Cardiovascular System Flashcards
0
Q
What does rate of diffusion depend on?
A
Area
Diffusion resistance
Concentration gradient
1
Q
Why do we need a CVS?
A
Most cells are far away from a source of oxygen and nutrients
Diffusion only occurs over short distances and so is insufficient to supply oxygen and nutrients
So large organisms like humans require a gas exchange and circulatory system with capillaries and blood flow bringing blood to cells deep within the body
2
Q
How does diffusion depend on area?
A
Larger the area availble for nutrient/ oxygen exchange the greater the rate of diffusion
Area for exchange between capillaries and tissues is generally very large- depends on capillary density
A tissue which is more metabolically active will have a higher capillary density and thus a larger area and greater rate of diffusion
3
Q
How does diffusion depend on diffusion resistance?
A
Diffusion resistance is the difficulty of movement through the barrier
Mostly low, not the factor that limits diffusion
Depends on the nature of the molecule (liphophilic, hydrophilic, size) nature of the barrier (pore size, number of pores for hydrophilic substances) and path length (depends on capillary density and is shortest in the most active tissues)
4
Q
How does diffusion depend on concentration gradient?
A
Rate of diffusion is dependent on the concentration gradient - greater the concentration gradient (between capillary blood and tissues) the greater the rate of diffusion
Concentration gradient must be maintained between capillary blood and tissues
A substance which is used by the tissues will have a lower conc in the capillary blood than in the arterial blood (difference depends on the rate that tissues use the substance and the rate of blood flow through the capillary bed)
5
Q
What is the importance of blood flow and diffusion rate in the CVS
A
Rate of metabolism is directly proportional to demand for oxygen and nutrients
Increases in metabolism must be met by increases in blood flow
Rate of blood flow is known as the perfusion rate
CVS must supply between 5-25l/min of blood to all the tissues whilst at all times maintaining perfusion to vital organs - brain, kidney and heart
6
Q
In the cvs what is the pump?
A
The heart- 2 pumps in series
Left - systemic
Right - pulmonary
7
Q
In the cvs what is the distribution system?
A
Vessels and blood
8
Q
In the cvs what is the exchange mechanism?
A
Capillaries
9
Q
In the cvs what is the flow control?
A
Arterioles and pre capillary spinchters (RESISTANCE)
10
Q
In the cvs what is the capacitance?
A
Capacitance- ability to store blood
Veins - total flow in the system has to be able to change- this requires a temporary store of blood which can be returned to the heart at a different rate
Veins have thin walls which can easily distend or collapse enabling them to act as a variable reservoir for blood
11
Q
What is the mediastinum?
A
Space between two pulmonary cavities
Central cavity of the chest
Transverse thoracic plane at vertebra 4&5 divides mediastinum into superior and inferior
Superior made up of the oesophagus, branch of the aorta, trachea
Inferior made up of anterior, middle and posterior
The heart and pericardial sac are found in the inferior middle mediastinum
12
Q
Describe the pericardium
A
Two layers
Outer fibrous layer - tough and inelastic - attached firmly to the diaphragm via the pericardiocophrenic ligament
Inner serous layer - thin, delicate mesothelium (simple squamous)
–> parietal (more outer; adjacent to fibrous)
Pericardial cavity between (serous fluid)
–> visceral (more inner)
(Parietal layer is reflected onto the heart at the great vessel as the visceral layer)
13
Q
What are the main nerves that supply the heart?
A
Vagus nerves CX - parasympathetic innervation to heart, GI and lungs
- left recurrent laryngeal
- right recurrent laryngeal
Phrenic nerves C3/4/5 - sensory supply of pericardium, muscle supply of the diaphragm –> breathing
- left and right
14
Q
What is the oblique sinus?
A
Blind ending space inferior to the heart - bound laterally by reflections of parietal and visceral reflections surrounding the IVC and pulmonary veins and posteriorly by the pericardium overlying the anterior aspect of the oesophagus
Between superior vena cava and pulmonary artery
No function
15
Q
What is the transverse sinus? And its clinical importance?
A
Between the pulmonary trunk and arch of the aorta leaving and vena cava and pulmonary veins entering
Clamps big vessels in cardiac surgery
16
Q
What are the main coronary arteries of the heart? And what do they supply?
A
Left and right coronary arteries are supplied with blood via 2 holes in the aorta
Left coronary artery has 3 main divisions:
-circumflex (left atria)
-left anterior descending / anterior interventricular branch (left and right ventricle)
- left marginal (left ventricle)
Right coronary artery (right atria) (lies in atrioventricular sulcus) has 4 main divisions:
-SANodal branch (SAN)
-right marginal (right ventricle)
-right posterior descending / posterior interventricular branch (right ventricle)
-AVNodal branch (AVN)
17
Q
What are the main coronary veins?
A
Coronary sinus Great cardiac vein Middle cardiac vein Small cardiac vein Left marginal vein Left posterior ventricular vein
Drain to a single hole/sinus in the right atrium
18
Q
When do coronary arteries fill?
A
When the heart is relaxed in diastole
19
Q
What is the arrangement of the large elastic artery?
A
Tunica intima- endothelial cells, sub endothelial layer, discontinuous internal elastic lamina
Tunica media- smooth muscle (40-70 layers of fibroblast in membranes with smooth muscle cells and collagen between) thin external elastic lamina
Tunica adventitia- thin, vasa vasorum (blood vessels, lymphatics and nerve fibres)
20
Q
What is the arrangement of the medium muscular artery?
A
Tunica intima- endothelial cells, sub endothelial layer, thicker internal elastic lamina
Tunica media- smooth muscle (40 smooth muscle cells with gap junctions) thicker external elastic lamina
Tunica adventitia- thin, vasa vasorum (blood vessels, lymphatics and nerve fibres) unmyelinated sympathetic nerve fibres- neurotransmitters diffuse through fenestrations in the EEL into the smooth muscle cells- propagate to all cells via gap junctions
21
Q
What is the arrangement of arteriole?
A
Tunica intima- endothelial cells, sub endothelial layer, thin internal elastic lamina
Tunica media- smooth muscle (1-3 smooth muscle cells) NO external elastic lamina
Tunica adventitia- scant
22
Q
What is the arrangement of metarterioles?
A
Tunica intima- endothelial cells, sub endothelial layer, NO internal elastic lamina
Tunica media- discontinuous smooth muscle layer and NO external elastic lamina
Tunica adventitia- scant/ absent
Individuals muscle cells are spaced apart and each encircles the endothelium of a capillary arising from one metarteriole- pre capillary spinchters (control blood flow into a capillary by opening and closing)
23
Q
What is the arrangement capillaries?
A
Tunica intima- endothelial cells and subendothelial layer
Pericytes- branching surface on outer surface of endothelium
Capable of dividing into muscle cells or fibroblasts in angiogenesis, tumour growth and wound healing
24
What are the three types of capillaries?
Continuous- most common, continuous cells joined by occluding junctions (nerves, muscles, CTs, exocrine glands)
Fenestrated- interruptions across the endothelium- bridges by thin membranes (gut, endocrine glands, renal glomerulus)
Sinsusoidal- larger diameter, slower blood flow, gaps exist in walls allowing whole cells to move between blood and tissue (liver, spleen, bone marrow)
25
What is the arrangement of the post capillary venules?
Tunica intima- endothelial cells and subendothelial layer
Pericytes- branching surface on outer surface of endothelium
Capable of dividing into muscle cells or fibroblasts in angiogenesis, tumour growth and wound healing
Pressure is lower than that of capillaries or surrounding tissue so that fluid drains into them; except when an INFLAMMATORY RESPONSE IS OPERATING- in which case fluid and leukocytes emigrate; these venules are the preferred location for emigration of leukocytes from the blood
26
What is the arrangement of venules?
Tunica intima- endothelial cells and subendothelial layer
| Tunica media- smooth muscle cells begin to appear
27
What is the arrangement of medium veins?
Tunica intima- endothelial cells, sub endothelial layer, thin internal elastic lamina
Tunica media- thin smooth muscle and NO external elastic lamina
Tunica adventitia- well developed
28
What is the arrangement of large veins?
Tunica intima- endothelial cells, sub endothelial layer, thicker internal elastic lamina
Tunica media- thin smooth muscle and NO external elastic lamina
Tunica adventitia- well developed
29
What are venae comitantes?
Deep paired veins with an artery
All wrapped together in one sheath
Pulsing of artery promotes venous returns within the adjacent parallel paired veins
E.g. Brachial ulnar tibial venae comitantes
30
What are end arteries?
Terminal arteries supplying all or most of the blood to a body part without significant collateral circulation
Undergo progressive branching without development of channels connecting with other arteries so that if occluded there is insufficient blood supply to dependent tissue
Coronary, renal and splenic nerve
Absolute end arteries: central artery to retina, labyrinthine artery of internal ear
31
What valves are found in the heart?
```
Atrioventricular valves ( tricuspid and mitral)
Outflow valves ( aortic and pulmonary)
```
32
Describe the cardiac muscle
Specialised form- myocardium, individual cells joined by low electrical resistance connections
Striated
T tubules
Diads
Z lines
Gap junctions
3 layers- endocardium (lining membrane that covers internal heart and valves), myocardium (cardiac muscle), epicardium (mesothelium on outer surface of heart= visceral)
33
Describe the process of contraction in the heart
SAN (pacemaker cells) produces an action potential spontaneously at regular intervals (1AP per second)
Excitation activity spreads over the atria to the atrioventricular node =atrial systole
Reaches AV node and is delayed for 120ms
Spreads down the muscular septum between the ventricles (via the bundle of his) to excite the ventricular muscle from the endocardial side towards the av junction where valves are located and outwards to the epicardium= ventricular systole
Contraction of each cell is produced by a rise in intracellular calcium concentration triggered by an all or nothing action potential
34
What are some features of the cardiac action potential?
Cardiac ap is very long
1 cardiac ap produces 1 contraction (280ms)
Ap spreads from cell to cell so at each heart beat all the cells in the heart normally contract
35
Define systole
Period when the myocardium is contracting
36
Define diastole
Period of relaxation between contractions
37
How is the ventricle muscle arranged to ensure maximum contraction?
Ventricular muscle is arranged in into figure of 8 bands which squeeze the ventricular chamber forcefully in a way most effective for ejection through the outflow valve - apex of the heart contacts first and relaxes last to prevent back flow
38
How do you calculate cardiac output?
Heart ejects a stroke volume with each heart beat
| Cardiac output= stroke volume x heart rate
39
What is the normal stroke volume of a 70kg individual?
80 ml
40
What is the normal resting heart rate of a 70 kg individual?
60
41
How long does ventricular systole last for?
280 ms
42
How long does diastole last?
700ms
43
In diastole where do the ventricles fill from?
Veins
| Atrial systole- only forces a small extra amount of blood into the ventricles
44
What are the main heart sounds?
Two main sounds associated with valves closing
- first sound - lup - closure of av inflow valves (at onset of ventricular systole)
- second sound - dup - closure of outflow valves (end of ventricular systole)
- third sound - early in diastole
- fourth sound - atrial sound
3rd and 4th are normal sounds = gallop rhythm
Murmurs- turbulent flow of blood through a valve (ABNORMAL)
* quality of sounds may change if valves are altered; sounds may split if valves of right and left heart do not close at the same time
45
What is a heart murmur?
