Heart

Heart

1. Cardiac Output

   • heart failure- insufficient cardiac output so under filling of arterial circulation
   • preload
     • preload= degree of streatch of the mycoardium at the end of diastole related to sarcomere length.  filling pressure of the heart
     • SV/ VEDV= ejection fraction- should be 52%
     • CVP - indicator of right ventricular preload
     • left atrial pressure indicator of left ventricular preload
     • preload determined by venous return, venous tone, myocardial compliance
     • Preload + stroke volume
       • frank starling mechanism- energy of contraction of cardiac muscle proportional to the fibre length
       • increase in ventricular end diastolic volume- increase pressure- more blood in ventricle- muscle stretch- muscle contracts more forcefully- increase SV- increase CO
       • stretching cardiac muscle increases exposure of myosin heads to actin- increasing cross bridge formation- increase force of contraction
     • venous return and preload
       • what controls central venous pressure?
         • volume of blood in circulation
         • distribution of blood between central and peripheral veins
         • sympathetic nerves- regulate peripheral venous tone
         • gravity- pools of blood in legs reduce CVP
         • movement- calf muscle movement increases central venous pressure
         • thoracic pump on inspiration
           • intrathoracic pressure negative- abdominal pressure positive- favours venous return 
       • increase in venous return- increase atrial pressure- increase VEDV and SV
     • Hypervolaemia-
       • controlled by barroreceptors and atrial volume receptors
       • depressor reflex
       • 1- increase in volume= increase in arterial pressure-increase firing of arterial barroreceptors
       • 2-decrease sympathetic outflow to the heart, arterioles and veins. increase parasympathetic outflow via medullary cardiovascular centre
       • 3-increased stimulation of atrial volume receptors- inhibit sympathetic vasoconstrictor pathways to kidneys= diuresis
         • reflex inhibition of ADH secretion from posterior pituitary
     • Haemorrhage
       • reduced preload
       • baroreceptor reflex
         • increase sympathetic outflow to heart- arterioles and veins, decrease parasympathetic outflow
       • atrial volume receptors- increase release of ADH
         • sympathetic pathway to kidneys inceases vasoconstriction- urine volume falls
         • RAAS triggered
     • ANP- atrial natriuretic peptide- released when atrial pressure is increased
       • reduces blood volume by increase salt and water secretion from kidney
       • vasodilator
       • inhibits RAAS
       • defence against volume overload
   • Chronotrophy
     • heart rate
     • pacemaker potentials
       • present in the SAN
       • 1-I-f = "funny" or "pacemaker" current- sodium ions leak into the cell
       • 2- potassium ions prevented from leaving
       • 3- calcium ions are also leaking in
       • 4- I-f passes threshold set off voltage sensitive calicum ion channels cause rapid depolarisation using calcium ions
         • threshold about -40
     • Ventricular Potentials
       • purkinje looks like a cross between the two potentials- slight spontaneous rhtyhmicity- more excitable than a casual ventricular cell
       • potentials driven by impulse reaching them
       • 1-voltage sensitive fast sodium ion channels open- rapid depolarisation
       • 2- fast sodium ion channels close- notch
       • 3- plateu- inward calcium current outward potassium current
       • 4-inward calcium ion channels stop- depolarisation as potassium moves out
     • Regulation of Heart Rate
       • controlling the pacemaker (SAN)
         • to increase heart rate- increase sympathetic stimulation to SAN
           • adrenaline and noradrenaline bind to beta adrenoreceptors - open more sodium leak channels to reach the threshold faster
         • To decrease HR- increase vagal tone to SAN
           • acetylcholine binds to muscarinic receptors- fewer sodium leak channels open- takes longer to reach threshold
       • Controlling cardiac muscle cells
         • norepinephrine - bind to B1 and B2 receptors- stimulate adenyl cyclase, increase cAMP- activate protein kinase A
           • and epinephrine GPCR
           • phosphorylate fast sodium ion channels- to increase fast current
           • phosphorylate calcium ion channels- increase slow inward calcium current
