Cardio Flashcards
Why are arterioles, and to a lesser extent, arteries called resistance vessels?
They act as muscular sphincters to provide vascular resistance and redirect flow as required. This is the main regulator of blood pressure
What is a name for capillaries, venous sinusoids and small vessels?
Exchange vessels
What is the distribution of blood normally?
65% in peripheral veins
20% in heart and lungs
10% in peripheral arteries
5% capillaries
What can change blood distribution?
Exercise, where blood is diverted to skeletal muscle and heart
What is the tunica intima?
The innermost layer of vessels.
Endothelium which lines the entire vascular system
What is the tunica media?
Middle layer of vessels (absent in capillaries)
Thickest layer in arteries
Comprised of muscle tissue, elastic fibres and collagen
What is the tunica adventitia?
Outermost layer
Comprised of connective tissues, nerves, vessel capillaries
What are the three types of capillaries?
Continuous - continuous cytoplasm, continuous basal lamina, bidirectional transport via transcytosis - in the brain, thyroid, bone and lung
Fenestrated - discontinuous cytoplasm, fenestrations may have a diaphragm, unidirectional filtration, continuous basal lamina. - villi, kidneys
Discontinuous - discontinuous cytoplasm, bidirectional filtration, discontinuous basal lamina. - spleen
What are the layers of the heart
Endocardium - innermost
Myocardium - heart muscle
Visceral later - inner serous layer
Pericardial cavity
Parietal layer - outer serous layer
Fibrous layer
What are the borders of the heart?
Upper left 2nd intercostal space Lower right 2nd intercostal space 6th right costal cartilage 5th left intercostal space T4/5 - T8/9
What is diastole
When the ventricles are relaxed. At the end of diastole, both atria contract. The volume of blood in the ventricles after this is the end diastolic volume
What is systole
When ventricles contact. Blood is also entering atria
What is isovolumetric contraction? And what happens after?
Between the closing of the AV valves and the opening of the aortic and pulmonic valves. Ventricular pressure increases as contraction doesn’t push out any blood
Then comes rapid ejection phase
As ventricular depolarisation occurs (t wave), pressure in ventricles reduce and force of ejection drops. This is reduced ejection phase as blood is pulled out by the movement of blood
What is stroke volume
Amount of blood pumped out of each ventricle per beat. Around 75ml but may double in exercise
What is cardiac output?
Stroke volume x heart rate
Around 5L at rest but up to 25L during exercise
What can affect cardiac output?
Preload - the stretch on the heart muscle due to the end diastolic volume - this increases sarcomere length and therefore an increase in contractile force, increasing stroke volume
Afterload - the load that the ventricles must pump blood against. If peripheral vascular resistance increases, cardiac output will decrease initially but then return to normal as Frank starling law takes place. Increased end diastolic volume due to increased resistance –> greater stretch of sarcomeres –> greater stroke volume increased
Functionality of the heart - encompasses heart rate and contractility which is modulated by the SNS and PSNS
Why is cardiac muscle termed myogenic?
Because cells in the sinoatrial node generate their own regular, spontaneous action potentials
Which ions cause the depolarisation in heart cells?
Calcium
What are the three phases in the sinoatrial nodal action potentials?
At the end of depolarisation, the membrane potential is around -60mv. Ion channels open which allow a slow inward flow of Na called funny currents. This depolarises the cell, and at around -50mv, T-type calcium channels open, causing phase 4
Phase 4 - spontaneous depolarisation that occurs during diastole and triggers the action potential once the membrane potential reaches threshold ~ -40mv
At -40mv L-type calcium channels open
Phase 0 - T-type calcium channels and funny current channels close.
Phase 3 - K channels open and flows outwards, depolarising the cell and L-type calcium channels close. Keep flowing out until the cell is at around -60mv again and the cycle is spontaneously repeated
Explain the action potentials in non-pacemaker cells in the heart
Have a true resting membrane potential - phase 4
When rapidly depolarised to threshold of around -70mv there is rapid depolarisation (phase 0) causes by sodium channels
Phase 1 is the initial repolarisation by opening of transient K channels
This repolarisation is delayed by the large inward slow Ca at the same time which is long lasting. This causes a plateau which distinguishes cardiac action potentials from skeletal muscle or nerves
Phase 3 is when calcium channels close and repolarisation happens quickly again
What are cardiomyocytes joined together with?
