The Alkali Metal Ions in Biology: I. The Alkali Metal Ions in Isolated Systems and Tissues. II. The Alkali Metal Ions in the Organism

609 Pages·1960·20.358 MB·English

by  Hans H. Ussing, P. Kruhøffer, J. Hess Thaysen, N. A. Thorn (auth.)

HANDBUCH
DER EXPERIMENTELLEN
PHARMAKOLOGIE
BEGRONDET VON A. HEFFTER
FORTGEFOHRT VON W. HEUBNER
ERGANZUNGSWERK
HERAUSGEGEBEN VON
O. EICHLER A.FARAH
UND
PROFESSOR DER PHARllAKOLOGIE I'ROFESSOR DER PHARMAKOLOGIE
AN DER UNIVERSITAT HEIDELBERG AN DER STATE UNIVERSITY OF NEW YORK
DREIZEHNTER BAND
THE ALKALI METAL IONS IN BIOLOGY
BY
H. H. USSING, P. KRUH0FFER, J. HESS THAYSEN AND N.A. THORN
SPRINGER-VERLAG
BERLIN· GOTTINGEN . HEIDELBERG
1960
THE ALKALI METAL IONS
IN BIOLOGY
I. THE ALKALI METAL IONS
IN ISOLATED SYSTEMS AND TISSUES
BY
HANS H. USSING
II. THE ALKALI METAL IONS
IN THE ORGANISM
BY
P. KRUH0FFER, J. HESS THAYSEN AND N. A. THORN
WITH 47 FIGURES
SPRINGER-VERLAG
BERLIN· GOTTINGEN . HEIDELBERG
1960
ISBN-13: 978-3-642-49248-8 e-ISBN-13: 978-3-642-49246-4
DOl: 10.1007/978-3-642-49246-4
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© by S pringer-Verlag oH G. Berlin· G6ttingen . Heidelberg 1959
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in diesem Werk bereehtigt aueh ollne besondere Kennzeiehnung niellt zu der
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werden d iirften
Contents
Part I: The alkali metal ions in isolated systems and tissues
By HANS H. Us SING
Page
I. General introduction .............. . 1
II. Physical and chemical properties of the alkali metal ions 2
a) Introduction . . . 2
b) Chemical properties . . . . . . . 3
c) Chemical binding . . . . . . . . 4
d) Chelates with low-molecular anions 4
e) Binding by ion exchange resins. . 5
f) Binding by phosphate esters and polyphosphates 6
g) Binding by nucleic acids. . . . . . . . . 8
h) Binding by polyvalent acid polysaccharides 8
i) Binding by proteins. . . . . . . . . . . 9
III. Role of alkali metal ions in enzymatic processes 10
a) Introduction . . . . . . . . . . . . 10
b) Specific effects on enzymatic processes II
1. Pyruvic phosphoferase 11
2. Fructokinasc 12
3. Bacterial hexokinase . 13
4. Phosphofructokinase . 13
5. Acetate-activating enzyme (and "choline acetylase") 14
6. Phosphotransacetylase . . . . . . . . 15
7. Glutathione synthesizing enzyme system 15
8. Aldehyde dehydrogenase (from yeast) 16
9. tJ-galactosidase (from Escherichia coli) 16
10. Apyrase (brain adenosinetriphosphatase) 17
11. Bacterial apyrase 17
12. ATP-ase from crab nerve 17
13. Myosin ATP-ase . . . . 18
14. Urease· ....... . 18
c) Non-specific effects of alkali metal ions 19
d) Comments . . . . . . . . . . . . . 20
IV. Effect of alkali metal ions on mitochondria 21
V. Metabolic effects on tissues and tissue slices 23
a) Effects on oxygen consumption. 24
1. Brain slices . . 24
2. Peripheral nerve 25
3. Liver slices . 25
4. Muscle .... 26
5. Kidney slices 27
6. Isolated frog skin 27
b) Effects on glycolysis 28
c) Effect on acetyl choline synthesis 28
d) Effect on glycogen synthesis . . 29
e) Effects on fatty acid metabolism 31
f) Effects on cellular accumulation of various substances. 31
g) Morphogenetic effects of lithium 32
1. The effects oflithium. . . . . . . . . . . . . . 32
2. Mechanism of the Li effect . . . . . . . . . . . 34
VI. Distribution of the alkali metal ions between cells and their surroundings 36
a) General remarks ...... . 36
b) State of potassium in living cells 37
c) State of Rb and Cs in living cells 43
d) State of sodium in living cells 44
VI Contents
Page
VII. Active and passive transport of the alkali metal ions . 45
A. Characterization and biological role . 45
a) Introduction . . . . . . 45
b) Passive transport . . . . 47
c) "Simple" passive transport 47
d) The flux ratio . . . . . . 49
e) The effect of solvent drag. 51
f) Passive permeability and membrane structure. 54
g) Permeability of intercellular cements. . . . . 55
h) Ionic permeability and the development of bioelectric potentials 56
i) Active transport of the alkali metal ions (The "Sodium pump") 57