           • phosphorylate internal calcium ion store- faster repolarisation
       • Acetylcholine and cardiac muscle
         • bind to muscarinic M2 receptors- switch off adenyl cyclase - less cAMP- also stimulate Kach- hyperpolarising current to oppose inward current
     • excessive HR change
       • heart rate too low- decreased cardiac output heart rate too high- inadequate filling- decreases SV therefore decreased cardiac output
   • Inotropy
     • myocardial contractility
     • contractility= strength of contraction at any given end diastolic volume
     • STRUCTURAL ADAPTATION- long term alterations in heart to cope with changes in volume or pressure loading mediated by catecholamines/ angiotensin II/ aldesterone/ caclium
     • cardiac muscle contraction
       • as calcium ions increase- so contractility increases
       • cardiac muscle has lots of l type calcium - voltage sensitive channels
       • 1- impulse reaches DHPR
         • bottom of T tubule (invagination in cell membrane) DHPR (dihydropyridine receptor channel)
       • 2- DHPR open and calcium ions enter the cell
       • 3- calcium binds to RyR2 receptor on sarcoplasmic reticulum
       • 4-calcium binds to troponin C- calcium induced calcium release
     • relaxing cardiac muscle
       • decrease calcium ion conc in cell
       • facilitated Na+/Ca2+ exchanger pumps calcium out of the cell
         • 3:1
       • ATPase calcium pump- pump out of the cell. also pump back into the sarcoplasmic reticulum
     • controlling blood flow- increasing cardiac work decreases cardiac efficiency- window for blood flow to the cardiac muscle is only when the heart is relaxed
     • controlling contractility
       • norepinephrine- binds to B1 and B2 trigger adenyl cyclase to increase cAMP- activate PKA- phosphorylate sodium and calcium channels- increase inward fast sodium current and slow calcium current
         • increase calcium in cell and fast sodium current
         • increase sensitivity of troponin C to calcium
         • increase calcium uptake in SR
       • acetylcholine can ONLY AFFECT THE ATRIA-
         • can bind to sympathetic nerve to decrease norepinephrine release in ventricles
         • decrease cAMP and increase hyperpolarising current
       • sympathetic and starling curves- increases force of contraction without change to VEDV- hop from one starling curve to the next
   • Afterload
     • force against which the heart ejects
     • systolic arterial pressure= peak pressure in arteries when LV is ejecting blood in systole
     • Diastolic arterial pressure= residual pressure in arteries when LV is filling during diastole
     • mean arterial pressure is the mean of diastolic vs systolic arterial pressure
       • remember cycle split into 3- since diastole lasts twice as long as systole 
       • MAP= CO x TPR
     • controlling blood pressure
       • long term= fluidbalance, short term= cardiac reflexes
       • barroreceptors + other receptors
         • carotid barroreceptors in carotid sinus
         • carotid chemoreceptors in carotid body
         • aortic arch baroreceptors and chemoreceptors in aortic arch body
         • in carotid sinus- tunica media is elastic tissue- tunica adventitia is thicker to make space for the nerve endings
         • baroreceptors have dynamic sensitivity and adaption
       • neural componant
         • pressor reflex- increase sympathetic output to heart, arterioles and veins
         • depressor reflex increase parasympathetic outflow to heart
     • Vascular tone
       • diameter of the vessels has large impact on blood pressure
       • sympathetic vasoconstrictor nerves increase tone
       • epinephrine, angiotensin II, ADH
       • local controls
         • vasoconstrictors act on cell pathways to increase calcium- increasing contraction
         • vasodilators alter cell pathways to decrease calcium- decrease contraction
         • all vascular muscle has basal tone- metabolism can influence basal tone- decrease oxygen- decrease basal tone- passive vasodilation to supply more oxygen
         • B2 receptors in heart and skeletal muscle cause vasodilation
     • lymph formation
       • fluid left outside of capillary returned to heart via lymphatic system
       • hypovolaemia- pressure too low to start with arterial end- internal transfusion- drags fluid into circulation to keep pressure up
   • CO= SV x HR
     • VEDV- venntricular end diastolic volume 

