Case 15 Flashcards
Diastasis
Middle phase of diastole when initial phase of passive filling has slowed down.
Absent during exercise.
Mitral annulus
Fibrous ring attached to mitral valve leaflets
Arrangement of cardiac muscle fibres
Subepicardial = left handed helix (clockwise) Subendocardial = right handed helix (anticlockwise)
Factors which increase systolic pressure:
Anything which increases afterload.
Aortic stenosis, hypertension, ventricular dilatation
Factors which increase diastolic pressure:
Anything which increases preload +/- increased diastolic pressure
Hypervolaemia, increased atrial contractility, decreased HR, increased ventricular compliance
End diastolic pressure volume relationship
Passive filling curve for the ventricle
Steep end diastolic pressure volume relationship suggests
A less compliant ventricle
Pressure increasing more with every unit increase in volume
Steep end systolic pressure volume relationship
Increased contractility
Causes of systolic heart failure
Dilated cardiomyopathy
Coronary artery disease (reduced blood supply to heart)
Valve disease - regurgitation/stenosis
Arrhythmias
Mechanism for systolic heart failure
Underlying disease causing death of cardiomyocytes.
Walls become thin, ventricles are large.
Weakened heart muscle has decreased inotropy.
Stroke volume reduced.
Reduced ejection fraction
Mechanism for diastolic heart failure
Hypertrophy and stiffening of cardiac muscle due to underlying disease.
More space taken up by muscle - less space for filling.
Large muscle requires greater O2 supply which cannot be reached - fibrotic scar tissue
Increased stiffness of muscle - reduced ejection.
Preserved ejection fraction
Causes of diastolic heart failure
Chronic hypertension
Aortic stenosis
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy
Left Ventricular Dysfunction
Decreased longitudinal function.
Increased radial function.
(Heart becomes more spherical)
How do we increase rate of ventricular filling during exercise?
Increased untwisting of left ventricle causes pressure in left ventricle to fall.
Pressure gradient across mitral valve between LA and LV
Suction of blood from LA into LV
Why does reduced relaxation affect cardiac output?
Less untwisting of ventricle - Reduced suction from LA into LV during ventricular filling = Reduced stroke volume
Tension causes compression of coronary arteries - ischaemia of cardiac myocytes.
First-pass Gadolinium MRI
Used to assess myoardial perfusion
Symptoms of right sided heart failure
Fatigue Palpitations Peripheral oedema Weight gain Raised JVP Frequent urination at night
Symptoms of left sided heart failure
Fatigue Palpitations Decreased urination Dyspnoea and coughing (worse when lying down) Weight gain
Heart Failure Functional Class I
Breathless only on marked exercise
Heart Failure Functional Class II
Breathless on moderate exercise
Heart Failure Functional Class III
Breathless on mild exercise
Heart Failure Functional Class IV
Breathless on minimal exercise
Heart Failure Functional Class V
Breathless at rest
How useful is breathlessness as a symptoms in diagnosis of heart failure?
87% sensitive i.e. seen in a lot of patients with heart failure
51% specific i.e. seen in a lot of other conditions as well
(Orthopnoea is less sensitive but more specific)
First line imaging technique for suspected heart failure
Echocardiogram
Kerley lines
Seen when interlobular septa in the pulmonary interstitium become prominent
A sign of pulmonary oedema
BNP is released in response to…
End diastolic wall stress (excessive stretching of ventricular wall)
Effects of BNP
Decreases Na+ reabsorption, therefore decreasing H2O reabsorption.
Overall, decrease in total blood volume.
How useful is BNP in diagnosis of heart failure?
90% sensitive
65% specific
Clinical measurement of BNP
N-terminal pro-BNP
Most common cause of restrictive cardiomyopathy in older people
Amyloid
Biplane Simpson Technique
Assesses volumes i.e. determines ejection fraction
L wave in mitral doppler velocity graph
Seen in impaired relaxation, between E and A waves.
Represents continued pulmonary vein mid diastolic flow through LA into LV after EARLY (passive) filling.
(i.e. Blood travelling from pulmonary vein to LV directly since mitral valve is open)
Mitral Doppler Velocity : E/A < 1
Impaired relaxation
Normal mitral valve inflow pattern
Rapid early (passive) phase of filling, slower late phase of filling generated by atrial contraction
Late ventricular filling may be faster than early filling due to…
Impaired relaxation.
Early filling is slow due to reduced gradient between LA and LV.
