книги студ / color atlas of physiology 5th ed[1]. (a. despopoulos et al, thieme 2003)

!

united to form a close electrical and metabolic

unit (syncytium), as is present in the

epithelium, many smooth muscles (single-

unit type, !p. 70), the myocardium, and the

glia of the central nervous system. Electric

coupling permits the transfer of excitation,

e.g., from excited muscle cells to their adjacent

Physiology

cells, making it possible to trigger a wave of ex-

citation across wide regions of an organ, such

as the stomach, intestine, biliary tract, uterus,

ureter, atrium, and ventricles of the heart. Cer-

tain neurons of the retina and CNS also com-

Cell

municate in this manner (electric synapses).

Gap junctions in the glia

(!p. 338) and

and

epithelia help to distribute the stresses that

occur in the course of transport and barrier ac-

Fundamentals

tivities (see below) throughout the entire cell

community. However, the connexons close

when the concentration of Ca2+ (in an extreme

case, due to a hole in cell membrane) or H+

concentration increases too rapidly ( !C3). In

1

other words, the individual (defective) cell is

left to deal with its own problems when neces-

sary to preserve the functionality of the cell

community.

Transport through Cell Layers

Multicellular organisms have cell layers that

are responsible for separating the “interior”

from the “exterior” of the organism and its

larger compartments. The epithelia of skin and

gastrointestinal, urogenital and respiratory

tracts, the endothelia of blood vessels, and neu-

roglia are examples of this type of extensive

barrier. They separate the immediate extra-

cellular space from other spaces that are

greatly different in composition, e.g., those

filled with air (skin, bronchial epithelia),

gastrointestinal contents, urine or bile

(tubules,

urinary bladder,

gallbladder),

aqueous humor of the eye, blood (endothelia)

and cerebrospinal fluid (blood–cerebrospinal

fluid barrier), and from the extracellular space

of the CNS (blood–brain barrier). Nonetheless,

certain substances must be able to pass

through these cell layers. This requires selec-

tive transcellular transport with import into

the cell followed by export from the cell. Un-

like cells with a completely uniform plasma

18

membrane

(e.g., blood cells), epiand en-

dothelial cells are polar cells,

as defined by

Diffusion is movement of a substance owing to

the random thermal motion (brownian move-

ment) of its molecules or ions (!A1) in all

directions throughout a solvent. Net diffusion

Physiology

or selective transport can occur only when the

solute concentration at the starting point is

higher than at the target site. (Note: uni-

directional fluxes also occur in absence of a

concentration gradient—i.e., at equilibrium—

Cell

but net diffusion is zero because there is equal

flux in both directions.) The driving force of

and

diffusion is, therefore, a concentration gra-

Fundamentals

dient. Hence, diffusion equalizes concentra-

tion differences and requires a driving force:

passive transport (= downhill transport).

Example: When a layer of O2 gas is placed

on water, the O2 quickly diffuses into the water

along the initially high gas pressure gradient

1

(!A2). As a result, the partial pressure of O2

(Po2) rises, and O2 can diffuse further

downward into the next O2-poor layer of water

(!A1). (Note: with gases, partial pressure is

used in lieu of concentration.) However, the

steepness of the Po2 profile or gradient (dPo2/

dx) decreases (exponentially) in each sub-

sequent layer situated at distance x from the

O2 source (!A3). Therefore, diffusion is only

feasible for transport across short distances

within the body. Diffusion in liquids is slower

than in gases.

The diffusion rate, Jdiff (mol·s–1), is the

amount of substance that diffuses per unit of

time. It is proportional to the area available for

diffusion (A) and the absolute temperature (T)

and is inversely proportional to the viscosity

(η) of the solvent and the radius (r) of the dif-

fused particles.

According to the Stokes–Einstein equation,

the coefficient of diffusion (D) is derived from T,

η, and r as

D !

R ! T

[m2 ! s–1],

[1.1]

NA · 6π ! r

! η

where R is

the general

gas constant

(8.3144 J·K–1 · mol–1) and NA Avogadro’s con-

stant (6.022 · 1023 mol–1). In Fick’s first law of

20

diffusion (Adolf Fick, 1855), the diffusion rate

is expressed as

Jdiff ! A ! D ! !

dC

"[mol ! s–1]

[1.2]

dx

Jdiff ! A ! D !

C

[mol ! s–1].

[1.3]

x

Jdiff ! k ! A ! D !

C

[mol ! s–1];

[1.4]

x

Whereas the molecular radius r (!Eq. 1.1) still

largely determines the magnitude of D when k re-

Physiology

mains constant (cf. diethylmalonamide with ethyl-

urea in D), k can vary by many powers of ten when r

remains constant (cf. urea with ethanol in D) and can

therefore have a decisive effect on the permeability

of the membrane.

Cell

Since the value of the variables k, D, and

x

within the body generally cannot be deter-

and

mined, they are usually summarized as the

Fundamentals

permeability coefficient P, where

P ! k !

D

[m ! s–1].

[1.5]

x

If the diffusion rate, Jdiff [mol!s–1], is related to

area A, Eq. 1.4 is transformed to yield

1

Jdiff

! P !

C [mol ! m–2 ! s–1].

[1.6]

A

The quantity of substance (net) diffused per

unit area and time is therefore proportional to

C and P (!E, blue line with slope P).

