Cardiology Flashcards
cardiac cycle
- flow into atria, continuous except when they contract. inflow leads to pressure rise
- opening of av valves, flow to ventricles
- atrial systole, completes filling of ventricles
- ventricular systole and atrial diastole, pressure rise closes a-v valves, opens aortic and pulmonary valves
- ventricular diastole - causes closure of aortic and pulmonary valves
heart sounds
1st = closing of AV valves 2nd = closing of semilunar valves 3rd = early diastole of young and trained athletes 4th = turbulent blood flow, due to stiffening of walls of left ventricle`
do heart chambers empty fully
no
stroke volume
volume of blood pumped out ~75ml can double during excercise
ejection fraction
% volume pumped out, ejection fraction = 55-60% , 80 in excercise, 20 in heart failure
cardiac output
volume of blood pumped per minute by each ventricle. CO=HR x SV ~5l/min
co = bp/peripheral resistance
contractility
force of contraction, adrenaline increases this
end diastolic volume
volume of blood in ventricle at the end of diastole
preload
volume of blood in ventricles at the end of diastole
afterload
peripheral resistance
increased peripheral resistance
decreased stroke volume, increased end systolic volume, increased end diastolic volume, increased stroke volume. so overall stroke volume doesnt change much`
cardiac excitation pathway
sinus rhythm = heart rate controlled by SA node approx 72 bpm, action potential then activates atria, atrial a.p activates a-v node. av node, small cells, slow conduction velocity introduces delay of 0.1 sec. av node activates bundle of his and purkinje fibres which activate ventricles
myogenic
cardiac muscle as it generates its own action potential
Action potential conduction
aps develop spontaneously at the SAN, aps are conducted from cell to cell via intercalated discs which have gap junctions
Action potential diagram described
dovna
nvr ok
ok
neurogenic
skeletal muscle, requires nerve impulse to activate
cardiac action potential describes
OVN
Q OK
LOCA V
ICA OK
Cardiac cell contraction
ca is normally released from sarcoplasmic reticulum but needs ca from outside (ca induced ca release)
where are 4 ecg limb leads placed
red - right arm, yellow- left arm, green- left leg, black - right leg (dummy)
where are 6 ecg chest leads placed
v1 - 4th intercostal space right of sternal angle
v2 - 4th intercostal space left of sternal angle
v4 - over heart apex (5th ics mid clavicular line)
v3- halfway between v2 and v4
v 5 - at the same level as v4 but on anterior axillary line
v6- same level as v4 and v5 but on the mid axillary line
Leads I, II, III
normal = I,ll +ve III -/+ve
left axis deviation = I +ve, II,III = -ve
right axis deviation= 1 -ve, II +/-ve, III +ve
calibration of ecg
10mm tall
large box vs small box ecg
large = 5mm / o.2 s small = 1 mm / o.o4 s
what causes waves on ecg
p= atrial depolarisation qrs = ventricular depolarisation t = ventricular repolarisation
normal waveform intervals
PR = o,12 - o,2 secs QRS = < o,12 secs QT = < o,44 (m), o,46 (f)
What is the pr interval
time to conduct through AVN/ His
what is QRS duration
time for ventricular depolarisation
what us ST segment
start of ventricular repolarisation. ST elevation due to acute infarction, pericarditis
ST depression due to ishaemia, LV strain (LVH)
lack of q dip
wolf- parkinson whits syndrome
ventricular hypertrophy
left or right same as william marrow but super deep troughs
RBBB and LBBB
v1 - v6 MaRRoW
v1-v6 WiLLiaM
anatomic groups of ecg leads
lateral = I, aVL, V5, V6 inferior = II,III, aVF septal = v1, v2 anterior = V3,4 Avr = none
how to calculate hr of regular rhythm
300 / count large squares between r waves and
how to calculate hr of irregular rhythm
6 x rhythm strip
brady
HR < 60 bpm
tachy
HR> 100 bpm
bradyarrhythmias
heart block
1st degree
regular rhythm, pr interval > 0,2 seconds constant. Causes: IHD, conduction system disease, healthy kids and athletes
no treatment req
bradyarrhythmias
heart block
2nd degree
aka mobitz 1 / wenckebach.
irregular rhythm, Pr interval continues to lengthen until a QRS is misssing
usually benign unless assoc with MI
bradyarrhythmias
heart block
2nd degree
aka mobitz 2
irregular rhythm, QRS complexes may be wide >0,12 seconds, non conducted sinus impulses appear at irregular intervals. can cause syncope or deteriotate into 3rd degree, if in conjuction with acute MI = high risk patient
causes: IHD, fibrosis of the conduction system
treatment: pacemaker
bradyarrhythmias
heart block
3rd degree
aka complete
atria and ventricles beat independant of one an other, QRS look different each time. May be caused by MI, cause angina or syncope.
