Hemodynamics and Blood Pressure

Hemodynamics and Blood Pressure 

Understanding hemodynamics—the study of blood flow through the cardiovascular system—is fundamental for pharmacy students. This knowledge forms the basis for comprehending how cardiovascular drugs work and how various disease states affect circulation. 

What is Blood Flow?

  • Blood flow is the volume of blood moving through a tissue per unit time (mL/min).

  • Total blood flow equals cardiac output (CO), the volume pumped by the heart each minute.

    • The Fundamental Equation

    Cardiac output depends on two key factors:

    CO = HR × SV

    Where:

    • HR = Heart Rate (beats per minute)
    • SV = Stroke Volume (volume of blood ejected per beat)

    Factors Determining Blood Flow Distribution

    Blood flow to various tissues depends on two critical factors:

    1. Pressure difference - Blood flows from regions of higher pressure to regions of lower pressure. The greater the pressure difference, the greater the blood flow.

    2. Vascular resistance - The opposition to blood flow in specific blood vessels. Higher resistance results in smaller blood flow.



    Blood Pressure: The Driving Force

    Definition and Generation

    Blood pressure (BP) is the hydrostatic pressure exerted by blood on the walls of blood vessels. It is generated by ventricular contraction and is determined by three factors:

    1. Cardiac output
    2. Blood volume
    3. Vascular resistance

    Blood Pressure Throughout the Circulation

    Blood pressure varies significantly throughout the cardiovascular system:

    • Aorta and large systemic arteries: Highest pressure

      • Systolic BP: ~110 mmHg (during ventricular contraction)
      • Diastolic BP: ~70 mmHg (during ventricular relaxation)

    Key Point: Blood pressure progressively decreases as distance from the left ventricle increases.

    Mean Arterial Pressure (MAP)

    MAP represents the average blood pressure in arteries and is calculated as:

    MAP = Diastolic BP + 1/3(Systolic BP - Diastolic BP)

    Example: For a BP of 110/70 mmHg: MAP = 70 + 1/3(110 - 70) = 70 + 13.3 = 83 mmHg

    Relationship Between MAP, CO, and Resistance

    Two important equations link these parameters:

    1. CO = MAP ÷ R
    2. MAP = CO × R (rearranged form)

    Clinical Implications:

    • If cardiac output increases (due to increased stroke volume or heart rate) while resistance remains constant, MAP rises
    • If cardiac output decreases while resistance remains constant, MAP falls

    Blood Volume and Blood Pressure

    The normal blood volume in adults is approximately 5 liters.

    • Decreased blood volume (e.g., hemorrhage >10% of total volume) → Decreased blood pressure
    • Increased blood volume (e.g., water retention) → Increased blood pressure


    Vascular Resistance: The Opposition to Flow

    Vascular resistance is the friction between blood and blood vessel walls. It depends on three factors:

    1. Size of the Blood Vessel Lumen

    This is the most important factor in determining resistance.

    Key Relationship: Resistance is inversely proportional to the fourth power of the vessel diameter:

    R ∝ 1/d⁴

    Clinical Example: If vessel diameter decreases by half, resistance increases 16-fold.

    • Vasoconstriction (narrowing) → Increased resistance → Increased blood pressure
    • Vasodilation (widening) → Decreased resistance → Decreased blood pressure

    2. Blood Viscosity

    Blood viscosity (thickness) depends on:

    • Ratio of red blood cells to plasma volume (primary factor)
    • Concentration of plasma proteins (secondary factor)

    Clinical Correlations:

    • Increased viscosity → Increased resistance → Increased blood pressure

      • Causes: Dehydration, polycythemia (elevated RBC count)

    • Decreased viscosity → Decreased resistance → Decreased blood pressure

      • Causes: Anemia, hemorrhage, plasma protein depletion

    3. Total Blood Vessel Length

    Resistance is directly proportional to vessel length.

    Clinical Example: Obesity and hypertension

    • Each kilogram (2.2 lb) of additional fat requires approximately 650 km (400 miles) of additional blood vessels
    • This increased vessel length contributes to elevated blood pressure in obese individuals

    Systemic Vascular Resistance (SVR)

    Also called total peripheral resistance (TPR), SVR represents all vascular resistances in systemic blood vessels.