Late filling higher since it is generated by atrial contraction
Mitral Doppler Velocity :
Features of impaired relaxation
Late filling greater than early filling since it is generated by contraction.
Prolonged isovolumetric relaxation time
Decreased blood velocity out of heart
Change in heart shape longitudinally
Pronounced L wave (continued mid diastolic flow between E and A)
Mitral Doppler Velocity :
How does a pseudonormal diastolic heart failure occur?
Early and late filling have increased in velocity due to higher LA and LV pressures.
Ratio of E:A appears normal
Mitral Doppler Velocity :
Features of restrictive diastolic heart failure?
Decreased mitral inflow (due to reduced press. gradient)
Short duration of ventricular filling (due to high press. in LV)
End diastolic mitral regurgitation (due to high pressure at end of diastole)
Retrograde flow from atria into pulmonary vein (not all blood can enter less compliant ventricle)
Secondary mitral regurgitation
Mitral valve is intact
Change in geometry and dysfunction of LV is causing regurgitation.
S2 Heart sound
Closure of aortic valve
Heaves
Parasternal impulse
Due to hypertrophy of right ventricle
Signs of tricuspid regurgitation
Pan systolic murmur
Raised JVP
Enlarged pulsatile liver
Systolic murmur
Starts at S1 and ends at S2
Causes of midsystolic murmur
Aortic or pulmonary valve stenosis
What does a midsystolic murmur sound like?
From S1 to S2
Starts softly, increases in intensity then decreases in intensity.
Causes of pansystolic murmur
Mitral/tricuspid regurgitation
Ventricular septal defect
What does a pansystolic murmur sound like?
From S1 to S2
Intensity is high throughout
Causes of diastolic murmurs
Aortic/Pulmonary valve regurgitation
Mitral/tricuspid valve stenosis
What does a diastolic murmur caused by Aortic/Pulmonary valve regurgitation sound like?
Begins immediately after S2 and quickly reaches maximal intensity.
Intensity then diminishes throughout diastole.
What does a diastolic murmur caused by Mitral/Tricuspid valve stenosis sound like?
Delayed beyond S2 (i.e. until AV valves open)
More intense early during diastole then decreases in intensity
Atrial contraction near the end of diastole can cause a brief increase in intensity just before S1
Normal Blood pressure
120/80
Blood pressure in premenopausal women
5-10mmHg lower than normal
Blood pressure at which antihypertensive treatment should be initiated
160/100mmHg
Blood pressure 140-150/90-99
Take into account other factors (heart and kidney problems, diabetes) prior to starting antihypertensive treatment
Conn’s Syndrome
Hyperaldosterone state
How does hypertension cause left ventricular hypertrophy?
HTN causes increased afterload.
Hypertrophy of myocytes since they must work harder during systole.
How does hypertension affect atherosclerosis?
Accelerates atherosclerosis due to wall stress
How does hypertension affect vascular walls?
Increases thickness of tunica media in muscular arteries
Hyperplasia of muscle and collagen deposition (increased stiffness).
How does hypertension cause renal failure?
Proliferation of small blood vessels in kidney.
Hypertrophic and hyaline changes in arterioles.
Sclerosis of glomeruli causes nephron to become ischaemic - undergo atrophy and fibrosis.
Eventually, kidney contracts with a finely scarred surface (Nephrosclerosis)
How does hypertension cause intracerebral haemorrhage?
Pathological changes in intracerebral vessels:
Microaneurysms of perforating arteries
Accelerated atherosclerosis
Hyaline arteriosclerosis
Hyperplastic arteriosclerosis
Pathological consequences of hypertension
LV hypertrophy Athersclerosis Changes in vascular walls Renal failure Intracerebral haemorrhage Subarachnoid haemorrhage Dissecting aneurysm of aorta
Renal Factors which increase cardiac output
Decrease GFR
Increase Na+ reabsorption
Activation of RAAS
Sympathetic drive
Renal Factors which decrease cardiac output
Renal production of prostaglandins (enhance GFR)
Renal factors which increase total peripheral resistance (vasoconstriction)
Sympathetic drive
Activation of RAAS
Endothelin
Renal factors which decrease total peripheral resistance (vasodilation)
Renal PGs
Renal kinins
NO
Platelet activating factor
How do natriuretic peptides lead to hypertension?
Inhibit Na+/K+ ATPase in smooth muscle cells of blood vessel walls.
