers. They need to be outcomes that patients can experience and that they care about.
e.g.
Fewer strokes and heart attacks
Reduced hip fractures
Hospitalisation for COPD
Absolute Risk Reduction
Control Event Rate (%) – Experimental Event Rate (%)
Relative Risk Reduction
Control Event Rate (%)– Experimental Event Rate(%)
Control Event Rate (%)
Relative Risk
RR = Experimental Event Rate/Control Event Rate
Number Needed to Treat
NNT =1/ARR
the number of people who would need to be treated to achieve the event of interest once.
Beta-lactam antibiotic resistance
Enzymes that catalyse the hydrolysis of the β-lactam ring inactivates the antibiotic
Carried on gene – chromosome and plasmids
Gram positive beta-lactamases released extracellularly
Gram negative beta-lactamases remain in periplasm
Overcoming beta-lactam antibiotic resistance
Two approaches:
beta-lactam drug structure cannot bind to beta-lactamase
e.g. dicloxacillin, flucloxacillin, methicillin
include an inhibitor of beta-lactamase e.g. clavulanic acid or tazobactam
e.g. co-amoxiclav = amoxicillin + clavulanic acid
Chloramphenicol resistance
can be acetylated by enzymes produced by bacteria.
The enzymes may be constitutive or induced upon application of chloramphenicol
Aminoglycoside antibiotics resistance
can be acetylated or phosphorylated by enzymes produced by bacteria.
In the presence of the antibacterial drug, the bacterial genes for producing the acetylating enzyme are upregulated.
Vancomycin resistance
Resistance occurs due to alteration of substrate and enzyme
Erythromycin resistance
mutation in 50S subunit of ribosome leads to resistance to erythromycin
Trimethoprim resistance
Altered dihydrofolate reductase – no longer inhibited by trimethoprim
MRSA
For resistance, bacteria produce a modified transpeptidase AND modified peptides
Antibiotic resistance due to 3. Reduced access/penetration
Removal of or down-regulation of porins (water-filled channels in outer membrane) means drug may not be able to cross
Antibiotic resistance due to Acquisition of efflux pump
Expression of a drug efflux pump
E.g. tetracyclines, macrolides, quinolones are removed from the bacterium
