Cardiovascular

Question 1

Vessel Wall Structure

Answer 1

o Tunica Intima – endothelium (typically first thing injured) and basement membrane
• Surveys blood and releases anti-inflammatory and anti-coagulants
 Internal elastic membrane
o Tunica Media – smooth muscle and elastic fibers
o Tunica Adventitia – connective tissue

Question 2

Active Role of Endothelium

Answer 2

o Secretory & Modulatory for vascular smooth muscle tone and growth, and platelet function
 Endothelial-derived vasodilators: nitric oxide and prostacyclin
 Endothelial-derived vasoconstrictors: endothelin
 Anti-aggregatory for platelets
 Anti-mitoenic for vascular smooth muscle
o Metabolic – processing of vasoactive factors – angiotensin-converting enzyme production of angiotensin II (vasoconstrictor) and breakdown of bradykinin (inflammation)
o Plasticity – angiogenesis (new vessel growth) in response to injury and ischemia

Question 3

Vascular Smooth Muscle Cell Functions

Answer 3

o Contractile – contraction and relaxation
o Secretory – formation of matrix, growth factors, proteases
o Plasticity – hypertrophy, proliferation, large changes in phenotype
o Vascular tone – tone or state of contraction due to myogenic tone (intrinsic factors) or neurogenic and humoral tone (extrinsic factors)
o Vasomotion – change in caliber of a blood vessel

Question 4

Control of Local Blood Flow

Answer 4

– flow through a region is governed mainly by the resistance of the microcirculation; Pressure = 8 (viscosity) x (length) x (flow rate) / (radius)4
o Metabolic regulation – local metabolites (vasodilation mostly)
o Autoregulation (myogenic regulation) – transmural pressure results in vasoconstriction
o Shear stress-induced vasodilation – force the fluid makes on the vascular wall

Question 5

Edema

Answer 5

– increased fluid in interstitial spaces
o Normally – fluid entering on arterial end = fluid leaving venous; excess drained via lymphatics
o Disturbances in fluid homeostasis
 Increased hydrostatic pressure – impaired venous drainage, congestive heart failure
 Decreased oncotic pressure – reduced albumin (nephrotic syndrome, cirrhosis, protein malnutrition)
 Increased capillary permeability
o Local disturbances result of regional insults
o Systemic disturbances result of kidneys
o Stasis of flow is major issue – toxic waste products and pathogens build up; endothelial cells overwork in area of insult and die
o Clinically Relevant: Edema indicates disease, inflammation and impairs ability to fight infection

Question 6

Shock Characteristics and Mechanism

Answer 6

– systemic hypoperfusion due to reduced cardiac output or circulating blood volume
 Results in cellular hypoxia that is initially reversible but becomes irreversible
 Progressive disorder that leads to multi-organ system failure (liver, kidneys, CNS)
• Nonpregressive stage-compensatory mechanisms activated, perfusion maintained
• Progressive stage – tissue hypoperfusion (hypoxia) and onset of worsening of circulatory and metabolic imbalances
• Irreversible stage – tissue/cellular injury too severe and necrosis occurs; decreased myocardial contractility; renal shutdown due to acute tubular necrosis; ischemic bowell allow flora into circulation (superimposed endotoxic shock)

Question 7

Cardiogenic Shock

Answer 7

– heart failure – intrinsic myocardial damage, ventricular arrhythmias, outflow obstruction
 Catecholamine release – increases HR, contractility, and systemic vascular resistance
 Renin aldosterone – attempts to maintain adequate BV

Question 8

Hypovolemic Shock

Answer 8

– loss of blood or plasma – hemorrhage, severe burns, trauma

 Spleen can try to compensate

Question 9

Neurogenic Shock

Answer 9

– anesthetic or spinal cord injury – lose vascular tone, peripheral pooling of blood
 Increased PNS output resulting in massive vasodilation

Question 10

Anaphylactic Shock

Answer 10

– IgE hypersensitivity – systemic vasodilation and increased vascular permeability
• End result is hypovolemia and decreased cardiac output and tissue perfusion
 Vasoconstriction of vascular smooth muscle in GI and unnecessary organs
 Increased capillary permeability
 Increased peripheral vasodilation

Question 11

Septic Shock

Answer 11

– systemic microbial infection – most by gram negative endotoxins
 Vasodilation (hypoperfusion), pump failure, and DIC (extracellular injury and activation of coagulation factors)  will lead to multi-system organ failure
 Consumptive coagulopathy – formation of spontaneous clots in unwanted areas and consume all the coagulation factors  no coagulation factors to fight potential trauma
 1st among deaths in ICUs

Question 12

Inflammatory Response

Answer 12

o Local Inflammation – low quantities – involves neutrophils, macrophages, and epithelial cells
o Systemic Effects – moderate quantities – fever
o Septic Shock – high quantities – BV depleted and vessel injury resulting in stasis of blood

Question 13

Hemorrhage

Answer 13

– extravasation of blood due to rupture in vessel wall
o Hematoma – blood accumulates within a tissue
 Petechiae (1-2mm) – minute in size; into skin, mucus, or serosal membranes
 Purporas (3-5mm)
 Bruises (ecchymoses) (1-2cm) – subcutaneous hematomas with RBC deposition which are then phagocytosed by macrophages
• Hemoglobin metabolized  bilirubin  hemosiderin (golden brown)

