Cardiovascular Flashcards
(223 cards)
1
Q
what layer does the cardiovascular system develop from in gastrulation
A
mesoderm
2
Q
what forms in cardiac looping during embryonic development
A
2 bulges form; bulbus cordis and primordial ventricle
3
Q
what are the 3 sources of blood flow to the embryonic heart
A
Vitelline Veins
Umbilical veins
Common cardinal veins
4
Q
what are the 4 stages of cardiac septation in the atria
A
Septum primum forms and grows downwards
Foramen primum ‘space’ formed
Foramen secumdum forms in septum primum
Septum secundum begins to form
5
Q
what is the foramen ovale
A
hole in the atrial septa that permits oxygen-rich blood to move from RA – LA (shunting)
6
Q
what does the foramen ovale form in adults
A
fossa ovalis
7
Q
what is a patent foramen ovale
A
Abnormal resorption of septum primum during formation of foramen secundum
Results in short septum primum and therefore foramen ovale is still open after birth
8
Q
3 types of congenital heart defects
A
Transposition of the great arteries
Rare but very serious – pulmonary artery and aorta are swapped over
Truncus arteriosus
Rare but very serious – pulmonary artery and aorta don’t develop and remain as single vessel
Patent ductus arteriosus
Connection between pulmonary artery and aorta in the fetus – remains open after birth
9
Q
what are the 3 layers of blood vessels
A
tunica intimida
tunica media
tunica adventitia
10
Q
what are the 2 layers of the pericardium
A
Fibrous (outer layer)
serous (inner layer)
11
Q
what are the functions of the pericardium
A
Fixation within mediastinum
Prevents over filling of heart
Lubrication (thin fluid film reduces friction)
Protection from infection
12
Q
innervation of the pericardium
A
Phrenic nerve (C 3, 4 & 5)
13
Q
what are the pericardial sinuses
A
Transverse pericardial sinus
Oblique pericardial sinus
14
Q
what are the layers of the heart wall
A
- Endocardium
- Subendocardial Layer
- Myocardium
- Subepicardial Layer
- Epicardium (Visceral Pericardium)
15
Q
the right atrium - anatomy
A
Receives blood from Superior & Inferior Vena Cavae, Coronary Veins • Right auricle • 2 distinct parts divided by Crista Terminalis • Coronary sinus (between IVC & right atrioventricular orifice)
16
Q
the right ventricle - anatomy
A
Receives blood from RA • Pumps blood to pulmonary artery via pulmonary orifice • Triangular shape • Anterior heart border • Inflow and outflow portions • Separated by supraventricular crest
17
Q
the left atrium - anatomy
A
Receives blood from pulmonary veins • Forms posterior border (base) of heart • Left auricle
18
Q
the left ventricle - anatomy
A
- Receives blood from left atrium
- Forms apex of the heart
- Left & inferior heart borders
- Inflow & outflow portions
19
Q
heart valves function
A
Ensure blood flow in one direction • Connective tissue & lined in endocardium • 4 heart valves - 2 atrioventricular 2 semilunar
20
Q
atrioventricular valves
A
Close at start of systole (first heart sound) • Valves are supported by chordae tendineae - tricuspid - right side - mitral - left side
21
Q
semi-lunar valves
A
Close at the start of diastole (second heart sound) • Found between ventricles & corresponding outflow tracts • Sinuses • Lunule (thickened free edge) • Nodule (widest area)
22
Q
auscultating heart sounds
A
First heart sound - start of systole • Tricuspid valve • Mitral valve Second heart sound - START of diastole • Aortic valve • Pulmonary valve
23
Q
coronary circulating - arteries
A
Vessels that supply & drain the heart • 2 main arteries - Right & left coronary arteries • Left coronary artery - Left anterior descending a. - Left marginal a. - Left circumflex a. • Right coronary artery - Right marginal a. - Posterior interventricular a. (85%)
24
Q
Coronary Circulation – Venous drainage
A
Venous drainage of myocardium • 5 tributaries - Great cardiac v. - Small cardiac v. - Middle cardiac v. - Left marginal v. - Left posterior ventricular v. . Converge at coronary sinus • Drain into RA between atrioventricular orifice & orifice of IVC
25
the sequence of events with each heart beat
1) Flow into atria, continuous except when they
contract. Inflow leads to pressure rise.
2) Opening of A-V valves - Flow to ventricles.
3) Atrial systole - completes filling of ventricles.
4) Ventricular systole (atrial diastole). Pressure rise
closes A-V valves, opens aortic and pulmonary
valves.
5) Ventricular diastole – causes closure of aortic and
pulmonary valves.
26
cardiac output
Cardiac output is the volume blood pumped
per minute (by each ventricle).
Cardiac output = Heart rate x Stroke volume
At rest C.O. = 5 l/min
In exercise > 25 l/min as heart rate increases
2-3 fold and stroke volume increases 2 fold.
27
stroke volume dependant on
a) Contractility (the force of contraction).
e.g. adrenaline ↑force, ↑stroke volume.
b) End diastolic volume (volume of blood
in ventricle at the end of diastole).
Force is stronger the more muscle fibres are
stretched (within limits):
Frank - Starling Mechanism or Starling’s Law of the Heart
Stroke volume ∝ Diastolic Filling
28
Frank-Starling Mechanism
```
Also known as the Preload.
Important in:
a)ensuring the heart can deal with wide variations in
venous return.
b)balancing the outputs of the two
sides of the heart
```
29
peripheral resistance - afterload
Resistance to blood flow away from the heart -
altered by dilation or constriction of blood
vessels (mainly pr-ecapillary resistance
arteries).
Cardiac Output = Blood pressure /
Peripheral Resistance
30
summary of excitation pathway
```
Sinus rhythm = heart rate controlled by
S.A. node, rest rate approx. 72 beats/min
(wide variation).
• Action potential then activates atria.
• Atrial A.P. activates A.-V. node.
• A.V. node - small cells, slow conduction
velocity - introduces delay of 0.1 sec.
• A.V. node activates Bundle of His /
Purkinje fibres.
