S. Faubel and J.

Topf

3 Starling’s Law

3 Starling’s Law

3

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The Fluid, Electrolyte and Acid-Base Companion

Introduction Three factors affect the movement of water between body water compartments.
Weight of water

1

Hydrostatic pressure

so

2

Osmotic pressure

lu

3

Membrane characteristics

The previous chapter took a brief look at the factors which influence the distribution of water between compartments. These factors are hydrostatic pressure, osmotic pressure and membrane characteristics. Hydrostatic pressure is a force generated by water. Hydrostatic pressure pushes water out of a compartment. Osmotic pressure is a force exerted by solutes. Osmotic pressure draws water into a compartment. This force is dependent only on the concentration of particles (osmolality) in solution. Membrane characteristics affect the ability of water and solute to move between compartments. This chapter focuses on how these factors are incorporated into Starling’s law. Starling’s law governs fluid shifts between compartments and can be used to understand all fluid accumulations, including peripheral edema, pleural effusions and ascites.

There are two forces governing the movement of water between compartments: __________ pressure and osmotic pressure. Osmotic ___________ is the ability of a solute to cause the movement of _______.

50

te

Aaa hydrostatic pressure water

S. Faubel and J. Topf

3 Starling’s Law

Starling’s law Net hydrostatic pressure and net osmotic pressure determine the movement of water between compartments.
capillary interstitium capillary interstitium

(capillaryhp– interstitial hp ) net hydrostatic pressure

(capillaryop– interstitial op ) net osmotic pressure

To determine where water will flow between the plasma and interstitial compartments, it is necessary to look at the net hydrostatic pressure and net osmotic pressure of each compartment. Net hydrostatic pressure is the difference between the hydrostatic pressure in the capillary and the hydrostatic pressure in the interstitium. Water flows out of the compartment with the greater hydrostatic pressure. In the diagram above, the capillary hydrostatic pressure is greater than the interstitial hydrostatic pressure; the net hydrostatic pressure causes movement of water out of the capillary. Net osmotic pressure is the difference between the osmotic pressures in the capillary and interstitium. Water flows into the compartment with the higher osmotic pressure. In the diagram above, the capillary osmotic pressure is higher; the net osmotic pressure causes the movement of water into the capillary.

___________ pressure pushes water out of a compartment. ___________ pressure draws water into a compartment. ______ hydrostatic pressure is the capillary hydrostatic pressure minus the interstitial hydrostatic pressure. Net osmotic pressure is the ________ osmotic pressure minus the interstitial osmotic pressure.

Hydrostatic Osmotic Net capillary

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The Fluid, Electrolyte and Acid-Base Companion

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

MEMBRANE CHARACTERISTICS

Lp and S porosity and surface area modulate hydrostatic pressure s permeability to a solute modulates osmotic pressure

There are three independent membrane characteristics which affect the movement of water between compartments. Two of them modulate hydrostatic pressure and one modulates osmotic pressure. Hydrostatic pressure is affected by membrane surface area and the ability of water to pass through the membrane. The surface area is represented by an uppercase S and the porosity is represented by Lp. The membrane factors affecting hydrostatic pressure are rarely clinically significant. Osmotic pressure is modified by the permeability of the membrane to a solute. If the membrane is perfectly permeable to a solute, then the solute diffuses across the membrane (instead of osmotically drawing in water). Permeability of a membrane to a solute is represented by a lowercase s and ranges from zero, completely permeable, to one, completely impermeable. Membrane permeability is clinically relevant in disorders which disrupt membrane integrity (e.g., sepsis).

The membrane factors which modulate hydrostatic and osmotic forces are: ___, S and s. Two membrane characteristics modulate hydrostatic pressure: Lp and ____. The membrane factor s represents the ___________ of the membrane to solutes, a clinically important factor.

aaa Lp S permeability

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S. Faubel and J. Topf

3 Starling’s Law

Starling’s law Starling’s law is the mathematical representation of the movement of water between compartments.
NET FILTRATION PRESSURE

Lp × S

(capillaryhp– interstitial hp ) net hydrostatic pressure

s

(capillaryop– interstitial op) net osmotic pressure

Positive net filtration pressure
If net filtration pressure is positive, water moves from the capillary into the interstitium.