2. Foetal heart development

   • primitive heart tube
     • gastrulation cardiac precursor cells are visible (mesenchymal cells of cardiac lineage)
     • horseshoe shaped divided into first hear field and second heart field
     • FHF- recieve signals and the lateral sides of the horseshoe zip together from top down to form a tube
       • gut closure helps bring together parts of the horse shoe to close
     • primitive heart tube has outflow tract, inflow tract, one ventricle, one atrium and 2 sinus venosi (primitive inflow)
     • primitive tube is a tube of endocardium within a tube of myocardium separated by cardiac jelly
     • EARLY LOOPING- have to flip so the ventricle sits at the bottom- early looping by differential growth of the tube
     • LATE LOOPING AND CONVERGENCE- ventricle grows faster and drags down atrium by outlow. outflow and inflow converge
     • PHT- part two
       • wedging- atrium divide in two- give 3 chambered structure- two atria, one ventricle- common outflow tract
       • septation- left and right ventricles divided- outflow tract divided
       • second heart field lies at the ends of the pharyngeal arches next to outflow- contribute to RIGHT VENTRICLE AND OUTFLOW- now have a four chambered heart
     • 1- ALIGNMENT OF ATRIA AND VENTRICLES
       • a- divide into left and right AV canals
       • formation of endocardial cushions by cardiac jelly- 1 superior, 1 inferior, 1 left, 1 right
         • endocardial cushions initially acellular from cardiac jelly but become populated by mesenchymal cells derived from endocardium 
       • superior and inferior endocardial cushions meet and fuse dividing into left and right AV canals
       • L & R endocardial cushions give rise to heart valves
   • 2- DIVIDE ATRIA
     • a-septum primum grows down to endocardial cushion and fuses
     • b- before it fusees, the middle of the septum primum breaks down- ostium secundum
       • ostium primim is the iniital gap between septum primum and the endocardial cushion
     • c-septum secundum just grows down past the o.s forming a flap valve allowing a right to left shunt
   • 3- VENTRICLE SEPARATION
     • a- don't need to maintain connectivity
     • b- muscular septum grows up towards the AV cushion. the septum has a mesenchymal cap so it can fuse
   • 4- OUTFLOW SEPARATION
     • separation of outflow tract in to aortic and pulmonary trunks
     • a- endocardial cushions form but are not sufficient to fuse
     • b- neural crest cells contribute forming a wall of tissue separating aortic and pulmonary trunk
   • AORTIC ARCH REMODELLING
     • bronchial arch arteries arise in sequence so don't all exist at the same time
     • 3,4 and 6 are the ones that are left- they are paired and symmetrical
     • 3rd form left and right carotid arteries and remain a poair
       • common and internal
     • 4- the left contributes to the aorta- right contributes to the right subclavian artery
     • 6th- left and right pulmonary arteries and ductus arteriousus
       • arteriousus - find out where it is
   • Cardiac Defects
     • Atrial spetal defects
       • septum primum doesn't fuse with AV cushions- persistant ostium primum- quite rare
       • septum secundum doesn't grow down far enough to cover ostium secundum
       • osteum secundum bigger than normal and septum secundum can't cover
     • ventricular septal defects
       • muscular- muscular septum fails to grow
       • membraneous- mesemnchymal cap can't fuse with endocardial cushions
     • failure of NCC to migrate
       • wide spectrum
       • extreme- common arterial trunk- total los of NCC supposed to divide the outflow
       • misposition- some but not all NCC - e.g. blood vessels are present but not connected to the RV
       • transposition- connected to the wrong ventricles
   • Foetal Circulation
     • liver and lungs must be protected by controlling blood flow to them
       • delecate vessels forming during development would be destroyed by high pressure circulation
     • ductus venosus
       • connects umbillical vein to vena cava - protects the liver
       • some blood goes to hepatic portal vein- rest goes to vena cava- controlled by sphincter
       • when ductus venosus is closed- blood can't go to vena cava so goes to liver
     • Ductus Arteriosus
       • pulmonary trunk connected to aorta
       • redirects blood going to lungs sending them to the aorta
     • foramen ovale
       • connects atria- protect developing lungs from high pressure blood that has bypassed the liver

