Capillaries and Vascular Regulation Notes (BIOL 2040)

Capillaries: Sites of Exchange

• Capillaries are thin-walled, small-radius, extensively branched vessels that serve as the primary site of exchange between blood and surrounding tissue cells.

  • Maximized surface area and minimized diffusion distance optimize exchange
  • Exchange occurs mainly by diffusion; some bulk flow via vesicular transport
  • There is no carrier-mediated transport system across capillaries except in the brain (blood-brain barrier)

• Factors that enhance diffusion across capillaries:

  • Diffusion distances are short
  • Enhanced surface area for diffusion is high
  • Slow velocity through capillaries due to extensive branching (this is emphasized in the text and notes)

Capillaries: Sites of Exchange (Key Figures)

• Capillaries are about 1 cell thick (~1 μm) with simple squamous endothelium; capillaries are very narrow (~7 μm diameter)
• Red blood cells are ~8 μm; when flowing, plasma is pressed against capillary walls, shortening diffusion distance
• It’s estimated that no cell is farther than ~0.01 cm from a capillary

Capillaries: Surface Area and Flow Velocity

• Estimated 10–40 billion capillaries exist, yielding up to ~600 m² surface area for exchange
• At any given time, only ~250 mL (about 5%) of blood volume is in capillaries
• Velocity of flow is inversely proportional to the total cross-sectional area (CSA) of all vessels at a given level of the circulation; capillaries have the slowest velocity because they collectively present the largest CSA
• Slow flow allows adequate time for exchange of materials
• Blood flow through the vasculature is constant (cardiac output ~5 L/min at rest); velocity varies across vessel types due to CSA
  • Figure relationship: Flow rate is constant through all vessels; velocity is slowest in capillaries due to their large CSA

Capillary Pores and Permeability

• Diffusion across capillary walls depends on permeability
• Capillary pores are water-filled gaps at junctions between endothelial cells that permit diffusion of water-soluble substances between plasma and interstitial fluid
• Lipid-soluble substances pass through endothelial cells by dissolving in the lipid bilayer
• Plasma proteins generally cannot cross capillary walls (vesicular transport can move some proteins); if proteins do cross, plasma oncotic/osmotic pressures in tissues increase
• Pore size varies by organ:
  • Most tissues: easy movement of small, water-soluble substances (ions, glucose, amino acids)
  • Brain: tight junctions form the blood-brain barrier, no pores (restricts harmful materials)
  • Liver: large pores allow movement of most items including proteins (reflects liver function)
• The leakiness of capillaries is a function of endothelial cell junction tightness and organ needs

Diffusion Across a Continuous Capillary Wall

• Water-filled pores allow passage of small, water-soluble substances (small ions, glucose, amino acids)
• Lipid-soluble substances pass by diffusion through endothelial cell membranes
• Plasma proteins generally cannot cross; those that do move via vesicular transport
• Exchangeable proteins can be moved across by vesicular transport

Exchanges Across the Capillary Wall: Summary Diagram (Continuous Capillary Wall)

• Plasma proteins generally cannot cross the capillary wall; exchangeable proteins may be moved by vesicular transport
• Small water-soluble substances pass through capillary pores into the interstitial fluid
• Water and solute exchange is driven by diffusion down concentration gradients; proteins tend to stay in plasma unless transported in vesicles

Capillaries Under Resting Conditions

• Capillaries arise directly from an arteriole or from a metarteriole and rejoin at a venule or metarteriole; a capillary bed is the network of capillaries
• Precapsillary sphincters encircle capillaries and regulate blood flow through the capillary bed
• At rest, only a fraction of precapillary sphincters are open (roughly ~10%), so much blood flows through metarterioles into arterioles rather than through full capillary beds
• Metarteriole: a thoroughfare channel between an arteriole and venule
• Metarterioles and capillary beds allow distribution of blood based on metabolic needs

