Lecture 32 - Cardiovascular Flashcards
Describe the cause and complications of Varicose veins
Etiology: Veins are highly distensible, contain up to 70% of blood at rest; saphenous veins are usually involved (great saphenous vein)
A. Standing for long periods of time without moving
B. Crossing the legs while sitting; it blocks venous flow
C. Wearing restrictive garments
Pathophysiology:
A. Gravity or obstruction causes blood to distend the veins
B. Distension progresses until the valves in the veins are damaged
C. Valves fail, venous pressure rises, and distension worsens to the point that vascular restructuring occurs
Define/Differentiate Thrombus vs Embolus. Delineate the etiology Thrombi vs Emboli and describe the pathophysiologic consequences of the two. Describe the best treatments is for
the prevention of Thrombus formation.
THROMBUS
Thrombus = clot that remains attached to the vessel wall
Etiology: Anything that triggers clotting mechanism
A. Rough intima of vessels –> Artherosclerosis
B. Inflammation/Injury of intima –> Phlebitis from non sterile needle
C. Low blood pressure leading to blood stasis –> Cardiac failure, CHF, or shock
D. Obstruction of blood flow –> crossing your legs, occluding blood flow through veins
note: standing or sitting for long periods of time without moving causes blood stasis leading to clot formation, varicose veins and risk for DVT’s
Pathophysiology:
A. Blocks/Occludes the vessels - in arteries it causes infarction of the tissue distal to the clot
B. Break lose and become and embolus which blocks the first capillary bed it comes in contact with, if venous it causes PE
***Treatment = Low molecular weight Heparin for DVT’s, Streptokinase (enzyme released from streptococcus that bind and activate human plasminogen), tPA (tissue Plasminogen Activator), and Angioplasty (surgical repair or unblocking of a blood vessel)
PREVENTION IS KEY –> MOBILIZE PATIENT AS SOON AS ABLE, THIS IS ESSENTIAL
Define/Differentiate Thrombus vs Embolus. Delineate the etiology Thrombi vs Emboli and describe the pathophysiologic consequences of the two. Describe the best treatments is for
the prevention of Thrombus formation.
EMBOLUS
Embolus = obstruction of a blood vessel by a bolus of matter
Etiology: Dislodged thrombus
In ARTERIAL side usually originates in L heart which is a result from
1. Dysfunctional valves causing turbulent blood flow
2. A fib
3. Stasis in aneurism (ballooning and weakened area in artery)
50% OF EMBOLI GO TO THE LEGS; CAN GO TO CORONARY ARTERIES OR CEREBRAL VASCULATURE –> HEART ATTACK AND STROKES
A. VENOUS side is usually due to phlebitis (inflammation of vein) or stasis or trauma; Highest risk is DVT
*** usually venous embolus goes to lung –> PE
obstructs L –> R flow in lungs
B. Air Embolus - air bubble from IV or from scuba diving
C. Amniotic Embolus - contraction during labor causes a large amount of amniotic fluid to go into mothers blood stream
D. Aggregate of fat - release with Fx of long bones, especially the femur bone; platelets aggregate around fatty emboli and cause it to adhere to endothelial wall
E. Vegetative aggregate of bacteria - usually released from valves during bacterial endocarditis
F. Cluster of cancer cells
Pathophysiology: Embolus floats through circulation until it hits a vessel too small to pass through, then it lodges and obstructs blood flow
Causes-
- Ischemia –> Hypoxia –> Pain from neural hypoxia
- Infarction = death of tissue distal to occlusion
Be prepared to list six different types of emboli, their cause and sources.
