Alterations in Blood Flow and Blood Pressure Notes

Alterations in Blood Flow and Blood Pressure

Diseases of Blood Vessels

• Blockage: Typically preceded by narrowing of the blood vessel.
• Rupture: Usually preceded by weakening of the vessel wall.
• Two vascular diseases to be discussed:
  • Atherosclerosis
  • Hypertension

Normal Blood Vessels

• Structure: Blood vessels consist of three layers:
  • Intima: Innermost layer, composed of endothelial cells.
  • Media: Middle layer, contains smooth muscle.
  • Adventitia: Outermost layer, connective tissue.
• Types of Vessels and Blood Pressure: Blood pressure varies across different types of blood vessels.
  • High Pressure: Aorta and muscular arteries have thicker walls to withstand high pressure.
    • They include the intima, internal elastic lamina, media, and adventitia.
  • Low Pressure: Large, medium veins, venules, and postcapillary venules.
  • Capillaries: Facilitate gas and nutrient exchange; comprised of:
    • Endothelial cells
    • Intima
    • Media
    • Adventitia
    • Pericytes
• Blood Pressure Control: Blood pressure is intricately controlled.

Arteriosclerosis

• Definition: Generic term for the hardening of arteries.
• Types: Includes different conditions:
  • Atherosclerosis (99%): The most common form.
  • Mönckeberg medial calcific sclerosis (1%): Calcification of the medial layer.
  • Arteriolar sclerosis: Affects small arteries and arterioles, associated with hypertension and/or diabetes.

Atherosclerosis

• Key Aspects: Focus on:
  • Etiology/Pathogenesis
  • Risk Factors
  • Morphology
  • Clinical Expression

Pathogenesis of Atherosclerosis

• Definition: Chronic inflammatory response of the arterial wall initiated by injury to the endothelium.
• Plaque Structure
  • Fibrous Cap: Contains smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, and neovascularization.
  • Necrotic Center: Contains cell debris, cholesterol crystals, foam cells, and calcium.
  • Media: The underlying smooth muscle layer.

Morphologic Concepts in Atherosclerosis

• Macrophages (monocytes) infiltrate the artery walls.
• Intimal Thickening occurs.
• Lipid Accumulation.
• Fatty Streak formation.
• Atheroma development.
• Smooth Muscle Hyperplasia and Migration.
• Fibrosis.
• Calcification.
• Aneurysm formation.
• Thrombosis.

Epidemiology and Risk Factors for Atherosclerosis

• Development and Geography: More prevalent in developed nations like the US and Western Europe.
• Decline: Significant decrease (50-70%) in prevalence from 1963 to 2000 due to increased awareness and dietary restrictions.
• Risk Factors:
  • Age
  • Sex: Males are more prone until menopause in females due to estrogen's protective effects.
  • Genetics

Risk Factors for Atherosclerosis: Major vs. Minor

• Non-Modifiable Risk Factors:
  • Increasing age
  • Male gender
  • Family history
  • Genetic abnormalities
• Modifiable Risk Factors:
  • Obesity
  • Physical inactivity
  • Stress ("type A" personality)
  • Postmenopausal estrogen deficiency
  • High carbohydrate intake
  • Hyperlipidemia
  • Hypertension
  • Lipoprotein Lp(a)
  • Cigarette smoking
  • Hardened (trans) unsaturated fat intake
  • Diabetes

Cigarettes

• Emphasized as a significant risk factor.

Pathogenesis of Atherosclerosis: Detailed Steps

• Damage/Injury initiates the process.
• Inflammatory Response is triggered.
• Vessel wall permeability increases, leading to LDL breach into the intima.
• Leukocytes are attracted to the site.
• Leukocytes Engulf lipids.
• Platelets are attracted and activated, releasing Platelet-Derived Growth Factor (PDGF).
• PDGF stimulates smooth muscle proliferation, resulting in plaque formation.

