What are the 3 structures of capillaries?

1. Continuous
2. Fenestrated
3. Sinusoid

Describe the MOST COMMON Capillary structure

• Continuous capillary
• Complete endothelial lining with tight junctions between endothelial. cells
• Found in the BBB

Describe the LEAST COMMON Capillary structure

• Sinusoid
• Extensive intercellular gaps and incomplete basement membranes + the clefts and fenestrations
• Liver, bone marrow, lymph nodes, pituitary and adrenal glands

Describe Fenestrated Capillary structure

• Pores + tight junctions (allowing the movement of substance, filtering int he kidneys)
• Small intestine, kidney

Capillaries and microcirculation

• ___________________ is the most important force for transfer
• Lipid soluble substance will ______________
• Lipid insoluble substance will _________________
• Concentration difference ___________ diffusion

• Diffusion is the most important force for transfer
• Lipid soluble substances will diffuse through capillary membrane
• Lipid insoluble substances will cross intercellular clefts (H ₂0, Na, Cl, glucose)
• Concentration difference enhances diffusion

Let's talk about the venous System:

• Returns blood to the heart
• Under low pressure because^^
• Serves as a blood reservoir
• Distensible -- small pressure increases result in a large volume increase

Talk about Pulmonary circulation

Site of O₂ and CO₂ exchange

Major Blood Vessels: What are their functions? (distribution, resistance, exchange, capacitance)

• Aorta
• Large Artery
• Small Artery
• Arteriole
• Capillaries
• Venule
• Vein
• Vena Cava

Tunica Intima

• Endothelium (longitudinal organized along the lumen, continues with endocardium and it's slick surface reduces friction
• Subendothelial Layer (found in vessels larger than 1mm; connective tissue basement membrane)
• Internal Elastic membrane (found only in the arteries!!!)

Tunica Media

• Smooth Muscle (Circular organization that helps with constriction/relaxation; controls the diameter)
• Elastic fibers, Nerve fibers (sympathetic nerve fibers cause vasoconstriction and vasodilation)
• External elastic membrane (found only in the arteries!!!)

Tunica Externa

• Collagen Fibers (protect, reinforce and anchor)
• Vasa Vasorum (for larger vessels to nourish their external layers)
• Poorly myleninated Nervi vasorum

Let's talk about Myoendothelial junctions

• Direct connection between _____________ and ____________.
• This is done via ___________________ and the __________
• Present in __________________________ arteries and arterioles
• Allows ___________________ (EDHF Response)

• Direct connection between endothelial and smooth muscle cells
• Via myoendothelial projection and the Gap junction
• Present in small, resistance-size arteries and arterioles
• Allows direct electrical coupling (EDHF Response)

Describe an EDHF Response

Change in membrane potential within endothelial cells can be passed onto smooth muscle

Mechanism of Vascular Smooth Muscle cell Contraction:

• Ca⁺⁺, Na⁺ influx and Cl^- efflux causes _______________ which in return causes __________.

Ca⁺⁺, Na⁺ influx and Cl^- efflux causes depolarization, which in return causes contraction.

Mechanism of Vascular Smooth Muscle cell Contraction:

• K⁺ efflux causes _______ which in return causes ___________.

K⁺ efflux causes hyperpolarization which in return causes relaxation.

Walk through the DEPOLARIZATION Mechanism of Vascular Smooth Muscle cell Contraction

Walk through the HYPERPOLARIZATION Mechanism of Vascular Smooth Muscle cell Contraction

Capillaries and Venules are only made up of what type of cell?

Endothelial cels

Describe Elastic Arteries/Conductin Arteries

• Arota and Major branches
• Elastin in all three tunics
• Low resistance
• Inactive vasoconstriction
• Act as pressure reservoirs

Describe Muscular arteries/Distributing arteries

• Distal and elastic arteris
• Deliver blood to body organs
• Thick tunica media with more smooth muscle
• Active in Vasoconstriction

Describe Arterioles/Resistance vessels

• Involved in autoregulation
• smallest arteries, lead to capillary beds
• control flow to capillaries by vasodilation and vasoconstriction

Describe the Precapillary Sphincter

• Smooth muscle "cuff"/gate
• Regulate capillary blood flow (contracting or relaxing)

Describe Vena Cava

• Capacitance vessles
• Return deoxygenated blood to heart
• Thoracic vena cava pressure = central venous pressure

Talk about the Lymphatic System

• Drainage of Large particles that cannot pass through capillary pores
• part of immune system
• Lymph nodes contain b and T lymphocytes, and other WBCs; filters out foreign products

Describe Systolic Pressure

• 120 mmHg
• Maximal aortic pressure after left ventricular contraction and blood ejection into the aorta

Describe Diastolic Pressure

• 80 mmHg
• Lowest pressure in the Aorta
• Occurs just before left ventricle ejects blood into the aorta

Describe Mean Arterial Pressure (MAP)

Average arterial pressure during a single cardiac cycle

Describe Pulse Pressure (PP)

• Difference between systolic and diastolic pressure
• Useful in detecting CVD
• 40-50mmHg under normal condition
• increases as aortic elasticity decreased with age or pathological alterations

Capillary pressure starts around ______ mmHg and drops to about ____ mmHg, averaging about ___ mmHg. These pressures allow transfer of materials to tissue from arteries and removal of waste from tissues into veins.

