03 Starling's Law

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S. Faubel and J. Topf 3 Starling’s Law

33 Starling’s Law

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The Fluid, Electrolyte and Acid-Base Companion

Weight� of�

water

solu

te

Introduction�Three factors affect the movement of water be-tween body water compartments.

The previous chapter took a brief look at the factors which influence thedistribution of water between compartments. These factors are hydrostaticpressure, osmotic pressure and membrane characteristics.

Hydrostatic pressure is a force generated by water. Hydrostatic pres-sure pushes water out of a compartment.

Osmotic pressure is a force exerted by solutes. Osmotic pressure drawswater into a compartment. This force is dependent only on the concentra-tion of particles (osmolality) in solution.

Membrane characteristics affect the ability of water and solute to movebetween compartments.

This chapter focuses on how these factors are incorporated into Starling’slaw. Starling’s law governs fluid shifts between compartments and can beused to understand all fluid accumulations, including peripheral edema,pleural effusions and ascites.

There are two forces governing the movement of water betweencompartments: __________ pressure and osmotic pressure.

Osmotic ___________ is the ability of a solute to cause the move-ment of _______.

Aaahydrostatic

pressurewater

1Hydrostatic pressure

2Osmotic pressure

3Membrane characteristics

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Starling’s law�Net hydrostatic pressure and net osmotic pressuredetermine the movement of water between compartments.

To determine where water will flow between the plasma and interstitialcompartments, it is necessary to look at the net hydrostatic pressure andnet osmotic pressure of each compartment.

Net hydrostatic pressure is the difference between the hydrostatic pres-sure in the capillary and the hydrostatic pressure in the interstitium. Wa-ter flows out of the compartment with the greater hydrostatic pressure. Inthe diagram above, the capillary hydrostatic pressure is greater than theinterstitial hydrostatic pressure; the net hydrostatic pressure causes move-ment of water out of the capillary.

Net osmotic pressure is the difference between the osmotic pressuresin the capillary and interstitium. Water flows into the compartment withthe higher osmotic pressure. In the diagram above, the capillary osmoticpressure is higher; the net osmotic pressure causes the movement of waterinto the capillary.

___________ pressure pushes water out of a compartment.

___________ pressure draws water into a compartment.

______ hydrostatic pressure is the capillary hydrostatic pressureminus the interstitial hydrostatic pressure.

Net osmotic pressure is the ________ osmotic pressure minus theinterstitial osmotic pressure.

Hydrostatic

Osmotic

Net

capillary

(capillaryhp

– interstitialhp

) (capillaryop

– interstitialop

)

net hydrostatic pressure net osmotic pressure

capillary capillaryinterstitium interstitium

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Starling’s law�The membrane factors Lp, S and s can effect themovement of water between compartments.

There are three independent membrane characteristics which affect themovement of water between compartments. Two of them modulate hydro-static pressure and one modulates osmotic pressure.

Hydrostatic pressure is affected by membrane surface area and the abil-ity of water to pass through the membrane. The surface area is representedby an uppercase S and the porosity is represented by Lp. The membranefactors affecting hydrostatic pressure are rarely clinically significant.

Osmotic pressure is modified by the permeability of the membrane to asolute. If the membrane is perfectly permeable to a solute, then the solutediffuses across the membrane (instead of osmotically drawing in water).Permeability of a membrane to a solute is represented by a lowercase s andranges from zero, completely permeable, to one, completely impermeable.Membrane permeability is clinically relevant in disorders which disruptmembrane integrity (e.g., sepsis).

The membrane factors which modulate hydrostatic and osmoticforces are: ___, S and s.

Two membrane characteristics modulate hydrostatic pressure: Lpand ____.

The membrane factor s represents the ___________ of the mem-brane to solutes, a clinically important factor.

aaaLp

S

permeability

MEMBRANE CHARACTERISTICS

porosity and surface areamodulate hydrostatic pressure

permeability to a solute mod-ulates osmotic pressure

Lp and S

s

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Starling’s law�Starling’s law is the mathematical representationof the movement of water between compartments.

Starling’s law is the mathematical representation of the principles of hy-drostatic pressure, osmotic pressure and membrane characteristics appliedto the movement of water between the capillaries and the interstitial space.

The formula is arranged so that if net filtration pressure is positive (nethydrostatic pressure greater than net osmotic pressure), water moves fromthe capillaries into the interstitium. If net filtration pressure is negative(net osmotic pressure greater than net hydrostatic pressure), then watermoves from the interstitium to the capillaries.

