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Smith & Tanagho’s General Urology

19th Edition Edition Jack W. Mcaninch


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Smith & Tanagho’s


General Urology
NINETEENTH EDITION

Edited by

Jack W. McAninch, MD, FACS, FRCS(E)(Hon)


Professor of Urology
University of California School of Medicine
Chief, Department of Urology
San Francisco General Hospital
San Francisco, California

Tom F. Lue, MD, FACS, ScD (Hon)


Professor of Urology
Department of Urology
University of California School of Medicine
San Francisco, California

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Contents
Contributors vii 10 Laparoscopic Surgery 149
Preface xi
David B. Bayne, MD, MPH;
J. Stuart Wolf, Jr., MD, FACS;
1 Anatomy of the Genitourinary Tract 1
Marshall L. Stoller, MD; & Thomas Chi, MD
Emil A. Tanagho, MD; &
Tom F. Lue, MD, ScD (Hon), FACS 11 Robotic Surgery in Urology 167
Maxwell V. Meng, MD, MPH
2 Embryology of the Genitourinary System 17
Emil A. Tanagho, MD; Hiep T. Nguyen, MD; 12 Urinary Obstruction & Stasis 177
& Michael DiSandro, MD
Marshall L. Stoller, MD; &
Tom F. Lue, MD, FACS, ScD (Hon)
3 Symptoms of Disorders of the
Genitourinary Tract 31
13 Vesicoureteral Reflux 191
Benjamin N. Breyer, MD, MAS, FACS
Thomas W. Gaither, MD, MAS; &
Hillary L. Copp, MD, MS
4 Physical Examination of the
Genitourinary Tract 41
14 Bacterial Infections of the
Maxwell V. Meng, MD, MPH; & Genitourinary Tract 201
Emil A. Tanagho, MD
Mary K. Wang, MD; &
Hillary L. Copp, MD, MS
5 Urologic Laboratory Examination 49
Anobel Y. Odisho, MD, MPH; 15 Specific Infections of the
Sima P. Porten, MD, MPH; & Genitourinary Tract 229
Kirsten L. Greene, MD, MS
Emil A. Tanagho, MD; &
Christopher J. Kane, MD, FACS
6 Radiology of the
Urinary Tract 63
16 Sexually Transmitted Infections 243
Daniela Franz, MD; Scott Gerst, MD; &
Hedvig Hricak, MD, PhD Kristin Madden, PharmD;
Amanda B. Reed-Maldonado, MD, FACS;
& John N. Krieger, MD
7 Vascular Interventional Radiology 107
Ryan Kohlbrenner, MD; & Roy L. Gordon, MD 17 Urinary Stone Disease 259
Marshall L. Stoller, MD
8 Retrograde Instrumentation of
the Urinary Tract 117
18 Injuries to the Genitourinary Tract 291
Marshall L. Stoller, MD
Benjamin N. Breyer, MD, MAS, FACS
9 Percutaneous Endourology and
Ureterorenoscopy 129 19 Urothelial Carcinoma: Cancers of the
Bladder, Ureter, and Renal Pelvis 309
David B. Bayne, MD, MPH;
Joachim W. Thüroff, MD; Badrinath R. Konety, MD, MBA; &
Rolf Gillitzer, MD; & Thomas Chi, MD Peter R. Carroll, MD, MPH

iii

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iv Contents

20 Renal Parenchymal Neoplasms 329 31 Disorders of the Adrenal Glands 509


Anobel Y. Odisho, MD, MPH; & Michelle L. McDonald, MD; &
Kirsten L. Greene, MD, MS Christopher J. Kane, MD, FACS

21 Cancer of the Prostate Gland 351 32 Disorders of the Kidneys 521


Matthew R. Cooperberg, MD, MPH; David B. Bayne, MD, MPH;
Samuel L. Washington III, MD; & Jack W. McAninch, MD, FACS, FRCS(E)(Hon); &
Peter R. Carroll, MD, MPH Thomas Chi, MD

