Ch.15 Arterial Disorders

What are arteries?

• muscular-walled blood vessels that move blood AWAY from the heart

• high pressure vessels: the higher the pressure, the greater the resistance the heart has to work against

Arteriosclerosis vs. Atherosclerosis

Arteriosclerosis: hardening and narrowing of arteries d/t plaque (result of atherosclerosis)

Atherosclerosis: plaque build up on arterial wall; can lead to CAD, PAD; increased risk with diabetes, HTN, obesity, sedentary lifestyle, high saturated fats, family hx

Arterial wall layers

TUNICA INTIMA: innermost lining of endothelial cells (damage to this = arteriosclerosis, atherosclerosis)

TUNICA MEDIA: smooth muscle, regulates blood flow

• alpha-adrenergic fibers: vasoconstriction, ↑ blood pressure

• beta-adrenergic fibers: vasodilation, ↓ blood pressure

• calcium channel blockers: vasoconstriction, ↓ blood pressure

TUNICA EXTERNA (ADVENTITIA): outer covering

Functions of the endothelium as active tissue

• fluid filtration

• maintain blood vessel tone

• semipermeable barrier

• neutrophil chemotaxis

• hormone secretion

Factors that the endothelium releases and their effects

1. nitric oxide: vessel dilation

2. endothelin: vessel constriction

3. VEGF: angiogenesis

4. C-type natriuretic peptide: diuresis

5. prostacyclin: clot prevention

6. thromboxane A2": clot formation

7. Von Willebrand Factor: activates clotting

Basic cardiac factors

• systole: contraction (<120)

• diastole: relaxation (<80)

• pulse pressure: SBP - DBP (ideal = 40 mmHg; shows when heart is failing)

• stroke volume: amount of blood ejected per beat (mL)

• cardiac output (aka blood flow) : HR x SV (approx. 5 L/min at rest) OR BP/PVR

Blood flow regulation

Blood flow and vessel diameter are inversely related

Resistance is affected by vessel diameter, vessel length, blood viscosity

Blood pressure relationships

Flow, resistance, and pressure are all related and factors can be CHANGED

• autonomic nervous system innervation affects PVR by changing vessel diameter

• changes in PVR affect BP
  changes in BP affect CO

• changes in HR and SV can affect CO and BP

Turbulent vs. Laminar flow

turbulent: rough flow perpendicular to vessel, result of endothelial injury, can hear whooshing sound AKA bruit

laminar: smooth flow parallel to vessel

sluggish, stagnant, or turbulent blood flow INCREASES risk of thrombus formation (clots) that can travel to the brain/heart

BP regulation: baroreceptors

• Baroreceptors are short term regulators of BP changes

• located in walls of aorta and carotid arteries that sense stretch of vessel walls

  • EX: lying down, then standing up

• sends signals to cardioregulatory center: medulla & pons

  • and if BP too high: activate PNS and decrease HR, contractility, increase vasodilation

  • if BP too low, activate SNS and increase HR, contractility, increase vasoconstriction

Orthostatic hypotension

1. drop in BP when changing positions from lying down to standing up

2. decreased cerebral perfusion: result is dizziness

3. decreased BP sensed by baroreceptors

4. activation of SNS to increase HR to compensate

BP regulation: what role does RAAS play?

1. RENIN: released from kidneys in response to low pressure/perfusion

2. converts ANGIOTENSINOGEN from liver into ANGIOTENSIN I

3. ANGIOTENSIN I converts to ANGIOTENSIN II by ACE enzymes in the lungs

4. ANGIOTENSIN II is a potent vasoconstrictor and activates ALDOSTERONE for adrenal cortex

5. ALDOSTERONE stimulates sodium and water retention

6. vasoconstriction + aldosterone = elevates BP

Role of ADH(aka vasopressin) in BP regulation

from posterior pituitary gland that is released in response to a drop in BP and/or increase in blood volume/osmolarity

• increases water reabsorption in kidneys to ↑ blood volume, BP

BP regulation: natriuresis

• increased urine output when blood volume is elevated

• with elevated blood volume = ANP released when atria stretch, BNP released when ventricles stretch to promote natriuresis

Effect of blood composition on arteries

ALL of these in EXCESS will damage arteries

• lipids

• glucose

• free radicals (causes inflammation)

• nicotine (POTENT vasoconstrictor that increase BP and SNS activation)

• homocysteine: lack of vitamin B12 to break this down

Lipids

• cholesterol: ingested from diet, made by liver

  • used in cell membrane, hormone synthesis

  • normal is okay, too much is bad

• triglycerides: ingested in diet

  • stored in adipose cells/tissue

Lipoproteins

Transport lipids in blood

• LDL (low density lipoprotein): the “bad” cholesterol involved in plaque formation in arteries that the liver removes