    Venous Return: Getting Blood Back to the Heart

    Venous return is the volume of blood flowing back to the heart through systemic veins.

    Primary Driving Force

    The pressure difference between venules (~16 mmHg) and the right ventricle (0 mmHg) drives venous return.

    When standing, gravity opposes venous return from lower limbs. Two mechanisms assist the heart:

    1. Skeletal Muscle Pump

    Mechanism:

    1. At rest: Proximal and distal venous valves are open; blood flows upward toward the heart

    2. During muscle contraction (e.g., standing on tiptoes, walking):

      • Vein compression pushes blood through proximal valve ("milking" action)
      • Distal valve closes as blood pushes against it

    3. After muscle relaxation:

      • Pressure falls in compressed vein section
      • Proximal valve closes
      • Distal valve opens
      • Vein refills with blood from the foot

    Clinical Significance: Immobilized patients (injury, disease) lack muscle contractions, leading to slower venous return and potential circulation problems.

    2. Respiratory Pump

    Mechanism:

    • During inhalation:

      • Diaphragm moves downward
      • Thoracic cavity pressure decreases
      • Abdominal cavity pressure increases
      • Abdominal veins compress
      • Blood moves from compressed abdominal veins → decompressed thoracic veins → right atrium

    • During exhalation:

      • Pressures reverse
      • Venous valves prevent backflow from thoracic to abdominal veins

    Control of Blood Pressure: Integrated Regulation

    Blood pressure is regulated by interconnected negative feedback systems that adjust:

    1. Heart rate
    2. Stroke volume
    3. Systemic vascular resistance
    4. Blood volume

    These systems operate at different speeds:

    • Rapid adjustments: Neural mechanisms (seconds)
    • Long-term regulation: Hormonal and renal mechanisms (minutes to hours)

    The Cardiovascular (CV) Center

    Located in the medulla oblongata, the CV center contains groups of neurons that regulate:

    1. Heart rate

      • Cardiostimulatory center (increases HR)
      • Cardioinhibitory center (decreases HR)

    2. Ventricular contractility (force of contraction)

    3. Blood vessel diameter (collectively called the vasomotor center)

      • Vasoconstrictor center (narrows vessels)
      • Vasodilator center (widens vessels)

    Note: These neurons communicate with each other, function together, and are not clearly anatomically separated.

    Inputs to the CV Center

    1. Higher Brain Regions

    • Cerebral cortex: Anticipatory responses (e.g., heart rate increases before starting a race)
    • Limbic system: Emotional influences on cardiovascular function
    • Hypothalamus: Temperature regulation (e.g., vasodilation during exercise to dissipate heat)

    2. Sensory Receptors

    Three main types provide input:

    a) Proprioceptors

    • Monitor joint and muscle movements
    • Account for rapid heart rate increase at exercise onset

    b) Baroreceptors

    • Monitor pressure and stretch in blood vessel walls
    • Key players in blood pressure regulation

    c) Chemoreceptors

    • Monitor blood chemical composition (O₂, CO₂, H⁺)
    • Influence both cardiovascular and respiratory function

    Outputs from the CV Center

    The CV center controls cardiovascular function through the autonomic nervous system (ANS):

    Sympathetic Pathways

    1. To the heart (via cardiac accelerator nerves):

      • Increased stimulation → Increased heart rate and contractility
      • Decreased stimulation → Decreased heart rate and contractility

    2. To blood vessels (via vasomotor nerves):

      • Maintain vasomotor tone: moderate tonic vasoconstriction that sets resting systemic vascular resistance
      • Stimulation of veins → Constriction → Blood moves from venous reservoirs → Increased blood pressure

    Parasympathetic Pathways

    To the heart (via vagus nerves):

    • Stimulation → Decreased heart rate

    Key Concept: The heart is under dual control—opposing sympathetic (stimulatory) and parasympathetic (inhibitory) influences.