22 Genital Tumors 377 33 Diagnosis of Medical Renal Diseases 539


Sima P. Porten, MD, MPH; & Brian K. Lee, MD; & Flavio G. Vincenti, MD
Joseph C. Presti, Jr., MD
34 Acute Kidney Injury and Oliguria 551
23 Urinary Diversion and
Brian K. Lee, MD; & Flavio G. Vincenti, MD
Bladder Substitutions 391
Maxwell V. Meng, MD, MPH; 35 Chronic Kidney Disease and
Susan Barbour, RN, MS, WOCN; & Renal Replacement Therapy 557
Peter R. Carroll, MD, MPH
Brian K. Lee, MD; &
Flavio G. Vincenti, MD
24 Systemic Therapy of Urologic Tumors 407
Vadim S. Koshkin, MD; & Eric J. Small, MD 36 Renal Transplantation 563
John M. Barry, MD
25 Immunotherapy in
Urologic Malignancies 415
37 Disorders of the Ureter and
Arpita Desai, MD; & Eric J. Small, MD Ureteropelvic Junction 571
Barry A. Kogan, MD
26 Radiotherapy of
Urologic Tumors 421
38 Disorders of the Bladder, Prostate,
Yun Rose Li, MD, PhD; and Seminal Vesicles 585
Alexander R. Gottschalk, MD, PhD; &
Mack Roach III, MD Samuel L. Washington III, MD; &
Katsuto Shinohara, MD
27 Neurophysiology and Pharmacology
of the Lower Urinary Tract 453 39 Male Sexual Dysfunction 605
Karl-Erik Andersson, MD, PhD Amanda B. Reed-Maldonado, MD, FACS; &
Tom F. Lue, MD
28 Neurogenic Bladder 473
40 Women’s Sexual Health 631
Anne M. Suskind, MD, MS, FACS
Alan W. Shindel, MD, MAS; &
Tami S. Rowen, MD, MS
29 Urodynamics 485
Anne M. Suskind, MD, MS, FACS 41 Disorders of the Penis and
Male Urethra 645
30 Urinary Incontinence 499
Benjamin N. Breyer, MD, MAS, FACS; &
Tom F. Lue, MD, FACS, ScD (Hon); & Jack W. McAninch, MD, FACS, FRCS(E)(Hon)
Emil A. Tanagho, MD

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Contents v

42 Disorders of the Female Urethra 659 46 Genital Gender-Affirming Surgery:


Patient Care, Decision Making, and
Donna Y. Deng, MD, MS
Surgery Options 747
43 Disorders of Sex Development 671 Maurice M. Garcia, MD, MAS

Laurence S. Baskin, MD
47 History and Physical Examination in
Pediatric Urology 769
44 Male Infertility 703
Michael DiSandro, MD
Thomas J. Walsh, MD, MS; &
James F. Smith, MD, MS
48 Introduction to Clinical
Research Design 781
45 The Aging Male 735
June M. Chan, ScD; David Tat, DO; &
James F. Smith, MD, MS; Stacey Kenfield, ScD
Bogdana Schmidt, MD, MPH; &
Thomas J. Walsh, MD, MS Index 793

