Cardio Mod 5 Flashcards
Varicose Veins
- pooling of blood in superficial veins of lower extremity
2. common in saphenous veins
Etiology of Varicose Veins
a. Trauma causing valve damage
• valves can’t close causing back flow of blood
b. Prolonged venous distention (prolonged standing, gravity) causing valve damage
• Distention of vein causes valves to be “stretched”
• “Stretched” valves cause a back flow of blood
c. Can lead to edema within local tissues
Strategies for symptom relief of Varicose Veins
• Elevating the legs - lay down or sit with footstool
1. relieves the symptoms of varicose veins
2. does not prevent new varicose veins from forming.
• Elastic stockings (support hose) compress the veins
Injections - sclerotherapy for Varicose Veins
• Goal of injection is to occlude blood flow through involved vein.
• A solution is injected into the vein to irritate it and produce a thrombus (blood clot).
(i) Forms a harmless superficial thrombophlebitis that scars over which blocks the blood flow
(ii) The thrombus may dissolve instead of becoming scar tissue, and the varicose vein then reopens.
Laser Therapy for Varicose Veins
- techniques to destroy vein
* technology and outcomes not fully established
Surgery for Varicose Veins
• Removal of involved veins – vein stripping
• Attempt to avoid removing saphenous vein because of it’s value in harvesting for other procedures (CABG, PAD)
e. NOTE: blood flow is directed at deep venous pathways if superficial vein is removed or therapeutically occluded.
Varicose Veins during pregnancy
a. Varicose veins that appear during pregnancy are often self limiting due to fluid volume changes
• Often resolve few weeks after delivery
CVI (Chronic venous insufficiency)
- CVI = insufficient venous return from lower extremities for chronic periods of time
- Caused by
a. DVT, valve deficiency/varicose veins or lack of muscular pump (sedentary/bed rest)
Interventions and Complications of CVI
- Intervention
a. Symptom relief (see above)
b. Address cause such as DVT
c. Removal of dysfunctional veins - Complications
a. Poor healing if local trauma/pressure sores may develop into venous stasis ulcers
Thrombus
clot still attached to blood vessel
Thromboembolism
dislodged thrombus that is released into circulation
Factors in formation of DVT
- venous stasis
- endothelial damage
- hypercoagulable states
Thrombus Formation
• Accumulation of clotting factors/platelets forms thrombus
• Thrombus composed of RBC, platelets, leukocytes held together with fibrin
• Inflammation perpetuates thrombus growth (increased platelets, etc…)
• Thrombus creates “back pressure” leading to edema
b. Thrombus often form near valves
Populations at risk for DVT
a. Age (> 60)
b. Smoking
c. Previous history of DVT/VTE (venous thromboembolism)
d. Venous stasis
• cardiovascular pathologies (CHF, MI, stroke, etc..), sedentary /obesity, CVI, immobilized patients – SCI, hospital patients, airline travel (“media attention” but statistically not that common), etc..
e. Damaged endothelium
• surgery, catheterization, trauma – fractures,
f. Hypercoagulation
• IBD, pregnancy, malignancy, genetics, etc…
Complications of DVT
pulmonary embolism
Aneurysm
- Localized dilation or outpouching of a vessel or a wall
- LaPlace’s law
a. Aneurysm = ↑ radius, ↑ internal pressure, and ↓ wall thickness require more force to contain blood volume
Blood Vessel Breakdown that causes Aneurysm
• Proteolytic degradation of aortic wall connective tissue
(i) destruction of elastin and collagen in the media and adventitia
(ii) loss of medial smooth muscle cells with thinning of the vessel wall
• Inflammation and immune responses
(i) transmural infiltration of lymphocytes and macrophages
• Biochemical wall stress
(i) Thoracic/abdominal aorta may be predisposed to AAA due to collagen/elastin make-up
(ii) Plaque formation in wall will redistribute wall stresses
(iii) Once AAA started – wall stress accelerates dilation/development of AAA
• Molecular genetics
(i) Family history
True aneurysm
- All three layers of a blood vessel are distended: the intima, the media, and the adventitia.