Intercalated discs made of:
- fascia adherens which are anchoring sites for actin and allow for transmission of force
- desmosomes which stop separation of myocytes via intermediate filaments
- gap junctions which allow for the passage of action potentials cell to cell via connexons
What is excitation-contraction coupling?
The process where an action potential triggers a myocyte to contract
When the myocyte is depolarised by an action potential, calcium ions enter (phase 2) through L-type channels located on the sarcolemma. This calcium triggers calcium to be released form the sarcoplasmic reticulum through ryanodine receptors. This is called calcium induced calcium release.
This free calcium binds to troponin C. This induced a conformational change which exposes a site on actin that is able to bind to the myosin ATPase on the myosin head. This results in ATP hydrolysis that supplies energy for a conformational change in the actin-myosin complex.
They slide past each other and contract the sarcomere.
At the end of phase 2, calcium concentration decreases leading to troponin 1 once again inhibiting the actin binding site and ATP binds to myosin head. The sarcomere returns to initial length
What is the order in which parts of the heart contract?
SAN –> atria –> AVN –> annulus fibrosis –> ventricles (bundle of His and Purkinje fibres)
What is the annulus fibrosis?
Non conducting band between atria and ventricles
How long is a large square on the ECG?
0.2 seconds and 0.5mV
What are the parts of the ECG
P - depolarisation of the atria
Q- left to right depolarisation of the interventricular septum
R- depolarisation of main mass of ventricles
S- depolarisation of last part of ventricles at base
T - repolarisation of ventricles
Why isn’t the repolarisation of the atria and other things seen on the ECG?
Too diffuse
Why is the T wave positive?
Although it is repolarisation, the wave progresses from the base towards the apex. The change in polarity and direction cancel each other out. In pathological conditions where the action potential is prolonged, or the conduction from apex to base is slow, the T wave may be inverted
Which vessels provide the most resistance?
Arterioles as they have the thickest walls in relation to their lumen
What is the role of capillary hydrostatic pressure?
To drive fluid out of the capillary into the interstitium
Pressure drops between the arteriole end and the venule end, meaning fluid is reabsorbed at the venule end.
What is the role of capillary oncotic pressure
Generates by proteins such as albumin
Fluid to protein ratio decreases towards the venule end which pulls fluid back into the capillary
What is oedema caused by?
Increased interstitial oncotic pressure Increased venule hydrostatic pressure Increased arteriolar hydrostatic pressure Decreased plasma oncotic pressure Lymphatic blockage
What are the body fluid volumes?
Intracellular - 25L
Extracellular - 15L total
- interstitial fluid -12L
- plasma - 3L
How is blood pressure calculated
Cardiac output x peripheral vascular resistance
How are vessels modulated?
Smooth muscle in the medial layer innervated by postganglionic sympathetic neurones
Noradrenaline acts at alpha 1 adrenoreceptors and causes vasoconstriction
Adrenaline acts at beta 2 adrenoreceptors and causes vasodilation
Angiotensin II and vasopressin cause vasoconstriction
Nitric oxide causes vasodilation
Endothelin causes vasoconstriction
Which cells are involved with the RAAS
Cells in the macula densa in the renal tubules are sensitive to sodium concentration
What happens if the cells in the macula densa sense low sodium concentrations
Send a signal to juxtaglomerular cells in the kidney glomerulus to release renin, which cleaves angiotensinogen into angiotensin I. This is in turn converted to angiotensin II by angiotensin converting enzyme (ACE) - synthesised in the lung
Angiotensin II has the following effects:
- arteriolar constrictor - preserves blood pressure
- aldosterone release - retention of sodium and water in kidney
- vasopressin secretion - retention of water
- Thirst
What’s the opposite of the RAAS system?
ANP and BNP
Cause excretion of water and sodium and powerful vasodilators when higher blood volume is sensed
What are the major afferent sensors other then the juxtaglomerular apparatus?