• Purkinje fibres activate ventricles.
```
31
cardiac muscle
‘myogenic’ – it generates its own action potentials.
Action potentials develop spontaneously at the
sino-atrial node.
32
SA node action potential
```
Pacemaker potential due to:↑gCa,↑gNa,↓gK
Action potential upstroke due to: ↑gCa
Repolarisation due to: ↑ gK, ↓ gCa
Noradrenaline - ↑gCa
Acetyl choline - ↑ gK, ↓ gCa
```
33
cardiac v skeletal muscle cells
1- neurogenic v myogenic
2-longer cardiac action potential (with plateau)
3-Action potential controls duration of contraction in heart.
4-Ion currents during action potential
– skeletal ‘simple’, cardiac complex
34
currents responsible for cardiac action potential
```
Depolarisation
- large gNa
Plateau
- small gNa
- increase gCa
- decrease gK
Repolarisation
- decrease gCa
- increase gK
```
35
source of Ca for contraction in cardiac muscle cells
Ca is released from the sarcoplasmic reticulum but
for heart cells Ca entry from outside is needed (‘Ca
induced Ca release’).
36
the mechanisms of ECG
Electrical impulse (wave of depolarisation) picked up by
placing electrodes on patient
The voltage change is sensed by measuring the current
change
If the electrical impulse travels towards the electrode
this results in a positive deflection
If the impulse travels away from the electrode this
results in a negative deflection
37
types of ecg leads
```
coronal plane (limb leads)
-bipolar leads - I, II, III
-unipolar leads - aVL, aVR, aVF
transverse plane
-chest leads , v1-v6
```
38
whats the paper speed in an ecg
25mm per second
Therefore one large box (5mm) corresponds to
0.2 seconds
39
causes of P QRS T ecg waves
```
P wave caused by atrial
depolarization
QRS complex caused by
ventricular depolarization
T wave results from
ventricular repolarization
```
40
intervals between ecg waves
```
PR = 0.12-0.20sec
QRS = <0.12s
QTc = <0.440s (m), 0.460s (f)
```
41
what does the PR interval tell us
the time to conduct through AVN/His
42
what does the QRS interval tell us
```
time for
ventricular depolarisation
Patterns of conduction disease
though Bundles
RBBB, LBBB
```
43
what does the ST segment tell us
```
start of
ventricular repolarisation
(should be isoelectric)
ST elevation
acute infarction
Other things pericarditis,
repolarisation abnormalities
ST depression
Ischaemia, LV strain (LVH)
```
44
what does the T wave tell us
ventricular depolarisation
45
right bundle branch block - RBBB
```
- RBBB in V1
no change in initial impulse travel
small r wave impulse depolarizes
LV by itself since RBBB (s wave)
RV depolarized late by impulse thru muscle (r’ wave
Hence RSR’ pattern (‘M’ shape)
‘MaRRoW’ pattern
```
46
left bundle branch block - LBBB
```
LBBB in V1
initial deflection altered since
travels right to left now
Q wave/ negative deflection
RV depolarizes unopposed
may produce small r wave
travels across septum to depolarize LV
deep S wave
W pattern in V1
‘WiLLiaM’ pattern
** note if patient has LBBB then
ST segments is uninterpretable
```
47
calculating regular HR
Count the number of large squares between R waves (RR
interval)
Rate = 300 divided by number of large squares between R waves
Example: if RR interval = 4 large squares
Heart rate = 300/4 = 75 beats per minute
48
calculating irregular HR
Use rhythm strip at the bottom of 12-lead ECG
Rhythm strip is a 10 second recording of the heart
Therefore, Rate = number of QRS complexes multiplied by 6
Example: if number of QRS complexes = 13
Heart rate = 13 X 6 = 78 beats per minute
49
bradyarrhythmia
Any abnormality of cardiac rhythm resulting in a slow heart
rate (heart block, slow AF) (c.f. sinus brady)
HR < 60bpm
50
tachyarrhythmia
Any abnormality of cardiac rhythm resulting in a fast heart
rate (SVT, uncontrolled AF/ Flutter, VT) (c.f. sinus tachy)
HR > 100bpm
51
first degree AV block
* Regular Rhythm
* PR interval > .20 seconds and is CONSTANT
* Causes: IHD, conduction system disease, seen in healthy children or athletes
* Usually does not require treatment
52
second degree AV block / Mobitz I
Irregular Rhythm
• PR interval continues to lengthen until a QRS is missing (non-conducted sinus beat)
• PR interval is NOT CONSTANT
• Rhythm is usually benign unless associated with underlying pathology, (i.e. MI)
53
second degree AV block / Mobitz II
* Irregular Rhythm
* QRS complexes may be wide (greater than .12 seconds)
* Non-conducted sinus impulses appear at irregular intervals
* Rhythm is somewhat dangerous as the block is lower in the conduction system (BB level)
* May cause syncope or may deteriorate into complete heart block (3rd degree block)
* It’s appearance in the setting of an acute MI identifies a high risk patient
* Cause: IHD, fibrosis of the conduction system
* Treatment: pacemaker
54
3rd degree AV block (complete heart block)
Atria and ventricles beat independent of one another (AV dissociation)
• QRS’s have their own rhythm, P-waves have their own rhythm
• May be caused by inferior MI and it’s presence worsens the prognosis
• Treatment: usually requires pacemaker +/- temporary pacing/ isoprenaline
55
narrow complex tachycardia
(QRS duration <0.12 s)
Uncontrolled (ie “fast”) Atrial Fibrillation or Flutter
Atrial tachycardia
AVNRT/ AVRT
56
broad complex tachycardia
(QRS duration >0.12 s)
Ventricular tachycardia
Ventricular fibrillation
**Is rhythm from above AVN with BBB/aberrancy??
57
physiological causes of arrhythmia
automacity increase
| re-entry
58
digoxin
INOTROPIC AGENT
used for Atrial fibrillation and heart failure
works on Na/K ATPase
increases ventricular contractibility
decreases conduction through AV node
side effect - anorexia, nausea, AV block,
visual problems,
59
atenolol
used for AF, hypertension, angina
beta-blocker (relatively beta 1 selective)
decrease sympathetic NS activity (B1) at heart
decrease conduction system
decrease ventricular response rate
side effects, lethargy, hypotension, bronchospasm
60
supraventricular tachycardia treatment
vagal stimulation - carotid massage, eyeball pressure...
| drugs - adenosine (short acting purine), verapamil (calcium channel blocker)
61
ventricular tachycardia treatment
```
lidocaine (rarely used) - class I anti-arrhythmic
blocks Na channels in excitable tissues, decreases excitability and cardiac conduction, effects CNS (drowsiness, confusions...)