j) Relation of the active transport to metabolism. . . . . . . . 60
k) Quantitative relationship between oxygen consumption and active ion
transport ....................... 61
1) Temperature dependency of the "sodium pump" ...... 62
m) Effects of drugs and hormones on active and passive transport 63
1. Steroid hormones . . . . . . . . . 63
2. Cardiac glycosides and their aglucones ......... 64
3. Different Hormones . . . . . . .. ......... 64
Acetyl choline p. 64. - Histamine p. 65. - Adrenaline p. 65. - Neuro
hypophyseal hormones p. 65.
n) Role of alkali ion transport in the regulation of the volume of living cells . . 65
0) Mechanisms proposed for the active transport of alkali metal ions . . . . 67
1. Simple membrane-carrier transport p. 67. - 2. Electron-linked carrier
transport p. 68. - 3. Propelled carrier transport p. 68. - 4. "Asymme
trically collapsing lattice" theories p. 69. - 5. The fluid circuit mecha
nisms p. 69. - 6. Pinocytosis p. 69.
B. Transport between cells and their surroundings 70
a) Erythrocytes . . . . . . . . . . . . . . 71
1. Transport of potassium in human erythrocytes 73
2. Transport of sodium in human erythrocytes. 75
3. Effect of PH on the Na transport . . . 76
4. Effect of temperature . . . . . . . . 76
5. Transport of Li in human erythrocytes 77
6. Transport of Rb in human erythrocytes 77
7. Transport of Cs in human erythrocytes 77
8. Evidence for a coupling between active sodium extrusion and potassium
uptake ....................... 77
9. Relation of the active and passive transports to metabolism 78
10. Effects of cardiac glucosides on the transport processes 79
11. Ion transport by red cell "ghosts" . . . . . . . . . 80
12. Mechanism of the active transport . . . . . . . . . 81
13. Nature of the diffusion of alkali metal ions through the erythrocyte
membrane . . . . . . . . . . . . . . . . . . . . 81
14. Alkali metal ion transport in other mammalian red c'ells 82
15. Transport of K and Na in bird red cells . . . . . . . 82
16. Transport of K and Na in red cells of lower vertebrates 83
b) Muscle . . . . . . . . . . . . . . . . . . 84
1. Development of the "sodium pump" concept . . . . . 85
2. Net transports of K and Na in muscle . . . . . . . . 88
3. The sodium flux across the frog-muscle fibre membrane 89
4. Energy requirement of the active Na transport in frog muscle 91
5. The potassium fluxes of frog muscle . . . . . . . . 93
6. The potassium fluxes of mammalian muscle 95
7. Alkali metal ion shifts in relation to muscular activity 95
c) Peripheral nerve. . . . . . . . . . . . . . . . . . 95
1. Movements of potassium and sodium in the resting nerve 96
2. Effect of temperature on cation fluxes in nerve . . . . . 98
3. Active transport of Na in cephalopod giant axons 99
4. Coupling between Na-outflux and K-influx . . . . . . . 99
5. Nature of the passive movement of K through the cephalopod giant axon
membrane . . . . . . . . . . . . . . . . . lOO
6. Passive potassium transport during current flow . . . . . . . . . . 101
Contents VII
Page
7. Passive transport of Na through the giant fibre membrane 101
8. Potassium and sodium shifts during activity 102
d) Leucocytes . . . . . . . . . 103
e) Brain slices and isolated retina. 103
f) Mouse ascites carcinoma cells 105
g) Liver slices . . . . . . 106
h) Kidney cortex slices . . 106
i) Seminal vesicle mucosa. 107
j ) Yeast cells . . . . . 108
k) VIva lactuca 109
I) Halicystis and Valonia 109
m) Nitellopsis (Characeae) III
n) Higher plants . . . . III
C. Transport through epithelial membranes 112
a) Introduction . . . . . . . . . . . 112
b) The amphibian skin . . . . . . . . 114
1. The active sodium transport of the frog skin and its relation to the skin
potential. . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
2. The relation between oxygen consumption and active sodium transport 120
3. The work performed by the active sodium transport mechanism 120
4. The electromotive force of the active sodium transport 122
5. Inhibitors of the active sodium transport .......... 125