treatment - pacemaker, isoprenaline
tachyarrhythmias
Narrow complex tachycardia
QRS duration <0.12s, uncontrolled fast atrial fib (almost straight line between complexes) or flutter ( n’s between complexes) , atrial tachycardia
Tachycardias
Broad complex tachycardia
a (QRS duration >0.12 s)
Ventricular tachycardia
Ventricular fibrillation
Sinus arrhythmia
Sinus node fires at a variable rate
• Speeds up during inspiration
• S l o w s d o w n during expiration
• Effect caused by variations in vagus nerve
activity (parasympathetic nervous system)
Sinus tachycardia
Sinus node fires > 100 per minute • Physiological causes: – anxiety, exercise • Pathological causes: – fever, anemia, hyperthyroidism, heart failure – shock (sepsis, bleeding, anaphylaxis) – almost any acute medical emergency
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
Sino-atrial disease
A degenerative condition affecting the atria,
including the sinoatrial (SA) and
atrioventricular (AV) nodes. Characterised by patchy atrial fibrosis,
atrial dilatation and altered conduction
• Common in individuals age > 70 years. Can lead to sinus tachycardia, sinus
bradycardia, atrial ‘ectopic’ beats, and atrial
fibrillation
treatment
• permanent pacemaker to prevent slow rhythms
• antiarrhythmic drugs to prevent or moderate
rapid rhythms
– beta blocker
– digoxin
– amiodarone
heart block
dizziness, fainting, tiredness and shortness of breath. Causes of AV nodal block • 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) • IV atropine or isoprenaline (acute treatment) • permanent pacemaker
Atrial fib and flutter
Sensations of a fast, fluttering or pounding heartbeat (palpitations) Chest pain. Dizziness. Fatigue. Lightheadedness. Reduced ability to exercise. Shortness of breath. Weakness. Causes of atrial flutter / fibrillation • sino-atrial disease • coronary heart disease • valve disease (esp. mitral valve) • hypertension • cardiomyopathy • hyperthyroidism • pneumonia, lung pathology Treatment • drugs to block AV node and therefore limit heart rate – digoxin – beta blocker – calcium channel blocker • electrical cardioversion • catheter ablation
ventricular fibrilation (squiggle line)
shockable ryhtmn so is ventricular tachycardiaTreatment ACUTE • defibrillation • IV antiarrhythmic drugs • remove any triggering cause LONG TERM • oral antiarrhythmic drugs • treat underlying heart conditions • implantable defibrillator for some patients
oedema
causes: low plasma oncotic pressure (malnutrition, liver disease, nephrosis), high interstitial oncotic pressure (inflammation), high venular hiydrostatic pressure (dvt), high arteriolar hydrostatic pressure (vasodilator drugs)
blood pressure
affferent: arterial baroreceptors
efferent: ANS - sympathetic and parasympathetic
hormones: angiotensin II (i), adrenaline (I), vasopressin (i)
local factors: nitric oxide (d), endothelin (I), kninins (d), prostaglandins (D)
effector organs - heart and arterioles
response time - seconds- minutes
blood volume
afferent: volume stretch receptors, juxtaglomerular cells (secrete renin)
ANS: sympathetic nervous system
hormones: aldoesterone (causes an increase in salt and water reabsorption, and increases blood volume) vasopressin (increases blood volume),
effector organs; kidneys
response time - minutes to hours
how is cardiovascular system mediated
by receptors responding to the influence of the autonomic nervous system
heart rate what receptors increase and decrease it?
increased by noradrenaline, adrenaline, beta-1 adrenoreceptors
decreased by acetylcholine, and muscarininc receptors
myocardial contractility
increased by noradrenaline, adrenaline, beta -1 adrenoreceptors
blood pressure nervous regulation
baroreceptor regulation providing second to second control of bp.
Afferent info: arterial baroreceptors carotid sinus - glossopharyngeal nerve
aortic arch - vagus nerve
CNS - vasomotor center in medulla
efferent signals : sympathetic nerves and parasympathetic
BP increase and decrease (vasoconstricor and vasodilator)
increase: vasoconstrictor, phenylephrine
decrease: vasodilator, glyceryl trinitrate
treatment of atrial fibrillation/ flutter
beta blockers (bisoprolol, atenolol @lol) calcium channel blocker (verapamil, diltiazem), cardiac glycosides (digoxin)
reduce the risk of thromboembolic stroke (Anticoagulants) vitamin k antagonists - warfarin, DOACs - apixaban
Beta- blockers
lol, b1 selective ant, indications: atrial fib, hypertension, angina , heart failure. oral administration
adverse effects: lethargy, bronchospasm, heart block
calcium channel blockers
verapamil, diltiazem. indications: atrial fib, supraventricular tachycardia, hypertension, angina. orally.
adverse: hypotension, headache, flushing, constipation, heart block
supraventricular tachycardia treatment
vagal stimulation manouevers, valsalva maneouvre, carotid massage. immediate treatment: adensoine (IV) adverse, dizzines, flushing, headache, chest pain, dyspnoae. verapamil
blood volume
intravascular - 4 L extracellular - 12l intracellular - 24;
how is blood volume sensed
the delivery of sodium and chloride in tubular fluid to the macula dense in every renal tubule and also low pressure stretch receptors in the atria of the heart
low blood volume
increases the activity of the renin-angiotensin system and sympathetic nervous system, r
renin
promotes release of angiotensin II which causes vasoconstriction and aldosterone release from the adrenal cortex
action of beta1-adrenoreceptors antagonists
beta blockers, inhibit actions of catecholamines on the SAN and AVN, reduce generation of secondary messenger cyclic amp
action of calcium channel blockers
inhibit the entry of calcium ions through L-type calcium channels
action of digoxin
cardiac glyceride that inhibits na/k atpase and increases vagal tone on avn
adenosine action
naturally occuring purine that is an agonist to A1 receptors which open potassium channels temporary block of impulse transmission
anti-arrhythmic drug class 1
block na, mainly active on myocardial cells
anti-arrhythmic drug class 2
beta 1 adrenoreceptor antagonists, active on pacemaker cells
anti-arrhythmic drug class 3
block k+ channels to lengthen action potential mainly active on myocardial cells
anti-arrhythmic drug class 4
block ca2+ channels mainly active on pacemaker cells
acute haemorrhage
reduces intravascular volume, venous retuen to the heart, cardiac output, atrial blood pressure - these changes are sensed by arterial baroreceptors, atrial stretch receptors and juxtaglomerular kidney
cardiovascular disease
diuretics, beta-blockers, ace inhibitors, calcium channel blockers, nitrates, anti-platlets, anti-coagulants, lipid lowering drugs
renin- angiotensin system
decrease in NaCl - liver releases angiotensinogen, kidney releases renin which makes angiotensin become angiotensin 1. lungs release ACE which then converts angiotensin 1 to 2, which causes vasoconstriction, NaCl reabsorption, ADH secretion, aldosterone secretion from adrenal cortex also causing NaCl reabsorption.
