Principles - advanced editor Flashcards
how do PT and APTT differ?
stimulate different arms of the coagulation cascade

what is the pressure-volume curve?
what does it reflect?
what does it look like in diastole/systole
yaxis = LV pressure
xaxis = LV volume
shows that as volume in the LV increases, the pressure inside increases
in diastole: - hits a limit where to increase volume further, have to massively increase pressure
in systole - get a plateau with a taller curve

annotate


annotate LV pressure loop


which heart sounds are found at which part of the LV pressure-volume loop?

describe how cardiac pacemaker cells set the intrinsic heart rate
3 phases
Phase 0 - upstroke
- depolarisation
- calcium channels open when threshold is released - calcium influx = depolarisation
phase 3
- repolarisation
- K+ flows out to repolarise celll
phase 4
- spontaneous depolarisation - no stable resting membrane potential, due to leaky Na+ hannels
- Na+ and Ca2+ are flowing in

how do parasympathetics slow the heart rate
Ach binds M2 receptors
- these are negatively coupled (inhibit) adenylate cyclase
- ↓cAMP
- inhibits L-type calcium channels from opening
- reduces the Ca2+ current in phase 0 of cardiac contraction
m2 also open K+ channels - this is a hyperpolarising current
- slowss the fluxes of Na and Ca
- slows phase 4 - it takes longer to reach threshold and fire - slows heart rate

how do sympathetics accelerate the sa node
NA -> binds B1 adrenoceptor
- GPCR (stimulatory)
- activates adenylate cyclase -> ↓cAMP
- cAMP -> activates protein kinase A -> phosphorylates sites on Ca2+ channels -> opens Ca2+ channels
- Ca2+ enters
- increased slope of phase 4 in SA and AV nnodes
- ↑rate of firing of SA node
- ↑conduction in AV ode
can trigger dysrhythmias
increase HR too much - can’t cope
dose determines effect

Histology of atheroma (low power)
- Fibrous cap - often exists on top of plaque
- Lumen - 1/4 size of normal; intima is a lot thicker
- Lipid rich core - necrotic tissues (dead foamy cells, extracellular lipid) has formed the white arrow
- see Blood Vessels - can have bleeding within the plaque
- Lymphocytes (dark purple dots) are also seen
Histology of atherosclerotic plaque
- Chronic inflammatory cells - lymphocytes
- dystrophic calcification
- ECM - laid down by infiltrating smooth muscle cells
- Medial smooth muscle cells
- Cholesterol clefts - point ends; deposition of cholesterol crystals
+ necrotic debris
+ lipids
+ foam cells

What is a foam cell?
Macrophage with foamy cytoplasm - lipid rich
Steps in healing of atherothrombus
heals by organisation
- granulation tissue grows in from the intima of the vessel wall
- infiltrates
=> thrombus is replaced by fibrovascular granulation tissue
this turns into scar tissue
in larger vessels - also see recanalisation
- larger vessels develop within the fibrovascular granulation tissue
What are important sites of atherosclerosis? (5)
- abdominal aorta
- carotid arteries - cerebral infarction
- leg vessels - eg femoral artery narrowing - infarction and damage to peripheries
- renal vessels
- mesenteric arteries - occlusion leads to small bowel infarct
Consequence of atherosclerosis in renal artery
renal artery stenosis - causes atrophy of one kidney -> can cause hypertension
renal infarct - embolism in a kidney - necrosis
Risk factors for atherosclerosis
- Age + gender
- Genetics
- Hypertension
- Diabetes mellitus
- Cigarette smoking
- Lipoproteins profile
- Obesity
- Metabolic syndrome
- Physical inactivity
- Proteinuria
- marker of renal disease
- may be overlap of RF’s (same ones lead to renal disease and atherosclerosis)
- ? Type A personality
- ? Role of low grade infection
How do age and gender impact on risk of atherosclerosis?
Age + gender
- Men >45yrs
- Women: post-menopause
Women
- ? protective role of oestrogen?
- relatively higher HDL in premenopausal women
How does hypertension increase risk of atherosclerosis?
shear stress on blood vessels- subtly damages endothelium
What is a genetic RF for atherosclerosis?
genetics= mutlifactorial
familial hypercholesterolaemia - small % of cases (atherosclerosis at young age)
How does diabetes predispose to atherosclerosis?
oxidative stress and endothelial alterations:
- chronic hyperglycaemia -> advanced gycation end products (AGEs) -> oxidative stress and endothelial alterations
Diabetics have altered balance of LDL and HDL - smaller denser LDL = ‘diabetic dyslipidaemia’
How does cigarette smoking predispose to atherosclerosis?
Toxic damage
May promote thrombosis -> increase risk of complications from atherosclerosis
How does your lipoproteins profile change susceptiblity to atherosclerosis
influenced by genetics, diet
- Elevated low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL)
- LDL and VLDL are taken up by cells in response to stress and form plaque
- risk is influenced by size and density of LDL
- -> smaller and more dense = more atherogenic
- lipoprotein (a) - elevated levels associated with increased coronary and cerebrovascular disease risk
- Low levels of HDLs
- HDL – prevent oxidation of LDL, and remove cholesterol from circulation
What are some possible complications of atherosclerosis (3)
- Ischaemia
- acute or chornic - depends on the tissue oxygen needs
- due to
- Fixed vessel narrowing +/- endothelial dysfunction leading to impaired release of vasodilators -> relative vasoconstriction of distal smaller vessels = reduces lumen size
- Increased demand for oxygen (other causes)
- Sometimes caused by thrombosis (following acute plaque event) or embolism
- on top of the atherosclerosis
- due to injury, fissuring, ulceration of endothelium
- Infarction
* Not due to the atherosclerosis itself - but something on top (usually thrombus)
* Thrombus may be partially or completely occlusive
* Embolic occlusion: by plaque (athero-embolism) or thrombus (thrombo-embolism)
- Aneurysm
- rupture
- atherosclerosis -> reduced O2 to media -> damage media, weakens, -> dilation
- most common associated wtih atherosclerosis: aorta
How does thrombus occur in atherosclerosis
- Thrombus forms following acute plaque event: ulceration, fissuring, coagulation etc
- Plaques with thin fibrous caps most susceptible to rupture/fissuring - thick caps reduce chance of rupture
- fissure of endothelial wall -> contents of plaque can extrude into blood vessel
- Thrombosis: balance between coagulation and spontaneous fibrinolysis
Aneurysm classifications
Which type does atherosclerosis usually form
True aneurysm (saccular) - focal dilation = berry aneurysm
True aneuryms (fusiform) - entire circumference
atherosclerosis: fusiform