- Causes: congenital malformations, infections, or hypertension
False aneurysm (aka pseudoaneurysm)
• Only the adventitia (outer layer is distended)
(i) Rupture in wall allows blood to leak out to overlying connective tissue
(ii) A blood-filled cavity forms outside the vessel wall (extravascular hematoma)
(iii) Seals the leak as it thromboses
• Common causes
(i) leak between a vascular graft and the artery
(ii) trauma involving the intima of the blood vessel (percutaneous arterial procedures)
Aneurysm Classification by Shape
• Saccular aneurysm
(i) “Unilateral” localized outpouchings of the artery wall
(ii) Sac like formation distended from one side of the blood vessel
• Fusiform aneurysm
(i) Circumferential widening of the artery
4 other types of arterial emboli
a. air – IV lines, chest trauma
b. fat – long bone fractures
• fracture may disrupt local fat metabolism
• fatty bone marrow releases fat globules
c. amniotic fluid
• intra-abdominal pressures of child birth may introduce amniotic fluid into mother’s blood stream
d. bacteria, foreign matter
Atherosclerotic PAD (commonly referred to as “PAD”) Peripheral Arterial Disease
a. Most common form of peripheral artery diseases
b. Number one reason for amputations in U.S.
c. 16x greater risk of heart disease or stroke within next 10 yrs
Pathogenesis of PAD
- Same pathology as CAD
- Artherosclerotic plaque formation in peripheral arteries
- Reduced blood flow results in ischemia of peripheral tissues
Risk factors for PAD
- Family history, Age and Sex (M > F)
- Smoking
- Diabetes
- Hypertension
- Dyslipidemia (elevated LDL, low HDL, elevated TG’s)
- Elevated homocysteine levels
- Obesity/sedentary lifestyle
Clinical for PAD
• MC in lower vs upper extremities
• Symptoms:
(i) Intermittent claudication = most common
1. Pain/cramping/tightness/uncomfortable, or fatigue in the legs that occurs during exercise (walking) and is relieved by rest.
a. this exertional pain pattern is similar to stable angina pectoris (reversible ischemia)
2. Common in the calves but may experience symptoms in feet or proximal LE (thighs/ hips/buttocks)
3. DDx - neurogenic vs intermittent claudication
a. neurogenic: “positional” relief
b. vascular (intermittent) claudication: “exertional” relief
4. As severity of peripheral plaques progress then exercise tolerance diminishes as noted by an earlier onset of symptoms with walking/exercise.
(ii) Rest pain
1. usually worse distally, is aggravated by leg elevation (often causing pain at night), and lessens when the leg is below heart level.
2. The pain may be burning, tightening, or aching, although this finding is nonspecific.
(iii) “Asymptomatic” patients with PAD
1. Estimated that 20% of patients with PAD are asymptomatic due to CAD limitations
a. i.e. patients simply aren’t active enough to provoke LE claudication
Thromboangiitis obliterians (Buerger disease)
- Inflammation of peripheral arteries
* STRONGLY associated with tobacco use (95% of cases related to smoking)
Thromboangiitis obliterians (Buerger disease) Pathogenesis
(i) Inflammatory response
(ii) Thrombi and arterial vasospasm may be present
(iii) Potential to damage small arteries
(iv) NO atherosclerotic changes in effected blood vessels
Thromboangiitis obliterians (Buerger disease) Clinical
(i) Common regions:
1. Arteries of distal extremities
(ii) Common symptoms:
1. Distal extremity ischemic pain of involved region at rest
2. Distal extremity ischemic ulcers
(iii) Intervention strategies:
1. eliminate tobacco exposure
2. pharmaceuticals to improve circulation (vasodilators, etc..)
