Problems with Circulation 2/16-2/2020 point quiz at end of class Monday: Bring scantron

What is the clinical significance of venous return?• What are the structural features of arteries and veins?• How do precapillary sphincters control the entry of blood into capillary beds?• If blood does not enter a capilllary bed can oxygen delivery to tissue occur?• How do we promote venous return and cardiac output?• Arteries and veins: compliance• Distribution of blood volume at rest and during exercise• Blood pressure throughout the systemic circuit.• Hypertension: its causes and effects• Hagen-Poiseuilli Formula and blood/oxygen delivery • Three kinds of shock and venous pooling• Atherosclerosis: its causes and effects

This or something like it will be on the next lecture examWhat letter would represent AV valve closure? A, B, C, D, E, F or GWhat letter would represent the start of the atrial “kick” into the ventricles? A, B, C, D, E, F or GWhat is the cardiac output of this ventricle? Show Math.

This is lead II, what is wrong with this persons ECG?

Lead II ECG Record

Finger Pulses that are associated with ECG tell us ventricular ejection occurred

Finger Pulse amplitude is a function of stroke volume, if ventricular filling is incomplete, ejection is smaller than normal and finger pulse is small or non-existent (plusus alternans may occur).

What is this MEA? Anything wrong with it? Why? Lead I Lead II Lead III

When your body is resting increased parasympathetic nervous system activity distributes blood to areas needed for growth and maintenance.

Preparation for Fight or Flight is associated with a change in blood flow due to the sympathetic nervous system and local autoregulation! Tissues that are heavily used generate heat and CO2 which cause local dilation and greater blood flow TO these tissues. NOTE Cardiac Output has changed from 5L/min15 L/min

Review of Systemic and Pulmonary Circuits in addition to portal systems (hepatic) and anastomoses (V.I.P. cardiac collateral flow)

BASIC VESSEL CROSS-SECTION: The Three Layers of a Blood Vessel larger than a capillary.

1) Tunica Externa (“adventitia”)-outer layer: ProtectionComposed of tough collagen, elastic elastin and nerves

2) Tunica Media-middle layer: Vasoactivity/Changing blood flow2 smooth muscle cell layers: inner-circular outer-longitudinalSMC contractions narrow vessel and increase resistanceSMC contractions squeeze blood towards heartSMC Dilation (relaxation) decreases resistance/pressure

3)Tunica Intima-inner layer: CommunicationComposed of a thin elastic laterSingle layer of endothelial cells (SSEC) that is very fragileCells signal health: Nitric oxide and prostacyclinCells signal injury: Prostaglandins and serotonin

SYSTEMIC FLOW:AortaArteryArterioleCapillaryVenule

VeinVenaCavaRt AtriumRt.VentLungLt Vent.AortaArteries: Resistance/High Pressure Veins: Capacitance/Low Pressure

Arteries: thick tunica media Veins: thin tunica media.

There are Three Types of Blood Vessel: Artery, Capillary and VeinArteries: high pressure/thick wall to maintain pressure“Resistance Vessels of Body”: Blood pressure conserved!Smooth muscle can help maintain pressure and determinesresistance/blood flow in/out! Arteriole and metarteriole: smallestConducting(high elastin)DistributingResistance(high SCM)Capillary: has a thin wall consisting of only one endothelial cell for

quick diffusion of materials. Plural: “Capillary Bed”“Exchange Vessels of Body”: things exchanged here!: Oxygen Delivery!If you have two capillary beds in a row it’s a portal: Gut/Liver Hypothalmus/Pituitary (also in kidney)Capilaries have a high surface area and Surprisingly tiny total volume!Veins: low pressure/thin wall to store blood

“Capacitance Vessels of Body”: Blood reserve!Venule: smallestVeinVenaCavaSmooth muscle contraction to help speed venous return!Valves help prevent blood from moving backwards! Faulty valves result in VARICOSE VEINS!Muscular contraction help pump blood towards the heart!

Blood can’t enter capillaries and deliver its oxygen if the smooth muscle cell at the pre-capillary sphincter is contracted. In this case it bypasses capillaries and returns to heart (this can cause angina). Alternately, collateral flow can permit small blood vessels to deliver blood and oxygen to other regions of the heart not normally supplied.

Gas Exchange OccursOnly InCapillariesWith Blood Flow

How do we promote the return of blood to the heart? Venous return is required for cardiac output!