Turbulent flow of blood generates murmurs - narrowed valves (stenosis) or valve not closing properly (incompetence) or absent/permanently fused valves (atresia)
Murmurs occur when blood flow is highest- So we can predict when in the cardiac cycle they should occur (aortic stenosis and incompetence- in rapid ejection phase)
46
Describe the cardiac cycle
```
Using poster
Isovolumetric relaxation
Rapid filling phase
Isovolumetric contraction
Rapid ejection phase
```
47
How frequent are congenital heart defects?
Congenital heart defects are common, with an incidence of 6-8 per 1,000 births
48
What are the most common congenital heart defects?
The most common heart defects are Ventricular Septal Defects (VSD), followed by Atrial Septal Defects (ASD)
49
What are the acyanotic heart defects?
```
Persistence of left to right shunts
Atrial septal defects (in particular PFO)
Ventricular septal defects
Patent ductus arteriosus
Aortic stenosis
Coarctation
Mitral stenosis
```
50
What are atrial septal defects?
An ASD is an opening in the septum between the two atria, which persists following birth. They have an incidence of 67 in 100,000 live births.
The foramen ovale exists to prenatally permit right to left shunting of oxygenated blood and is designed to close promptly after birth. Failure of it to close, allows blood to continue to flow between the two atria postnatally. Because left atrial pressure > right atrial pressure, flow will be mainly from left to right, meaning no mixing of deoxygenated blood with the oxygenated blood being pumped around the circulation.
ASDs can occur almost anywhere along the septum, but the most common site is the foramen ovale (Ostium secundum ASD). An ostium primum ASD occurs at the inferior part of the septum, and is less common.
51
What is a specific example of an ASD?
Patent foramen ovale (PFO)
52
What is PFO?
PFOs are not a true ASD. PFOs may be present in ~20% of the population and are generally clinically silent, since the higher left atrial pressure causes functional closure of the flap valve.
A PFO may however be the route by which a venous embolism reaches the systemic circulation if pressure on the right side of the heart increases even transiently. This is called a paradoxical embolism.
53
What is a ventricular septal defect?
VSDs are an opening in the Interventricular Septum. This most commonly occurs in the membranous portion of the septum, but can occur at any point. Since left ventricular pressure is much > than right, blood will flow left to right.
54
What is patent ductus arteriosus?
The Ductus Arteriosus is a vessel that exists in the foetus to shunt blood from the pulmonary artery to the aorta before the lungs are functioning. This vessel should close shortly after birth as the pressure in the pulmonary artery drops following perfusion of the lungs. Failure to close leads to a PDA. Blood flow through a PDA will be from the aorta to pulmonary artery after birth (High to Low pressure).
55
What is a mechanical murmur and when is it heard?
A Mechanical Murmur is heard constantly throughout systole/diastole, as pressure in the aorta is always greater than in the pulmonary artery.
56
If untreated how can conditions of left to right shunting, become problematic?
Although left to right shunting of blood does not cause cyanosis it can be problematic later on if untreated, with the extent of the problems depending on the degree of shunting. Chronic left to right shunting can lead to vascular remodelling of the pulmonary circulation and an increase in pulmonary resistance. If the resistance of the pulmonary circulation increases beyond that of the systemic circulation the shunt with reverse direction as pressures on the right side of the heart increase (Eisenmenger Syndrome).
57
What is coarctation of the aorta?
Coarctation of the Aorta is a narrowing of the aortic lumen in the region of the ligamemtum arteriosum (former ductus arteriosus). The narrowing of the aorta increases the afterload on the left ventricle and can lead to left ventricular hypertrophy. Because the vessels to the head and upper limbs usually emerge proximal to the Coarctation, the blood supply to these regions is not compromised. However blood flow to the rest of the body is reduced. The extent of the symptoms depends on the severity of the Coarctation.
In very severe cases, an infant may present with symptoms of heart failure shortly after birth. In mild cases, the defect may be detected in adult life. Femoral pulses will be weak and delayed, with upper body hypertension.
58
What are the cyanosis heart defects?
```
Persistence of right to left shunts
Tetralogy of fallot
Tricuspid atresia
Transposition of great arteries
Hypoplastic great/ left heart
Univentricular heart
Pulmonary atresia
```
59
What is tetralogy of fallot?
The Tetralogy of Fallot is a group of 4 lesions occurring together as a result of a single developmental defect placing the outflow portion of the interventricular septum too far in the anterior and cephalad directions. The four abnormalities are:
- VSD
- Overriding Aorta
- Pulmonary Stenosis (variable degree)
- Right Ventricular Hypertrophy (variable degree)
Pulmonary stenosis causes persistence of the foetal right ventricular hypertrophy, as the right ventricle must operate at a higher pressure to pump blood through the pulmonary artery. The increased pressure on the right side of the heart, along with the VSD and overriding aorta allow right à left shunting and therefore the mix of deoxygenated blood with the oxygenated blood going to the systemic circulation, resulting in cyanosis.
The magnitude of the shunt and level of severity depends on the severity of the pulmonary stenosis. Affected individuals may present with cyanosis in infancy, but mild cases can present in adulthood.
60
What is tricuspid atresia?
Tricuspid Atresia is the lack of development of the tricuspid valve. This leaves no inlet to the right ventricle (2). There must be a complete Right to Left shunt of all blood returning to the right atrium (ASD or PFO) (1) and a VSD or PDA to allow blood to flow to the lungs (3).
61
What is the transposition of the great arteries?
Results in two unconnected parallel circulations instead of two in series. In this defect, the right ventricle is connected to the aorta and the left ventricle to the pulmonary trunk. This condition is not compatible with life after birth, unless a shunt exists to allow the two circulations to communicate. A shunt must be maintained or created immediately following birth to sustain life until surgical correction can be made. The ductus arteriosus can be maintained patent and/or an atrial septal defect formed.
62
What is hypoplastic left heart?
In some cases the left ventricle and ascending aorta fail to develop properly resulting in a condition called Hypoplastic left heart. A PFO or ASD are also present and blood supply to the systemic circulation is via a PDA. Without surgical correction this is lethal.
63
What is Univentricular heart?
```
A/v valves and subsequent ventricles do not form
Can occur with or without the transposition of the great arteries
Results in a unified mass
LV (viable)
RV (less viable)
No RV outlet
R to L shunt of entire venous return
Blood flow to lungs (PDA)
```
64
What is the resting membrane potential largely established by?
Due to the potassium permeability of the cell membrane at rest
- due to the leak of potassium channel
- due to the inward rectifier potassium channels being open
- due to little permeability of other ions
65
Describe how a resting membrane potential is established
Potassium ions move out of the cells - down their concentration gradient; small movements of ions makes the inside negative wrt the outside
Electrical gradient is set up as charge builds up
Rmp exists when the movement of potassium ions into the cell (electrical gradient) is equal to the movement of potassium ions out of the cell (conc grad) = Eqm K
(Ions are still moving but there is equal movement)
66
Describe the ventricular cardiac action potential
```
Steep depolarisation (upstroke)- opening of voltage gated sodium channels
Steep and rapid repolarisation- transient outward potassium current; voltage gated potassium channels open very quickly and then inactivate very quickly (like sodium channels)
Plateau region with slight repolarisation- influx of calcium ions, but slight depolarisation still occurs because potassium out flux exceeds calcium influx
Further steep and rapid repolarisation (hyper too; downstroke)- calcium channels inactivate, voltage gated potassium channels and inward rectifier potassium channels open
```
67
Describe the sino atrial node action potential
Slow depolarisation to threshold- PACEMAKER POTENTIAL (funny current) influx of sodium ions via Hyperpolarisation Cyclic Nucleotide (HCN) gated channels (activated by membrane potential more negative than -50mV, and so become inactivated as membrane depolarises) unstable
Steep and Rapid depolarisation (upstroke)- opening of voltage gated calcium channels
Steep and rapid repolarisation- opening of voltage gated potassium channels
68
Why is the SAN Favoured as the pacemaker of the heart over AVN, atrial muscle, ventricular muscle and PURKINJE fibres?
SAN is the fastest out of the AVN, SAN, atrial muscle, ventricular muscle and PURKINJE fibres to depolarise - automatic
Shortest pacemaker potential
69
Describe some basic features of cardiac muscle
```
Striated- actin and myosin filaments
Single central nucleus
Cells joined at intercalated disks (desmosomes and gap junctions)
T tubules (Z lines) are diads
Indistinct fibres
Branching
```
70
What do desmosomes do?
Rivet cells together allowing cardiac cells to contract as one unit
71
What do gap junctions do?
Permit the movement of ions and electrically couple cells together (spread of depolarisation)
72
Describe the process of contraction of cardiac muscle
Depolarisation opens the L type calcium channels in the T. Tubule system (25%)
Localised calcium entry opens the calcium induced calcium release (CICR) channels in the SR (75%)
Calcium binds to troponin c causing a conformational change in tropomyosin, shifting it from actin to reveal the myosin binding site on the actin filament
Sliding filament mechanism
73
Describe the process of relaxation of cardiac muscle
Calcium is pumped back into the SR via SERCA (stimulated by raised calcium)
Or leaves across the cell membrane (sarcolemmal calcium ATPase OR sodium/calcium exchanger NCE)
74
What control the tone of blood vessels?
Contraction and relaxation of vascular smooth muscle cells
75
How does the contraction and relaxation of vascular smooth muscle cells control the tone of blood vessels?
Controls the resistance of blood flow
Contracts veins en route to the heart- to increase BP
Increases blood pressure
76
Where are vascular smooth muscle cells found in arteries, arterioles and veins?
Located in the tunica media
77
Are actin and myosin still involved in contraction and if so how?
Yes
Diagonal arrangement f acting and myosin filaments
Cells are electrically coupled via gap junctions
78
Describe the contraction of smooth muscle cells
Depolarisation of cells causes an influx of calcium via the L type voltage gated calcium channels
Inside the cell 4 calciums bind to the calmodulin molecule activating myosin light chain kinase (mlck) by binding to it
Mlck phosphorylates the light myosin chain using ATP phosphate, allowing the interaction of myosin light chain with actin and hence contraction
79
Describe the relaxation of smooth muscle cells
As calcium levels decline, after contraction mlc phosphatase (which is always active) dephosphorylates the myosin light chain
80
What inhibits mlck and contraction of smooth muscle cells?
Phosphorylation by protein kinase A
81
What is vascular smooth muscle contraction dependent on?
Relative activation of mlck and activity of mlcp
82
What is the autonomic nervous system important for?
Balance- (homeostasis) heart rate, blood pressure, body temperature
Coordinating the body's response to exercise and stress
83
What three areas of the body does the autonomic nervous system exert control over?
Smooth muscle (vascular and visceral)
Exocrine secretion
Rate and force of contraction in the heart
84
What are the 2 divisions of the autonomic nervous system?
Sympathetic and parasympathetic
85
Describe the arrangement of the sympathetic nervous system
2 neurones
Thoracolumbar outflow from spinal cord
Short preganglionic neurone (ACh --> nicotinic receptors)
Long postganglionic neurone (noradrenaline, norepinephrine --> adrenergic alpha/beta receptors)
Preganglionic neurone synapses at paravertebral origin, above or below on the sympathetic chain or somewhere else (coeliac, superior mesenteric, inferior mesenteric ganglia)
86
Describe two exceptions to the arrangement of the sympathetic nervous system
Sweat glands, erectile tissue
Short preganglionic neurone (ACh --> nicotinic receptors)
Long postganglionic neurone (ACh --> muscarinic receptors)
87
Describe the arrangement of chromaffin cells of the adrenal medulla
```
Sympathetic
Preganglionic neurone (ACh ---> nicotinic receptors)
Directly int chromaffin cell which releases adrenaline/ epinephrine into the blood stream
```
88
When is the activity of the sympathetic nervous system increased?