Increased Na+
Inhibits Na+/Ca2+ exchanger
Increased Ca2+ in smooth muscle cell = VASOCONSTRICTION
Liddle’s Syndrome
Overexpression of Na+ channel in apical membrane of CD
Elevated Na+ reabsorption in nephron
Therefore, elevated blood pressure early in life
How does metabolic syndrome increase risk of hypertension?
Increased Na+/H+ exchanged in PCT.
(H+ excreted, Na+ reabsorbed)
i.e. abnormally high Na+ reabsorption
How does obesity cause hypertension?
High insulin, activates Na+/K+ ATPase
Increased Na+ reabsorption in PCT
Medications which increase risk of hypertension
NSAIDs
Oestrogen
Corticosteroids
Stage 1 Hypertension
Clinic BP > 140/90
Daytime BP > 135/85
Stage 2 Hypertension
Clinic BP > 160/100
Daytime BP > 150/95
Stage 3 Hypertension
Clinic BP
Systolic > 180
Diastolic > 110
Investigations using urinalysis in hypertension
Protein
Albumin:Creatinine ratio
Haematuria
Blood tests used in investigation of hypertension
Glucose Electrolytes Creatinine estimated GFR Total and HDL cholesterol
Grade 1 Hypertensive retinopathy
Tortuosity of retinal veins (silver wiring)
Grade 2 Hypertensive retinopathy
Tortuosity of retinal veins (silver wiring) Arteriovenous nipping (thickened arteries passing over veins)
Grade 3 Hypertensive retinopathy
Tortuosity of retinal veins (silver wiring)
Arteriovenous nipping (thickened arteries passing over veins)
Flame haemorrhages
Cotton wool exudates
Grade 4 Hypertensive retinopathy
Tortuosity of retinal veins (silver wiring)
Arteriovenous nipping (thickened arteries passing over veins)
Flame haemorrhages
Cotton wool exudates
Papilloedema
Why is a 12 lead ECG performed in investigation of hypertension?
To detect LV hypertrophy
Conn’s Syndrome
Primary Hyperaldosteronism
XS K+ secretion and Na+ reabsorption
How would you distinguish between primary and secondary hyperaldosteronism?
Primary - renin is low
Secondary - renin is high
Causes of secondary hyperaldosteronism
Coronary heart failure
Renal artery stenosis
Cirrhosis
Nephrotic syndrome
Adrenal causes of secondary hypertension
Conn’s Syndrome
Secondary Hyperaldosteronism - coronary heart failure, RAS, cirrhosis and nephrotic syndrome
Phaeochromocytoma
Phaeochromocytoma
Adrenal medullary tumor secreting catecholamines
Labile hypertension
Spasms of vasoconstriction and organ ischaemia.
Associated with phaeochromocytoma (XS catecholamines)
Renal causes of secondary hypertension
Renal ischaemia (Renal vascular disease) Renal parenchymal disease
When do we suspect renal artery stenosis?
Sudden appearance of HTN in an older person.
Resistant to usual HTN medication
Abrupt deterioration in BP control (previously stable)
Deterioration of renal function.
How does renal parenchymal disease cause hypertension?
Loss of renal vasodilator substances
Reduced GFR = salt and water retention = increased ECF volume and cardiac output
Macula Densa Cells release…
Adenosine
Macula densa cells are activated by…
Increased [Na+] in distal tubule
Effect of adenosine
Vasodilator
Most common cause of secondary hypertension
Renal parenchymal disease
Compensated Heart Failure
Stroke volume can be maintained as a result of increased preload
Decompensated Heart Failure
Volume expansion and increased preload does not bring stroke volume back up to normal
Why does left sided heart failure cause pulmonary hypertension ?
Right ventricle pumps blood into the pulmonary circulation until left ventricular preload is increased sufficiently.
Organ responsible for EPO production
Kidney
EPO and renal dysfunction
Less EPO produced by dysfunctional kidney.
Exacerbates free radical production and poor O2 supply
Direct effect of Angiotensin II on the heart
Positive inotrope
Most common cause of cardiomyopathy
Ischaemic heart disease
Definition of hypertrophic cardiomyopathy
A condition causing increased wall thickness that is not explained solely by loading conditions.