• 1) Pressure Gradient: Systolic/Diastolic difference is very small– Central Venous Pressure: average (4.7 mmHg)– Why might you see a negative pressure develop?

• 2) Gravity: You loose or gain about 1.92 mmHg/inch above or below the heart– Why does your ankle swell if you stand on it?

• 3) Skeletal Muscle Pumping of venous valves in muscle.– Why is activity good for the elderly?

• 4) Thoracic Pumping: increase/decrease pressure gradient when you breath.– Why might your heart rate increase when you inhale and decrease a bit

when you exhale

Compliance is a measure of blood vessel distensibility (∆volume/∆pressure). Compliance determines if changes in vessel volume will cause the blood pressure to change.

• Arteries have a LOW compliance in order to maintain a High pressure:They maintain blood pressure due to a low complianceA small change in volume creates a large change in pressureBlood enters the aorta and keeps the blood pressure high!

• Veins have a HIGH compliance and as a result maintain a low pressureThey permit blood pooling/storage due to a high complianceA large change in volume creates a small change in pressureI takes a lot of blood in the vena cava before the pressure will increase

How could alterations in vessel compliance and smooth muscle cell contractile state and blood volume contribute to HYPERTENSION?

How could these alterations create HYPOTENSION?

Vasoconstriction/Vasodilation allow you constrict/relax smooth muscle and modify vessel compliance/diameter and as a result flow through the vessel.

How many liters out of the total would you find in each type of blood vessel in your body at rest?

Compliant vessels contain more blood!

Flow (L/minute) is different very from Volume (L)!

Most of your blood pools inThe large veins!

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LOCAL AUTOREGULATION OF BLOOD (O2) DELIVERY TO CAPILLARIES DEPENDS ON THE CONTRACTILE STATE OF

SMOOTH MUSCLE CELLS AT THE PRE-CAPILLARY SPHINCTERS!

Capillaries themselves have no smooth muscle:Control of flow into capillaries comes from Pre-capillary

sphincters where single smooth muscle cells control diameter:

SMC Contraction:↓Flow SMC Relaxation: ↑Flow1)Hypercapnia (high pCO2)2)Heat3)Metabolites like acetate and acetaldehyde

4)If blood enters a capillary it can exchange CO2/O2

Any of these metabolic signals can cause pre-capillary SMC to dilate! (or constrict in their absence).

Because these metabolites are locally produced around the arterioles it is called “LOCAL” regulation.

The further away from the heart, the lower your mean blood pressure and pulse pressure. Pulse Pressure= Systolic Pressure – Diastolic PressureMean Art. Pressure= Diastolic Pressure +1/3(Pulse Pressure)

Pulmonary Circuit pressures are more like 20mmHg/8mmHg in the pulmonary artery and 2 mmHg/1mmHg in the pulmonary vein.

What is hypertension? Why is hypertension such a huge What is hypertension? Why is hypertension such a huge health problem? What are the causes/treatments?health problem? What are the causes/treatments?

Definition: Systolic Pressure above 150mmHg Pulse Pressure above 60 mmHgHow is age correlated with Hypertension?Diabetes and Insulin cause blood vessels to become less sensitive to Nitric

Oxide (less able to dilate)HYPERTENSIONHypertension creates an insidious Positive Feedback Loop that Destroys the

ability of the body to regulate its own blood pressure.Typically results in heart disease/stroke/kidney failure

• Primary Hypertension: Unknown cause• Secondary Hypertension: Specific Known CauseTreatments:• With Drugs: Ace inhibitors, Beta-blockers, Calcium channel blockers,

Diuretic• These drugs reduce blood vessel constriction or reduce the volume of blood.• With Diets: Reduced dietary sodium, and High Fruit Diet• Diets reduce the volume by reducing the sodium content in blood.

Why do very small changes in blood vessel diameter have massive effects on oxygen delivery through a blood vessel?• What do we know about Q (flow) , R (resistance) and P (pressure)?

– Increased pressure increases flow through a tube right?

– Increased resistance increases pressure in a tube right?

– Increased resistance decreases flow through a tube right?

– What does this mean mathematically?

– Answer: P= Q(R) or R=P/Q

• What else effects Q, R and P?

– Increased viscosity decreases flow right?