    Neural Regulation of Blood Pressure

    Baroreceptor Reflexes

    Baroreceptors are pressure-sensitive sensory receptors located in:

    • Aorta
    • Internal carotid arteries
    • Other large arteries in neck and chest

    1. Carotid Sinus Reflex

    Location: Carotid sinuses (small widenings of internal carotid arteries just above their branch from common carotid arteries)

    Function: Regulates blood pressure in the brain

    Pathway:

    • Blood pressure stretches carotid sinus wall → Stimulates baroreceptors
    • Nerve impulses travel via glossopharyngeal (IX) nerves → CV center in medulla

    2. Aortic Reflex

    Location: Ascending aorta and aortic arch

    Function: Regulates systemic blood pressure

    Pathway:

    • Aortic baroreceptors send impulses via vagus (X) nerves → CV center

    Response to Decreased Blood Pressure

    1. Baroreceptors stretched less → Send impulses at slower rate
    2. CV center responds:
      • Decreases parasympathetic stimulation (via vagus nerves)
      • Increases sympathetic stimulation (via cardiac accelerator nerves)
      • Increases adrenal medulla secretion of epinephrine and norepinephrine
    3. Results:
      • Heart beats faster and more forcefully
      • Systemic vascular resistance increases
      • Cardiac output increases
      • Blood pressure returns to normal

    Response to Increased Blood Pressure

    1. Baroreceptors send impulses at faster rate
    2. CV center responds:
      • Increases parasympathetic stimulation
      • Decreases sympathetic stimulation
      • Slows sympathetic impulses along vasomotor neurons
    3. Results:
      • Decreased heart rate and contractility → Decreased cardiac output
      • Vasodilation → Decreased systemic vascular resistance
      • Blood pressure returns to normal

    Chemoreceptor Reflexes

    Chemoreceptors monitor blood chemical composition and are located in:

    • Carotid bodies (near carotid sinus)
    • Aortic bodies (near aortic arch)

    Stimuli Detected:

    • Hypoxia: Lowered O₂ availability
    • Acidosis: Increased H⁺ concentration
    • Hypercapnia: Excess CO₂

    Response:

    1. Chemoreceptors send impulses → CV center
    2. CV center increases sympathetic stimulation to arterioles and veins
    3. Vasoconstriction occurs
    4. Blood pressure increases
    5. Additional effect: Input to respiratory center adjusts breathing rate

    Hormonal Regulation of Blood Pressure

    1. Renin-Angiotensin-Aldosterone (RAA) System

    Trigger: Decreased blood volume or decreased renal blood flow

    Mechanism:

    1. Juxtaglomerular cells in kidneys secrete renin into bloodstream
    2. Renin and angiotensin converting enzyme (ACE) act sequentially on substrates
    3. Produce active hormone angiotensin II

    Effects of Angiotensin II (raises BP in two ways):

    a) Direct vasoconstriction

    • Potent vasoconstrictor
    • Increases systemic vascular resistance
    • Increases blood pressure

    b) Aldosterone secretion

    • Stimulates aldosterone release from adrenal cortex
    • Aldosterone increases Na⁺ and water reabsorption by kidneys
    • Increased blood volume → Increased blood pressure

    Pharmaceutical Relevance: ACE inhibitors are major antihypertensive drugs that block this system.

    2. Epinephrine and Norepinephrine

    Source: Adrenal medulla (in response to sympathetic stimulation)

    Effects:

    1. Increase cardiac output:

      • Increase heart rate
      • Increase force of heart contractions

    2. Selective vasoconstriction and vasodilation:

      • Vasoconstriction in skin and abdominal organs
      • Vasodilation in cardiac and skeletal muscle
      • Helps increase blood flow to muscles during exercise

    3. Antidiuretic Hormone (ADH)

    Also called: Vasopressin

    Source: Produced by hypothalamus, released from posterior pituitary

    Trigger: Dehydration or decreased blood volume

    Effects:

    • Causes vasoconstriction
    • Increases blood pressure
    • Promotes water retention by kidneys

    4. Atrial Natriuretic Peptide (ANP)

    Source: Cells in the atria of the heart

    Effects (lowers blood pressure):

    • Causes vasodilation
    • Promotes salt and water loss in urine
    • Reduces blood volume

    Note: ANP acts as a natural counterbalance to the RAA system.


    Autoregulation of Blood Pressure

    Autoregulation is the ability of a tissue to automatically adjust its blood flow to match its metabolic demands.

