Arteriosclerosis

Arteriosclerosis


Hardening and thickening of artery walls
• 3 types
– Atherosclerosis
– Medial Calcification
– Arteriolarsclerosis


Atherosclerosis
• Aorta - common
• Coronary Arteries - common
• Cerebral arteries - basilar and middle cerebral most affected
• Carotid arteries
• Abdominal arteries
– Splenic artery
• Peripheral arteries
• Pulmonary arteries - least common

Pathogenesis of Atherosclerosis

• Intimal injury - injury - markers for LDL.

– Aging

– Hemodynamic factors - turbulence; e.g., HTN

– High cholesterol

• Inflammation

– Monocyte adhesion and migration - turn into macrophages - eats debri = becomes foamy mac

– Oxidation of LDL

– Inflammatory response

monocytes become foamy macrophages after combining with LDL in plasma

Risk Factors

• Not changeable

– Age, Sex, Genetics

• Major reversible

– Smoking** Diabetes, HBP*, Hyperlipidemia

• Minor reversible

– Obesity, Life Style, Personality

*Hypertension
• Increases the severity of atherosclerosis at any age
• Mechanism is mechanical stress on arteries
– Intimal injury
– Medial degeneration

**smoking doubles or triples risk of sudden death


Clinical Effects of Atherosclerosis
• Arterial narrowing

• Bulging plaques
• Calcification
• Hemorrhage 

• Thrombosis

• Acute change in plaque
• – Erosion or ulceration
• – Plaque hemorrhage
• – Plaque rupture
• Vulnerable plaque
• – Moderate luminal narrowing
• – Lipid rich center
• – Thin fibrous cap

• Embolism

• Initiated by 
  rupture or erosion 
  of plaque
• Most from aorta
• – To Kidneys, Pancreas and 
  Spleen
• – To Lower limbs
• Dry gangrene

• Aneurysm - cystic medial degeneration - proteoglycan deposition - weakens walls

1. Atherosclerotic Aneurysm

• • Abdominal aorta belo w renal arteries
• • Iliac arteries
• • Usually over age 60
• • Men > women
• • Clinically significant when > 5 cm. in diameter

  2. Dissecting Aneurysm

• Hypertensive
•  Genetic
• – Marfan Syndrome
• Both types have cystic medial degeneration - 
• Dissection usually starts in arch of aorta

Coronary Artery Artherosclerosis

Myocardial Ischemia

• • Amount of coronary flow
• – Size/narrowing of coronary artery
• – Hypotension
• – Collaterals
• – Arrhythmias
• • Myocardial oxygen requirements
• – Anemia
• – Exercise/Excitement/Fever/Hyperthyroidism

Infarct Location

• Left anterior 

descending: Anterior 

wall, apex and 

septum

• Right: Posterior base 

and posterior septum

• Left Circumflex: 

lateral wall

Sequela of Infarct

• Death from arrhythmia or CHF

• Healing

• Aneurysm

• Rupture

• Postmyocardial syndrome

Sudden Cardiac Death
• Usually not Myocardial Infarct
• Mechanism is cardiac arrhythmia
• Thrombus not usually present
• Severe coronary narrowing
• Previous myocardial infarcts

Shunts

 Shunts

response to exercise = increased stroke volume = increased pulse pressure (Sys - Dia)BP

Qp/Qs  is the ratio of Fick principle calculations for pulmonary flow and systemic flow.
Qp = VO2/(PVO2 -  PAO2)

Qs = VO2/(CaO2 - CvO2)

when algebra is done and sats are used instead of content 
Qp/Qs = (AoSat - MVSat)/(PVsat - PAsat)

Coarctation of the Aorta

Pulses are difference between systolic and diastolic.   with collateral flow through parallel circuits; e.g., intercostal arteries, MAP can be normal but pulses are weak.

