Cardio Exam #1

Changes in heart rate via an increase or decrease of the SA node. Primarily influenced by rate of phase 4 in pacemaker cells (inward Na⁺ current); also rate of phase 0 in AV node of pacemaker cells (inward Ca²⁺ current).

Changes in conduction velocity primarily at the AV node and influences the PR interval on EKG. Negative dromotropic effect slows conduction from atrium thru the AV node, prolonging the PR interval. Primarily influenced rate of phase 0 in AV node of pacemaker cells (inward Ca²⁺ current).

Force of contraction. Influenced by preload or EDV, the free cytosolic Ca²⁺ concentrations, sarcomere length.

Calcium

Skeletal muscle predominantly utilizes pools of calcium stored in the SR rather than calcium moving thru VG calcium channels to induce contraction. SR is MUCH larger in skeletal muscle as compared to smooth muscle.

The EDV more specifically related to the right atrial pressure.

Preload will increase which will stretch the sarcomere further and increasing the contractility (forward flow).

Baroreceptor reflex is activated resulting in reflex tachycardia and angina.

The reflected aortic pressures that must be overcome by the left ventricle or pulmonary artery pressures that must be overcome by the right ventricle. Afterload increases work load and can worsen angina (if ischemic heart disease is present).

• Provide sufficient blood to body tissues
• Convery a highly pulsatile flow into a more continuous flow at the level of smaller arteries

• It is dampened by elastin-containing central arteries (thoracic aorta and proximal branches).
• 1. Expansion during systole to store some of each stroke volume.
• 2. Recoil during diastole.

PP = SBP-DBP; assumes a constant CO and HR

Decreased elasticity or increased arterial stiffness

Average blood pressure over time; 100 mmHg

• Norepinephrine (NE)
• Epinephrine (Epi)
• Dopamine (DA)

• Nicotine
• Angiotensin II

Alpha 1 adrenoreceptors

Alpha 2 adrenoreceptors

Stimulates

Inhibits

Stimulates

Inhibits

Beta 1 adrenoreceptors

Stimulates

Inhibits

Inhibits

• Found in vascular smooth muscle and heart.
• Response is constriction (+ inotropic effect)

• Found in brain, sympathetic nerve endings, and kidneys.
• Response is inhibition of NE release and renin release.

• Found in heart and kidneys.
• Response is (+) inotropic and chronotropic effect, cell growth, hypertrophy, and renin is released.

• Found in bronchial smooth muscle of the lungs.
• Response is relaxation.

Presynaptic

Postsynaptic

Postsynaptic

• 1. Renal baroreceptor - respond to volume
• 2. Macula densa - distal tubular salt sensor
• 3. Renal nerves - sympathetic outflow
• 4. Humoral factors - angiontensin, endothelin, ANP

Renin

• 1. Stimultes vascular smooth muscle contraction and aldosterone synthesis.
• 2. Stimulates formation of superoxide which deactivates NO (vasodilator).
• 3. Stimulates the activation, release, and synthesis of several growth factors.

Antagonism of all the effects of binding to AT1. Major rationale for propsed superiority of ARBs.

• Vasoconstriction
• Hypertrophy
• Hyperplasia

Prostaglandin, NO, and endothelin production

Extracellular matrix synthesis

• Strength of contraction
• Hypertrophy

Aggregation by catecholamines

Adhesion to vessel wall

Aldosterone secretion

Catecholamine release

Cortisol secretion

ADH release

Inhibits renin release

Sodium reabsorption

NE release

• Pressor center activation
• Baroreceptor blunting
• ADH synthesis
• Promotes thirst
• Prostaglandin release

Salt and water absorption

• Glycogenolysis
• Angiotensinogen synthesis

• Changes in:
• 1. blood pressure
• 2. local inflammation
• 3. fibrosis
• 4. remodeling

• peripheral veins and arterioles;
• HR, blood flow, and BP

Maintains SNS activity based on sensory information received from baroreceptors and chemoreceptors.

Coordinates BP thru alterations in neurohormonal release.

Alter CV function based on emotion and stress. So basically, it wigs the hell out when the ex-wife calls.

Drop in arterial pressure --> drop in the stretch on walls of carotid sinus --> decrease in firing of the carotid sinus nerve to the nucleus regions in the medulla oblongata --> decreaced outflow of the PNS to the heart via efferent vagus nerve and increase in SNS outflow down descending tract of intermediolateral column of gray matter in spinal cord --> some preganglionic nerve fibers synapse eventually to heart and blood vessels where post-ganglionic sympathetic nerve fibers release NE and other preganglionic sympathetic nerves synapse on adrenal glands releasing both NE and Epi into circulation

High pressure

• Aortic arch and carotid bifurcations
• Kidneys

Low pressure

• Cardiac atria and ventricles
• Lungs

Hell no! Are you crazy?

Best get on that with the quickness.

• Isolated Systolic Hypertension (ISH)
• These patients are salt sensitive.

• 1. Aging
• 2. Obesity
• 3. Sleep Apnea

Diastolic hypertension. Associated with increased vascular resistance and MAP.

• Resurgence of ISH due to central artery stiffness.
• Significance: DBP is highly dependent on the stiffness of central arteries. Elasticity in these is lost as we age, manifesting as a rise in SBP, a decrease in DBP, and thus a rise in pulse pressure.

False. 78% of men and 65% of women with HTN are overweight or obese. Get off the couch fatty and run a lap around the house!