Epidemiology of Hypertrophic cardiomyopathy
Prevalence ~ 0.1%
Males affected more than females
Seen in athletes
Leading cause of death in young adults
Features of hypertrophic cardiomyopathy
Wall thickness >15mm (normally <12mm) Myocardial fibrosis Disarray (loss of uniform architecture) Abnormal mitral valve apparatus Abnormal microcirculation Abnormal ECG
Most common cause of hypertrophic cardiomyopathy
40-60% are caused by sarcomeric protein gene mutations
Most sarcomeric protein mutations causing hypertrophic cardiomyopathy
Myosin Heavy Chain 7 (MYH7)
Myosin binding protein C3 (MYBPC3)
Pathophysiology of hypertrophic cardiomyopathy
Disarray
Myocyte hypertrophy
Abnormal coronary arteries (hypertrophy decreases luminal area) - ischaemic episodes leading to fibrosis
How does hypertrophic cardiomyopathy cause mitral regurgitation?
Septal hypertrophy causes narrowing of outflow tract.
Narrow outflow tract has a suction effect (Venturi Effect).
Pulls mitral valve leaflet towards septum - opening of mitral valve
How does hypertrophic cardiomyopathy cause atrial fibrillation?
Results in mitral regurgitation.
Increased pressure in right atrium.
Dilatation of atrium - a cause of AF
Why does hypertrophic cardiomyopathy cause angina?
Hypertrophic myocardium has a higher O2 demand.
Hypertrophy also compresses coronary vessels - microvascular diease
O2 supply:demand mismatch
Symptoms of hypertrophic cardiomyopathy
Angina Syncope Dyspnoea Sudden death (May be asymptomatic prior to sudden death)
Examination findings in hypertrophic cardiomyopathy
Pulse has a rapid upstroke/downstroke
Ejection systolic murmur (between S1 and S2)
Sokolov-Lyon equation
(S wave in V2) + (R wave in V5) > 35mm
More than 35mm in left ventricular hypertrophy
ECG changes in hypertrophic cardiomyopathy
LV Hypertrophy - deep S wave in V2 and tall R wave in V5
May show atrial fibrillation
ST segment changes
T wave inversion
Cardiac MRI in hypertrophic cardiomyopathy would show:
Fibrotic changes - patchy, midwall
Ventricular hypertrophy
Abnormal papillary muscle insertion
Elongated anterior mitral valve leaflet (due to venturi effect)
Ideal echocardiogram view for viewing hypertrophic cardiomyopathy
Parasternal short axis
When is LV myomectomy indicated?
HCM
Outflow gradient > 50mmHg
NYHA III/IV
Syncope despite optimal medical therapy
What is LV mymectomy?
Removal of left ventricular wall
Used in treatment of HCM
Complications of myomectomy
AV block
Aortic regurgitation
Mortality (3-4% with mitral valve surgery)
Advantage of myomectomy over Alcohol septal ablation
Lower risk of AV block
Septal ablation is dependent on septal branch anatomy.
Can treat mitral valve pathology at the same time
Advantages of alcohol septal ablation over myomectomy
Less invasive (percutaneous)
Better recovery - better for elderly px with many comorbidities
No risk of aortic regurgitation
When is alcohol septal ablation indicated?
HCM
Outflow gradient > 50mmHg
NYHA III/IV
Syncope despite optimal medical therapy
Procedure for Alcohol Septal Ablation
Percutaneous route.
Small amount of pure alcohol infused into septal artery to produce a small heart attack
Alcohol septal ablation is not recommended in cases with…
Concurrent mitral valve/apparatus pathology
First line surgery for asymmetrical septal hypertrophy
Left ventricular myomectomy
Second line surgery for asymmetrical septal hypertrophy
Pacing of RV apex - to maintain AV synchrony
Risk Factors for Sudden Cardiac Death:
Family History of SCD Syncope Non sustained ventricular tachycardia Blood pressure response to exercise Septum > 30mm
High risk of Sudden Cardiac Death:
> 2/5 of the following:
Family History of SCD Syncope Non sustained ventricular tachycardia Blood pressure response to exercise Septum > 30mm
Management of individuals at high risk of sudden cardiac death
ICD - terminates life threatening ventricular tachycardias in HCM
Definition of Dilated Cardiomyopathy
A condition characterised by cardiac enlargement with reduced systolic function, absence of primary valve disease, and non significant coronary artery disease.
Epidemiology of Dilated cardiomyopathy
Prevalence ~ 0.5%
Males > females
Blacks > whites (2:1)
Accounts for 1/3 of all heart failure and a majority of heart transplantation
Myotonic Dystrophy is a cause of which cardiomyopathy?