- Arterial/Venous embolus:
If ARTERIAL it is usually from the L Heart this could be a result of a) Dysfunctional valves causing turbulent blood flow b) A fib or c) blood stasis in aneurism
If VENOUS it is usually from phlebitis, trauma, or injury; the most dangerous type is DVT; usually goes to the lungs and causes PE which bloods L–> R flow of blood in lungs - Air Embolus: usually from air in IV or from scuba diving
- Amniotic Embolus: from labor when a large amount of amniotic fluid enters mother’s blood stream
- Fatty aggregates: from Fx of long bones (usually femur); platelets aggregate around the fatty embolus and it adheres to the endothelial wall
- Accumulation of bacteria
- Cluster of cancer cells
Define/Differentiate: primary hypertension vs secondary hypertension. Describe how
hypertension is diagnosed, the definition of hypertension, and differentiate between:
A) Normal BP C) Stage I hypertension
B) Prehypertension D) Stage II hypertension
HTN = two separate measurements of BP
systolic > 140 mmHg and diastolic > 80 mmHg
Causes:
- Increased CO (either increased HR or SV or both)
- Increased peripheral resistance (greater viscosity of blood or vasoconstriction)
a) NORMAL BP: 160/>100
I. Primary HTN: combined genetic and environmental factors
Genetic =
a) Decreased Na+ excretion and decreased response to aldosterone (causes oversecretion of aldosterone)
- Inherited defects in renal Na+ secretion
- Hypertensive individuals secrete less Na+ in urine
b) Increased production or activation of angiotensin II - this thickens the vasc. smooth mm. (hypertrophy/hyperplasia) thus narrowing the artery; it is a powerful vasoconstrictor; causes cardiac hypertrophy because heart has to work harder
c) Insulin resistance is very common in hypertension
Risk factors = a) age and gender (young males, older women) b) high Na+ intake c) smoking/heavy alcohol consumption d) glucose intolerance (diabetes), microvascular damage e) low intake of K, Ca, Mg f) obesity --> leptin is secreted by adipose cells, meant to suppress appetite Chronically high levels of leptin cause: . insulin resistance (DM II) . increased sympathetic tone . decreased Na+ excretion . stimulates myocyte hypertrophy
Metabolic Syndrome –> Leads to DM II
a) central obesity
b) high normal fasting blood glucose
c) increased LDL and decreased HDL
d) high BP
*** ACE inhibitors and blockers of aldosterone are becoming primary treatment for primary HTN
II. Secondary HTN = altered hemodynamics due to an underlying disease
Tx: treat or remove underlying disease
ex) Renal Atherosclerosis, we would decrease blood flow to kidney
Describe complicated HTN
***Complicated HTN can be either primary or secondary
Pathophysiology:
a) Damage to endothelial membrane. Loss of endothelial vasodilators, NO(relaxes smooth mm.), and prostaglandins (control BP by contracting or dilating)
b) smooth mm. hypertrophy and hyperplasia
c) narrowing of the vessel lumina
d) leads to ischemia –> hypoxia –> organ dysfunction
Complications:
a) Turbulent blood flow –> leads to development of atherosclerosis
b) L ventricular hypertrophy –> stimulated by SNS and angiotensin II
c) CHF
d) CAD and cerebral vascular disease
e) PRIMARY CAUSE for formation of aneurism
f) Malignant HTN causes cerebral edema encephalopathy (general term for any brain disease) which leads to death
Clinical Manifestations: The silent death
No s/s until too late; symptoms are secondary to organ damage
Evaluation: sequential BP readings
Treatment:
Behavioral - exercise, smoking cessation, salt restriction
Pharmacological - . ACE inhibitors . Angi II receptor blocker (natriuretic - process of excretion of Na+ into urine) . B blockers . Ca2+ channel blockers
Delineate the role of each of the following in hypertension:
Metabolic Syndrome
Metabolic Syndrome: Leads to DM II
a) Obesity
b) High normal blood glucose
c) Increased LDL and decreased HDL
d) High BP
This leads to DM II which is seen in Primary HTN
DM is a risk factor for HTN
Delineate the role of each of the following in hypertension:
Leptin
Leptin is secreted by adipose cells. It a) leads to insulin resistance b) reduces Na+ excretion c) induces myocyte hyperplasia and d) increases sympathetic tone
This is a result of obesity which is a risk factor for primary HTN
Delineate the role of each of the following in hypertension:
RAAS system
aka the Renin angiotensin aldosterone system
Renin to angiotensin –> angiotensin II
Angiotensin II leads to powerful vasoconstriction, hypertrophy and hyperplasia of vascular smooth muscle thus narrowing the lumen, and hypertrophy of the L ventricular hypertrophy thus worsening HTN
Angiotensin II –> Aldosterone
Aldosterone causes the kidneys to reabsorb salt water, increasing blood volume and worsens an already hypertensive individual
Delineate the role of each of the following in hypertension:
The Sympathetic nervous system
The sympathetic nervous system causes the vascular smooth mm. to vasoconstrict thus worsening HTN and can lead to L ventricular hypertrophy
Describe the mechanism and benefits of using each of the following to control hypertension.