Endothelial Injury and Atherosclerosis: Step-by-Step

1. Chronic Endothelial "Injury": Caused by:
   • Hyperlipidemia
   • Hypertension
   • Smoking
   • Homocysteine
   • Hemodynamic factors
   • Toxins
   • Viruses
   • Immune reactions
2. Endothelial Dysfunction: Leads to increased permeability and leukocyte adhesion.
3. Smooth Muscle Emigration: Smooth muscle cells move from the media to the intima; Macrophage activation.
4. Lipid Engulfment: Macrophages and smooth muscle cells engulf lipids, forming foam cells.
5. Smooth Muscle Proliferation: Collagen and ECM deposition occur, leading to the formation of a fibrofatty atheroma.

Progression of Atherosclerosis: Mild to Advanced Stages

• Mild Stage: Characterized by fatty streaks.
• Advanced Stage: Includes:
  • Rupture
  • Ulceration
  • Erosion
  • Atheroemboli
  • Hemorrhage
  • Thrombosis
  • Aneurysm

Stages of Atherosclerosis: From Normal Artery to Occlusion/Rupture

• Pre-Clinical Phase:
  • Normal Artery
  • Fatty Streak: Occurs at lesion-prone areas, accelerated by risk factors, endothelial dysfunction, monocyte adhesion/emigration, SMC migration to intima, SMC proliferation, ECM elaboration, and lipid accumulation.
  • Fibrofatty Plaque
  • Advanced/Vulnerable Plaque: Characterized by Cell death/degeneration, Inflammation, Plaque growth, Remodeling of plaque and wall ECM, Organization of thrombus and Calcification
• Clinical Phase:
  • Mural thrombosis
  • Embolization
  • Wall weakening
  • Plaque rupture
  • Plaque erosion
  • Plaque hemorrhage
  • Mural thrombosis
  • Embolization
  • Aneurysm and Rupture
  • Occlusion by Thrombus
  • Progressive plaque growth leading to Critical Stenosis

Detailed Pathogenesis: Endothelial Injury to Plaque Development

• Endothelial Injury/Dysfunction: Caused by Hyperlipidemia, Hypertension, Smoking, Toxins, Hemodynamic factors, Immune reactions, and Viruses.
• Monocyte adhesion and emigration into the intima.
• LDL cholesterol breaches into the intima.
• Oxidation of LDL occurs.
• Macrophages uptake oxidized LDL, forming foam cells.
• Cytokines (e.g., IL-1, MCP-1) are released.
• Proliferation and migration of smooth muscle cells.
• Extracellular matrix synthesis.
• Progressive development of atherosclerotic plaque.
• Accumulation of extracellular lipids and necrotic cells.

Reversibility of Atherosclerosis

• The possibility of reversing atherosclerosis is questioned.

Treatment of Atherosclerosis

• Weight reduction
• Smoking cessation
• Drug therapy
• Balloon angioplasty
• Laser angioplasty
• Coronary bypass

Blood Pressure: Systemic Movement

• Pressure differences between the left and right sides of the heart produce the gradient allowing systemic movement of blood.
• Arterial blood pressure results from left ventricular contraction overcoming the resistance of the aorta to open the aortic valve.

Blood Pressure Regulation

• Factors Influencing Blood Pressure:
  • Blood Volume: Affected by sodium, mineralocorticoids, and atrial natriuretic peptide
  • Humoral Factors: Constrictors (Angiotensin II, Catecholamines, Thromboxane, Leukotrienes, Endothelin); Dilators (Prostaglandins, Kinins, NO)
  • Cardiac Output: Influenced by heart rate and contractility
  • Peripheral Resistance: Affected by constrictors (α-adrenergic) and dilators (β-adrenergic)
  • Neural Factors
  • Local Factors: Autoregulation via pH and hypoxia
• Blood Pressure = Cardiac Output \times Peripheral Resistance

Regulation of Systemic Blood Pressure

• Affected by neural, humoral, and renal factors.
• Blood pressure fluctuates over 24 hours due to circadian rhythm.
  • Suprachiasmatic nuclei in the brain govern daily variations in bodily functions.
  • Neural and hormonal regulation influences BP.
  • Lifestyle influences can affect BP.