Raynaud Phenomenon and Disease
- Vasospasms of small arteries/arterioles in distal UE (occasionally distal LE)
- Abnormal temperature tolerance/responses
Raynaud Phenomenon and Disease Pathogenesis
(i) Dysfunction of NO (nitric oxide) and sympathetic feedback mechanisms for blood vessel dilation/constriction
(ii) Genetic predisposition
2 Types of Raynaud
(i) Raynaud Phenomenon (secondary Raynaud)
1. Secondary complication of other systemic conditions
a. scleroderma, chemotherapy, malignancy, hypothyroidism, etc… (see text for list)
(ii) Raynaud Disease (primary Raynaud)
1. Primary vasospastic disorder – etiology not clear
2. Primary Raynaud is not usually as severe as secondary
Interventions for Raynauds
(i) Raynaud Phenonmenon (secondary)
1. address primary condition/disease causing the Raynaud’s
(ii) Raynaud Disease (primary)
1. pharmaceutical strategies to optimize blood flow (vasodilators)
2. avoid vasocontricting triggers (nicotine, cold, stress, etc…)
HTN classified by
• Normal < 120/80 mmHg
• Pre-hypertension: systolic = 120-139 or diastolic = 80-89
• Stage 1 = systolic = 140-159 or diastolic = 90-99
• Stage 2 = systolic >160 or diastolic > 100
b. Elevated systolic can be most damaging to organs in the long run
c. Diagnosed on two or more separate readings of HTN
Primary vs. Secondary HTN
a. Primary HTN • “essential HTN” or “idiopathic HTN” • MC form of HTN 90 -95% individuals with HTN b. Secondary HTN • HTN 2° to a primary disease process • Ex: renal or endocrine disorders
Sympathetic dysfunction of HTN
- increased HR
- increased vascular resistance
a. chronic vascular remolding (“new normal” vasoconstriction) - promote insulin resistance
a. insulin plays role in NO production/signaling - promotes coagulation
a. increased vasospasm and thrombus formation
Renal-angiotensin-aldosterone system (RAAS) of HTN
- RAAS responds to decreased pressure/volume and encourage renal retention of salt and H2O
- Dysfunction of RAAS can result in:
a. increased blood volume (salt and water retain via kidney)
b. promotes vasoconstriction
c. promotes insulin resistance
Natriuretic peptides: ANP (atrial natriuretic peptide)/BNP (brain natriuretic peptide) of HTN
- ANP/BNP respond to elevated pressure/volume and encourage renal excretion of salt and H2O
- Normal pressure response equilibrium of these hormone feedback mechanisms can be disrupted by:
a. excessive intake of sodium or insufficient intake other electrolytes (potassium, calcium, magnesium)
b. obesity - Dysfunction of natriuretc peptide homeostasis can result in:
a. Increased vascular tone and promotes increased blood volume/pressure
Risk Factors Associated with Essential HTN
a. Age & gender
• younger men and older women …men < 55 and women > 74
b. Race
• African American
c. High dietary intake of sodium and low intake potassium, calcium and magnesium
d. Glucose intolerance (insulin resistance)
e. Cigarette smoking
• Nicotine acts as vasoconstrictor
f. Obesity
• metabolic syndrome (HTN, CAD and glucose intolerance)
g. Excessive alcohol intake
• 3 drinks per day elevates likelihood of HTN however, moderate alcohol 2- 4 drinks per week appear to do better than non-drinkers
Chronic inflammation response to endothelial injury/ischemia of HTN
(i) Normal inflammatory response
1. cytokines (histamine, prostoglandins) signal cascade of events leading to vasodilation/permeability changes
2. these changes promote healthy healing response to acute injury
(ii) Chronic inflammatory response = negative endothelial response
1. vasoconstriction: abnormal vascular remodeling/smooth muscle contraction
2. Note: atherosclerotic plaque development causes chronic inflammatory response
Insulin Resistance of HTN
(i) Healthy individual:
1. Insulin plays role in endothelial function (constriction/dilation mechanisms)
2. Insulin promotes NO production
(ii) Insulin resistance:
1. Abnormal response to insulin is altered in viscous cycle
a. cells become less sensitive to insulin (receptors or insulin itself)
b. feedback mechanism to pancreas result in increased insulin secretion (hyperinsulemia)
c. hyperinsulinemia promotes more insulin resistance