Baroreceptors in the arch of the aorta (vagus nerve) and corotid sinus (glossopharyngeal nerve)
What causes the release of endothelin I and reduction of Nitric oxide synthesis
Endothelial damage
Describe nitric oxide
Anti aggregatory vasodilator
Formed from L-arginine by NO synthase in response to stress, blood flow, acetylcholine and bradykinin. It converts GTP into cGMP in target cells causing relaxation.
L-monomethyl arginine is an inhibitor of NO synthase
Describe endothelin 1
Released by the endothelium in response to many vasoconstrictors.
It is a a potent vasoconstrictor which stimulates two types of receptor, ETa and ETb
ETa - vasoconstriction, hypertension, endothelial dysfunction, arterial stiffness, atherosclerosis, inflammation, fibrosis, insulin resistance
ETb - natriuresis, vasodilation, ETa clearance
How does the body respond to haemorrhage
Decreased:
Intravascular volume Ventricular filling Blood pressure Capillary hydrostatic pressure Venous return Cardiac output Renal perfusion
Afferent receptors are activated:
Carotid baroreceptors and aortic arch baroreceptors sense decrease in pressure
Atrial volume stretch receptors and juxtaglomerular sensors sense decrease in volume
Efferent signals are activated:
Tachycardia and increased contractility stimulated by Beta 1 adrenoreceptors to increase cardiac output and blood pressure
Alpha 1 adrenoreceptors cause vasoconstriction to increase peripheral resistance and sacrifice blood flow to less vital systems e.g. GI and skin - become cold and pale
Venoconstriction by A1 reduce reservoir function, reduce venous return to the heart and increase cardiac output via Frank starling mechanism
Catecholamine release
Renin release to reduce loss of water and salt in kidney
What symptoms does hypovolemic shock produce
Sweating
Low urine output
Confusion due to reduced cerebral perfusion
Describe the process of atheroma
Tunica intima is damaged by chemicals in the blood, components of cigarette smoke, hypertension or infections
Injured cells release chemotactic agents and begin to transport band modify lipids, particularly LDLs. The built up LDLs are oxidised in the inflammatory environment, damaging nearby cells. This also attracts macrophages. Some of these macrophages become engorged with LDL and become foam cells. Built up foam cells form a fatty streak.
Smooth muscle cells from the media migrate and deposit elastic and collagen fibres, thickening the intima and producing lesions with a core of dead and dying foam cells called atherosclerotic plaques. Initially, vessel walls will expand to accommodate the growing plaque but, eventually, it will start to block parts of the lumen. This is classed as atherosclerosis.
Cells in the centre continue to die and calcium is deposited. Collagen production decreases and the plaque may rupture. - complicated plaque
What is the main function of a lipoprotein
Transportation of triacylglycerol and cholesterol
Describe a lipoprotein
Triacylglycerol (TAG), cholesterol and cholesteryl esters surrounded by a phospholipid monolayer
Have apolipoproteins which have a key role in movement of the lipoprotein
Describe chylomicrons
Biggest Lowest density Dietary source TAG rich Hydrolysed in adipose and muscle tissue ApoB receptors
Dietary lipids, bile and cholesterol form chylomicrons in the gut
Transport TAG into the body
Release free fatty acids (FFAs) and form chylomicron remnants which are either recycled in the liver or absorbed by macrophages
Describe VLDL
Second biggest Second least dense Synthesised in liver TAG rich Transportation function ApoB receptors
Progressively become more dense through release of FFAs due to lipoprotein lipase (LPL), forming IDLs and LDLs. This happens on cell membranes
The resultant LDL is recycled in the liver or absorbed by macrophages
Describe LDL
Second smallest Second densest Derived from VLDL, with the same function Cholesterol rich ApoB receptors
Describe HDL
Smallest Densest Synthesised from APO-A1 in the liver Cholesterol rich Function of removing cholesterol "Good" cholesterol ApoA-1 receptors
APO-A1 is converted to HDL3 at the ABC-A1 receptor in macrophages, catalysed by LCAT
HDL3 is then converted to HDL2 at the SR-B1 receptor on macrophages, catalysed by LCAT
HDL2 exchanges cholesterol esters for cholesterol with LDLs, reducing body cholesterol.