Role of Precapillary Sphincters

• Contraction/relaxation of precapillary sphincters regulates blood flow through capillary beds
• Sphincters relax when tissue oxygen and nutrient concentrations decrease and CO₂ increases; pH decreases
• Sphincters contract when tissue oxygen and nutrients increase and CO₂ decreases; pH increases
• Local control of blood flow through capillary beds

Visual: Precapillary Sphincters and Capillary Bed Flow

• (a) When precapillary sphincters are relaxed, blood flows through the entire capillary bed
• (b) When precapillary sphincters are contracted, blood flows only through the metarteriole, bypassing the capillary bed

Role of Precapillary Sphincters: Metabolic Activity and Capillary Recruitment

• Metabolically active tissues have more capillaries overall
• Precapillary sphincters have high myogenic tone (e.g., skeletal muscles)
• At rest, ~10% of precapillary sphincters are open; most blood flows through metarterioles to arterioles
• With increased metabolic activity (e.g., exercising muscle):
  • More arterioles vasodilate
  • More precapillary sphincters relax and open
  • More blood flow, O₂ delivery, and nutrients reach capillaries
  • Diffusion distance decreases; larger surface area for exchange
  • Increased capillary surface area enhances exchange

Regulation of Blood Flow Through Capillary Beds

• After metabolic needs are satisfied, local factors increase arteriolar tone and precapillary sphincters close, reducing flow to capillaries and normalizing tone

Fluid Compartments: Quick Review

• In adults, body fluids constitute roughly 55%–65% of total body mass
• Two main compartments: Intracellular fluid (ICF) and Extracellular fluid (ECF)
  • ICF: within cells (cytosol)
  • ECF: outside cells, includes blood plasma (~20% of ECF), interstitial fluid (~80% of ECF)

Body Fluid Distribution (Lean Adult Male/Female)

• Total body water ~55% (female) to ~60% (male) of body mass
• Interstitial fluid (tissue spaces) is a portion of the ECF
• Plasma is the fluid within blood vessels
• Intracellular fluid accounts for about 2/3 of total body water; extracellular fluid accounts for about 1/3
• Interstitial fluid makes up ~20% of body weight; plasma accounts for ~20% of extracellular fluid

Interstitial Fluid: Passive Intermediary in Exchange

• Plasma membrane transport can be passive or active; capillary–interstitial fluid exchange is largely passive due to high capillary permeability
• Exchange across capillary walls uses two main mechanisms:
  1) Passive diffusion (primary for solutes)
  2) Bulk flow (distribution of extracellular fluid volume between vessels and interstitium)

1. Diffusion Across the Capillary Walls

• Solutes cross mainly by diffusion along concentration gradients (high to low)

• Arterial concentrations of nutrients and oxygen are maintained to meet tissue needs; cells use nutrients and O₂ and produce wastes, which are carried away by blood

• Capillary walls permit free exchange of solutes (except proteins)

• Extent of exchange depends on the concentration gradient between blood and tissue cells

• Conceptual Illustration: As cells utilize nutrients and O₂, their intracellular concentrations fall; diffusion favors movement from blood (higher) into cells (lower). Conversely, wastes accumulate in cells and diffuse into blood (higher in blood, lower in tissue) to be carried away

2. Bulk Flow Across the Capillary Walls

• Plasma (without proteins) can move out of capillaries and mix with interstitial fluid, then be reabsorbed; this is bulk flow (the plasma and its solutes move as a unit)
• Capillary wall acts like a sieve with water-filled pores; movement occurs in both directions
• Ultrafiltration: outward movement of fluid when capillary pressure exceeds interstitial pressures
• Reabsorption: inward movement of interstitial fluid into capillaries when inward pressures exceed outward pressures

Forces Influencing Bulk Flow (Starling Forces)

• Hydrostatic pressures:

  • Capillary hydrostatic pressure, P_C: fluid pressure within capillaries
  • Interstitial fluid hydrostatic pressure, P_IF

• Colloid osmotic pressures:

  • Plasma colloid osmotic (oncotic) pressure, π_P
  • Interstitial fluid colloid osmotic pressure, π_IF