Blood volume increases
diuretic drugs
reduce the reabsorption of sodium and water by the renal tubules and increase urinary flow (loop, thiazide (hypertension), potassium sparing)
adverse effects of thiazide diuretics
adverse: hypokalaemia, hyponatremia, hypomagnesaemia, alkalosis, hyperuricemia, hyperglycaemia, fluid depletion, incontinence, erectile dysfuntion
calcium channel blockers
peripherally acting (amlodipine, nifedipine) and centrally acting drugs (verapamil, diltiazem). used for angina pectoris, svt, hypertension (oral) peripheral oedema,headache, flushing, constipation,
ACE inhibitors
ramipril, lisinopril reduce arterial bp, and water retetnion, first line treatment of hypertension, chronic heart failure
can cause dry cough
resistant hypertension
potassium sparing diuretics - hyperkaelemia, dizzy
Pulse pressure
SBP-DBP
Mean Arterial BP
PP/ 3 + DBP (<60 risk of ischaemia)
Total peripheral resistance
MAP/CO
When does BP change
drops at night
White coat hypertension
therefore must be meausred on at least two separate occasions to obtain BP clinic AND home/ambulatory
How many yearly deaths due to hypertension
9.4 million
10mmHg SBP reduction
32% CVA (stroke)
1 4% CHD (coronary heart disease)
20% MI
50% HF
Risk factors for CVD
Age, high BP (hypertension), high LDL cholestero (hypercholerterolaemia), High bmi (obesity/overweight), impaired glucose tolerance (diabetes mellitus) , decreased renal function (chronic kidney disease)
diagnosis of hypertension
BOTH conventional BP 140/90 AND ABPM/home 135/80`
white coat hypertension
> 20/10 higher that at home/ abpm
hypertension target organ damage
heart (left ventricular hypertrophy), kidneys (reduced eGFR, increased albumin/creatine ration), eyes (hypertensive retinopathy)
general advice on reducing hypertension
weight in ideal range, limit salt, regular excercise
Hypertension initial investigation
past BP levels, CVD and risk factors ,
blood tests (U+E/eGFR (low is bad) , lipids, HbA1c/glucose, LFTs, gamma GT (high in liver damage), urate
urinalysis : protein, glucose, blood
ECG
Hypertension treatments in patient with type 2 diabetes or aged under 55 and NOT of black African or African-Caribbean family origin
- ACE Inhibitor / ARB
- ACE Inhibitor / ARB + CCB / tl D
- ACE Inhibitor / ARB + CCB + thiazide like Diuretic
- Confirm resistant hypertension
Add low dose spironolactone if blood potassium level is 4.5 mmol/l
Add alpha-blocker or beta-blocker if blood potassium level is >4.5mmol/l
Hypertension in patient without type 2 diabetes AND aged 55 or over OR of Black African or African-Caribbean family origin (any age)
- CCB
- CCB + ACEi/ARB or tlD
- ACEi or ARB + CCB + tlD
- Confirm resistant hypertension
Add low dose spironolactone if blood potassium level is 4.5 mmol/l
Add alpha-blocker or beta-blocker if blood potassium level is >4.5mmol/l
Common anti-hypertensive drugs
ACE inhibitors - enalapril, lisinopril, ramipril
ANG-II receptor blockers - losartan, candesartan
Calcium channel blockers - nifedipine, amlodipine
[+ rate limiting: verapamil, diltiazem]
Diuretics* - bendroflumethiazide, [chlortalidone/
indapamide]
Beta-blockers - atenolol, metoprolol, bisoprolol
Mineralocorticoid-Blockers** – spironolactone, eplerenone
Alpha-Blockers - doxazosin
Mechanisms of action of common anti-hypertensives
• ACE inhibitors - inhibit ACE, block RAAS, increase BK*, dilate
arteries (and veins), AngII receptor blockers-similar (no BK effect)
• Calcium channel blockers - block voltage-operated calcium
channels, dilate arteries (± heart rate reduction)
• Thiazides - inhibit Na+
-Clsymport, distal tubular natriuresis,
dilate arteries and veins
• Beta-blockers - block beta-adrenoceptors, reduce cardiac rate
and output, block RAAS, initial vasoconstriction (ultimately
vasodilate)
• Mineralocorticoid blockers – block mineralocorticoid
receptors, distal nephron natriuresis/limit potassium loss
• Alpha-blockers – block alpha1-adrenoceptors, dilate arteries
and veins.
*BK = bradykinin a vasodilator
side effects of common antihypertensive drugs
ACE inhibitors - cough, rise in/high K+
,renal dysfunction
• Angiotensin receptor blockers – few, rise in/high K+
, renal
dysfunction
• Calcium channel blockers - headaches, flushing, ankle swelling,
tachycardia;
• [different for rate limiting CCBs eg verapamil- bradycardia,
constipation, other gastrointestinal symptoms]
• Diuretics - impotence, rashes, biochemical – low Na+, low K+,
raised glucose (risk of diabetes), high urate (risk of gout)
• Beta-blockers – wheeze [caution with asthma/COPD], cold
peripheries, lassitude, exercise intolerance, impotence,
bradycardia, heart block, raised glucose
• Mineralocorticoid blockers - rise in/high K+
, gynaecomastia
(just spironolactone)
• Alpha-blockers – dizziness (especially on standing), urinary
symptoms, tachycardia, oedema [caution with heart failure]
Indications and cautions of ACEi/ARB
i: Heart failure Diabetic Nephropathy c: Severe renal artery stenosis, High K+ Contraindicated in Pregnancy
Indications and cautions of CCB (Amlodipine, Verapamil)
i:Older patients,
high pulse pressure
Angina
c:Heart block, Heart failure
Indications and cautions of Thiazides
i: Older patients, High pulse pressure Heart Failure c: Contraindicated in Gout Low K
Indications and cautions of Beta-Blockers
i: Coronary Artery Disease
Stable heart failure
c: Heart block, Asthma/COPD
Indications and cautions of MC Blocker
i: Heart failure
Diabetic nephropathy
c: High K+
, MC deficiency
Indications and cautions of Alpha-Blocker
i: Benign prostatic hypertrophy
c: Impaired urine continence
Postural hypotension
Heart failure
Primary vs Secondary hypertension
primary: lifestyle ‘you’ caused it 95%
secondary: caused by disease
Causes of secondary hypertension
Primary aldosteronism, oestrogen oral contraceptives. NSAIDs, Alcohol, renal artery stenosis, vasculitis, liquorice, glucocorticoids
Renal artery stenosis presentation
May see:-
Severe, seems sudden, resistant Hypertension
recent decline in eGFR
eGFR dip on ACEI/ARB treatment (can be major dip)
1 kidney smaller, size difference >1.5cm (imaging). Severe hypertension with sudden attacks of “flash”
pulmonary oedema and no cardiac basis found
Severe hypertension in patient with evidence of
widespread atherosclerosis, (>50 yrs old)
Causes and management of renal artery stenosis
causes: – atherosclerotic stenosis (older, commonest))
- -Fibromuscular dysplasia (often <40, more women)
management: ACE-I/ARB treatment with eGFR monitoring
- +/- diuretic (eg Thiazide)
- Consider intervention eg renal stent(across stenosis)
Diagnosis and management of Phaeochromocytoma / Paraganglioma
very rare. features of excess noradrenaline/adrenaline: Headache
sweating,
palpitations,
high blood pressure
+/- in fearful/panicky “attacks”
+/- paroxysms of such symptoms
Management- special medical treatment, surgery, consider genetics
Dangerous tumour,
Initiate α-blockade – doxazosin (or a long acting α -blocker–phenoxybenzamine)
Then β-blockade – atenolol
At surgery – experienced anaesthetic/surgical team
primary aldosteronism
Potentially consider if Hypertension, + suspect 2O Hypertension - with relatively low K+ (+/- relatively alkalotic) investigate : if A/RR is above 40 causes: conn's tumour, bilateral adrenal hyperplasia
What are lipids and examples
poorly soluble in water but miscible in organic solvents
triglycerides
steroids - cholesterol and hormones like testosterone
fat soluble vitamins - A,D,E,K
phospholipids
sphingolipids
lipoproteins
transport cholesterol and triglycerides around the body in circulation. Dietary ones are created in the small intestine, whilst endogenous ones are created in the liver
types:
chylomicrons
VLDL, LDL,IDL,HDL
exogenous lipid pathway
chylomicrons synthesised in gut deliver triglycerides to muscle and adipose tissue where converted to NEFA (post-prandial)
endogenous lipid pathways
VLDL synthesised in liver also deliver triglycerides to muscle, adipose again converted to NEFA
LDL: cholesterol - peripheral tissues
Reverse cholesterol transport
HDL returns cholesterol to the liver but CETP can disrupt this
Lipoprotein types described
chylomicrons: biggest, mostly triglycerides
VLDL: quite big, mainly triglycerides
IDL: medium, very short lived
LDL: small, cholesterol rich, long lived
HDL: smallest cholesterol rich, long lived
apolipoproteins
determine lipoprotein behaviour
Triglycerides
energy
Cholesterol
essential building block precursor to steroid hormones and vit D and membrane. Liver is site of synthesis, secretion,uptake.
