Pathopharm Cardiovascular

Function of circulatory system

-Deliver oxygen, nutrients,
-Remove CO2 and metabolic waste products

Circulatory system composition

-Vessels, fluids, pumps
-Arteries, arterioles, capillaries, venules, veins,

Arteries

-Transport blood to tissues
-High pressure ssytem

Arterioles

-Regulates amount of blood flow to tissue

Capillaries

-Exchange of fluid, oxygen, nutrients, hormones, and waste products

Venules

-Collect blood from capillaries

Veins

-Transport blood back to heart
-Reservoir for blood
-low pressure system

Blood flow

-Forces that drive flow are greater than resisstance to flow

Resistance

-Opposition to force
-Things that affect: length, diameter, viscocity of blood

Normal viscosity of blood

-Normal is 35-50%

Liters pumped out heart

-5 l per min
-2.4 ounces every contraction

Right heart

-Thin walled ventricle
-Low pressure pump
-Receives from systemic circulation
-Pumps to lungs

Left Heart

-Ventricle muscle is thick
-High pressure pump
-Receives oxygenated blood from lungs
-Pumps to systemic circulation

Pericardium

-Outer layer of heart
-Contains pain receptors, changes in blood pressure and heart rate
-Pacts as a physical barrier

Myocardium

-Thick middle layer
-Composed of cardiac muscle

Endocardium

-Internal lining of heart
-Connects with arteries and capillaries and vein to create continuous closed system

1 Diastole

-Atria fill
-All valves are closed

2 Diastole

-Increased atrial pressure, opens AV valves, ventricles fill

3. Systole begins

-Atria contract and empty
-Ventricles are full

4. Systole

-Ventricles begin contraction
-Pressure closes AV valve
-Atria relax

5. Systole

-Ventricles contract
-Increased pressure in ventricles
-Aortic and pulmonic valves open
-Blood ejected into aorta and pulmonary artery

6. Diastole

-Ventricles empty
-Ventricles relax
-Semilunar valves close

Oxygen supply to myocardium

-Right coronary artery: supplies the upper right ventricle, right marginal branch supplies right ventricle, posterior descending supplies smaller branches
-Left coronary artery: left anterior descending supplies both ventricles

Collateral circulation

-circulation by secondary channels after obstruction of the principal channel supplying the heart

Myocardial metabolism

-Cardiac muscle depends on constant ATP
-Needs glucose, fatty acids, lactate

Energy Produced used for

-Muscle contraction, relaxation
-electrical excitation

Cardiac output

-Volume of blood ejected by a ventricle in 1 minute
-Normal amount is 5 L

Cardiac output equation

CO= Heart rate x stroke volume

Factors that determine cardiac output

-Preload
-Afterload
-Myocardial contractiliity
-Heart rate

Stroke volume

-Amount of blood ejected from ventricle with each contraction
-Volume of blood at the end is subtracted by volume right before contraction

Stroke volume equation

SV= end diastolic volume- end systolic volume

Ejection fraction

-Fraction of blood ejected by left ventricle during systole
-Cardiac echogram
-Normal is 60-70%

Ejection fraction equation

-EF= SV/EDV

Increased Ejection fraction

-Sympathetic stimulation

Decreased EF

-Ventricular heart failure

Preload

-amount the ventricles stretch at the end of diastole, end diastolic volume
-Factors: amount of venous return, blood left in ventricle after systole

Factors that increase preload

-Increased venous pressure
-Vasoconstriction
-Increased total blood volume
-Increased aortic pressure
-decreased heart rate

Factors that decrease preload

-Increased heart
-Decreased blood volume
-Standing
-Impaired atrial contractions
-Ventricular diastolic failure
-Steenosis of AV valves

Starling mechanism

-Relationship between length of muscle fibers and tension during systole
-Increased preload causes rubber band to stretch, beyond certain point the heart will over stretch or break

Afterload

-Resistance to ejection of blood from left ventricle
-Telling on myocardial energy consumption
-Vascular resistance, high vascular resistance increases afterload

Factors that increase afterload

-Aortic and pulmonary stenosis
-Systemic or pulmonary hypertension
-Increased systemic vascular resistance

2 ways cardiac output is controlled

Extrinsic and intrinsic

Extrinsic control of heart

-Control outside
-Autonomic nervous system
-Hormones
-Vessels

Intrinsic control

-Control in heart
-Rhythm, rate
-Force of contraction
-End diastolic volume

Sympathetic stimulation of heart

-Increased myocardial contractility
-Increased heart rate
-Increased venous return

Parasympathetic stimulation

-Decrease heart rate

Thyroid hormone

-Increases heart rate

Epinephrine

-Increases heart rate

Cardiac reserve

-Ability for heart to increase output due to increased demand

Myocardial oxygen supply

-Coronary artery
-Diastolic pressure
-Diastolic filling time
-O2

Blood pressure

-Pressure in the aorta caused by left ventricle as blood is pumped

Systolic blood pressure

Arterial pressure during ventricular contraction
-Afecteed by SV, aortic stiffness, and ejection velocity

Diastolic blood pressure

-Atrial pressure during ventricular releaxation

Mean arterial pressure

diastolic pressure + 1/3 pulse pressure

Baroreceptor control of bp

-Stretch receptors
-Aortic and carotid arteries
-Chemoreceptors

Orthostatic hypotension

-Decrease in both systolic and diastolic pressure
-Occurs when moving from laying and standing

