Cardiovascular Physiology Jim Pierce Bi 145a Lecture 14, 2009-10.

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Transcript of Cardiovascular Physiology Jim Pierce Bi 145a Lecture 14, 2009-10.

Cardiovascular Physiology

Jim PierceJim Pierce

Bi 145aBi 145a

Lecture 14, 2009-10Lecture 14, 2009-10

Arterial Blood Pressure:Escaped from the Heart

Blood Flow, Velocity, and Pressure

• We have talked about flow and velocity

• We know that flow and velocity are a function of the pressure gradient.

• Let’s consider Pressure.

Blood Pressure

• Pressure is force on an area

• If there is a fluid in a containerwe measure the pressure on the surface area of the container.

• That pressure is related to the number of particles that crash into that surface area per unit time

Blood Pressure

• Pressure in the reservoir is easy

– Since there is no net flow, the force on all sides of the reservoir is equal. Thus, measuring pressure anywhere measures pressure.

Blood Pressure

• Pressure in a pipe is hard

– Since there is net flow, there are fewer particles hitting the inflow area than the wall and more particles hitting the outflow area than the wall.

Blood Pressure

Blood Pressure

• There are two types of pressure:

• Static Pressure– Pressure from the blood distending the vessel

against the vascular smooth muscle– LaPlace: T=Pr (tension, pressure, radius)

Blood Pressure

• There are two types of pressure

• Dynamic Pressure– Pressure from the movement of particles along

the blood stream– Pitot: P=v2/2 (density, velocity)

Blood Pressure

Blood Pressure

• The Total Pressure is the sum of the static and dynamic pressures.

• This is much like Total Energy is the sum of the kinetic and potential energies.

Blood Pressure

• Where there is a high velocity (the aorta) there is a large component of “dynamic pressure” to the blood pressure.

• Where there is a low velocity (the peripheral arteries), the pressure is predominantly static.

Blood Pressure

• From a practical standpoint…

• THE blood pressure is what we measure if we stick a catheter into the lumen of a vessel and measure the outflow pressure.

Blood Pressure

Blood Pressure

• That is why we get away with our medical definition of “THE blood pressure”

• Regardless of the positioning of the catheter (intended to be along the middle of the blood vessel in line with outflow), we will see static pressure changes.

Blood Pressure Cuff

Afterload and Blood Pressure

• So when the heart produces aCardiac Output…

• It is putting FLOW into the Aorta

Afterload and Blood Pressure

• This FLOW has kinetic energy

• The energy of FLOW is converted into:– STATIC PRESSURE that stretches

the vessel walls– DYNAMIC PRESSURE of the blood moving

forward

Blood Velocity

This DECREASE in velocity reflects the ability of theAorta to ABSORB Static Pressure (i.e. store energy)

Afterload and Blood Pressure

• So AFTERLOAD = Vascular Resistance

• Blood Pressure reflects:– Cardiac Output (Flow = Total Energy)– Afterload (Vascular Resistance)

Afterload and Blood Pressure

• The take home point:

• Blood pressure is important becauseit gives information about:– The Heart Output– The Arterial Resistance

• But it is not Afterload

Blood Flow

• Preload is dominated by Cardiac Compliance

• Afterload is dominated byAortic Compliance

• Their relationship isCardiac Contractility

Blood Flow

• The heart takes Preload and converts it into flow against Afterload

• CO = HR * SV

• CO = BPsystemic / SVR

Womersley Number

• Dimensionless Number• Describes unsteady fluid flow resulting from an

unsteady pressure gradient.

• r=tube radius, f=frequency, n=order of harmonics, =fluid density, =viscosity index

fn

r

2

fn

r

2

fn

r

2

Womersley Number

• Dimensionless Number• Describes unsteady fluid flow resulting

from an unsteady pressure gradient.

• The Womersley Number is the “engineering” version of cardiac output

fn

r

2

fn

r

2

fn

r

2

The Circuit

• Perfusate• Pump• Pipes

Systemic Blood Flow

• Everything before these organs is designed to maximize efficiency of cardiac output.– AORTA

• Everything leading to these organs is designed to regulate flow to the organs.– LARGE ARTERIES

• Everything leading to each vascular bed is designed to regulate flow inside the organs.– MEDIUM and SMALL ARTERIES

Microcirculation

AV Shunts andMetarteriolesdetermineCapillary flow.