3. pharmacology

   • drugs and vasculature
     • factors controlling vascular tone
       • maintained by balance between opposing action of vasodilators and vasoconstrictors
       • Vasoconstrictor action- adrenaline and noradrenaline, ATP, angiotensin ii, ADH
       • vasodilators- adenosine/ NO/ B2/ atrial natriuretic peptide
         • vessels supplying skeletal muscle, cardiac muscle and supplyin brain
       • vasoconstriction raise intracellular calcium, vasodilators decrease intracellular calcium
     • sties where drugs act
       • vasodilators- by mechanism of action - arterial dilators reduce afterload, increase SV, decrease mycoardial oxygen consumption
         • vein- venodilators- reduce preload by trapping blood in venous circulations
         • arterioles and veins- balanced dilators
       • Drugs that interfere with natural vasoconstrictors
         • alpha 1 adrenoreceptor antagonist- acts on both sides= balanced
           • seen best when sympathetic tone in blood vessels is high 
         • RAAS system can be influenced at 3 points
           • beta antagonists block renin secreation
           • ACE inhibitors block angiotensin ii production
             • captopril- biovalabilty reduced by food in GIT-cleared in kidney
             • Enalapril- prodrug metabolised to enalprilat in liver cleared by kidney
             • Benazepril- pro drug metabolised to benzeprilat in liver- excreted by liver and kidney
           • ATi receptors- agonists- antagonise receptors where angiotensin ii acts
         • ENDOTHELIN -1 constrictor peptide in many endothelial cells- converted by ECE- ECE inhibitors stop vasoconstriction
       • drugs that mimic or enhance natural vasodilator systems
         • cGMP elevation in smooth muscle produces relaxation- stimulate production of organic nitrates and sodium nitroprusside and ANP analouges
         • cAMP also promotes relaxation in smooth muscle
           • DA1 receptors e.g. dopamine
           • Beta adreno 2 receptors e.g. porstacyclin analouges- iloprost
           • enzyme inhibition- phosphodiesterase inhibitors e.g. methylxanthines
       • drugs that block pathways contributing to the response of vasoconstrictors
         • block voltage dependant calcium channels like amlodipine- functional antagonists of a number of natural vasoconstrictors
         • drugs that activate potassium channels in smooth muscle cell membranes- hyper polarise the cell inhibit the opening of voltage dependant calcium ion channels
           • intracellular ATP prevents opening of the potassium channels- drugs that antagonise intracellular ATP on potassium channels opens them- causing relaxation
       • drugs with unknown mechanism- hydralazine- arterial dilator
       • kidney- reduce water retention e.g. diuretic drugs increaese NaCl excretion by the kidney
   • Drugs and the heart
     • Drugs that affect heart rate
       • slow down HR
         • muscarinic receptor agonists
         • cardiac glycosides- increase in vagal tone
         • B adrenoreceptor antagonists- propranolol
       • sped up HR
         • muscarinic receptor antagonists e.g. atropine
         • B adrenoreceptor agonists- isoprenaline- non selective
           • vasodilation by beta 2 effect
     • drugs that affect heart rhythm
       • class 1- block voltage- dependant sodium channels- decrease rate and magnitude of epolarisation and reduce conduction velocity e.g. lidocane
       • class 2- antagonise beta adrenoreceptors -propranolol- reduce xs sympathetic tone
       • class 3- block potassium channels involved in cardiac repolarisation
       • class 4- inhibit calcium channels- reduce plateu current- shorten actin potential negative inotropic effect- reduce cardiac work slow AV node conduction
     • drugs that affect cardiac muscle contratillity
       • increase cardiac contractility
         • sympathomimetics- selectivity for beta adrenoreceptors- dobutamine and dopamine
         • phosphodiesterase inhibitors- keep cAMP high in the cell for longer- milrinone
         • cardiac glycosides- digoxin - slow calcium leaving the cell and inhibit sodium potassium exchanger
         • benzimidazoles- inhibit type 3 cAMP phosphodiesterase and increase calcium sensitivity of cardiac myofribrils
       • reduce cardiac contractillity
         • beta adrenoreceptor antagonists
         • calcium channel blockers
         • sodium channel blockers