• Four active forces govern capillary exchange (Starling’s law):

  • Net outward tendency (filtration) when outward pressures exceed inward pressures
  • Net inward tendency (reabsorption) when inward pressures exceed outward pressures

• Capillary hydrostatic pressure (Pc) values across the capillary: approximately

  • Arterial end: $P_C \approx 37 \,\text{mmHg}$
  • Venular end: $P_C \approx 17 \,\text{mmHg}$

• Plasma colloid osmotic pressure (π_P): typically about $25 \,\text{mmHg}$

• Interstitial fluid hydrostatic pressure (PIF): typically low, about $1 \,\text{mmHg}$

• Interstitial fluid colloid osmotic pressure (π_IF): approximately zero or very close to zero

• Net Exchange Pressure (NEP) expression (outward/filtration vs inward/reabsorption):
  $ext{NEP} = (P<em>C + \pi</em>{IF}) - (\pi<em>P + P</em>{IF})$

  • When NEP is positive, filtration dominates (outward flow)
  • When NEP is negative, reabsorption dominates (inward flow)

• Example calculations for clarity:

  • At the arterial end: $\text{NEP}_{arterial} = (37 + 0) - (25 + 1) = 11 \text{mmHg}$ (outward/filtration)
  • At the venous end: $\text{NEP}_{venous} = (17 + 0) - (25 + 1) = -9 \text{mmHg}$ (inward/reabsorption)

• Net exchange of fluid across the capillary wall is depicted in a summary figure (e.g., Fig. 9-22)

• Lymphatic vessels pick up excess interstitial fluid not reabsorbed at the venular end

Net Exchange of Fluid Across the Capillary Wall (Summary)

• Positive NEP indicates filtration (outward movement of fluid into interstitium)
• Negative NEP indicates reabsorption (fluid moves from interstitium into capillary)
• Lymphatics drain the excess fluid to maintain plasma volume and interstitial fluid balance

Lymphatic System: Structure and Function

• The lymphatic system includes lymphatic vessels (capillaries, vessels, trunks, ducts) that collect interstitial fluid and return it to the blood

• Lymph: fluid that flows within lymphatic vessels

• Lymph nodes filter lymph and contain lymphocytes and macrophages to defend against microbes

• Lymphatic tissues include bone marrow

• Initial lymphatics are blind-ended (start as closed-ended vessels) in the interstitial spaces near capillaries

• Lymphatic capillaries are composed of a single layer of overlapping endothelial cells with incomplete basement membrane; overlapping cells form microvalves

• Fluid enters lymphatics easily but does not readily leak out

• Lymph flow to the heart is driven by:

  • A lymphatic pump: smooth muscle in larger lymphatic vessels contracts when stretched by lymph
  • Skeletal muscle movement: contraction squeezes lymphatics and pushes lymph forward
  • One-way valves prevent backflow

• Lymph capillaries and vessels lack a central pumping organ (no heart-like pump)

• Lymphatic return is essential for maintaining plasma volume, defense, fat absorption, and protein return

• Functions of the lymphatic system include:

  • Return of excess filtered fluid to the cardiovascular system: typical daily filtration and reabsorption balance
  • ~7200 L of blood passes through capillaries daily
  • ~20 L filtered by capillaries; ~17 L reabsorbed; ~3 L returned via lymphatics to subclavian veins
  • Defense against disease: lymph nodes filter microbes from interstitial fluid
  • Transport of absorbed fat from the digestive tract (chylomicrons)
  • Return of filtered proteins that are too large to re-enter capillaries

Edema and Interstitial Fluid Accumulation

• Edema is excess interstitial fluid accumulation in tissues
• Causes:
  1) Reduced plasma protein concentration → lowers plasma colloid osmotic pressure (inward pressure) → more fluid leaves capillaries and cannot be reabsorbed
  2) Increased capillary permeability → greater plasma protein leak into interstitium → lowers plasma oncotic pressure
  3) Increased venous pressure (e.g., venous damming) → higher capillary hydrostatic pressure → more fluid outflow
  4) Blockage of lymph vessels → reduced lymph drainage → interstitial fluid accumulates
• Examples: inflammation, allergies (hives), heart failure, mastectomy (lymphedema risk)
• Elephantiasis: severe edema caused by parasitic infection blocking lymphatics

