U N I T IV

Textbook of Medical Physiology, 11th Edition

Chapter 16:
The Microcirculation and Lymphatic System

By Dr. Mudassar Ali Roomi (MBBS, M. Phil)

GUYTON & HALL

Copyright 2006 by Elsevier, Inc.

The Microcirculation
Important in the transport of nutrients to tissues. Site of waste product removal. Over 10 billion capillaries with surface area of 500-700 square meters perform function of solute and fluid exchange.

Figure 16-1; Guyton and Hall

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Structure of Capillary Wall

Composed of unicellular layer of endothelial cells surrounded by a basement membrane. Diameter of capillaries is 4 to 9 microns (um).

Figure 16-2; Guyton and Hall

Solute and water move across capillary wall via intercellular cleft (space between cells) or by plasmalemma vesicles.
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Solute and Fluid Exchange Across Capillaries

Most important means by which substances are transferred between plasma and interstitial fluid is by diffusion. Lipid soluble substances diffuse directly through cell membrane of capillaries (i.e. CO2, O2).
Lipid insoluble substances such as H2O, Na, Cl, glucose cross capillary walls via intercellular clefts. Concentration differences across capillary enhances diffusion.
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Effect of Molecular Size on Passage Through Capillary Pores

The width of capillary intercellular slit pores is 6 to 7 nanometers. The permeability of the capillary pores for different substances varies according to their molecular diameters. The capillaries in different tissues have extreme differences in their permeabilities. Intestine, liver, kidney, choroid plexus have highly permeable capillaries. Brain, lungs and skeletal muscles capillaries are less permeable.
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Figure 16-2; Guyton and Hall

Relative Permeability of Muscle Capillary Pores to Different-sized Molecules

Substance
Water NaCl Urea Glucose Sucrose Insulin Myoglobin Hemoglobin Albumin

Molecular Weight
18 58.5 60 180 342 5000 17,600 69,000 69,000

Permeability
1.00 0.96 0.8 0.6 0.4 0.2 0.03 0.01 .0001

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Interstitium and Interstitial Fluid

Space between cells is called interstitium; fluid in this space is called interstitial fluid.

Two major types of solid structures in interstitium are collagen fibers and proteoglycan filaments (coiled molecules composed of hyaluronic acid).
Almost all fluid in interstitium is in form of gel (fluid proteoglycan mixtures); there is very little free fluid under normal conditions. Advantages of tissue gel are as follows:
1. It keep the cells in the tissues held apart so that spaces are available for the movement of fluid. 2. Tissue gel prevents the movement of fluid from the upper part of the body to lower part due to gravity. 3. It immobilizes the bacteria so prevents the spread of infection
Figure 16-4; Guyton and Hall

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Determinants of Net Fluid Movement across Capillaries (Starling forces)

Figure 16-5; Guyton and Hall

Capillary hydrostatic pressure (Pc)-tends to force fluid outward through the capillary membrane.
Interstitial fluid pressure (Pif)- opposes filtration when value is positive.
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Determinants of Net Fluid Movement across Capillaries

Figure 16-5; Guyton and Hall

Plasma colloid osmotic pressure ( c)- opposes filtration causing osmosis of water inward through the membrane Interstitial fluid colloid pressure ( if) promotes filtration by causing osmosis of fluid outward through the membrane NP = (Pc Pif)- ( p - if)
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Starling Forces (Part I)

Normal Capillary hydrostatic pressure is approximately 17 mmHg.
Interstitial fluid pressure in most tissues is negative 3. Encapsulated organs have positive interstitial pressures (+5 to +10 mmHg). Negative interstitial fluid pressure is caused by pumping of lymphatic system. Colloid osmotic pressure is caused by presence of large proteins.
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Starling Forces (Part II)

Presence of negative ions on proteins increases the colloid osmotic effect of proteinsDonnan effect.
Plasma colloid osmotic = 28mmHg Plasma protein conc. = 7.3mg/dl The reflection coefficient of capillaries quantitates the amount of protein that is reflected away from the capillary membrane. Reflection coefficient of 1 means all proteins are reflected and none pass through pores, reflection coefficient of 0 means membrane is permeable to all proteins.
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Plasma Proteins and Colloid Osmotic Pressure

75% of the total colloid osmotic pressure of plasma results from the presence of albumin and 25% is due to globulins.
gm/dl 4.5 2.5 0.3 7.3

p(mmHg)
21.8 6.0 0.2 28.0

Albumin Globulins Fibrinogen Total

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Interstitial Colloid Osmotic Pressure

Interstitial protein conc. is approx. 3gm/dl The interstitial colloid osmotic pressure is normally 8mmHg

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Determinants of Net Fluid Movement Across Capillaries