Negative net filtration pressure
If net filtration pressure is negative, water moves from the interstitium into the capillary.

Starling’s law is the mathematical representation of the principles of hydrostatic pressure, osmotic pressure and membrane characteristics applied to the movement of water between the capillaries and the interstitial space. The formula is arranged so that if net filtration pressure is positive (net hydrostatic pressure greater than net osmotic pressure), water moves from the capillaries into the interstitium. If net filtration pressure is negative (net osmotic pressure greater than net hydrostatic pressure), then water moves from the interstitium to the capillaries. The following pages review the clinical consequences of alterations in the variables of Starling’s Law which cause the movement of water out of the capillaries.

The movement of ______ between capillaries and the interstitium is ____________ represented by Starling’s law. The equation for Starling’s law contains _______ forces: hydrostatic pressure and _______ pressure.

water mathematically two osmotic

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The Fluid, Electrolyte and Acid-Base Companion

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

lymphatic drainage

ARTERIAL END

At the proximal end of the capillary, the net filtration pressure is positive and water moves out of the capillary.

At the distal end of the capillary, the net filtration pressure is negative and water moves into the capillary.

The application of Starling’s law to the flow of fluid in and out of the capillary is a dynamic process. At the arterial end of the capillary, the net filtration pressure is positive, which causes the movement of water from the capillary into the interstitium. This movement of fluid out of the capillary concentrates plasma protein and dilutes interstitial protein. As fluid moves through the capillary, hydrostatic pressure falls due to friction against the capillary walls. The sum of these changes causes the venous end of the capillary to have a negative net filtration pressure and resorb fluid from the interstitium. This push-and-pull pattern in the capillary bed is useful because it allows 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 positive: the net outward movement of water is greater than the net inward movement of water. The excess water which is filtered but not resorbed does not accumulate in the interstitial space. The lymphatic system absorbs this excess fluid and returns it to the circulation via the thoracic duct.

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VENOUS END

S. Faubel and J. Topf

3 Starling’s Law

Water movement out of the capillary Increased net filtration can be due to increased net hydrostatic pressure.

ARTERIAL END OF CAPILLARY

VENOUS END OF CAPILLARY

pre-capillary sphincter increased arterial pressure increased venous pressure

normal pressure
no change in net filtration pressure

elevated pressure
increased net filtration pressure

Increased capillary hydrostatic pressure increases net filtration pressure resulting in the movement of fluid from capillaries into the interstitium. It is an increase in venous hydrostatic pressure which results in a change in net filtration pressure. The arterial ends of capillaries contain pressuresensitive precapillary sphincters which compensate for changes in blood pressure. Therefore, the increased arterial blood pressure of hypertension does not affect hydrostatic pressure and does not cause edema. Clinically, increased hydrostatic pressure is seen in congestive heart failure and cirrhosis. The consequences of increased hydrostatic pressure include peripheral edema, pulmonary edema and ascites.
Increased venous hydrostatic pressure is the cause of the vast majority of cases of peripheral edema. Peripheral edema is discussed further in Chapter 4, Volume Regulation .

The clinical consequences of increased hydrostatic pressure include peripheral ________, pulmonary _______ and ascites. Increased _________ blood pressure does not cause an increase in capillary hydrostatic pressure. Increased venous hydrostatic pressure _________ net filtration pressure.

aaa edema; edema arterial increases

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The Fluid, Electrolyte and Acid-Base Companion

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

heart failure

pulmonary edema

Congestive heart failure (CHF) is characterized by the inability of the heart to maintain adequate tissue perfusion. With severe CHF, the forward flow of blood from the heart is so poor that blood accumulates in the pulmonary venous circulation which increases the hydrostatic pressure in the pulmonary capillaries. Elevated hydrostatic pressure in the pulmonary capillaries increases the movement of fluid from the capillaries into the alveoli. The accumulation of fluid in the alveoli is pulmonary edema. Clinically, pulmonary edema is characterized by shortness of breath and crackles in the lung bases by auscultation. Other signs of heart failure include increased jugular venous distension, peripheral edema and an S3 gallop. Acute pulmonary edema can be treated with furosemide and morphine, both of which decrease venous hydrostatic pressure (pre-load). Furosemide decreases hydrostatic pressure by increasing urine output which decreases the amount of fluid in circulation; it also is thought to dilate the pulmonary veins and directly reduce hydrostatic pressure. Morphine dilates venous vessels and has the additional effect of calming an anxious patient.