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Contributors
Karl-Erik Andersson, MD, PhD June M. Chan, ScD
Institute for Regenerative Medicine Program Director, Genitourinary Cancer Epidemiology and
Wake Forest University School of Medicine Population Sciences
Winston Salem, North Carolina Department of Urology
UCSF School of Medicine
Susan Barbour, RN, MS, WOCN San Francisco, California
Palliative Care Services
UCSF School of Medicine Thomas Chi, MD
San Francisco, California Associate Professor and Katzman Endowed Professor in
Clinical Urology
John M. Barry, MD Department of Urology
Professor of Urology and Professor of Surgery UCSF School of Medicine
Division of Abdominal Organ Transplantation San Francisco, California
Organ Health and Science University
Portland, Oregon Matthew R. Cooperberg, MD, MPH
Associate Professor
Laurence S. Baskin, MD Department of Urology
Chief of Pediatric Urology Helen Diller Family Comprehensive Cancer Center
University of California Children’s Medical Center UCSF School of Medicine
UCSF School of Medicine San Francisco, California
San Francisco, California
Attending Urologist Hillary L. Copp, MD, MS
Children’s Hospital Oakland Associate Professor of Urology and Pediatric Urology
Oakland, California Fellowship Director
Benioff Children’s Hospital
David B. Bayne, MD, MPH UCSF School of Medicine
Endourology Fellow San Francisco, California
Department of Urology
UCSF School of Medicine Donna Y. Deng, MD, MS
San Francisco, California Neurourology Lead, Kaiser Permanente Northern
California
Benjamin N. Breyer, MD, MAS, FACS Medical Director, Kaiser NorCal Regional Spina Bifida
Associate Professor and Vice Chair Program
Department of Urology Associate Fellowship Director, Female Pelvic Medicine
UCSF School of Medicine Reconstructive Surgery, Kaiser East Bay/UCSF
San Francisco, California Oakland, California

Peter R. Carroll, MD, MPH Arpita Desai, MD


Professor Clinical Instructor
Ken and Donna Derr-Chevron Endowed Chair in Department of Genitourinary Medical Oncology
Prostate Cancer Helen Diller Family Comprehensive Cancer Center
Department of Urology UCSF School of Medicine
UCSF School of Medicine San Francisco, California
San Francisco, California

vii

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viii Contributors

Michael DiSandro, MD Kirsten L. Greene, MD, MS


Professor of Urology Professor and Chair
Department of Urology Department of Urology
UCSF School of Medicine University of Virginia
San Francisco, California Charlottesville, Virginia

Daniela Franz, MD Hedvig Hricak, MD, PhD


Department of Diagnostic and Interventional Radiology Chair
Klinikum rechts der Isar Department of Radiology
Munich Technical University Memorial Sloan-Kettering Cancer Center
Munich, Germany Professor of Radiology
Cornell University
Thomas W. Gaither, MD, MAS New York, New York
Urology resident
University of California Christopher J. Kane, MD, FACS
Los Angeles, California Dean of Clinical Affairs
UC San Diego School of Medicine
Maurice M. Garcia, MD, MAS CEO, UC San Diego Health Physician Group
Associate Professor of Urology and Anatomy (Adjunct) La Jolla, California
Departments of Urology and Anatomy
UCSF Medical Center Stacey A. Kenfield, ScD
San Francisco, California Associate Professor
Director, Cedars-Sinai Transgender Surgery and Department of Urology
Health Program UCSF School of Medicine
Division of Urology San Francisco, California
Cedars-Sinai Medical Center
Los Angeles, California Barry A. Kogan, MD
Professor, Surgery and Pediatrics
Scott Gerst, MD Falk Chair in Urology
Associate Attending Physician Albany Medical College
Department of Radiology Albany, New York
Memorial Hospital, Memorial Sloane-Kettering
Cancer Center Ryan Kohlbrenner, MD
New York, New York Assistant Professor of Interventional Radiology
Departments of Radiology and Biomedical Imaging
Rolf Gillitzer, MD UCSF School of Medicine
Clinical Director San Francisco, California
Department of Urology
Johannes Gutenberg University Medical Center Mainz Badrinath R. Konety, MD, MBA
Mainz, Germany Associate Dean for Innovation
Professor of Urology
Roy L. Gordon, MD Director of the Institute for Prostate and Urologic Cancers
Professor of Interventional Radiology University of Iowa
Department of Radiology Iowa City, Iowa
UCSF School of Medicine
San Francisco, California Vadim S. Koshkin, MD
Assistant Clinical Professor
Alexander R. Gottschalk, MD, PhD Genitourinary Medical Oncologist
Professor of Radiation Oncology Departments of Hematology and Oncology
Director of CyberKnife UCSF School of Medicine
Departments of Radiation and Oncology San Francisco, California
UCSF School of Medicine
San Francisco, California

