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Lecture

BCH210H1 Lecture Notes - Internal Carotid Artery, Transient Ischemic Attack, Cholesteryl Ester


Department
Biochemistry
Course Code
BCH210H1
Professor
Michael Baker

Page:
of 5
BCH210H © Lisa Zhao 2012 | Page 1
LECTURE 23-24: TRANSIENT ISCHEMIC ATTACK
CASE STUDY: NAT
59 year-old male
has a high-stress occupation
known to be very talkative
quit smoking 10 months ago
82 kg, 175 cm tall
BMI = mass[kg]/(height[m])2
BMI = 26.8
he is overweightassociated w hypertension
recently began hypertension medication
before meds BP 145/90 (optimal BP 120/80)
w meds BP 125/80
medications for hypertension:
water pillsreduce blood volume
β-blockerscontrol HR
aphasiacondition where the patient can move, see, and hear, but can’t talk
indication of a problem in the circulation to the brain
(dysphasiacan speak gibberish, or sound like they are drunk [makes sense to them])
trouble with writing during aphasia
problem with output of nervous sys
possibilities: block in blood flow (most common), or broken vessel in brain
stenosisnarrowing of blood vessel due to an occlusion
in ER, Nat is able to talk again but has a tingling sensation in his right arm
CT head scan reveals no bleed or tumour in brain
neurologist listens to blood flow in carotid artery and detects an unusual noise over the left carotid
artery
bruitunusual vascular noise where there is a high-pitched noise (normally lower pitch blood
flowing sound)
indicates stenosisblood flowing through a narrower tube
stenosis led to the formation of emboli (mini-clots) in the artery which then flowed into his brain
and blocked the blood supply to the centre controlling speech
stenosis resulted in turbulence on platelets
thrombus will form on the surface of the stenosis bump, and emboli will break off and clot an
artery, resulting in an ischemic area blocking speech momentarily
transient ischemic attack (TIA)can be forecasting something more serious like a stroke (loss
of complete control in one brain hemisphere)
these problems usually occur at branch points in blood vessels under high pressure
crescendoworsening symptoms, which lead to a major event ex. a stroke
symptoms: aphasia, dysphasia, blindness, vertigo (dizziness), loss of spatial control momentarily
no O2, no glucose, falling pH, loss of fx in that area
obstruction in left side resulted in problem with right arm motor fx due to crossover of the
hemispheres
3 major blood supplies to the brain (to supply glucose and O2)
left and right vertebral arteries ending in basilar artery
left internal carotid artery
BCH210H © Lisa Zhao 2012 | Page 2
right internal carotid artery
they come together to form circle of Willis in the brain (circle of arteriole blood flow)
bloodwork reveals
LDL cholesterol 6.2 mM
HDL cholesterol 1.05 mM
Nat’s age, past smoking history elevate his risk for vascular disease
25% risk
LIPOPROTEINS
lipoproteins are small particles that have a shell of phospholipids, cholesterol, and proteins w a
core-interior made up of cholesterol esters and triglycerides
free cholesterol has an OHfound on shell of LDL
cholesterol ester has fatty acylfound in core
triglycerides are fatty acid esters of glycerol
they are the major components of fatare found in fat cells
also found in LPs circulating in the blood
has long hydrophobic FFA chains
LPs can be made in 2 major ways:
when you digest fat in your intestine, cells lining the intestine take up the fatty acids and
cholesterol, make triglycerides, cholesterol esters, and proteins, and assemble large
lipoproteins called chylomicrons
CM enter the blood and supply tissues w FFA from their TG as fuel
other tissues (mainly liver) can make LPs using TG, cholesterol, cholesterol esters, and proteins
liver readily converts excess dietary CHO (starch) into TG (fat)
liver breaks excess glucose down and converts it to long FFA chains
the liver LPs are VLDLs (very low-density lipoproteins)
VLDLs are smaller than CM but are still effective transporters of cholesterol esterase and TG
around the body
VLDLs and CMs enter the blood and are attacked by an enzyme, lipoprotein lipase (LPL)
LPL recognize proteins on the surface of CM
LPL releases FFA from TG which diffuse out from the blood and enter nearby fat and muscle
cells to be used as fuel
w the loss of TG, VLDL and CM decrease in size
the smaller CM remnants are readily taken up by liver and broken down
VLDL is converted into IDLs (intermediate size), but ultimately becomes smaller, denser LPs, LDLs
(low-density lipoproteins)
LDL (LOW-DENSITY LIPOPROTEINS)
LDLs are highly enriched in cholesterol and cholesterol esters (no TG)
are smaller and denser than VLDLs
can be removed from the blood by the liver
the liver has a surface protein, LDL receptor which binds LDL and allows uptake by the liver
(receptor-mediated endocytosis)
AAs are broken, cholesterol is freed
cholesterol can be used and eliminated by the liver, sent out into the bile, changed to bile acids
forms vesicle which is digested by the lysosomal system and removed through the intestine
if LPL uptake is impaired, LDL levels remain elevated in the blood
results in hypercholesterolemia
BCH210H © Lisa Zhao 2012 | Page 3
it is often inheritedfamilial hypercholesterolemia (FH)
risk indicator for CVD
LDL can be modified by oxidation rxns (increased risk for smokers) if they exist in the body for
prolonged periods of time
these altered LDL particles are taken up by special scavenger LDL receptors in arteries
LDL entry into arterial walls (LDL arterial pathology)
LDL can enter arterial walls but can’t get out
cholesterol is difficult to degrade and accumulates
arterial walls aren’t supplied w a lot of blood (blood flows through artery), so it is hard to get rid
of cholesterol by diffusion
results in enlarged cholesterol deposits in muscle wall
LDL in artery wall triggers an inflammatory responsethe vortex of high pressure blood flow
that encounters a bulge, and the denuding endothelial cell which exposes connective tissue
activates platelets in the circulation
LDL particles release signals which draw in monocytes that develop into macrophages (WBCs)
they digest everything but cholesterol (can’t digest it)
WBCs become foam cells w cholesterol droplets inside them
o they are now too big to exit the artery wall membrane, and die in the wall
o results in the formation of a cholesterol pool
proliferation of smooth muscle cells and connective tissue results in a plaque
after years of buildup, the cholesterol-rich lipid pool and connective tissue cap form a large
atherosclerotic plaque
bulge in the wall
reduces the size of the artery lumen, leading to artery narrowing and stenosis
leads to irregular bloodflow patterns
platelets are activated by the irregular surface of an artery that has a bulging plaque
they are small, enucleate cells (1/10th of a RBC)
are imp in blood coagulationthey stick together when they are activated (following a cut or
vessel injury)
they form thrombi which breaks off and form emboli
LDL is a major contributor to stenosis and plaque formation
LDL is an indicator for risk, normally <5mM, above is risk factor
Nat is given aspirin and has a surgery to removed the plaque in his carotid artery
used to prevent platelets getting together and forming a thrombus (anticoagulant)
must check CT first to make sure no bleed in brainanticoagulant would be detrimental
he is also given a statin drug (Lipitor) which reduces his liver cholesterol synthesis, and thus lowers
LDL liver produces less VLDLs, or VLDLs w lower cholesterol content
HDL (HIGH-DENSITY LIPOPROTEIN)
HDL is made by the liver and other tissues
functions to pick up cholesterol from other LPs and tissues and return it to the liver
HDL levels can be elevated by estrogen, exercise, and moderate alcohol intake
estrogen is a promoter of HDL
women live longer
exercise increases HDL
moderate alcohol intake can elevate HDL level
TRANS FAT