Capillary pressure starts around 35 mmHg and drops to about 10 mmHg, averaging about 17 mmHg. These pressures allow transfer of materials to tissue from arteries and removal of waste from tissues into veins.

What is Venous Return?

The rate of blood flow into the heart from the vein, important controller of CO

Let's discuss the determinants of venous return

What is distensibility?

Ability to distend/expand; veins

What is compliance?

ability to distend and increase volume with increasing pressure, big arteris

What is resistance?

Opposition or impediment to blood flow; small arteries

Cannot be measured, only calculated

Discuss Damping

• Progressive diminishment of pressure pulsations in the periphery
• Caused by resistance of small vessels and compliance of large vessels
• D = C x R

Discuss blood flow

Quantity of blood that passes a given point in the circulation point in a given period of time (mL/min or L/min)

What is Laminar Flow?

Velocity of the flow in the center of the vessel is far greater than at the outer edges (max speed is @ the center)

What is Turbulent flow?

Disordered flow caused by fast flow rate, obstruction in the vessel, sharp turn in the vessel, or passing over a rough surface -- INCREASES RESISTANCE

Discuss the relationship between pressure, flow and resistance

• Flow through a blood vessel is related to pressure and resistance by the equation pictured
• Blood flow is equivalent to CO for entire vascular system

Total Peripheral Resistance (TPR)/Systemic Vascular Resistance (SVR)

The resistance of the entire systemic circulation

Factors Affecting resistance and blood flow (3)

1. Vessel Diameter (related to conductance)
2. Hematocrit and blood viscosity
3. Pressure

What is Conductance?

A measure of blood flow through a vessel for a given pressure, sensitive to diameter changes, flow changes to the 4th power of the diameter

Discuss blood flow autoregulation:

• Active mechanism used by tissues in our body to maintain constance perfusion despite fluctuations in arterial pressure
• occurs between 70 and 175 mmHg
• local regulation of blood flow assures tissues receive the nutrients they need and assures that pressure spikes do not affect nutrient distribution

The 2 types of Local control of blood flow?

Acute

Long-term

Discuss Acute local control of blood flow

Rapid changes in local artery vasodilation or constriction: results in partial blood flow adjustment (75% of actual needs), reduces flow to about 10-15% above normal

• Metabolic theory (Vasodilatory and Oxygen lack theories)
• Myogenic Theory

Discuss Metabolic Theory

Tissue metabolism and oxygen needs control local blood flow

Discuss the Vasodilator theory

The greater the rate of metabolism or the Lower the Availability of oxygen/nutrients, the greater the formation of vasodilators by tissues

Discuss the Oxygen (nutrient) lack theory

In the absence of Oxygen or other nutrients required for contraction, vascular smooth muscle will relax causing vasodilation of met arterioles and precapillary sphincters

Walk through the mechanism of myogenic response is there is an INCREASE IN INTRALUMINAL PRESSURE

Walk through the mechanism of myogenic response is there is an DECREASE IN INTRALUMINAL PRESSURE

Discuss the Myogenic theory (aka Bayliss Effect)

An increase in intraluminal pressure stimulates vasoconstriction of small arteries and arterioles

• caused by smooth muscle cells in the tunica media
• controls arterial diameter and vascular resistance
• maintains constant blood flow to the tissues/steady tissue perfusion
• pathological alteration of myogenic tone seen in HTN, stroke and DM

Discuss long-term local control of blood flow

Slow increase or decrease in the physical size and number of vessels supplying tissues: adjusts flow the remaining 10-15%, critical when the metabolic demands of a tissue change.

• Angiogenesis (increases vascularity/, collateral vessels)

Describe Angiogenesis

Formation of new blood vessels or vascular networks, resulting in long-term reduction of vascular pressure

Describe Collateral Vessels

Formation of alternate flow pathways, resulting in long-term reduction of vascular pressure

Shear stress/ACh/Bradykinin stimulate what vasodilators?

• NO
• PGI₂
• EDHF

Endothelial injury/AngII-produces what vasoconstrictors?

