Internal Environment: Circulation (2)

Be able to differentiate between flow and velocity in terms of units and concept

• Flow: CO is flow, volume of blood per minute

• Velocity: d/t

Increasing which of the following factors in a tissue will increase blood flow to that tissue? (ICQ1)

• Oxygen (dec. oxygen if tissue is hypoxic, arteriole will relax)

• pH

• Carbon dioxide

• Sympathetic stimulation (didn’t do anything with it)

• All of these are correct

ICQ Explanation

• deals w/ arterioles

• talking about regulation of blood flow to the tissues outside the autonomic nervous system → purely based on metabolism

  • doesn’t happen unless in repro

  • no sympathetic

• tissue metabolic activity determines how much blood flow it gets

  • one of the signs of inc. metabolic activity is inc. CO2 production

    • oxidative phosphorylation

    • inc. hydrogen, make more acidity (pH dropping will inc. blood flow to tissue)

If a vessel has the conformation as shown below and blood is flowing from A to D, where is pressure the greatest? ICQ2

• A

• B

• C (blood would flow both ways)

• D

• Pressure is the same at A, B, C & D

ICQ2

• For C, blood would go from H → L pressure… resistance is higher at C

  • pressure is higher in capillaries

  • pressure in circulatory system is lowest at vena cava

    • pulmonary side → pulmonary vein

    • close to 0

If a vessel has the conformation as shown below and blood is flowing from A to D, where is flow the greatest? ICQ3

• A

• B

• C

• D

• Flow is the same at A, B, C, & D

ICQ3

• flow is liters/minute

• CO on both sides of heart is same

• shock: pressure becomes lower in the capillaries than it does in the veins

• arterioles: controlling fraction of flow they get

  • lunch eaters sending higher fraction of CO to digestive system

Have lunch

• metabolic activity of digestive system increases, it starts producing more CO2, using more oxygen

• Blood flow to the arterioles to the GI tract dilate, open up to increase blood flow to that tissue

• Did not trigger parasympathetic to dilate

Exercise

• Increase temperature will increase blood flow to the skin

• Increase temperature will increase muscle blood flow

• Decrease pH will increase blood flow

Organ system itself gets to choose how much blood you need (intrinsic)

Input

• Endocrine

  • Cortisol regulates a1 expression on smooth muscle of arterioles

• CNS

  • Sympathetic

    • a1 on most arterioles and veins

    • B2 on arterioles to skeletal muscle and cardiac muscle

  • Parasympathetic

    • Only to reproductive organs

    • m2

Blood Flow

• Dependent upon pressure gradients and vascular resistance

F = ∆P/R

• Bernuolli’s Principle - deals with P (pressure foes from H → L)

• Resistance (based on radius)

  • Viscosity

  • Surface area

  • Radius

Blood Flow (cont’d)

• Radius - major determinant of resistance

  • Under smooth muscle control (i.e. sympathetic)

Poiseuille’s Law (conceptual formula, if this changes how does this impact flow?)

Flow rate = π∆Pr⁴/8nL

• if values in the numerator go up, flow goes up

  • pressure, radius

• if values in the denominator go up, flow goes down

  • viscosity

Arteries

• Roles

  • Blood transportation away from the heart (anatomy)

  • Pressure reserve (physiology → arteries supply pressure bc they are plastic & recoil, keep the blood moving during diastole)

• Functional anatomy

  • Large diameter

  • Low resistance

  • Elastic fibers

  • Collagen fibers

Arteries as a pressure reservoir

Arterial blood pressure

Regulation of Flow

• Arterioles

  • role is to regulate CO to the diff. tissues

    • if everything is normal, organ systems get to choose

• Pressure Drop

  • Starts at 93 mm Hg (MAP)

  • Ends at 37 mm Hg

• had lunch, didn’t wait an hour & went swimming → putting your life at risk

  • blood going bc of lunch → digestive system

  • bc of swimming → muscles

    • could be a disaster

    • have enough blood to go around, tell CO to go up

• give blood, eat lunch & go swimming → might not have enough

  • sympathetic nervous system will override in case of emergency

Regulation of Flow (cont’d) (in normal conditions w/out any emergency, based upon metabolism of target tissues)

• Vasoconstriction

  • ⬇︎ Tissue activity, CO2, H+, etc.

  • ⬆︎ O2, sympathetic stimulation (tissue that is well oxygenated don’t need to send blood there, constricts & shunts blood to another part)

  • Cold, angiotensin II

    • ex: hypothermic

      • tissue ends up being hypoxic

      • heart is continuing to have a high oxygen demand & if they’re cold, heart doesn’t get its own blood supply as much… go into fibrillation)

• Vasodilation

  • ⬆︎ tissue activity, CO2, H+, K+, osmolarity, adenosine, prostaglandins

  • ︎︎︎⬇︎ O2, sympathetic stimulation

  • Histamine, heat

    • body doesn’t use it physiologically to dilate

      • if we encounter something that triggers histamine, it will dilate

        • doesn’t inc. blood flow to a tissue

Regulation of Flow (cont’d 2)