2. Insulin resistance = less NO production and endothelial dysfunction
3. Insulin resistance is pathological consequence of diabetes however:
a. Insulin resistance can be identified in 50% individuals with HTN and are non-diabetic
Interventions for HTN
a. Lifestyle changes
b. Pharmaceuticals aimed at the specific mechanisms of cardiac pump mechanics or blood volume/sodium excretion pathways
• Ex: ACE inhibitors, angiotensin II blockers, aldosterone receptors blockers, beta blockers, calcium channel blockers, renin inhibitors, diuretics (many act at different points in the kidney filtration system), central and peripheral adrenergic antagonist (sympathetic inhibition), endothelial vasodilators, etc…
c. If secondary HTN – address primary pathology + functional pressure/volume/pump changes
Hypotension (orthostatic)
- Decreased systolic, diastolic or both from supine to upright position change
a. Normal pressure compensation with standing:
• Increased HR and venous/arteriole vasoconstriction
(i) Stretch receptors stimulus of increased sympathetic response
• Mechanical systems – muscular pump, valve function
b. Orthostatic hypotension is dysfunction of one of these mechanisms
Criteria of Orthostatic Hypotension
a. BP changes within 3 minutes of standing
• Systolic decrease > 20 mmHg or diastolic decrease > 10 mmHg
Clinical Presentation Transient/acute orthostatic hypertension
- temporary decrease of BP requires patient to take a few extra minutes to transfer from supine to stand (usually supine to sit, wait, sit to stand)
- medications, chronic bed rest/immobility, anatomical/physiological anomaly, starvation/dehydration, venous pooling (pregnancy, varicose veins/CVI, etc…)
Clinical Presentation of Chronic orthostatic hypotension
• Disease causing orthostatic hypotension
(i) Endocrine, metabolic, CNS/PNS disorders
• Idiopathetic orthostatic hypotension
(i) No known cause
Atherosclerosis
a. Inflammatory/immune process
b. Exact pathological mechanisms continue to be debated
Four stages of plaque development/pathogenesis
(i) Endothelial injury
(ii) Fatty streaks
(iii) Fibrous plaque formation
(iv) Complicated plaques or unstable plaque
Stage 1: Endothelial Injury
• Initial damage to endothelial lining causes inflammatory response
(i) allows cascade of events to progress to atherosclerotic plaque…“opens the door” to development of fatty streak
Inflammation response to endothelial damage results in?
(i) Endothelial cells can’t produce anti-thrombotic and vasodilator cytokines
1. sets the stage for thrombus formation and vasoconstriction
(ii) Excessive release of inflammatory mediators (cytokines)
1. TNF-alpha, IL-1, Interferon-gamma (IFN), oxygen radicals, heat shock proteins
(iii) Growth factors are released that will promote smooth muscle proliferation
(iv) Macrophages accumulate and adhere to injury
1. Macrophages release enzymes that oxidize LDL and add to endothelial damage
a. LDL oxidation is critical step in atherosclerosis
i. Diabetes, hypertension, smoking all associated with increased LDL oxidation (i.e. “oxidative stress”)
2. Macrophages ingest oxidized LDL and “become” foam cells
Causes of endothelial damage include?
(i) Smoking and other infectious toxins
(ii) Hyperglycemia (diabetes)
(iii) Hypertension and other changes in blood flow dynamics
(iv) Dyslipidemia (elevated LDL, low HDL, elevated TG’s)
(v) Elevated homocysteine levels
(vi) Additional factors
1. insulin resistance
2. elevated CRP (C reactive protein)
3. oxidative stress (LDL oxidation) – promote free radicals
4. infection/periodontal disease
5. elevated fibrinogen
Stage 2: Fatty Streak
• Fatty streak is “earliest” gross pathological lesion in atherosclerosis
(i) Accumulation of foam cells (“packed full” of LDL) results in fatty streak
(ii) Other events accompanying the growth of fatty streaks
1. Platelets attach to the damaged endothelium
2. Migration of smooth muscle into the area
(iii) Fatty streaks promote more endothelial damage/inflammatory responses which turns into a viscous cycle of negative pathology
• Current lifestyle of our society – observation of fatty streaks at younger ages