Short-Term Regulation of Systemic Blood Pressure

• Changes in BP are mediated through activation of the sympathetic nervous system.
• Results in the release of neurotransmitters epinephrine and norepinephrine.
• Vasomotor center indirectly activated via baroreceptors.
  • Activates α1 receptors in smooth muscle of arterioles.
  • Activates β1 receptors of the heart.

Long-Term Regulation of Systemic Blood Pressure

• Increased serum sodium level = increased osmolality = increased ADH secretion.
• Increase in extracellular fluid volume.
• Renin–angiotensin–aldosterone system (RAAS) important regulator of BP.

Renin–Angiotensin–Aldosterone System (RAAS)

• Functions as a neurohormonal regulatory mechanism for body water and Na+.
  • \uparrow water volume
  • \uparrow Na+ reabsorption

RAAS Mechanism

• Liver: Produces Angiotensinogen.
• Kidney: Renin is released in response to renal pressure and Na+ sensors.
• Angiotensin I: Formed by the action of renin on angiotensinogen.
• Lungs: Angiotensin-converting enzyme (ACE) converts Angiotensin I to Angiotensin II.
• Adrenal Gland: Angiotensin II stimulates the release of Aldosterone.
• Aldosterone: Causes the kidneys to resorb Na+ and water, increasing blood volume and blood pressure.
• Atrial natriuretic peptide: Leads to vasodilation and excretion of Na+ and water, decreasing blood volume and blood pressure.

Disorders of Blood Pressure

• Focus on hypertension and hypotension.

Hypertension: Fun Fact

• Which of the following is TRUE regarding hypertension?
  • One in 10 adults in the United States have been diagnosed.
  • Fifty percent are unaware that they have hypertension.
  • It is defined as a systolic pressure of greater than 90 mm Hg.
  • It is defined as systolic pressure of 130 mm Hg or greater.

Definition of Hypertension

• Sustained diastolic pressure >80 mm Hg.
• Sustained systolic pressure >130 mm Hg.

Hypertension: Blood Pressure Categories

Hypertension: "The Silent Killer"

• Most common primary diagnosis in the United States.
• Increases morbidity and mortality associated with heart disease, kidney disease, peripheral vascular disease, and stroke.
• Responsible for an annual worldwide death rate of 7 million.

Hypertension and Atherosclerosis

• Hypertension causes atherosclerosis. Why?

Hypertension: Classification

• Primary hypertension
• Secondary hypertension

Primary Hypertension

• Idiopathic disorder
• Most common form of hypertension
• Rare prior to the age of 10

Primary Hypertension: Subtypes

• Isolated systolic hypertension
• Isolated diastolic hypertension
• Combined systolic and diastolic hypertension

Primary Hypertension: Risk Factors

• Uncontrollable
  • Genetics
  • Family history
  • Age
• Controllable
  • Dietary factors
  • Stress
  • Sedentary lifestyle
  • Obesity
  • Metabolic syndrome
  • NaCl intake

Primary Hypertension: Outcomes

• End-organ damage
  • Increased myocardial work results in HEART FAILURE.
  • Glomerular damage results in KIDNEY FAILURE.
  • Affects microcirculation of the eyes leading to BLINDNESS.
  • Increased pressure in cerebral vasculature can result in HEMORRHAGE.