    Importance

    • Critical in tissues with variable metabolic demands (heart, skeletal muscle)
    • Blood flow can increase up to 10-fold during physical activity 
    • Blood distribution changes dramatically for different mental and physical activities

    Example: During conversation:

    • Blood flow increases to motor speech areas when talking
    • Blood flow increases to auditory areas when listening

    Mechanisms of Autoregulation

    1. Physical Changes

    a) Temperature

    • Warming → Vasodilation
    • Cooling → Vasoconstriction

    b) Myogenic response

    • Smooth muscle in arteriole walls responds to stretch
    • Increased stretch → Stronger contraction
    • Decreased stretch → Relaxation

    Example: If blood flow through an arteriole decreases:

    • Wall stretching decreases
    • Smooth muscle relaxes
    • Vasodilation occurs
    • Blood flow increases

    2. Vasodilating and Vasoconstricting Chemicals

    Sources: White blood cells, platelets, smooth muscle fibers, macrophages, endothelial cells

    Vasodilators:

    • Released by metabolically active tissue cells:
      • K⁺ (potassium ions)
      • H⁺ (hydrogen ions)
      • Lactic acid (lactate)
      • Adenosine (from ATP)
    • Released by endothelial cells:
      • Nitric oxide (NO) - important vasodilator
    • Released during trauma or inflammation:
      • Kinins
      • Histamine

    Vasoconstrictors:

    • Thromboxane A₂
    • Superoxide radicals
    • Serotonin (from platelets)
    • Endothelins (from endothelial cells)

    Special Case: Pulmonary vs. Systemic Circulation

    Important Difference in autoregulatory response to O₂ levels:

    Systemic Circulation:

    • Low O₂ → Vasodilation
    • Increased O₂ delivery → Normal O₂ restored

    Pulmonary Circulation:

    • Low O₂ → Vasoconstriction
    • Blood bypasses poorly ventilated alveoli
    • Blood flows to better-ventilated lung areas
    • Ensures efficient gas exchange

    Summary: Factors That Increase Blood Pressure

    Blood pressure increases through two main pathways:

    1. Increased Cardiac Output

    • Increased heart rate
    • Increased stroke volume (contractility)

    2. Increased Systemic Vascular Resistance

    • Vasoconstriction of arterioles
    • Increased blood viscosity
    • Increased total blood vessel length

    3. Increased Blood Volume

    • Water retention
    • Hormonal effects (aldosterone, ADH)

    Clinical Pearls for Pharmacy Students

    1. Drug targets: Most cardiovascular drugs work by modifying one or more factors discussed:

      • Beta-blockers: Decrease heart rate and contractility
      • ACE inhibitors: Block RAA system
      • Calcium channel blockers: Cause vasodilation
      • Diuretics: Decrease blood volume

    2. Orthostatic hypotension: Understanding baroreceptor reflexes explains why blood pressure drops when standing quickly and why some drugs cause dizziness.

    3. Exercise physiology: Autoregulation and sympathetic activation explain cardiovascular responses to physical activity.

    4. Shock states: Understanding the relationship between cardiac output, vascular resistance, and blood pressure is crucial for managing shock.

    5. Hypertension management: Multiple control mechanisms explain why combination therapy is often needed.


    Exam Preparation Tips

    Key equations to memorize:

    • CO = HR × SV
    • MAP = Diastolic BP + 1/3(Systolic BP - Diastolic BP)
    • MAP = CO × R
    • R ∝ 1/d⁴

    Important numerical values:

    • Normal blood volume: 5 liters
    • Normal circulation time: 1 minute
    • Normal BP: 110/70 mmHg
    • Pressure at venous end of capillaries: 16 mmHg
    • Additional vessels per kg fat: 650 km

    Understand the pathways:

    • Baroreceptor reflex (both carotid sinus and aortic)
    • Chemoreceptor reflex
    • RAA system
    • Sympathetic and parasympathetic control

    Compare and contrast:

    • Systemic vs. pulmonary autoregulation
    • Vasodilators vs. vasoconstrictors
    • Sympathetic vs. parasympathetic effects
    • Short-term vs. long-term BP regulation


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