Chapter 18 - Disorders of Blood Flow and Blood Pressure Flashcards
How many layers (tunica) do blood vessels have?
Three.
What is the name of the outermost layer of a blood vessel?
Externa or Adventitia.
What is the outermost layer of a blood vessel made of?
Loosely woven collagen fibers that protect the blood vessel and anchor it to surrounding structures. It is also infiltrated with nerve fibers, and sometimes vasa vasorum.
What is the middle layer of a blood vessel called?
Tunica media.
What is the middle layer of a blood vessel made of?
Circularly arranged smooth muscle cells and sheets of elastin.
What is the innermost layer of a blood vessel called?
Tunica intima.
What is the innermost layer of a blood vessel made of?
A single layer of flattened endothelial cells with minimal underlying subendothelial connective tissue.
What are the functions of endothelial cells of the blood vessels? (6)
Controls transfer of molecules across the vessel wall.
Plays a role in modulation of blood flow and vascular resistance.
Controls platelet adhesion and blood clotting.
Metabolism of hormones.
Regulation of immune and inflammatory reactions.
Elaboration of factors that influence the growth of other cell types, especially vascular smooth muscle cells.
What are the risk factors for endothelial dysfunction?
Smoking, hypercholesteremia, hypertension, insulin resistance, diabetes, obesity, and aging. (All related to the pathogenesis of atherosclerosis).
What do dysfunctional endothelial cells produce? (5)
Proinflammatory cytokines.
Growth factors. (eg. vascular endothelial growth factor).
Reactive oxygen species.
Procoagulant or anticoagulant substances.
Other disease producing products.
How do dysfunctional endothelial cells influence the reactivity of underlying smooth muscle cells?
Production of relaxing factors (eg. nitric oxide).
Production of contracting factors (eg. endothelins).
What is the role of vascular smooth muscle cells?
They produce vasoconstriction and vasodilation.
What do vascular smooth muscle cells do besides controlling vessel radius?
Collagen, elastin, and other components of the extracellular matrix.
Elaborate growth factors and cytokines.
Migrate into the intima and proliferate after an injury.
What stimulates the migratory and proliferative activities of smooth muscle cells?
Growth promoters and inhibitors.
What are some growth promoters that effect vascular smooth muscle cells? (4)
Platelet derived growth factor.
Thrombin.
Fibroblast growth factor.
Cytokines such as interferon-y and interleukin-1.
What growth inhibitor effects vascular smooth muscle cells?
Nitric oxide.
What are other regulators of vascular smooth muscle? (Besides growth promoters and growth inhibitors).
Renin-angiotensin system (Angiotensin II).
The catecholamines.
What are the five categories of lipoproteins?
Chylomicrons Very low density lipoprotein (VLDL) Intermediate density lipoprotein (IDL) Low density lipoprotein (LDL) High density lipoprotein (HDL)
What are the components of HDL?
5% triglycerides
20% cholesterol
50% protein
What are the components of LDL?
10% triglycerides
50% cholesterol
25% protein
What are the components of VLDL?
55%-65% triglycerides
10% cholesterol
5%-10% protein
What are the components of chylomicrons?
80%-90% triglycerides
2% protein
What are the functions of apoproteins?
Increase the stability and solubility of a lipoprotein.
Activate certain enzymes required for normal lipoprotein metabolism.
Serve as reactive sites that specific receptors on peripheral tissues can recognize and use in the endocytosis and metabolism of the lipoproteins.
What is the role of apoproteins in atherosclerosis?
Research suggests that genetic defects in the apoproteins may be involved in hyperlipidemia and accelerated atherosclerosis.
Where does lipoprotein synthesis take place?
The liver and the small intestine.
Where are chylomicrons synthesized?
The wall of the small intestine.
What is the role of chylomicrons?
They are involved, through the exogenous pathway, in the transport of dietary triglycerides and cholesterol that have been absorbed from the gastrointestinal tract. They transfer triglycerides to the cells of adipose and skeletal muscle tissue.
How are chylomicrons broken down?
Taken up by the liver and their cholesterol is used in the synthesis of VLDL or excreted in the bile.
