ISchaemic Flashcards
Ischaemic heart disease
hich a lack of blood flow to the myocardium
occurs
Usually as a result of coronary artery disease
(atherosclerosis)
Angina (pectoris)
refers to pain related to cardiac
ischaemia that does not involve cell death
Myocardial infarction (heart attack)
refers to
cardiac ischaemia that results in
significant cell
death – leads to immediate death or prolonged
cardiac ejection problem – systolic heart failure
Stroke
Stroke (usually refers to a blockage of a cerebral artery causing brain ischaemia, neuronal cell death and death or congitive / motor impairment
congestive heart failure
lack of effective ejection of blood by the heart
systolic or diastolic types
Arrythmia
Refers to irregular or altered rate (too slow /
fast) of action potential development in the
heart, or movement throughout the heart (!)
Many causes – often ischaemic damage
causes changes to ion channel function or
can be drug-induced
BP = CO x TPR
BP = CO x TPR
RAAS
wo systems that work together to control blood pressure
(negative feedback loops)
Both work by linking sensory information to homeostatic
changes in cardiac output and or total peripheral resistance
RAAS – Kidney senses NaCl levels
Low NaCl levels trigger renin release – angiotensin II produced
activates AT
1
R - vasoconstriction and fluid retention
Baroreceptors sense arterial pressure
Low pressure causes increased sympathetic nerve activity to
increase cardiac output and cause vasoconstriction
The 2 systems also share a positive feedback loop
Renin-releasing cells are stimulated by
1
receptor activation
Angiotensin II release increases sympathetic nerve activation
pacemaker cells FOR M2 and B1
M2 decreases pacemaker cell rate and B1 increaee
Arthesclorosis
Process in which deposits of fatty substa
nces, cholesterol, cellular waste products,
calcium and other substances build up in the
inner lining of an artery. This buildup is
called plaque.
Usually affects large and medium-sized art
eries. Some hardening of arteries often
occurs when people grow older.
Events involved in atherosclerosis
ROS and hypertension
cause changes to the endothelium
less NO = more clotting and reduced dilation
intercellular adhesion molecule expressed on endothelial cells
————————————————–
ROS and
high LDL cholesterol
cause oxidised LDL to
enter the vascular wall
Monocytes enter the vascular wall via ICAM-1 and engulf
LDL-chol, become “foam cells”
Vascular smooth muscle cells hypertrophy making wall
stiffer
Plaque made of foam cells, smooth muscle cells, collagen
cap bulges out into lumen, altering flow
Plaque can rupture if too much matrix metalloprotease is
made by macrophages etc = clotting
ROS effects
Cause inflammation – recruitment of leukocytes - atherosclerosis Inactivate NO . , causing reduced dilation in increased clotting ----------------------------------------------- Cause hypertrophy of vascular smooth muscle cells and cardiomyocytes Remodelling of arteries and the heart Cause fibrosis of arteries and the myocardium Remodelling of arteries and the heart
causes of blood pressure to rise
Too much angiotensin II Too much salt Too much sympathetic nerve activity Not enough nitric oxide Stiffened arteries (via collagen deposition and hypertrophy of muscle cells)
Hypertension effects
A number of signaling molecules including angiotensin II and atrial natriuretic peptide are released Cause cardiomyocyte enlargement – hypertrophy Causes collagen deposition by fibroblasts These both decrease compliance – increased resistance to filling of ventricles
Consequences of a big thick heart and
remodelled arterioles
Thick heart: Increased resistance to blood flow into the cardiac chambers Less efficient filling = lower stroke volume = less cardiac output (CO) Remodelled arteries: Increased resistance to blood flow out of the heart (afterload) Reduced stroke volume = reduced CO Signal for even more cardiac hypertrophy Lower stroke volume means lower BP, renin-angiotensin-aldosterone system activation
Angiotensin II effects via AT1 receptor
activation (ACE inhibitor e.g. Lisinopril)
Kidney Direct and indirect fluid retention Aldosterone secretion leading to fluid retention (Lisinopril causes diuresis) ------------------------------------------ Vascular wall Vasoconstriction Hypertrophy - bigger cardiomyocytes, Fibrosis - collagen deposition - stiffening Reactive oxygen species (ROS) production (Lisinopril causes vasodilation, and reduces hypertr ophy and fibrosis of arteries) -------------------------------- Heart Cardiomyocyte hypertrophy and fibrosis Reactive oxygen species (ROS) production (Lisinopril reverses cardiac remodelling) ------------------------------------ Sympathetic nerves AT 1 R activation leads to increased release of noradrenaline (Lisinopril reduces sympathetic nerve activity
Combination good with ACE?
Thiazide reduces blood volume which reduces blood flow to kidneys