Dilated cardiomyopathy
Infective causes of dilated cardiomyopathy
HIV
Lyme disease
Medical treatment of dilated cardiomyopathy
Diuretics
B-blockers (reduce HR)
ACE-I/ARB (reduce afterload)
Aldosterone antagonists (reduce ECF volume)
Protein affected in Duchenne Muscular dystrophy
Dystrophin
Prevention of Cardiomyopathy in Duchenne Muscular Dystrophy
ACE-I (perindopril)
Anthracyclines are used in…
Cancers (>50% of cancers use this treatment)
Common long term cardiac effects of Anthracyclines
Left ventricular systolic dysfunction occurs in 40% of patients more than a year after treatment
How does anthracycline induce cardiomyopathy?
Produces potent reactive oxygen species
Cancer drugs associated with cardiomyopathy
Anthracycline
Trastuzumab
Cardiac effect of Trastuzumab
Reduced LV ejection fraction
Trastuzumab (cancer treatment) must be stopped if…
Ejection fraction falls by more than 10% and EF is less than 50%
Arrhythmogenic RV Cardiomyopathy
A condition mainly affecting the right ventricle (15% involve LV) characterised by fibro fatty infiltration, ventricular dilatation and hypertrabeculation.
ECG for Arrhythmogenic RV Cardiomyopathy
T wave inversion in V1-V3 Epsilon wave (small positive deflection buried in the end of the QRS complex)
Ventricular trabeculation
Two layered myocardium, with a non compacted inner layer and a compacted outer layer
Deep recesses in communication with ventricular chamber.
Echocardiogram for Arrhythmogenic RV Cardiomyopathy
RV dilatation and aneurysm
RV hypertrabeculation
Definition of restrictive cardiomyopathy
Normal cardiac size
Reduced systolic function
Biatrial dilatation
Usually resulting from myocardial infiltration
Most common cause of restrictive cardiomyopathy
Amyloid
Causes of restrictive cardiomyopathy
Amyloid Haemachromatosis Sarcoidosis Radiation fibrosis Endomyocardial fibrosis
ECG changes in restrictive cardiomyopathy
ECG may show: Low voltage QRS Bundle branch block AV block Pathological Q waves Atrial and ventricular dysrhythmias
How does increased Ca2+ in cardiomyocytes cause contraction?
Binds to troponin, allowing tropomyosin to move away from myosin binding sites on actin.
Myosin and actin can bind - cross bridge formation
MLCK is found in..
Smooth muscle cells
How does Angiotensin II cause vasoconstriction?
Binds to AT1R (GPCR)
Activation of PLC which converts PIP2 to IP3 and DAG.
IP3 binds to its receptor on SR.
SR releases Ca2+
Ca2+ binds to calmodulin forming a complex which activates MLCK.
MLCK phosphorylates myosin, allowing actin and myosin to interact.
Effects of Angiotensin II
Dipsogenic (increased thirst) Vasoconstriction Cardiac hypertrophy Aldosterone secretion (Na+ reabsorption) ADH secretion
MOA of ramipril
ACE-I
Indication for ramipril
Hypertension Cardiac failure (with LV dysfunction)
Common ADRs of Ramipril
Cough and dyspnoea Hyperkalaemia Headache/drowsiness Weakness/fatigue Chest pain Sun sensitivity
Serious ADRs of ramipril
Renal Failure Liver dysfunction Allergic reaction Increased WBCs Angioedema Pancreatitis
Contraindications for ramipril
Renal Artery Stenosis
Afro-Caribbean Px (may respond less well)
Previous angioedema associated with ACE-I
Indication for Candesartan/Losartan
Hypertension
Cardiac Failure
In patients intolerant to ACE-I e.g. Afro-Caribbean background
Common ADRs of Losartan/Candesartan
Cough and dyspnoea Hyperkalaemia Headache/drowsiness Weakness/fatigue Indigestion Upper respiratory tract infection Abnormal taste
Serious ADRs of Candesartan/Losartan
Kidney/Liver failure Allergic reaction Angioedema Arthralgia and myalgia (joint and muscle pain) Hyponatraemia
Contraindications of Candesartan/Losartan
Pregnancy Renal Artery Stenosis Mitral/Aortic valve stenosis Elderly HCM Hx of angioedema Primary aldosteronism
Why is bisoprolol used in heart failure?
Reduces work load of the heart.