delivered to peripheral tissues by LDL
uptaken from circulation by IDL,LDL,HDL
returned to liver from peripheral tissues by HDL
formation of fatty streaks
LDLs oxidised by O-free radicals are consumed by macrophages, now known as foam cells, this is a fatty streak
formation of atheromatous plaque
LDLs oxidised by O-free radicals are consumed by macrophages, now known as foam cells, this is a fatty streak Smooth muscle cells (SMCs) are
stimulated by macrophages to
migrate, proliferate, differentiate, SMCs differentiate into fibroblasts
which produce a fibrous collagen cap , Foam cells undergo necrosis or
apoptosis to leave a pool of
extracellular cholesterol. cholesterol pool
beneath a fibrous cap
within the arterial wall = atheroma
familial hypercholesterolemia
- tendon xanthoma (nondules)
- corneal arcus (white ring)
- xanthelasma whitish lumps on eyelids
treatment of high cholesterol
smoking cessation, reduce sat fat and salt, bmi
ACEi, Beta-blocker = reduce post MI mortality
Aspirin + Clopidigrel = reduce CVD recurrence and mortality
Statins - reduce CVD recurrence and mortality. (headache, dizzy, muscle pain, increased risk of developing diabetes)
Statins
10 year CV risk , calculate using ASSIGN or QRISK3
mechanisms of lipid lowering drugs
statins: reduce LDL, lower risk of coronary heart disease (1st choice. HMG-CoA reductase inhibitors, inhibit rate limiting step of cholesterol synthesis.
Ezetimibe: reduce LDL, lower risk of coronary heart disease. Inhibits cholesterol absorption at small intestine, binds to NPC1L1 protein which is a critical mediator of cholesterol absorption in GI epithelial cells
Fibrates: reduce LDL and triglycerides, increase HDL. stimulate PPAR a which is a nuclear transcription factor, causes increased LPL activity and LDL uptake, reduced VLDL synthesis
PCSK9-inhibitors
monoclonal antibodies, delivered fortnightly by s/c injection. Alirocumab, evolocumab. expensive
sites of haematopoiesis
fetus: yolk sac (0-2m), liver and spleen (2-7m), bone marrow (5-9m)
infant: all bone marrow
adult: central skeleton, proximal ends of femur
stromal cells of bone marrow
fibroblasts, adipocytes, macrophages, endothelial cells, osteoblasts/clasts
control of adult haematopoiesis
extrinsic: growth factors , adhesion molecules
intrinsic: transcription factors
lineage of erythropoiesis
regulated by renal erythropoietin whihc is stimulated by tissue oxygen
myelopoiesis (he process in which innate immune cells, such as neutrophils, dendritic cells and monocytes, develop from a myeloid progenitor cell)
G-CSF – granulocytes
M-CSF – macrophages
IL-5 – eosinophils
types of WBC
neutrophils, lymphocytes, monocytyes, eosinophils, basophils
cytosis
too much
penia
too little
anemia symptoms
lethargy, breathlessness, chest pain, headache, dizzy, pallor
anemia causes
Blood loss Reduced RBC production • Deficiency - Iron, B12/folate • Malignancy • Chronic disease, kidney disease • Thalassaemia • Bone marrow failure Increase RBC destruction • Haemolysis e.g. autoimmune • Sickle cell disease
causes of iron deficiency
Chronic blood loss • Menstruation • Gastrointestinal bleeding •Dietary • Vegetarian, vegan, toddlers •Malabsorption • Coeliac disease, gastric surgery Increased requirements • Pregnancy, growth
megaloblastic anaemia
Defective DNA synthesis during RBC production causing
cell growth without division
macrocytic anaemia
increased MCV, usually due to B12/folate deficiency
folate
Dietary sources • Green vegetables • Folate free diet causes deficiency in weeks • Deficiency • Inadequate intake • Malabsorption – coeliac disease • Excess consumption – pregnancy Drugs eg anticonvulsants
Vitamin B12
Dietary • Meat, dairy, fish Deficiency • Vegan diet • Autoimmune –pernicious anaemia • Malabsorption • gastric or ileal surger
Haemolytic anaemia
excessive /premature RBC breakdown raised bilirubin and LDH causes :Inherited (Hereditary spherocytosis), Acquired (Autoimmune haemolytic anaemia)
Polycythaemia/ Erythrocytosis
absolute increased red cell mass
primary - assoc with thrombosis risk of malignancy
secondary - increased erythropoieten , COPD, renal tumours
relative (reduced plasma volume) acute dehydration, alcohol, diuretics
Leucocytosis
too many wBcs leukemia, lymphoma,
neutrophilia
infection, inflammation, pregnancy, steroids
monocytosis
acute or chronic infection, connective tissue damage
eosinophilia
allergy, parasites, skin diseases, drugs
leucopaenia
mainly neutropenia NR 2-7.5)
infections :
recurrent bacterial skin infections, mouth ulcers, sepsis
causes: chemotherapy, B12/folate deficiency
thrombocytosis
platelets >450
primary: essential thrombocytosis
secondary : infection, surgery, iron deficiency, malignancy
thrombocytopenia
platelets <150
symptoms: bruising, gum bleeding, nose bleeds, petechiae, prolonged bleeding time
pancytopenia
red flag everything low severe infection hypersplenism bone marrow failure TB
formation of a thrombus
PLATELET ADHESION
- PLATELET ACTIVATION / SECRETION
- PLATELET AGGREGATION
PLATELET/VESSEL WALL DEFECTS
All give rise to a “prolonged bleeding time
reduced number of platelets: thrombocytopenia
abnormal platelet function: aspirin, clopidogrel, renal failure
abnormal vessel wall: scurvy, ehlers danlos syndroms, Henoch Schӧnlein purpura, Hereditary Haemorrhagic Telangiectasia
Abnormal interactions between platelets and vessel wall : Von Willebrands disease
Scurvy
feel very tired and weak all the time.