```
```
amiodarone - class III anti-arrhythmic
blocks K channels, prolong cardiac action potential, TOXICITY
```
62
biomarkers of myocardial injury
```
total creatine kinase
myoglobin
CK-MB
lactate dehydrogenase (LDH)
cardiac troponin - TnT, TnI
```
63
role of natriuretic peptides (BNP and ANP)
counter vasoconstriction
| oppose renal salt and H2O retention
64
risk factors for thrombus
hyper coagulability
abnormal blood flow
endothelial injury
65
different types of thrombi
mural thrombi - on the walls of spacious cavities -eg aorta
arterial thrombi - may be mural or occlusive - eg in coronary, carotid, cerebral, femoral
venous thrombi - phlebothrombosis, - eg, pelvis and leg veins
66
what are lines of Zahn
```
in thrombi
alternating pale(fibrin and platelets) and dark(RBC) lines
```
67
different types of embolism
arterial - away the heart
venous - towards from the heart
superficial - saphenous system
deep - may be asymptomatic until embolised in lungs
68
thrombus
A thrombus is a solidification of blood constituents that
| forms within the vascular system during life
69
embolism
An embolus is a detached intravascular solid,
liquid, or gaseous mass that is carried by the
blood to a site distant from its point of origin
70
types of embolism
```
Pulmonary embolism
• Systemic embolism
• Amniotic fluid embolism
• Air embolism
• Fat embolism
```
71
paradoxical embolism
In the presence of an interatrial or interventricular
defect, embolisms may gain access to the systemic
circulation
72
systemic embolism
This term refers to emboli that travel through
the systemic arterial circulation
arise mostly from thrombi within the heart
almost always cause infarction in eg
-lower extremities
-the brain
73
infarct defintion
• Is an area of ischaemic necrosis caused by
occlusion of arterial supply or venous drainage in a
particular tissue
74
necrosis definition
Refers to a spectrum of morphological changes that
follow cell death in living tissue, largely resulting
from the progressive action of enzymes on the
lethally injured cells
75
causes of infarction
```
• Thrombosis and thromboembolism account
for the vast majority
• Other causes include:
• Vasospasm
• Expansion of atheroma
• Compression of a vessel
• Twisting of the vessels through torsion
• Traumatic rupture
```
76
types of infarct
```
Red (haemorrhagic):
• Venous occlusion e.g. torsion
• Loose tissues
• Tissues with a dual circulation e.g. lung
White (anaemic):
• Arterial occlusions
• Solid organs e.g. heart, spleen
Septic
• Infected infarcts
```
77
what are the 2 blood circulations
pulmonary - low pressure
| systemic - high pressure
78
primary systemic hypertension
```
idiopathic
Risk factors
• Genetic susceptibility
• High salt intake
• Chronic stress (excessive sympathetic activity)
• Abnormalities in renin/angiotensin-aldosterone
• Obesity
• Diabetes mellitus
```
79
secondary systemic hypertension
```
Renal disease
• Chronic renal failure
• Polycystic kidneys
Endocrine causes
• Pituitary - ACTH
• Adrenal cortex - glucocorticoid; mineralocorticoid
• Adrenal medulla - catecholamines
Drug treatment e.g. steroids
Others e.g. coarctation of the aorta
Potentially treatable
• Careful clinical assessment
• Test the urine!
```
80
systemic hypertension effects on the heart
```
Left ventricular hypertrophy
• Fibrosis
• Arrhythmias
• Coronary artery atheroma
• Ischaemic heart disease
• Cardiac failure
```
81
systemic hypertension effects on the kidney
• Nephrosclerosis
• ‘Drop-out’ of nephrons due to vascular narrowing
• Proteinuria
• Chronic renal failure
• Malignant hypertension is associated with acute
renal failure
82
vascular changes in systemic hypertension
```
Benign hypertension
• Acceleration of atherosclerosis
• Intimal proliferation and hyalinisation of
arteries and arterioles
Malignant hypertension
• Fibrinoid necrosis
```
83
ischaemic heart disease
```
Blood supply to the heart is insufficient for its
metabolic demands
• Deficient supply
• Coronary artery disease (commonest)
• Reduced coronary artery perfusion
```
84
coronary artery disease
Coronary blood flow is normally independent of
aortic pressure
• Initial response to narrowing is autoregulatory
compensation
• >75% occlusion leads to ischaemia
85
myocardial infarction
• An area of necrosis of heart muscle resulting
from reduction (usually sudden) in coronary
blood supply
• Due to
• Coronary artery thrombosis
• Haemorrhage into a coronary plaque
• Increase in demand in the presence of ischaemia
86
chronic ischaemic heart disease
Chronic angina
• Exercise-induced chest pain
• Heart failure
• Related to reduced myocardial function
• Usually widespread coronary artery atheroma
• Areas of fibrosis often present in the myocardium
87
cardiac failure
• Failure of the heart to pump sufficient blood to
satisfy metabolic demands
• Leads to underperfusion which causes fluid
retention and increased blood volume
• Two different, but linked, circulations
• Systemic
• Pulmonary
88
left ventricular failure general info
• Dominates hypertensive and ischaemic heart
failure
• Causes pulmonary oedema, with associated
symptoms
• Leads to pulmonary hypertension and,
eventually, right ventricular failure
• Combined left and right ventricular failure is
often called ‘congestive’ cardiac failure
89
right ventricular failure CAUSES
• Secondary to left ventricular failure
• Related to intrinsic lung disease – ‘cor’ pulmonale
e.g. chronic obstructive pulmonary disease (COPD)
90
forward heart failure
* Reduced perfusion of tissues
| * Tends to be more associated with advanced failure
91
backward heart failure
Due to increased venous pressures
• Dominated by fluid retention and tissue congestion
• Pulmonary oedema (left ventricular failure)
• Hepatic congestion and ankle oedema (right ventricular
failure)
92
left failure clinical features
* Hypotension
* Pulmonary oedema
* Paroxysmal nocturnal dyspnoea
* Orthopnoea
* Breathlessness on exertion
* Acute pulmonary oedema with production of frothy fluid
93
right failure clinical features
Right ventricular failure
• Ankle swelling
• Hepatic congestion (may be painful)
94
cardiac preload
Volume of blood in the ventricles at the end of diastole.