Decreased sympathetic activity.
Reduced slope of phase 4 of pacemaker action potential - negative chronotrope
Reduced Ca2+ to myocytes - negative inotrope
Indications for bisoprolol
Cardiac failure
Hypertension
SVT
Common ADRs of Bisoprolol
Bronchospasm Cold extremities Loss of libido Sleep disturbance Dizziness Dyspnoea GI disturbance
Serious ADRs of bisprolol
Raynaud’s
Bronchospasm
Serious allergic reaction
(Skin conditions: Toxic epidermal necrosis, Stevens Johnsons Syndrome, Lupus erythema, Erythema multiforme)
Contraindications of bisprolol
Asthma/COPD Cardiogenic shock Bradycardia Heart block Phaeochromocytoma Sick sinus syndrome
MOA of Digoxin
Na+/K+-ATPase inhibitor
Increased Na+ in cells inhibits Na+/Ca2+ exchange, Increased Ca2+ in cells = positive inotropy
How does digoxin act as an antiarrhythmic agent?
Inhibits Na+/K+-ATPase in brainstem cardiac centre. Increased vagal stimulation of AVN. Therefore, decreased chronotropy.
Indication for Digoxin
Systolic heart failure
Atrial Fibrillation
Atrial Flutter
Age group more likely to be given digoxin for heart failure
Elderly
Common ADRs of Digoxin
Arrhythmias Blurred/Yellow vision Nausea/Vomiting/Diarrhoea Dizziness Hyperkalaemia
Serious ADRs of Digoxin
Confusion Depression + Psychosis Anorexia Gynaecomastia Thrombocytopenia
Contraindications of digoxin
Constrictive pericarditis
HCM
Heart Block
Arrhythmias (SVT w/ accessory pathway e.g. WPW OR VT)
MOA of furosemide/bumetanide
Inhibits Na+/K+/2Cl- symporter in thick ascending limb.
High concentration of ions in urine, reduces reabsorption of H2O
Why is furosemide the strongest diuretic?
Acts in the ascending limb of the loop of Henle (Loop diuretic)
Acts earlier in the tubule than others, therefore more time to prevent reabsorption of water.
Indication for furosemide
Oedema
Cardiac failure
ADRs of furosemide
HYPOKALAEMIA
Acute urinary retention Blood disorders Metabolic alkalosis GI disturbance Pancreatitis Postural hypotension Increased serum cholesterol
Contraindications of Furosemide (loop diuretics)
Anuria Comatosed/Precomatosed Liver cirrhosis Renal failure Severely hypokalaemic or hyponatraemic
Why is bendroflumethiazide a weaker diuretic than furosemide?
Furosemide acts in ascending limb, bendroflumethiazide acts in DCT.
Thiazide diuretics act later in the tubule, therefore have less time to inhibit H2O reabsorption.
Indication for bendroflumethiazdie
Hypertension
Oedema
Cardiac failure
Common ADRs of bendroflumethiazide
Hypokalaemia Altered plasma lipid concentration Gout Electrolyte disturbance GI disturbance
Serious ADRs of bendroflumethiazide
Blood disorders:
Agranulocytosis and leucopenia (causes low WBCs)
Thrombocytopenia
Pancreatitis
Severe skin reactions
Visual disturbance
Contraindications of Bendroflumethiazide
Pregnancy Addison's - hypocortisolism (Causes dehydration and electrolyte imbalance) Hypercalcaemia Hyponatraemia Refractory hypokalaemia Symptomatic hyperuricaemia
MOA of spironolactone
Competitive inhibitor of aldosterone receptor. Prevents Na+ reabsorption and K+ secretion.
Therefore, K+ sparing diuretic.
Indications for spironolactone
Hypertension
Cardiac failure
Common ADRs of spironolactone
Hyperkalaemia
Serious ADRs of Spironolactone
Acute renal failure Hepatotoxicity Hyperkalaemia Stevens Johnson Syndrome Thrombocytopenia
Contraindications of Spironolactone
Addison’s
Anuria
Hyperkalaemia
ECG changes in hyperkalaemia
Peaked T waves
Prolonged QRS (and abnormal morphology)
Eventual loss of P waves
Bradycardia (and even eventual asystole)
ECG changes in hypokalaemia
Large P waves prolonged PR interval ST depression T wave flattening/inversion U waves
Pathogenesis of Anaemia of Chronic Disease
Reduced RBC survival
Reduced EPO production
Reduced response to EPO due to apoptosis of RBC precursors
Hepcidin-induced Altered iron metabolism - reduced plasma iron levels
Why is EPO production reduced in chronic disease?