Increased under stress
89
What receptors are found on target tissues in the sympathetic nervous system?
Adrenoreceptors - alpha 1&2 beta 1&2 (&3)
Respond to noradrenaline and adrenaline
GPCR (no integral ion channel)
Different tissues can have different types of adrenoreceptors
90
Why is it important for different target tissues to have different subtypes of adrenoreceptors in the sympathetic nervous system?
Allows for diversity of action- operates through different signalling mechanisms
Selectivity of drug action
91
Describe the arrangement of the parasympathetic nervous system
2 neurones
Craniosacro outflow from spinal cord
Long preganglionic neurone (ACh --> nicotinic receptors)
Short postganglionic neurone (ACh --> muscarinic receptors)
Ganglion is located near to the target tissue
92
When is the activity of the parasympathetic nervous system increased?
Increased under basal conditions
93
What receptors are found on target tissues in the parasympathetic nervous system
Muscarinic receptors
Respond to ACh
GPCR (no integral ion channel)
M1,2 and 3
94
Regarding the heart what three things is the autonomic nervous system important for?
Heart rate
Force of contraction of the heart
Peripheral resistance of blood vessels (arterioles)
95
In the heart, what three structures does the sympathetic nervous system innervate?
The sinoatrial node
The atrioventricular node
Myocardium
96
In the heart in the sympathetic nervous system where does the postganglionic fibre come from?
The sympathetic chain
97
In the heart what neurotransmitter does the postganglionic neurone release in the sympathetic nervous system?
Noradrenaline
98
In the heart what receptors on the target tissues does the noradrenaline from the postganglionic fibre act on?
Beta 1 receptors
99
In what two ways does the sympathetic nervous system affect the heart?
Increases heart rate (positive chronotropic effect)
| Increases force of contraction (positive inotropic effect)
100
How does the sympathetic nervous system increase heart rate?
Noradrenaline binds to the beta 1 receptors
This increases cAMP
Increases the opening of the HCN channels
Speeds up the pacemaker potential
Increases heart rate
101
How does the sympathetic nervous system increase the force of contraction of the heart?
Noradrenaline binds to beta-1 receptors
Increase in cAMP
Activates protein kinase A
Phosphorylation of calcium channels
Increased calcium entry during the action potential
Increased uptake of calcium in the sarcoplasmic reticulum
Increased sensitivity of contractile machinery to calcium
Increased force of contraction
102
In the heart what 4 structures are innervated by the parasympathetic nervous system?
Epicardial surface
Within the walls of the heart
SAN
AVN
103
In the heart where does the preganglionic fibre originate from the spinal-cord in the parasympathetic nervous system?
From the 10th cranial nerve
| Vagus nerve
104
In the heart what neurotransmitter does the postganglionic nerve release in the Parasympathetic nervous system?
Acetyl choline
105
In the heart what receptors does the acetylene choline from the postganglionic fibres act on in the parasympathetic nervous system?
M2 receptors
106
In what two ways does the parasympathetic nervous system affect the heart?
Decreases heart rate (negative chronotropic effect)
| Decreases AVN conduction velocity
107
How does the parasympathetic nervous system decrease heart rate?
```
Acetylcholine binds to the M2 receptors
This increases potassium conductance
This decreases cAMP
Decreases HCN channel activity
This slows down the pacemaker potential
This decreases the Heart rate
```
108
What type of innervation do most vessels receive?
Sympathetic
109
What is the effect of a decreased sympathetic output on vessels?
Binds to Alpha 1 receptors
| Vasodilation
110
What is the effect of a normal sympathetic output on vessels?
Vasomotor tone
111
What is the effect of increased sympathetic output on vessels?
Binds to alpha-1 receptors
| Vaso constriction
112
Where can blood vessels which have beta 2 adrenoreceptors and alpha-1 adrenoreceptors be found?
Skeletal muscle
Myocardium
Liver
113
How does noradrenaline affect blood vessels?
Binds to alpha-1 receptors
| Causing vasoconstriction
114
How does circulating adrenaline affect blood vessels?
Binds to beta-2 receptors
Causing vasodilation
In high amounts, circulating adrenaline can bind to alpha-1 receptors causing vasoconstriction
115
Does circulating adrenaline have a higher affinity for alpha-1 receptors or beta 2 receptors?
Beta two receptors
116
In blood vessels how are the beta 2 adrenoreceptors activated?
Increase in cAMP
Opens a type of potassium channel
Causes relaxation of the smooth-muscle
Vasodilation
117
In blood vessels how are the alpha-1 adrenoreceptors activated?
Increasing calcium from the stores in the sarcoplasmic reticulum and via the influx of extracellular calcium
Causes contraction of smooth smooth muscle
Vasoconstriction
118
What is the importance of local metabolites in vasodilation and vasoconstriction?
Active tissue produces more metabolites
Local increases in metabolites has a strong vasodilator effect
Local metabolites are more important for ensuring adequate perfusion of skeletal and coronary muscle than the activation of beta 2 receptors
119
What are baroreceptors?
Nerve endings in the carotid sinus and aortic arch which are sensitive to stretch
120
How do you baroreceptors work?
Baroreceptors detect stretch in artery walls and hence increased mean arterial pressure
They send signals via afferent Pathways to medulla of the brain
This decreases the heart rate (bradycardia) and causes vasodilation so tired station
Bradycardia and vasodilation counteract the increased mean arterial pressure
121
What three classes of drugs act on the autonomic nervous system?
Sympathomimetics
Adrenoreceptor antagonists
Cholinergics
122
How do sympathomimetics work?
They mimic the effects of the sympathetic nervous system
123
How do sympathomimetics exist?
As alpha adrenoreceptor agonists or beta adrenoreceptor agonists
124
What is the meaning of flow?
The volume of fluid passing a given point per unit time
Must be the same at all points along the vessel
Flow= volume/time
125
What is the meaning of velocity?
The rate of movement of fluid particles along the tube
Can vary along the length of the vessel if the radius of the tube changes
Velocity= distance/ time
126
At a fixed flow, what is the relationship between velocity and cross-sectional area of a vessel?
Velocity is inversely proportional to the cross-sectional area
So the bigger the cross-sectional area – the lower velocity (capillaries)
The smaller the cross-sectional area – the higher velocity (aorta)
127
What does laminar flow mean?
In laminar flow, there is a gradient of velocity from the middle to the edge of the vessel. Velocity is highest in the centre and fluid is stationary at the edge. The flow in most blood vessels is laminar.
128
What does turbulent flow mean?
As the mean velocity increases, flow eventually becomes turbulent. The velocity gradient breaks down as layers of fluid try to move over each other faster than physics will allow. The fluid tumbles over, greatly increasing flow resistance.
Turbulent flow has associated sound which is a key feature of clinical examination
129
What is viscosity?
The extent to which fluid layers resist sliding over one another in laminar flow
Viscosity determines the slope of the gradient of velocity
130
How does viscosity affect flow?
The higher the viscosity, the slower the central layers will flow, and the lower the average velocity. In a low viscosity fluid, the difference between the centre and edge is large, and in a high viscosity fluid the difference is smaller.
131
At a constant pressure, what is flow affected by?
Mean velocity which in itself is affected by the viscosity of the fluid and the radius of the tube
132
What is the relationship between mean velocity and viscosity?
Mean velocity is inversely proportional to viscosity
133
What is the relationship between mean velocity and cross-sectional area?
Mean velocity is directly proportional to cross-sectional area
134
How does the radius of the tube affect mean velocity?
At a constant gradient, the wider the Tube the faster the middle layers move
135
What is Poisseulles law?
Flow is directly proportional to the change in pressure x the radius x the radius squared / (viscosity x length)
136
What is ohms law?
Pressure = flow x resistance
137
What is the relationship between resistance and viscosity?
Resistance is directly proportional to viscosity
| Resistance increases as viscosity increases
138
What is the relationship between resistance and radius?
Resistance decreases with fourth power of radius
139
What is the relationship between resistance and pressure when flow is fixed?
The higher the resistance, the greater the pressure change from one end of the vessel to the other
140
What is the relationship between resistance and flow when pressure is fixed?
If pressure is fixed, higher the resistance, the lower the flow
141
How do resistances in blood vessels combine?
Just like electrical resistances
For vessels in series, resistances add together
For vessels in parallel, the effective resistance is lower, as there is more than one path for the current to flow down
-e.g. For two vessels in the series, the resistance of one of the vessels in the series is half of the original, as the blood has two paths
142
Dscribe the pattern of flow resistance and pressure over the systemic circulation
o Over the whole circulation, flow is the same at all points
o Arteries are low resistance
• Pressure drop over arteries is small
o Arterioles are high resistance
• Pressure drop over arterioles is large
o Venules and veins are low resistance
• Pressure drop over venules and veins is small
The pressure within arteries is high because of the high resistance of the arterioles. It is difficult to push blood into them, therefore pressure increases.
For a given total flow, the higher the resistance of the arterioles the higher the arterial pressure.
If the heart pumps more blood and the resistance of arterioles remains the same, the arterial pressure will rise.
143
How does the distensibility of blood vessels affect the relationship between flow and pressure?
Blood vessels have distensible walls, and the pressure within the vessel generates a transmural pressure across the wall. This stretches the vessel.
As the vessel stretches, the diameter of the lumen increases, so resistance falls and flow increases. So the higher the pressure in a vessel, the easier it is for blood to flow through it.
As the pressure within a distensible vessel falls, the walls eventually collapse, and blood flow ceases before the driving pressure falls to zero.
144
How does the distensibility blood vessels produce the property of capacitance?
As vessels widen with increasing pressure more blood transiently flows in then out
This allows the distensible vessels to store blood – they have capacitance
Veins are the most distensible vessel with 67% of the blood in them at rest
145
Define systolic arterial pressure
The maximum arterial pressure
| Typically 120 mmHg
146
What is systolic arterial pressure affected by?
How hard the heart pumps
Total peripheral resistance
Compliance (stretchiness) of the arteries
147
Define diastolic arterial pressure
The minimum arterial pressure
| Typically 80 mmHg
148
What is diastolic arterial pressure affected by?
Systolic pressure
| Total peripheral resistance
149
What is pulse pressure?
The difference between systolic and diastolic pressure
| Typically 40mmHg
150
What is average pressure?
Diastolic + 1/3 pulse pressure (systole is shorter than diastole)
151
What is total peripheral resistance?
Sum of the resistance of all the peripheral vasculature in the systemic circulation
152
How does the elastic nature of the arteries act to reduce arterial pressure fluctuation between systole and diastole?
If arteries had rigid walls, the pressure in them would rise enough in systole to force the whole stroke volume through the total peripheral resistance, and fall to zero in diastole.
But arteries have distensible walls, allowing them to stretch in systole. More blood flows in than out, so pressure does not rise so much. The arteries recoil in diastole and flow continues through the arterioles.
153
Describe the pulse wave
Contraction of the ventricles generates a pulse wave, which propagates along the arteries faster than blood. This is felt at a variety of locations where arteries come close to the surface and can be pushed against a reasonably hard surface.
Dicrotic Notch
The slight dip seen in the pulse wave is known as the Dicrotic Notch. This is due to pressure in the left ventricle falling below aortic pressure and the subsequent backflow of blood (this backflow is responsible for closing the aortic valve)
Dicrotic Wave
The slight rise seen in the pulse wave directly after the dicrotic notch is the Dicrotic Wave. This slight increase in pressure is due to the recoil of blood off the closed aortic valve.