HDL2 is then recycled in the liver at scavenger receptors or recycled to HDL3
What is the treatment for hyperlipidemia?
Diet, weight, stop smoking, moderate alcohol
Statins - inhibit HMG-CoA reductase, preventing production of cholesterol
Ezetimibe - inhibits chylomicron absorption
Stanol esters - reduces chylomicron absorption (weak)
Nicotinic acid - increases HDL, decreases triglycerides
What is ehlers-danlos syndrome
Genetic connective tissue disorder, autosomal dominant, collagen related
What is Marfan syndrome
Genetic connective tissue disorder, autosomal dominant, fibrillin related
What is Virchow’s triad
Endothelial injury
- ulcerated atheromatous plaque
- left ventricular endocardium after MI
- abnormal cardiac valves
Abnormal/stasis of blood flow
- disrupts laminar flow
- prevents dilution of clotting factors
- retards inflow of inhibitors to clotting factors
- promotes endothelial cell activation
Hypercoagulabilty
- alteration of copying cascade
- genetic predisposition
- acquired (e.g. after surgery)
What are mural thrombi?
Applied to one wall of underlying structure
Occur in capacious structures such as cardiac cavities and aorta
What are lines of zahn?
Alternating bands if fibrin/platelets (white) and erythrocytes (pink)
Occur in thrombi (especially formed near the heart or aorta)
Do not occur in clots formed after death. Can be used to tell if the clot was a cause of death
What is an embolism
A detached intravascular solid, liquid or gaseous mass that is carried by the blood to a site that is distant from its point of origin.
Almost always thromboembolism
Can also be:
Amniotic fluid
Gas such as nitrogen in divers or injected
Bone fragments
Large emboli may lodge at the bifurcation of the pulmonary artery and can cause sudden death as they obstruct the entire pulmonary circulation
What are the types of infarct
Red (haemorrhagic) - dual circulation e.g. lung or venous occlusion
White - anaemic - arterial occlusion with a single blood supply e.g. heart
Septic - infected infarcts
What are factors which influence development of an infarction
Dual or single blood supply
Rate of development - rapid due to embolism or gradual such as atheroma build up
Vulnerability of tissue - heart and kidney susceptible
Oxygen content of blood - hypoxia worsens
Describe the clotting cascade
Endothelial damage - platelet attracted to lower prostacyclin levels and exposed collagen. Thromboxane (TXA2) and serotonin are released causing vasoconstriction
Platelets bind to glycoprotein receptors aided by collagen bound von-willebrand factor in microfibrils
This causes confirmation change
Platelets bind to different glycoprotein receptors aided by vWF
Platelets adhere to more glycoprotein receptors aided by fibrinogen
TXA2 causes release of dense granules
Thrombin and tissue factors activate clotting cascade
Intrinsic pathway initiated by collagen exposure - eventually producing factor Xa
Extrinsic pathway initiated by TF and also produces Xa
Xa then converts prothrombin to thrombin which converts fibrinogen to fibrin
What is the fibrinolysis pathway
Plasminogen –> plasmin –> fibrin degradation products
What does prothrombin time measure?
Extrinsic + common pathway
What does the activated partial thromboplastin time measure?
Intrinsic + common pathways
What are examples of hypocoagulation
Haemophilia A - sex linked recessive, factor VIII dysfunction/deficiency
Haemophilia B - sex linked recessive, factor IX dysfunction/deficiency
Factor underproduction - commonly due to liver failure resulting in reduced vit K - factors dependent on vit K
are II, VII, IX and X
Von willebrand disease - autosomal dominant, vWF dysfunction/deficiency - carries fVIII - most common heritable bleeding disorder
Thrombocytopenia - decrease in platelets
Scurvy - no collagen strengthening due to lack of vit C
Ehlers-danlos syndrome - connective tissue disorder
Bone marrow failure
What are examples of hypercoagulabilty
Disseminated intravascular coagulation (DIC) - widespread overactivation of the clotting cascade
Thrombophilia - increased tendency to clot