Cytokines released in chronic disease
Why do many patients with heart failure have anaemia/iron deficiency?
Absolute iron deficiency i.e. malnourished or malabsorption
Anaemia of chronic disease (low RBCs, low EPO, altered iron metabolism)
ACE-I and ARBs result in reduced EPO synthesis.
Obstructive sleep apnoea
Collapse of pharyngeal airway
Sleep test shows complete cessation of airflow for >10s, thoracoabdominal movements present
Central Sleep Apnoea
Unstable feedback of respiratory control system
Sleep test shows complete cessation of airflow for >10s, thoracoabdominal movements absent (brain not stimulating respiratory muscles)
Apnoea/Hypopnoea Index
Total number of apnoea/hypopnoea events per hour of sleep
Mild Sleep Apnoea
5-15 apnoea/hypopnoea events per hour of sleep
Moderate sleep apnoea
16-30 apnoea/hypopnoea events per hour of sleep
Severe sleep apnoea
> 30 apnoea/hypopnoea events per hour of sleep
Why are external jugular veins not used to measure JVP?
They become small and barely visible in hypertension.
They are superficial and prone to kinking.
Why are left jugular veins not used to measure JVP?
They are not in a straight line - transmission of haemodynamic changes in right atrium is disrupted.
Features of Jugular Venous Pulses
Non palpable
Obliterated by pressure on clavicle
Decreased by inspiration, increased by expiration
Usually 2 pulsations/systole
Prominent descents
More prominent with increased abdo pressure
Measuring and calculating JVP
Measure vertical distance from sternal angle to vertical ruler at the level of JVP.
Add 5cm
1.3cm = 1mmHg
How far does the right atrium lie below the sternal angle?
5cm
Normal vertical distance from sternal angle to JVP
<4cm
Normal vertical distance from centre of right atrium to JVP
<9cm
Normal jugular venous pressure
<7mmHg
JVP Waveform: A wave
Active atrial contraction
Ascent
JVP Waveform: X
Atrial relaxation
Descent
JVP Waveform: C
Bulging of tricuspid valve with ventricular contraction
Ascent
JVP Waveform: X’
Downward movement of tricuspid valve with ventricular contraction
(Descent)
JVP Waveform: V
Passive atrial filling
Ascent
JVP Waveform: Y
Atrial emptying with opening of tricuspid valve
JVP Waveform: H
Relatively slow ventricular filling - diastasis
Between bottom of y descent and beginning of A ascent.
JVP waveform which corresponds with S1
A (Ascent)
JVP waveform which comes after S1
X (descent)
JVP waveform which corresponds with S2
V (ascent)
JVP waveform which comes after S2
Y (descent)
Cause of prominent a waves in JVP waveform
Tricuspid stenosis
Aortic stenosis
RV hypertrophy
Tricuspid regurgitation
Causes of Cannon Waves in JVP waveform
i.e. Very prominent a waves
Caused by atrial contraction against a closed tricuspid valve due to dissociated between atrial and ventricular contraction
Causes of absent a waves in JVP waveform
Atrial fibrillation Hyperkalaemia
Cause of single wave wavepattern in JVP waveform
HR > 120/min
Tricuspid regurgitation
Absent X wave in JVP waveform
Atrial fibrillation
Tricuspid regurgitation
Constrictive pericarditis
(Prevention of relaxation of RA)
Prominent X wave in JVP waveform
Cardiac tamponade
Prominent V wave in JVP waveform
RV failure
Tricuspid regurgitation
Atrial septal defect
(Increased passive atrial filling)
Diminished V wave in JVP waveform
Hypovolaemia
Venodilators
(Decreased passive atrial filling)
Rapid Y descent in JVP waveform
Constrictive pericarditis
Slow Y descent in JVP waveform
Tricuspid stenosis
Pericardial tamponade
Tension pneumothorax
(Prevention of atrial emptying)
Kussmaul’s sign
Paradoxical rise in JVP during inspiration
Caused by constrictive pericarditis, cardiac tamponade, restrictive cardiomyopathy
WHY?
Increased venous return on inspiration
Positive test for hepatojugular reflux.
What does this indicate?