154
How do arterioles act as resistance vessels?
Arteriolels control blood flow to tissues by variable flow restriction. Their walls contain much smooth-muscle, and it's state of contraction determines lumen diameter and therefore flow resistance
Vasoconstriction --> decrease in the flow
Vasodilation --> increase in flow
155
What is meant by vasomotor tone?
Muscles do not actively relax, so except under maximum flow conditions there must always be some vasoconstriction. Vasodilation is therefore reduced vasoconstriction. This continuous contraction of the muscle is known as vasomotor tone.
156
Where is vasomotor tone mainly produced?
In the sympathetic branch of the ANS
157
What factors affect the contraction of vascular smooth muscle?
Antagonised by vasodilator factors (H+, K+, Adenosine)
Resistance is determined by vaso motor tone and vasodilator factors
These metabolites cause the relaxation of local smooth-muscle, lowering resistance and increasing bloodflow
158
What is the relationship between blood flow and metabolism?
If metabolism increases, more metabolites are produced
So the concentration increases, vasodilation occurs and washes away the metabolites
More metabolism = more blood flow
159
What is reactive hyperaemia?
If the circulation to an organ or limb is cut off for a minute or two, then restored, a large amount of blood enters after a period of no blood flow.
As the organ/limb has continued metabolising and producing vasodilators (H+, K+, Adenosine) during the period of no circulation, with no blood flow to remove them, when circulation is restored, the local arterioles dilate maximally and blood flow is very high.
160
What is auto regulation?
At most levels of metabolic activity, most organs can automatically take the blood flow they need so as long as the pressure in the arteries supplying them is kept within a certain range.
161
What is central venous pressure?
The pressure in the great veins supplying the heart.
162
What is Venous return?
The rate of flow of blood back to the heart
| Limits cardiac output
163
What is cardiac output?
Stroke volume x Heart rate
164
How is TPR through arterioles modified?
Action of metabolites (vasodilators) will modify flow resistance through arterioles to suit metabolic demand
Total peripheral resistance is inversely proportional to the bodies need for bloodflow by metabolism
165
At a constant cardiac output what happens to arterial pressure and venous pressure when TPR is decreased?
Arterial pressure decreases
| Venous pressure increases
166
At a constant cardiac output what happens to arterial pressure and venous pressure when TPR is increased?
Arterial pressure increases
| Venous pressure decreases
167
At a constant TPR what happens to arterial pressure and venous pressure when cardiac output is decreased?
Arterial pressure decreases
| Venous pressure increases
168
At a constant cardiac output what happens to arterial pressure and venous pressure when TPR is increased?
Arterial pressure increases
| Venous pressure decreases
169
Describe TPR, AP, VP and CO in a stable cardiovascular system?
```
High metabolic demand
Low TPR
Low AP
High VP
High CO
Can meet demand and bring AP and VP back to normal
And vice versa at low metabolic demand
```
170
What is end diastolic volume?
The volume of blood in the ventricle at the end of diastole (during which the heart fills)
171
What is end-systolic volume?
The volume of blood in the ventricle at the end of systole
172
What is stroke volume?
The difference between end-diastolic and systolic volume
| I.e. The volume of blood pumped out of the heart in systole
173
What does end-diastolic volume depend on?
Venous pressure
| The ventricle fills until the walls stretch enough to produce an intraventricular pressure = venous pressure
174
What does the ventricular compliance curve show?
The relationship between end-diastolic volume and venous pressure
175
What is preload?
End diastolic stretch of myocardium, determined by venous pressure
176
What is after load?
Force necessary to expel blood into the arteries
177
What is the starling law of the heart?
```
Increase venous pressure
Increase ventricular filling in diastole
Increased in EDV
Increase in stretch of muscle fibres
Increase in contraction
Increase in stroke volume
Increase CO
More in more out
```
178
Describe the starling curve
At a constant afterload
The more the heart fills due to increased VP the harder it contracts (at a constant after load) and greater SV
There is however a limit when the heart becomes over filled and myocardium is over stretched
So curve increases and then decreases
179
What is contractility?
Ability of the heart fibres to contract
| Not the force of contraction of the heart but the stroke volume you get for a given venous pressure
180
What causes contractility to increase?
Sympathetic activity - makes heart more susceptible to VP
Adrenaline
Exercise
181
What causes contractility to decrease?
Heart failure
182
What does ventricle emptying and end systolic volume depend on?
Force of contraction - determined by- EDV (starlings law) and contractility
Difficulty ejecting blood - aortic impedance, dependent mainly on TPR - increase in TPR, increase in AP, decrease ESV, decrease in SV (the easier it is to eject blood, the more comes out in systole so a decrease in AP, causes a decrease in ESV and an increase in SV)
183
How is SV affected by VP?
Increase in VP causes an increase in SV
184
How is SV affected by AP?
Decrease in AP causes an increase in SV
185
What are the relative levels of AP and VP that cause a high SV?
Low AP
| high VP
186
How is heart rate controlled?
Autonomic outflow to heart controlled by signals from baroreceptors which are located in the aortic arch and carotid sinus.
Baroreceptors sense AP and send signals to the medulla which controls the heart
187
What is the effect of a low AP on heart rate and contractility?
Decrease in parasympathetic and increase in sympathetic activity and hence increased heart rate
Increase in sympathetic activity causes increased contractility
Increase in cardiac output
188
What is the effect of a high VP on heart rate?
Sensed in right atrium
Leads to a decrease in parasympathetic activity- increasing heart rate
Brainbridge reflex
189
How is cardiac output calculated?
SV x HR
190
How is blood pressure calculated?
TPR x CO
| TPR x SV x HR
191
What are the 5 rules of short term changes in the CVS?
1) TPR is inversely proportional to the metabolic need for blood flow, causing an increase in metabolic activity, and decrease in TPR
2) If CO is constant, TPR affects VP and AP - decrease in TPR= increase in VP= decrease in AP (vv)
3) Changes in AP and VP affects the heart- increase in VP causes increase in CO (vv)
4) At a constant TPR, CO affects VP and AP- decrease in CO causes an increase in VP and decrease in AP
5) AP changes reflexly affects TPR and venous capacitance- if AP falls, resistance to blood flow through the certain vascular beds such as gut and skin normally rises; if AP falls venous capacitance will be reduced by venoconstriction
192
What is the response of the CVS to eating a meal?
o Increased activity of the gut leads to the release of metabolites and local vasodilation. The total peripheral resistance falls, causing the arterial pressure to fall and the venous pressure to rise.
o The rise in venous pressure causes a rise in cardiac output.
o The fall in arterial pressure triggers a rise in heart rate and cardiac output.
o The extra pumping of the heart reduces venous pressure
o The extra pumping of the heart raises arterial pressure
o Demand met – System Stable
193
What is the response of the CVS to exercise?
o Enormous increase in demand
o ‘Muscle pumping’ forces extra blood back to the heart
With no other changes, venous pressure would rise greatly, and arterial pressure would fall greatly. These changes may be too big to cope with. The large increase in venous pressure pushes starling’s curve onto the flat part (over filling of the ventricles leading to stretching, see above).
There is a risk of pulmonary oedema, because the outputs of the right and left ventricle can only be matched by stroke volume, which relies on Starling’s curve. If the right heart pumps more, the left fills more and so pumps more. But if at the top of the starling curve the left heart cannot respond to the right, blood accumulates in the lungs.
o Overfilling of the ventricles is prevented by a rise in heart rate
o When venous pressure starts to rise, heart rate is already high
o Stroke volume kept down, but CO increased
o Demand met – System Stable
194
What is the response of the CVS to standing up and postural hypotension?
o On standing, blood pools in the superficial veins of the legs (Great/Short Saphenous veins) due to gravity
o Central venous pressure falls
o Cardiac output falls due to the fall in venous pressure (starling’s law)
o Arterial pressure falls
o Both arterial and venous pressure falling
o Baroreceptors detect fall in arterial pressure
o Raise HR, but venous pressure is still low
o TPR increased to defend arterial pressure (skin, gut)
Sometimes these reflexes (Baroreceptor Reflex) don’t work. This is referred to as postural hypotension.
195
What is the response of the CVS to haemorrhage?
o Reduced blood volume lowers venous pressure
o So cardiac output falls (Starlings law)
o Arterial pressure falls
o Baroreceptors detect fall in arterial pressure, HR rises, TPR increased
o Rise in HR lowers venous pressure further ß Problem is worse, not better
o HR can become very high
o Venous pressure needs to be increased to solve original problem
o Veno-constriction
o Blood transfusion to replace lost volume
196
What is the response of the CVS to a long term increase in blood volume?
Blood volume is under the control of the kidney
o If blood volume increases for days à Increase in venous pressure
o Cardiac output rises
o Arterial pressure rises
o More blood peruses tissues, which auto-regulate and increase TPR
o Arterial pressure rises further, and stays up
197
What is the perfusion rate?
Rate of blood flow
198
What is cardiac output at rest of a normal individual?
5Lmin-1
199
What is cardiac output during exercise in a normal individual?
25Lmin-1
200
Where is blood flow fastest (related to total cross sectional area)
Where the TOTAL cross sectional area is at its least
Aorta= 2.5cm^2 (fast flow)
Capillaries= 4500cm^2 (slow flow)
201
What is a clinical point about the vagus nerve?
Left recurrent laryngeal innervates the heart and loops back round to supply the around hence people with pericarditis or extra pressure on the heart may present with a hoarse voice
202
What is cardiac tamponade? (Pericardial effusion)
Passage of fluid from pericardial capillaries into the pericardial cavity, accumulation of pus or accumulation of blood
Heart becomes compressed and ineffective
Leads to obstructive shock as the heart fills less
Presents with Becks Triad - hypotension, raised jugular venous pressure, distant muffled heart sounds on examination
203
What is pericardiocentesis?
Needle used for drainage of fluid from the pericardial sac- as in cardiac tamponade
Wide bore needle may be inserted left 5th/6th intercostal space near the sternum
204
What is pericarditis?
Inflammation of pericardium
Causes chest pain
ECG shows ST elevation with ward concavity in all leads
Serous layer can become rough and fibrosed (may calcify) --> sounds like rustle of silk on auscultation
205
Describe the auscultation of the valves
ALL- Aortic (2nd intercostal space right sternal edge)
PROSTITUTES- Pulmonary (2nd intercostal space left sternal edge)
TAKE- Tricuspid (4th intercostal space left sternal edge)
MONEY- Mitral (5th intercostal space mid clavicular line)
206
What is interesting about the great cardiac vein?
When it turns left- one of the only times that the (left circumflex) artery and vein are running in the same direction
207
What two things fill in diastole?
Ventricles
| Aortic sinus
208
Describe the spread of excitation over a normal heart
An action potential is generated by the pacemaker cells in the SAN (1), and electrical activity spreads over the surface of the heart to the AV node, where there is a delay of ~120ms (2).
After the delay, the excitation spreads down the septum via the right and left bundle branches (3), then out over the ventricular myocardium, from inside to outside (endocardial to epicardial surface) until all ventricular cells are depolarised. (4/5)
After ~280ms the cells begin to repolarise. Repolarisation spreads in the opposite direction over the ventricle to depolarisation (epicardial to endocardial surface).
209
How do intracellular electrodes view systole in cardiac myocytes?
Normal membrane potential versus time graph of an action potential of a cardiac myocytes- so an increase, transient decrease, plateau, rapid decrease
210
How do extracellular electrodes view systole in cardiac myocytes?