```
determined by -
- blood volume
- venous ‘tone’,
capacity of the
venous circulation to
hold blood
```
95
what increases cardiac preload
* Sympathetic NS activation
* renal failure
* heart failure
96
cardiac afterload
Resistance the heart
must overcome to
circulate blood
determined by -
tone in arterial circulation
97
what increases cardiac afterload
* SNS activation
| * hypertension
98
what does vascular endothelium regulate
```
• blood vessel tone
• permeability
• leukocyte adhesion,
platelet aggregation
& tendancy for thrombus
formation
```
99
causes of endothelial dysfunction
§ elevated and modified low density lipoprotein e.g.
in familial hypercholesterolaemia
• oxygen free radicals caused by smoking, hypertension, activated inflammatory cells
• infectious microorganisms:
herpes virus, Chlamydia pneumoniae, H.pylori
• physical damage and gene activation by turbulent flow, high blood pressure
diabetes, ageing, being male!
100
foam cells
macrophages take up LDL oxidised by interaction with oxygen free radicals
101
statins
eg - simvastatin
- lower cholesterol and LDL
- inhibit HMG CoA reductase
- increase expression of LDL receptors
102
fibrates
eg - bezafibrate, gemfibrozil, fenofibrate
- activate intracellular PRAR (alpha)
- decrease circulating VLDL and triglyceride, small effect on LDL, increase HDL
103
ezetimibe
lowers cholesterol absorption from small intestine via action in epithelial cells
104
angina pectoris
intermittent chest pain caused by mismatch between
demand of oxygen by the heart and supply of oxygen
to the heart
105
nitrates
eg - glycerol trinitrate (sub-lingual, rapid acting- leads to tolerance), iosorbide ditrinitrate (oral, long-lasting)
VEINS
- dilate veins, decrease venous return and preload, reduce O2 demand
ARTERIOLES
- dilate and reduce afterload on heart, reduce O2 demand
106
nicorandil
blood vessel dilation by opening ATP sensitive K+ channels in smooth muscle cells
has nitrate moiety (part)
reduces preload and afterload
dilates coronary arteries
107
ivabradine
blocks 'funny currents' in SA node cells - reduces rate of spontaneous depolarisation during AP generation
reduce HR and O2 demand
less side effects than B-blockers
108
calcium antagonist
eg - nifedipine, dilthiazem
- prevent opening of voltage Ca2+ channels
- reduce contractibility
- reduce force of contraction and therefore O2 demand
109
anti-platelet drugs
taken prophylactically to reduce risk of thrombus
- cyclooxygenase inhibitor e.g. aspirin
• irreversible inhibition of COX, prevents formation of TxA2 &
platelet activation
- P2Y12 inhibitor e.g.clopidogrel, ticagrelor
• blocks effect of ADP and prevents platelet activation
- thrombin-receptor antagonist e.g. voripaxar
• prevent activation of PAR-1 receptors on platelets
risk - bleeding - new drugs are shorter acting or reversible
110
anticoagulant drugs
prevent the formation of fibrin to stabilise platelet plug
- intravenous - heparin
- orally active - warfarin, rivaroxaban
111
warfarin
anticoagulant
- orally active
- Common clinical indications
atrial fibrillation, the presence of artificial heart valves, deep venous thrombosis, pulmonary embolism and, occasionally, after myocardial infarction.
risks
• narrow optimal range, high risk of bleeding
• broken down in liver, enzymes induced by other drugs, environmental infuences
• blood levels must be checked regularly
112
fibrinolysis - pro and anti
pro- (tissue plasminogen activator)
| anti- (PAI-1, antiplasmin)
113
fibrinolytic 'clot busting' drugs
to remove clot and restore blood flow
•most effective to reduce mortality if given immediately (<3h) after MI or stroke
• accelerates conversion of plasminogen to plasmin,
which degrades fibrin in thrombus
tissue plasminogen activator (tPA. Activase) or streptokinase
can cause bleeding (reverse by tranexamic acid)
114
surgical vascular interventions
balloon angioplasty
| stenting
115
most common heart failure
impaired contractility and emptying of ventricle (HF with reduced ejection fraction, HFrEF)
116
less common heart failure
impaired relaxation and filling of ventricle (HF with preserved ejection
fraction, HFpEF): growing recognition, more common in women, diabetes, mechanisms less understood
117
common causes of heart failure
l Myocardial infarction: damage to heart muscle
after loss of blood supply due to ischaemic heart
disease
l Volume Overload: due to damage to heart valves or
increased plasma volume
l Pressure Overload: due to uncontrolled
hypertension & increased afterload
l Myocarditis :bacterial infection of myocardium
l Cardiomyopathy: inherited defect in muscle
structure influencing function
118
heart failure - Inotropic agents
digoxin
dobutamine (B1 adrenoreceptor agonist iv for rapid response), increases HR and contractility
Provide support in acute heart failure, but results in
increased oxygen and energy demand so not helpful long term in chronic heart failure
119
heart failure - drugs for renin-angiotensin system
renin inhibitor - aliskiren
ACE inhibitor - enalapril, lisinopril
AT receptor antagonist - losartan, valsartan
120
renin-angiotensin-aldosterone-system (RAAS)
pressure detected in juxtaglomerular cells, close to the afferent arteriole, when pressure is low renin is secreted into plasma