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S. Faubel and J. Topf

3 Starling’s Law

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

DECREASED PRODUCTION OF PLASMA PROTEIN

INCREASED LOSS OF PLASMA PROTEIN

cirrhosis

severe malnutrition

nephrotic syndrome

protein-losing enteropathies

Since proteins are the primary factor influencing osmotic pressure between the plasma and interstitium, changes in plasma protein concentration can affect net filtration pressure. A decrease in the plasma protein concentration relative to the interstitial compartment increases net filtration pressure and causes the movement of water out of the capillaries and into the interstitium. Changes in net osmotic pressure do not become clinically significant until the 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., nephrotic syndrome, protein losing enteropathies).

Albumin represents the majority of plasma proteins. As reviewed in Chapter 2, Water, Where Are You, the capillary membrane is permeable to electrolytes and nonelectrolytes, but not to protein. For a solute to exert osmotic pressure (draw water in), the membrane has to be impermeable to it. This explains why plasma protein is the primary solute which influences osmotic pressure.
Decreased plasma protein can _________ net filtration pressure. Increased net filtration pressure from low plasma albumin does not occur until the plasma albumin falls below _______ g/dL. increase albumin 2

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The Fluid, Electrolyte and Acid-Base Companion

Water movement out of the capillary Increased net filtration can be due to increased membrane permeability.

water

protein

water

protein

The final factor of Starling’s law which affects the movement of fluid out of capillaries is membrane permeability. Factors which increase membrane permeability are those which damage the membrane. Capillary membrane damage may be caused by infection, inflammation, sepsis, trauma, malignancy and adult respiratory distress syndrome (ARDS). Direct membrane damage causes the extravasation of both water and proteins. With membrane damage, s rises and more water can exit without a rise in hydrostatic pressure.

Capillary ___________ increases membrane permeability. Capillary damage increases the loss of water and _________ from the capillary.

damage proteins

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S. Faubel and J. Topf

3 Starling’s Law

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

ascites

peripheral edema

pleural effusion

pulmonary edema

All fluid accumulations in the body are due to a change in one of the components of Starling's law: hydrostatic pressure, osmotic pressure or capillary permeability. This rule is the basis for the laboratory analysis of a fluid accumulation. Determining the amount of protein and other factors contained in the fluid can help determine if the fluid collection is due to a change in hydrostatic pressure, osmotic pressure or capillary permeability. In general, a fluid collection with a low protein content is due to a change in hydrostatic pressure and is called a transudate. Transudative effusions are associated with disorders characterized by increased venous hydrostatic pressure such as congestive heart failure and cirrhosis. A change in osmotic pressure also results in a transudative fluid collection. A fluid collection with a high protein content is due to capillary damage and is called an exudate. Exudative effusions are caused by disorders which directly damage capillary membranes, such as inflammation, infection and malignancy. Although the fluid from peripheral edema cannot be analyzed, thinking about the differential diagnosis in terms of which aspect of Starling’s law has been altered is useful. A “transudative peripheral edema” is associated with CHF and cirrhosis while an “exudative peripheral edema” is associated with infection (local or systemic), trauma and malignancy.