• Local control

  • Influences CO to organ (system)

  • Chemical mediators

    • Believed to act on vascular endothelium, not directly smooth muscle

    • NO- smooth muscle relaxation

    • Endothelin- smooth muscle contraction

    • Angiogenesis (creating new capillaries)

• Histamine

• 90% of all cases of high BP have no discernible cause

  • endothelial cells are not doing their job properly, not sending right signal at right time

Regulation of Flow (cont’d 3) (stress relaxation if you stretch smooth muscle, it relaxes (stomach)

• Local Physical Influences

  • Heat/Cold

  • Stretch

    • Arteriolar smooth muscle: stretch increases tone (not stress-relaxation response)

      • if we have inc. pressure & are stretching it, it’s going to reflexively constrict blowing out bc of too much pressure → myogenic effect

    • Decrease in stretch decrease in tone

• Extrinsic Control

  • MAP regulation

  • MAP = CO x TPR (resistance)

    • conceptual

    • will calculate CO, HR, & SV

Regulation of Flow (cont’d 4)

• Extrinsic control (external control, main site is autonomic nervous system)

  • Sympathetic tone (centrally mediated vasoconstriction)

    • Overridden in exercise

    • Norepinephrine

    • Cerebral vasculature is under local control

  • sympathetic tone is overridden by heat

    • body temp. is going up, dilating to skin to lose heat

    • sympathetic response should constrict to skin

  • BP during exercise doesn’t jump that much

    • rate & CO pick up, dilating (resistance drops)

  • in cooler temp., forcing skin to constrict

    • inc. BP higher than it should be during exercise

  • exercise & stress are similar, but not identical

    • BP does jump during stress

  • Cardiovascular Control Center (of autonomic nervous system)

    • Medulla

    • Regulation of MAP via baroreceptors

Normal Arteriolar Tone

Arteriolar vasoconstriction

• low metabolic activity is going to constrict

  • don’t need blood going to that tissue bc it’s not metabolically active

What is Incorrect in the Image

The list incorrectly pairs metabolic factors with vasoconstriction. Those specific changes actually trigger vasodilation(opening the vessel, not narrowing it):

• ↓ Oxygen & ↑ Carbon Dioxide

Image claims: Causes vasoconstriction.

Correction: Low O2​ and high CO2​ indicate active tissue needing more blood flow, which triggers local vasodilation (arteriolar relaxation) to deliver oxygen and remove waste.

Vasoconstriction is caused by ↑O2​ and ↓CO2​ (low metabolic demand).

• ↓ Myogenic activity:

Image claims: Causes vasoconstriction.

Correction: Decreased myogenic activity (less stretch/pressure) leads to smooth muscle relaxation, causing vasodilation. Vasoconstriction is caused by ↑↑ Myogenic activity (increased stretch/pressure).

Notice how the handwritten pink note at the top contradicts the slide text by correctly stating: "low metabolic activity is going to constrict... don't need blood going to that tissue be it's not metabolically active."

Arteriolar vasodilation

all indicators of high metabolic activity is going to dilate bc you need more blood there

Autoregulation of tissue blood flow (Myogenic Effect)

• capillaries are fragile, will tear apart if pressure is too high

• one of ways we manage hypertension physiologically is inc. urine production

  • clinical sign: unable to sleep through night w/out having to get up to urinate

• pressure goes up, arteriole will constrict a little, but not to bring it back to normal

  • if it doesn’t stay with flow, can’t get rid of extra volume, can’t bring pressure down

Factors affecting TPR

Exchanges across a continuous capillary wall

How do we get stuff from inside capillaries pushed into circulation so that it can go out & provide nutrients to the cell & pick up waste products

Diffusion

• Interstitial fluid from capillaries

• Passive diffusion (whether it’s water-soluble or lipid)

  • Down gradients

  • Solubility

• Bulk flow

  • Ultrafiltration (pushing fluid out into interstitial space)

  • Reabsorption (pulling fluid back in & putting it on the venous side & sending it off to the heart)

Bulk flow across the capillary wall (Starling’s foces)

• major force pushing out is BP

  • abbreviated Pc → called capillary BP

• flow requires a change

  • no change in pressure (37 → 37)… no flow

    • has to drop

• inward force is constant

• what if this was a person living in the country with poor nutrition?

  • poor nutrition leads to liver failure

  • liver is responsible for producing most of plasma proteins

    • have low plasma proteins, low nutritional source for protein

  • value of 25 goes down

    • outward force stays the same, inward goes down

    • fluid production in interstitial space goes uo

  • edema

    • gathers in abdomen

Bulk Flow

• Capillary blood pressure (hydrostatic pressure, Pc)

  • Outward force

    • Starts at 37 mm Hg, ends at 17 mm Hg

    • Determined by blood pressure

• Plasma-colloid osmotic pressure (oncotic pressure, πp)

  • Inward force

    • proteins, ~25 mm Hg

Bulk Flow 2

• Interstitial-fluid hydrostatic pressure (Pif)

  • Inward

    • Atmospheric

    • 1 mm Hg

• Interstitial-fluid colloid osmotic pressure (πif)

