Patho: Cardio -regulation of CVS and vascular diseases

What are examples of vasodilator metabolites?

What are examples of vasodilator metabolites?

CO2, K+, adenosine

What is the role of vasodilator metabolites?

ensure increased blood flow necessary to support increased tissue activity

What hormone causes platelet aggregation and vasoconstriction?

Thromboxane A2

What hormone promotes vasodilation?

prostacyclin

What promotes irreversible inhibition of cyclooxygenase?

ASA

Why is ASA valuable in preventing MIs, angina, and strokes?

reduces intravascular clotting for prolonged periods

What catalyzes the synthesis of NO from arginine?

nitric oxide synthase (NOS)

Where is NOS1 found?

nervous system

Where is NOS2 found?

macrophages and related immune cells

Where is NO3 found?

endothelial cells

What activates NOS2?

cytokines

What activates NOS1 and NOS3?

agents that increase intracellular Ca2+

*includes vasodilators acetylcholine an bradykinin

What hormones are the principal vasoconstrictors?

NE, epi

What hormones are the principal vasodilators?

VIP, Kinins, Natriuretic peptides

NO stemming from NOS3 produces cGMP which in turn does what?

mediates relaxation of vascular smooth muscle

If NO doesn’t relieve pain is it likely to be a cardiac issue?

no

What neurotransmitter is a regulator of blood flow, keeps the vascular system dilated, and is responsible for reactive hyperemia?

NO

What is the most potent vasoconstrictor agent?

endothelin-1 (ET-1)

What produces ET-1?

endothelial cells

What contributes to extracellular matrix remodeling in vascular, cardia, and kidney disease?

ET-1

What kinins are potent vasodilators?

bradykinin and lysyl-bradykinin

How do kinins increased blood flow?

producing vasodilation

Which hormone is secreted from the atria when atrial myocytes are stretched?

ANP

Which hormone is secreted by the ventricular myocytes and is a marker of HF?

BNP

Which type of hormone is an additional form of natriuretic peptide found in humans?

CNP

In a healthy person, what should the BNP level be at rest?

<100

Where is renin secreted from?

kidneys

Where is vasopressin secreted from?

hypothalamus

How does vasopressin increase BP?

reabsorbs more water → inc BV

What effects to noradrenergic vasomotor nerves have?

• arteriolar constriction → inc BP

• inhibits vagal stimulation → dec HR and dec CO

What effects do sympathetic noradregergic nerves have?

• inc force and rate of contractility

• inc BP, inc SV, inc CO

Where are baroreceptors controlling vasomotor discharge located?

• carotid sinuses and aortic arch on arterial side

• wall of great veins and cardiac atria on venous side

What accelerates atherosclerosis?

genetic and environmental factors

What vascular disease is characterized by localized fibrous thickenings of the arterial walls with calcified plaques?

atherosclerosis

How do fatty streaks form?

LDL oxidized → recognized by scavenger receptors → receptors uptake into macrophages → foam cells → fatty streaks

What cells form fatty streak in arteries?

foam cells

When do fatty streaks appear in the aorta?

1st decade of life

When do fatty streaks appear in the coronary arteries?

2nd decade of life

What do fatty streaks appear in the cerebral arteries?

3rd and 4th decade of life

What are the deleterious effects of oxidized LDLs?

• inhibition of NO production

• release of pro inflammatory cytokines

What forms as plaques mature?

fibrous caps

*need to keep stable

What happens if you infuse acetylcholine via catheter into normal coronary arteries?

vessels dilate

What happens if you infuse acetylcholine via catheter into arteries with atherosclerosis?

vessels constrict

What are dietary cholesterol and triglycerides packed into?

chylomicrons

What causes chylomicrons to release triglycerides?

lipoprotein lipase

What do VLDLs turn into after donating triglycerides?

IDLs and LDLs

Where do HDLs transport cholesterol to?

liver

What is the ideal range for HDL?

>40

*higher = better

Atherosclerosis causes angina pectoris when it narrow the lumen of a coronary artery by ____

>75%

What happens if there is an arterial blockage at the site of atherosclerotic plaques within the cerebral circulation?

thrombotic strokes

What can lead to the rupture of the abdominal aorta?

aneurysmal dilation

What does atherosclerotic plaque cause when lodged in the renal vessels?

renovascular hypertension

What is it called when there are blockages in the legs causing fatigue and pain when walking?

intermittent claudication

What reduces a women’s risk of developing atherosclerosis by increasing cholesterol removal?

estrogen

When increased in plasma levels, what is associated with accelerated atherosclerosis?

homocysteine

How much does smoking increase the chances of men developing ischemic heart disease compared to nonsmokers?

