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MHD 1 > L41 Atherosclerosis - Hyperlipidemia > Flashcards

L41 Atherosclerosis - Hyperlipidemia Flashcards

1
Q

What is atherosclerosis?

A

A disease of formation and growth of intimal lesions (atheromas) which protrude into and obstruct vascular lumens as well as weaken the underlying media.

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2
Q

What are the pathologic changes to blood vessels that occur as a result of AS?

A
  1. Wall dilatation (aneurysm) and rupture
  2. Damage to endothelium causing thrombosis
  3. Alteration in blood flow (can also cause thrombosis)
  4. Narrowing of the vessel lumen leading to ischemia and downstream infarction
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3
Q

AS is also a chronic ___ disease.

A

Inflammatory

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4
Q

Describe the pre-clinical phase of AS.

A

Usually occurs in young age

Normal arteries develop fatty streaks, which go on to become fibrofatty and then advanced/vulnerable plaques.

At lesion-prone areas, we see endothelial dysfunction, monocyte adhesion/emigration, SMC migration tot he intima + proliferation, ECM elaboration, and lipid accumulation

Later, we see cell death/degeneration, inflammation, remodeling of plaque and wall ECM, organization of thrombus, and calcification

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5
Q

Describe the response to injury hypothesis of atherogenesis.

A
  1. Endothelial injury (hyperlipidemia, HBP, smoking, viruses, hemodynamic factors) with monocyte and platelet adhesion
  2. Monocyte and smooth muscle cell migration into the intima with macrophage activation
  3. Macrophage and SM cells uptake lipids and become further activated
  4. Initmal smooth muscle cell proliferation with ECM elaboration, forming a well-developed plaque
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6
Q

There is a ___ relationship between serum cholesterol levels and risk for coronary heart disease.

A

Direct

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7
Q

What are the ranges of serum cholesterol for minimal risk, increased risk, and very increased risk?

A

Minimal: 0-200 mg/dL
Increased: 200-239 mg/dL
Very increased: 240+ mg/DL

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8
Q

What is the earliest known risk factor for AS?

A

Total cholesterol (hypercholesterolemia)

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9
Q

What are the major non-modifiable risk factors for AS?

A
  1. Age
  2. Male gender
  3. Family history
  4. Genetic abnormalities
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10
Q

What are the major modifiable risk factors for AS?

A
  1. Hyperlipidemia
  2. Hypertension
  3. Cigarette smoking
  4. Diabetes mellitus
  5. Inflammation
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11
Q

What are some minor risk factors for AS?

A
  1. Physical inactivity
  2. Obesity
  3. Stress (type A)
  4. Post-menopausal estrogen deficiency
  5. High carbohydrate intake
  6. Hardened trans/saturated fat intake
  7. C. pneumoniae
  8. Homocysteine
  9. Lipoprotein a
  10. Alcohol
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12
Q

What risk factors does the MRFIT study look at?

A
  1. High BP
  2. High cholesterol
  3. Low HDL
  4. Diabetes
  5. Cigarrettes
  6. LV hypertrophy
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13
Q

What are the 5 major lipoproteins that transport cholesterol and other lipids in the blood?

A
  1. Chylomicrons
  2. VLDL
  3. IDL
  4. LDL
  5. HDL
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14
Q

What is the least dense lipoprotein? The most dense?

A

Least dense: chylomicrons

Most dense: HDL

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15
Q

Which lipoproteins carry triglycerides?

A

Chylomicrons, VLDL, IDL

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16
Q

Which lipoproteins carry cholesteryl esters?

A

IDL, LDL

17
Q

Which lipoproteins carry cholesterol?

A

HDL (also carries phopholipids and proteins)

18
Q

What are the major apoproteins of chylomicrons?

A

B48, A1, A4

19
Q

What are the major apoproteins of VLDL?

A

B100, E, C1, 2, 3

20
Q

What are the major apoproteins of IDL?

A

B100, E

21
Q

What are the major apoproteins of LDL?

A

B100

22
Q

What are the major apoproteins of HDL?

A

A1, A2

23
Q

On which chromosome is the LDL receptor found?

A

Chromosome 19

24
Q

Genetic defects in the LDL receptor can lead to ___.

A

Familial hypercholesterolemia

25
Q

How does elevated homocysteine contribute to ES?

A
  1. Platelet activation/increased platelet adhesiveness
  2. Promotion of inflammatory response, DVT, activation of coagulation cascade
  3. Endothelial dysfunction/SMC proliferation
  4. Enhanced LDL oxidation and deposition
26
Q

What is Lp(a)?

A

An LDL particle with apo-B100 linked to apo (a)

27
Q

What is the role of Lp(a) in AS?

A

May inhibit fibrinolysis as a homologue of plasminogen

28
Q

What is the most atherogenic lipoprotein paritcle?

A

Small, dense LDL

29
Q

What is an important marker of chronic inflammation?

A

High sensitivity C-reactive protein (CRP)

30
Q

What are the optimal, near/above optimal, borderline high, high, and very high levels of LDL?

A 
Optimal: <100
Near/above optimal: 100-129
Borderline high: 130-159
High: 160-189
Very high: 190+
31
Q

What are the bad and very good levels of HDL?

A

Bad: <40

Very good: 60+

32
Q

How is LDL quantitated?

A

Friedewald Equation:

LDL = Total cholesterol - (HDL cholesterol + [Triglyceride/5])

MHD 1 (58 decks)

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