renin converts angiotensinogen > angiotensin I
angiotensin-converting enzyme converts angiotensin I > angiotensin II
angiotensin II increases after-load
angiotensin II is converted to ALDOSTERONE in the adrenal cortex
aldosterone causes NA and H2O retention in renal tubules and increases blood volume and pre-load
121
sympathetic nervous system
```
baroreceptor feedback
>
sympathetic nervous system
>increased HR (B1 receptor)
>activate renin release
>smooth muscle constriction (a1 adrenoreceptor)
- arteriolar constriction = increased afterload
- venoconstriction =
increased venous return and preload
```
122
heart failure - drugs that reduce blood volume and preload
loop diuretics - frusemide, bumetamide
- impair Na+/K+/CL- readsorption in ascending loop of Henle
mineralocortoid receptor antagonists - spironolactone, eplerenone
- block effects of aldosterone on Na/K readsorption
123
herat failure - drugs that affect the sympathetic NS
beta adrenoreceptor antagonists - atenolol, metoprolol (B1 selective)
reduce sympathetic drive to the heart (reduce O2 demand)
block renin release from kidney > decrease RAAS activation, decrease pre-load and after-load
few side effects - but not useful in asthmatics
124
heart failure - vasodilators
nitrovasodilators - isosorbide mononitrate (long acting, risk of tolerance)
- venous circulation > decrease venous return and preload arterioles - reduce PVR and afterload
hydralazine
dilators that target arteries > veins and reduce afterload
used for acute and chronic heart failure
125
structural changes in heart failure
aldosterone leads to fibrosis
| AngII leads to hypertrophy
126
what are lipids
organic compounds: poorly soluble in water but miscible in organic solvents
127
important lipids in human physiology
```
steroids - cholesterol, hormones
fat soluble vitamins-A D E K
phospholipids
sphingolipids
triglycerides
```
128
lipoproteins
Transport cholesterol & triglycerides around the body via the circulation
```
types
-chylomicrons
-VLDL
-IDL
LDL
HDL
```
129
Where are lipoproteins created
- small intestine - dietary lipids
- liver - endogenous lipids
formed in the epithelium of the gut and synthesised in liver
130
3 main pathways of transport and metabolism
- exogenous lipid pathways
- endogenous lipid pathways
- reverse cholesterol transport
131
triglycerides
Triglycerides = energy
Chylomicrons, created in the gut, deliver triglycerides to muscle & adipose tissue (where converted to NEFA)
VLDLs, synthesized in liver, also deliver triglycerides to muscle & adipose tissue (again converted to NEFA)
132
cholesterol
Cholesterol = essential building block & precursor*
Liver is the master organ: synthesis, secretion, uptake, excretion
Delivered to peripheral tissues via LDL
Uptake from circulation via remnants, IDL, LDL, HDL
Returned to liver (from peripheral tissues) via HDL
133
lipid driven CV disease
inherited disorders of lipoprotein metabolism eg familial hypercholesterolaemia (FH)
```
Autosomal dominant
Mutation in LDL receptor
Common ~1:500 to 1:200
High LDL-C levels
Untreated leads to premature CHD onset:
~50% men by 55 yr, ~33% women by 60 yr
Statin treatment shown to reduce CVD risk to that of general population
```
134
prevention of CV disease
```
primary prevention (individuals without disease)
secondary prevention (patients with disease)
```
135
drugs for CV disease
ACE-inhibitor, Beta-blocker – reduce post-MI mortality
Aspirin + Clopidogrel – reduce CVD recurrence & mortality
Statins – reduce CVD recurrence & mortality
136
lipid lowering drugs -effects
statins - reduce LDL-C
ezetimibe - reduce LDL-C
Fibrates - reduce VLDL, increase HDL
137
lipid lowering drugs - MOA
statins - HMG-CoA reductase inhibitors
ezetimibe - inhibit chol absorption in S. Intestine
fibrates - stimulates PRAR (alpha) - a nuclear transcription factor
138
next generation of lipid-lowering drugs
PCSK9-inhibitors
- Monoclonal antibodies, delivered by fortnightly s/c injection
- Alirocumab, Evolocumab
- Capable of ~60% reduction of LDL-C (as adjunct to statin)
139
sinus arrhythmia
```
Sinus node fires at a variable rate
• Speeds up during inspiration
• Slows down during expiration
• Effect caused by variations in vagus nerve
activity (parasympathetic)
```
140
sinus tachycardia
```
• Sinus node fires > 100 per minute
• Physiological causes:
– anxiety, exercise
• Pathological causes:
– fever, anemia, hyperthyroidism, heart failure
– many others
```
141
sino-atrial disease
Mixture of sinus tachycardia, bradycardia
| and atrial ‘ectopic’ beats, atrial fibrillation
142
sinus bradycardia
```
• Sinus node fires < 60 per minute
• Physiological causes:
– Sleep, athletic training
• Pathological causes:
– hypothyroidism
– hypothermia
– sinus node disease
– raised intracranial pressure, many others
```
143
AV nodal block
```
causes -
sino-atrial disease
• coronary heart disease
• aortic valve disease
• damage during heart surgery
• drugs
– beta-blockers
– digoxin
– calcium channel blockers
```
treatment-
• Remove any triggering cause (e.g. drugs)
• atropine or isoprenaline (acute treatment)
• permanent pacemaker
144
atrial flutter / fibrillation
```
causes -
• sino-atrial disease
• coronary heart disease
• valve disease (esp. mitral valve)
• hypertension
• cardiomyopathy
