16. Integrative Cardiovascular Pathophysiology

What are the ABCD of drugs for cardiovascular issues?

A= ACE inhibitors; B= Beta blockers; C= CCBs; D= Diuretics

What organs/tissues are targeted for immediate changes to BP?

• Heart: cardiac output can be adjusted to change hydrostatic pressure

• Arteries/arterioles: responsible for total peripheral resistance (TPR)

What organs/tissues are targeted for long-term change to BP?

• Kidneys: responsible for blood volume

What is baroreflex?

Reflexive mechanism to maintain constant BP. Uses PNS and SNS with negative feedback loops.

Where are baroreceptors located?

In the Aortic arch and carotid sinus

What CN are the afferent portions of the baroreflex?

CN IX and X

What parts of the brain are responsible for the baroreflex?

• Medullary nucleus tractus solitarius

• Cardiovascular center of medulla and pons coordinate PNS and SNS regulation via sympathetic vasomotor center and cardiac control center

What is the efferent nerves of the baroreflex?

• Sympathetic stimulation (NorE then Epi)

• PNS inhibition

What is the mechanism for baroreflex?

1. Decrease in BP (MAP <100mmHg)

2. Decreased stretch of baroreceptors in carotid and aortic arch

3. Less stretch causes the firing of CN IX and X to medullary nucleus tractus solitarius

4. SNS and PNS cause various effects: increase in chronotropy, increase inotropy, increase preload; increase total peripheral resistance; Volume expansion via renal artery constriction and renin secretion

5. Stimulates Endocrine system for redundancy: Epinephrine release and renin release

6. BP increased

What are Antidiuretic hormone (ADH) and arginine vasopressin (AVP)

Peptide hormone from the posterior pituitary that regulates blood pressure (vasopressin) and osmolarity (antidiuretic)

What does vasopressin do?

It cause vasoconstrction and volume expansion by increasing water reabsorption

What does antidiuretic hormone do?

Decreases osmolarity by increasing water reabsorption in kidneys

When is ADH and AVP secreted and from where?

ADH and AVP is secreted when there is low BP or high osmolarity sensed by neurons of the hypothalamus. The posterior pituitary gland is then stimulated to secrete ADH/AVP, causing an increase in BP.

What stimulates the neurons of the hypothalamus to let it know the BP is low/high osmolarity?

• High SNS

• High Angiotensin II

• Hyperosmotic plasma

What is the Renin-Angiotensin-Aldosterone system (RAAS) do?

A powerful hormon system that is responsible for long-term control of blood volume and BP

What is initially secreted in the RAAS?

Renin is secreted first to start RAAS

What does RAAS target?

SNS, ADH/AVP, Vessels, and salt to increase BP and osmolarity

What is the mechanism of RAAS?

1. Low BP sensed by juxtaglomerular cells in the kidneys

2. Renin is secreted into blood and converts angiotensinogen to angiotensin I

3. Ang I is converted to Ang II by Angiotensin Converting Enzyme (ACE) in pulmonary capillaries

4. Ang II stimulates secretion of aldosterone from zona glomerulosa of the adrenal cortex

5. Functions of all 3 hormones increase BP

How do juxtaglomerular cells sense low BP?

• SNS (Beta 1) stimulation

• Respond to low Cl conc in tubule

• Baroreceptors

What effects does Renin have?

• Increase TPR

• Causes volume expansion

• Stimulates Ang II production

What effects does Ang II have?

• Stimulates SNS

• Stimulates ADH/AVP from posterior pituitary

• Increases TPR

• Volume Expansion

• Stimulates aldosterone

What effects does Aldosterone have?

• Volume expansion

• Regulates osmolarity via sodium and potassium exchange

• Regulates electrolytes via sodium and potassium exchange

What is the function of Atrial Natriuretic Peptide?