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Contributors ix

John N. Krieger, MD Anobel Y. Odisho, MD, MPH


Professor of Urology Assistant Professor
University of Washington School of Medicine Department of Urologic Oncology
Seattle, Washington UCSF School of Medicine
San Francisco, California
Brian K. Lee, MD
Professor of Medicine Sima P. Porten, MD, MPH
The Connie Frank Kidney Transplant Center Assistant professor
UCSF School of Medicine Department of Urology
San Francisco, California UCSF School of Medicine
San Francisco, California
Yun Rose Li, MD, PhD
Resident Physician Joseph C. Presti, Jr., MD
Departments of Radiation and Oncology Lead for Urologic Oncology
UCSF School of Medicine Kaiser Permanente Northern California
San Francisco, California Oakland, California

Tom F. Lue, MD, FACS, ScD (Hon) Amanda B. Reed-Maldonado, MD, FACS
Professor of Urology Chief, Male Reproductive Urology
Emil Tanagho Endowed Chair in Clinical Urology Department of Urology
Department of Urology Tripler Army Medical Center
UCSF School of Medicine Honolulu, Hawaii
San Francisco, California
Mack Roach III, MD
Kristin Madden, PharmD Professor of Radiation Oncology and Urology
Pharmacist Department of Urology
Department of Veterans Affairs UCSF School of Medicine
San Antonio, Texas San Francisco Comprehensive Cancer Center
San Francisco, California
Jack W. McAninch, MD, FACS, FRCS(E)(Hon)
Professor of Urology Tami S. Rowen, MD, MS
UCSF School of Medicine Assistant Professor
San Francisco, California Departments of Obstetrics, Gynecology, and
Reproductive Sciences
Michelle L. McDonald, MD UCSF School of Medicine
Urologist San Francisco, California
San Diego, California
Bogdana Schmidt, MD, MPH
Maxwell V. Meng, MD, MPH Urologic Oncology Fellow
Professor Stanford University Medical Center
Department of Urology Stanford, California
UCSF School of Medicine
San Francisco, California Alan W. Shindel, MD, MAS
Associate Professor
Hiep T. Nguyen, MD Department of Urology
Associate Professor University of California
Surgery and Urology Davis, California
Harvard Medical School and Children’s Hospital
Boston, Massachusetts

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x Contributors

Katsuto Shinohara, MD David Tat, DO


Professor Infectious Disease Specialist
Helen Diller Family Chair in Clinical Urology Moses H. Cone Memorial Hospital
Department of Urology Greensboro, North Carolina
UCSF School of Medicine
San Francisco, California Joachim W. Thüroff, MD
Professor
Eric J. Small, MD Department of Urology
Professor of Medicine and Urology University Medical Center
Urologic Oncology Program and Program Member, Mannheim, Germany
Comprehensive Cancer Center
UCSF School of Medicine Flavio G. Vincenti, MD
San Francisco, California Professor of Medicine
The Connie Frank Kidney Transplant Center
James F. Smith, MD, MS UCSF School of Medicine
Associate Professor San Francisco, California
Director, Male Reproductive Health
Departments of Urology, Obstetrics, Gynecology, and Thomas J. Walsh, MD, MS
Reproductive Sciences Associate Professor
UCSF School of Medicine Department of Urology
San Francisco, California University of Washington School of Medicine
Seattle, Washington
Marshall L. Stoller, MD
Professor of Urology Mary K. Wang, MD
Department of Urology Childrens’ Urology
UCSF School of Medicine Austin, Texas
San Francisco, California
Samuel L. Washington, III, MD
Anne M. Suskind, MD, MS, FACS Urologic Oncology Clinical Fellow
Associate Professor of Urology, Obstetrics, Gynecology, and Department of Urology
Reproductive Sciences UCSF School of Medicine
Director, Neurourology, Female Pelvic Medicine & San Francisco, California
Reconstructive Surgery
UCSF School of Medicine J. Stuart Wolf, Jr., MD, FACS
San Francisco, California Professor, Department of Surgery and Perioperative Care
Dell Medical School
Emil A. Tanagho, MD The University of Texas at Austin
Professor of Urology Austin, Texas
Department of Urology
UCSF School of Medicine
San Francisco, California

