The physiology of edema.The physiology of edema.

ByBy

Dr Irum JunaidDr Irum Junaid

Body Fluid Body Fluid DistrbutionDistrbution

Total body water(TBW): 2/3 body Total body water(TBW): 2/3 body weightweight

TBW

intracellular 2/3

extracellular 1/3

Interstitial 3/4

intravascular 1/4

starling force

Copyright 2009, John Wiley & Copyright 2009, John Wiley & Sons, Inc.Sons, Inc.

Body Fluid CompartmentsBody Fluid Compartments

Functions of Fluids

Body fluids: Facilitate in the transport [nutrients,

hormones, proteins, & others…] Aid in removal of cellular metabolic

wastes Provide medium for cellular

metabolism Regulate body temperature Provide lubrication of musculoskeletal

jts. Component in all body cavities

[parietal, pleural… fluids]

Water is the principal body fluid & essential for life.

EdemaEdema

Edema refers to the presence of Edema refers to the presence of excess fluid in the body tissues.excess fluid in the body tissues.

It is abnormal accumulation of fluid It is abnormal accumulation of fluid beneath the skin or in one or more beneath the skin or in one or more cavities of the body. cavities of the body.

TypesTypes

It can be intracellular or extracellularIt can be intracellular or extracellular

Intracellular Edema

• Hyponatremia

• Depression of tissue metabolic systems(e.g. hypothyroidism)

• Inadequate tissue nutrition(e.g. ischemia)

• Inflammation of tissues (increased cell membrane permeability)

• Increased interstitial fluid Increased interstitial fluid volumevolume

• Increased Capillary Filtration

• Failure of lymphatics to return interstitial fluid to circulation

Extracellular Edema

Determinants of Capillary Filtration

CapillaryPressure (Pc)

Plasma ColloidOsmotic Pressure (πc)

InterstitialFluid Pressure (Pif)

Interstitial ColloidOsmotic Pressure (πif)

Kf

FILT = Kf (Pc - Pif - πc + π if)

Causes of Increased Capillary Filtration

FILT = Kf (Pc - Pif - πc + πif)

Increased Kf: Toxins, ischemic damage, infections, etc.

Increased Pc:• Increased arterial pressure, excess fluid retention, • Decreased arteriolar resistance• Increased venous resistance, increased venous pressure

Decreased πc:• Nephrotic syndrome• Cirrhosis• Malnutrition• Burns

““PRINCIPALES OF PRINCIPALES OF EQUILIBRIUM OF FORCES EQUILIBRIUM OF FORCES ACROSS CAPILLARIESACROSS CAPILLARIES””

• MEAN FORCES TENDING TO MOVE MEAN FORCES TENDING TO MOVE FLUID OUTWARD.FLUID OUTWARD.

MEAN CAPILLARY HYDROSTATIC PRESSURE MEAN CAPILLARY HYDROSTATIC PRESSURE 17.317.3

NEGATIVE INTERSTITIAL FREE FLUID PRESSURE NEGATIVE INTERSTITIAL FREE FLUID PRESSURE 3.03.0

INTERSTITIAL FLUID COLLOID OSMOTIC PRESSURE INTERSTITIAL FLUID COLLOID OSMOTIC PRESSURE 8.0 8.0

• TOTAL OUTWARD FORCE TOTAL OUTWARD FORCE 28.328.3

““PRINCIPALES OF PRINCIPALES OF EQUILIBRIUM OF FORCES EQUILIBRIUM OF FORCES ACROSS CAPILLARIESACROSS CAPILLARIES””

• MEAN FORCE TENDING TO MOVE MEAN FORCE TENDING TO MOVE FLUID INWARD.FLUID INWARD.

• PLASMA COLLOID OSMOTIC PRESSURE PLASMA COLLOID OSMOTIC PRESSURE 28.028.0

• TOTAL INWARD FORCE TOTAL INWARD FORCE 28.028.0

““PRINCIPALES OF PRINCIPALES OF EQUILIBRIUM OF FORCES EQUILIBRIUM OF FORCES ACROSS CAPILLARIESACROSS CAPILLARIES””

• SUMMATION OF MEAN FORCESSUMMATION OF MEAN FORCES

OUTWARD OUTWARD 28.3 28.3

INWARD INWARD -28.0 -28.0

• NET OUTWARD FORCE -----------NET OUTWARD FORCE -----------0.30.3

Normal FiltrationNormal FiltrationFILT = Kf x Net Filt Pressure

= 6.6 x ( 17.3 - (-3) - 28 +8)

= 6.6 x ( + 0.3)= 1.89 ml/min

FILT = 2722 ml/dayWhere does all of this fluid (and protein in it) go?

