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In the AV node the conduction is delayed by ___ millisecs. This time allows blood to flow from the atria to the ventricles. (allows for the atrial kick to fill the ventricles).
In the AV node the conduction is delayed by 200 millisecs. This time allows blood to flow from the atria to the ventricles. (allows for the atrial kick to fill the ventricles).
Arrythmias result from changes in ____, ____, and ____
Arrythmias result from changes in rate, regularity, and conduction.
How do the APs of hte SA and AV node differ from the APs of the atria and the ventricles?
Phase 0 (upstroke) of the SA node is due to Ca channels (slow fibers) and is not as steep as in the atria/ventricles (fast fibers).

Phase 0 (Upstroke) of the atria and ventricles is due to Na channels..which are FAST. It is steeper in slope and correllates with the P wave or QRS complex of the ECG.

The SA and AV nodes also have a Phase 4, which is a slow depolarization caused by the opening of slow funny Na channels. this phase controls automaticity and HR.

The AP duration is MUCH LONGER in the atria and ventricles due to the opening of L-type Ca channels during phase 2...this caues a plateau in repolarization as long as the Ca channels are open. It also keeps Ca in the cell for contraction, and keeps the Na channels in an inactive state...which allows for a VITAL refractory period. (The heart cannot have tetany due to this..which is good because you have ot maintain HR...tetany would put the heart at a standstill).
The following ECG sections reflect what part of what APs?

P wave
PR Interval
QRS
QT Interval
Twave
P wave - upstroke (Phase 0)of atrial APs (Na Channels)

PR Interval - upstroke (Phase 0) of AV node APs (Ca channels)

QRS: Upstroke (Phase 0) of ventricular APs (Na channels)

QT Interval: Ventricular Phase 2: the plateau phase (Ca channels open)

T-wave: The end of the ventricular Plateau Phase 2, and the start of ventricular Phase 3. (K channels open)
Describe the phases of the atrial/ ventricular APs
Phase 0 = Rapid depolarization, upstroke phase. (voltage gated Na Channels – rapid). W/n millisecs (rapid) Na Channels are inactivated.

Phase 1= Small repolarization phase (d/t rapid inactivation of the Na channels .

Phase 2 =Long Plateau ( makes the hearts AP diff. from other APs) – d/t opening of voltage gated, L-type Ca channels. Ca runs in slowly…maintaining the MP/ depolarization. This has two functions:
1) Keeps the Na channel in the inactivated state. This is very important for maintaining a refractory period (HR).
2) Influx of Ca also maintains intracellular Ca conc…which is needed for cardiac myocyte contraction.

Phase 3 = Repolarization Phase: Ca channels close. K channels open even more. The late peak of K conductance is d/t “delayed rectifier” K+ channels Ik, opening.

Phase 4 = Resting Membrane Potential.
The delayed rectifer K channels that allow for repolarizaton of the ventricles are blocked by what drugs, causing a risk of torsades? (ie the duration of the AP is lengthened...)
Procainamide
Cisapride
Amitriptyline, Amiodarone
Imipramine
Sotalol
Quinidine
Flecainide

(Mneumonic: Potassium Channels Are Inhibited Slows QT F*ck!).
What are the 4 classes of antiarrythmic agents?
Class I: Na+ Channel Blockers
Class II: β-Adrenergic Receptor Blockers
Class III: K+ Channel Blockers
Class IV: Ca2+ Channel Blockers

"Pneumonic: Nude Beaches Kinda Contagious"
What are the two effects of CCBs on the what AP in the heart?
Block the Ca channels in the SA and the AV node causing increased threshold for firing (longer Phase 4) and decr slope of phase 0 upstroke.

This causes
1) Decreased HR (automaticity)
2) Decr AV nodal conduciton (prolonged QR interval).
What 3 effects do Beta Blockers have on what APs?
*BB's pvt the cat activation of Na funny channels and L-type Ca channels (via incr cAMP).

1) Decreased HR/ Automaticity: Decr Slope of PHASE 4 of the SA node AP. (blocked funny channels) and Decr slope of Phase 0 (Inhibited Ca channels).

2) Lengthened PR Interval - Decr Slope of the PHASE 4 of the AV node AP (blocked funny channels), Decr Slope of Phase 0 (Blocked Ca channels)...- decreases AV node conduction.