The following pages review the clinical consequences of alterations in thevariables of Starling’s Law which cause the movement of water out of thecapillaries.

(capillaryop

– interstitialop

)

net osmotic pressure

s(capillaryhp

– interstitialhp

)

net hydrostatic pressure

Lp × S

NET FILTRATION PRESSURE

The movement of ______ between capillaries and the interstitiumis ____________ represented by Starling’s law.

The equation for Starling’s law contains _______ forces: hydro-static pressure and _______ pressure.

watermathematically

twoosmotic

Negative net filtration pressureIf net filtration pressure is negative, watermoves from the interstitium into the capillary.

Positive net filtration pressureIf net filtration pressure is positive, watermoves from the capillary into the interstitium.

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AR

TE

RIA

L E

ND

VE

NO

US

EN

D

The application of Starling’s law to the flow of fluid in and out of thecapillary is a dynamic process. At the arterial end of the capillary, thenet filtration pressure is positive, which causes the movement of waterfrom the capillary into the interstitium. This movement of fluid out ofthe capillary concentrates plasma protein and dilutes interstitial pro-tein. As fluid moves through the capillary, hydrostatic pressure fallsdue to friction against the capillary walls. The sum of these changescauses the venous end of the capillary to have a negative net filtrationpressure and resorb fluid from the interstitium.

This push-and-pull pattern in the capillary bed is useful because itallows the capillary to deliver oxygen and nutrients (at the arterial end)and pick up carbon dioxide and other waste (at the venous end).

The average net filtration pressure across the entire capillary is posi-tive: the net outward movement of water is greater than the net inwardmovement of water. The excess water which is filtered but not resorbeddoes not accumulate in the interstitial space. The lymphatic systemabsorbs this excess fluid and returns it to the circulation via the tho-racic duct.

At the proximal end of the capillary, thenet filtration pressure is positive and wa-ter moves out of the capillary.

At the distal end of the capillary, the netfiltration pressure is negative and watermoves into the capillary.

lymphatic drainage

Net osmotic pressure and net hydrostatic pressure changefrom one end of the capillary bed to the other.

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Water movement out of the capillary�Increased net filtrationcan be due to increased net hydrostatic pressure.

Increased capillary hydrostatic pressure increases net filtration pressureresulting in the movement of fluid from capillaries into the interstitium.

It is an increase in venous hydrostatic pressure which results in a changein net filtration pressure. The arterial ends of capillaries contain pressure-sensitive precapillary sphincters which compensate for changes in bloodpressure. Therefore, the increased arterial blood pressure of hypertensiondoes not affect hydrostatic pressure and does not cause edema.

Clinically, increased hydrostatic pressure is seen in congestive heart fail-ure and cirrhosis. The consequences of increased hydrostatic pressure in-clude peripheral edema, pulmonary edema and ascites.

The clinical consequences of increased hydrostatic pressure includeperipheral ________, pulmonary _______ and ascites.

Increased _________ blood pressure does not cause an increase incapillary hydrostatic pressure.

Increased venous hydrostatic pressure _________ net filtration pressure.

aaaedema; edema

arterial

increases

Increased venous hydrostatic pressure is the cause of the vast majority of cases of periph-eral edema. Peripheral edema is discussed further in Chapter 4, Volume Regulation.

normal pressure elevated pressure

pre-capillary sphincter

increased�arterial�pressure

increased�venous�pressure

increased net filtration pressureno change in net �filtration pressure

VENOUS END OF CAPILLARYARTERIAL END OF CAPILLARY

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Clinical correlation: Increased venous hydrostatic pressurefrom congestive heart failure causes pulmonary edema.

Congestive heart failure (CHF) is characterized by the inability ofthe heart to maintain adequate tissue perfusion. With severe CHF, theforward flow of blood from the heart is so poor that blood accumulatesin the pulmonary venous circulation which increases the hydrostaticpressure in the pulmonary capillaries. Elevated hydrostatic pressurein the pulmonary capillaries increases the movement of fluid from thecapillaries into the alveoli. The accumulation of fluid in the alveoli ispulmonary edema.

Clinically, pulmonary edema is characterized by shortness of breathand crackles in the lung bases by auscultation. Other signs of heartfailure include increased jugular venous distension, peripheral edemaand an S3 gallop.