Question 14

Thrombosis

Answer 14

– formation of a clot inside of a blood vessel
o Result of dysregulation of hemostasis described by Virchow triad (endothelial injury, abnormal blood flow, hypercoagulability)
 Propagation (accumulation of platelets/fibrin)  embolization (dislodged)  dissolution (fibrinolytic activity)  organization (inflammation,fibrosis, EC smooth muscle cell ingrowth) & recanalization results in thickened vascular wall & re-established blood flow

Question 15

Virchow’s Triad

Answer 15

– endothelial injury, abnormal blood flow, and hypercoagulability
o Hypercoagulability – tends to be more genetic factors
o Abnormal blood flow – result of either stasis or turbulence
o Endothelial injury – compromises the ability to regulate both in front and behind
 Often due to lipid deposition causing abnormal vasoconstriction or inflammation that leads to progressive vessel damage
 Or due to the endothelium stop making normal antithrombic and vasodilatory substance like prostaglandins and nitric oxide

Question 16

Cardiac/Arterial Thrombi

Answer 16

– cardiac dysfunction often origin of thrombi; thrombus formation begins at site of injury (plaque) or turbulence (bifurcation); associated with retrograde growth
o Myocardial infarction  mural thrombus (clot in heart)
o Rheumatic heart disease  mitral valve stenosis  left atrial dilation with atrial fibrillation  augments blood stasis  mural thrombus
o Atherosclerosis

Question 17

Venous Thrombi

Answer 17

– commonly occur at sites of stasis; either superficial varicosities or deep veins of leg
o Local congestion, pain, swelling, tenderness  rarely embolize
 Edema and impaired venous drainage predispose skin to infection from slight trauma and can develop varicose ulcers
o Deep thrombi (larger veins above knee) embolize, and are often asymptomatic
o Bypass channels commonly open to facilitate proper venous drainage
o Clinical Relevance – result of detached intravascular solid, liquid or gaseous mass, almost always a thrombus

Question 18

Atherosclerosis

Answer 18

– can start as early as age of 13
o Intimal Thickening – healing response to vascular injury; process by which smooth muscle cells migrate, proliferate, and deposit extracellular matrix  can lead to stenosis or occlusion
 New layer of vessel wall contains smooth muscle cells that lose the ability to contract
o Atheroma/plaque Formation – endothelial dysfunction  oxidized LDL  foam cell formation  atheroma formation (intimal lesion from fatty streak; lipid core covered by fibrous cap)
o Preclinical phase (begins age 10) – formation of fatty streak and fibrous cap that advance
o Clinical phase – aneurysm and rupture; occlusion by thrombus; critical stenosis
o Factors that decrease coronary blood supply (coronal plaque) or increase myocardial oxygen demand (increased HR/preload/afterload/contractility) can lead to ischemia and anginal pain

Question 19

Pulmonary Thromboembolism

Answer 19

– can start as early as age of 13
o Intimal Thickening – healing response to vascular injury; process by which smooth muscle cells migrate, proliferate, and deposit extracellular matrix  can lead to stenosis or occlusion
 New layer of vessel wall contains smooth muscle cells that lose the ability to contract
o Atheroma/plaque Formation – endothelial dysfunction  oxidized LDL  foam cell formation  atheroma formation (intimal lesion from fatty streak; lipid core covered by fibrous cap)
o Preclinical phase (begins age 10) – formation of fatty streak and fibrous cap that advance
o Clinical phase – aneurysm and rupture; occlusion by thrombus; critical stenosis
o Factors that decrease coronary blood supply (coronal plaque) or increase myocardial oxygen demand (increased HR/preload/afterload/contractility) can lead to ischemia and anginal pain

Question 20

Systemic Thromboembolism

Answer 20

– emboli that migrate through arterial circulation – forward failure
• Can cause complications within lower limbs, brain, intestines, kidneys and spleen dependent on origin and relative blood flow
• Consequences dependent on collateral blood supply & caliber of vessels occluded
 Intracardiac thrombi – left ventricular wall infarcts; dilated left atrium
 Ulcerated atherosclerotic plaques
 Aortic aneurysms

Question 21

Hypertension

Answer 21

– contributes to several conditions of cardio- and cerebrovascular disease
o BP = cardiac output x peripheral resistance; cardiac output = HR x SV
 Peripheral constrictors = alpha-adrenergics
 Peripheral vasodilators = beta-adrenergics
 Humoral constrictors = angII, catecholamines, thromboxane, leukotrienes, endothelin
 Humoral vasodilators = prostaglandins, kinins, NO
 Local factors – autoregulation and ionic (pH, hypoxia)
o Genetics and environmental factors play a role – cause defects in renal sodium homeostasis, functional vasoconstriction, and defects in vascular smooth muscle growth and structure
o 95% of cases idiopathic (unknown); essential (benign) hypertension secondary to renal disease
o 5% can have rapidly increasing BP if not treated & can result in death = malignant hypertension
 Presents with BP >120mmHg, renal failure, and retinal damage