3) Shorten QT interval: Decr Opening of L-type Ca channels..shortens Phase 2 of the ventricular AP. ..DOC for Prolonged QT Syndrome.
What regulates SA and AV node APs and what phase does it regulate?
The SNS and the PNS regulate the slope of PHASE 4 of the SA and AV node APs (via funny Na channels). AND regulate the slope of PHASE 0 (via L-type Ca channels)
* they can also regulate QT interval (in the atria and ventricles) via the L-type Ca Channels in Phase 2 of the ventricles.

SNS STIMULATION: Beta 1 stim of Adenyl Cyclase and Incr cAMP
1) Opens Na Funny Channels: Incr Slope of Phase 4
----> Incr Automaticity (HR)
2) Opens L-Type Ca Channels
----> Incr Length of Phase 2 of Ventricles: (Prolonged QT Interval).
----> Decr firing Threshold, Incr Slope of Phase 0 of SA/ AV nodes
* Causes incr HR/ Automaticity. Decr Refractoriness of SA/AV node.

PNS STIMULATION: Ach to a M2 Receptor: Decreases cAMP
1) Inhibits Funny Na Channel Opening
----> Decr Slope of PHASE 4 in SA/AV node
----> Decr Automaticity (HR)
2) Inhibits L-Type Ca channel opening
----> Incr Firing Threshold, Decr Slope of PHASE 0 of SA and AV node
----> (INCR Refractoriness of SA/ AV node).
----> (Decr SA Automaticity, Decr AV nodal conduction).
-----> DECR refractorness of Atrial and Ventricles....PHASE 2 of their AP is shorter.
Ex: Digoxin (vagal act is a side effect),
What are three drugs that DECR VENTRICULAR RESPONSE TO A-FIB? (ie slow AV nodal conduction
1) BETA-BLOCKERS: decr the slope of AV nodal phase 4 (also decr HR).
2) CCBs (Verapamil and Dilitiazem) - decr the slope of Phase 0 in AV and SA node, and also incr the firing threshold ...so make Phase 4 LONGER.
3) DIGOXIN - has a side effect of vagal activity so it causes Musc stim of the heart, which decr the slope of Phase 4, decr-ing HR and AV conduction.
Conduction velocity in the ventricles is determined by...?

What is the relevance of this?
Conduction velocity is determined by the size of the Na current...ie...how many open channels do you have?

Means that ischemic heart cells will have a higher RMP (d/t inactive Na/K ATPase) and more inactive Na channels. So their conduction velocity will be SLOWER.
What classes of antiarrythmics will bind best to ischemic heart tissue?

Tachycardic Tissue?
Ischemic:
* Class IB - LIdocaine (binds to inactivated Na channels).

Tachycardic:
*All Class I agents: Quinidine, Procainamide, Lidocaine, Flecainide. Bind best to open or inactive Na channels.
* Class IV - CCBs - Verapamil and Dilitazem - BInd best to Open/ stimulated CC's.
Binding of anti-arrythmic agents is _____ and _____ dependent.
Binding of anti-arrhythmic agents is membrane potential-dependent (diseased, depolarized tissue) and frequency-dependent (tachycardia).
Define the Effective and Relative refractory periods and tell me where they appear on the ECG.
Effective Refractory Periods
* PHASE 2: The plateau phase of the ventricular AP. All the Na channels are either open or inactivated.
* The cells will not respond no matter how great the stimulation.
* Very LONG - pvts tetany.

Relative Refractory Periods
* PHASE 3: The repolarization phase due to delayed rectifier K channels.
* A really LARGE stimulus will trigger an AP.....(early after deplorization).
Drugs that increase refractoriness
1) Na Channel Blockers: Class I agents delay the recovery of the Na+ channel from inactivation (FREEZE INACTIVE)

2) K Channel Blockers: Class III agents prolong the AP DURATION
Most common cause of arrythmias
reentry pathways.

Ex: WPW
What drugs do you use to treat Sinus tachycardia via SNS stimulation? How do they work?
Beta blockers (Class II) :decr the slope of Phase 4 depolarization.