Stage 3: Fibrous Plaque
• Smooth muscle continues to proliferate in area and then produce collagen
• Collagen forms a fibrous plaque over the fatty streak
(i) Growth factors released initially promote smooth muscle and collagen formation
• The fibrous plaque may, or may not, calcify
• Plaque and blood flow
(i) Impair laminar flow (aka create turbulent flow)
(ii) If large enough – may occlude blood flow
• Fissures may develop
Stage 4: Complicated Plaque
• Ruptured plaque = complicated plaque
(i) Some plaques can be prone to “rupture”
(ii) Clinical concern regardless of size
(iii) Hemorrhaging within the plaque leads to rupture
• Bleeding from rupture leads to:
(i) Platelet adhesion, clotting factor cascade and quick thrombus formation
• “New” thrombus may abruptly occlude blood flow causing ischemia or infarction
CAD
a. Atherosclerotic plaque formation the coronary arteries
Non-modifiable Risk Factors for Coronary Artery Disease (CAD)
• Age
• Gender
(i) males > females
(ii) females after menopause
• Family history: MI, cardio revascularization or sudden death
(i) 1st degree male relative: 55 yrs or younger
(ii) 1st degree female relative: 65 yrs or younger
(iii) 1st degree = father, mother, brother or sister
Modifiable Risk Factors for Coronary Artery Disease (CAD)
Dyslipidemia HTN Obesity Smoking DM (increase insulin resistance)
Dyslipidemia for CAD
(i) Elevated plasma lipoprotein levels (lipids, phospholipids, cholesterol, TG’s all bind to carrier proteins hence “lipo”protein)
(ii) “Major risk” of CAD = combination of elevated LDL (> 160) with low HDL (<40)
Dyslipidemia Values
- LDL cholesterol (mg/dl)
a. 240 - “High” - Triglycerides
a. > 200 - “high” - HDL cholesterol
a. > 60 - ideal
b. < 40 - undesirable
Cigarette Smoking for CAD
(i) Primary and secondary both ↑ CAD risk
(ii) Risks may ↓ by as much as 50% within first year of quitting
(iii) Smoking contributes to
1. decreased HDL, elevated LDL and LDL oxidation
2. endothelial inflammation/thrombus formation
DM risk factor for CAD
(i) Numerous negative effects on cardiovascular system
(ii) Impaired fasting glucose (delayed GTT)
(iii) Insulin dependent vs non-insulin dependent
Other factors associated with CAD
(i) Infections
(ii) Elevated C-reactive protein and other inflammation markers
(iii) Elevated homocysteine levels
1. Homocysteine – what is it?
a. Amino acid that is similar to the A.A. cysteine (it is homolgue therefore…the name homo-cysteine.)
b. It is a temporary A.A. molecule that occurs naturally in a cascade of protein metabolic pathways
c. Requires B6 (pyridoxine), B9 (folic acid) & B12 to avoid accumulating in the blood stream
What causes elevated homocysteine levels?
a. lack of enzyme that breaks down homocysteine
b. dietary deficiencies – some of the B vitamins (B6 pyrydoxine, B9 folate, B12 cobalamin)
What happens if too much homocysteine (normal A.A. pathway disrupted)?
a. Inhibits a key enzyme in collagen and elastin production
What are the health consequences of too much homocysteine?
a. ↑ CAD risk – d/t damaged blood vessels
b. ↑ risk of fractures in elderly
MC cause of myocardial ischemia
atheroclerosis in form of CAD
• Initially – impairment may only be evident under increased demand (exercise, stress, etc..)
• As pathology progresses impairment becomes evident at low levels of demand (rest, ADL’s, etc..)
Myocardial ischemia Pathophys
• Narrowing of coronary artery (>50%) will result in impairment of cellular metabolism
• Myocardial cells become ischemic within 10 seconds of blood flow occlusion
• Attempt to rely on myoglobin O2 stores for first 6 – 10 seconds
• After 2-3 minutes
(i) Loss of contractility followed by drop in cardiac output
(ii) Conduction abnormalities (EKG changes, etc…) leading to dysrhythmias
(iii) Anaerobic metabolism is only mechanism to provide energy with lactic acid accumulation
• If flow is restored then return to aerobic metabolism, contractility returns followed by cellular repair
• If flow is not restored then myocardial infarction occurs (damage and/or potential tissue necrosis)
Other causes of myocardial ischemia—Decreased delivery of blood to myocardium..
