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Ganong's Review of Medical Physiology, 23rd Edition

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ECF<br />

Cytoplasm<br />

FIGURE 2–18 Na + –K + ATPase. The intracellular portion <strong>of</strong> the<br />

α subunit has a Na + -binding site (1), a phosphorylation site (4), and<br />

an ATP-binding site (5). The extracellular portion has a K + -binding<br />

site (2) and an ouabain-binding site (3). (From Horisberger J-D et al:<br />

Structure–function relationship <strong>of</strong> Na–K-ATPase. Annu Rev Physiol 1991;53:565.<br />

Reproduced with permission from the Annual <strong>Review</strong> <strong>of</strong> <strong>Physiology</strong>, vol. 53.<br />

Copyright © 1991 by Annual <strong>Review</strong>s)<br />

about 24% <strong>of</strong> the energy utilized by cells, and in neurons it<br />

accounts for 70%. Thus, it accounts for a large part <strong>of</strong> the<br />

basal metabolism. A major pay<strong>of</strong>f for this energy use is the<br />

establishment <strong>of</strong> the electrochemical gradient in cells.<br />

TRANSPORT ACROSS EPITHELIA<br />

In the gastrointestinal tract, the pulmonary airways, the renal<br />

tubules, and other structures, substances enter one side <strong>of</strong> a cell<br />

and exit another, producing movement <strong>of</strong> the substance from<br />

one side <strong>of</strong> the epithelium to the other. For transepithelial transport<br />

to occur, the cells need to be bound by tight junctions and,<br />

obviously, have different ion channels and transport proteins in<br />

different parts <strong>of</strong> their membranes. Most <strong>of</strong> the instances <strong>of</strong> secondary<br />

active transport cited in the preceding paragraph involve<br />

transepithelial movement <strong>of</strong> ions and other molecules.<br />

THE CAPILLARY WALL<br />

FILTRATION<br />

The capillary wall separating plasma from interstitial fluid is<br />

different from the cell membranes separating interstitial fluid<br />

from intracellular fluid because the pressure difference across<br />

it makes filtration a significant factor in producing movement<br />

<strong>of</strong> water and solute. By definition, filtration is the process by<br />

which fluid is forced through a membrane or other barrier because<br />

<strong>of</strong> a difference in pressure on the two sides.<br />

ONCOTIC PRESSURE<br />

β<br />

3Na +<br />

1<br />

2K +<br />

The structure <strong>of</strong> the capillary wall varies from one vascular bed<br />

to another. However, in skeletal muscle and many other organs,<br />

2<br />

4<br />

3<br />

Ouabain<br />

α<br />

5<br />

CHAPTER 2 Overview <strong>of</strong> Cellular <strong>Physiology</strong> in <strong>Medical</strong> <strong>Physiology</strong> 49<br />

Countertransport<br />

3Na +<br />

Na +<br />

H +<br />

Ca 2+<br />

FIGURE 2–19 Composite diagram <strong>of</strong> main secondary effects<br />

<strong>of</strong> active transport <strong>of</strong> Na + and K + . Na,K ATPase converts the chemical<br />

energy <strong>of</strong> ATP hydrolysis into maintenance <strong>of</strong> an inward gradient<br />

for Na + and an outward gradient for K + . The energy <strong>of</strong> the gradients is<br />

used for countertransport, cotransport, and maintenance <strong>of</strong> the membrane<br />

potential. Some examples <strong>of</strong> cotransport and countertransport<br />

that use these gradients are shown. (Reproduced with permission from Skou<br />

JC: The Na–K pump. News Physiol Sci 1992;7:95.)<br />

water and relatively small solutes are the only substances that<br />

cross the wall with ease. The apertures in the junctions between<br />

the endothelial cells are too small to permit plasma proteins and<br />

other colloids to pass through in significant quantities. The colloids<br />

have a high molecular weight but are present in large<br />

amounts. Small amounts cross the capillary wall by vesicular<br />

transport, but their effect is slight. Therefore, the capillary wall<br />

behaves like a membrane impermeable to colloids, and these exert<br />

an osmotic pressure <strong>of</strong> about 25 mm Hg. The colloid osmotic<br />

pressure due to the plasma colloids is called the oncotic<br />

pressure. Filtration across the capillary membrane as a result <strong>of</strong><br />

the hydrostatic pressure head in the vascular system is opposed<br />

by the oncotic pressure. The way the balance between the hydrostatic<br />

and oncotic pressures controls exchanges across the<br />

capillary wall is considered in detail in Chapter 32.<br />

TRANSCYTOSIS<br />

Active transport<br />

2K +<br />

Ouabain<br />

ATP<br />

3Na + Na +<br />

Na +<br />

ADP + Pi<br />

Cl− Na +<br />

H +<br />

K +<br />

K +<br />

Cl− Vm = −70 mV<br />

Na + 140 meq/L<br />

K + 4 −<br />

Cl− Na<br />

− − − −<br />

+ + + +<br />

105 −<br />

+ 15 meq/L<br />

K + 150 −<br />

Cl− 7 −<br />

Na +<br />

K + , 2Cl− Sugars<br />

or amino<br />

acids<br />

Vesicles are present in the cytoplasm <strong>of</strong> endothelial cells, and<br />

tagged protein molecules injected into the bloodstream have<br />

been found in the vesicles and in the interstitium. This indicates<br />

that small amounts <strong>of</strong> protein are transported out <strong>of</strong> capillaries<br />

across endothelial cells by endocytosis on the capillary<br />

side followed by exocytosis on the interstitial side <strong>of</strong> the cells.<br />

The transport mechanism makes use <strong>of</strong> coated vesicles that<br />

appear to be coated with caveolin and is called transcytosis,<br />

vesicular transport, or cytopempsis.<br />

Cotransport

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