CCBs (Class IV) : decr slope AND amplitude of Phase 0 (Ca current) depolarization. Incr the threshold for stim...make phase 4 last longer. FREQUENCY (rate) DEPENDENT BINDING!!.
How do you tx sinus bradycardia?
Pacemaker
What drugs do you give to treat an Ectopic Pacemaker than has overriden the SA node? (SVT, etc).
Na Channel Blockers (Class I): Decr firing of fast response fibers (ectopic only)…also will only bind to the ones that are firing..(open and inactive Na channels only).

(BBs and CCBs would not work because they will hit the SA node).

K+ Channel Blockers (Class III)
Prolonged AP duration (slows HR d/t incr refractoriness)
What causes an early after depolarization arrythmia and how do you treat it?
* The Relative Refractory Period (PHASE 3)...K channels are open, cell is repolarizing...and a LARGE stimulus will TRIGGER an early AP...causing a tachycardia. This a "R on T" phenomenon that can cause Torsades de Pointes.

*This arrythmia has a high occurence when there is a PROLONGED QT INTERVAL.

TX:
* Class I Agents: Na Channel Blockers: Incr Refractoriness by freezing Na channels in the inactive state.

*Class II Agents: BBs - Decr the opening of L-type Ca Channels, which shortens PHASE 2. .
DOC FOR PROLONGED QT SYNDROME?
BBS - Propanolol, Carvidelol.
(NOT sotalol!)

Better than Na channel blockers becasue they allow the normal AP to continue.
What causes reentry arrythmias?
For reentry to occur, you need to have an area of ischemic tissue that causes an UNIDIRECTIONAL BLOCK OF THE AP CONDUCTION. This block will pvt the signal from traveling anterograde thru that region, BUT when the signal reaches it from the other side, if can now travel RETROGRADE through it…and eventually reach the other zone (zone 1 here). Conduction thru the diseased area is SLOW. By the time it gets there, the some of the cells in zone 1 are not longer in the refractory period. TADA…you have a reentry beat.
Treatment for reentry arrythmias?
1) Class I Agents: Na channel blockers: Quinidine and Procainamide ("Quick Pulse).
* Block AP in ectopic areas.

2) Class III Agents: K channel blockers...prolong the AP and thereby INCREASE REFRACTORINESS. EX: Amiodarone, Sotalol
Least cardiotoxic antiarrythmic agent
Lidocaine.

BInds to Na channels in the inactive state ...such as ischemic and arrythmic areas. So the normal areas are unaffected.
Oral Class IB alternatives to IV Lidocaine are...
Mexiletine and Tocainide.
Difference b/n procainamide and Quinidine
Procainamide does not have the INDIRECT arrythmic effects of Quinidine: TACHYCARDIA AND SHORTENED PR INTERVAL.

1) Anti muscarinic - incr AV nodal conduction
2) Alpha-1 Blockade: VD and reflex tachycardia
Anti-arrythmic drugs that affect Slow Response Fibers (SA and AV node)

What are they usually used for?
BBs
CCBs
Digoxin
Adenosine

Used for PSVTs and rate control for afib.
Anti-arrythmic Drugs that affect Fast Response Fibers (Atrial and Ventricular cells)?

What are they generally used for?
Class I and III Antiarrythmics.

Quinidine
Procainamide
Lidocaine
Flecainide
Amiodarone
Sotalol

Used for ventricular or atrial arrythmias..reduce ectopy.
What anti-arrythmic drugs affect both slow and fast response fibers?

What are they generally used for?
Beta Blockers
(I think it is more than this but this is all the teacher said.).

USE: PSVTs, Rate control in A-fib, DOC for prolonged QT Syndrome.
Describe Delayed After Depolarizations (not early).

What caues them and how do you treat them?
Delayed after depolarization: occur when there are fast heart rates, Triggered activity, or a calcium overload.

Can occur in a pt who is taking digoxin and has toxicity. This creates a delayed afterdepolarization: a smaller AP is generated right after the normal AP.

Ca channel blockers can be used to treat these that are caused by digoxin toxcity..but both will slow AV node conduction and inhibit the P glycoprotein..so Ca channel blockers are not used much anymore…

Fast beta-blockers and Mg are now the DOC!!!! for tx of DAD!!!
_____ is the first result of excess demand relative to supply of O2 in the heart.
Angina Pecotoris d/t the accumulation of anaerobic metabolites.
Differentiate b/n the 3 Types of Angina
CLASSIC (STABLE) ANGINA
* Associated with fixed coronary stenosis (stable..does not change).
* Causes Exertional (exercise induced) chest pain (d/t incr O2 demand) that is relieved by rest.