When considering the diffusion of gases,

C

in Eq. 1.4 is replaced by α·

P (solubility coeffi-

cient

times

partial

pressure. difference;

!p. 126) and Jdiff [mol !

s–1] by Vdiff

[m3! s–1].

k · α · D is then summarized as diffusion con-

ductance, or Krogh’s diffusion coefficient K [m2 !

s–1 ! Pa–1]. Substitution into Fick’s first diffusion

equation yields

.

Vdiff

! K !

P

[m ! s–1].

[1.7]

A

x

Since

A and

x of

alveolar gas exchange

(!p. 120) cannot be determined in living or-

ganisms, K · F/

x for O2 is often expressed as

the O2

diffusion capacity of the lung, DL:

.

PO2 [m3 ! s–1].

VO2diff ! DL !

[1.8]

Nonionic diffusion occurs when the uncharged

form of a weak base (e.g., ammonia = NH3) or

acid (e.g., formic acid, HCOOH) passes through

a membrane more readily than the charged

22

form (!F). In this case, the membrane would

be more permeable

to

NH3 than

to NH4+

gx ! ! Px ! zx2 ! F2 R–1 ! T–1 !

x [S ! m–2]

[1.9]

c

c !

c1

–c2 .

[1.10]

lnc1

– lnc2

Active Transport

and, thus, for maintenance of the cell mem-

brane potential. During each transport cycle

Active transport occurs in many parts of the

(!A1, A2), 3 Na+ and 2 K+ are “pumped” out of

body when solutes are transported against

and into the cell, respectively, while 1 ATP

their concentration gradient (uphill transport)

molecule is used to phosphorylate the carrier

and/or, in the case of ions, against an electrical

protein (!A2b). Phosphorylation first

potential (! p. 22). All in all, active transport

changes the conformation of the protein and

occurs against the electrochemical gradient or

subsequently alters the affinities of the Na+

potential of the solute. Since passive transport

and K+ binding sites. The conformational

mechanisms represent “downhill” transport

change is the actual ion transport step since it

(! p. 20 ff.), they are not appropriate for this

moves the binding sites to the opposite side of

task. Active transport requires the expenditure

the membrane (!A2b – d). Dephosphoryla-

of energy. A large portion of chemical energy

tion restores the pump to its original state

provided by foodstuffs is utilized for active

(!A2e – f). The Na+/K+ pumping rate increases

transport once it has been made readily avail-

when the cytosolic Na+ concentration rises—

able in the form of ATP (! p. 41). The energy

due, for instance, to increased Na+ influx, or

created by ATP hydrolysis is used to drive the

when the extracellular K+ rises. Therefore,

transmembrane transport of numerous ions,

Na+,K+-activatable ATPase is the full name of

metabolites, and waste products. According to

the pump. Na-+K+-ATPase

is inhibited by

the laws of thermodynamics, the energy ex-

ouabain and cardiac glycosides.

pended in these reactions produces order in

Secondary active transport occurs when

cells and organelles—a prerequisite for sur-

uphill transport of a compound (e.g., glucose)

vival and normal function of cells and, there-

via a carrier protein (e.g., sodium glucose

fore, for the whole organism (! p. 38 ff.).

transporter type 2, SGLT2) is coupled with the

In primary active transport, the energy pro-

passive (downhill) transport of an ion (in this

duced by hydrolysis of ATP goes directly into

example Na+; !B1). In this case, the electro-

ion transport through an ion pump. This type

chemical Na+ gradient into the cell (created by

of ion pump is called an ATPase. They establish

Na+-K+-ATPase at another site on the cell mem-

the electrochemical gradients rather slowly,

brane; !A) provides the driving force needed

e.g., at a rate of around 1 µmol ! s–1 ! m–2 of

for secondary active uptake of glucose into the

membrane surface area in the case of Na+-K+-

cell. Coupling of the transport of two com-

ATPase. The gradient can be exploited to

pounds across a membrane is called cotrans-

achieve rapid ionic currents in the opposite

port, which may be in the form of symport or

direction after the permeability of ion chan-

antiport. Symport occurs when the two com-

nels has been increased (! p. 32 ff.). Na+ can,

pounds (i.e., compound and driving ion) are

for example, be driven into a nerve cell at a rate

transported across the membrane in the same

of up to 1000 µmol ! s–1 ! m–2 during an action

direction (!B1–3). Antiport (countertrans-

potential.

port) occurs when they are transported in op-

ATPases occur ubiquitously in cell mem-

posite directions. Antiport occurs, for example,

branes (Na+-K+-ATPase) and in the endo-

when an electrochemical Na+ gradient drives

plasmic reticulum and plasma membrane

H+ in the opposite direction by secondary ac-

(Ca2+-ATPase), renal collecting duct and stom-

tive transport (!B4). The resulting H+ gradient

ach glands (H+,K+ -ATPase), and in lysosomes

can then be exploited for tertiary active sym-

(H+-ATPase). They transport Na+, K+, Ca2+ and

port of molecules such as peptides (!B5).

H+, respectively, by primarily active mecha-

Electroneutral transport occurs when the

nisms. All except H+-ATPase consist of 2 α-sub-

net electrical charge remains balanced during

units and 2 "-subunits (P-type ATPases). The

transport, e.g., during Na+/H+ antiport (!B4)

α-subunits are phosphorylated and form the

and Na+-Cl– symport (!B2). Small charge sep-

ion transport channel (!A1).

aration occurs in electrogenic (rheogenic)

Na+-K+-ATPase is responsible for main-

transport, e.g., in

Na+-glucose0

symport

tenance of intracellular Na+ and K+ homeostasis

(!B1), Na+-amino

acid0

symport

(!B3),