4. haemostasis

   • platelet adhesion and activation
     • 1- cut vessel- platlets are exposed to collagen
     • 2- platelets bind to collagen= platlet adhesion
       • requires von willebrand to bind to exposed glycoproteins. thrombin increases adhesion and aggregation of platlets
     • 3- platelets recruit other platelets and they stick together= aggregation form temporary haemostatic plug
     • 4- activated platelets synthesise TxA2- a vasoconstrictor that recruits other platelets
       • they also express GpIIb and GPIIIa on platlet surface
         • -ve surface charge
       • linkage of adjacent platlets by fibrinogen binding to GPIIb and GPIIIa
       • release seretonin and ADP- which activates other platlets
     • CAN BE BLOCKED BY RAISING cAMP OR cGMP INSIDE THE PLATELETS
   • coagulation cascade
     • process converting proenzymes into enzymes (coagulation factors)
     • can be extrinsic or intrinsic
     • extrinsic coagulation- tissue factor produced by damaged endothelial cell binds to circulating factors (VII)
     • intrinsic coagulation- doesn't require tissue factor
     • both types of coagulation cascade generate thrombin which converts fibrinogen to fibrin
       • fibrinolysis is the cascade to dissolve the clot
       • antithrombin III inactivates coagulation factors
   • antiplatlet drugs
     • inhibit synthesis of TxA2
     • block TxA2 receptors
     • inhibit thrombin activity
     • elevate cAMP or cGMP levels
     • block receptors of ADP
     • *asprin COX inhibitor but low dosing affects platlets
   • drugs that inhibit coagulation
     • calcium is involved in coagulation cascade - drugs that complex calcium prevent blood clotting
       • sodium citrate EDTA sodium oxaletate
     • drugs that activate antithrombin iii
       • heparin- naturally in mast and endothelial cells- large sulphated mucopolysachharide inhibits blood clot formation
         • heparin binds antithrombin iii and increase rate of inactivation of clotting factors- short half life
       • low molecular weight heparin like molecules
         • longer half life, lower molecular weight, enhance inhibition of coagulation factors but not thrombin
     • Vitamin K- required for some post transational modification of some clotting factors
     • anticoagulants indipendant of ATIII
       • hirudin- binds directly to thrombin to decrease activity
       • drugs that antagonise vitamin k to decrease formation of some clotting factors- warforin
     • clinical use of these drugs
       • in thromboembolic disease
         • aortic thromboembolism blood vascular parasites loss of antithrombin iii- glom disease, cushings  navicular disease- improve blood flow to bone in horses 
         • use anticoagulants
       • bleeding disorders
         • replace deficient clotting factors, stimulate production new factors or provide antidote for poisoning
         • fresh whole blood or blood plasma contains active clotting factors
         • vitamin k
       • clot busters- enhance fibrinolysis
         • adverse effect- bleeding
         • tissue plasminogen activator- acts on fibrin bound plasminogen
         • activated plasmin converts fibrin to soluble products
         • streptokinase- streptococcal enzymes which activates plasminogen
         • urokinase- extracted from human urine- activator of plasminogen

