Circulation and Blood Pressure Regulation Notes

Circulation

Basic Principles of Circulatory Function

• Blood flow to most tissues is controlled according to tissue needs.
• Cardiac output is the sum of all the local tissue flows.
• Arterial pressure regulation is generally independent of either local blood flow control or cardiac output control.

Blood Flow According to Tissue Needs

• Active tissue requires an increased supply of nutrients.
• Blood flow can increase significantly during activity, potentially 20-30 times more than at rest.
• The heart's capacity to increase cardiac output is limited to 4-7 times its resting level.
• Microvessels, particularly arterioles, adjust local blood flow by dilating or constricting.

Cardiac Output and Local Tissue Flows

• Blood returns to the heart via veins after flowing through tissues.
• The heart responds to increased blood inflow by pumping it into the arteries.
• A normally functioning heart adjusts its output to meet tissue demands.
• Nerve signals often assist the heart in pumping the appropriate amount of blood.

Arterial Pressure Regulation

• The circulatory system has mechanisms for controlling arterial blood pressure.
• If blood pressure falls below the normal level of approximately 100 mmHg, nervous reflexes trigger circulatory changes to restore it to normal.

Mechanisms for Increasing Arterial Pressure

• Nervous signals:
  • Increase the force of heart pumping.
  • Cause contraction of large venous reservoirs to provide more blood to the heart.
  • Cause generalized constriction of arterioles, leading to greater blood accumulation in large arteries and increased arterial pressure.

Functional Model of Cardiovascular System

• The cardiovascular system includes the heart (left and right atria and ventricles), aorta, elastic arteries, arterioles, capillaries, venules, veins, vena cavae, pulmonary artery, and pulmonary veins.
• Blood flows from the left heart to the aorta, then through arteries, arterioles (with variable radius), and capillaries where exchange of material with cells occurs.
• Blood returns via venules to veins and back to the right heart.
• The right heart pumps blood to the lungs, and the oxygenated blood returns to the left heart.

Blood Vessels: Pressure, Area, and Velocity

• Artery vs Vein: Schematic diagrams illustrating key differences. Artery and Vein diagram showing relative sizes.
• Blood Pressure: Relative blood pressure in large arteries, small arteries, Arterioles, Capillaries, Venules and Veins.
• Total area (cm²): Relative cross sectional area in Large arteries, Small arteries, Arterioles, Capillaries, Venules and Veins
• Velocity (cm/sec): Velocity of blood flow Large arteries, Small arteries, Arterioles, Capillaries, Venules and Vein.

Nutrient Exchange in Capillaries

• Gases, nutrients, hormones, and waste products move through capillaries.
• Capillaries consist of a single endothelial layer.
• Three categories of capillaries exist, classified by their degree of permeability:
  • Continuous: most numerous and least permeable, featuring tight junctions and intercellular clefts that allow passage of water, ions, glucose, gas, and hormones.
  • Fenestrated: contain pores, making them more permeable than continuous capillaries, allowing passage of small molecules and some proteins.
  • Sinusoidal: have the largest holes, allowing RBCs, WBCs, and serum proteins to pass through.
• Continuous capillaries form the blood-brain barrier but have specialized permeable zones.

Interrelationship of Pressure, Flow, and Resistance

• Blood flow is determined by:
  1. The pressure difference (pressure gradient) between two ends of the vessel, which pushes blood through the vessel.
  2. Vascular resistance, which impedes blood flow through the vessel.

Hemodynamics

1. Capillaries have the largest cross-sectional area, facilitating nutrient and waste exchange; the aorta has the lowest.
2. The aorta has the fastest blood flow velocity, approximately 1000 times faster than capillaries.
3. Blood flow in vessels is normally silent (laminar flow), characterized by streamlined or concentric circles.
4. Blood pressure is related to flow and resistance (Ohm’s Law).
5. The relationship between vessel radius, length, and blood viscosity is described by Poiseuille’s Law.