Acute pulmonary edema can be treated with furosemide and mor-phine, both of which decrease venous hydrostatic pressure (pre-load).Furosemide decreases hydrostatic pressure by increasing urine outputwhich decreases the amount of fluid in circulation; it also is thought todilate the pulmonary veins and directly reduce hydrostatic pressure.Morphine dilates venous vessels and has the additional effect of calm-ing an anxious patient.

pulmonary edemaheart failure

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cirrhosis severemalnutrition

DECREASED PRODUCTION OF PLASMA PROTEIN

Since proteins are the primary factor influencing osmotic pressure betweenthe plasma and interstitium, changes in plasma protein concentration can af-fect net filtration pressure. A decrease in the plasma protein concentration rela-tive to the interstitial compartment increases net filtration pressure and causesthe movement of water out of the capillaries and into the interstitium.

Changes in net osmotic pressure do not become clinically significant untilthe plasma albumin concentration is less than 2 g/dL (normal 3.5 to 5.5 g/dL).Decreased plasma protein concentration can be due to decreased production(e.g., chronic liver disease, severe malnutrition) or increased loss (e.g., neph-rotic syndrome, protein losing enteropathies).

Water movement out of the capillary�Increased net filtrationpressure can be due to decreased net osmotic pressure.

Decreased plasma protein can _________ net filtration pressure.

Increased net filtration pressure from low plasma albumin does not oc-cur until the plasma albumin falls below _______ g/dL.

increase

albumin2

nephroticsyndrome

protein-losingenteropathies

INCREASED LOSS OF PLASMA PROTEIN

Albumin represents the majority of plasma proteins. As reviewed in Chapter 2, Water, WhereAre You, the capillary membrane is permeable to electrolytes and nonelectrolytes, but not toprotein. For a solute to exert osmotic pressure (draw water in), the membrane has to beimpermeable to it. This explains why plasma protein is the primary solute which influencesosmotic pressure.

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Water movement out of the capillary�Increased net filtrationcan be due to increased membrane permeability.

The final factor of Starling’s law which affects the movement of fluid outof capillaries is membrane permeability.

Factors which increase membrane permeability are those which damagethe membrane. Capillary membrane damage may be caused by infection,inflammation, sepsis, trauma, malignancy and adult respiratory distresssyndrome (ARDS). Direct membrane damage causes the extravasation ofboth water and proteins.

With membrane damage, s rises and more water can exit without a risein hydrostatic pressure.

Capillary ___________ increases membrane permeability.

Capillary damage increases the loss of water and _________ fromthe capillary.

damage

proteins

waterprotein

waterprotein

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All fluid accumulations in the body are due to a change in one of thecomponents of Starling's law: hydrostatic pressure, osmotic pressure orcapillary permeability. This rule is the basis for the laboratory analysisof a fluid accumulation. Determining the amount of protein and otherfactors contained in the fluid can help determine if the fluid collectionis due to a change in hydrostatic pressure, osmotic pressure or capillarypermeability.

In general, a fluid collection with a low protein content is due to achange in hydrostatic pressure and is called a transudate. Transuda-tive effusions are associated with disorders characterized by increasedvenous hydrostatic pressure such as congestive heart failure and cir-rhosis. A change in osmotic pressure also results in a transudative fluidcollection.

A fluid collection with a high protein content is due to capillary dam-age and is called an exudate. Exudative effusions are caused by disor-ders which directly damage capillary membranes, such as inflamma-tion, infection and malignancy.

Although the fluid from peripheral edema cannot be analyzed, think-ing about the differential diagnosis in terms of which aspect of Starling’slaw has been altered is useful. A “transudative peripheral edema” isassociated with CHF and cirrhosis while an “exudative peripheraledema” is associated with infection (local or systemic), trauma and ma-lignancy.

Clinical correlation: Fluid collections are always due to achange in one of the components of Starling's law.

ascites peripheral edema pulmonary edemapleural effusion

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A pleural effusion is an accumulation of fluid between the parietaland visceral pleura of the lungs*. The parietal pleura lines the thoraciccavity and is connected to the visceral pleura which lines the surface ofthe lungs. The space between the visceral and parietal pleura normallycontains only a small amount of fluid.

Pleural effusions can accumulate due to a wide variety of insults whichinterfere with the absorptive capacity of the capillaries and lymphaticsof the visceral pleura. Although the differential diagnosis of a pleuraleffusion is extensive, the first step in identifying the cause of a pleuraleffusion is determining if it is a transudate or an exudate. For a pleuraleffusion to be an exudate, one of the following characteristics must bepresent (if none are present, the fluid is a transudate):

• pleural fluid protein/plasma protein greater than 0.5• pleural fluid LDH/plasma LDH greater than 0.6• pleural fluid LDH > two-thirds upper limit of normal plasma LDH

Conditions resulting in an exudative pleural effusion include thosewhich damage the capillary wall and increase membrane permeability.With capillary damage, substances such as protein and LDH, which arenormally confined to the vascular space, are able to enter the pleuralspace. The most common causes of an exudative pleural effusion areinfection and malignancy.