Veins: The Venous System and Return to the Heart

• Veins transport blood back to the heart; capillaries drain into venules, which merge into larger veins and eventually into the venae cavae
• Veins are a significant reservoir of blood due to their high distensibility and large capacitance
• Distensibility means veins can store large volumes of blood; at rest, veins contain 60%+ of total blood volume
• Compared with arteries, veins have:
  • Thinner walls, less smooth muscle, less elastin, more collagen
  • Little myogenic tone
  • High compliance (capacitance vessels)

Venous Return: Definition and Determinants

• Venous return: the volume of blood entering each atrium per minute from the veins
• Venous return is crucial for matching cardiac output (CO) to avoid pooling and edema
• Venous return is influenced by several short-term and longer-term mechanisms
• Key determinants of mean arterial pressure (MAP) and flow include: $MAP \approx CO \times TPR$
  • CO can be expressed as $CO = HR \times SV$
  • TPR (total peripheral resistance) is largely determined by arteriolar radius and tone

Factors That Enhance Venous Return (Figure 9-28 Concept)

• Sympathetic venous vasoconstriction increases venous pressure and pressure gradient toward the right atrium, enhancing venous return
• Skeletal muscle activity (muscle pump) squeezes veins, increasing venous pressure and forward flow; valves prevent backflow
• Venous valves prevent backflow and maintain one-way flow toward the heart
• Respiratory activity (respiratory pump) alters thoracic and abdominal pressures to augment venous return to the heart
• Cardiac suction effect (during ventricular systole and diastole) creates pressure gradients that enhance venous return
• Salt and water retention can increase blood volume, thereby increasing venous return via increased venous pressure
• The overall control is a combination of short-term autonomic adjustments and longer-term volume regulation

Sympathetic Activity and Venous Return (Short-Term Regulation)

• Sympathetic stimulation causes venous vasoconstriction, increasing venous pressure and decreasing venous capacity, which elevates venous return
• This also increases cardiac output by increasing heart rate and contractility, thereby maintaining venous return
• Compare with arterioles: sympathetic vasoconstriction increases resistance (reduces flow), whereas venous constriction increases flow toward heart by reducing capacity

Skeletal Muscle Activity and Venous Return

• Large veins traverse skeletal muscle regions; muscle contraction exerts external pressure on veins, reducing venous capacity and increasing venous pressure
• Valves prevent backflow; the skeletal muscle pump is crucial for moving blood toward the heart, counteracting gravity

Effect of Gravity on Venous Return

• Standing increases hydrostatic pressure in vessels below the heart (e.g., ~100 mmHg at the ankle)
• Blood pooling in leg veins reduces venous return, reducing CO and circulating volume, and increasing capillary pressure in the region (edema risk)
• Countermeasures:
  • Baroreceptor-mediated reflexes (short-term) fail to fully compensate; skeletal muscle pump is essential
  • Skeletal muscle movement enhances venous return and prevents excessive pooling

Varicose Veins

• Superficial veins become visibly swollen and twisted when gravity is not sufficiently countered by muscle activity and valves
• Varicose veins can cause pain, itching, and risk of clots, edema, and ulcers

Venous Valves and the Respiratory Pump

• Veins contain valves at intervals of ~2–4 cm to prevent backflow and promote one-way flow toward the heart
• The respiratory pump: breathing changes chest and abdominal pressures, moving blood toward the heart during inspiration
• Cardiac suction: the heart acts as a suction pump, increasing venous return during certain phases of the cardiac cycle

Blood Pressure: Regulation and Determinants

• Blood pressure (mean arterial pressure, MAP) is the main driving force for propelling blood into tissues and is typically targeted to be around 120/80 mmHg (NIH guideline) or 140/80 mmHg (Canadian guideline)