Laminar Flow of Blood in Vessels

• Blood flows in streamlines or concentric circles, with the fastest flow at the center, known as laminar flow.
• Each layer of blood maintains a constant distance from the blood vessel wall.
• (Diagram illustrating parabolic velocity profile)

Laminar Flow Characteristics

• Blood in the ring touching the vascular endothelium barely flows due to adherence.
• The next ring slips past the outer ring, flowing faster.
• All following rings flow at increased speed.
• Blood near vessel walls flows slowly.
• In small vessels, all blood is near the wall.

Turbulent Flow

• Eddy currents or whorls are created, resulting in greater resistance and friction, producing murmurs or bruits.
• Causes of turbulent flow:
  • High velocities
  • Sharp turns in the circulation
  • Aorta exhibiting the greatest turbulent flow
  • Passage over rough surfaces in vessels
  • Passage by an obstruction or rapid narrowing

Ohm’s Law and Blood Flow

• Ohm’s Law calculates blood flow through a vessel: F = \frac{\Delta P}{R}, where:
  • F = Blood Flow
  • \Delta P = Pressure Difference
  • R = Resistance
• Blood flow is directly proportional to the pressure difference and inversely proportional to resistance.

Blood Flow Measurement

• F = Blood flow, measured in ml/min.
• Normal blood flow in total circulation equals cardiac output (amount of blood pumped into the aorta each minute), which is approximately 5000 ml/min.
• Measured by Doppler ultrasound.

Resistance to Blood Flow

• Increased resistance decreases blood flow.
• Resistance to flow increases with:
  • Length of the vessel
  • Viscosity of the fluid
  • Decreased radius

Poiseuille’s Law

• Relates vessel radius, vessel length, and blood viscosity: F = \frac{\pi\Delta Pr^4}{8\eta l} Where:
  • F = rate of blood flow
  • \eta = viscosity of blood
  • r = radius of vessel
  • l = length of vessel
  • P = pressure difference between vessel ends
• This law considers all the velocities of the rings in a blood vessel, identifying the source of variable resistance.

Flow and Vessel Radius

• Flow is proportional to r^4.
• Conductance (Flow) is the reciprocal of resistance.
• At constant pressure, blood flow through a vessel increases in proportion to the fourth power of the radius (or diameter).
• Resistance plays the greatest role in determining the rate of blood flow through a vessel.

Flow and Viscosity

• Flow is inversely proportional to viscosity.
• RBCs contribute to blood viscosity as they exert frictional drag against the vessel wall.
• The viscosity of blood is about 3 times the viscosity of water.
• Measured by hematocrit (% cells).

Hematocrit

• Cellular component of blood.
• A hematocrit of 40 means 40% of blood volume is cells, with the rest being plasma.
• Average values:
  • Men = 42
  • Women = 38

Blood Flow Control

• Determined by tissue needs.
• Two basic theories:
  • The vasodilator theory
  • The oxygen/nutrient lack theory
• Neural control
• Hormonal control
• Kidney (Renin-Angiotensin system)
• Long Term Regulation: Change in the size and number of vessels (Angiogenesis)
  • Vascular endothelial growth factor (VEGF)
  • Fibroblast growth factor
  • Angiogenin

Local Control of Blood Flow

• Vasodilator Theory: Tissue metabolism leads to the release of vasodilators, increasing blood flow. Or, Tissue metabolism (or oxygen delivery to tissues) impacts oxygen concentration, which impacts arteriole resistance which effects blood flow.
• Copyrighted diagrammatic representation of blood flow.

Vasodilator Theory

• Vasodilator paracrines are released from tissue due to increased metabolism:
  • Adenosine
  • AMP, ADP
  • CO2
  • H+
  • K+
  • Lactic Acid
• Other vasodilators:
  • Nitric oxide (NO)
  • Bradykinin (& other kinins)
  • Histamine
  • Leukotrienes
• Serotonin: Also causes increased peristalsis in intestines.
• Vasoconstrictor substances: Hormones like norepinephrine & epinephrine, angiotensin II, vasopressin (ADH), and endothelin.

Oxygen (nutrient) Lack Theory

• Oxygen is required for vascular sphincter muscle contraction.
• Absence of oxygen causes the sphincter to relax and dilate.