FILT = Kf (Pc - Pif - πc + πif)

Figure 25-1; Guyton and Hall

XLymphatic

Failure = EdemaCauses:•InfectionsFilarial nematodes•SurgeryRemoval of lymph nodes

Lymphatic Failure and Edema

Conditions Causing Conditions Causing EdemaEdema1. High capillary hydrostatic pressure

•Excess fluid retention by kidneys- acute or chronic kidney failure- glomerulonephritis- mineralocorticoid excess

1. High capillary hydrostatic pressure (cont’d)

• Decreased arteriolar resistance- vasodilator drugs- autonomic insufficiency

• Increased venous pressure- congestive heart failure- high output heart failure (e.g.

anemia)- venous obstruction- venous valve failure- cirrhosis

2. Decreased plasma proteins (low oncotic pressure)

• Loss of proteins- burns, wounds- nephrosis- gastroenteropathy

• Failure to produce proteins- malnutrition (“kwashiorkor”)- cirrhosis- analbuminemia

3. Increased capillary permeability• Immune reactions (histamine)• Toxins• Burns• Prolonged ischemia• Vitamin deficiency (e.g. vitamin C)• Pre-eclampsia and eclampsia in

pregnancy

4. Blockage of lymphatics• Cancer• Surgery• Infections (e.g. filarial nematodes) •Congenital absence or abnormality of lymphatic vessels

Conditions Causing Edema

Safety Factors Against Edema

• Low compliance of interstitium when = 3 mmHg interstitial fluid pressure is negative

• Increased lymph flow = 7 mmHg

• “ Wash-down” of interstitial protein = 7 mmHg at high lymph flow rates

Total Safety factor = 17 mmHg

I. Low Tissue Compliance I. Low Tissue Compliance and Negative Interstitial and Negative Interstitial Fluid Hydrostatic PressureFluid Hydrostatic Pressure

InterstitialVolume

Interstitial FluidHydrostatic Pressure

Capillary Filtration

- 8 - 4 0 + 4

12

24

36

48

60

0

Inte

rstit

ial F

luid

Vol

ume

(lite

rs)

Interstitial Fluid Pressure (mmHg)

FreeFluid

GelFluid

Low compliance

HighCompliance

Copyright © 2006 by Elsevier, Inc.

Importance of Interstitial Gel in Preventing Fluid Accumulation inthe Interstitium.

• The fluid is bound in a proteoglycan meshwork so there are no “free” fluid spaces larger than a few hundredths of a micrometer in diameter.

• Secondly, when the interstitial fluid pressure falls to very negative values, the gel does not contract greatly.

Thus, the compliance of the tissues is very low in the negative pressure range.

- 8 - 4 0 + 4

12

24

36

48

60

0

Inte

rstit

ial F

luid

Vol

ume

(lite

rs)

Interstitial Fluid Pressure (mmHg)

FreeFluid

GelFluid

Low compliance

HighCompliance

Copyright © 2006 by Elsevier, Inc.

• Pitting edemaPitting edema• The brush pile of proteoglycan

filaments is pushed apart.• Non-pitting edemaNon-pitting edema• Tissue cells swell instead of the

interstitium or• When the fluid in the interstitium

becomes clotted with fibrinogen so that it cannot move freely within the tissue spaces.

•The proteoglycan filaments act as a “spacer” for the cells and prevent rapid flow of fluid in the tissues.

•However, the usual diffusion of nutrients to the cells and the removal of waste products from the cells are not compromised by the proteoglycan filaments of the interstitium.

II. Increased Lymph II. Increased Lymph FlowFlow

InterstitialVolume

Interstitial FluidHydrostatic Pressure

Lymph Flow

Lymph Flow( x normal)

20

10

1

- 6 - 4 - 2 0 2 4Interstitial Fluid Pressure ( mmHg)

Effect of Interstitial Fluid Pressure on Lymph Flow

III. “Wash-down” of Interstitial Fluid Proteins

InterstitialVolume

Interstitial FluidOncotic Pressure

Capillary Filtration

Interstitial FluidHydrostatic Pressure

Lymph Flow

Protein Removal From Tissues

2

4

6

8

0

0 20 40 60 80 100 120 140 160 180

Plasma Protein Concentration

Rate of Non-Visceral Lymph Flow (ml/hr)

Int

erst

itia

l Flu

idP

rote

in c

once

ntra

tion

(

gm/1

00 m

l)

Wash-down of Interstitial Proteins

Safety Factors Against Safety Factors Against EdemaEdema

• Low compliance of interstitium when= 3 mmHg interstitial fluid pressure is negative

• Increased lymph flow = 7 mmHg

• “ Wash-down” of interstitial protein = 7 mmHg at high lymph flow rates

Total Safety factor = 17 mmHg

Hydrostatic pressure:Hydrostatic pressure:• Intra-capillary vs interstitial pressure:Intra-capillary vs interstitial pressure:

• Capillary pressures vary:Capillary pressures vary:

• Interstitial hydrostatic pressure:Interstitial hydrostatic pressure:Varies from one organ to another:Varies from one organ to another:

Subcutaneous tissue: Subatmospheric (-2 mmHg)Subcutaneous tissue: Subatmospheric (-2 mmHg)

Liver, kidney: +Liver, kidney: +

Brain: As high as 6 mmHgBrain: As high as 6 mmHg

• Hydrostatic pressure gradient:Hydrostatic pressure gradient:Intra-capillary hydrostatic pressure – Intra-capillary hydrostatic pressure –

interstitial fluid hydrostatic pressureinterstitial fluid hydrostatic pressure

Organ specific:Organ specific:

• Brain: Cerebral edemaBrain: Cerebral edema

• Lung: Intra-alveolar=pulmonary edema, Lung: Intra-alveolar=pulmonary edema, intra-pleural=pleural effusionintra-pleural=pleural effusion

• Peritoneum=ascitesPeritoneum=ascites

• Severe generalized edema=anasarcaSevere generalized edema=anasarca