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Preface
Smith & Tanagho’s General Urology, nineteenth edition, provides the updated information for the understanding, diagnosis,
and treatment of urological diseases in a concise and well-organized format. The book is up-to-date, to the point, and readable.
Medical students will find this book useful because of its concise, easy-to-follow format, and its breadth of information on
common urological diseases. Residents, as well as practicing physicians in urology, family practice, or general medicine, will find
it an efficient and current reference, particularly because of its emphasis on diagnosis and treatment.
This nineteenth edition has been thoroughly updated with clinical information and current references. The reader will find
that this edition is written in an uncomplicated, straightforward manner that provides relevant clinical information and guide-
lines for diagnosis and management of urologic conditions. Chapters on immunotherapy in urologic malignancies, radiotherapy
of urologic tumors, urinary incontinence, and vascular interventional radiology have all undergone extensive revision. For
this current edition, we have added two chapters on the timely topic of gender dysphoria and introduction to clinical research
design.
Many illustrations and figures have been modernized and improved with added color. The classic fine anatomic drawings
demonstrate well the important clinical findings.
This book has been one of the leading sources of information for students, trainees, and urologists around the world. In addi-
tion to English, this book has been published in many other foreign languages, like Chinese, French, Greek, Italian, Japanese,
Korean, Portuguese, Russian, Spanish, and Turkish.
We greatly appreciate the patience and efforts of our McGraw-Hill staff, the expertise of our contributors, and the support
of our readers.

Jack W. McAninch, MD, FACS, FRCS(E) (Hon)


Tom F. Lue, MD, FACS, ScD (Hon)
San Francisco, California, January 2020

xi

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1

1
Anatomy of the
Genitourinary Tract

Emil A. Tanagho, MD; & Tom F. Lue, MD, ScD (Hon), FACS

Urology deals with diseases and disorders of the adrenal ▶▶Blood Supply
gland, the male genitourinary tract, and the female
urinary tract. These systems are illustrated in Figures 1–1 A. Arterial
and 1–2. Each adrenal gland receives three arteries: one from the infe-
rior phrenic artery, one from the aorta, and one from the
ADRENALS renal artery.

B. Venous
▶▶Gross Appearance
A. Anatomy Blood from the right adrenal gland is drained by a very short
vein into the vena cava; the left adrenal vein terminates in the
Each kidney is capped by an adrenal gland, and both left renal vein.
organs are enclosed within Gerota’s (perirenal) fascia.
Each adrenal gland weighs 4–5 g. The right adrenal is tri- ▶▶Lymphatics
angular in shape; the left is more rounded and crescentic.
The average dimensions are 3 cm width, 5 cm length, and The lymphatic vessels accompany the suprarenal vein and
1 cm thickness. Each gland is composed of a cortex, chiefly drain into the lumbar lymph nodes.
influenced by the pituitary gland, and a medulla derived
from chromaffin tissue (Avisse et al, 2000; O’Donoghue KIDNEYS
et al, 2010).
▶▶Gross Appearance
B. Relations A. Anatomy
Figure 1–2 shows the relationships between the adrenals and The kidneys lie along the borders of the psoas muscles and
other organs. The right adrenal lies between the liver and are therefore obliquely placed. The position of the liver
the vena cava. The left adrenal lies close to the aorta and is causes the right kidney to be lower than the left (Figures 1–2
covered on its lower surface by the pancreas. The spleen lies and 1–3). The adult kidney weighs between 125 and 170 g in
superior and lateral to it. men and 115 and 155 g in women. It is about 10–12 cm long,
5–7 cm wide, and 3–5 cm thick.
The kidneys are supported by the perirenal fat (which is
▶▶Histology enclosed in the perirenal fascia), the renal vascular pedicle,
The adrenal cortex, which makes up 85% of the mass, is com- abdominal muscle tone, and the general bulk of the abdomi-
posed of three distinct layers: the outer zona glomerulosa, the nal viscera (Rusinek et al, 2004). Variations in these factors
middle zona fasciculata, and the inner zona reticularis. The permit variations in the degree of renal mobility. The aver-
medulla lies centrally and is made up of polyhedral cells with age descent on inspiration or on assuming the upright posi-
hormone-containing granular cytoplasm. These chromaf- tion is 4–5 cm. Lack of mobility suggests abnormal fixation
fin cells are accompanied by a small number of sympathetic (eg, perinephritis), but extreme mobility is not necessarily
ganglion cells. pathologic.