5. circulatory disturbances

   • oedema
     • oedema- abnormal accumulation of fluid in interstitial tissues
     • non inflammatory oedema- fluid is low in protein . inflammatory oedema high in protein and cell rich
     • 4 pathogenesis= increase in hydrostatic pressure, inrease in capilary permeability, decrease in osmotic pressure and blockage of lymphatic flow
     • high hydrostatic pressure
       • can be due to increased volume of blood in microvasculature
       • can be an active increase in the flow of blood- hyperaemia, or passive accumulation- congestion
       • regional increase in hydrostatic pressure= localised oedema
       • venous congestion - systemic increase in blood pressure
         • potal venous system RHS heart failure- ascites
         • pulmonary venous system- lhs heart failure- pulmonary oedema
     • low osmotic pressure
       • decrease in plasma protein (albumin) can be a decrease in hepatic production due to liver disease / protein malnutrition or malabsorption. or can be a los from circulation- haemmorrhage- severe burns, parasites
     • increased capilary permeabilty
       • inflammatory or immunogenic stimuli increases capilary permeability
       • proteins escape into interstitial fluid and water follow
       • oedema aims to dilute the inflammatory agent. if the stimulus continous cells will leak also
     • decreased lymphatic drainage
       • decreased removal of lymph fluid
       • anything blocking or compressing the lymph causes localised lymphoedema
     • OEDEMA CLINICAL : INTESTINAL LYMPHANGIECTASIA
       • multifactoral
       • congential= decreased number of lymphatic vessels present
       • aquired= obstructive lesions in lymphatic system
       • presentation= ascities/ meseneteric lymphatic vessels dilated/ dilation and rupture of lecteals- loose plasma proteins causing hypoprotenaemia/ lymph leakage causing granulomatous lymphangitis
     • hyperaemia
       • increase volume of blood-incrase in BP= oedema
       • normal- digestion, exercise and heat dissipation
       • pathological- vascular response to inflammatory stimulus
         • e..g cat gingivitis
     • congestion
       • passive decrease in outflow of blood
       • local- obstruction or compression of venous outflow
       • generalised- decrease in passage of blood through heart and lungs- heart failure/ pulmonary fibrosis or cirrhosis
       • acute- accute destruction of venous flow back to the heart- liver, lungs nd spleen enlarged and dark red
       • chronic- lack of blood flow- tissue hypoxia and ischaemia and fibrosis- lungs brown and haemosiderophages - nutmeg liver
   • THROMBOSIS AND HAEMORRHAGE
     • thrombosis= inappropriate clot on wall of lymphatic vessel, blood vessel or heart
       • endothelial injury, abnormal blood flow or hypercoaguability all can contribute
         • endothelial injury- produces VWF- platlets adhere to collegen. endothelial injury also syntehsise tissue factors which stimulate the extrinsic clotting cascade
         • abnormal blood flow- normal blood flow is laminar with platelets central, separated from endothelium by slower moving plasma. abnormal blood flow (stasis or turbulence) disrupts laminar flow.
           • caused by local stasis e.g. intestinal torsion cardiac disease aneuyreism hypocolaemia
           • causes endothelial injury or dysfunction, allows platelets to interact more readily with endothelium, prevents dilution of activated coagulation factors- turbulence allows interaction of the factors
         • hypercoagulability - increase in activated coagulation factors and decrease in coagulation inhibitors. increase in fibrolytic inhibitors. can be caused by inflammation, increase in platelet activity, increae in clotting factor activation or antiIII deficiency
     • embolus- particulate matter traveling in the vascular system- lodge and obstruct vessles
       • small vessel=embolus
       • eventual tissue death= infarction
       • thromboemboli- emboli fragments from a thrombus
       • infarction- peracute ishaemia coagulative necrosis
     • fate of the thrombus
       • propogation, embolisation, dissolution by fibrinolysis, organisation (macrophages remove thrombotic debris) recanalisation (ingrowth of endothelial cells and fibroblasts)
       • *DISSEMINATED INTRAVASCULAR COAGULATION*
         • disease causes diffuse vascular damage= XS thrombin
         • extensive thrombin in microciruclation- platelet and coagulation factors consumed- leading to widespread haemorrhages
       • clinical consequences
         • depends on vessel, tissue supply and perfusion
           • arterial would result in immediate infarction venous would lead to congestion and oedema then infarction
           • atrial thrombus- firmly attched, reddish grey and laminated venous- dark red and gelatinous poorly attached and moulded to lumen 
         • hypertrophic cardiomyopathy-atrial dilation and stasis- clot develops which can break off into the aorta
           • affect kidney and spleen-en -hind limbs cold and paralysed
     • HAEMORRHAGE
       • "extravation of erythrocytes into extravascular space"
         • cuases abnormal platelets abnormal endothelium abnormal coagulation factors
       • decrease in platelet numbers- either due to decreased production (megakaryocyte damage) or increased destruction (immune mediated) or DIC
         • DIC- diseminated intravascular coagulation
         • abnormal platelet function- inability to aggregate (GPIIB and IIIa) or VWF
       • diapedesis - decrease in concetration or function of coagulation factors, decreae in production in the liver, decrease in vitamin K. increase in use e.g. DIC
         • movement of cells outside of the blood vessel
       • Gutteral pouch mycosis - fungal disease aspergillus is angioinvasive can invade the carotid arteries from the gutteral pouch. can also get facial paralysis and laryngeal paralysis
       • gastric ulcuer- entire loss of epithelium. common cause is use of NSAIDs and neoplasia

6. imaging- see notes on how to read an ECG, Radiograph and ultrasound

Imagens e arquivos do mapa