• hyperthyroidism
• pneumonia, lung pathology
```
treatment -
drug to block AV node and therefore limit
heart rate (e.g. digoxin or beta-blocker)
• electrical cardioversion
• catheter ablation
145
ventricular tachycarida / fibrillation
```
• defibrillation
• antiarrhythmic drugs
• remove any triggering cause
• implantable defibrillator for some
patients
```
146
epidemiology of venous thromboembolism
Incidence: 1 per 1000 per annum
May present as sudden death (up to 30% of
pulmonary embolism)
30% develop recurrent venous thrombosis in 10 years
28% develop post thrombotic syndrome
Mortality of promptly diagnosed and adequately
treated pulmonary embolism (PE) is 2%
147
venous thrombosis
Deep venous thrombosis (DVT)
Pulmonary embolus (PE)
Cerebral, mesenteric, axillary, splanchnic,
splenic
148
lower limb dvt - clinical features
Pain, swelling, increased temperature of limb,
dilatation of superficial veins
Usually unilateral
May be bilateral if thrombosis sited in inferior
vena cava
Differential diagnosis: calf haematoma, ruptured
Baker’s cyst, cellulitis
149
testing for dvt
contrast venography
venous ultrasonography - USS
D-Dimer test
150
venous ultrasonography (USS)
Non-compressibility of the common femoral vein or
popliteal vein are diagnostic of DVT
Compression B-mode ultrasonography +/- colour
duplex imaging: sensitivity 95%, specificity 96%
for diagnosis of symptomatic proximal DVT
But sensitivity and specificity of 60-70% for
isolated calf vein thrombosis
151
pulmonary embolism - clinical features
Depends on number, size and distribution of
emboli
Collapse, faintness, crushing central chest pain
Pleuritic chest pain
Difficulty breathing
Haemoptysis
Exertional dyspnoea
152
diagnosis of PE
```
Chest X-ray (to exclude other pathology)
Electrocardiogram (ECG)
Arterial blood gases
D-dimer
Ventilation Perfusion (V/Q) scan
CT-pulmonary angiogram
Echocardiogram
```
153
1 - rapid initial anticoagulation
parenteral anticoagulant : heparin, low molecular weight
heparin, fondaparinux, OR
direct oral anticoagulant
Aim: to reduce the risk of thrombus extension and
fatal pulmonary embolism
154
2 - extended anticoagulation therapy
orally active anticoagulant : vitamin K antagonist
OR direct oral anticoagulant
Aim: to prevent recurrent thrombosis and
chronic complications such as post-phlebitic
syndrome
155
management of VTE - traditional way
Give LMWH or UFH for a minimum of 5 days if
uncomplicated thrombosis; or for 7 days or longer if
extensive disease
Start warfarin therapy on day 1
Overlap with LMWH or UFH until INR* is 2.0 for 2
days (INR refers to International Normalised Ratio)
156
direct oral anticoagulants (DOACs)
Refer to as “DOACS”
Used for VTE over past few years
Dabigatran, Rivaroxaban, Edoxaban & Apixaban
licensed in UK for treatment of acute DVT
Enables rapid initial anticoagulation orally
Then continue a maintenance dose for 6 months, or
longer for secondary prevention of VTE
Apixaban and Rivaroxaban do not need any overlap
with heparin – big advantage in outpatient setting
157
investigation of procoagulant tendency
```
Full Blood Count
Antithrombin
Protein C
Free protein S
Antiphospholipid antibodies and lupus anticoagulant
Thrombin time/reptilase time
```
158
heparins
Unfractionated
Low-molecular weight heparin
biological
product derived from porcine intestine
Binds antithrombin and potentiates its inhibitory
action towards factor Xa and thrombin
159
unfractionated heparin (UFH)
UFH is a heterogeneous group of
molecules with a range in MW from 3000
to 30,000D
Unpredictable anticoagulant
response due to binding to
plasma proteins
Monitoring required by
activated partial
thromboplastin time (APTT)
continuous IV infusion or 2x a day
risk of osteoporosis and HIT
reverse with protamine
160
low molecular weight heparin (LMWH)
Produced by enzymatic or chemical depolymerisation of UFH with a
mean MW of 5000; due to the reduction in chain length there is
reduced capacity to inhibit thrombin compared with UFH.
Better bioavailability, more predictable anticoagulant response and
dose-dependent renal clearance. No lab monitoring usually necessary.
once daily dosing
reduced risk of osteoporosis, and HIT
cannot be reversed
161
coumarins eg warfarin
Inhibit vit K dependent carboxylation of factors II,
VII, IX and X in the liver
Causes a relative deficiency of these coagulation
factors
Monitored by the International Normalised Ratio (INR),
derived from the prothrombin time (PT)
Takes around 5 days to establish maintenance dosing
Loading regimens assist early dosing
Individual dose for each patient;
racial differences reflect natural occurring polymorphisms in CYP2C9 and VKORC1 genes
Dietary intake of vit K also affects warfarin dose
many drug interactions
162
reversal of warfarin
```
Management depends on whether the
patient is bleeding or not
National reversal policies
Vitamin K – oral or intravenous routes
Reverse by administering the deficient
clotting factors
Tendency to use factor concentrate
(factor II, IX and X) in place of fresh
frozen plasma (prothrombin complex
concentrate, “PCC”)
```
163
DOACs - indications
Treatment of deep vein thrombosis and pulmonary
embolism nd PE
Prevention of cardioembolic events in patients with
atrial fibrillation
```
Benefits over warfarin:
MORE PREDICTABLE ANTICOAGULANT PROFILE
FEWER DRUG AND FOOD INTERACTIONS
WIDER THERAPEUTIC WINDOW COMPARED TO WARFARIN
ORAL ADMINISTRATION
NO NEED FOR MONITORING
SIMPLE DOSING
```
164
reversal of DOACs
Antidotes being developed
New antidote now in use for reversing dabigatran (IDARUCIZAMAB)
For Xa-inhibitors - basic measures:
Determine how long since last dose
Start standard resuscitation measures
Moderate to severe bleeding
Local measures
Fluid replacement
Consider fresh frozen plasma or platelets
Antifibrinolytic inhibitors
Consider use of factor concentrates if extreme bleeding
165
principles of heamostasis
Platelets - normal number, normal
function
Functional coagulation cascade
Normal vascular endothelium
166
generation of the haemostatic plug
PLATELET ADHESION
- PLATELET ACTIVATION / SECRETION
- PLATELET AGGREGATION
The conversion of fibrinogen to fibrin by thrombin,
and polymerisation of fibrin stabilises the platelet
thrombus, resulting in a platelet-fibrin (“white”) clot
167
reduced number of platelets
Thrombocytopenia (TP): long list of causes
bone marrow failure
peripheral consumption (e.g. immune TP,
disseminated intravascular coagulation (DIC), druginduced)
168
abnormal platelet function
Most commonly drugs such as aspirin,
clopidogrel
Renal failure: uraemia causes platelet
dysfunction
169
abnormal vessel wall
Scurvy
| Ehlers Danlos syndrome
170
abnormal interaction between platelets and vessel wall
Von Willebrand disease
171
drugs that inhibit platelet function
Aspirin and COX inhibitors
Reversible COX inhibitors eg. NSAIDs
Dipyridamole - inhibits phosphodiesterase
Thienopyridines - inhibit ADP-mediated activation, eg clopidogrel
Integrin GPIIb/IIIa receptor antagonists
172
coagulation cascade. - waterfall theory
```
(intrinsic)
XII -> XIIa
XI -> XIa
IX -> IXa VIIIa
II - Va Xa - > IIa. (X--> Xa ^^^ = extrinsic P - VIIa TF)
fibrinogen -> fibrin (common pathway)
```
173
why waterfall theory fails to reflect haemostasis
Patients with fXII deficiency do not bleed
• Patients with fVII deficiency bleed abnormally
Patients with fVIII and fIX deficiency have severe
hemorrhagic diathesis despite a normal extrinsic
coagulation pathway
• Patients with fXI deficiency have a variable and mild
bleeding diathesis
174
cell based model of coagulation
```
A series of overlapping steps that lead to
coagulation:
Initiation
Amplification
Propagation
Termination
```
175
regulation of coagulation cascade - natural inhibitors
TF-VIIa complex/fXa inhibited by TFPI, tissue
factor pathway inhibitor
Thrombin and fXa activity inhibited by
Antithrombin
Protein C pathway inhibits fVa and fVIIIa
176
prothrombin time - PT
Measured in seconds
Reflects the ‘extrinsic pathway’
and the ‘common pathway’
177
Activated Partial
Thromboplastin Time
(APTT)’
Measured in seconds
Reflects the ‘intrinsic pathway’
and the ‘common pathway
178
firbrinogen
Measured in grams/L
Reflects the functional
activity of the fibrinogen
protein
179
haemophilia A
- x linked recessive disorder
- 1 : 5-8000 males
- 30% sporadic mutations
- deficiency of fVIII
- severity is the same within diff generations
180
severity of Haemophilia A
Clinical severity of haemophilia correlates to fVIII level
<1% : SEVERE : frequent haemarthroses
2 - 10% : MODERATE : bleeding after minor trauma
11 - 30% : MILD : bleeding after surgical challenge
A “normal” FVIII level ranges from 50-150%
181
traditional management of haemophilia
- Supportive Measures
Ice, immobilisation, rest
- Replacement of missing clotting protein by
Coagulation factor concentrates, Desmopressin (DDAVP) – (used to increase factor VIII levels in mild/moderate haemophilia A)
- Novel therapies
monoclonal antibodies, Tranexamic acid
182
von willebrand disease
Roles of Von Willebrand Factor
promote platelet adhesion to subendothelium at high shear
rates
carrier molecule for FVIII
Most common heritable bleeding disorder
Mainly autosomal dominant inheritance
Men and women affected
Associated with defective primary haemostasis
Variable reduction in Factor VIII levels
Mucocutaneous bleeding including menorrhagia
Post-operative and post partum bleeding
183
von willebrand disease - management
```
Antifibrinolytics: tranexamic acid
DDAVP (for type 1 vWD)
Factor concentrates containing vWD
Vaccination against hepatitis A and B
Contraceptive pill for menorrhagia
```
184
acquired coagulation disorders
underproduction of coagulation factors
- liver failure
- vit K deficiency
anticoagulants
-warfarin, DOACs,
Immune
- acquired haemophilia, acquired VWS
- DIC
185
liver disease
Reduced hepatic synthesis of clotting factors
Thrombocytopenia secondary to hypersplenism
Reduced vitamin K absorption due to cholestatic
jaundice causing deficiencies of factors II, VII, IX & X
Treat with plasma products and platelets to cover
procedures, and vitamin K
186
the syndrome of DIC
An acquired syndrome of systemic intravascular
activation of coagulation – “thrombin explosion”
Widespread deposition of fibrin in circulation
Tissue ischaemia and multi-organ failure
Consumption of platelets and coagulation factors to
generate thrombin, may induce severe bleeding
187
DIC - coagulation parameters
- prolonged PT
- prolonged APTT
- low fibrinogen
- raised d-dimers
188
Stiff arteries are bad because...