VARIANT (PRINZMETAL'S ANGINA)
* Coronary Vasospasm induced Angina (from decr blood flow - (an O2 supply issue)
* Can occur at rest and even during sleep.

UNSTABLE ANGINA
* Type of acute coronary syndrome
* Abrupt onset, prolonged, unassociated with an identifiable precipitant.
* There is underlying platelet aggregation (decr O2 supply results).
* Pain is more severe and frequent.
Determinants of O2 Demand
Heart Rate
Contractility
Preload (incr wall stress)
Afterload
Determinants of O2 Supply
Coronary Blood Flow
Regional Myocardial Blood Flow
Drugs that decrease O2 Demand of the heart
Organic Nitrates: (decr preload - decr wall stress)

CCBs: (decr HR, contractility, and Afterload via VD).

BBs: decr HR, contractility.
Preload is due to ________ and afterload is due to ____________.
Preload is due to venous constriction and afterload is due to arterial constriction.
Explain the Mechanism of Action of Nitrates.
Organic Nitrates diffuse across the cell membrane of endothelial cells of the blood vessels.

Once inside, in the presence of a sulfhydryl grp inside the cell, they are converted to Nitric Oxide (NO.).

NO binds to the SOLUBLE (non-membrane bound) form of Guanylyl Cyclase inside the cell and activates it.

Guanylyl Cyclase converts GTP into cGMP.

cGMP activates Protein Kinase G.

Protein Kinase G DEphosphoylates the myosin light chains causing RELAXATION.
What is Nesiritide adn what is it's mechanism of action inside the BV?
Nesiritide is a drug from of BNP which is released by the brain when you have volume overload. It causes a naturesis and VD.

MOA for the VD:
* Nesiritide binds to receptors on the endothelial cells of BV's. Attached to these receptors if the INSOLUBLE (membrane bound) form of Guanylyl Cyclase.

Activated rGuanylyl Cyclase then converts GTP into cGMP in the cell.

cGMP activates Protein Kinase G.

Protein Kinase G DEphosphorrylates the Myosin Light Chains, causing RELAXATION.
What is the mechanism of action of CCB's that causes VD?
* CCBs block the Ca in the endothelial cells of BV.

Normally, Ca enters the cell, binds w/ calmodulin, and this complex activates MYOSIN LIGHT CHAIN KINASE enzyme.

This enzyme phosphorylates teh MLC, causing CONTRACTION.
Why are beta blockers given with nifedipine or nitrates>
To pvt the reflex tachycardia and decreased preload.
Why can't you give BBs with CCBs?
C +B = CB (Conduction Block).

Due to extremely decreased AV nodal conduction.
Why are beta blockers given with nifedipine or nitrates>
To pvt the reflex tachycardia and decreased preload.
Explain how ischemic heart disease leads to Heart failure
Hypoxia/ hypercarbia an initial decr in CO cause SNS activation. Cats are released.

Cats cause venoconstriction and RAAS activation, both of which incr preload. They also incr HR and contractility, both of which incr O2 demand to the heart. But initially, it works and the CO is increased.

The heart hypertropies (concentric). Overtime, it wears out and dilates (eccentric). SNS compensatory mechanisms become maladaptive. (Incr afteroad, incr EDV, etc.). CO falls. Decr renal BP incr RAAS (renin is released). ANGII causes more VC and incr afterload. Aldosterone causes Na and water retention, hyperkalemia and metabolic acidosis.

Overtime, the cats cause apoptosis of myocardial myocytes.

ANGII and aldosterone can cause coronary fibrosis.
How does CHF change the frank starling curve?
The Frank Starling Curve is SV vs LV filling pressures (x-axis). The ascending limb is the frank starling relationship...as preload (filling pressure) increases, so does SV.

In CHF the curve is SHIFTED DOWN (lower). Why? The heart has increased preloads (filling pressures) to get the same stroke volume. The curve is also more plateaued...meaning SV is more constant...preload is increasing...