Primary Hypertension and Atherosclerosis: Organ-Specific Effects

• Heart and Arteries
  • Increased myocardial work
  • Left ventricular hypertrophy
  • Increased myocardial oxygen demand
  • Heart failure
  • Aneurysm
  • Acute coronary syndrome: Unstable angina and myocardial infarction
  • Stable angina
• Kidneys
  • Increased pressure and decreased flow
  • Hemorrhage
  • Atrophy
  • End-stage renal failure
• Brain
  • Increased pressure and decreased flow
  • Autoregulation failure
  • Hemorrhagic stroke
  • Transient Ischemic Attacks (TIA)
  • Ischemic stroke
• Eyes
  • Retinal detachment
  • Hemorrhage
  • Ischemia
  • Blindness

Primary Hypertension: Treatment Interventions

• Lifestyle modifications are the first and most important prevention and treatment strategy.
• Drug therapy for hypertension addresses heart rate and stroke volume.

Treatment Recommendations for Hypertension

• Principles of Hypertension Treatment
  • Treat to BP <140/90 mm Hg or BP <130/80 mm Hg in patients with diabetes or chronic kidney disease.
  • Majority of patients will require two medications to reach goal.
• Algorithm for Treatment of Hypertension
  • Lifestyle Modifications
  • Initial Drug Choices:
    • Without compelling indications:
      • Stage 1 Hypertension (SBP 130-139 or DBP 80-89 mm Hg): Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination.
      • Stage 2 Hypertension SBP ≥140 or DBP ≥90 mm Hg): 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB).
    • With compelling indications: Drug(s) for the compelling indications.
  • Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.

Pharmacologic Treatment of Hypertension: Goals

1. Decrease blood volume
2. Decrease arterial resistance

• Congestive Heart Failure Treatment
  • Digitalis & Inotropes (increase myocardial contractility) used for decreased myocardial contractility.
• Renin Pathway Blockade
  • Beta Blockers: Block sympathetic activity and renin secretion.
  • ACE Inhibitors: Block the conversion of Angiotensin I to Angiotensin II.
  • ARBs: Block Angiotensin II receptors.
• Vasodilators: Hydralazine, Nitrates: Inhibit vasoconstriction, reducing peripheral vascular resistance.
• Aldosterone Antagonists: Block aldosterone, reducing salt and water retention.

Lifestyle Modifications to Prevent and Treat Primary Hypertension

Drug Classifications Used to Treat Hypertension

• Reduce Stroke Volume
  • Thiazide diuretics
  • Loop diuretics
  • Potassium-sparing diuretics
  • Aldosterone receptor blockers
  • Angiotensin (ACE) inhibitors
  • Angiotensin II receptor blockers
  • Venodilators
• Reduce Systemic Vascular Resistance
  • Combination β- and α 1-blockers
  • Angiotensin (ACE) inhibitors
  • Angiotensin II receptor blockers
  • Calcium channel blockers
  • α1-blockers
  • Central α2 agonists
  • Direct-acting vasodilators (arterial)
• Decrease Heart Rate
  • B-Blockers
  • Combination β- and α₁-blockers

Secondary Hypertension

• Hypertension attributed to a specific identifiable pathology or condition.
• Most common form in children <10 years of age.
• May be related to:
  • Renal disease
  • Coarctation of the heart
  • Pregnancy
  • Obesity/obstructive sleep apnea
  • Endocrine disorders

Low Blood Pressure (Hypotension)

• Orthostatic (postural) hypotension is a decrease in systolic blood pressure (>20 mm Hg or >10 mm Hg within 3 minutes) when moving to an upright position.
• Excessive increase in heart rate (by 20-30 beats/minute) may also be diagnostic.
• May be a result of:
  • Problem with vasomotor or baroreceptor response
  • Adverse effect of drug therapy
  • Arterial stiffness
  • Volume depletion
  • Secondary disease process

Low Blood Pressure (Hypotension): Treatment

• Review medication history
• Slow positional changes
• Avoid hot environments
• Avoid large or carbohydrate-heavy meals
• When symptoms begin, squatting/bending forward or crossing legs may reduce effects