transport, and bulk ﬂ ow. Mediated transport constitutes a
fourth mechanism in the capillaries of the brain. Diffusion
and vesicle transport are described in this section, and bulk
ﬂ ow in the next.
In all capillaries, excluding those in the brain, diffusion
is the only important means by which net movement of nutri-
ents, oxygen, and metabolic end products occurs across the cap-
As described in the next section, there is some
movement of these substances by bulk ﬂ ow, but the amount
Chapter 4 described the factors determining diffusion
rates. Lipid-soluble substances, including oxygen and carbon
dioxide, easily diffuse through the plasma membranes of the
capillary endothelial cells. In contrast, ions and polar mole-
cules are poorly soluble in lipid and must pass through small
water-ﬁ lled channels in the endothelial lining.
The presence of water-ﬁ lled channels in the capillary
walls causes the permeability of ions and small polar molecules
to be quite high, although still much lower than that of lipid-
soluble molecules. One location where these channels exist
is in the intercellular clefts—that is, the narrow water-ﬁ lled
spaces between adjacent cells. The fused-vesicle channels that
penetrate the endothelial cells provide another set of water-
ﬁ l l e d c h a n n e l s .
The water-ﬁ lled channels allow only very small amounts
of protein to diffuse through them. Very small amounts of pro-
tein may also cross the endothelial cells by vesicle transport—
endocytosis of plasma at the luminal border and exocytosis of
the endocytotic vesicle at the interstitial side.
Variations in the size of the water-ﬁ lled channels account
for great differences in the “leakiness” of capillaries in differ-
ent organs. At one extreme are the “tight” capillaries of the
brain, which have no intercellular clefts, only tight junctions.
Therefore, water-soluble substances, even those of low molec-
ular weight, can gain access to or exit from the brain inter-
stitial space only by carrier-mediated transport through the
At the other end of the spectrum are liver capillaries,
which have large intercellular clefts as well as large holes in the
plasma membranes of the endothelial cells so that even pro-
tein molecules can readily pass across them. This is important
because two of the major functions of the liver are the synthe-
sis of plasma proteins and the metabolism of substances bound
to plasma proteins.
The leakiness of capillaries in most organs and tissues
lies between these extremes of brain and liver capillaries.
What sequence of events is involved in the transfers of
nutrients and metabolic end products between capillary blood
and cells? Nutrients diffuse ﬁ rst from the plasma across the cap-
illary wall into the interstitial ﬂ
uid, where they gain entry to
cells. Conversely, metabolic end products from the tissues move
across the cells’ plasma membranes into interstitial ﬂ
they diffuse across the capillary endothelium into the plasma.
Transcapillary diffusion gradients for oxygen and nutri-
ents occur as a result of cellular utilization of the substance.
Those for metabolic end products arise as a result of cellular
production of the substance. Consider two examples: glu-
cose and carbon dioxide in muscle (
is continuously transported from interstitial ﬂ uid into the
muscle cell by carrier-mediated transport mechanisms. The
removal of glucose from interstitial ﬂ uid lowers the interstitial
ﬂ uid glucose concentration below the glucose concentration
in capillary plasma and creates the gradient for glucose diffu-
sion from the capillary into the interstitial ﬂ
Simultaneously, carbon dioxide, which is continuously
produced by muscle cells, diffuses into the interstitial ﬂ
This causes the carbon dioxide concentration in interstitial
ﬂ uid to be greater than that in capillary plasma, producing a
gradient for carbon dioxide diffusion from the interstitial ﬂ
into the capillary.
Note that in both examples, metabolism—either utiliza-
tion or production—of the substance is the event that ulti-
mately establishes the transcapillary diffusion gradients.
If a tissue is to increase its metabolic rate, it must obtain
more nutrients from the blood and must eliminate more meta-
bolic end products. One mechanism for achieving that is active
hyperemia. The second important mechanism is increased dif-
fusion gradients between plasma and tissue: Increased cellular
Diffusion gradients at a systemic capillary.
If cellular metabolism was not changed, but the blood ﬂ ow
through a tissue’s capillaries was reduced, how would the
venous blood leaving that tissue differ compared to that
before ﬂ ow reduction?
Answer can be found at end of chapter.