As the HF worsens, the point on the CHF curve moves to the left...preload is increasing more and more to maintain the same SV...which is slightly decreasing (decompensation).
How does Digoxin affect the Frank Starling Curve?
The Frank Starling Curve is SV vs LV filling pressures (x-axis).

The ascending limb is the frank starling relationship...as preload (filling pressure) increases, so does SV.

In CHF the curve is SHIFTED DOWN (lower). Why? The heart has increased preloads (filling pressures) to get the same stroke volume.

DIGOXIN (or any Inotrope WILL MOVE THE CURVE UPWARD (upward shift towards normal again). How? By increasing contractility...the heart needs less preload now to get the same stroke volume.

After this occurs, RAAS and SNS stim will turn off and preload will fall. This is seen as a movement of a point on the Digoxin/ Inotrope curve to the LEFT. (decr filling pressure, decr SV (high SV not needed anymore).
Why are BBs 1st line tx of CHF despite the fact that they decr contractility???
They block the deleterious effects of catecholamines on the heart. (cats cause apoptosis of cardiac myocytes, and remodeling of the heart).
How do vasodilators effect the Frank Starling Curve?
The Frank Starling Curve is SV vs LV filling pressures (x-axis). The ascending limb is the frank starling relationship ...as preload (filling pressure) increases, so does SV. In CHF the curve is SHIFTED DOWN (lower). Why? The heart has increased preloads (filling pressures) to get the same stroke volume.

VDrs effect on this curve will depend on whether the VDr primarily acts to decrease AFTERLOAD or PRELOAD.

VDrs that ONLY REDUCE PRELOAD (venodilators) will cause a LEFTWARD SHIFT of a POINT on the curve.
* Decr Preload...SV decr only SLIGHTLY d/t a more plateaued CHF curve.
* Ex: NTG

VDrs that ONLY REDUCE AFTERLOAD cause an UPWARD SHIFT in the curve.
* Can get a higher SV at the same preload.
* Ex: Hydralazine.

VDrs that reduce PRELOAD AND AFTERLOAD cause an UPWARD SHIFT of the curve and LEFT MOVEMENT of a point on the curve.
* Ex: Nitroprusside, High dose NTG.
* Decr preload = decr SV BUT Decr afterload, incr SV.
What effects do Diuretics have on the Frank Starling Curve?
The Frank Starling Curve is SV vs LV filling pressures (x-axis). The ascending limb is the frank starling relationship...as preload (filling pressure) increases, so does SV.

CHF: In CHF the curve is SHIFTED DOWN (lower). Why? The heart has increased preloads (filling pressures) to get the same stroke volume. As the HF worsens, the point on the CHF curve moves to the left...decr SV and filling pressures d/t dilation. (decompensation).

DIURETICS:
* Diuretics will decrease preload and move a point on the curve to the LEFT. The effect is a decr load on the heart (decr filling pressures or preload) but no real decr in SV because the CHF curve is FLATTER than the normal curve. They do not reduce CO despite decr preload b/c they are reducing it at a plateau in the curve.
ACC Stages of Heart Failure and their treatments.
STAGE A
* HIgh risk of heart failure w. no structual damage or heart failure symptoms.
----> TX THE COMPELLING INDICATIONS

STAGE B
* Structural Damage with no heart failure symptoms. TX WITH ACEIS AND BBs....or if you are AA or geriatric tx with Isosorbide Dinitrate and Hydralazine.

STAGE C
* Structural damage with current heart failure symptoms. TX WITH ACEIs BBs, ALDOSTERONE ANTAGS (spirinolactone), & LOOP DIURETICS (furosemide).

STAGE D
* Refractory Heart Failure. TX WITH MECHANICAL ASSISTANCE, INOTROPIC AGENTS (digoxin, dobutamine, inamrinone) , AND TRANSPLANT
T/F the majority of HTN pts are symptomatic
False.

The majority are asymptomatic.
Low renin levels are common in what populations?
African American and Geriatric populations. '

Makes them unsensitive to ACEIs and ARBs.
What are some secondary causes of HTN
Renal disease
Pheochromocytoma
Primary Aldosteronism
Imported LIcorice - inhibits cortisol degredation.
Glucocorticoid use.
Estrogen use
Sympathomimetric Amine Use.
White Coat Syndrome.
The most common cause of HTN is...
Essential HTN - unknown.
Normal BP =
Prehypertension =
Stage 1 Hypertension =
Stage 2 Hypertension =
Normal BP : < 120/80

Prehypertension : 120/80 - 139/89
(Tx w/ lifestyle, diet changes).