Hyperemia

• Active: Increased blood flow accompanies increased metabolic activity due to decreased oxygen and increased carbon dioxide and other metabolites.
• Reactive: Buildup of paracrine molecules due to decreased blood flow increases blood flow to wash away the vasodilators, returning the arteriole radius to normal.

Autoregulation of Local Pressure

1. Metabolic Theory: Increased arterial pressure provides increased oxygen and nutrients, leading to arteriole constriction to decrease arterial pressure.
2. Myogenic Theory: Increased arterial pressure stretches the smooth muscle, causing them to contract, leading to arteriole constriction to decrease arterial pressure.

Partition of Blood in Circulation

• Systemic or Peripheral Circulation: Serves all tissues except the lungs and contains 84% of blood volume (64% in veins, 13% in arteries, 7% in systemic arterioles and capillaries).
• Cardio-Pulmonary Circulation: Serves the lungs and contains 16% of blood volume (Heart: 7%, Pulmonary vessels: 9%).

Vascular Compliance

• Vascular compliance allows veins to hold the largest percentage of blood.
• (Image depicting difference in lumen size compared to vessel size in compliant vs non-compliant vessels).

Veins as a Reservoir for Blood

• Veins contain 64% of blood.
• Venous blood return to the heart is facilitated by:
  • Skeletal muscle pump
  • Respiratory pump
  • Sympathetic nerve supply
• During inactivity, the muscle pump does not function.
• Valves in veins prevent back flow, especially in the legs.

Venous Pressure

• The pressure in the right atria equals central venous pressure, normally a low number near 0 up to +4 mm Hg.
• Pressure in the chest or abdomen can reduce blood return and increase pressure in the veins, leading to varicose veins.

Arterial Compliance and Blood Pressure

• Arteries have low compliance, leading to measurable blood pressures.
• Normal blood pressure is measured when a person is lying down.
• MAP = \frac{2}{3} \text{diastolic} + \frac{1}{3} \text{systolic}

Pulse Pressure

• Pulse Pressure = Systolic - Diastolic
• Causes of Increased Pulse Pressure:
  • Increased Stroke volume
  • Decreased arterial compliance

Measuring Blood Pressure

• Clinicians measure systolic and diastolic pressures indirectly via the auscultatory method.
• Cuff inflation beyond 120 mm Hg occludes the brachial artery.
• As cuff pressure is released, turbulence is generated when blood from the heart side of the cuff meets the downstream blood, resulting in Korotkoff sounds.

Neural Control of Circulation

• Vasomotor Center & Reflexes

Sympathetic Nerve Supply to Blood Vessels

• All blood vessels are supplied by sympathetic nerves.
  • Visceral tissue (like the heart and organs) has specific sympathetic nerves such as celiac ganglia.
  • Peripheral vasculature exits the sympathetic chain ganglia and travels with the spinal nerve.
• Exception: There is no sympathetic innervation to capillaries & precapillary sphincters.

Central Nervous System Control

• The vasomotor center in the reticular area of the medulla and lower pons (bilateral) controls blood vessels.

Organization of Vasomotor Center

• Afferent (Sensory): Receives sensory input from CN IX and X.
• Efferent:
  1. Vasoconstrictor area:
     • Neurons projecting to sympathetic preganglionic fibers in the cord (lateral horn T1-L2)
     • Maintains vasomotor tone.
  2. Vasodilator area:
     • Neurons project up to the vasoconstrictor area to turn off vasoconstriction.

Vasomotor Control of Heart - Lateral & Superior portion

• Vasomotor control of the Heart - Lateral & Superior portion:
  • Increases heart rate and contractility via sympathetic efferent fibers.
  • Excites the heart
• Vasomotor control of the Heart - Medial and Inferior portion:
  • Decreases heart rate and contractility via the dorsal motor nucleus of the vagus.
  • Inhibits the heart.