Figure 16-5; Guyton and Hall

Filtration rate = net filtration pressure (NFP) multiplied by the filtration coefficient Filtration coefficient (Kf) is a product of surface area times the hydraulic conductivity of membrane
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Net Starting Forces in Capillaries

Mean forces tending to move fluid outward: Mean Capillary pressure Negative interstitial free fluid pressure Interstitial fluid colloid osmotic pressure TOTAL OUTWARD FORCE Mean force tending to move fluid inward: Plasma colloid osmotic pressure TOTAL INWARD FORCE Summation of mean forces: Outward Inward NET OUTWARD FORCE
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mmHg
17.3 3.0 8.0 28.3 28.0 28.0

28.3 28.0 0.3

Net Starting Forces in Capillaries

Figure opener; Guyton and Hall

Net filtration pressure of .3 mmHg which causes a net filtration rate of 2ml/min for entire body.
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Lymphatic System
An accessory route by which fluid and protein can flow from interstitial spaces to the blood Important in preventing edema Lymph is derived from interstitial fluid that flows into the lymphatics

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FUNCTIONS OF THE LYMPHATIC SYSTEM:

1. It carries excess of interstitial fluid from interstitium into the blood. Rate of lymph flow is more than 3 liters/day. So this amount is drained by lym phatic system. 2. It drains proteins and electrolytes from Interstitial space into lymphatic system. Lymphatic system drain 195 grams of blood proteins from interstitium back into the blood. 3. It provides lymphocytes and antibodies into the circulation 4. Removes bacteria and other microorganisims from the tissues. 5. Lacteals are involved in the absorption and transport of lipids. 6. Many large enzymes which are produced in the tissues get entry into the circulation through lymphatic system like histaminases and lipase. 7. It maintains the negative interstitial fluid hydrostatic pressure.

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Determinants of Lymph Flow:

Figure 16-11; Guyton and Hall

The degree of activity of the lymphatic pump

- smooth muscle filaments in lymph vessel cause them to contract - external compression also contributes to lymphatic pumping
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Determinants of Lymph Flow (cont..)

Interstitial fluid hydrostatic pressure Lymph Flow

Figure 16-9; Guyton and Hall

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Figure 16-10; Guyton and Hall

Determinants of Lymph Flow (cont..)

Pressure on Lymphatics from outside:

1. Skeletal Muscle Contraction 2. Movements of different parts of body 3. Pressure by objects which come in contact on the outer surface of the body 4. Pulsations of nearby arteries

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FACTORS CONTROLLING THE FORMATION OF TISSUE FLUID

1. Starlings Forces 2. Capillary permeability 3. Lymphatic obstruction

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Causes of Extracellular Edema

I. Increased capillary pressure
A. Excessive kidney retention of salt and water 1. Acute or chronic kidney failure 2. Mineralocorticoid excess B. High venous pressure and venous constriction
1. Heart failure 2. Venous obstruction 3. Failure of venous pumps
(a) Paralysis of muscles (b) Immobilization of parts of the body (c) Failure of venous valves

C. Decreased arteriolar resistance 1. Excessive body heat 2. Insufficiency of sympathetic nervous system 3. Vasodilator drugs

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Causes of Extracellular Edema (cont..)

II. Decreased plasma proteins A. Loss of proteins in urine (nephrotic syndrome) B. Loss of protein from denuded skin areas
1. Burns 2. Wounds

C. Failure to produce proteins

1. Liver disease (e.g., cirrhosis) 2. Serious protein or caloric malnutrition

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Causes of Extracellular Edema (cont)

III. Increased capillary permeability
A. Immune reactions that cause release of histamine and other immune products B. Toxins C. Bacterial infections D. Vitamin deficiency, especially vitamin C E. Prolonged ischemia F. Burns

IV. Blockage of lymph return

A. Cancer B. Infections (e.g., filaria nematodes) C. Surgery D. Congenital absence or abnormality of lymphatic vessels

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SAFETY FACTOR to prevent the development of edema

The development of edema is not an easy process. First the safety factor has to be overcome to cause edema. Safety factor is equal to 17 mm of Hg. It has three components i.e.
1. Negative Interstitial Fluid Hydrostatic pressure: which contributes -3 mm of Hg. 2. Capacity of Lymphatic System: Increased amount of tissue fluid formed by 7 mm of Hg increase in Capillary pressure can be drained by lymphatic flow 3. Increased Washout of proteins from Interstitium: it contributes 7 mmHg. When there is increased formation of tissue fluid there is increased amount of fluid along with proteins that will enter the interstitium and then lymphatics for washing out. So the interstitial fluid colloid osmotic pressure can decrease from 8 mm of Hg upto 1mm of Hg before edema can start.

Copyright 2006 by Elsevier, Inc.