ACE inhibitors
ACE inhibitors will prevent the formation of angiotensin I to angiotensin II thus preventing powerful vasoconstriction, vascular smooth mm. hypertrophy/hyperplasia, and L ventricular hypertrophy.
Describe the mechanism and benefits of using each of the following to control hypertension.
β blockers
B blockers will inhibit the sympathetic nervous response and prevent vasoconstriction of the vascular smooth mm.
Describe the mechanism and benefits of using each of the following to control hypertension.
Ca++ Blockers
Ca++ blockers will prevent the Ca++ from entering the blood vessel walls resulting in lower BP.
Describe the mechanism and benefits of using each of the following to control hypertension.
Salt Restriction diet
A salt restriction diet will prevent HTN, edema in pt’s with kidney failure and hypertension due to reabsorption of water, it will prevent proteins from being excreted into urine, and it will prevent loss of kidney function.
Define aneurism, identify some possible causes of aneurisms and describe the pathological
consequences of aneurisms.
Aneurism = out pouching of the vessel wall or heart wall
Etiology:
a) Constant mechanical stress, once the out pouching occurs, Law of Laplace causes it to accelerate (the larger the radius the less the pressure) P = 2XT/R
b) Artherosclerosis: MOST COMMON CAUSE, causes a weakening of vessel wall leading to aneurism formation
c) Most often occurs in Aorta - aortic arch or abdominal aorta
Pathophysiology:
a) formation of clots due to blood stasis in aneurism
b) hemorrhage due to aneurism rupture
c) dissecting aneurism - will cause much pain and rupture
What is LDL Familial Hypercholesterolemia (FH)?
All cells require cholesterol as a component of their plasma membrane. They can synthesize their own or preferably bring it in via endocytosis on LDL’s. FH is most commonly caused by a reduction of LDL receptors on cell surfaces. Lacking the normal number of LDL receptors cellular cholesterol uptake is reduced and circulating cholesterol is increased.
–> This leads to early artherosclerosis and MI’s
This is a result of more than 1000 mutations in the LDL receptor gene.
Tx:
a) reduce cholesterol in diet
b) take cholesterol reducing agents (statins)
c) Liver transplants (less successful due to lack of donors)
What is atherosclerosis?
Atherosclerosis: thickening and hardening of the blood vessels caused by soft deposits of fat and fibrin; decrease the ability of the vessel to change lumen size (vasoconstrict and vasodilate)
Mechanism: smooth mm. and fibroblasts migrate to the intima, hypertrophy of vascular smooth mm. and collagen deposition causes vessel wall the thicken and stiffen
Pathophysiology: 4 steps in the formation of artherosclerosis
a) endothelial injury
b) fatty streak
c) fibrotic plaque
d) complicated lesion
Define/describe/differentiate between the four levels or stages of atherosclerosis. Describe
the evolution of a normal epithelium from normal to a complicated lesion.
- Endothelial Injury
- Endothelial Injury - little is known about how it is formed but here are some causes
a) Smoking - chemicals cause certain endothelial damage and dysfunction
b) HTN - increased pressure causes mechanical injury to the cells by causing turbulent blood flow
c) Diabetes - glycation and thickening of the basement membrane of microvascular vessels and increased LDL and decreased HDL accelerating fat deposition in large vessels + glycosylation
d) Turbulent blood flow - increased sheer forces and mechanical injury
e) Increased plasma fibrinogen???