Stage 1 Hypertension : 140/90 - 159/99
(Tx w/ Thiazide Diuretic, more drugs for compelling indications: ACEI, ARB, CCB).

Stage 2 Hypertension: >=160/100
(Tx w/ 2 drug combos: HCTZ, ACEI, ARB, CCBs).
CHF is treated with...
Diuretics, BBs, ACEIs, ARBs, Spirinolactone.

DO NOT GIVE CCBs WITH HEART FAILURE!!! WILL DECREASE CONTRACTILITY AND CO!!!!
Diabetics with CHF/ HTN are tx with...
ACEIs and ARBs. d/t benefits in diabetic Nephropathy/ neuropathy.
Pts w. Benign Prothetic Hyperplasia are tx with...
An alpha 1 receptor antagonist

Ex: Prazosin

These pts have trouble peeing... prazosin helps them to pee. (a1 constricts sphincters).
Pts with migraines are tx prophylactically with...
Beta Blockers.
Two medicinal approaches to treating HTN...
1) Drugs that decrease SVR/ TPR
2) Drugs that decrease SV or HR

BP = TPR x CO.
What drugs cause orthostatic HOTN?
1) Agents interfering with SNS tone. (Prazosin)

2) Direct Acting Venodilators (NTG).

Prazosin
Phentolamine
Carvidelol
Quinidine
Labetalol
NTG
Na Nitroprusside
Isosorbide Dinitrate
Describe the changes that occur with a decreased blood pressure......
1) EDEMA d/t incr ECF...d/t VD
2) Reflex Tachycardia d/t SNS stimulation
3) Renin Release
Describe the tx regimen for HTN...what drugs when...
Thiazide diuretic FIRST.

For pts in whom HTN is not controlled by a thiazide, CCB, or an ARB, can be give BB, Alpha1 blocker.
In severe, refractory HTN, can use a direct VDr such as Minoxidil or hydralazine.

Alpha2 agonists are not commonly used d/t severe side effects that they cause.

HTN emergency: DBP is above 120 mmHg. High risk of encephalopathy, damage to the kidneys, etc.
IV Na Nitroprusside is the DOC. …but you can get cynadie poisoning.
CCBs such as the dihydropyridines are more commonly used for HTN emergencies. …to pvt the cyanide poisoning.
What HTN drugs are CI with dyslipidemia?
Thiazide diuretics
Beta Blockers
What HTN drugs are CI with Diabetes?
Beta Blockers
Thiazide Diuretics (decr insulin release from pancreatic beta cells).
What HTN drugs are CI with Gout?
HCTZ - cause uremia - compete at the OATS with uric acid for secretion.
What HTN drugs are CI in depression?
BBs
Reserpine
Clonidine

Anything that depletes cats.
What HTN drugs are CI in pregnancy?
ACEIs - teratogenic!!!
Describe the tx regimen for HTN...what drugs when...
Thiazide diuretic FIRST.

For pts in whom HTN is not controlled by a thiazide, CCB, or an ARB, can be give BB, Alpha1 blocker.
In severe, refractory HTN, can use a direct VDr such as Minoxidil or hydralazine.

Alpha2 agonists are not commonly used d/t severe side effects that they cause.

HTN emergency: DBP is above 120 mmHg. High risk of encephalopathy, damage to the kidneys, etc.
IV Na Nitroprusside is the DOC. …but you can get cynadie poisoning.
CCBs such as the dihydropyridines are more commonly used for HTN emergencies. …to pvt the cyanide poisoning.
What enzyme converts Acetyl CoA to cholesterol in the hepatocytes?
HMG CoA reductase.
How is cholesterol metabolized in the hepatocytes?
It is converted to Bile Acid
What is the rate limiting step in cholesterol synthesis?
the HMG CoA reductase Enzyme.
How are VLDLs formed? what is their composition?
In the hepatocytes, Cholesterol made and then combines with Apo Proteins AB&C. (including the B100 apo protein). This complex then enters teh Golgi apparatus and is turned into VLDL. (at some point triglycerides are added to it.).