6. Stimulants of active sodium transport . . . . . . . . . . . . 126
7. The action of neurohypophyseal hormones upon thc transfer of water and
salt across the frog skin . . . . . . . . . . . . . . . . . . . . . 127
8. The relationship between active sodium transport and transport of water
across the skin . . . 128
c) The rumen of ruminants 129
d) The toad urinary bladder 130
e) Intestinal mucosa . . . 131
1. Net transport of sodium 131
2. The dependency of the sodium transport upon different factors 133
3. The unidirectional sodium fluxes . . . . . . . . . . . . . 134
4. Intestinal potentials and their relation to active sodium transport 136
5. The transport of potassium across the intestinal wall 138
f) Kidney tubulus . . . . . . . . . . . . . . . . . . . 139
g) The Malpighian tubules of insects . . . . . . . . . . . 140
h) The formation of the endolymph ........... 141
i) Active K transport in the formation of bull seminal plasma 142
j) The gills of Eriocheir sinensis (The "woolhanded crab") 142
VIII. Relation of the alkali metal ions to bioelectric phenomena 144
A. Relation to maintained potentials . . . . . . . . . 144
a) Introduction . . . . . . . . . . . . . . . . . 144
b) Effect of K on the resting potential of muscle and nerve 144
1. Striated muscle 144
2. Heart muscle. 147
3. Smooth muscle 147
4. Nerve . . . . 148
c) Dependency of the K effect upon other ion species 150
d) Effect of external Na upon the resting potential of nerve and muscle 150
e) Effects of the non-biological alkali metal ions upon the resting potential 151
B. Relation to the electric activity of nerve and muscle . . . . . . . .. 151
a) The "sodium" theory of excitation (HODGKIN-HuXLEy-KATZ) . . .. 151
b) The relation of the external Na concentration to the action potential of
single nerve fibres . . . . . . . . . . . . . . . . . . . . . . .. 153
c) Effect of Li upon the action potential of single nerve fibres . . . . .. 154
d) Relation of K to the action potential of single nerve fibres . . . . .. 154
e) The contributions of Na and K to the membrane current in squid axons 154
f) The applicability and limitations of the sodium theory of electric activity 160
g) Effect of external Na concentration upon excitation and conduction 162
1. Effects on nerve . . . . . . . . . . 162
2. The nerve sheath as a diffusion barrier. 162
3. Effects on striated muscle . . . . . . 163
VIII Contents
Page
4. Effects on heart muscle . . . . . . . . . . . . . . . . . 164
h) Effect of internal Na concentration on electric activity in muscle 164
i) Effects of K upon excitation and conduction 165
1. Nerve .... 165
2. Striated muscle 166
3. Heart muscle . 167
C. Relations to the electric activity of neuromuscular junctions and synapses 168
a) Neuromuscular junctions . . 168
1. Effects of Na . . . . . . 169
2. Effects of potassium. . . 170
b) The sub-synaptic membrane 170
D. Relation to the electric activity of electric organs 171
IX. Role of the alkali metal ions in muscular contraction 172
A. Introduction: Non-living models 172
B. Effects on skeletal muscle 174
a) Effects ofNa . 174
b) Effects of K 174
1. Introduction . . . 174
2. Potassium contracture 175
3. Effects of K on the mechanical response 177
4. The Fleckenstein hypothesis 179
C_ Effects on heart muscle . . . _ . . . . . . 183
a) Introduction . . . . . . . . . . . . . 183
b) Temperature and ionic effects on the heart 185
c) Effects on the heart rate (the rhythm) . . 186
d) Effects upon the mechanical response of the heart 186
e) The Hajdu hypothesis . . . . . . . . . . . . 188
1. The "staircase" phenomenon . . . . . . . . 188
2. Potassium ions and the development of tension 189
3. Potassium ions and contracture 189
4. Effect of Na upon the staircase 190
5. Formulation of the hypothesis 190
D. Effects on smooth muscle 191
a) Effect of sodium ions 191
1. Intestinal muscle . 191
2. Uterus muscle. . . 192
b) Effect of potassium ions 192
1. Intestinal muscle 192
2. Uterus muscle. . . . 193
3. Vascular muscle 195
Part: II The alkali metal ions in the organism
By P. KRUHOFFER, J. HESS THAYSEN and N. A. THORN.