• Et-1
• PGH₂/Thromboxane (TXA₂)
• Superoxide

Discuss Nervous Control of Blood Flow

• Primarily autonomic control
• Mostly sympathetic = vasoconstriction primarily
• Parasympathetic = regulation of heart function via vagus nerve, decrease in HR, and slight decrease in contractility

Sympathetic nerve fibers innervate all vessels except _______________

Sympathetic nerve fibers innervate all vessels except capillaries and precapillary sphincters and some metarterioles

innervation of small arteries and arterioles allow sympathetic nerves to increase vascular resistance

Large veins and the heart are ______________ innervated

Sympathetically innervated

Name the following areas of the Vasomotor Center:

1. Neurons from this area excite preganglionic vasoconstrictor neurons in the SNS; CNS ischemic response
2. Neurons project upward and inhibit the vasoconstrictor area
3. Receives signals from the circulatory system and output signals control vasodilator and vasoconstrictor areas
4. Sympathetic control through the vasoconstrictor areas; Parasymptahetic control through the cardioinhibitory are
5. Can excite or inhibit the vasomotor center

1. Vasoconstrictor area
2. Vasodilator area
3. Sensory Areas (lower pons and medulla)
4. Heart control
5. Higher Nervous System Control

Describe the baroreceptor reflex

Senses changes in blood pressure and sends signal to CNS which initiates appropriate response to maintain nearly constant bp

• maintains an AP within 85-100mmHg
• not related to tissue needs

Let's Discuss Baroreceptors:

• Baroreceptors are __________ in the arterial wall, located in ________ and ______________
• ____________ receptors respond to 60-180 mmHg, and are more important for ______________ than ___________ Baroreceptors (more sensitive)
• Baroreceptors in the aortic arch are __________ than ones in the carotid sinus
• Baroreceptors can ____________

• Baroreceptors are nerve endings in the arterial wall, located in aortic arch and carotid sinus
• Carotid sinus receptors respond to 60-180 mmHg, and are more important for BP regulation than aortic Baroreceptors (more sensitive)
• Baroreceptors in the aortic arch are less sensitive than ones in the carotid sinus
• Baroreceptors can reset

Describe the Chemoreceptor reflex

• Chemoreceptors (peripheral or central) sense O₂ lack, CO₂ excess or H⁺ ion excess and stimulate vasomotor center
• cerebral ischemia, impaired lung function can activate chemoreceptor reflex mechanism

• ____________ chemoreceptors are located in carotid and aortic bodies
• ____________ chemoreceptors are located in the medullary neurons

• Peripheral
• Central

Chemoreceptors are NOT stimulated until PRESSURE FALLS BELOW ______

80mmHg

CNS Ischemic response for BP regulation (acute control)

Reduced cerebral blood flow causes CO₂ buildup which stimulated vasomotor center = increase AP

One of the most powerful activators of the sympathetic vasoconstrictor system

CNS Ischemic response is not activated until pressure falls below _____mmhGwith greatest activation at ______ mmHg.

• < 60
• 15-20

**Crisis response

Walk through the mechanism of vascular smooth muscle contraction and relaxation

Walk through the mechanism of vascular smooth muscle contraction and relaxation

Where are the Following Adrenoreceptors found?

1. A1
2. A2
3. B1
4. B2
5. B3

Epinephrine and norepinephrine effect on Alpha Receptors

• A₁ = Vasoconstriction of blood vessels (primary)
• A₂= " " (minor)
• A₂ Brain = inhibition of NE release
• A₂ kidney = inhibition of renin release

Epinephrine and norepinephrine effect on Beta Receptors

• B₁ Heart = Stimulation (+ chronotropy, iontropy, dromotropy)
• B₁ Kidney = Renin release
• B₂ Blood vessels = Smooth muscle relaxation causing vasodilation and bronchodilation

Walk through Adrenergic Activity within smooth muscle (blood vessels)

Walk through Adrenergic Activity within the brain (vasomotor center)

Walk through adrenergic activity within the heart (SA and AV nodes)

Walk through adrenergic activity within the heart (cardiac muscle)

Walk through the production and inactivation of Bradykinin

Walk through the mechanism of Bradykinin-mediated Vasodilation via B₂

As blood volume increases _________________ increases

As blood volume increases arterial pressure increases

**the increase causes kidneys to lose Na+ and water which returns extracellular fluid volume to normal

What is pressure diuresis?

Increased pressure causes excretion of water

What is pressure natriuresis?

Increased pressure causes excretion of salt

What's the most potent vasoconstrictor?

Angiotensin

What does RAAS stand for?

Renin- Angiotensin-Aldosterone System

Let's talk about the Renin-Angiotension-Aldosterone System

RAAS and Angiotensin II

• AngII binds to AT₁ (G_Q coupled) on vascular SMCs = vasoconstriction
• Constricts small arterioles (kidney)
• Increases release of NE
• Decreases NE reuptake

ADH is also known as

Vasopressin

Why is Vasopressin important?

• Enhances water reabsorption in the kidney via V₂ receptors
• Moderate vasoconstriction via V₁ and SMCs
• important in hemorrhages
• neural origin but secreted into blood from posterior pituitary
• similar to EPI but doesn't affect heart contractility

Discuss Aldosterone

• Mineralocorticoid
• Causes Na⁺ retention and K⁺ excretion from the kidney (hypokalemia)

Summary of Blood Pressure Regulatory Mechanisms