f) Autoimmunity - Type III Hypersensitivity responses; antigen-antibody complexes precipitate out of blood and trigger neutrophils to attach and degranulate, digesting the endothelial cells
g) Bacteria and Viruses - lysis of endothelial cells through digestion; phlebitis
Steps of Endothelial Injury:
a) Cessation of synthesis of antithrombin factors and vasodilatory substances such a NO, prostaglandins, and vasodilatory cytokines
b) Release of inflammatory cytokines (IL-1, TNF alpha, Interferon, oxygen free radicals)
c) Release of growth factors stimulating mitosis and proliferation of vascular smooth mm. and fibroblasts –> collagen
ex) Angi II, Fibroblast growth factor, Platelet growth factors
d) Margination of macrophages
–> enter lesion and phagocytize oxidized LDL’s = foam cells, release toxic oxygen free radicals and further damage vessel wall
e) Accumulation of LDL in lesion, oxidation of LDL’s phagocytized by macrophages attracts more macrophages
f) Accumulation of foam cells (macrophages full of LDL’s) which penetrate further into lesion –> now called fatty streak
Define/describe/differentiate between the four levels or stages of atherosclerosis. Describe
the evolution of a normal epithelium from normal to a complicated lesion.
- Fatty Streak
Fatty streaks are found in most people and can be reversed by lowering LDL intake and increasing HDL intake.
- Increases formation of oxygen free radicals (Vit A,C,E) which trigger inflammatory changes
- Activation of fibroblast to secrete fibrous connective tissue in an attempt to heal the lesion –> forms a fibrous plaque made of collagen protein also at this point a risk of triggering the clotting mechanism
Define/describe/differentiate between the four levels or stages of atherosclerosis. Describe
the evolution of a normal epithelium from normal to a complicated lesion.
Fibrous plaque
Smooth mm. migrate, proliferate; Fibroblasts secrete collagen forming a cover over the lesion –> Decreases the size of the lumen and increases resistance to blood flow
This area of the vessel is no longer responsive to vasodilation, and may cause ischemia to tissue distal to occlusion especially if there is increased O2 demand
The fibrous tissue can ulcerate or rupture due to
a) Sheer forces on the vessel
b) Continued necrosis of the tissue
*** The fibrous plaque can cause platelet aggregation due to exposed collagen on ruptured plaque thus triggering the clotting cascade
–> This is now called a complicated lesion
Define/describe/differentiate between the four levels or stages of atherosclerosis. Describe
the evolution of a normal epithelium from normal to a complicated lesion.
Complicated Lesion
Complicated lesions can occur quite rapidly and result in infarction (obstruction of blood flow to tissue)
Clinical manifestation:
a) Ischemia - ST segment depression of T wave inversion
b) Angina - chest pain or pressure
- this is due to decreased blood flow to the heart
c) Transient ischemic events
d) Assume that if this has occurred in one area, then it has probably occurred in other areas ex) coronary, cerebral, and other arteries
Evaluation:
a) complete health history including risk factors
b) ECG either resting or stress test
c) Nuclear scanning
d) Angiography - can see where blockage is on x ray
e) CT or MRI - for coronary aa.
Tx: Primary goal is to restore adequate blood supply
a) Remove initial cause of lesion
- smoking cessation
- control HTN
- control DM
- Reduce LDL/cholesterol
- Remove US diet
- Exercise
Be prepared to list and explain the mechanisms of endothelial injury leading to
atherosclerotic disease for each of the following etiologies.
Smoking
Smoking causes endothelial cell damage which can lead to atherosclerotic disease
Be prepared to list and explain the mechanisms of endothelial injury leading to
atherosclerotic disease for each of the following etiologies.
Hypertension
HTN also damages endothelial cells by increased pressure which results in mechanical injury through turbulent blood flow.
Be prepared to list and explain the mechanisms of endothelial injury leading to
atherosclerotic disease for each of the following etiologies.
Diabetes Mellitus
DM causes glycosylation of the endothelial cells as well as LDL increase and deposition and HDL decrease –> Thickens the basement membrane
Be prepared to list and explain the mechanisms of endothelial injury leading to
atherosclerotic disease for each of the following etiologies.
Bacteria or viral infections
Bacteria/Viral infections cause release of damaging toxins that digest the endothelial cells or cause them to lyse –> phlebitis
Be prepared to list and explain the mechanisms of endothelial injury leading to
atherosclerotic disease for each of the following etiologies.
Turbulent blood flow
Increased sheer forces and mechanical injury.