feel irritable and sad all the time.
have severe joint or leg pain.
have swollen, bleeding gums (sometimes teeth can fall out)
develop red or blue spots on the skin, usually on your shins.
have skin that bruises easily.
Ehlers-Danlos Syndrome
joint hypermobility.
loose, unstable joints that dislocate easily.
joint pain and clicking joints.
extreme tiredness (fatigue)
skin that bruises easily.
digestive problems, such as heartburn and constipation.
dizziness and an increased heart rate after standing up.
Henoch-Schonlein Purpura
rash, joint pain and swelling, abdominal pain, and/or related kidney disease, including blood in urine.
Hereditary Haemorrhagic Telangiectasia
Nosebleeds, sometimes on a daily basis and often starting in childhood.
Lacy red vessels or tiny red spots, particularly on the lips, face, fingertips, tongue and inside surfaces of the mouth.
Iron deficiency anemia.
Shortness of breath.
Headaches.
Seizures.
von willebrand
Excessive bleeding from an injury or after surgery or dental work.
Frequent nosebleeds that don’t stop within 10 minutes.
Heavy or long menstrual bleeding.
Heavy bleeding during labor and delivery.
Blood in your urine or stool.
Easy bruising or lumpy bruises.
Autosomal dominant
tranexamic acid
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
petecial rash
pinpoint red lesions
Ecchymosis
under skin bleeding
Purpura
non-blanchable
coagulation cascade
intrinsic pathway first: 12 → 11 → 9 → 10.In order for factor 9 to activate factor 10, there needs to be factor 8 present.
extrinsic pathway second: 3 → 7 → 10.
Common pathway. 10 needs factor 5 and calcium to activate prothrombin, which becomes thrombin 2 which activates fibrinogen then fibrin
what triggers the extrinsic and intrinsic pathway of the coagulation cascade
The extrinsic pathway: This is triggered by external trauma which causes blood to escape the circulation
The intrinsic pathway: This is triggered by internal damage to the vessel wall
f XII deficiency
do not bleed
f VII deficiency
bleed abnormally
f VIII deficiency
severe hemorrhagic
f IX deficiency
severe hemorrhagic
f XI deficiency
variable and mild bleeding
steps of coagulation
Initiation
Amplification
Propagation
Termination
natural coagulation inhibitors
tissue factor pathway inhibitor ( VIII a and f Xa)
antithrombin ( thrombin and fXa)
protein c pathway (f Va and fVIIIIa)
prothrombin time PT
reflects the extrinsic and common pathway. how long it takes a clot to form. Checked when taking warfarin
Activated Partial
Thromboplastin Time
(APTT)
Reflects the ‘intrinsic pathway’
and the ‘common pathway’. blood clot to form
used if patient is recieving heparin by intermittent injection
fibrinogen
reflects the functional activity of fibrinogen used in diagnosis of bleeding disorder
haemophilia A
X-linked recessive disorder Typically expressed i Deficiency of fVIII (or dysfunction) Patients can have chronic arthopathy (joint space narrowing)
management of hameophlia
coagulation factor concentrates
desmopressin (h A)
antifibrinolytic agents (tranexamic acid)
congenital haemophila
Haemarthroses (bleeding into a joint)
Muscle bleeds
Soft tissue bleeds`
acquired haemophilia
Large haematomas (blood clot) Gross haematuria Retropharyngeal & retroperitoneal haematomas Cerebral haemorrhages Compartment syndromes
liver disease and clotting factors
reduced hepatic synthesis of clotting factors due to reduced vitamin K absorption
DIC syndrome
An acquired syndrome of systemic intravascular
activation of coagulation
Widespread deposition of fibrin in circulation
Tissue ischaemia and multi-organ failure.
can be caused by sepsis, tumor, burns, pancreatitis , snake bites, recreational drugs, pre-eclampsia
Prolonged PT time, Prolonged APTT time, low fibrinogen
raised D -dimers
virchow’s triad
stasis, hypercoagulability, vascular injury
venous thromboembolism
many present as sudden death, some as pulmonary embolism
DVT
symptoms: swelling in affected leg (unilateral), pain in leg like cramping, red skin, warmth
Causes: age, immobility, pregnancy, obesity, smoking
diagnosis : ultrasound, venogram with dye
treatment: warfarin, rivaroxaban.
likely high d dimer
Well’s score: shows risk of DVT ( Clinical signs and symptoms, current PE, heart rate > 100bpm, immobilisation >/ 3 days OR surgery in past 4 weeks, previous PE or DVT, hemoptysis, mailgnacy. score 4 = PE unlikely
pulmonary embolism
symptoms: Sudden shortness of breath (most common)
Chest pain (usually worse with breathing)
A feeling of anxiety.
A feeling of dizziness, lightheadedness, or fainting.
Irregular heartbeat.
Palpitations (heart racing)
Coughing and/or coughing up blood.