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
II. Distribution of alkali metals in body compartments and tissues. By N. A. THORN 198
A. The sodium and potassium of the extracellular compartment (and some tissues
built mainly of extracellular components) 198
a) Blood plasma . . 198
b) Lymph. . . . . 203
c) Interstitial spaces 204
d) Tendon 206
e) Corium. . . . . 207
f) Cornea . . . . . 207
B. The sodium and potassium of cartilage and bone 208
a) Cartilage . . . . . . . . . . . . . . . . 208
b) Bone. . . . . . . . . . . . . . . . . . 210
Amount of sodium in bone p. 210. - Nature of sodium in bone p. 211. -
"Availability", function of sodium in bone p. 212.
C. The sodium and potassium of fluids contained in special extracellular cavities 214
a) Synovial fluid. . . 214
b) Cerebrospinal fluid. 215
c) Aqueous humour 216
Contents IX
Page
d) Vitreous humour 217
e) Endolymph, perilymph. 217
f) Amniotic fluid 218
g) Transport over placenta 219
D. The sodium and potassium of different tissues mainly composed of cells 219
a) Introduction 219
b) Epidermis, lens 220
c) Muscular tissues 221
d) Blood cells . . 222
e ) Neural tissues . 222
f) Glandular tissues 222
g) Miscellaneous . . 222
E. Distribution of lithium, rubidium and cesium. 223
Distribution of naturally occurring lithium p. 223. - Distribution of lithium
after administration p. 223. - Distribution of naturally occurring rubidium
p. 224. - Distribution of rubidium after administration p. 224. - Distribu-
tion of naturally occurring cesium p. 225. - Distribution of cesium after
administration p. 225.
III. Total body contents of sodium and potassium. Total exchangeable sodium and
potassium. By N. A. THORN. . . . . . . . . 226
A. Total body contents. . . . . . . . . . . . . . . . . . . . . . . 226
B. Total exchangeable sodium and potassium (N a" K,). . . . . . . . . 227
C. Relation between total body contents and total exchangeable contents 231
D. Relation between isotope dilution data and data from metabolic balance studies 232
E. Relation between Na. and K, and serum concentrations. . . 232
IV. Handling of alkali metal ions by the kidney. By P. KRUH0FFER . 233
A. Introduction. . . . . . . . . . . . . . . . . . . . . . 233
B. Processes involved in tubular transport of water and the predominant ions of
plasma; their nature and localization . . . . 234
a) The proximal tubules . . . . . . . . . . . . . . . . . . . . 234
b) The distal tubular system ....... . . . . . . . . . . . 242
Distal tubular processes concerned with water (and salt) reabsorption
p. 242. - Distal reabsorption of sodium (and secretion of potassium)
p. 251. - Concluding remarks p. 260.
C. Transport of fluid in the nephron as a whole (relationship between glomerular
and tubular factors) .. . . . . . . . . . . . . . . . . . . 261
D. Physical factors (pressures) affecting sodium (and water) excretion 268
a) Effect of changes in the oncotic pressure of plasma 269
b) Effect of changes in renal arterial pressure 271
c) Effect of increase in ureteral (pelvic) pressure . . . 272
d) Effect of elevation of renal venous pressure . . . . 274
e) Effects of pressures acting on the outside of the kidney. 276
E. Effects of changes in plasma sodium (and chloride) concentration on sodium
excretion . . . . . . . . . . . . . . . . . . . . . 277
F. "Osmotic diuresis" and sodium (and potassium) excretion . . 280
G. Interrelationship between urinary acidification and sodium and potassium
excretion . . . . . . . . . . . . . . . . . . . . . . . 285
a) Potassium excretion as related to sodium excretion . . . . . 286
bj The effects of primary changes in the acid-base status of the body fluids . . 288
Hyperventilation (respiratory alkalosis) p. 288. - Increased pCO.