Extracellular electrodes only record changes in membrane potential, therefore skin electrodes ‘see’ two signals with each systole- so an upwards and downwards deflected signal
211
What rules govern the sign and size of the deflection in an ECG?
Depolarisation moving towards an electrode – Upward Signal
Depolarisation moving away from an electrode – Downward Signal
Repolarisation moving towards an electrode – Downward signal
Repolarisation moving away from an electrode – Upward Signal
The more muscle (greater thickness) depolarising and the more directly towards the electrode the signal is moving, the bigger the amplitude.
212
What does the P wave correspond to and why is it that shape?
Atrial depolarisation will produce a small upward deflection. It is small because there is little muscle, and upward as it is moving towards the electrode.
213
What does the P-Q interval correspond to?
~120ms delay
| At which signal is held at AVN allow g ventricles to fill
214
What does the Q wave correspond to and why is it that shape?
Excitation spreads about halfway down the septum, then out across the axis of the heart. Produces a small downward deflection, downward as it is moving away and small because it is not moving directly away.
215
What does the R wave correspond to and why is it that shape?
Depolarisation spreads through the ventricular muscle along an axis slightly to the left of the septum, producing a large upward deflection. Upwards because it is moving towards the electrode, and large because there is lots of muscle and the signal is moving directly towards the electrode.
216
What does the S wave correspond to and why is it that shape?
Depolarisation spreads upwards to the base of the ventricles, producing a small downward deflection. Downwards because moving away, small because not moving directly away.
217
What does the S-T interval correspond to?
Ventricular contraction (~280ms)
219
What is an ecg?
Electrical signal recorded on electrodes on the body-surface which reflects the electrical activity in the heart muscle
220
How can electrodes change as an electrode is moved?
As the electrode moves around the heart, the directions and amplitude of the waves changes predictably
Corresponds to the rules
An electrode viewing the R wave head on will see a large upward deflection, viewing sideways on sees no signal, viewing end of sees a large downward signal.
221
What is a lead wrt ECGs?
A lead refers to an imaginary line between 2 ECG Electrodes
| There are 12 leads but 10 electrodes
222
What are the 6 limb leads and where are the 4 electrodes placed?
LeadI- views heart from the left side (L)
LeadII- views heart from the apex (I)
LeadIII- views heart from the bottom (I)
aVL- (L)
aVR-(L)
aVF- (I)
Red- right arm - right upper
Yellow- left arm -left upper
Green- left leg - left lower
Bue- right leg - right lower
Provides a vertical view of the heart
223
What are the 6 chest leads and where are the 6 electrodes placed?
V1 - red- 4th intercostal space - right sternal edge (S)
V2 - yellow- 4th intercostal space – left sternal edge (S)
V3 - brown- 5th rib (between 1 and 2) (A)
V4 - green- 5th intercostal space - mid clavicular (A)
V5 – black- anterior axillary line - 5th intercostal space (between 4 and 6) (L)
V6 – purple- mid-axillary - 5th intercostal space (L)
224
What 8 things should be looked at when assessing an ECG?
```
Rate
Rhythm
Axis
P wave
P-R segment
QRS segment
Q-T interval
T wave
```
225
How can RATE be interpreted in an ECG?
An ECG is always ran at a standard rate
Some ECGs have a rhythm strip corresponding to lead II which can be used to calculate the rate
Standard- small square= 0.04s // large square= 0.2s // 5 large squares= 1s // 300 large squares= 1 minute
Therefore rate = 300/ number of large squares in the R-R interval
~60bpm
226
How can RHYTHM be interpreted in an ECG?
Can be detained from any lead
Regular or irregular
Consistent relationship between atrial and ventricular depolarisation
227
How can AXIS be interpreted in an ECG?
Relationship between the thickness of the muscle and the overall direction of qRs depolarisation of ventricles
Relates to the main spread depolarisation through the wall of the ventricles – R wave
Combination of depolarisation of the right and left ventricle generate a single vector normally pointing slightly to the left
More muscle in the left ventricle means the left shift
More muscle in the right ventricle means the right shift
Look at Limb leads to estimate the axes
Find the lead with the smallest and most equiphasic deflection
The net deflection is Zero indicating that the electrical axes must run at right angles to that view
Usually parallel to lead II
228
What is right axis deviation in an ECG?
When there is right ventricular hypertrophy
I: deflection becomes negative
I&II: deflection becomes more positive
229
What is left axis deviation in an ECG?
Due to a conduction defect/ not left ventricular hypertrophy
II: deflection becomes negative- deviation is SIGNIFICANT
III: deflection becomes negative
230
How can the P WAVE be interpreted in an ECG?
Reflects atrial depolarisation
| Absent in atrial fibrillation
231
How can The P-R SEGMENT be interpreted in an ECG?
Time taken to reach the ventricles/ conduction time of AVN
Useful in identifying e pathology of the AVN
The P-R interval should be between 0.12-2.0 seconds (3-5 small squares)
FIRST DEGREE HEART BLOCK- elongate P-R segment
TYPE 1 SECOND DEGREE HEART BLOCK- very erratic P- R segment; P-R segment elongates until a QRS complex is dropped
TYPE 2 SECOND DEGREE HEART BLOCK- constant P-R segment with randomly absent QRS complexes
COMPLETE THIRD DEGREE HEART BLOCK- no relationship between P wave and QRS complex
232
How can QRS Complex be interpreted in an ECG?
Tells us about the axis of the heart and pattern of conduction through the ventricles
The QRS complex should be 0.12 seconds (3 small squares)
If longer than 0.12 seconds it suggests the complex originated in the ventricles
If shorter than 0.12 seconds it suggests the complex is supra-ventricular in origin
Bundle branch block- damage to conducting pathways alters the route of spread of depolarisation and changes the shape of the QRS complex
233
How can the ST SEGMENT be interpreted in an ECG?
The ST segment is the part of the ECG between the end of the S wave & start of the T wave
In a healthy individual it should be an isoelectric line (neither elevated or depressed)
Abnormalities of the ST segment should be investigated to rule out pathology
ST elevation is significant when it is > 1mm (1 small square) in relation to the baseline
It is most commonly caused by acute myocardial infarction
The morphology of the ST elevation differs depending on how long ago the MI occured
ST depression is significant when it is >1mm (1 small square) in relation to the baseline
ST-depression lacks specificity, therefore you shouldn’t jump to any diagnostic conclusions
It can be caused by many different things including;
Anxiety, Tachycardia, Digoxin toxicity, Haemorrhage, Hypokalaemia, Myocarditis, Coronary artery insufficiency, MI
As a result you must take this ECG finding & apply it in the context of your patient
234
How can the T WAVE be interpreted in an ECG?
Inverted T waves are one of the most common abnormalities found on ECG
They lack specificity as they are affected by lots of processes & thus should not be used alone to form a diagnosis
Inverted T-waves in V1 & V2 are not significant & seen in healthy individuals
Some of the causes of inverted T-waves are: Smoking, Anxiety, Tachycardia, Haemorrhage & Shock, Hypokalaemia, Pericarditis,, MI (new & previous), Bundle branch block, WPW syndrome
As a result you must take this ECG finding & apply it in the context of your patient
A T-wave is considered tall when it is greater than;
5mm in the standard leads and 10mm in the precordial leads
Tall T-waves can be caused by: Hyperkalaemia, Myocardial Ischaemia (usually hyper-acute MI)
In hyperkalaemia the T-waves are described as “Tall Tented T-waves”
This is because alongside been tall they are also very narrow, with a sharp apex
In hyper-acute MI you also get tall T-waves however they are not as narrow as in hyperkalaemia
235
What does the T wave correspond to and why is it that shape?
7. Repolarisation begins on the epicardial surface. Spread through the ventricular myocardium in the opposite direction to depolarisation. Produces a medium upward deflection. Upwards because it is moving away, medium because timing in different cells is dispersed.
236
Describe what happens with a ventricular ectopic beat
Ventricular cells gain pacemaker activity, causing ventricular contraction before the underlying rhythm would normally depolarise the ventricles. The resulting ECG often appears wider and taller than that seen with the underlying rhythm.
Ventricular ectopic beats may occur every other beat, every third beat, every fourth beat etc, or in groups such as couplets, triplets, etc.
237
Describes what happens in atrial fibrillation
The P wave reflects atrial depolarisation, and if the muscles are not contracting in a coordinated way (atrial fibrillation), the P wave will be absent. In its place are irregular fibrillation waves.
There is no regular stimulus reaching the AV node, so other pacemakers must generate rhythm.
238
Describe what happens in ventricular fibrillation
Uncoordinated contraction of the ventricular myocardium causes it to quiver rather than contract properly.
239
What is heart block?
Communication between the atria and ventricles- related to AVN
240
Describe what happens in first degree heart block
In First-Degree heart block, the P-R interval is elongated from its normal 200ms. There is a conduction delay through the AV node, but all electrical signals reach the ventricles.
241
Describe what happens in type 1 second degree heart block
In Type 1 Second-Degree heart block, the P-R interval is erratic. It follows a pattern of the PR interval elongating, until eventually a QRS complex is dropped. The system is then reset. Some, but not all atrial beats get through to the ventricles.
242
Describe what happens in type 2 second degree heart block
In Type 2 Second-Degree heart block, electrical excitation sometimes fails to pass through the AV node or bundle of His. Electrical conduction usually has a constant P-R interval, but not all atrial contractions are following by ventricular contraction.
243
Describe what happens in third degree complete heart block
In Complete, Third-Degree heart block, atrial contractions are normal, but no electrical conduction is conveyed to the ventricles. The ventricles then generate their own signal through an ectopic pacemaker. These beats are usually slow.
244
What are the effects of bundle branch block on the QRS complex?
A Bundle Branch Block lengthens and changes the shape of the QRS complex. There are many variations depending on the location of the block.
245
What is the effect of a myocardial infraction on an ECG?
Death of part of the myocardium leads to myocardial infarction
This affects the spread of electrical activity and generates a current flow during systole
Current flows in systole produce extra signals in the ST segment
This often reduces ST ELEVATION=STEMI
The lead with the most prominent view helps us t identify which art of the heart is affected and how badly (which coronary artery is blocked and whether the whole thickness of the ventricular wall has been affected)
246
When can you get ST depression?
When part if the myocardium becomes temporarily short of oxygen, there is a reduced blood flow, and one can get angina and ST DEPRESSION
247
What are three main features of a myocardial infarction which appear in an ECG?
ST ELEVATION
PATHOLOGICAL Q WAVES
INVERTED T WAVES
248
What are the 5 main special circulations of the body?
```
Pulmonary
Cerebral
Coronary
Skeletal
Cutaneous
```
249
What are the 2 circulations of the lungs?
Pulmonary circulation- blood supply to the alveoli, required for gas exchange, must be able to accept entire cardiac output from the RV (at rest- 5l/min and max cardiac output- 20-25l/min)
Bronchial circulation- part of the systemic circulation, meets metabolic requirements of the lungs
250
What is the ideal pressure and resistance of the pulmonary circulation?
Low pressure
| Low resistance
251
Describe the low pressure of the pulmonary circulation
Mean arterial pressure ~12-15mmHg (lower than RV)
Man capillary pressure ~9-12mmHg (lower than arterial)
Mean venous pressure ~5mmHg (lower than capillary)
Allows movement from high pressure to low pressure
252
Describe the low resistance of the pulmonary circulation
Short, wide vessels
Lots of capillaries (many parallel elements)
Arterioles have relatively little smooth muscle
253
What are some adaptations of pulmonary circulation to promote efficient gas exchange?