• MAP is the average driving pressure over the cardiac cycle and is influenced by multiple factors

• Determinants:

  • $MAP = CO \times TPR$
  • $CO = HR \times SV$
  • Cardiac output and total peripheral resistance interplay with venous return and other regulators

• Short-term vs long-term regulation:

  • Short-term: baroreceptors rapidly adjust heart rate, stroke volume, and vessel tone to maintain MAP
  • Long-term: regulate blood volume via kidneys (salt and water balance) and thirst

The Baroreceptor Reflex

• Baroreceptors in the carotid sinus and aortic arch sense stretch (pressure)

• They send signals to the cardiovascular control center in the medulla, which then modulates heart rate, contractility, and vascular tone

• The control center alternates between sympathetic and parasympathetic output to restore MAP toward normal

• Mechanism:

  • If BP increases: increased stretch leads to higher firing rates, driving effects that decrease heart rate and cardiac output and promote vasodilation to reduce BP
  • If BP decreases: reduced stretch lowers afferent firing, increasing sympathetic activity and decreasing parasympathetic activity to raise BP

Effects of Parasympathetic and Sympathetic Nervous Systems on MAP (Summary from the lecture)

• Parasympathetic stimulation:
  • Heart rate: increases (note: the slide text shows an inconsistency; classic physiology has parasympathetic activity reducing heart rate)
  • Cardiac output: increases (as stated, though typically parasympathetic reduces CO)
  • Blood pressure: decreases
• Sympathetic stimulation:
  • Heart rate: increases
  • Contractility: increases
  • Stroke volume: increases
  • Blood pressure: increases
  • Arterioles: vasoconstriction increases total peripheral resistance
  • Veins: vasoconstriction increases venous return
• The apparent inconsistency in the notes regarding parasympathetic effects on heart rate reflects a potential typo; standard physiology is included here for clarity and should be cross-checked with your course materials

Baroreceptor Reflexes to Restore Blood Pressure to Normal

• If BP increases above normal: increased firing from carotid/aortic receptors → cardiovascular center → reduces sympathetic activity and increases parasympathetic activity → decreases heart rate/contractility and causes vasodilation; BP moves toward normal
• If BP falls below normal: decreased firing → increased sympathetic activity and decreased parasympathetic activity → increases heart rate, stroke volume, and vasoconstriction to raise BP

Other Reflexes and Responses That Regulate CV Function

• Carotid and aortic chemoreceptors respond to low O₂ or high H⁺ (acid) by increasing respiratory activity (to increase O₂ and remove CO₂)
• Left atrial volume receptors and hypothalamic osmoreceptors influence long-term BP by controlling plasma volume
• Cerebral-hypothalamic pathways mediate responses related to behavior and emotion (fight-or-flight)
• Exercise modifies cardiac responses (see course table)
• Hypothalamus regulates skin arterioles for temperature control
• Endothelial cells release vasoactive substances (e.g., nitric oxide) to regulate BP

Hypertension: Overview and Classifications

• Hypertension is when BP remains above normal ranges; “silent killer” because it may be asymptomatic until complications occur

• Hypertension definition: commonly >$140/90\ \,\text{mmHg}$ (varies by guideline)

• Two broad classes:

  • Secondary hypertension: due to another identifiable primary problem (≈10% of cases)
  • Primary (essential) hypertension: no single identifiable cause; multifactorial

• Secondary hypertension causes:

  • Renal hypertension (kidney lesions affecting the renin-angiotensin-aldosterone system)
  • Endocrine hypertension (e.g., tumors producing excessive epinephrine/norepinephrine)
  • Neurogenic hypertension (defects in CV control center)

• Primary hypertension potential causes (area of investigation):

  • Defects in renal salt handling; excessive salt intake; low K⁺ or Ca²⁺ in diet
  • Plasma membrane abnormalities affecting Na⁺/K⁺ pumps
  • Gene variations in angiotensinogen
  • Endogenous digitalis-like substances; NO/endothelin abnormalities; excess vasopressin (ADH)