(i) Coronary spasm (prinzmetal angina)
(ii) Hypotension
(iii) Arrhythmias
(iv) Decreased O2 capacity of the blood (anemia, hypoxemia, altitude)
Other causes of myocardial ischemia—Increased demand for O2 by myocardium
(i) Tachycardia and exercise - (both more work for the heart)
(ii) Hypertension (more work to overcome increased afterload)
(iii) Cardiac hypertrophy (bigger muscle demands more O2)
(iv) Valve dysfunction/disease
Stable Angina
(i) Transient episode of blood flow impairment in relation to O2 demand of the cardiac muscle
(ii) This scenario is usually the individual with gradual narrowing of the lumen and stable plaque development within the blood vessel walls
(iii) Recurrent episodes lasting 3-5 minutes
(iv) Onset usually some form of exercise/exertion or stress
(v) Pain is often relieved with rest
(vi) S/S include
1. “Angina pectoris” - substernal chest discomfort (heaviness – pressure – pain)
a. Pain vs discomfort – “open ended” questioning
2. Other “classic” signs/symptoms (see text)
(vii) Discuss patient interview: pain vs discomfort
(viii) Other classic myocardial ischemia s/s
Silent Angina
(i) Myocardial ischemia that does not cause obvious signs/symptoms
(ii) Common following conditions/surgical procedures that may impair innervation
1. Ex: heart transplant, CABG (coronary artery bypass graft surgery), emotional stress, diabetes, etc…
Unstable Angina
• UA - Thrombus breaks up before cell death, allows return of blood flow (perfusion)
• “Reversible” myocardial ischemia – no cell damage
• Occurrence of UA increases the likelihood of MI within “relative” near future
(i) 20% of patients with UA will have MI or death from MI within 30 days
cell injury pathophysiology
- 6 – 10 seconds of impaired blood flow the cell becomes ischemic (cooler and cyanotic)
- Anaerobic metabolism attempts to supply ATP for muscle contraction…can’t supply adequate amount compared to aerobic metabolism
- Lactic acid and H+ ions accumulate as a result of anaerobic metabolism…acidic environment impairs conductivity
- Electrolytes disturbances also occur due to the lack of blood flow (potassium, calcium and magnesium) – alter conduction.
- Myocardial cells release catecholamines (EPI and NE)
Angiotensin 2 is released during ischemia
- Promotes vasoconstriction and sodium retention
a. obviously counterproductive….systemically it increases BP and work demand on heart - Angio-2 also stimulates smooth muscle proliferation coronary vasoconstriction/spasm
- Promotes catecholamine release – sympathetic response
- Clinical
a. ACE inhibitors (limit the Angio response) and Beta blockers (limit the sympathetic response)
Cell Repair pathophysiology
(i) Inflammatory response (immediately first 4 days)
1. leukocytes/proteolytic enzymes accumulate to remove damaged/necrotic cells
2. glycogenolysis and FFA release to increase fuel availability during recovery
(ii) Soft scar formation (4-10 days)
1. weak soft collagen matrix forms
2. potential for re-injury
(iii) Mature scar tissue formation (6+ weeks)
1. soft scar replaced by mature collagen formation
2. mature scar
a. not susceptible to “mechanical” injury
b. however it DOES NOT contract – cardiac wall function permanently impaired
Pathophsyiology – secondary area around damaged cells
(i) Myocardial stunning – transient (hours – days) loss of contractility
(ii) Hibernating myocardium - ischemic tissue goes into metabolic survival state to survive until return of blood flow
(iii) Myocardial remodeling
1. Hypertrophy and loss of contractility of myocardial cells throughout heart in response to infarction
2. Stimulated by angio-2, aldosterone, catecholamines and inflammatory cytokines
3. Clinical goal to limit via restoration of blood flow and pharmaceuticals aimed at the above
MI complications
(i) Arrhythmias
1. cellular and mechanical response to MI may trigger arrhythmic patterns
2. V-fib and re-entrant patterns
(ii) Pericarditis
1. inflammatory responses may lead to pericarditis
(iii) Ventricular wall aneurysm
1. mechanical changes from scar formation/weakened wall lead to structural displacement