Very high density of capillaries in alveolar wall - large capillary surface area
Short diffusion instance- very thin layer separating gas phase from plasma; combined endothelium and epithelium thickness is ~0.3 micro metres
Large surface area and short diffusion distance produces high carbon dioxide and oxygen transport capacity
254
What is the ventilation perfusion ratio and what is the optimal value?
Alveoli are perfused with blood and ventilated with air
For sufficient oxygenation we need to match ventilation of the alveoli with perfusion of the alveoli
Optimal V/Q ratio= 0.8
Maintaining this V/Q ratio means that we need to divert blood from alveoli which are not well ventilated (does this by hypoxia pulmonary vasoconstriction)
255
How does the body maintain an optimal ventilation perfusion ratio?
Hypoxic pulmonary vasoconstriction ensures optimal ventilation perfusion ratio (vsmc contract in response to low oxygen levels and reduces blood flow to match ventilation)
- most important mechanism regulating pulmonary vascular tone
- alveolar hypoxia results in vasoconstriction of pulmonary vessels
- ensures that perfusion matches ventilation
- poorly ventilated alveoli are less well perfused
- helps to optimise gas exchange
256
What can result when there is increased pulmonary vasoconstriction as a result of poor ventilation?
Chronic hypoxic vasoconstriction which can cause right ventricular failure
- chronic hypoxia can occur at a high altitude OR as a consequence of lung disease (such as emphysema)
- results in chronic vasoconstriction and chronic increase in vascular resistance - chronic pulmonary hypertension
- high after load on right ventricle can lead to right ventricular heart failure
257
Why are pulmonary vessels strongly influenced by gravity?
Los pressure pulmonary vessels are strongly influenced by gravity
In the upright position (orthostasis) there is a greater hydrostatic pressure on vessels in the lower part of the lung
Apex- vessels collapse during diastole
Heart- vessels are continuously patent
Base- vessels are distended by gravity (hydrostatic pressure)
258
How does exercise affect pulmonary blood flow?
Increased cardiac output
Small increase in pulmonary arterial pressure
Opens apical capillaries
Increased oxygen uptake by lungs
As blood flow increases capillary transit time is reduced- at rest transit time ~1s; can fall to ~0.3s w/o compromising gas exchange
259
How is tissue fluid formed in the lungs?
Starling forces determine fluid formation
Hydrostatic pressure of blood within the capillary – influenced more by venous pressure in systemic circulation/pushes fluid out of the capillary
Oncotic pressure (colloid osmotic pressure) – pressure exerted by large molecules such as plasma proteins – draws fluid into the capillaries
Fluid moves out at arterial end and in at venous end
260
How is capillary pressure related to the formation of lung lymph?
Low capillary pressure minimises the formation of lung lymph
Filtration~= absorption – but there is some tissue fluid formed – enough for the lungs to cope with without the buildup of fluid which would cause an impairment on gas exchange
Low capillary pressure prevents pulmonary oedema – pulmonary capillary pressure is normally low (9 to 12 mmHg); only a small amount of fluid leaves the capillaries (lung lymph)
Can get pulmonary oedema if capillary pressure increases causing more fluid to filter out- if left atrial pressure rises to 20 to 25 mmHg- mitral valve stenosis/ left ventricular heart failure
261
What can cause pulmonary oedema?
```
Mitral valve stenosis, left ventricular heart failure
Increase in left atrial pressure
Pulmonary capillary pressure increases
More fluid filters out
Pulmonary oedema
```
262
What are some effects of pulmonary oedema and how is it managed?
```
Pulmonary oedema impairs gas exchange
- affected by posture (changes in hydrostatic pressure due to gravity)
- mainly at base when upright
- throughout lungs when lying down
Use diuretics to relieve symptoms
Treat underlying cause
```
263
Describe how the brain has a high oxygen demand and why?
Receives 15% of the cardiac output - but only accounts for 2% of the body mass
Oxygen consumption of grey matter accounts for about 20% of total body consumption at rest
- must provide a secure oxygen supply - neurones cannot last without an oxygen supply
264
How does this cerebral circulation meet the high demand for oxygen?
```
High capillary density
– large surface area for gas exchange
– Reduced diffusion distance (<10micrometres)
High basal flow rate
– x10 average for whole
High oxygen extraction
– 35% above average
```
265
Why is a secure oxygen supply to the brain vital?
Neurones are very sensitive to hypoxia
Loss of consciousness after a few seconds of cerebral ischaemia
Begin to get irreversible damage to neurones in about four minutes
Interruption to blood supply e.g. a stroke causes neuronal death
266
How is a secure blood supply to the brain ensured?
Structurally – anastomosis between basilar and internal carotid arteries
Functionally – brain stream regulates other circulations- alters systemic outflow to rest of the body/maintains and increases blood to brain; Myogenic autoregulation maintains perfusion during hypotension; Metabolic factors control blood flow
267
What is myogenic autoregulation?
Cerebral resistance vessels have a well-developed myogenic response to changes in transmural pressure (Changes in structure of smooth-muscle cells/blood vessels)
Increase in blood pressure – vasoconstriction
Decrease in blood pressure – vasodilatation
- Serves to maintain cerebral blood flow when BP changes
- Fails below 50mmHg
Myogenic autoregulation keeps a very stable crabplover large range of pressures (60- 180mmHg)
268
What is metabolic regulation?
Cerebral vessels are very sensitive to changes in arterial partial pressure of carbon dioxide
Hypercapnia – high partial pressure of carbon dioxide – vasodilatation
Hypocapnia – low partial pressure of carbon dioxide – vasoconstriction
– Panic-ventilation can cause hypocapnia and cerebral vasoconstriction – dizziness/fainting
269
How does regional activity affect blood flow?
Regional activity produces local increases in blood flow seen with an MRI)
– Areas with increased neuronal activity have increased blood flow
Increase in partial pressure of carbon dioxide
Increase in [K+]
Increase in adenosine
Causing vasodilatation and increased blood flow
Decrease in partial pressure of carbon dioxide
(Regions where there is activity, there is an increase in metabolites, vasodilatation of cerebral arterioles and increased blood supply for activity and increases removal of waste (CO2) )
270
What is the Cushing's reflex?
Rigid cranium protects brain – but does not allow for volume expansion
Increases in intracranial pressure impairs cerebral bloodflow – cerebral tumour /haemorrhage
Impaired blood flow to vasomotor control regions of the brain stem increases sympathetic vasomotor activity- increases arterial blood pressure and helps maintain cerebral blood flow
-increased sympathetic output to peripheral arterioles maintains cerebral blood flow
271
Describe the blood brain barrier
Cerebral capillaries form a tight blood brain barrier
Lipid soluble molecules such as oxygen and carbon dioxide can diffuse freely
Lipid insoluble solutes (potassium and catecholamines) can't diffuse freely
272
What are three symptoms indicative of high inter cranial pressure?
High arterial blood pressure
Irregular breathing
Decreased heart rate
273
Describe some key features of coronary circulation
High capillary density facilitates efficient oxygen delivery
Diffusion distance is less than nine micrometres
Continuous production of nitric oxide by coronary endothelium maintains a high basal flow - via vasodilatation
274
How does coronary bloodflow increase to meet myocardial oxygen demand?
Extra oxygen required at high workload is supplied mainly by increased blood flow
Almost a linear relationship until very high in demand
Small increase in amount of oxygen extracted
Vasodilation due to metabolic hyperaemia
Vasodilators – adenosine, potassium and hydrogen
275
What type of arteries are coronary arteries and how is this clinically relevant?
Functional end arteries
- few arterio arterial anastomoses
- prone to atheromas
- narrowed coronary arteries leads to angina on exercise (increased oxygen demand) – bloodflow mostly during diastole- diastole reduced as heart rate increases
- stress and cold can also cause sympathetic coronary vasoconstriction and angina
- sudden obstruction by thrombus causes a myocardial infarction
276
Describe skeletal muscle circulation
Must increase oxygen and nutrient delivery and removal of metabolites during exercise
Important role in helping to regulate arterial blood pressure – 40% of adults body-mass
Resistance vessels have rich innervation by sympathetic vasoconstrictor fibres – baroreceptor reflex maintains BP
Capillary density depends on muscle type – postural muscles have a higher capillary density
Very high vascular tone – Permits and lots of time notation; bloke can increase more than 20 times and active muscle
At first only about half of the capillaries are perfused at any one time (pre capillary spinchters); allows for increased recruitment when necessary
277
How is capillary recruitment increased in skeletal muscle?
Opening of more capillaries increases blood flow and reduces diffusion distance
Pre capillary spinchters
278
How does metabolic hyperaemia cause increased blood flow in skeletal muscle?
-Various agents are thought to act as vasodilators
Increase in K+ conc
Increase in osmolarity
Inorganic phosphates
Adenosine
Increases H+ conc
-adrenaline also acts as a vasodilator at arterioles in skeletal muscle
Acts through B2 receptors
Vasoconstrictor response via NA on alpha1 receptors
279
Describe the cutaneous circulation
Special role in temperature regulation
Core temp is normally maintained around 37°C – balance of heat production and heat loss
Skin is the main dissipating surface – regulated by cutaneous blood flow; also has a role in maintaining blood pressure; vasoconstriction in cutaneous circulation to maintain blood pressure (pale in shock)
280
What are the specialised structures of acral (apical) skin?
Arterovenous anastomoses AVAs)
281
How do AVAs regulate heat loss from apical skin?
Apical skin has a high surface area to volume ratio
AVAs under neural control – sympathetic vasoconstrictor fibres
Not regulated by local metabolites
Decrease core temperature increases sympathetic tone in a AVAs – decreases blood flow to apical skin
Increased core temperature opens AVAs
Reduced vasomotor drive to AVAs allows them to dilate
Low resistance shunt to venous plexus
Allows skin temperature to rise so dissipating heat
* You can also get vasodilation in non apical skin
282
How does vasodilation in non-apical skin occur?
Sympathetic/cholinergic/sweat glands
Bradykinin
Vasodilator
Lose heat
283
What are cardiovascular drugs used to treat?
Arrhythmias - NB BB kb cb adenosine
Heart failure- increase co (cardiac glycosides, bags) decrease workload (ace inhibitors, diuretics, bb
Angina - b2b, on, cb
Hypertension - bb, diuretics and ace inhibitors, cb and a1b
Risk of thrombus formation
284
What can cardiovascular drugs alter?
Rate and rhythm of the heart
Force of contraction
Peripheral resistance and bloodflow
Blood volume
285
Define arrhythmia
Abnormality of heart rate or rhythm
286
Give five examples of heart arrhythmias
Bradycardia- slow heart rate
Atrial flutter – rapid succession of heart beats – lots of P-waves
Atrial fibrillation – atria contract in random manner – loss of P-waves
Tachycardia – fast heart rate
VENTRICULAR FIBRILLATION – EMERGENCY – NOT PUMPING BLOOD FROM VENTRICLES - DEATH
287
Describe two examples of tachycardia
- Ventricular tachycardia (arises due to problems in bundle of His, Purkinje fibres or ventricular myocytes – following an MI due to ectopic pacemaker activity from damaged myocardium) - can lead to VF
- Supraventricular tachycardia (arises due to problems in the atria or AVN)
288
What are three main causes of arrhythmia?