Which two lipoproteins are synthesized by the liver?
VLDL and HDL.
Which lipoprotein is the main carrier of cholesterol?
LDL.
What is the role of HDL?
It participates in the reverse-transport of cholesterol. (i.e. it carries cholesterol away from the tissues back to the liver).
What is hypercholesteremia?
Increased levels of cholesterol in the blood.
What are the NCEP Adult Treatment Panel III Classifications of LDL, total, and HDL cholesterol? (mg/dl)
LDL cholesterol:
190 very high
Total cholesterol:
240 high
HDL cholesterol:
60 High
How is hyperlipidemia diagnosed?
Blood lipid studies. Fasting serum lipoprotein profile.
What does a fasting serum lipoprotein profile show?
Total serum cholesterol, LDL, HDL, and triglycerides.
What factors can raise blood lipid levels? (5)
Nutrition Genetics Comorbid conditions Medications Metabolic diseases
What is familial hypercholesteremia (type 2A)?
An autosomal dominant type of hyperlipoproteinemia that results from a mutation in the gene specifying the receptor for LDL. This results in elevated levels of blood cholesterol.
What are some secondary causes of hyperlipoproteinemia? (3)
Obesity with high-calorie intake
Sedentary lifestyle
Diabetes mellitus
What are some systemic disorders that can elevate lipids? (3)
Hypothyroidism
The nephrotic syndrome
Obstructive liver disease
What are three medications that can increase lipid levels?
Beta blockers
Estrogens
Protease Inhibitors (an HIV med)
What is the aim of cholesterol-lowering therapy?
A reduction in LDL cholesterol.
What are the major risk factors for coronary artery disease (exclusive of LDL cholesterol levels)?
Cigarette smoking
Hypertension
Family history of premature CAD in a first-degree relative
Age (men >45 years, women >55 years)
HDL cholesterol levels less than 40 mg/dl
Diabetes mellitus
What are the treatment methods for hypercholesterolemia?
Dietary and theraputic lifestyle changes. If unsuccessful, pharmacological treatment may be necessary.
In what three ways can lipid-lowering drugs act?
Decreasing cholesterol production
Decreasing cholesterol absorption from the intestine
Removing cholesterol from the bloodstream
What are the five major types of medications available for treating hypercholesterolemia?
3-hydroxyl-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) Bile acid-binding resins Cholesterol absorption inhibitor agents Niacin and its cogeners The Fibrates
What is HMG-CoA reductase inhibitor?
HMG-CoA reductase is key enzyme in the cholesterol biosynthetic pathway. HMG-CoA reductase inhibitors can can reduce or block the hepatic synthesis of cholesterol. They also reduce triglyceride levels.
Which arteries can be affected by atherosclerosis?
The large and medium arteries such as the aorta and its branches, coronary arteries, and the cerebral arteries that supply the brain.
What is the leading risk factor for developing atherosclerosis?
Hypercholesteremia.
List the risk factors for developing atherosclerosis.
Age, male gender, family history of premature coronary artery disease.
Cigarette smoking, obesity, hypertension, hyperlipidemia, elevated LDL cholesterol, diabetes mellitus.
How does smoking affect atherosclerosis?
It has adverse hemostatic and inflammatory effects, and it may enhance oxidation of LDL cholesterol, causing damage to the endothelial lining of blood vessels.
What are the non-traditional risk factors for developing atherosclerosis?
C-reactive protein, serum homocysteine, and lipoprotein (a). There is also a possible connection between infectious agents and vascular disease.
What is C-reactive protein?
It is an acute phase reactant synthesized in the liver that is a marker for systemic inflammation.
What is homocysteine?
It is derived from the metabolism of dietary methionine, and inhibits elements of the anticoagulant cascade. It is associated with endothelial damage.
What is lipoprotein(a) (Lp[a])?
It is an altered form of LDL that enhances cholesterol delivery to injured blood vessels, suppresses the generation of plasmin, and promotes smooth muscle proliferation.
What are the three types of lesions associated with atherosclerosis?
Fatty streak
Fibrous atheromatous plaque
Complicated lesion
What are fatty streaks?