70%

How can the atherosclerotic process be reversed?

lower cholesterol and TRG; increase HDL

What has the greatest effect in reducing the incidence of stroke?

lowering hypertension

What diseases increase chances of developing atherosclerosis?

DM, hypothyroidism, nephrotic syndrome

What is the cause of essential (primary) HTN?

unknown

What is the cause of secondary HTN?

renal HTN, Cushing’s, pheochromocytoma, estrogen

What causes pill HTN?

OC

At what point is BP officially classified as hypertension?

>140/90

Symptoms of HTN?

usually none (silent killer)

What leads to the development of HTN?

• inc PVR

• prolonged inc in CO

• inc BV

• inc plasma renin activity

If left untreated, HTN can decrease life expectancy by how much?

10-20 yrs

Complications of HTN

MI, CHF, stroke, HTN encephalopathy, renal failure

How do you manage HTN?

B-blockers, ACE inhibitors, Ca channel blocker, diuretics

Causes of HTN:

coarctation of the aorta, salt sensitivity, renal abnormalities, renin-angiotensin abnormalities, adrenal disorders, obesity

What percentage of AA are salt sensitive and have essential hypertension?

55%

Pheochromocytoma is a tumor located where?

adrenal medulla

What disease is characterized by excess glucocorticoid?

Cushing’s

What disease is caused by a tumor in the adrenal cortex causing a large secretion of aldosterone?

Conn’s disease (hyperaldosteronism)

What are the 4 groups of shock?

hypovolemic, distributive, cardiogenic, obstructive

What causes the skin to be cool, pale, and clammy during shock?

vasoconstriction

At what pressure do carotid and aortic baroreceptors susceptible to fail?

~70 mmHg

Baroreceptors increase levels of what vasopressor hormones?

AT II, epi, NE, vasopressin

What is the reason behind hypovolemic shock?

inadequate volume to fill vascular system

What are some causes of hypovolemic shock?

hemorrhage, trauma, surgery, burns, fluid loss

In shock, the skin is cold, pale, and clammy expect for?

distributive shock

What are the three types of distributive shock?

anaphylactic, neurogenic, septic

What causes the skin to be warm in distributive shock?

vasodilation

What type of shock is caused by large amounts of histamine causing vasodilation and low BP?

distributive: anaphylactic

What type of shock is seen in head/spine injuries and is marked by a sudden loss of autonomic activity leading to vasodilation, pooling of blood in veins, and syncope?

distributive: neurogenic

What form of shock is the most common form of death in ICU’s?

distributive: septic

What type of shock results from inadequate pumping of the heart to meet resting metabolic demands?

cardiogenic

What additional symptoms are present in Cardiogenic shock?

congestion of lungs and viscera

What is the usual cause of cardiogenic shock?

LV infarct

DVTs increase risk for ___

pulmonary emboli

What are the two causes of obstructive shock?

pulm/vascular and mechanical

What causes mechanical obstructive shock?

filling (preload) problem

tension pneumothorax, pericardial tamponade, constrictive pericarditis, restrictive cardiomyopathy

What causes pulmonary/vascular obstructive shock?

right sided failure from a massive PE or pulmonary HTN

What vasoactive mediators are released in pulm/vascular obstructive shock?

serotonin and thromboxane → vasoconstriction

What is a stationary clot formed within a vessel or chamber of the heart?

thrombus

What vessels are the most commonly involved with a thrombus?

coronary arteries, cerebral arteries, mesenteric arteries, renal arteries

Thrombosis risk factors:

immobilization, metabolic syndrome, advanced age, tobacco use, previous thrombosis, cancer

What are the three factors of Virchow’s triad for a DVT?

venous stasis, vessel wall injury & inflammation, hypercoagulability

What are the possible outcomes for a thrombus?

lysis, propagation, organization, canalization, embolization

Symptoms of a DVT

unilateral swelling, heat and tenderness, ± Homan’s sign (squeeze calf for pain)

What causes PAD?

atherosclerosis