Pressure applied to liver for 30s. Rise in JVP for >10s
Early cardiac failure
Cause of false positive Hepatojugular reflux test
Valsalva - abdominal guarding
Fluid overload
Cause of false negative Hepatojugular reflux
Budd Chiari
Compression of SVC/IVC
Frailty
Reduced homeostatic reserve. Small stressors have a massive impact.
Sarcopenia
Loss of muscle mass with loss of muscle strength and function
Delirium
Acute disorder of mental processes accompanying organic brain disease.
May be manifested by hallucination, delusions, disorientation.
Can be caused by intoxication, infection, deficiency and metabolic disorders.
Barthel Score
Activities of daily living including: Continence Grooming Feeding Transfer Dressing Mobility Stairs
Out of 16
(Only useful in hospital)
Cranial nerves which carry information on blood pressure to the brain
Vagus (X)
Glossopharyngeal (IX)
Information on blood pressure from baroceptors in aortic arch are carried to the brain via…
Vagus nerve (X)
Information on blood pressure from baroreceptors in carotid sinus are carried to the brain via…
Glossopharyngeal nerve (IX)
NTS is located in…
The medulla
Bainbridge Reflex
Stretch receptors in vana cava and right atrium detect an increase in blood volume.
Generate an increase in heart rate to prevent congestion of venous system
Central chemoreceptors detect…
Changes in pCO2 ([H+] in CSF)
Central chemorecpetors are located in…
Ventrolateral surface of medulla
Central chemoreceptors respons (quickly/slowly)
Slowly
Peripheral chemorecepetors detect…
low O2, high CO2 and high H+
Peripheral chemoreceptors are located in
Carotid and aortic bodies
Peripheral chemoreceptors respond (quickly/slowly)
Quickly
Myogenic Mechanism in regulation of GFR
Constriction of preglomerular (afferent) resistance vessels.
Rapid - responds in 3-10s
Tubuloglomerular feedback mechanism in regulation of GFR
Macula densa cells detect an increased [Na+] in DCT when GFR is increased.
Macula densa cells then release adenosine which causes vasoconstriction of afferent arteriole.
Therefore, GFR decreases.
Why does adenosine not cause vasoconstriction of efferent arteriole?
Efferent arteriole does not have voltage gated Ca2+ channels
Effect of SNS on GFR
Reduces GFR to normal level (when it has increased during exercise/haemorrhage)
Causes vasoconstriction of renal arterioles (afferent > efferent)
Effect on GFR of Vasoconstriction of afferent arteriole
Decreased GFR
Effect on GFR of Vasoconstriction of efferent arteriole
Increased GFR
Effect of ANP/BNP on GFR
Increased due to relaxation of interglomerular mesangial cells
+ Afferent dilatation
Effect of angiotensin II on GFR
Low dose = increased GFR (Efferent constriction)
High dose = decreased GFR (afferent constriction
Aldosterone is released from
Zona glomerulosa of adrenal cortex
Effect of aldosterone on sodium reabsorption
Increased sodium reabsorption by activation of Na+/K+-ATPase
Effect of prostaglandins on the kidney
Afferent arteriole dilatation therefore GFR is increased.
Decreased Na+ reabsorption
Effect of aldosterone on ion levels in blood
Increased Na+
Decreased K+ and H+
S3 sound is generated by
Sudden deceleration of blood into LV from LA
Due to thin walled, dilated left ventricle with generalised decreased contraction.
When in the cardiac cycle is S3 heard?
Early in diastole
S4 sound is generated by
Contraction of atria against a stiffened vessel wall
When in the cardiac cycle is S4 heard?
Late diastole
Pathological causes of S4 additional heart sound
Hypertrophy due to: Hypertension, Aortic stenosis etc
Scar tissue formation due to coronary heart disease.
Causes of raised JVP
RV failure Pericardial compression Tricuspid stenosis SVC obtruction Circulatory overload Renal failure Atrial septal defect with mitral valve disease
Causes of displacement of apex beat
Obesity - deviation of heart axis
Change in shape of heart e.g. more spherical in HF
Cardiothoracic ratio should normally be:
50% (i.e. heart should take up 50% of the width of the thoracic cavity)
Causes of poor pulses in lower limb
Hypertension - damage to vessel walls due to stress
Diabetes - wall damage due to hyperglycaemia
Renal bruit is due to..
Turbulent flow in a renal artery
Renal bruits are ausculated for at…
the periumbilical region
Protein ++ in urine suggests
Kidney damage