(respiratory acidosis) p. 290. - Effects of non-respiratory ("metabolic")
alkalosis on potassium excretion p. 291. - Potassium excretion in non-re
spiratory acidosis p. 292.
c) The effects of potassium deficiency and potassium excess . . . . . . . . 292
Effects of potassium deficiency upon bicarbonate reabsorption p. 293. -
Effects of administration of potassium salts (potassium excess) p. 294.
d) The effects of carbonic anhydrase inhibitors. . . . . . . . . . . . . . 296
x
Contents
Page
H. Hormonal factors affecting the renal handling of sodium, potassium (and water) 301
a) Hormones of the adrenal cortex and other steroids. . . . . . . . . . . 301
Effects of adrenocortieal insufficiency p. 301. - Natural corticosteroids
p. 304. - Effects of corticoids on renal sodium and potassium excre
tions (and renal function in general) p. 316. - Corticoid derivatives
p. 336. - Licorice extract p. 338 - Progesterone p. 339. - Oestrogens p.
339. - Androgens p. 340.
b) Hormon€s of the adrenal medulla 340
c) Hormones of the adenohypophysis. . 340
d) Neurohypophyseal hormones 342
Vasopressin (antidiuretic hormone, ADH, tl-hypophamine) p. 343. -
Oxytocin p. 353.
e) Hormones of the pancreas . . . . . 354
Insulin p. 354. - Glucagon p. 354.
f) Miscellaneous . . . . . . . . . . . 355
Renin and hypertensin p. 355. - Serotonin p. 355_
£. Effect of the renal nerves and sympathicomimetic amines on sodium and
potassium excretion . . . . . . 356
a) The renal nerves ..... . . . . . . . . . . . . . . . . . . . . 356
b) Effects of sympathomimetic amines ................ 359
J. Influence of the central nervous system on body contents and renal excretion
of sodium (and water) ........................ 362
K. Effects of changes in the state of the cardiovascular system on sodium excretion 368
a) Effects of changes in total blood volume . . . . . . . . . . . . 369
b) Procedures causing redistribution of the blood volume . . . . . . 372
c) Influence of posture . . _ . . . . . . . . . . . . . . . . . . 375
d) Sodium retention in circulatory failure (formation of cardiac oedema) 378
L. Effect of exercise on renal sodium excretion . . . . . . . . . . 387
M. Diurnal variations in the renal excretion of sodium and potassium 387
N. Diuretic and natriuretic agents. . . . . . . . . 388
a) Introduction (definitions and types of diureses) 388
b) Water . . . . . 389
c) Osmotic diuretics 390
d) Salts. . . . . . 391
e) Acidifying diuretics 393
f) Mercurial diuretics . 395
The typical response p. 396. - Mechanism of the renal response p. 397. -
Cellular site of action p. 405. - Factors influencing the diuretic response
to mercurials p. 406. - Effects of mercurials on urinary potassium excre-
tion p. 408.
g) Xanthine diuretics. . . . . . . . . . . . . . . . . . . . . . . . . 4lO
The typical response p. 411. - The mechanism of xanthine diuresis p. 411.
h) Diuretics chemically related to xanthines . . . . . . . . . 415
i) Unsubstituted sulphonamides (carbonic anhydrase inhititors) 416
j) Chlorothiazide (and derivatives) . . . . . . . . 416
k) Antialdosterones .............. 417
O. The renal excretion of lithium, rubidium and cesium 419
a) Lithium . . . . . . 419
b) Rubidium and cesium . . . . . . . . . . . . 422
c) Note on thallous ions ............ 423
P. Transport of sodium and potassium across the urinary bladder wall. 423
V. Handling of alkali metals by exocrine glands other than the kidney. By J. HESS
THAYSEN _ . . . . . . . . . 424
A. The duct possessing glands . . . . . . . . . . . . . . . . . . . . . . 424
a) Introduction _ . . . . . . . . . . . . . . . . . . . . . . . . . . 424
The outward transfer of electrolytes p. 427. - The morphological site of
the outward transport of electrolytes p. 430. - The reabsorption of
sodium p. 431. - The morphological site of sodium reabsorption p. 434. -
Glandular sodium and potassium balance during sacretion p. 434. -
Glandular oxygen consumption in relation to electrolyte transport p. 435.