Nervous Control of Arterial Pressure

• Baroreceptors:
  • Location: Carotid sinus and Aortic arch
  • Responds to: Arterial BP between 60-180 mm Hg, most sensitive at 100 mm Hg
  • Action: Inhibits the vasoconstrictor center and excites the vagus.
  • Impact: Excitation of baroreceptors by high BP causes arterial pressure to decrease by decreasing arterial resistance.
• Chemoreceptors:
  • Location: Carotid bodies and Aortic arch
  • Responds to: Decreased O2 or increased CO2 and H+ levels, active only at arterial BP below 80 mm Hg
  • Action: Excites the vasoconstrictor center.
  • Impact: Excitation of chemoreceptors by low oxygen or high carbon dioxide causes arterial pressure to increase.

Anatomy of Baroreceptors

• Pathway from Carotid Sinus: Hering’s nerve → CNIX → solitary tract → medulla → vagus
• Pathway from Aortic Arch: CNX (Vagus) → solitary tract → medulla → vagus
• High blood pressure increases the rate of firing of the baroreceptors.
• Low blood pressure decreases the rate of firing of the baroreceptors.
• Reset in 1-2 days of sustained new pressure allowing for BP drift.

Orthostatic Hypotension

• Baroreceptors function when changing position from lying to sitting to standing.
• Upon standing, gravity causes blood to pool in lower extremities, causing arterial pressure to decrease: termed orthostatic hypotension.
• Carotid sinus and aortic arch receptors decrease the rate of firing, which results in increased sympathetic activity.
• Results in increasing heart rate, contractility, increased vasomotor constriction, and therefore increases blood pressure.

Bainbridge Reflex

• Responds to increased blood pressure.
• Receptor: stretch receptor in atria.
• Pathway: CNX → VMC → sympathetic.
• Impact: increases heart rate and contractility to prevent damming of blood in veins, atria, and the pulmonary circulation.
• Bainbridge reflex explains why increased blood pressure increases the heart rate. (Bainbridge – heart rate, Frank-Starling – stroke volume)

Blood Volume & Blood Pressure

• When blood volume increases, blood pressure increases.
• Receptors are located in atria and pulmonary arteries.
• Responds to increased blood volume.
• Impact:
  1. Kidney:
     • Increases glomerular filtration rate
     • Increases sodium and water loss in urine
  2. Hypothalamus:
     • Decreases ADH secretion (increases water loss)

CNS Ischemic Response

• Lack of blood supply to the brain increases the concentration of carbon dioxide.
• Stimulates chemoreceptors to increase blood pressure.
• Sympathetic vasoconstriction can occlude some blood vessels (kidney can cease urine production).
• One of the most powerful activators of sympathetic vasoconstriction.
• Active only at arterial BP below 60 mm Hg, greatest at 15-20 mm Hg (“last ditch stand”).
• CNS ischemic response explains organ failure when blood lacks oxygen.

Autoregulation

• Autoregulation Attenuates the Effect of Arterial Pressure on Tissue Blood Flow.
• Increase in arterial pressure increases force that pushes blood thru vessels.
• Also initiates compensatory increases in vascular resistance.
• Reductions in arterial pressure see vascular resistance reduced leading to maintained blood flow.
• Known as blood flow autoregulation.

Vascular Wall Tension

• Tension develops in response to transmural pressure gradients.
• Causes vascular smooth muscle to stretch in all directions.
• Larger blood vessels (such as the aorta) must have stronger walls to withstand more tension – reinforced with collagen.
• Capillaries have lower wall tension.
• Chronic changes in blood pressure lead to blood vessel remodeling to accommodate for increased tension.

Vascular Sheer Stress

• Blood flow creates frictional force (or drag), termed sheer stress.
• Sheer stress is proportional to the flow velocity and viscosity of blood.
• Sheer stress is important in the development and adaptation of the vascular system to accommodate blood flow requirements in tissues.

Cushing Reaction

• Special CNS ischemic response.
• Ischemia (lack of blood supply) is caused by increased cerebrospinal fluid (CSF) pressure.
• When CSF pressure exceeds arterial blood pressure in the brain, the blood vessels are occluded.
• This causes the CNS ischemic response to increase blood pressure to the brain to protect the brain from oxygen and nutrient loss.