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The Fluid, Electrolyte and Acid-Base Companion

Clinical correlation: Pleural effusions are categorized as either transudates or exudates.
Transudate
congestive heart failure cirrhosis with ascites nephrotic syndrome peritoneal dialysis superior vena cava obstruction myxedema pulmonary embolism Meigs’ syndrome

Exudate
pneumonia other infections malignancy collagen vascular diseases (rheumatoid arthritis, lupus) sarcoidosis drugs uremia

pleural effusion

A pleural effusion is an accumulation of fluid between the parietal and visceral pleura of the lungs*. The parietal pleura lines the thoracic cavity and is connected to the visceral pleura which lines the surface of the lungs. The space between the visceral and parietal pleura normally contains only a small amount of fluid. Pleural effusions can accumulate due to a wide variety of insults which interfere with the absorptive capacity of the capillaries and lymphatics of the visceral pleura. Although the differential diagnosis of a pleural effusion is extensive, the first step in identifying the cause of a pleural effusion is determining if it is a transudate or an exudate. For a pleural effusion to be an exudate, one of the following characteristics must be present (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 those which damage the capillary wall and increase membrane permeability. With capillary damage, substances such as protein and LDH, which are normally confined to the vascular space, are able to enter the pleural space. The most common causes of an exudative pleural effusion are infection and malignancy. Conditions resulting in a transudative pleural effusion are caused by conditions which alter hydrostatic and/or osmotic pressure. The most common causes of transudative pleural effusions are due to increased hydrostatic pressure from congestive heart failure and cirrhosis.
*Don't confuse pleural effusion with pulmonary edema; pulmonary edema is the accumulation of fluid in the alveoli of the lungs.

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S. Faubel and J. Topf

3 Starling’s Law

Clinical correlation: Ascites is categorized by the albumin gradient.
albumin gradient plasma albumin (mg/dL) ascitic albumin (mg/dL)

High gradient ( > 1.1 g/dL)
cirrhosis hepatitis congestive heart failure portal vein thrombosis myxedema

Low gradient ( < 1.1 g/dL)
malignancy tuberculosis pancreatic disease nephrotic syndrome

Ascites is the accumulation of fluid within the peritoneal cavity. The most common etiology of ascites is extensive liver disease. Extensive liver disease increases the hydrostatic pressure of the portal system which 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 ascitic albumin 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 transudate; it is due to increased hydrostatic pressure from portal hypertension. A high albumin gradient means that the difference between the plasma albumin and the ascitic albumin is large and that little albumin was able to pass from the capillaries into the ascitic fluid. Ascitic fluid with a low albumin gradient is equivalent to an exudate; it is due to factors other than portal hypertension, such as alterations in membrane permeability from malignancy or infection. The low albumin gradient indicates that there is little difference between the plasma and ascitic albumin concentration and that a large amount of plasma albumin was able to cross through damaged capillaries and enter the ascitic fluid.

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The Fluid, Electrolyte and Acid-Base Companion

Summary

Starling’s law.

The movement of water out of capillaries is governed by three factors:
hydrostatic pressure osmotic pressure membrane characteristics

These factors are mathematically represented by Starling’s law.
NET FILTRATION PRESSURE

Lp × S

(capillaryhp– interstitial hp ) net hydrostatic pressure

s

(capillaryop– interstitial op ) net osmotic pressure

Factors which increase net filtration pressure increase the movement of fluid out of the capillary. Increased net filtration pressure can be caused by increased hydrostatic pressure, decreased osmotic pressure and increased capillary permeability. The clinical applications of Starling’s law are vast. All fluid accumulations are due to an alteration in one of the factors of Starling’s law.

ascites

peripheral edema

pleural effusion

pulmonary edema

Fluid collections with a low protein content are transudates and are due to an increase in hydrostatic pressure while fluid collections with a high protein content are exudates and are due to an increase in membrane permeability. Because it so effectively narrows the differential diagnosis, analysis of pleural and ascitic fluid is commonly performed to establish whether the fluid is a transudate or exudate.
PLEURAL FLUID ANALYSIS * ALBUMIN GRADIENT

=

PLASMA ALBUMIN

– ASCITES

ALBUMIN

• 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 of normal for serum LDH * one of the three is required for the fluid to be an exudate

HIGH GRADIENT ( > 1.1 g/dL)

LOW GRADIENT ( < 1.1 g/dL)

• • • • •

cirrhosis hepatitis congestive heart failure portal vein thrombosis myxedema

• • • •

malignancy tuberculosis pancreatic disease nephrotic syndrome

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