HES 311: Cardiovascular Disorders II

• HES 311 - Pathophysiology covers Cardiovascular System Disorders II
• The material covered includes disorders of blood pressure and heart pathologies
• Key content is based on Gould's Patho Chapter 12
• UBC Okanagan Campus and the City of Kelowna are located on the traditional, ancestral, and unceded territory of the Syilx Okanagan Nation

Determinants of Blood Pressure

• Mean Arterial Pressure (MAP) is the product of Cardiac Output (CO) and Peripheral Resistance (PR)
• Cardiac output relies on both Stroke Volume and Heart Rate
• Peripheral resistance depends on the the radius of small arteries

Stroke Volume Factors

• Preload is the among of blood filling the ventricle, also known as End-Diastolic volume, and is modulated by blood volume
• Contractility is the ventricular force of contraction that determines the blood ejected in each stroke and is modulated by the SNS (increased contractility)

Heart Rate Factors

• Heart Rate (HR) is modulated by the SNS (increased HR) and the PNS (decreased HR)

Peripheral Resistance Factors

• Peripheral Resistance is porportional to 1/radius^4
• Radius of the small arteries modulates peripheral resistance
• Vasoconstriction decreases the radius, increasing vascular resistance
• Vasodilation increases the radius, decreasing vascular resistance

Mechanisms of Blood Pressure Regulation

• Baroreceptors send signals to the medulla to modify heart rate (HR), stroke volume (SV), and vascular resistance via the SNS and PNS output
• Renal/Hormonal regulation involves regulating blood volume via filtration rate into the nephron
• The filtration rate directly impacts Na+ and H2O reabsorption/excretion
• Renin release activates the Renin-Angiotensin-Aldosterone System(RAAS)
• ADH release promotes H2O reabsorption
• Endothelial cells vasodilation via Nitric Oxide and vasoconstriction via Endothelin

The Renin-Angiotensin-Aldosterone System (RAAS)

• RAAS overall net result = Increased MAP
• Decreased MAP and filtration into the kidneys
• Renin is released by the kidneys, which then increases Angiotensinogen into Antiotensin I
• ACE converts Angiotensin I into Angiotensin II
• Angiotensin-converting enzyme (ACE) is found on endothelial cells of the vasculature
• Angiotensin II causes thirst and vasoconstriction
• Thirst increases Blood volume
• Aldosterone gets released, increasing Na+ and H2O reabsorption by the kidneys
• Vasoconstriction increases Peripheral Vascular Resistance

Primary Hypertension - Pathophysiology

• Increased blood volume is due to a defect in Na+ handling, leading to excess Na+ intake and/or reabsorption
• Primary Hypertension has increased peripheral vascular resistance
• Endothelial cell dysfunction promotes vasoconstriction
• The activation of RAAS causes higher blood pressure
• Increased activation of the SNS increases cardiac output and peripheral resistance

Hypertension - Treatments

• Hypertension can be managed with pharmaceuticals like Vasodilators, Diuretics, and Cardioinhibitory Drugs
• Dietary Approaches to Stop Hypertension(DASH) diet, involves reducing Na+ and caffeine intake
• Lifestyle modifications like increasing physical activity, smoking cessation, decreasing alcohol intake, and reducing stress

Exercise as Treatment for Hypertension

• Post-exercise hypotension is a BP-lowering physiological response after exercise that can be observed following multiple types of exercise, likley due to vasodilation
• Exercise can be a treatment for reducing BP with a dose of 20-30 minutes per session daily

Acute Hypotension (Shock)

• Shock happens when there is inadequate tissue perfusion, leading to tissue ischemia/hypoxia, and cellular damage
• Mean Arterial Pressure (MAP) = Cardiac Output (CO) x Systemic Vascular Resistance (R)
• General signs/symptoms of shock include tachycardia, decreased urine output, dizziness, feeling faint, and altered mental status
• Main classifications of shock are: hypovolemic, cardiogenic, anaphylactic, septic, and neurogenic

Cold Shock

• Decreased cardiac output initiates 'Cold' Shock
• The body compensates with vasoconstriction, which increases resistance and increases MAP
• Blood flow is redirected to vital organs
• Hemmorhagic and non-hemorrhagic (diarrhea, vomiting) initiate hypovolemic shock
• Decreased blood volume, resulting in decreased venous return and decreased cardiac output
• Cardiogenic shock is due to heart disfunction, with the decreased ability for the heart to pump(CO)
• Potential causes of cardiogenic shock are heart failure, arrhythmia, myocardial infarction, and valve dysfunction

Warm Shock: Distributive

• Systemic vascular resistance decreases due to peripheral vasodilation, in turn body compensate with increased heart rate
• Anaphylactic shock is an extreme reaction to an allergen
• Mast cells release histamine & bradykinin that leads to increased vasodilation, edema, and bronchoconstriction
• Treatment involves IM Epinephrine to increase CO and cause smooth muscle relaxation (airways) and vasoconstriction
• Septic Shock is due to an infection in the bloodstream
• Macrophage activation triggers cytokine release, leading to increased vasodilation
• Treatment is with IV fluids & antibiotics