Orthostatic hypotension causes

-Immobile for long time
-Dehydration or volume loss
-Medication

Orthostatic hypotension symptoms

-Dizziness, blurred vision

Orthostatic hypotension treatment

-Slow transitions
-Fluids
-Medication adjustments

Primary hypertension risk factors

-Aging
-Male
-African American
-Family history
-Smoking
-Obesity
-Stress

Idiopathic Hypertension

-Chronic, progressive
-Often no symptoms
-Sustained BP greater than

Patho of HTN

-Multi-causal increase in tpr
-Sclerotic changes
-Compensatory rise in BP to move move blood against resistance
-Possible defecet in sodium excretion (increase TBW, renin)

Secondary Hypertension

-Identifiable causes (renal, vascular, endocrine)
Possible to treat cause directly

Secondary HTN genetiics

-African americans develop at younger age, affects more women, produce less renin, increased risk of taking angioedema when taking ACE inhibitors

Hispanic americans and HTN

-Less likely to receive treatment treatment
-Lower ratees of BP control

Gender differences in HTN

-More common in men before 45
-More common in women after 64
-Women who take oral contraceptives

Complicated HTN

-Caused by high pressure damage to blood vessel wall
-Smooth muscle hypertrophy with fibrosis (hardening) of tunica intima and media

Malignant HTN

-Rapidly progressing HTN

Treatment of HTN

-Lifestyle changes
-Stop smoking
-Sodium restriction
-Alcohol restriction
-Exercise
-Weight loss if needed
-Proper K and Ca intake

Medication options for HTN

-Meds that activate RAAS
-Direct vasodilators

ACE inhibitor MOA

-Reduces levels of Angiotensin II by blocking conversion of Angiotensin I to II in the lungs
-Increases bradykinin

ACE Inhibitor pharmacokinetics

-Most often oral
-Converted to active form iin liver
-Excreted by kidneys

ACE Inhibitor adverse effects

-Persistent, dry, irritating, nonproductive cough
-Hyperkalemia
-Renal Failure
-Angioedema
-Injury in pregnancy

Decrease in angiotensin II leads to

-Vasodilation
-Lowered blood volume
-Lowered cardiac and vascular remodeling
-Potassium retention
-Fetal injury

Increased bradykinin leads to

-Vasodilation
-Cough
-Angioedema

ACE-I drugs

-End in -pril
-Lisinopril
-Enalapril
-Captopril
-Ramipril
-Drug of CHOICE

ARBs

-Angiotensin receptor blockers

MOA of ARBs

-Block access of angiotensin II to receptor in blood vessels
-causes dilation of arterioles and veins
-Preccent against changes in heart structure
-Reduce excretion of potassium
-Decrease release of aldosterone
-Increase excretion of sodium and water

Adverse effects of ARBs

-Hyperkalemia, renal failure, hypotension
-Low risk of angioedema
-DOESN'T cause cough

ARB drugs

-Losartan
-Valsartan
-Candesartan
-SARTANS

Direct renin inhibitors MOA

-Binds tightly with renin and prevents cleavage of angiotensinogen into angiotensin I

DRI patient teaching

-Don't take with fatty meal, decreases bioavailability

DRI adverse effects

-Angioedema
-Cough
-Diarrhea
-Hyperkalemia
-Fetal injury

DRI drug

-Aliskiren

Aldosterone antagonists

-Used to treat hypertension and heart failure

Aldosterone antagonists MOA

-Blocks receptors for aldosterone in kidney
-Promotes retention of potassium
-Promotes excretion of sodium and water

Spironolactone

-Type of aldosterone antagonist
-Binds with other steroid hormones
-More side effects

Eplerenone

-Selective aldosterone receptor blocker
-less selective so less side effects

Vasodilators

-Reduce peripheral resistance thus reducing work load of heart
-Dilate coronary vessels, better balance of O2

Prazosin MOA

-Dilates both arterioles and veins

Hydralazine MOA

-Dilate just arteries and decrease afterload

Nitroglycerin MOA

-Dilation of veins, decreases preload

Vasodilator adverse effects

-Postural hypotension
-Reflex tachycardia
-expansion of blood volume

Hydralazine therapeutic uses

-Essential hypertension
-Hypertensive crisis
-Heart failure

Hydralazine adverse effects

-Reflex tachycardia
-Increased blood volume
-Systemic lupus ` syndrome
-Headache, weakness, fatigue

Hydralazine drug interactions

-Don't take with other hypertensive agents
-combine with beta blocker to prevent tachycardia and diuretics to prevent water retention

Sodium nitroprusside

-Fastest-acting hypertensive agent
-causes venous and arteriolar dilation
-IV infusion
-Immediate onset
-Used in emergencies

Adverse effects of sodium nitroprusside

-Excessive hypotension
-Cyanide poisoning
-Thiocyanate toxicity after 3 days (disorientation, psychosis, delirium)

What is heart failure

-Ventricular dysfunction
-Reduced cardiac output
-Insufficient tissue perfusion
-Fluid retention
-Instability of cardiac output to meet tissues
-Output of ventricles is less than inflow

Symptoms of heart failure

-Edema and weight gain, secondary to fluid retention
-Tachycardia
-Increased heart size
-Oliguria due to decreased renal perfusion