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2 SMITH & TANAGHO’S GENERAL UROLOGY

▲▲Figure 1–1. Anatomy of the male genitourinary tract. The upper tract and midtract have urologic function only.
The lower tract has both genital and urinary functions.

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ANATOMY OF THE GENITOURINARY TRACT CHAPTER 1 3

▲▲Figure 1–2. Relations between the kidneys, ureters, and bladder (anterior aspect).

On longitudinal section (Figure 1–4), the kidney is seen gastrointestinal symptoms that accompany kidney diseases
to be made up of an outer cortex, a central medulla, and the (Glassberg, 2002).
internal calices and pelvis. The cortex is homogeneous in
appearance. Portions of it project toward the pelvis between ▶▶Histology
the papillae and fornices and are called the columns of A. Nephron
Bertin. The medulla consists of numerous pyramids formed
by the converging collecting renal tubules, which drain into The functioning unit of the kidney is the nephron, which is
the minor calices at the tip of the papillae. composed of a tubule that has both secretory and excretory
functions (Figure 1–4). The secretory portion is contained
largely within the cortex and consists of a renal corpuscle and
B. Relations
the secretory part of the renal tubule. The excretory portion of
Figures 1–2 and 1–3 show the relationships between the this duct lies in the medulla. The renal corpuscle is composed
kidneys and adjacent organs and structures. Their intimacy of the vascular glomerulus, which projects into Bowman’s cap-
with intraperitoneal organs and the autonomic innervation sule, which, in turn, is continuous with the epithelium of the
that they share with these organs explain, in part, some of the proximal convoluted tubule. The secretory portion of the renal

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4 SMITH & TANAGHO’S GENERAL UROLOGY

▲▲Figure 1–3. Relations between the kidneys (posterior aspect). The dashed lines represent the outline of the kidneys,
where they are obscured by overlying structures.

tubule is made up of the proximal convoluted tubule, the loop of the posterior surface. The anterior branch supplies both
of Henle, and the distal convoluted tubule. upper and lower poles as well as the entire anterior surface.
The excretory portion of the nephron is the collecting The renal arteries are all end arteries.
tubule, which is continuous with the distal end of the ascend- The renal artery branches further divide into interlobar
ing limb of the convoluted tubule. It empties its contents arteries, which travel in the columns of Bertin (between the
through the tip (papilla) of a pyramid into a minor calyx. pyramids) and then arch along the base of the pyramids
(arcuate arteries). These arteries then divide as interlobular
B. Supporting Tissue arteries. From these vessels, smaller (afferent) branches pass
to the glomeruli. From the glomerular tuft, efferent arterioles
The renal stroma is composed of loose connective tissue and
pass to the tubules in the stroma.
contains blood vessels, capillaries, nerves, and lymphatics.
B. Venous
▶▶Blood Supply (Figures 1–2, 1–4, and 1–5)
The renal veins are paired with the arteries, but any of them
A. Arterial
will drain the entire kidney if the others are tied off.
Usually there is one renal artery, a branch of the aorta that Although the renal artery and vein are usually the sole blood
enters the hilum of the kidney between the pelvis, which vessels of the kidney, accessory renal vessels are common and
normally lies posteriorly, and the renal vein. It may branch may be of clinical importance if they are so placed so as to com-
before it reaches the kidney, and two or more separate arter- press the ureter, in which case hydronephrosis may result.
ies may be noted (Budhiraja et al, 2010). In duplication of the
pelvis and ureter, it is common for each renal segment to have
its own arterial supply. ▶▶Nerve Supply
The renal artery divides into anterior and posterior The renal nerves derived from the renal plexus accompany
branches. The posterior branch supplies the midsegment the renal vessels throughout the renal parenchyma.