Ectopic pacemaker activity
– Damaged areas myocardium becomes depolarised and spontaneously active
– Leak of potassium ions depolarises adjacent cells
– latent pacemaker region activated due to ischaemia – dominates over sinoatrial node (SAN)
After depolarisations – abnormal depolarisations following action potential (= triggered activity)
– Delayed after depolarisation - more likely to happen if IC [Ca2+] is high
– Early after depolarisation- more likely to happen if AP is prolonged - longer QT interval ; can lead to oscillations
Reentrant mechanism
- conduction delay and accessory pathways- alternate routes around damaged tissue
- reentrant loop forms when there is incomplete conduction damage
(E.g. Mitral valve stenosis can cause several small reentrant loops in atria- AF- pulmonary oedema- thrombus- brain- stroke
289
What are the 4 main classes of anti arrhythmic drugs?
Class I - drugs that block voltage gated Na+ channels
Class II - Beta adrenoreceptor antagonists
Class III - drugs that block voltage gated K+ channels
Class IV - drugs that block voltage gated Ca 2+ channels
Also a 5th class- misc
290
What is an example of a class I anti-arrhythmic drug and how does it work?
Drugs that block voltage gated sodium channels
E.g. lidocaine – local anaesthetic
– Blocks voltage gated sodium channels in open or inactive state for just enough time between action potentials preventing any abnormal depolarisations and electrical activity between action potentials (USE DEPENDENT)
– Disassociates rapidly in time for next action potential so won't stop normal action potentials from occurring
– Used following myocardial infarction – damaged myocardium – depolarised (abnormal electrolyte balance)– so there are more sodium channels open in depolarised tissue needed to be blocked-- fire randomly and automatically, tachycardia
– Not given prophylactically following a myocardial infarction
– Weak bases- hydrophobic and hydrophilic (use dependent) pathway
291
What is an example of a class II anti-arrhythmic drug and how does it work?
Beta adrenoreceptor antagonist/ Beta blockers
E.g.propranolol, atenolol
– Block sympathetic action by acting at Beta1 adrenoreceptors in the heart, reducing the IC [Ca2+] and hence storage of calcium so upon arrival of action potential there is decreased force of contraction of the heart
– Decreases slope of pacemaker potential in SAN
– Used following myocardial infarction – since myocardial infarction causes increased sympathetic activity – beta-blockers decrease sympathetic activity – prevents ventricular tachycardia
– Reduced oxygen demand – reduced myocardial ischaemia, beneficial following myocardial infarction
– Beta blockers slow conduction in AVN – prevents supraventricular tachycardias
292
What is an example of a class III anti-arrhythmic drug and how does it work?
Drugs that block voltage gated K+ channels
E.g. Amiodarone
– Prolong action potential by blocking potassium channels, by increasing length of absolute refractory period
– Prevents another action potential occurring too soon – can be proarrhythmic
– Class III are not generally used as can be proarrhythmic- Amiodarone is the only known used one
– Has other actions – Beta2 receptor antagonist and Na+ channel blocker
– Used to treat tachycardia associated with Wolff-Parkinson-White syndrome – re-entry loop due to an extra conduction pathway
293
What is an example of a class IV anti-arrhythmic drug and how does it work?
Drugs that block voltage gated calcium channels
E.g. Verapamil
Decreases slope of pacemaker potential at SAN
Decreases AVN conduction
Decreases force of Contraction (negative inotropy)
Coronary and peripheral vasodilation
Dihydropyridine calcium channel blockers ineffective in preventing arrhythmias- but act on vascular smooth muscle
294
What anti arrhythmic drug is a drug that does not belong to the main 4 classes and how does it work?
```
Adenosine
Does not belong to a class
Produced endogenously
Acts on A1 receptors (GPCR) at AVN
Enhances K+ conductance- hyper polarises cells of conducting tissues- decreases cAMP levels- slows conduction rapidly at AVN- stops conduction for 10 seconds- reforms proper rhythm
Short acting
```
295
What is heart failure?
Chronic failure of heart to provide sufficient output to meet the bodies requirements
– Reduced force of contraction
– Reduced cardiac output
– Reduced tissue perfusion
– Oedema- (peripheral right and pulmonary left)
296
What two types of drugs can be used in the treatment of heart failure?
Positive inotropes which increase cardiac output
| Drugs which reduce workload of the heart
297
What are some examples of positive inotropes which increase cardiac output in treatment of heart failure and how do they work?
Cardiac glycosides
– Improved symptoms but not long-term outcome
Example digoxin (leaves of foxglove)
– Block Na+/K+ ATPase pump
– Rise in IC [Na+]
– Sodium calcium exchanger (NCX- normally extrudes Ca2+-driven by Na+ moving down its conc grad) cannot function very well
– So not as much Ca2+ leaves – rise in IC [Ca2+]
– more Ca2+ stored in SR
– Arrival of AP - CICR releases more Ca2+
– increased force of contraction of heart
– cardiac glycosides can also cause increased vagal activity- action via CNS to increase basal activity; slows AV conduction; slows heart rate (PSNS)
```
Beta adrenoreceptor agonists
Dobutamine
– acts on B1 receptors
– cardiogenic shock
– acute but reversible heart failure (after cardiac surgery)
– increases myocardial contractility
```
Generally make the heart work harder and so are not used often
298
What are some examples of drugs which reduce the workload of the heart in treatment of heart failure and how do they work?
Reduce afterload and preload
Ace inhibitors
– Inhibits action angiotensin-converting enzyme
– Prevents conversion of angiotensin 1 into angiotensin II
– Angiotensin II acts on kidneys to increase sodium and water reabsorption – increasing blood volume – vasoconstriction – increase resistance – harder for the heart to contract
(Angiotensin II is a strong vasoconstrictor)
– Reduces workload of the heart
– Decreases vasomotor tone – decreases blood pressure
– Reduces afterload of the heart
– Decreases fluid retention – decreases blood volume
– Reduces preload of the heart
Beta adrenoreceptor antagonists/ Beta-blockers- block SNS
Diuretics- reduce blood volume by targeting kidneys to lose more water; reduces preload of the heart
299
What is angina?
Occurs when oxygen supply to the heart does not meet its need
Ischaemia of heart tissue – chest pain
Usually pain with exertion
Due to narrowing of the coronary arteries- atheromatous disease
300
What drugs are used to treat angina?
– Beta2 adrenoreceptor blockers
– Calcium channel antagonist
– Organic nitrates
301
How do B2 adrenoreceptor antagonist (B blockers) reduce the workload of the heart and prevent angina?
Causes vasodilatation in myocardium by increasing cAMP and opening K+ channels and relaxing smooth muscle
Reduces the force of contraction required to push through the narrowed arteries and reduces work load of heart
302
How do Ca2+ channel antagonists reduce the workload of the heart, improve blood supply to the heart and prevent angina?
Causes peripheral vasodilation, vsmc's relax
Less Ca2+ entry in ventricular AP, less Ca2+ stored in SR
Reduced force of contraction and workload of heart
303
How do organic nitrates reduce the workload of the heart, improve blood supply to the heart and prevent/ treat angina?
Organic nitrates + thiols (-SH) vsmc's --> NO2- released --> reduced to NO (powerful vasodilator)--> vasodilation
E.g. Glyceryl trinitrate (GTN SPRAY) - fast acting
E.g. Isosorbide dinitrate- long acting
NO stimulates guanylate cyclase to convert GTP to cGMP
cGMP activates PKG within vascular smooth muscle cells causing a decrease in IC [Ca2+] and hence relaxation of vsmc's
Main action-
VENOdilation - lowers preload and venous pressure, heart fills less so there is reduced force of contraction of heart (starlings law), lowers oxygen demand
Secondary action- acts on collateral coronary arteries- improves oxygen delivery to ischaemic myocardium NOT ARTERIOLES
304
What conditions increase the likelihood of thrombus formation?
Certain heart conditions-
AF
Acute MI
Mechanical prosthetic heart valves
305
What two categories of drugs are used to prevent/treat thrombus formation?
Anticoagulants
| Antiplatelet drugs
306
How do anticoagulants stop/reduce thrombus formation and give some examples?
```
Heparin (IV)
- inhibits thrombin
- used acutely for SHORT TERM action
Fractionated Heparin (SC)
Warfarin (oral)
- antagonises action of vitamin K
- can be used LONG TERM
```
307
How do antiplatelet drugs stop/ reduce thrombus formation and give some examples?
Aspirin (low dose)
- following acute MI or high risk of MI
- reduces risk of thrombus formation in Cardiac Arrest
- irreversibly acetylates in platelets an enzyme (Cox) of prostaglandin metabolism so that platelets can't produce thromboxane A2 - platelet activator
- The formation of a haemostatic plug is inhibited and bleeding time is prolonged
308
What is hypertension?
Increase in pressure in the vasculature
Associated with an increased blood volume or increase in TPR
Na+ and H2O retention by kidneys
>140/90
309
What drugs can be used to treat hypertension?
Beta blockers- decrease cardiac output
Diuretics or ACE inhibitors- decrease blood volume, decrease TPR, decrease sodium and water retention by kidney
Ca2+ channel blockers (vsmc's) and alpha1 adrenoreceptor antagonists- vasodilation
310
What three equations are associated with hypertension?
```
CO = SV x HR
P = F x R
BP = CO x TPR
```
311
What are the 4 main broad areas of the body where a cause of chest pain can result from?
Heart and great vessels
Lungs and pleura
Gastrointestinal system
Chest wall
312
What are some causes of chest pain in the heart and great vessels? And what does the pain present as?
Central chest pain
Myocardium- angina, MI - tightening, typical radiation, risk factors
Pericardium- pericarditis - sharp, increases with breathing, decreases with leaning forward
Aorta- aortic dissection - tearing pain, radiates to between shoulder blades and down the back
313
What are some causes of chest pain in the lungs and pleura? And what does the pain present as?
Lateral chest pain, increases on inspiration, associated respiratory symptoms
Pulmonary embolism- sudden onset breathlessness, DVT, risks of DVT present
Spontaneous pneumothorax- sudden onset, breathlessness
Pneumonia- also fever and yellow sputum
314
What are some causes of chest pain in the gastrointestinal system? And what does the pain present as?
With epigastric pain and GI symptoms
Oesophagus- gastro-oespphagal reflux disease (GORD)- burning pain, radiation upwards, worse on lying down, bending down, after some foods, decrease with antacids
Peptic ulcer disease
GB- biliary colic and cholecystitis
315
What are some causes of chest pain in the chest wall? And what does the pain present as?
```
Often localised pain, movements may increase pain, history of trauma/ use
Ribs- fractures, bone metastases
Costochondral joints
Muscles
Skin (herpes zoster neuralgic pain)
```
316
What are some non modifiable risk factors of coronary atheroma and IHD?
Increasing age
Male gender (females catch up after menopause)
Family history
317
What are some modifiable risk factors of coronary atheroma and IHD?
```
Hyperlipidaemia*
Smoking*
Hypertension*
Diabetes mellitus*
Exercise
Obesity
Stress
```
318
Describe ischaemic chest pain
Any IHD can cause chest pain that is central, retrosternal, or left sided.
The pain may also radiate to the shoulders and arms, with the left side more common than the right along with the neck, jaw, epigastrium and back. It may even present with pain at these sites without chest pain.
The pain is described as ‘tightening’, ‘heavy’, ‘crushing’, ‘constricting’, and ‘pressure’. Occasionally the pain is described as burning epigastric pain, particularly in inferior MI.
The pain varies in intensity and duration, the onset, precipitating, aggravating and relieving factors and associated symptoms all vary and get progressively worse from stable angina to unstable angina to MI.
319
What is stable angina?