Sweating.
causes : DVT
diagnosis: CTPA to se blood vessels in lungs, V/Q scan. D dimer , ECG, ABG
rapid initial anticoagulation
heparin, low molecular weight
heparin, fondaparinux, OR
direct oral anticoagulant
Extended therapy
orally active anticoagulant : vitamin K antagonist
OR direct oral anticoagulant
Direct Oral Anticoagulants
DOACs
Dabigatran, Rivaroxaban, Edoxaban & Apixaban
licensed in UK for treatment of acute DVT
Enables rapid initial anticoagulation orally
Heparins
Sulphated glycosaminoglycan, biological product derived from porcine intestine Binds to unique pentasaccharide on antithrombin and potentiates its inhibitory action towards factor Xa and thrombin
Unfractioned Heparin (UH) vs Low molecular weight heparin (LMWH)
UFH: Binds to plasma proteins so requires monitoring Monitor using APTT Continuous iv infusion or twice daily sc administration Risk of osteoporosis, heparin-induced thrombocytopenia (HIT) Reverse by d/c (vit c( infusion; also protamine
LMWH: e.g (enoxaparin) Nearly 100% bioavailability means reliable dose dependent a’coagulant effect No monitoring required (unless renal impairment or extremes of body weight) Once daily dosing Reduced risk of osteoporosis, and HIT Cannot be reversed
Coumarins e.g.warfarin
Inhibit vit K dependent carboxylation of factors II,
VII, IX and X in the liver
Takes around 5 days to establish maintenance dosing
Loading regimens assist early dosing
Dietary intake of vit K also affects warfarin dose
reversal: Dietary intake of vit K also affects warfarin dose
DOACs vs Warfarin
DOACs are: MORE PREDICTABLE ANTICOAGULANT PROFILE
FEWER DRUG AND FOOD INTERACTIONS
WIDER THERAPEUTIC WINDOW COMPARED TO WARFARIN
ORAL ADMINISTRATION
NO NEED FOR MONITORING
SIMPLE DOSING
reverse dabigatran
dabigatran is a DOACs reversed with
IDARUCIZAMAB (Binds to free and thrombin-bound dabigatran to
neutralise activity, iv dosing by bolus or rapid infusion, immediate onset of action)
reverse apixaban and rivaroxaban
both DOACs reversed by ANDEXANET,
Atheroma
Refers to plaques found particularly in elastic and medium-tolarge muscular arteries. rfs: Age Male sex Genetics Hyperlipidaemia Hypertension Smoking Diabetes mellitus
Atherosclerosis
The consequence of atheroma
Arteriosclerosis
‘Hardening of the arteries’
• Atheroma is one cause
• Other causes include age-related sclerosis and calcification
Pathogenesis of atheroma
Chronic endothelial injury / dysfunction
• Accumulation of intimal lipid and foamy
macrophages
• Smooth muscle proliferation
• Fibrosis forming a fibro-lipid plaque
• Plaque injury – thrombosis and haemorrhage
complications of atheroma
Calcification • Ulceration • Plaque rupture • Haemorrhage • Thrombosis • Aneurysmal dilatation vessel obstruction and downstream ischaemia
thrombus
A thrombus is a solidification of blood constituents that
forms within the vascular system during life (virchow’s triad)
haematoma
Solidification of blood constituents outside the vascular
system or after death is termed blood clot or
haematoma
Endothelial Injury
Ulcerated atheromatous plaques, Abnormal cardiac valves
• Rheumatic fever
• Infective endocarditis
• Prosthetic valves
• Left ventricular endocardium after myocardial
infarction
Abnormal Blood Flow
Disrupts laminar flow
• Prevents the dilution of clotting factors
• Retards the inflow of inhibitors of clotting factors
• Promotes endothelial cell activation
• Turbulence
• Contributes to the development of arterial and
cardiac thrombi
• Stasis
• Important in the formation of venous thromb
Complications of Thrombosis
Occlusion of artery or vein (Arterial occlusion
Loss of pulses distal to the thrombus
Area becomes cold, pale, painful
Eventually tissue dies and gangrene results)
• Embolism
Venous Thrombosis
Superficial (saphenous system) varicose veins
• Congestion, swelling, pain, tenderness (rarely
embolise)
Deep
• Foot and ankle oedema
• May be asymptomatic and recognised only when
they have embolised (to the lung)
embolus
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
Infarct
• Is an area of ischaemic necrosis caused by
occlusion of arterial supply or venous drainage in a
particular tissue
Necrosis
• 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
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
Factors That Influence
Development of an Infarct
Nature of the vascular supply
• Single (e.g. spleen) or dual (e.g. lung, small bowel)
• Rate of development of occlusion
• Rapid occlusion more likely to cause infarction
• Vulnerability of affected tissue to hypoxia
• More metabolically active tissues more vulnerable e.g.
heart
• Oxygen content of blood
• Hypoxia increases risk
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
Systemic Hypertension
Classification by cause: • ~ 90% primary (essential) ( obesity, diabetes, high salt) • ~ 10% secondary • ~ 90% due to renal disease • ~ 10% due to other causes especially endocrine disease
end organ effects of systemic hypertension on heart
- Left ventricular hypertrophy
- Fibrosis
- Arrhythmias
- Coronary artery atheroma
- Ischaemic heart disease
- Cardiac failure
end organ effects of systemic hypertension on kidney
Nephrosclerosis
• ‘Drop-out’ of nephrons due to vascular narrowing
• Proteinuria
• Chronic renal failure
• Malignant hypertension is associated with acute
renal failure
end organ effects of systemic hypertension on brain
intracerebral haemorrhage causing stroke
end organ effects of systemic hypertension on eye
hypertensive retinopathy
Ischaemic Heart Disease
Blood supply to the heart is insufficient for its metabolic demands • Deficient supply • Coronary artery disease (commonest) • Reduced coronary artery perfusion • Shock • Severe aortic valve stenosis • Excessive demand • Pressure overload: e.g. hypertension, valve disease • Volume overload: e.g. valve disease
Coronary Artery Disease
• Coronary blood flow is normally independent of
aortic pressure
• Initial response to narrowing is autoregulatory
compensation
• >75% occlusion leads to ischaema
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 Clinical features • Central, ‘crushing’ chest pain • Features of heart failure • Diagnosis • Clinical history • ECG changes • Blood markers • enzymes e.g. creatine kinase • other proteins e.g. troponin
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
What is 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
Acute heart failure
Rapid onset of symptoms, often with definable
cause e.g. myocardial infarction
Chronic heart failure
Slow onset of symptoms, associated with, for
example, ischaemic or valvular heart disease
• Acute-on-chronic heart failure
Chronic failure becomes decompensated by an
acute event
Causes of heart failure
Pressure overload • Hypertension (pulmonary or systemic) • Valve disease e.g. aortic stenosis • Volume overload • Valve disease e.g. aortic incompetence • Intrinsic cardiac disease • Ischaemic heart disease • Primary heart muscle disease • Myocarditis • Pericardial disease • Conducting system disorders
Left Ventricular Failure
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
Right Ventricular Failure
Common causes
• Secondary to left ventricular failure
• Related to intrinsic lung disease – ‘cor’ pulmonale
e.g. chronic obstructive pulmonary disease (COPD)
Clinical Features
• Left ventricular failure
Hypotension • Pulmonary oedema • Paroxysmal nocturnal dyspnoea • Orthopnoea • Breathlessness on exertion • Acute pulmonary oedema with production of frothy fluid
Clinical Feature • Right ventricular failure
Ankle swelling
• Hepatic congestion (may be painful)
Clinical Features• Forward failure
Reduced perfusion of tissues
• Tends to be more associated with advanced failure
Clinical Features • Backward 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)
layers of artery
Intima, media, adventia (Strong, smooth, flexible)
aneurysm
Dilated
stenosis
Narrowed
occluded
Blocked
dissection
Split
vasospasm
Over sensitive
vasculitis
Inflamed
Claudication
Stenosis Pain on walking a fixed distance • Worse uphill • Eases rapidly when you stop • ANGINA of the leg!
