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Chapter 26: Disorders of Blood Flow and Blood Pressure Regulation

Endothelial Cells

Controls the transfer of molecules across the vascular wall

Control of platelet adhesion and blood clotting

Modulation of blood flow and vascular resistance

Metabolism of hormones

Regulation of immune and inflammatory reactions

Influence the growth of other cell types

Endothelial Dysfunction

Endothelial dysfunction describes potentially reversible changes in endothelial function that occur in response to environmental stimuli

Products that cause inflammation

Cytokines, bacteria, viruses

Hemodynamic stresses

Lipid products

Hypoxia

Vascular Smooth Muscle Cells

Vasoconstriction or dilation of blood vessels

ANS regulation

Sympathetic

Local regulation

ECM and growth factor elaboration

Essential for healing

Contribute to pathologic processes

Regulation of Systemic Arterial Blood Pressure

Mechanisms of blood pressure regulation

Acute regulation

Long-term regulation

Circadian variations in blood pressure

Diseases of the Arterial System

Dyslipidemia

Atherosclerosis

Disorders of Systemic Arterial Blood Flow

Vasculitis

Arterial disease of the extremities

Arterial aneurysms

Dyslipidemia #1

Triglycerides

Used in energy metabolism

Phospholipids

Important structural constituents of lipoproteins, blood clotting components, the myelin sheath, and cell membranes

Cholesterol

Chemical activity similar to other lipid substances

Hyperlipidemia

Elevated levels of one or all of the above

Classification of Lipoproteins

Chylomicrons

Very–low-density lipoprotein (VLDL)

Carries large amounts of triglycerides

Intermediate-density lipoprotein (IDL)

Low-density lipoprotein (LDL)

Main carrier of cholesterol

High-density lipoprotein (HDL)

50% protein

Dyslipidemia #2

Primary dyslipidemia

Familial hypercholesterolemia

Secondary dyslipidemia

Hypercholesterolemia

Serum cholesterol levels

240 mg/dL or greater

Levels that could contribute to a heart attack, stroke, or other cardiovascular event associated with atherosclerosis

Primary hypercholesterolemia describes elevated cholesterol levels that develop independent of other health problems or lifestyle behaviors.

Secondary hypercholesterolemia is associated with other health problems and behaviors.

Question #1

Which of the following is considered the “good” cholesterol. Discuss why in small groups.

Chylomicrons

Very–low-density lipoprotein (VLDL)

Intermediate-density lipoprotein (IDL)

Low-density lipoprotein (LDL)

High-density lipoprotein

Answer to Question #1

E. High-density lipoprotein

Rationale: Due to its function of taking cholesterol from the tissues and moving it to the liver for metabolic breakdown

Pathology of the Arterial System

Atherosclerosis

Vasculitis

Arterial disease of the extremities

Arterial aneurysms

Mechanisms of Development of Atherosclerosis

Types of lesions associated with atherosclerosis

Fatty streaks

Thin, flat yellow intimal discolorations that progressively enlarge

Fibrous atheromatous plaque

The accumulation of intracellular and extracellular lipids, proliferation of vascular smooth muscle cells, and formation of scar tissue

Complicated lesion

Contains hemorrhage, ulceration, and scar tissue deposits

Major Risk Factors for Atherosclerosis

Hypercholesterolemia

Cigarette smoking

Hypertension

Family history of premature CHD in a first-degree relative

Age (men ≥45 years; women ≥55 years)

HDL cholesterol <40 mg/dL

CRP levels

Homocysteine levels

Major Complications of Atherosclerosis

Ischemic heart disease

Stroke

Peripheral vascular disease

Clinical manifestations of atherosclerosis

Narrowing of the vessel and resulting ischemia

Vessel obstruction due to plaque hemorrhage or rupture

Thrombosis and formation of emboli

Aneurysm formation

Specific Arterial Involvement in Atherosclerosis

In larger vessels, the important complications are those of thrombus formation and weakening of the vessel wall.

In medium-sized arteries, ischemia and infarction due to vessel occlusion are more common.

Arteries supplying the heart, brain, kidneys, lower extremities, and small intestine are most frequently involved.

Clinical Manifestations of Atherosclerosis

Narrowing of the vessel and production of ischemia

Sudden vessel obstruction due to plaque hemorrhage or rupture

Thrombosis and formation of emboli resulting from damage to the vessel endothelium

Aneurysm formation due to weakening of the vessel wall

Vasculitis

Inflammation of the blood vessel wall resulting in vascular injury and necrosis.

Arteries, capillaries and veins may be affected.

The inflammatory process may be initiated by direct injury, infectious agents, or immune processes.