Microcirculation

Microcirculation

CapillaryNetworks

Capillary Endothelium

Microcirculation andFluid Movements

• There are two significant forces on the blood and fluid around the microcirculation

• There is a Hydrostatic Pressure

• There is an Oncotic Pressure

Microcirculation andFluid Movements

• The Hydrostatic Pressure– Is the pressure from fluid volume and flow

– Inside the blood vessel, it is ultimately derived from the work of the heart

– Outside the blood vessel, it is primarily derived from the presence of interstitial fluid trapped in the organ compartment.

Microcirculation andFluid Movements

• The Oncotic Pressure– Is the osmotic pressure of fluid and represents

the tendency to suck fluid in.

– Inside the blood vessel, it is derived from the plasma proteins (particularly albumin) and blood cells

– Outside the blood vessel, it is derived from the ground substance of the tissue

Microcirculation andFluid Movements

• Starling’s Law

• Qf = k [ (Pc+i) - (Pi + p) ]• Qf = net flow across membrane

• k = reflection coefficent (“fudge factor” like the rate constant or diffusion constant)

• Pc = Capillary Hydrostatic Pressure

• i = Interstital Fluid Oncotic Pressure

• Pi = Interstitial Fluid Hydrostatic Pressure

• p = Plasma Fluid Oncotic Pressure

Starling Forces in the Capillary Bed

Control of “Leakage”

• Different Endothelial phenotypes lead to different reflection coefficients (K)

Veins and Lymphatics

• Both are vascular systems for returning the perfusate to the heart.

• They are BOTH low pressure

• They are BOTH high compliance

Veins and Lymphatics

• The veins receive from the microcirculation

– Thus, the veins are part of a closed

cardiovascular system

– The veins receive blood

Veins and Lymphatics

• The lymphatics receive from the tissues

– Thus, the lymphatics are open

– The lymphatics receive interstitial fluid, or

ultrafiltrate, from the blood

Veins and Lymphatics

• Veins have a low venous resistance

• This determines flow rates across the hydrostatic pressure gradient between the microcirculation and the heart.

• Small change in resistance =Large change in compliance

Veins and Lymphatics

• Lymphatics have no actual resistance

• The mean tissue pressure is less than (or equal to) central venous pressure.

• Flow occurs by increases in tissue pressure above mean and valves to prevent backflow.

Veins and Lymphatics

• Veins drain into the large central veins, which act as the precardiac reservoir.

• Lymphatics drain to large lymphatic vessels which empty into the central venous system

– at the junction of internal jugular and subclavian veins.

Veins: From Small to Large

• Venules and Small Veins– Directly affect Starling Forces on Capillaries

• Medium Veins– Indirectly affect Tissue Bed Forces– Indirectly affect Cardiac Filling– Are the Largest Venous Reservoir of Blood

• Large Veins– Directly affect rate of Cardiac Filling

Special Circulations

• Cutaneous

• Splanchnic

• Portal Venous System

• Cerebral

• Coronary

• Fetal and Neonatal

Muscle Unit• Fascia wraps the “muscle meat”

• Tendon connects meat to bone

• Loose connective tissuesurrounds bunches of muscle

• Nerves and Vesselstravel between muscle

• Open ends of LymphaticVessels sit free inside the fascia compartment

Muscle Compartment

• Compartment Pressure– Generally 8-10 mmHg at rest– Can be affected by

• Inflow (Artery)

• Outflow (Vein and Lymphatic)

• Extravascular Volume– Extracellular Matrix

– Cell Volume

Connective Tissue

• Extracellular Matrix– Fibers

• Collagen• Elastin• Reticular Fibers

– Ground Substance• Blood Ultrafiltrate• Proteoglycans• Glycosaminoglycans

Body Fluids

• To understand ground substance,we must first talk about body waterand electrolytes

• Approximately 60% of the body is water.

Body Fluids

Body Fluids

• For a 70 kg man whose body read the book:

• Total Body Water = 42 Liters

• Intracellular Water = 28 Liters

• Extracellular Water = 14 Liters

Body Fluids

• Intracellular Fluid is easy:It’s all inside the cells

• Extracellular Fluid exists in two locations:– Intravascular (1/4 in blood vessels)– Interstitial (3/4 in tissues)

Body Fluids

Body Fluids

• What are the barriers between thesethree body spaces?– Intracellular– Interstitial– Intravascular

Body Fluids

• Between Intracellular and Interstitialis the CELL MEMBRANE

• Between Interstitial and Intravascularis the CAPILLARY MEMBRANE

Body Fluids

Body Fluids

• Why are these barriers important?Why are these barriers important?

• Only blood (intravascular) goesOnly blood (intravascular) goesto the kidney for processing.to the kidney for processing.