• Adaptation of baroreceptors during hypertension: baroreceptors reset to a higher operating level; they still regulate but at a higher baseline

• Complications of hypertension (long-term): congestive heart failure, stroke, heart attack, spontaneous hemorrhage, renal failure, retinal damage; often symptomless until complications arise

Orthostatic Hypotension

• Hypotension defined as BP < $100/60\ \text{mmHg}$
• Orthostatic (postural) hypotension: transient hypotension due to insufficient compensatory responses to gravitational shifts when moving from lying to standing; dizziness on standing or after prolonged lying

Circulatory Shock

• Shock: severe hypotension with inadequate tissue perfusion
• Four main types:
  • Hypovolemic shock: due to extensive blood loss
  • Cardiogenic shock: heart failure to pump blood adequately
  • Vasogenic (vasodilatory) shock: widespread arteriolar vasodilation
  • Neurogenic shock: defective vasoconstrictor tone due to nerve problems
• Figures 9-39 and 9-40 illustrate causes and consequences/compensations of hemorrhage and shock

Quick Practice / Review Questions (from slides 96–104)

• Where does blood flow travel in the vascular system from heart back to the heart? arteries → arterioles → capillaries → venules → veins → heart (return via venous system)
• Which layer of blood vessels is composed of thin endothelium to reduce friction? Tunica intima
• Which layer changes the diameter of vessels (vasodilation/constriction)? Tunica media
• Arterial walls are thicker and more elastic than venous walls because they need to withstand higher pressures and pulse waves
• Why do larger veins tend to have valves? To prevent backflow and aid one-way flow toward the heart
• Capillary walls are only one cell thick; what is the significance? Maximizes surface area for exchange and minimizes diffusion distance
• Since the heart alternates contractions, two arterial pressures are measured: systolic and diastolic. What are they called? Systolic pressure (maximum during contraction) and diastolic pressure (minimum during relaxation)
• Normal blood pressure is around what value? Approximately $120/80\ \text{mmHg}$ (guidelines vary slightly by organization)

Equations and Key Expressions (LaTeX)

• Net Exchange Pressure across capillary wall:
  $ext{NEP} = (P<em>C + \pi</em>{IF}) - (\pi<em>P + P</em>{IF})$
• Capillary hydrostatic pressure varies along the capillary:
  • Arterial end: $P_C \approx 37\ \text{mmHg}$
  • Venular end: $P_C \approx 17\ \text{mmHg}$
• Plasma colloid osmotic pressure: $\pi_P \approx 25\ \text{mmHg}$
• Interstitial fluid hydrostatic pressure: $P_{IF} \approx 1\ \text{mmHg}$
• Interstitial fluid colloid osmotic pressure: $\pi_{IF} \approx 0\ \text{mmHg}$
• Mean arterial pressure: $MAP \approx CO \times TPR$
• Cardiac output: $CO = HR \times SV$
• Capillary surface area (approximate clinical note): total capillary surface area ≈ $6.0 \times 10^2\ \text{m}^2$
• Proportion of blood in capillaries at any moment: $ext{capillary blood volume} \approx 250\ \text{mL} \quad \left(\approx 5\%\right)$
• Blood volume distribution (typical teaching points): veins contain roughly $60\%+$ of total blood at rest; capillaries hold a minority of the circulating volume; arteries carry a smaller fraction of the total blood volume

Supplementary Notes and References

• This set mirrors BIOL 2040, Lecture 7 Part 2 content, including Capillaries, Veins, Lymphatics, and Cardio-Regulatory mechanisms
• Figures referenced: 9-16, 9-18, 9-19, 9-20, 9-22, 9-27, 9-28, 9-29, 9-30, 9-31, 9-34, 9-37, 9-38, and related captions in the textbook
• Practice prompts include short-answer and fill-in-the-blank questions from slides 96–104 (e.g., naming vessel layers, flow directions, and pressures)