The triglyceride to Cholesterol ratio of VLDL is 10:1 - Triglyceride Rich!!!
The Apo Proteins A, B, C that combine with cholesterol in the formation of VLDL play what 3 roles in LDL structure/ function?
1) Structural Integrity
2) Enzymatic Activity
3) Serve as LIGANDS for receptors - EX: B100 is the ligand for LDL receptors..which remove LDLs from the plasma).
How do triglycerides get delivered to the body from what we eat?
They are attached to VLDL (10:1 ratio) in the hepatocyte. Them VLDL is released into the plasma.

The enzyme LIPOPROTEIN LIPASE found in the CAPILLARY ENDOTHELIUM removes TGs from the VLDLs.

As a result of the removal, the VLDL becomes "VLDL remnant"...an intermediate with a 5:1 ratio. The remnants are later converted to LDL, which is very cholesterol rich!
What is the job of LDL...when is it dangerous?
The job of LDL is to deliver cholesterol throughout the body. It's ligand (B100) binds to LDL receptors in the body and LDL is absorbed from the plasma.

It is dangerous when the levels are too high. This causes deposition in blood vessels. The deposits become oxidized and eaten by macrophages that turn them into "Foam Cells"...the precursors for atherosclerotic plaque.
What are the 4 Functions of Cholesterol in the Body
1) Component of cell membranes
2) Precursor for steroid synthesis.
3) Precursor for Bile Synthesis
4) Precursor for Myelin Synthesis.
What is the job of HDL?
"Reverse Cholesterol Transport" - Removing excess Cholesterol from tissue and returning it to the liver hepatocytes.

Once in the liver, the cholesterol is secreted and converted into bile salts.
Increases in _____ and ____ are directly correlated to an increased risk of CAD.
Increases in LDL and cholesterol levels is directly related to an increased risk of coronary heart disease.
Decreased LDL and cholesterol levels is directly related to a decreased risk of coronary heart disease.
Risk Factors that Increase the Deposition of LDL into the Vascular Space
1) Increased LDL levels
2) HTN
3) Obesity
4) Diabetes
5) Genetic Predispositions
Explain atherosclerosis as it relates to increased LDL levels.
Pts have risk factors: HTN, DM, Obesity, Genetic Predisposition.

Incr LDL levels occur.

LDL is deposited into the intimal layer of the BV, where it is oxidized. Monocyte recruitment occurs via chemoattractants. Monocytes are convereted to active macrophages. Macrophages eat the LDL, and turn into "Foam Cells", which are the precursors for Fatty Streak development. The fatty streak turns into Soft Plaque, which is a lipid core and a thin fibrous cap. It can easily rupture and cause emboli.

Over time, the plaque hardens and becomes more stable. (but has a higher risk of occlusion).

With hard plaque, arterial remodeling occurs...BV cannot VD with ischemia...causing decreased blood supply to the heart and other tissues. (impaired reactivity).
Three ways smoking can affect CAD
Smoking is bad for CAD in three ways:

1) Decreases plasma HDL levels. (can't get cholesterol out of blood)
2) Damages/ Impairs vascular reactivity..damages endothelial cells.
3) Enhances the oxidation of LDLs. ….which is the first step in the cascade to development of a plaque.
Diet Changes for CAD, Atherosclerosis

Fat % of diet?
Sat Fat % of diet?
Cholesterol max daily intake?
what else?
Limit total calories from fat to < 20% of daily intake
Limit saturated fats to ~ 8% daily intake
Limit cholesterol intake to < 200 mg/day
Complex carbohydrates & fiber: GOOD
Alcohol: BAD – increases your triglyceride levels, which will lead to increases in VLDL secretions from hepatocytes.
Plt function and formation of the _____ is monitored ______. The coagulation cascade and formation of the _____ is monitored ______.
Plt function and formation of the plt plug is monitored in vivo (bleeding time). The coagulation cascade and formation of the fibrin clot is monitored in vitro (PT, PTT). .
Hepatotoxic anti-lipid/ cholesterol agents.
Statins

Sustained Release Niacin
Which anti-lipid/ cholesterol agents are nephrotoxic?
Statins

Fibrates - potentiate statin induced rhabdo.
Which anti-lipid/ cholesterol agents sig incr HDL?
Niacin

Fibrates (mildly)