Classification of Vasculitides

Vasculitis, angiitis, and arteritis often are used interchangeably

Group I

Systemic necrotizing vasculitides

Group II

Hypersensitivity vasculitides

Group III

Giant cell arteritis

Group IV

Miscellaneous

Arterial Disease of the Extremities

Atherosclerotic occlusive disease

Sudden event that interrupts arterial flow to the affected tissues or organ

Thromboangiitis obliterans

Inflammatory arterial disorder that causes thrombus formation

Raynaud disease and phenomenon

Intense vasospasm of the arteries and arterioles in the fingers and, less often, the toes

The Seven “P”s of Acute Arterial Embolism

Pistol shot (acute onset)

Pallor

Polar (cold)

Pulselessness

Pain

Paresthesia

Paralysis

Atherosclerotic Occlusive Disease (Peripheral Artery Disease)

Risk factors similar to atherosclerosis

Clinical manifestations

Diagnosis

Treatment

Thromboangiitis Obliterans (Buerger Disease)

Inflammatory arterial disorder that causes thrombus formation

Etiology

Pathogenesis

Clinical manifestations

Raynaud Disease and Phenomenon

Functional disorder causes by intense vasospasm of the arteries and arterioles in the fingers and, less often, the toes.

Etiology and pathogenesis

Clinical manifestations

Aneurysms

Abnormal localized dilation of a blood vessel.

Can occur in veins or arteries

Types of Aneurysms #1

Berry aneurysm

Most often found in the circle of Willis in the brain circulation

Consists of a small, spherical vessel dilation

Fusiform and saccular aneurysms

Most often found in the thoracic and abdominal aorta

Characterized by gradual and progressive enlargement of the aorta

Types of Aneurysms #2

Dissecting aneurysm

Acute, life-threatening condition

Involves hemorrhage into the vessel wall with longitudinal tearing (dissection) of the vessel wall to form a blood-filled channel

Aortic Dissection (Dissecting Aneurysm)

Acute, life-threatening condition.

Hemorrhage into the vessel wall with longitudinal tearing of the vessel wall to form a blood-filled channel (see Figure 16-16)

Etiology and pathogenesis

Clinical manifestations

Diagnosis and treatment

Venous Circulation

One way valves in large veins

Limited contractility

Skeletal muscle pump

Decreased driving pressure

Thin-walled vessel

Disorders of the Venous Circulation

Produce congestion of the affected tissues

Predispose to clot formation because of stagnation of flow and activation of the clotting system

Types of disorders

Varicose veins

Primary

Secondary

Thrombophlebitis

Virchow’s Triad Associated with Venous Thrombosis

Stasis of blood

Increased blood coagulability

Vessel wall injury

Risk Factors Associated with Venous Stasis

Bed rest

Immobility

Spinal cord injury

Acute myocardial infarction

Congestive heart failure

Shock

Venous obstruction

Venous Insufficiency

Deep vein thrombosis (DVT)

Causes deformity of the valve leaflets

Valvular incompetence

Loss of unidirectional blood flow

Combination of both conditions

Stasis dermatitis

Venous ulcers

Question #2

Which of the following is not a risk factor for atherosclerosis?

Hypercholesterolemia

Cigarette smoking

Hypertension

Venous stasis

Age (men ≥45 years; women ≥55 years)

HDL cholesterol <40 mg/dL

Answer to Question #2

D. Venous stasis

Rationale: Venous stasis is responsible for disorders in the venous system and is not related to atherosclerosis.

Question #3

DVTs may be the direct result of _______________.

smoking

hypersensitivity reaction

hypercholesterolemia

bed rest

Answer to Question #3

D. bed rest

Rationale: Bed rest can cause DVT formation due to blood stasis and lack of skeletal muscle pumping.

Disorders of Blood Pressure Regulation

Blood pressure must be closely regulated throughout the body to ensure adequate perfusion of body tissues and to prevent damage to blood vessels.

Low blood pressure- tissues don’t receive sufficient blood flow to ensure delivery of nutrients and oxygen and removal of cellular wastes

High blood pressure- can damage endothelial tissue, increasing the likelihood of both atherosclerotic vascular disease and vascular rupture.

Hypertension

Sustained condition of elevation of the blood pressure within the arterial circuit.

Etiology and pathogenesis

Clinical manifestations

Diagnosis and treatment

Risk Factors for Hypertension

Age

Gender and race

Family history and genetics

Dietary factors

Tobacco

Alcohol consumption

Obesity

Secondary Hypertension

Elevation of blood pressure that results from some other disorder, such as kidney disease

May be corrected by surgery or specific medical treatment

Largest single cause is renal disease-renal hypertension

Causes of Secondary Hypertension

Primary hyperaldosteronism

Cushing disease or syndrome

Pheochromocytoma

Oral contraceptive drugs

Target Organ Damage

Heart—hypertrophy

Brain—dementia and cognitive impairment

Peripheral vascular—atherosclerosis

Kidney—nephrosclerosis

Retinal complications

Can lead to hypertensive emergency!

Hypertension in Pregnancy

Preeclampsia—eclampsia

Chronic hypertension

Chronic hypertension with superimposed preeclampsia

Gestational hypertension

Orthostatic Hypertension (Postural Hypotension)

Abnormal drop in blood pressure on assumption of the standing position

“Sustained reduction in systolic pressure of at least 20 mmHg or more or diastolic blood pressure of 10 mm Hg within 3 minutes of standing or head-up tilt on a tilt table to at least 60 degrees”

Etiology

Pathogenesis

Diagnosis and treatment

Causative Factors of Orthostatic Hypotension

Fluid deficit

Medications

Aging

Defective function of ANS

Effects of immobility