Thin, flat, yellow intimal discolorations that progressively enlarge by becoming thicker and slightly elevated as they grow in length.
What is fibrous atheromatous plaque, and what are its characteristics?
It is the basic lesion of clinical atherosclerosis. It is characterized by the accumulation of intracellular and extracellular lipids, proliferation of vascular smooth muscle cells, formation of scar tissue, and calcification.
What is the most important complication of atherosclerosis?
Thrombosis.
How does atherosclerosis cause thrombosis?
It is caused by slowing and turbulence of blood flow in the region of the plaque and ulceration of the plaque.
What is peripheral arterial disease (PAD)?
It is the presence of systemic atherosclerosis distal to the arch of the aorta.
What is the primary symptom of peripheral arterial disease?
Intermittent claudication (pain with walking).
What are the signs and symptoms of peripheral arterial disease?
Pain in the legs when walking, especially the calf muscle.
Atrophic changes - thinning of the skin and subcutaneous tissues of the lower leg, and diminution in the size of leg muscles.
Cool feet.
Weak or absent pedal pulses.
Limb color blanches with elevation.
Limb becomes deep red when in the dependent position.
Ischemic pain at rest.
Ulceration.
Necrosis.
What are some methods of diagnosing peripheral arterial disease?
Inspection of limbs for chronic low grade ischemia (subcutaneous atrophy, brittle toenails, hair loss, pallor, coolness, dependent rubor). Palpation of the femoral, popliteal, posterior tibial, and dorsalis pedis pulses. Ratio of arm to leg blood pressure. Ultrasound MRI CT Arteriography Invasive contrast angiography
What is the aim of treatment for peripheral arterial disease?
Protection of unaffected tissues and preservation of functional capacity.
Why is walking encouraged in patients with peripheral arterial disease?
It increases circulation.
What is thromboangiitis obliterans?
It is a vasculitis affecting the medium-sized arteries.
Which arteries are most commonly affected by thromboangiitis obliterans?
Plantar and digital vessels in the foot and lower leg. Also sometimes arteries in the arm and hand.
What is the primary symptom of thromboangiitis obliterans?
Pain (in the arch of the foot and the toes when walking, which may progress to pain when at rest).
What are the signs and symptoms of thromboangiities obliterans?
Pain Sensitivity to cold Diminished or absent peripheral pulses Changes in colour of the affected extremity/extremities Thin, shiny skin Thick, malformed nails Ulceration Necrosis
What is Raynaud phenomenon?
It is a functional disorder caused by intense vasospasm of the arteries and arterioles in the fingers (and sometimes the toes).
What are the two types of raynaud phenomenon, and what makes them different from each other?
Primary type - occurs without demonstrable cause
Secondary type - associated with other disease states or known causes that cause vasospasm
What causes secondary raynaud phenomenon?
Previous vessel injury (eg. frostbite, occupational trauma from using vibrating tools, exposure to alternating hot and cold temperatures, collagen diseases, neurologic disorders, and chronic arterial occlusive disorders.
Which disorder always includes raynaud phenomenon as a symptom?
Scleroderma
What are the symptoms experienced during the ischemic phase of Raynaud phenomenon?
Changes in skin colour that progress from pallor to cyanosis
Cold sensation
Changes in sensory perception eg. numbness and tingling
What symptoms occur after the ischemic phase of Raynaud phenomenon?
Hyperemia Intense redness Throbbing Paresthesias Finally, return to normal colour
What are the effects of severe progressive Raynaud phenomenon?
Trophic skin changes: Nails become brittle Skin on fingertips thickens Ulceration Superficial gangrene
What are the aims of treatment for Raynaud phenomenon?
Elimination of factors that cause vasospasm
Protecting the digits from trauma during an ischemic episode
What can trigger an episode of Raynaud phenomenon?
Exposure to cold
Emotional stress
What are the treatment measures for Raynaud phenomenon?
Smoking cessation
Protection from cold
Stress reduction
Avoiding vasoconstricting medications (eg. decongestants)
Vasodilator drugs
Sympathectomy (surgical interruption of sympathetic nerve pathways) in severe cases.