Conditions resulting in a transudative pleural effusion are caused byconditions which alter hydrostatic and/or osmotic pressure. The mostcommon causes of transudative pleural effusions are due to increasedhydrostatic pressure from congestive heart failure and cirrhosis.

*Don't confuse pleural effusion with pulmonary edema; pulmonary edema is the accumu-lation of fluid in the alveoli of the lungs.

Clinical correlation: Pleural effusions are categorized as ei-ther transudates or exudates.

pleural effusion

congestive heart failurecirrhosis with ascitesnephrotic syndromeperitoneal dialysissuperior vena cava obstructionmyxedemapulmonary embolismMeigs’ syndrome

Transudate Exudatepneumoniaother infectionsmalignancycollagen vascular diseases (rheumatoid arthritis, lupus)sarcoidosisdrugsuremia

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Ascites is the accumulation of fluid within the peritoneal cavity. Themost common etiology of ascites is extensive liver disease. Extensiveliver disease increases the hydrostatic pressure of the portal systemwhich results in an ascitic fluid with a low protein concentration.

Instead of referring to ascitic fluid as either a transudate or exudate,the terms high albumin gradient and low albumin gradient are used.The albumin gradient is the difference between the plasma and asciticalbumin concentrations. A high albumin gradient is greater than 1.1 g/dL and a low albumin gradient is less than 1.1 g/dL.

Ascitic fluid with a high albumin gradient is equivalent to a transu-date; it is due to increased hydrostatic pressure from portal hyperten-sion. A high albumin gradient means that the difference between theplasma albumin and the ascitic albumin is large and that little albu-min was able to pass from the capillaries into the ascitic fluid.

Ascitic fluid with a low albumin gradient is equivalent to an exu-date; it is due to factors other than portal hypertension, such as alter-ations in membrane permeability from malignancy or infection. Thelow albumin gradient indicates that there is little difference betweenthe plasma and ascitic albumin concentration and that a large amountof plasma albumin was able to cross through damaged capillaries andenter the ascitic fluid.

Clinical correlation: Ascites is categorized by the albumingradient.

albumingradient

plasmaalbumin (mg/dL)

asciticalbumin (mg/dL)

cirrhosishepatitiscongestive heart failureportal vein thrombosismyxedema

High gradient ( > 1.1 g/dL) Low gradient ( < 1.1 g/dL)malignancytuberculosispancreatic diseasenephrotic syndrome

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ALBUMIN GRADIENT = PLASMA ALBUMIN – ASCITES ALBUMIN

Summary�Starling’s law.The movement of water out of capillaries is governed by three factors:

These factors are mathematically represented by Starling’s law.

hydrostatic pressure osmotic pressure membranecharacteristics

Fluid collections with a low protein content are transudates and are dueto an increase in hydrostatic pressure while fluid collections with a highprotein content are exudates and are due to an increase in membrane per-meability. Because it so effectively narrows the differential diagnosis, analysisof pleural and ascitic fluid is commonly performed to establish whether thefluid is a transudate or exudate.

(capillaryop

– interstitialop

)

net osmotic pressure

s(capillaryhp

– interstitialhp

)

net hydrostatic pressure

Lp × S

NET FILTRATION PRESSURE

Factors which increase net filtration pressure increase the movement offluid out of the capillary. Increased net filtration pressure can be caused byincreased hydrostatic pressure, decreased osmotic pressure and increasedcapillary permeability.

The clinical applications of Starling’s law are vast. All fluid accumula-tions are due to an alteration in one of the factors of Starling’s law.

ascites peripheral edema pulmonary edemapleural effusion

PLEURAL FLUID ANALYSIS*• pleural fluid protein more

than 50% of serum protein• pleural fluid LDH more than

60% of serum LDH• pleural fluid LDH more than

66% of the upper limit ofnormal for serum LDH

* one of the three is required for the fluid to be an exudate

HIGH GRADIENT ( > 1.1 g/dL)• cirrhosis• hepatitis• congestive heart failure• portal vein thrombosis• myxedema

• malignancy• tuberculosis• pancreatic disease• nephrotic syndrome

LOW GRADIENT ( < 1.1 g/dL)

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03 Starling's Law