• HDL (high density lipoprotein): the “good” cholesterol as it helps excrete cholesterol from the body - transports to the liver to get rid of it (“the higher the better”)

Effect of Glucose on Arteries

Glucose interacts with endothelial cells and glycosylation forms AGE’s (advanced glycosylation end products) that can injure the endothelium and is a precursor to plaque (atherosclerosis)

• AGE increases endothelin release leading to vasoconstriction

  • this is why T2DM is a risk factor for CAD as it damages arterial walls

Hyperlipedemia/Dyslipidemia

Elevated levels of lipids: cholesterol, triglycerides

• CVD: associated with high LDL and low HDL

• increased risk with T2DM, hypothyroidism, obesity, high saturated fat diet, progestins, corticosteroids

Liver synthesis/metabolism of cholesterol

• HMG CoA reductase is what makes cholesterol (statins stop it)

• liver LDL receptors help with uptake of cholesterol

  • higher receptor numbers = lower blood cholesterol levels

• PCSK9 enzyme decreases LDL receptors

Packaging of lipids (apolipoproteins)

• proathergenic": chylomicrons, VLDL, IDL, LDL, Lp(a)

• antiatherogenic: HDL

  • bile acids help absorb fat; HDL helps make this

Dietary sources of lipids

Saturated: sold, raise blood cholesterol

Unsaturated: liquids, mono and poly bonds

Transfatty acids: manufactured, extend shelf life - increase LDL, decrease HDL, increase formation of arterial plaque

Hypercholesterolemia risk factors

• family history (genetic testing possible)

• T2DM

• obesity

• hypothyroidism

• lack of physical activity

• some medications

Signs and symptoms of hyperlipidemia

• plaque formation along vessel walls with lipid filled WBCs (foam cells)

these are from prolonged, sustained levels of cholesterol

• xanthoma: cholesterol deposits under skin

• xanthelasma: cholesterol deposits around eyes

• arcus senilis: yellow-white ring around cornea

Diagnosis of hyperlipidemia

• blood samples: lipoproteins, Cholesterol, trigylcerides

• ACC risk estimator app to determine 10 year atherosclerotic cardiovascular disease risk

• FH genetic testing

Treatment of hyperlipidemia

• lifestyle modifications

  • <300 mg/day of dietary cholesterol

  • intermittent fasting

  • limit saturated fats, simple carbs

  • regular physical activity

• medications: statins

• supplements: fish oil, red yeast rice

Hypertension types and symptoms

Types

• primary AKA essential HTN: 95% of cases; etiology unknown

• secondary HTNL 5% of cases; due to underlying disease (EX: Cushing’s disease)

Symptoms

• often no symptoms

• chest pain, headaches, vision disturbance, dizziness

Sources of HTN

• high shearing stress on arterial walls causing microtears which injure the retina, kidneys, brain, lower extremities (areas with smaller vessels); end target is organ damage

• LV hypertrophy where coronary blood supply is unable to support additional ventricular tissue, greater oxygen demands

Risk factors of HTN

• age, ethnicity, obesity, DM, tobacco, family hx

• hypersensitibity to angiotensin II, high renin

• too much Na+ = less vasodilation

• not enough K+

How to measure BP

1. seated for 5 minutes, no caffeine, exercise, smoking 30 min prior to reading

2. with two measurements, use average

3. size matters! (wrist least accurate)

Criteria/Categories of HTN

• known as “silent killer”

• criteria: 2 or more BP readings of DBP > 80 or SBP > 130 mmHg

• categories:

  • normal: <120/<80

  • elevated: 120-129/80 or less

  • Stage 1: 130-139/80-89

  • Stage 2: 140/90 or more

  • hypertensive crisis: 180/120 or more

• hypotensive: 90/60

Assessment of HTN and characteristics to look for

• fundoscopic exam - retinal vessels

• chest - alteration of PMI (EX: midclavicular, 5th intercostal space - if these are displaced, can suggest artery has moved)

• bruits - turbulent flow

• peripheral arteries - temperature, sensation, pulses

• 12-lead ECH - LVH

• urinalysis - proteins in urine (kidney damage)

• blood lab tests - factors associated with HTN

Pharmacological treatments of HTN

• diuretics: increase urine output, decrease blood volume

• ACE inhibitors: inhibit ACE enzymes and reduce angiotensin II levels

• ARBs: reduce angiotensin II activity

• calcium channel blockers: decrease vasoconstriction

• beta-adrenergic blockers: decrease HR and vasoconstriction (“-olol”)

Complications of HTN

• LVH: may lead to MI or heart failure

• aneurysms: bulge in weakened area of arterial wall

• cerebral hemorrhage

• hypertensive encephalopathy

• hypertensive retinopathy (arteriovenous narrowing d/t damage at connection point between arteriole and venule