Atheromatous plaques, with a necrotic centre and fibrous cap build up in the coronary vessels, occluding more and more of the lumen, leaving less space for the passage of blood. This leads to ischaemia of the myocardium.
Angina occurs when the plaque occludes more than 70% of the lumen.
Chest pain in stable angina is typical ischaemic chest pain (see above) in brief episodes, brought on by exertion, emotion particularly after meals and in cold weather. It is described as mild to moderate pain.
320
How can stable angina be treated?
Acute Episodes – Sub lingual nitrate spray/tablet
Prevent Episodes - b-blockers, Ca2+ channel blockers, Oral nitrates
Prevent Cardiac Events – Aspirin, Statins, ACE Inhibitors
Long Term – Consider revascularisation (see below)
321
What is unstable angina?
As angina worsens due to the progression of the formation of the Atheromatous plaque, it progresses from Stable to Unstable Angina. This happens due to increased occlusion of the lumen.
Unstable Angina is classified as Ischaemic Chest Pain that occurs at rest (or with minimal exertion) described as severe pain and occurring with a crescendo pattern (distinctly more severe, prolonged, or frequent than before)
322
Describe an MI
A MI is a complete occlusion of a coronary vessel, leading to an infarct (death) of the myocardium it supplies.
The fibrous cap of the Atheromatous plaque can undergo erosion or fissuring, exposing blood to the thombogenic material in the necrotic core. The platelet ‘clot’ is followed by a fibrin thrombus, which can either occlude the entire vessel where it forms or break off to form an embolism.
MI presents with typical ischaemic chest pain (see above) that is very severe, persistent, at rest and often with no precipitant. It is not relieved by rest or nitrate spray. The patient may also be breathless, faint (due to LV dysfunction) have a ‘feeling of impending death’ and will have autonomic features present such as sweating, pallor, nausea and vomiting.
323
What is a STEMI?
- ST Elevated Myocardial Infarction
| - Infarct is full thickness of myocardium
324
What is a NSTEMI?
– Non ST Elevated Myocardial Infarction
| – Infarct is not full thickness of myocardium
325
How would you investigate a patient with angina?
The clinical diagnosis of Angina is based on history. There are no specific signs on examination, but may show signs related to…:
Risk Factors
- Elevated BP
- Corneal Arcus
LV Dysfunction
Evidence of atheroma elsewhere
- E.g. signs of peripheral vascular disease
The resting ECG is usually normal, but may show signs of a previous MI (pathological Q wave). To confirm angina and assess it’s severity, an exercise stress test is undertaken.
Exercise Stress Test
Graded exercise on a treatment connected to an ECG until:
- Target heart rate reached
OR
- Chest Pain
OR
- ECG changes
OR
- Other problems – arrhythmias, low BP etc…
Test is positive is the ECG shows ST Depressions of > 1mm. A strong positive test indicates critical stenosis.
326
What is acute coronary syndrome?
Acute Coronary Syndrome (ACS) relates to a group of symptoms attributed to the obstruction of the coronary arteries. ACS is a result of:
- Unstable Angina
- NSTEMI
- STEMI
327
Describe how an ECG can be used to diagnose and MI
...
328
How can troponins be used in the diagnosis of MI?
Troponins
Cardiac Troponin I (cTnI) and Troponin T (cTnT) are proteins important in actin/myosin interaction, which are released in myocyte death.
It is a very sensitive and specific marker, rising 3-4hrs after the first onset of pain and peaking at 18-36hrs. They will then decline slowly for up to 10-14 days.
329
How can creatine kinase be used in the diagnosis of MI?
```
Creatine Kinase (CK)
Three iso-enzymes present in the skeletal muscle, heart, brain.
```
CK-MB is the cardiac iso-enzyme, rising 3-8hrs after onset, peaking at 24hrs.
Levels will return to normal in 48-72hrs.
The presence of either of these enzymes means there has been death of the myocardium. It therefore distinguishes between unstable angina and NSTEMI, as there is no tissue death in unstable angina and there is in NSTEMI.
330
Describe the treatment of unstable angina/ MI
```
Goal : Prevent UA from progressing to MI and limiting muscle loss in MI
Prevent progression of thrombosis
- Anti Thrombotic therapy
o Anti platelet agents: Aspirin
o Anticoagulants: Heparin
Restore perfusion of partially occluded vessels
- High risk
o Early Percutaneous Coronary Intervention (Angioplasty) (PCI)
o Coronary Artery Bypass Graft (CABG)
- Low Risk
o Initially medical treatment
- General
o Pain control
o O2
o Organic Nitrates
o b-blockers
o Statins
o ACE-Inhibitors
```
331
Describe the three main treatments used in coronary heart disease
Angiography can be used to view any vessel occlusions, and from the findings choices can be made about revascularisation surgeries
Percutaneous Coronary Intervention (PCI) – Angioplasty and stenting. Inflation of a balloon inside the occluded vessel expands a mesh that holds the vessel open, increasing the lumen size and allowing for more blood to flow.
Coronary By Pass Grafting (CBPG) involves taking an artery from elsewhere in the body, e.g. internal mammary artery, radial artery, saphenous vein (reversed because of valves) and grafting it to the heart.
332
What are some causes of acute pericarditis?
Causes
- Infections (viral, TB)
- Post MI/cardiac surgery
- Autoimmune
- Uraemia (kidney failure)
- Malignant Deposits
333
What are some symptoms of acute pericarditis?
Symptoms
- Central/left sided chest pain
- Sharp, worse than inspiration
- Improved by leaning forward
334
What is heart failure?
Heart failure is ‘a state in which the heart fails to maintain an adequate circulation for the needs of the body despite an adequate filling pressure’.
335
What is the primary cause of systolic heart failure?
Ischaemic heart disease
336
What are some causes of ischaemic heart disease?
- Ischaemic heart disease
- Hypertension
- Dilated cardiomyopathy
o Bugs
o Alcohol/Drugs/Poisoning
o Pregnancy
- Valvular heart disease / Congenital
- Restrictive cardiomyopathy e.g. amyloidosis
- Hypertrophic cardiomyopathy
- Pericardial disease
- High-Output heart failure
- Arrhythmia
337
Describe starlings law of the heart and the effect of heart failure on starlings law
The force developed in the myocardium depends on the degree to which the fibres are stretched (or how much the heart is filled). In heart failure the heart can no longer produce the same amount of force (or cardiac output) for a given level of filling.
338
What are the 4 stages of heart disease?
Class I
- No symptomatic limitation of physical activity
Class II
- Slight limitation of physical activity
- Ordinary physical activity results in symptoms
- No symptoms at rest
Class III
- Marked limitation of physical activity
- Less than ordinary physical activity results in symptoms
- No symptoms at rest
Class IV
- Inability to carry out any physical activity without symptoms
- May have symptoms at rest
- Discomfort increases with any degree of physical activity
339
How many sides of the heart can heart failure affect?
One or both sides.
Heart failure can affect one or both sides of the heart. However, right-sided heart failure rarely occurs on its own (although it can in the case of chronic lung disease). The most common scenario is one of left-sided heart failure that raises pulmonary arterial pressure leading to additional right-sided heart failure.
340
What is congestive heart failure?
When both ventricles are affected it is referred to as congestive heart failure.
341
What are some signs and symptoms of left sided heart failure?
Signs/Symptoms of Left Sided Heart Failure
- Fatigue, shortness of breath upon exertion or when lying flat, waking from sleep with shortness of breath
- Tachycardia
- Cardiomegaly (displaced apex beat)
- 3rd or 4th heart sound (‘Gallop rhythm’)
- Functional murmur of mitral regurgitation
- Basal pulmonary crackles
- Peripheral oedema
342
What is right sided heart failure?
Most common is 2ndary to Left Heart Failure
- Chronic lung disease
- Pulmonary embolism/hypertension
- Pulmonary/tricuspid Valvular disease
- Left to Right shunts (ASD/VSD)
- Isolated right ventricular cardiomyopathy
343
What are some signs and symptoms of right sides heart failure?
Signs/Symptoms of Right Sided Heart Failure
- Relate to distension and fluid accumulation (Peripheral Oedema) in areas drained by the systemic veins
- Fatigue, dyspnoea, anorexia, nausea
- Raised JVP
- Tender, smooth hepatic enlargement
- Dependent pitting oedema
- Ascites
- Pleural effusion
344
Describe the involvement of the renin-angiotensin-aldosterone system and the sympathetic nervous system in heart failure
The Renin-Angiotensin-Aldosterone-System (RAAS) system are both activated in heart failure in an attempt to maintain cardiac output. This has the effect of making an already struggling heart work harder.
A drop in blood pressure, such as in heart failure, stimulates renin release from the kidneys.
Renin is an enzyme which catalyses the conversion of angiotensin to angiotensin I. Angiotensin I is converted to II by ACE. Angiotensin II is a powerful vasoconstrictor and promotes the release of aldosterone from the kidneys.
Aldosterone causes salt and water retention in the kidneys, increasing blood volume.
The sympathetic nervous system causes vasoconstriction of blood vessels via the a1 receptor. This increases blood pressure, increasing the workload of the heart by increasing both the preload and afterload on the heart.
Sympathetic innervation of the heart’s b1 receptors will also cause an increase in both Chronotropy and Inotropy.
345
What are some drugs used to treat heart failure?
- ACE-Inhibitors are used in the treatment of heart failure to prevent the conversion of angiotensin I to II. ACE inhibitors thus have an indirect vasodilatory and diuretic effect, both of which are beneficially in the treatment of heart failure by reducing the work load of the heart.
- Diuretics are also important in the treatment of heart failure to reduce blood volume and thus oedema.
- B-blockers are used to prevent the sympathetic innervation of the myocardium, again in an attempt to reduce the heart’s work load. Block b1 receptors on the myocardium
- Ca2+ channel blockers- Reduce contractility of the myocardium
- Organic Nitrates- Veno/Vasodilator à Reduce B.P.
- Cardiac Glycosides- Increase CO and heart contractility by inhibiting the Na/K pump. Raising intracellular Na inhibits NCX, so intracellular Ca2+ increases à in. contractility
346
How is heart failure managed?
- Correct underlying cause
- Non-pharmacological measures
- Pharmacological therapy
o Symptomatic improvement
o Delay progression of heart failure
o Reduce mortality
- Treat complications/associated conditions/cvs risk factors
o Eg arrhythmias
347
What is shock?
There is no unique definition of the term ‘shock’. It is used to describe acute circulatory failure with either inadequate or inappropriately distributed tissue perfusion, resulting in generalised lack of oxygen supply to cells.
348
What is carcinogenic shock?
The inability of the heart to eject enough blood
- Ischaemic cardiac damage
- Arrhythmias
349
What is mechanical shock?
Due to a restriction on the filling of the Heart
- Cardiac tamponade
o Pressure outside the heart impairs filling
Obstruction to blood flow through the lungs
- Pulmonary embolism
o RV cannot empty, reduced return to LA
350
What is hypovolaemic shock?
Loss of circulating fluid volume
- Haemorrhage
o Venous pressure falls, CO falls (Starling’s Law)
o Treat by infusing fluid, colloid/blood
351
What is normovolaemic distributive shock?
Due to uncontrolled falls in peripheral resistance
- Dramatic drop in arterial pressure
- Sepsis
o Endotoxins released by circulating bacteria cause profound peripheral vasodilation
o Treat with adrenaline (Vasoconstriction, a1 receptors) and antibioitcs
- Anaphylaxis
o Release of histamine from mast cells causing profound vasodilation
o Treat with adrenaline (Vasoconstriction, a1 receptors)