• 1. Insulin resistance
• 2. Fluid volume
• 3. SNS
• 4. Leptin resistance/hyperleptinemia
• 5. RAAS
• 6. Inflammation

• 1. Insulin increases absorption of Na⁺ in the distal nephron resulting in water retention (increased volume).
• 2. Insulin increases adrenergic activity.
• 3. Insulin causes vascular smooth muscle hypertrophy.
• 4. Insulin resistance/hyperinsulinemia impairs insulin-mediated vascular signaling pathways associated with vasorelaxation.

They have a higher total body volume which largely distributes centrally and leads to augmented venous return, ventricular filling, and cardiac output.

• 1. Peripheral catecholamine levels/sympathetic activity is not always increased in obese patients.
• 2. Organ-specific sympathetic activity in muscle and kidneys is elevated.
• 3. Increased activity in the kidneys is likely related to elevated leptin levels.

• Hormone produced by adipose tissue that is responsible fore regulating food intake.
• Contributes to HTN due to increasing sympathetic activity.
• Acute infusion leads to natriuresis and NO production.
• Chronic infusion decreases natriuresis and NO production and increases renal sympathetic activity and BP.
• Correlation between leptin levels, adipose tissue mass, and HTN suggests a leptin resistance mechanism, however this concept is still being researched and not sure at this time.

BMI is positively correlated with plasma angiotensinogen, plasma renin activity, plasma ACE concentration, and plasma aldosterone.

Inflammatory cytokines are released from adipose tissue that initiate and/or sustain the low-grade inflammatory state characteristic of the progression of HTN.

True.

• Apnea and hypopnea produce transient hyposemia, hypercapnia, and respiratory acidosis, and each event triggers activation of SNS. Enhanced sympathetic activity is present during sleep and wake times.
• Alteration of peripheral (carotid) and central regulation of sympathetic outflow contribute to elevated arterial pressure.

False. These patients have ELEVATED angiotensin II and aldosterone levels.

Hypoxia leads to endothelial dysfunction - endothelin increase, NO decrease

• Leads to increased carotid intima-media thickness and arterial stiffness.
• 1. Hypoxia stimulates PDGF, endothelin-1, VEGF; 2. alters balance between extracellurlar matrix metalloproteinases/their inhibitors; 3. stimulates vascular RAS via cyclical stretch of vascular smooth muscle; and 4. causes hypertrophy secondary to chronic sympathetic activation.

• 1. Heart
• 2. Brain
• 3. Kidney
• 4. Eye

• 1. White coat HTN - lame crutch to use
• 2. Masked HTN - not as in Freddy Kruger or Jason
• 3. Anxiety and Stress - avoid the ex
• 4. Obesity, fat distribution, & insulin resistance - avoid McD's
• 5. Physical activity - turn off Jersey Shore and The Real Housewives of BFE
• 6. Diet & alcohol - moderation is the key
• 7. Sodium and Potassium - put down the salt and pick up a banana (just don't eat the whole banana tree)
• 8. Calcium and Magnesium

120-139/80-89 mmHg

140-159/90-99 mmHg

160+/100+ mmHg

• Blockade of beta-1 receptors in kidney decreases renin release.
• The decreased NE binding results in lower HR and lower CO.
• Na⁺ current slows down --> HR slows down --> slower firing of action potentials

• 1. Initiate/adjust with caution in patients with HF (no crackles!)
• 2. Avoid in asthma/COPD patients unless benefit > potential risks
• 3. Avoid abrupt discontinuation - relfex tachycardia

Norepinephrine (NE)

• Agonism of alpha-2 receptors turns of NE release.
• Example: clonidine

• Atenolol, metoprolol, and bisoprolol
• beta-1 receptors
• bradycardia, ED, insomnia, heart palpitations, dizziness

• Propranolol and nadolol
• beta-1 and beta-2 receptors
• bronchoconstriction

Carvedilol and labetalol

Reduction in SVR

False. They are not used primarily for HTN but are used if patient has BPH.

True.

False. They do NOT respond well to ACEi monotherapy.

0.8mg/day; usually divided BID

0.6mg/24 hrs; patches changed once weekly. Don't have a "senior moment" and forget to remove old patch before applying a new patch.

• Orthostasis
• Drowsiness
• Dizziness

• Bind to receptors on the luminal side of the DCT
• Compete for the Cl^- binding site, thus inhibiting the Na⁺/Cl^- symporter causing increased excretion of Na⁺, Cl^-, H₂0, and K⁺

Reduced extracellular and plasma fluid volume (Na⁺ and H₂O

12.5-25 mg/day

• African Americans (+)
• Elderly (-) --> hyponatremia, hypokalemia

• Binds receptors on the luminal side of the thick ascending limb of the loop of Henle.
• Compete for the Cl^- binding site of the Na⁺, K⁺, 2Cl^- symporter causing increased excretion of Na⁺, Cl^-, H₂O, K⁺, Mg²⁺, Ca²⁺

True.

Block Na⁺ channels in the laste distal tubule and collecting duct.

• Bind the mineralocorticoid receptor in the late distal tubule and collecting duct.
• Net result is blockade of sodium movement from luminal to interstitial space through dosium channels and pumps.

In the early proximal convoluted tubule (PCT)

In the distal convoluted tubule (DCT)

In the thick ascending loop of Henle

In the late DCT and collecting duct

In the late DCT and collecting duct

• Inhibits the conversion of Angiotensin I to Angiotensin II which causes a drop in SVR due to vasoconstriction and a rise in Na⁺ and H₂O excretion due to a drop in aldosterone.
• Inhibits conversion of active bradykinin to inactive bradykinin.