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ANATOMY OF THE GENITOURINARY TRACT CHAPTER 1 5

▲▲Figure 1–4. Anatomy and histology of the kidney and ureter. Upper left: Diagram of the nephron and its blood supply.
(Courtesy of Merck, Sharp, Dohme: Seminar. 1947; 9[3].) Upper right: Cast of the pelvic caliceal system and the arterial
supply of the kidney. Middle: Renal calices, pelvis, and ureter (posterior aspect). Lower left: Histology of the ureter. The
smooth-muscle bundles are arranged in both spirally and longitudinally. Lower right: Longitudinal section of kidney
showing calices, pelvis, ureter, and renal blood supply (posterior aspect).

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6 SMITH & TANAGHO’S GENERAL UROLOGY

▲▲Figure 1–5. (A) The posterior branch of the renal artery and its distribution to the central segment of the posterior
surface of the kidney. (B) Branches of the anterior division of the renal artery supplying the entire anterior surface of the
kidney as well as the upper and lower poles at both surfaces. The segmental branches lead to interlobar, arcuate, and
interlobular arteries. (C) The lateral convex margin of the kidney. Brödel’s line, which is 1 cm from the convex margin, is
the bloodless plane demarcated by the distribution of the posterior branch of the renal artery.

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ANATOMY OF THE GENITOURINARY TRACT CHAPTER 1 7

▶▶Lymphatics
The lymphatics of the kidney drain into the lumbar lymph
nodes.

CALICES, RENAL PELVIS, AND URETER

▶▶Gross Appearance
A. Anatomy

1. Calices—The tips of the minor calices (8–12 in number)


are indented by the projecting pyramids (Figure 1–4). These
calices unite to form two or three major calices that join to
form the renal pelvis (Sozen et al, 2008).
2. Renal pelvis—The pelvis may be entirely intrarenal or
partly intrarenal and partly extrarenal. Inferomedially, it
tapers to join the ureter.
▲▲Figure 1–6. Anatomy and relations between the
3. Ureter—The adult ureter is about 30 cm long, varying ureters, bladder, prostate, seminal vesicles, and vasa
in direct relation to the height of the individual. It follows a deferentia (anterior view).
rather smooth S curve. Areas that stones are often impacted
are (a) at the ureteropelvic junction, (b) where the ureter
crosses over the iliac vessels, and (c) where it courses through helical and longitudinal smooth-muscle fibers. They are not
the bladder wall. arranged in discrete layers. The outermost adventitial coat is
composed of fibrous connective tissue.
B. Relations
▶▶Blood Supply
1. Calices—The calices are intrarenal and are intimately A. Arterial
related to the renal parenchyma.
The renal calices, pelvis, and upper ureters derive their blood
2. Renal pelvis—If the pelvis is partly extrarenal, it lies along supply from the renal arteries; the midureter is fed by the
the lateral border of the psoas muscle and on the quadratus internal spermatic (or ovarian) arteries. The lowermost por-
lumborum muscle; the renal vascular pedicle is just anterior tion of the ureter is served by branches from the common
to it. The left renal pelvis lies at the level of the first or second iliac, internal iliac (hypogastric), and vesical arteries.
lumbar vertebra; the right pelvis is a little lower.
3. Ureter—On their course downward, the ureters lie on the B. Venous
psoas muscles, pass medially to the sacroiliac joints, and then The veins of the renal calices, pelvis, and ureters are paired
swing laterally near the ischial spines before passing medi- with the arteries.
ally to enter the base of the bladder (Figure 1–2). In females,
the uterine arteries are closely related to the juxtavesical por-
tion of the ureters. The ureters are covered by the posterior
▶▶Lymphatics
peritoneum; their lowermost portions are closely attached to The lymphatics of the upper portions of the ureters as well
it, while the juxtavesical portions are embedded in vascular as those from the pelvis and calices enter the lumbar lymph
retroperitoneal fat (Koff, 2008). nodes. The lymphatics of the midureter pass to the internal
The vasa deferentia, as they leave the internal inguinal iliac (hypogastric) and common iliac lymph nodes; the lower
rings, sweep over the lateral pelvic walls anterior to the ureteral lymphatics empty into the vesical and hypogastric
ureters (Figure 1–6). They lie medial to the latter before join- lymph nodes.
ing the seminal vesicle and penetrating the base of the pros-
tate to become the ejaculatory ducts. BLADDER