Acute Blocked arteries
Pain (sudden onset) • Palor • Perishingly cold • Parasthesia • Pulselessness • Paralysis
Chronic Blocked arteries
Short distance claudication • Nocturnal pain • Pain at rest • Numbness • Tissue necrosis • Gangrene • Things falling off
Acute limb ischaemia
(sudden event with <2 weeks ischaemia)
• 7.5% limb loss at 1 year
• 25% mortality at 30 days
Chronic Limb Ischaemia
(ischaemia >2 weeks with rest pain/tissue loss = Critical)
• 5 year survival of 71%
• 43% limb loss rate at 5 years
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
vasospasm
Over active vasoconstriction • Capillary beds shut down • Triggers – cold, stress • Can have underlying connective tissue disease
Vasculitis
Inflamed arteries
Large vessel – Takayasu’s disease – “the pulseless disease”
• Medium vessel – Giant Cell Arteritis / Polymyalgia
• Small vessel – lots of polyangiitis conditions usually involving the
kidneys
treated with steroids
Diabetic foot
• Neuropathic
• Ischaemic
• Infected
• Calcified vessels
• Small vessel arterial disease
• Patients can’t see their feet (retinopathy)
The lifetime incidence of diabetic foot ulceration is 19-34%
• At 1 year
• 46% of patients will have a healed ulcer at 1 year with 10% recurrence thereafter
• 15% will have died
• 17% require an amputation
Charcot Foot
– end stage diabetic foot changes Neuropathic • Warm (>2℃ than normal) • AV shunting • Multiple fractures • “Rocker bottom” sole
Venous return
Muscle pumps – venous pressure at ankle 100mmHg standing, 25mmHg walking
• Thoracic pump action during respiration
• Gravity – lying down
• Right heart function
• Requires functioning competent valves
Venous reservoir –
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
Venous insufficiency
Failure of the muscle pump (typically calf muscle) • Immobility • Dependency • Fixed ankle • Loss of muscle mass • Failure of the valves
Venous hypertension
Haemosiderin (brown stain discolouration) staining • Swollen legs • Itchy, fragile skin • “Gaiter” distribution (shinpad) • Risk of ulceration
can cause Right heart failure • Liver failure • Compression of the pelvic veins (baby/tumour etc) • Deep venous occlusion (ilio- femoral DVT) • Morbid obesity • Valve failure • Immobility
treatment of venous hypertension
Emollient to stop skin cracks • Compression • Bandages • Wraps • Stockings • Elevate and mobilise
Valve failure
Superficial veins = Varicose veins • Deep veins = venous hypertension treatment: Superficial veins • Endothermal ablation • Surgical removal • Foam sclerotherapy • Adhesive occlusion • Compression • Deep veins • Compression
Superficial thrombophlebitis
Minor trauma • Usually underlying varicose veins • Symptomatic treatment • Heparin to stop propagation • Consider treating varicose veins
Porto-systemic 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
Dilated systemic veins from portal hypertension
Oesophageal
Varices
Caput
Medusa
vein layers
adventia, media, intima
lymphatic vessel layers
adventia, media, intima
Lymphoedema
If the lymphatic channels are blocked interstitial fluid accumulates
most common cause worldwide of lymphodema
filariasis aka elephantitis
caused by parasitic worm infection (Wuchereria bancrofti) spread by mosquitos or black flies
treated by antihelminitic drugs
general treatment of lymphoedema
Compression • Skin care • Exercise • Manual lymphatic drainage • Specialised massage technique • Rarely surgery to debulk, liposuction or connecting lymph channel to veins
Reduced oncotic pressure
Oncotic pressure is the colloid osmotic pressure induced by protein in the blood plasma • Low protein (albumin) states lead to limb swelling and oedema Liver failure • Renal disease • Low protein • Too much water • Malnutrition - kwashiorkor
Lower limb cellulitis
caused by streptococcus aureus ot swollen leg • Tissue oedema • Unfortunately chronic cellulitis can lead to lymphatic obstruction
Right ventricular failure
Central venous pressure rises
• Peripheral venous pressure rises
• Increased interstitial fluid
• Oedema
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 Increased • Sympathetic NS activation • renal failure • heart failure
Afterload
Resistance the heart must overcome to circulate blood Determined by • tone in arterial circulation Increased • SNS activation • hypertension
Angina pectoris
intermittent chest pain caused by mismatch between
demand of oxygen by the heart and supply of oxygen
to the heart
treatment:
during attack = Rapid acting organic nitrate
e.g.Glyceryl Trinitrate
prophylactic = Nicorandil Targets blood vessels longer lasting nitrate KATP channel opener Targets heart β adrenoreceptor antagonist Calcium ‘antagonist’
Nitrates
Venous circulation: dilate veins, decrease venous return and preload on heart, reduce O2 demand
Coronary arteries: improves
supply (coronary spasm)
Arterioles: dilate and reduce afterload on heart, therefore reduce O2 demand
Nitrates examples
Glyceryl trinitrate Acute (sub-lingual or spray), chronic
use leads to tolerance ie loss of responsiveness
Isosorbide dinitrite (slow release patch or oral), can be
prophylactic, nitrate free periods required
Nicorandil
used in treatment of angina reduces preload and afterload on heart and
therefore O2 demand
• dilates coronary arteries and can increase O2
supply in coronary spasm
β-adrenoreceptor
antagonists e.g. atenolol
used in treatment of angina blocks cardiac β1 adrenoreceptor - reduce heart rate and therefore O2 demand blocks renal β1 adrenoreceptor - reduce blood volume by reducing renin release & activation of RAAS, reduce preload, therefore O2 demand
Ivabradine
Treatment of angina in patients in normal sinus rhythm
reduce heart rate
and therefore O2 demand
Calcium antagonist
lower blood pressure.