• The diffusion limitations of theseThe diffusion limitations of thesebarriers determine how accessiblebarriers determine how accessiblethings are to the kidneythings are to the kidney

Body Fluids

IntracellularInterstitialIntravascular

Body Fluids

• The body is not just “free water”

• There are many things that float around inside this water:

Body Fluids

• Proteins and their bound water• Small covalent compounds

– Some bound to protein (lipophilic)– Some with bound water

• Lipoproteins• Salts and their bound water

– Sodium, Chlorine– Bicarbonate

Interstitial Space

• The source of the Interstitial ECM is regional.The source of the Interstitial ECM is regional.

• Proteins (Fibers and Ground substance) often Proteins (Fibers and Ground substance) often come from the connective tissue cellscome from the connective tissue cells

• Salt, Water, and small molecules are Salt, Water, and small molecules are “Filtered” by the capillary membrane“Filtered” by the capillary membrane

• Waste Products are removed by theWaste Products are removed by theBlood and LymphaticsBlood and Lymphatics

• Hormones are produced and consumed Hormones are produced and consumed everywhere.everywhere.

Interstitial Space

• The source of the ICM is the Cell Itself.The source of the ICM is the Cell Itself.

• Proteins and Membranes are made.Proteins and Membranes are made.

• Salt, Water, and small molecules are Salt, Water, and small molecules are “Filtered” by the cell membrane. “Filtered” by the cell membrane.

Body Fluids

• Thus, the barriers determine the distribution Thus, the barriers determine the distribution of salts, small molecules, and waterof salts, small molecules, and water

• It is barrier function that maintainsIt is barrier function that maintainsthe differences between compartmentsthe differences between compartments

Body Fluids

Body Fluids

• Because the Capillary Membraneis rather “leaky”

• The Interstitialand Intravascularcompartments arequite similar

Body Fluids

• Because the Cell Membraneis not “leaky”

• The Interstitialand Intracellularcompartments are very different

Muscle Compartment

• Fluid Flux:– Blood comes in vi arteries– Both Osmosis and Diffusion occurs– Ultrafiltration produces Interstitial fluid

bathing Extracellular Matrix– Blood leaves via Veins– Interstitial fluid leaves via Lymphatics

Starling Forces in the Capillary Bed

Microcirculation andFluid Movements

• Starling’s Law

• Qf = k [ (Pc+i) - (Pi + p) ]• Qf = net flow across membrane

• k = reflection coefficent (“fudge factor” like the rate constant or diffusion constant)

• Pc = Capillary Hydrostatic Pressure

• i = Interstital Fluid Oncotic Pressure

• Pi = Interstitial Fluid Hydrostatic Pressure

• p = Plasma Fluid Oncotic Pressure

Muscle Compartment

• Mean arterial pressure – 32 mm Hg

• Mean venous pressure – 15 mm Hg

• Mean compartment pressure – 10 mm Hg

• Mean lymphatic pressure – 2 mm Hg

Starling Forces in the Capillary Bed

Glomerulus

• Fine Capillary Fine Capillary NetworkNetwork

Glomerular Filtration

Starling’s Forces are Starling’s Forces are alive and well in the capillary!alive and well in the capillary!

(They’re a little different, though)

RBF and GFR

By controlling theBy controlling theafferent and efferentafferent and efferentarterioles, we controlarterioles, we control

Glomerular Filtration RateGlomerular Filtration Rate

RBF and GFR

By controlling theBy controlling theafferent and efferentafferent and efferentarterioles, we also controlarterioles, we also control

Renal Blood FlowRenal Blood Flow

RBF and GFR

Thus: the “arterial”Thus: the “arterial”nature of the glomerulusnature of the glomerulusallows us to apply steadyallows us to apply steadyhydrostatic pressurehydrostatic pressureacross the glomerulus,across the glomerulus,making a filtrate.making a filtrate.

Glomerular Membrane

• Made from:

– Endothelium– Basement

Membrane– Podocytes

The “Urine Filter”The “Urine Filter”

Glomerulus

• The endothelialmesh is coatedby cells called

Podocytes

Podocytes

Part of GlomerularMembrane

TEM Podocytes

Glomerular Filter

• This filter has several effects because it is a gel:

– Its composition makes a “Pore Size”– Its composition makes a “Charge Barrier”

– (Just like gel electrophoresis)

Glomerular Filtration

Glomerular Filtration

Glomerular Filtration

Starling’s Forces are Starling’s Forces are alive and well in the capillary!alive and well in the capillary!

(They’re a little different, though)

Questions?