Coronary artery disease (CAD)

CAD

O2 supply vs. demand

supply = Flow x CaO2

• Q = P/R
• R - autoregulation; neural, local (adenosine)
• P - diastolic aortic pressure

demand = rate, inotropy, pressure, wall tension

• VO2 proportional to HR x Systolic BP (double product)

CAD

Fixed

• •Congenital anomalies
• •Vasculitides (collagen diseases)
• •Aortic dissection
• •Tumors
• •Scarring from trauma, radiation

Transient

• •Vasospasm
• •Embolus
• •Trombus in situ

Angina = Greek word ankhon (ἄγχω) meaning to strangle, throttle, or choke

• Classic (effort)
• Vasospastic or variant (Prinzmetal)
• Localized spasms associated with atheroma
• Unstable (medical emergency)
• Angina at rest or when it becomes longer or more frequent

Factors that Can Aggravate Myocardial Ischemia

Increased myocardial oxygen demand

• Tachycardia
• Hypertension 
• Thyrotoxicosis
• Heart failure
• Valvular heart disease
• Catecholamine analogues (eg, bronchodilators, tricyclic antidepressants)

Reduced myocardial oxygen supply 

• Tachycardia - reduces diastolic (flow) time
• Anemia
• Hypoxia
• Hypotension
• Smoking - produces HbCO

Treatment of CAD

1. Nitrates

Nitrates relax veins >>> arteries

• Increase venous capacitance
• Decrease preload
• Decrease pulmonary vascular pressure
• Heart size is decreased
• Decrease cardiac output
• Net:  decrease O2 demand, NOT increase O2 supply

•Dilate coronaries (normal individuals):

• Epicardial are sensitive (but not with concentric atheromas)
• Arterioles and precapillary spinchters are dilated least

Nitroglycerine is an arterial and venous dilator = reduces afterload and preload.

http://cvpharmacology.com/vasodilator/nitro.htm

Nitrates should not be used for right heart MI because reduced preload will worsen condition.

Adverse effects of nitrates

• Reflex tachycardia
• Increased myocardial O2 demand
• Decrease coronary perfusion (↓ diastole)
• Reflex increase in contractility
• Increased myocardial O2 demand
• formation of methemoglobin
• hypotension
• increase intracranial pressure
• tachyphylaxis (tolerance)

Other uses of nitrovasodilators

1.Hypertensive Emergencies: Na+ Nitroprusside

2.Congestive heart failure: isosorbide dinitrate + 

hydralazine

Congestive heart failure: isosorbide dinitrate + hydralazine (BiDil. Bi = two; Dil = dilators)

Na+ Nitroprusside

• Complex of cyanide, iron and nitrosomoiety

• Powerful, parentheral vasodilator. Rapid onset and dissapearance of action.

• Used for hypertensive emergencies and severe heart failure

• Dilates both veins and arteries

• Decreases peripheral resistance; ↔ or ↓cardiac output

• Rapidly metabolized in red blood cells; cyanide is metabolized by rhodanase, combined to less toxic thiocyanate in presence of a sulfur donor (thiosulfate). Thiocyanate is slowly eliminated by kidneys

• Side Effects:

1. Excessive decrease in blood pressure

2. Cyanide toxicity-to decrease risk co-administer thiocyanate or hydroxocobalamin

3. Thiocyanide toxicity in patients with renal failure (psychosis, seizures)

2. Beta blockers

-- ↓

Heart rate and 

contractility 

-- ↓

Cardiac Output

-- ↓

renin secretion

β1 selective blockers - name starts with letter A - M; e.g., metopralol = β1 blocker

Complications

1. bronchconstriction
2. decrease cardiac output
3. hypoglycemia
4. intermittent claudication
5. increase LDL decrease HDL
6. impotence
7. depression, sedation, nightmares
1. atenolol does not cross BBB - others do

The 70 year-old male patient being treated with dinitrate isosorbide returns to the 

family practice clinic because his angina pectoris symptoms have returned. He 

complains of palpitations. A decision is made to add metoprolol to his treatment 

regimen. The patient feels better a few days after the addition of this medication. 

What is the most likely mechanism responsible for the improvement in this 

patient’s condition:

A. Afterload reduction - no vasoconstricters

B. Coronary dilation - no beta receptors

C. Decreased heart rate

D. Increased renin levels  - decrease

E. Increased diastolic volume - not best choice

3. Ca channel blockers

Amlodipine (Norvasc (Pfizer) and generics) (as besylate, mesylate or maleate) is a long-acting calcium channel blocker dihydropyridine (DHP) class

• Slow, smooth onset of action
• •Long half life (once a day administration)
• •Antiatherogenic action (hyperlipidemia increases Ca2+
• influx to smooth muscle?). Decreased progression of 
• carotid atherosclerosis (but not coronary).
• •Reduced risk of major cardiovascular events
• •Minimum negative ionotropic effects (useful in patients 
• with LV dysfunction)

summary - angina drugs

4. Coronary revascularization

Compensatory Responses to Vasodilators - prevented by "polypharmacy"