Neurogenic Shock

• Autonomic balance tips toward parasympathetic nervous system activity, leading to vasodilation and bradycardia
• Neurogenic shock causes can be Spinal Cord Injury, Traumatic Brain Injury, or a Vasovagal reflex
• Vasovagal reflex is caused by an overreaction of the vagus nerve or an abnormal response to pain, fear, emotion, sight of blood, etc. (parasympathetic)`

Orthostatic Hypotension

• Sudden and Sustained drop in blood pressure caused by standing up from a sitting/lying position
• Systolic blood pressure (SBP) decreases by at least 20mmHg, or Diastolic blood pressure (DBP) decreases by at least 10mmHg for the first 3 minutes in an upright position
• Causes include impaired baroreceptor reflex function, hypovolemia, and blood pooling in the legs which are most commonly due to medication
• There is an increased Orthostatic Hypotension risk in older adults
• Signs and Symptoms include pallor, blurred vision, feeling faint, dizziness, and nausea
• Treatment involves: water intake, salt intake, compression stockings, sleeping in a slightly inclined position, and leg resistance exercises

Part 2: Heart Pathologies

• Discusses various heart conditions, focusing on arrhythmias

Cardiac Conduction Review

• Normal Sinus Rhythm is determined by the action potential frequency of the Sinoatrial Node cells, with a rate of 60-100 BPM

Pathway of Excitation through the Heart

• Electrical signaling begins in the SA node
• Purple shaded areas represent the spread of depolarization across the heart
• The signal is the trigger for contraction of atrial and then ventricular myocytes
• Conduction slows at the AV node, which allows for blood to flow, and then is given the electrical signal to contract

Cardiac Arrhythmias

• Abormalities in either rate or electrical conduction leads to disorganized contractions and impaired cardiac output

Abnormalities in Heart Rate (HR)

• Sinus Tachycardia is when HR is faster than normal (>100 BPM at rest), and Sinus Bradycardia is when HR is slower than normal (<60 BPM at rest)
• Issues are due to the heart Automaticity

Automaticity Factors

• Sinoatrial node (SAN) automatically sets the pace of the heart regardless of nervous system input
• Epinephrine & Norepinephrine release onto SA node cells & bind to Beta-adrenergic receptors: increased phase 4 slope leads to increased SA Node AP frequency, increased Phase 4 slope, leading to increased SA Node AP Frequency
• Acetylcholine releases onto the SA node cells & binds to 'muscarinic' receptors; decreased phase 4 slope leads to decreased SA Node AP frequency

Abnormal Automaticity

• Increased Automaticity comes from increased Sympathetic NS activity
• This can be caused by Hypovolemia
• Hypercapnia (high blood CO2) or Hypoxia (low blood O2) can cause Abnormal Automaticity
• Pain or Anxiety can cuase Abnormal Automaticity
• Increased Metabolic activity of pacemaker cells can cause Abnormal Automaticity
• Drugs that act like NE or Epinephrine (Sympathomimetics)

Decreased Automaticity

• Decreased Automaticity is due to to increased Parasympathetic NS activity
• Decreased metabolic acitivity in pacemaker cells, or electrolyte imblance
• Heart damage or disease

Arrhythmias due to Altered Electrical Conduction

• Irritable area somewhere in the atria or ventricles, triggering ‘ectopic firing' (spontaneous action potentials fired outside of normal stimulus from conduction system)
• Abnormal conduction pathway forms either due to an additional 'accessory' path or a block in the regular path

Common Arrhythmias

• Electrical signal initiates by Purkinje fibers instead of the SA node, known as premature ventricular contractions
• Ventricles contract prematurely
• New conduction pathway begins somewhere in atria (outside normal conduction,) sending a new signal trails down to the ventricles, known as paroxysmal supraventricular tachycardia

Clinical Arrythmias

• A type of Fibrillation includes electrical activity independent of the SA node leading to chaotic contractions
• Atrial fibrillation still functions as a pump, and palpitations, chest discomfort, and shortness of breath can result
• Ventricular fibrillation is when theheart does not function as an effective pump
• Collapse and electrical shock are required to reset normal sinus rhythm

Treatment for Arrhythmias

• Beta Blockers(block SNS effect) and various Na+, K+, or CA2+ channel blockers are drugs that control heart rate and rhythm
• Ablation therapy maps out the electrical activity of the heart to destroy the specific region of the heart tissue that is causing the issue
• A Pacemaker regulates the rhythm through low energy electrical pulses
• 'Implantable Cardio defibrillator' (ICD) senses a stopped heart and delivers an electrical shock to restart the heart