nifedipine, dilthiazem
prevent opening of voltage dependent Ca2+ channels, prevents Ca2+ entry into cardiac muscle
cells from extracellular space, therefore
reduce availability to contractile apparatus,
reduce force of contraction and
therefore O2 demand,
aspirin
taken prophylactically to reduce the risk of thrombus
cyclooxygenase inhibitor
rreversible inhibition of COX, prevents formation of TxA2 & platelet
activation
clopidogrel, ticagrelor
taken prophylactically to reduce the risk of thrombus
P2Y12 inhibitor blocks effect of ADP and prevents platelet activation
voripaxar
taken prophylactically to reduce the risk of thrombus
thrombin-receptor antagonist
• prevent activation of PAR-1 receptors on platelets
Fondaparinux
Anti-coagulant not orally active
Synthetic pentasaccharide
• Also acts through anti-thrombin III but selective
for factor Xa inhibition
Bivalirudin
Anti-coagulants not orally active
Directly binds thrombin and inhibits thrombin induced
conversion of fibrinogen to fibrin, synthetic congener of hirudin
warfarin
orally active
Common clinical indications
atrial fibrillation, the presence of artificial heart valves, deep venous
thrombosis, pulmonary embolism and, occasionally, after myocardial
infarction.
Dabigatran
Directly Acting Oral Anti-Coagulants
Direct inhibitor of thrombin (factor II) enzyme activity
• Competitive and reversible
severe bleeding can be reversed by Idarucizumab
Fibrinolytic drugs
clot buster
•most effective to reduce mortality if given immediately (<3h) after MI
or stroke
• accelerates conversion of plasminogen to plasmin, which degrades
fibrin in thrombus
• can cause bleeding (reversed by tranexamic acid)
Heart Failure
two types:
impaired contractility and emptying of ventricle HF with
reduced ejection fraction, HFrEF, systolic HF): most
common and drugs directed here
impaired relaxation and filling of ventricle (HF with preserved ejection
fraction, HFpEF, diastolic HF): growing recognition, more common in
women, diabetes, mechanisms less understood
common causes of heart failure
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
Drugs for Heart failure
Digoxin cardiac glycoside hat
increase the force of contraction: +ve inotrope,
therefore increases kidney perfusion and fluid loss
Cardiac glycosides inhibit Na+/K+ ATPase
dobutamine (ß1 adrenoreceptor agonist iv for rapid
response), increases heart rate and contractility
Renin inhibitor
aliskiren heart failure
ACE inhibitor examples
enalapril, lisinopril heart failure
AT receptor antagonists
AT receptor antagonists heart failure
Loop diuretics
for heart failure
. frusemide, bumetamide
impair Na+/K+/Cl- readsorption in the ascending
loop of Henle
Mineralocortoid receptor antagonists
heart failure
spironolactone, eplerenone
• block effects of aldosterone on Na/K
readsorption
ß adrenoreceptor antagonists and the RAAS
block renin release from the kidney, therefore
decrease RAAS activation, decrease pre-load &
after-load
reduce sympathetic drive to the heart (reduced O2
demand)
few side-effects, but not useful in asthmatics
(especially non-selective)
Nitrovasodilators
heart failure isosorbide mononitrate (long acting but risk of tolerance) venous circulation: decrease venous return and preload arterioles: reduce PVR and afterload
Hydralazine
dilator that targets arteries > veins and reduces afterload
nitrates and hydralazine can be used to treat
acute heart failure or in patients with chronic
heart failure who fail to respond to other drugs
High Sensitivity CRP
Acute phase protein produced by liver and
adipose tissue.
- Assists in complement binding and phagocytosis
of damaged cells
Creatine Kinase
Not cardiac specific
Present in Skeletal
Muscle
Troponin
The troponin complex is a component of the thin filaments in
striated muscle complexed to actin. Regulates muscle contraction
Troponin – 3 subunit complex: Predicts Future Cardiac Events
gender specific
heart disease diagnosis
naturitic peptides
Naturetic peptides can be used for the rule out of
chronic heart failure and have a role in stratifying
treatment
VȩO2
is dependent upon:
Ventilatory capacity to provide oxygen - Circulation to deliver O2 to exercising muscle - Muscle ability to utilise O2 for energy conversion
VȩO2 max
Maximal oxygen uptake
– Used as a global measure of fitness
Ventilation adapts to meet needs for
- Uptake of oxygen
- Clearance of CO2 produced
Respiratory quotient (RQ) also known as Respiratory Exchange Ratio (RER):
- CO2 produced / O2
consumed - RQ increases with exercise
Increased ventilation achieved by:
Increases in respiratory rate (RR) – Increased size (tidal volume - VT) of each breath
–Ventilation per minute (V̇E)= RR x VT
Maximal exercise ventilation (V̇E max) can be estimated as
maximal
voluntary ventilation (MVV)
- MVV = FEV1
x 40
increase in cardiac output during exercise
Five-fold.
Increases in HR
- Increases in stroke volume
Rate-limiting factor to maximal exercise in health
CARDIAC PHYSIOLOGY
maximal heart rate
Anaerobic Threshold
Point at which ventilation increases at a faster rate than oxygen uptake (VO2
) and reflects the point at which anaerobic
metabolism begins to predominate with exponentially increasing carbon dioxide production and accumulation of fatigue-related metabolites including lactate.
Ventilatory threshold
This is actually what we are measuring if non-invasively when performingexercise tests keep incorrectly referring to it as AT
Effects of deconditioning
Reduced muscular capillary numbers
(reduced O2 transfer at muscular level)
• Reduced mitochondrial density
(reduced O2 utilisation at muscular level)
• Reduced oxidative enzyme concentrations
(reduced energy transformation in muscles)
Impaired ability for exercising muscle to extract and utilise oxygen
from blood
CPET
limitations of excercise capacity
Diagnostic Importance:
Exercise-induced arrhythmias
Exercise-induced asthma
EXERCISE-INDUCED ASTHMA
Acute, reversible, usually self-terminating airway obstruction– During or after strenuous exercise or hyperpnoea – Especially if breathing dry and/or cold air – May occur in atypical or latent asthmatics.