– Longer tube length means more friction and lower flow right?

– Wider tube radius means flow is easier right?

• Hagen-Poiseuilli Formula pulls all these characteristics together!

• Q=P r4/8L or R= 8L/r4 (formula will be written for you on the lecture test)

• TRICK: flow increases and radius increases to FOURTH POWER!

Common Sense Radius Applications!If the LAD of your heart had a 2mm radius (causing angina) and you took a

nitro pill to vasodilate the artery by +25% 2.0mm 2.5 mm. How much would blood flow to the anterior Left Ventricle increase?

Flow is proportional to radius to 4th power!

• Flow at 2mm 2X2X2X2=16 times

• Flow at 2.5 mm2.5X2.5X2.5X2.5=39 times

• Flow over doubled! Oxygen supply doubled! Pain goes away!

Flow is inversely proportional to viscosity. If the viscosity of your blood doubled (2-4), what would happen to flow?

• Flow 1/viscosity Flow would be decreased half if viscosity X2!

Flow is proportional to the magnitude of the pressure gradient.

Which pressure gradient would yield the greatest flow to capillaries?

Pats Pressure: (MAP in Aorta:100-Arteriole:15) Gradient =85mmHg

Pete’s Pressure: (MAP in Aorta:140-Arteriole: 80) Gradient=60mmHg

IMPORTANT for determining hypertensive patient cardiac work load!

WHAT COMPENSATORY MECHANISMS ARE ACTIVATED BY LACK OF PRESSURE??

• Minor Problem: Syncope (fainting)• Vasoconstriction and tachycardia• Thoracic and skeletal muscle pumping• Interstitial fluid moves into capillaries

• Secrete Hormones to maintain pressure, generate thirst and make more blood!

• Helpful Hormones to increase blood pressure and oxygen delivery: Angiotensin, Epinephrine, Aldosterone, Vasopressin and Erythropoeitin

• Would a saline infusion help or hurt?

• You try to maintain homeostasis, but what if you can’t keep up with blood flow needs? SHOCK RESULTS!

What happens when your body is unable to maintain blood flow and oxygen supply? SHOCK CAN RESULT!

Three Kinds of Shock: Inability to maintain flow homeostasis• 1)Hypovolemic Shock: not enough blood volume.• 2)Obstructed Venous Return: loss of cardiac output.• 3)Venous Pooling: blood not returned to heart

Three Kinds of Venous Pooling:• 1) Neurogenic Shock-brainstem/emotions• 2) Septic Shock-toxins lead to dilation and excess capillary

permeability AND increases in capillary permeability and inflammation to surrounding tissues.

• 3) Anaphylactic Shock-Histamine causes excess dilation AND increases in capillary permeability and inflammation

• Compensated Shock Uncompensated Shock Homeostasis Attained Feedback leads to death

Flow in the center of an artery is non-turbulent, fast and efficient “laminar”. Flow at the edge is slower and more turbulent because of friction with the sides of a blood vessel… flow here is less efficient.

Blood turbulence can irritate underlying endothelial cells and the smooth muscle cells of an artery, especially in the heart where there is a large flow rate and tremendous numbers of blood vessel bifurcations.Turbulence leads to atheroclerotic plaques and platelet aggregation of the side of the blood vessel that may lead to a heart attack.

What do atherosclerotic plaques look like? What happens to the plaque when the amount of LDL-cholesterol, collagen and calcium deposited inside increases? What happens lumen becomes 100% occluded? when the plaque rupture (tears) or What if a thrombosis blocks the lumen?

Why will nitric oxide from the endothelium fail to dilate the vascular smooth muscle? When the vessel constricts what happens to oxygen supply through this vessel? Why is the vasodilator nitroglycerine used to treat angina?

Does nitric oxide remove the plaque/problem? No

The solution is Cardiac Bypass Surgery(about $40-50,000 if you

have good insurance)

Lipid Core Of Arterial Plaque

Narrow Lumen

Healthy Artery: Wide Lumen

The two arteries below are from two rabbits that had atherosclerotic deposits (RED) especially where the arch and where vertebral arteries branched off. In terms of turbulence and flow why would this be expected? Why does your heart (very high blood flow and velocity) have so many great places for atherosclerosis to get started? Why don’t plaques form as frequently in the arteries of our adipose tissue (low oxygen demand/blood flow)?