Contents XI
Page
- Factors affecting sodium and potassium excretion by the duct-possessing
glands p. 436. - Criticism of the present theory of sodium and potassium
secretion p. 438.
b) The sweat glands . . . . . . . . . . . . . . . . . . . . . . . . . 438
Type of gland p. 439. - Rate of secretion p. 440. - Skin temperature
p. 442. - Duration of secretion p. 442. - Type of stimulus p. 443. -
Plasma concentration of N a und K p. 443. - Glandular blood flow p. 443.
- Adaptation to salt depletion p. 444. - Adrenal cortical steroids p. 445.
Drugs p. 445. - Individual differences in sweat composition p. 445. -
- The secretion of Li, Cs and Rb p. 447. - The effect of prolonged
sweating on the homeostasis of water, sodium and potassium p. 447. -
Water loss p. 447. - Electrolyte loss p. 448. - Replacements p. 448. -
The effect of sweating without replacement of water and salt p. 449. -
The effect of sweating with replacement of water but not of salt p. 450. -
The effect of sweating with replacement of salt but not of water loss p. 450.
c) The salivary glands .. . . . . . . . . . . . . . . . . . . . . . . 450
Type of gland p. 451. - Rate of secretion p. 452. - Gland temperature
p. 454. - Duration of secretion p. 454. - Type of stimulation p. 455. -
Glandular blood flow p. 455.-Plasma concentration of N a and K p. 455.-
Salt depletion p. 456. - Adrenal cortical steroids p. 457. - The effect of
various drugs p. 458. - Individual variations p. 459. - The secretion of
Li, Cs and Rb p. 459.
d) The pancreatic gland. . . . . . . . . . . . . . . . . . . . . . . . 460
Rate of secretion p. 461. - Duration of secretion p. 461. - Type of
stimulation p. 461. - Plasma concentration of the alkali metals p. 462. -
The effect of certain drugs p. 463. - Individual variations p. 463.
e) The lacrymal gland . . . . . . . . . . . . . . . . . . . . . . . . 463
Rate of secretion p. 464. - Duration of secretion p. 464. - Plasma
concentration 'p. 464.
B. The glands of the gastrointestinal tract . . . . . . . . . . . . . . . . . 464
a) The oesophageal glands ...................... 464
b) The gastric mucosa . . . . . . . . . . . . . . . . . . . . . . . . 465
Type of gland p. 467. - Rate of secretion p. 468. - Type of stimulus
p. 471. - Duration of secretion p. 473. - Plasma concentrations of Na
and K (total osmolar concentration) p.473. - Mucosal blood flow and
oxygen supply p. 474. - Gland temperature p. 475. - Salt depletion and
adreno-cortical steroids p.475. - Individual differences p.477. - The
secretion of lithium p. 477. - The alkali metal content of the gastric mucosa
p. 477. - Mechanism of alkali metal secretion p. 478.
c) The intestinal mucosa . . . . . . . . . . . . . . . . . . . . . . . 483
Type of gland p. 483. - Rate of secretion p. 485. - Plasma concentration
of the alkali metals (total osmolar concentration of the plasma) p. 485. -
The alkali metals in the intestine p. 486. - The mechanism of intestinal
secretion p. 486.
C. The liver and the gall bladder . . . . . . . . . . . . . . . . . . . . . 486
a) Hepatic bile ........................... 486
Collection of hepatic bile p. 486. - The electrolyte composition of
hepatic bile p. 487. - Rate of secretion p. 488. - Plasma concentration
of the alkali metals (total osmolar concentration of the plasma) p. 489. -
Hepatic blood flow and oxygen supply p. 489. - Temperature p. 490. -
The excretion of lithium in the hepatic bile p. 490. - The mechanism of
alkali metal excretion in the bile p. 490.
h) Gall bladder bile ......................... 492
The electrolyte composition of gall bladder bile p. 492. - The reabsorptive
functions of the gall bladder p. 493. - The secretory functions of the gall
bladder p. 496.
c) The alkali metals in hepatic tissue 496
D. The mammary gland . . . . 497
E. Male organs of reproduction . . . 499
F. Female organs of reproduction . . 501
G. The glands of the respiratory tract 502