• Hormone protects heart from high afterload to decrease hypertrophy

• Decreases BP

• Counter-regulatory system to RAAS

What is the mechanism for Atrial natriuretic peptide?

1. High BP causes sheer stress in right atrium, stimulating ANP secretion

2. ANP then causes vasodilation and diuresis

   • Vasodilation increases urine output and decreases blood volume

   • Natiuresis: salt and water wasting

3. BP decreases

What are some etiologies for hypotension?

• Shock:

  • Septic shock d/t LPS release

  • Anaphylactic shock d/t severe allergic reaction

  • Neurogenic shock d/t trauma to the brain or spinal cord

  • Cardiogenic shock d/t heart failure or arrest

  • Hypovolemic shock d/t hemorrhage

• Diurnal effects (Nadir)

• Therapeutics for HTN (at night before bed)

How is low BP compensated?

• Increasing cardiac output

  • increase heart rate

  • increase inotropy

  • increase preload

• Increasing TPR

  • vasoconstriction

• Volume expansion

  • Decrease filtration (GFR)

  • Tubule

    • increase sodium and water reabsorption

What is the goal of BP?

To ensure proper nutrient delivery

What does HTN cause?

End-organ damage with increased risk for CVA and CHF

What are the types of hypertension?

• Essential or primary HTN

• Secondary HTN

What are some factors that increases risk for primary HTN?

• Non-modifiable:

  • age 65+

  • rage: african americans

  • FHx

• Modifiable:

  • Overweight

  • smoking

  • high sodium

  • stress

  • alcohol intake

What are some factors that increase the risk of secondary HTN?

• Pheochromocytoma

• Conn’s Syndrome

• Cushing’s syndrome

• Hyperthyroidism

• Acromegaly/gigantism

• sympathetic dysregulation

• renal disease

• obstructive sleep apnea

• medications: Estrogens; Decongestants; NSAIDs; Recreational drugs (Cocaine)

What are the stages of blood pressure?

What needs to be present for stage 1 HTN patient to receive further treatment?

• Hx: Heart attack/stroke

• Diabetes mellitus

• Renal disease

• Hyperlipidemia

What is done for stage 2 HTN?

2 or more medications, often combined for compliance

What is hypertensive crisis:

When >180/120. Risks of organ damage and complications. Crisis retests after 5 minutes. Call 911 or have family take to emergency room.

When does malignant HTN occur?

During hypertensive crisis, where extremely high BP causes organ damage.

What is malignant hypertensive retinopathy?

When there is bilateral swelling of the optic nerve head (not papilledema) causing: Reduced vision, eye pain, flame-shaped hemorrhages, and headaches.

What is the body’s response to HTN?

• Heart decrease CO: Decrease HR, Inotropy, and preload

• Vasodilation

• Kidney decreases blood volume

  • Increase filtration

  • Decrease sodium and water reabsorption to increase excretion

What are some lifestyle changes to decrease BP?

• smoking cessation

• alcohol rehabilitation

• diabetes in control

• low salt diet

• eat better

• exercise

What are some cardioinhibitory drugs for HTN?

Negative iontropic and chronotropic:

• Beta blockers: metoprolol

• CCB: Verapamil (phenylalkylamine) and Diltiazem (benzothiazepine)

Other:

• Cardiac Glycosides (digoxin, oubain)

• Nitroglycerin (NO)

What are some vasodilators to treat HTN?

• CCB: amlodipine - dihydropyridine; diltazem - benzothiazepine

• Alpha1 blockers: terazosin (hytrin)

• Renin receptor blockers

• Angiotensin II receptor blockers: losartan

• ACE inhibitors: Lotensin (benazepril)

• Vasopression Receptor Blockers (vaptan)

• Endothelin receptor blockers

• ANP agonists

What are some diuretics to treat HTN?

• Furosemide

• Thiazide

• Spironolactone

• Amiloride

• Vaptan

• Acetazolamide

• Flosin: SGLT-2 blockers