  • Outward

  • Protein in the interstitial spaces (negligible)

Bulk flow across the capillary wall (again)

Bulk Flow 3

• Net Exchange Pressure

  • (Pc + πif) - (πp + P if)

  • Positive number = ultrafiltration

  • Negative number = reabsorption

• Problems lead to edema

Lymphatic System

• Returns interstitial fluid to the heart

  • 11 mm Hg on arterial-end of the capillary

  • 9 mm Hg on venous-end of the capillary

  • 2 mm Hg absorbed into Lymph Vessels

  • 3 liters of lymph per day

    • 7200 liters of blood in the capillaries per day

• Anatomy

  • Slight overlap with endothelial cells

  • Allows fluid in, but not out

  • Can transport plasma proteins and bacteria

  • Travels to lymphnode

Edema

• Reduction in plasma proteins

  • Decreases reabsorption

  • Increases permeability of capillary walls

• Increased venous pressure

• Blockage of lymph vessels (blocks lymphatic drainage)

• interstitial fluid accumulation due to parasitic infection (microfilarin gets bigger & stuck)

• any time tissues get pushed away from blood supply it dies

• breast cancer

  • take lymph nodes out

    • axilla

    • lymphedema

Veins

• Return blood to the heart

• Serve as blood reservoir (64% of blood volume in veins)

• Anatomy

  • Low level of smooth muscle
    Low levels of elastic fibers

  • High levels of collagen

  • 64% of total blood volume

• people can be hypertensive, but they don’t have swelling everywhere bc tissues are being protected

Factors that facilitate venous return

Venous Return

• Venous Capacity (how much blood the veins hold)

  • Increase in capacity diminishes return

• Blood volume

• Sympathetic activity

  • Minimal constriction increases flow

  • Decreases venous capacity

  • if we have an arteriole & sympathetic squeezes it, flow, the volume of blood going through that arteriole drops

    • veins are like tubes of toothpaste with cap off

      • flow goes up

  • sympathetic stimulation to veins squeezes them & dec. volume they can hold

    • bc we have valves, only place blood can go back to is heart, inc. venous return

• Skeletal muscle activity

• Respiratory pump

Fig. 10-34, p. 376

Control

• Short-term

  • Baroreceptor reflex (measured by carotid bodies, carotid sinus)

• Long-term (long-term regulation of BP is through fluid control, sympathetic & parasympathetic are short-term)

  • Osmoreceptors & Volume receptors

    • Hypothalamus, kidney, atria

    • Alters salt and water balance to alter volume

Firing rate in the afferent neuron from the carotid sinus baroreceptor

In the capillaries, the greatest force that moves fluid from the interstitial space and returns it to circulation is:

• Capillary hydrostatic pressure

• Plasma colloid oncotic pressure

• Interstitial fluid hydrostatic pressure

• Interstitial fluid oncotic pressure

• None of these are correct

Hypertension, Hypotension, & Shock

• Hypertension

  • 140/90

  • SECONDARY (10% of cases, can fix it if you treat, patient isn’t hypertensive anymore)

    • Due to definitive cause

    • Cardiovascular

    • Renal

    • Endocrine

    • Neurogenic

Hypertension

• Primary (idiopathic, 90%, all we can do is manage symptoms, don’t know cause)

  • Salt management

  • Na+/K+ pump problems

  • Pressure on the medulla

  • Nitric Oxide

    • endothelial cells are not releasing nitric oxide, or smooth muscle is not responding to nitrous oxide

    • causes arterioles to open up, dilate (relaxer)

  • Digitalis-like compounds

Pathophysiology

Hypotension (drop in BP, so brain is not perfused adequately, give into gravity, loss of consciousness)

• > 90/60 ±

• Orthostatic (from standing too long)

• Emotional stress

• Shock (if hypotension goes bad enough, 4 types, perfusion is 0)

  • Hypovolemic

  • Cardiogenic

  • Vasogenic

    • Septic

    • Anaphylactic

  • Neurogenic

Circulatory Shock

MAP = CO x TPR

• if resistance goes down, pressure goes down

• if CO goes down, pressure goes down

The most common cause of hypertension is:

• Poor diet

• Lack of exercise

• Sodium consumption

  • Na+ does not cause hypertension

  • if you have hypertension, Na+ is not a good idea

  • can contribute, will make heart failure worse… fail faster

• Heart failure

• Unknown

Pathophysiology 2

• Positive feedback loops

  • Decreased tissue perfusion

    • Increased cellular death

    • Increased resistance in capillary beds

    • Decreased tissue perfusion

  • Decreased venous return

    • Decreased cardiac output

      • Metabolic acidosis

      • Increased interstitial fluid volume

    • Decreased venous return

  • Decreased blood pressure

    • Decreased coronary perfusion

    • Decreased blood pressure

• Shock index = HR/SBP

• SO2 = (HR x SV) x (1.39 x [Hb] x SaO2 + 0.03 x PaO2)

Three Positive Feedback Loops in Shock

Consequences and compensations of hemorrhage