```
Stiff large arteries cause a wider
pulse pressure so:
• They cause a higher systolic BP,
leading to higher stroke and
coronary risk
• They cause a lower diastole BP,
reducing coronary artery filling
```
189
molecular mechanisms of hypertension
salt handling in the kidney is critical for high blood pressure
190
population approaches to hypertension
```
Increase exercise
• Increase potassium intake (fruit & vegetables)
• Increase nitrate intake (fruit & vegetables)
• Reduce sodium/salt intake
• Reduce alcohol intake (if excessive)
• Reduce calorie intake (if excessive)
• [Reduce (saturated) fat intake]
• [Reduce smoking]
```
191
hypertension - working definition
Hypertension is having a
blood pressure at which
treatment does more good
than harm”
192
stages of hypertension
Stage 1: Clinic BP >140/90 or home BP >135/85
Stage 2: Clinic BP >160/90
Stage 3: Clinic BP >180/110
Target BP <140/90
Cardiovascular risk ≥10% - lowers treatment
threshold
193
assessment of hypertension
```
History & examination
• Blood pressure – home or ambulatory
• ECG – arrhythmia, AMI
• Electrolytes – low sodium or potassium
• Creatinine/eGFR – renal function
• Urate – gout
• Glucose/HbA1c – diabetes
• Lipid profile – hypercholesterolaemia
• Urinalysis – protein, glucose, blood
```
194
drug treatment for hypertension
ACE inhibitor/ANGII receptor blocker (ARB)
- enalapril
Beta- (adrenoceptor) blocker
- atenolol
Calcium entry blocker
- nifedipine
Diuretic (thiazide-type)
- bendroflumethiazide
195
drug treatment for hypertension - what they dp
• ACE inhibitors have particular benefits
– Post -MI
– Heart failure
– Diabetic nephropathy
• Beta-blockers improve outcomes in IHD*
• Calcium antagonists reduce symptoms in angina
and isolated systolic hypertension
• Diuretics (thiazide-like) have benefits in heart failure
196
reasons for treatment failure
```
Poor adherence (extremely common)
• Ineffective combinations (common)
• Other drugs (e.g. NSAIDs; common)
• Inappropriately low doses (common)
• Secondary causes (uncommon: <5%)
```
197
radiator
end of the arterial tree
198
starling force across capillary bed
BP artery - 35mmHg
osmotic - 25MMg
BP vein - 16mmHg
osmotic - 25mmHg
199
common arterial pathologies
* Dilated = aneurysm
* Narrowed = stenosis
* Blocked = occluded
200
uncommon arterial pathologies
Split = dissection
• Over sensitive = vasospasm
• Inflamed = vasculitis
• Broken = a problem!
201
aneurysms
* Definition = 1.5 x the normal diameter
* Degenerative aneurysms are the most common
* Inflammatory, mycotic (infective), traumatic can also occur
* Connective tissue disease – Marfans
202
stenosis symptoms
```
Claudication
• Pain on walking a fixed distance
• Worse uphill
• Eases rapidly when you stop
• ANGINA of the leg!
```
* Short distance Claudication
* Nocturnal pain / rest pain
203
occlusion
```
Acute
• Pain (sudden onset)
• Palor
• Perishingly cold
• Parasthesia
• Pulselessness
• Paralysis
• The SIX P’s
```
```
Chronic
• Short distance claudication
• Nocturnal pain
• Pain at rest
• Numbness
• Tissue necrosis
• Gangrene
• Things falling off
```
204
amputation
```
Median survival after
amputation is 2.25 years
• 30 day mortality of 17%
• 30% lose the other leg with 2
years
• 6000 per year in UK
```
205
vasculitis
Large vessel – Takayasu’s disease – “the pulseless disease”
• Medium vessel – Giant Cell Arteritis / Polymyalgia
• Small vessel – lots of polyangiitis conditions usually involving the
kidneys
treat - steroids and immunosuppressive agents
206
diabetic foot
```
Neuropathic
• Ischaemic
• Infected
• Calcified vessels
• Small vessel arterial disease
• Patients can’t see their feet (retinopathy
```
207
charcot foot
```
end stage diabetic foot changes
• Neuropathic
• Warm (>2℃ than normal)
• AV shunting
• Multiple fractures
• “Rocker bottom” sole
```
208
venous resevoir
* 64% of the total systemic circulation is within the veins
* 18% in the large veins
* 21% in large venous networks such as liver, bone marrow
* 25% in venules and medium sized veins
209
venous insufficiency
```
Failure of the muscle pump
(typically calf muscle)
fixed ankle
• Immobility
• Dependency
• Loss of muscle mass
```
* Failure of the valves
* Or both
210
venous hypertension
* Haemosiderin staining
* Swollen legs
* Itchy, fragile skin
* “Gaiter” distribution (shinpad)
* Risk of ulceration
211
venous hypertension - treatment
* Emollient to stop skin cracks
* Compression
* Bandages
* Wraps
* Stockings
* Elevate and mobilise
212
valve failure treatment
* Superficial veins
* Endothermal ablation
* Surgical removal
* Foam sclerotherapy
* Adhesive occlusion
* Compression
* Deep veins
* Compression
213
phlegmasia and venous gangrene
Rare
• Often with underlying cancer
• Thrombolysis?
214
porto-systemis venous system
```
• Mesenteric or ‘portal venous’
drainage is via the liver before
the heart
• Systemic circulation is returns to
the heart directly
• The two circulation systems
combine a number of points
```
in liver disease - portal hypertension - Porto-systemic venous anastomosis
215
oncotic pressure
```
Oncotic pressure also known as colloid
osmotic pressure is induced by
protein in the blood plasma
• Low protein (albumin) states
lead to limb swelling and
oedema
```
if reduced -
liver failure
renal disease
malnutrition
216
arterial septal defect
- Flow between the two atria
| - L->R shunting which may eventually switch to R->L due to RV hypertrophy-e.g. patent foramen ovale
217
ventricular septal defect
- Flow between the two ventricles
| - Resultant L->R shunting
218
tetralogy of fallot
- Ventricular septal defect
- Pulmonary valve stenosis
- RV hypertrophy
- Resultant R->L shunting
219
how does body respond to haemorrhage
```
Decrease on intravascular volume
venous return to the heart
ventricular filling
cardiac output
blood pressure
renal perfusion
capillary hydrostatic pressure
```
220
hypovaeleamic shock
hypotension, reduction in renal perfusion
– lower urine output, lower cerebral perfusion
– confusion, unconsciousness
221
ST elevation linked with what kind of MI
V1 and V2 - septal
V3 and V4 - anterior
I, aVL, V5 and V6 – lateral
II, III and aVF – inferior
aVR - non
222
cardiac troponin
Troponin complex is 1:1:1 of three regulatory proteins (TnT, TnI, TnC)
Exclusively present in striated muscle
Regulates the interaction between actin and myosin
Cardiac specific forms exist, denoted as cTnI, cTn
223
methmaemoglobin
when one or more iron atoms has been oxidized from ferrous to ferric state
produces super oxide O2- which is a dangerous free radical – superoxide dismutase converts this to hydrogen peroxide which catalase then breaks down to O2.
Methaemoglobin reductase reduces this back to Hb
Methaemoglobinaemia is when a mutation stabilizes methaemoglobin and the reductase cannot keep up causing elevated levels in the blood