• renal disease: glomerular injury

Pathophysiology of atherosclerosis

1. injury to endothelium

2. produce adhesion molecules that attract WBCs which starts the inflammatory process

3. WBCs differentiate into macrophages and eat LDLs which become foam cells

4. Foam cells store cholesterol and release lipids into tunica media

5. fibroblasts are attracted by inflammatory cytokines and form fatty streaks

6. fatty streaks lead to plaques

7. plaques calcify and become covered with fibrous platelet cap

8. plaque ruptures and causes bleeding when they break lose

9. can travel and obstruct blood flow, creating ischemic tissue from lack of perfusion

CRP is made by the liver in response to inflammation and increases with plaque formation; matters because atherosclerosis is an inflammatory process

Clinical manifestations of atherosclerosis

• symptoms appear gradually, so may have no symptoms until end organ dysfunction

• can be examined for risk factors like obesity, SOB, cyanosis, rapid pulse, elevated BP, weak pulse in extremities

• bruits

• arteriosclerotic changes to retina

Diagnosis of atherosclerosis

• lipid profile: cholesterol, triglycerides, LDL, HDL

• endothelial function assessment: doppler

• CRP

• homocysteine levels: high levels = endothelial injury

• CT scan to detect calcified plaques

• cardiac angiography using dye through catheterization to examine blocked vessel

• intravascular ultrasonography to shoe cross sectional images of coronary arteries

Treatment for atherosclerosis

• same as hyperlipedemia

• CABG, percutaneous coronary intervention (PCI) such as angioplasty with stent placement to reperfuse ischemic areas of heart

• common warning signs: angina, transient ischemic attack that can progress to MI and CVA d/t plaque rupture or complete occlusion

Peripheral arterial disease

Arteriosclerosis and atherosclerosis outside coronary arteries

• most commonly: femoral artery above knee

Same risk factors as atherosclerosis with diabetes accelerating the process

Peripheral neuropathy may be present

Gradual onset with symptoms not presenting until 70% occlusion

Signs of PAD

Intermittent claudication is the primary sign

• pain with exertion, relieved by rest

• occlusion decreases oxygenation of tissue leading to ADP and lactic acid formation

• reducing activity allows oxygen levels to meet changed metabolic demand, eliminating pain

• metabolic changes in muscle occur with ischemia and reperfusion cycles and these changes contribute to spasms that trigger acute PAD pain

Examine for signs of arteriosclerosis and atherosclerosis

Assessment of PAD

• intermittent claudication

• diminished/absent pulses

• palpable coolness

• paresthesia

• pallor

• pain

DIagnosis of PAD

• ankle brachial index: compares blood pressure from ankle to arm (ankle systolic/ arm systolic

• CBC, lipid profile

• inflammatory markers

• ultrasonography, CT

Treatment for PAD

• lifestyle modifications

• medications

• thrombolytic agents

• surgical vascular bypass grafting

Aneurysm

• weakening of arterial wall causing bulging or dilation

• can be found in the…

  • cerebral arteries (“berry aneurysms”)

  • aorta (AAA)

• caused by arteriosclerotic damage

• risk factors for rupture: atherosclerosis, smoking, HTN

Aneurysm classification

By size, shape and location

• true aneurysm involves all 3 layers of vessel wall

• fusiform shape: all layers of vessel wall dilate equally

• saccular shape: weakness on one side of vessel

• false aneurysm: hematoma where the clot is outside arterial wall

may be missed until rupture, most are incidental findings through ultrasonography

AAA vs. cerebral aneurysms

AAA: may present with abdominal/back pain

• may compress organs causing nausea and vomiting

• in thin patients, may see pulsatile mass

• deep palpation should NOT be performed

• bruit may be present

Cerebral” normally silent

• if rupture, subarachnoid hemorrhage

• thunderclap headache

Treatment for aneurysms

• smoking cessation, BP regulation

• periodic follow up

• surgical treatment

• coiling or clipping of saccular out-pouchings

Aortic dissection

Tear in lining between tunica intima and media of aorta, causing layers to spit, introducing blood flow between layers

• potentially lethal

• symptom onset is sudden: patient hears ripping or tearing sound

• pallow, tachycardia, hypotension

Signs, diagnosis, treatment of aortic dissection

signs:

• bounding pulse

• wide pulse pressure (>40 mmHg)

• diastolic murmur

• signs of heart failure

• cardiac tamponade: blood pooling between the lining of muscle

• syncope

diagnosis: ECG, chest CT, MRI, transesophageal echo

treatment; surgery

Vasculitis

Inflammation of arterial walls, autoimmune

classified based on vessel size

• large: temporal arteritis and Takasayu arteritis

• medium: polyarteritis nodosa and Kawasaki disease

• small: Raynaud’s disease and thromboangitis obliterans