▶▶Histology (Figure 1–4) ▶▶Gross Appearance


The walls of the calices, pelvis, and ureters are composed of The bladder is a hollow muscular organ that serves as a res-
transitional cell epithelium under which lies loose connec- ervoir for urine. In women, its posterior wall and dome are
tive tissue (lamina propria). External to these are a mixture of invaginated by the uterus. The adult bladder normally has

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8 SMITH & TANAGHO’S GENERAL UROLOGY

a capacity of 400–500 mL. The wall of the bladder is about ▶▶Blood Supply
3–5 mm in thickness; it is thinner when it is distended.
A. Arterial
A. Anatomy The bladder is supplied by the superior, middle, and inferior
When empty, the adult bladder lies behind the pubic sym- vesical arteries, which arise from the anterior trunk of the
physis and is largely a pelvic organ. In infants and children, internal iliac (hypogastric) artery, and by smaller branches
it is situated higher (Berrocal et al, 2002). When it is full, it from the obturator and inferior gluteal arteries. In females,
rises well above the symphysis and can readily be palpated the uterine and vaginal arteries also send branches to the
or percussed. When overdistended, as in acute or chronic bladder.
urinary retention, it may cause the lower abdomen to bulge
visibly. B. Venous
Extending from the dome of the bladder to the umbilicus Surrounding the bladder is a rich plexus of veins that ulti-
is a fibrous cord, the median umbilical ligament, which rep- mately empties into the internal iliac (hypogastric) veins.
resents the obliterated urachus. The ureters enter the bladder
posteroinferiorly in an oblique manner and at these points ▶▶Nerve Supply
are about 5 cm apart (Figure 1–6). The orifices, situated at
the extremities of the crescent-shaped interureteric ridge that The bladder receives innervation from sympathetic and
forms the proximal border of the trigone, are about 2.5 cm parasympathetic nervous systems. The sensory afferent of
apart. The trigone occupies the area between the ridge and the bladder originates from both subepithelial nerve endings
the bladder neck. and nerve fibers between detrusor muscle bundles (Andersson,
The internal sphincter, or bladder neck, is not a true cir- 2010; Birder et al, 2010; McCloskey, 2010).
cular sphincter but a thickening formed by interlaced and
converging muscle fibers of the detrusor as they pass distally ▶▶Lymphatics
to become the smooth muscle component of the urethra. The lymphatics of the bladder drain into the vesical, external
iliac, internal iliac (hypogastric), and common iliac lymph
B. Relations nodes.
In males, the bladder is related posteriorly to the seminal
vesicles, vasa deferentia, ureters, and rectum (Figures 1–7 PROSTATE GLAND
and 1–8). In females, the uterus and vagina are interposed
between the bladder and rectum (Figure 1–9). The dome ▶▶Gross Appearance
and posterior surfaces are covered by peritoneum; hence, in
A. Anatomy
this area, the bladder is closely related to the small intestine
and sigmoid colon. In both males and females, the bladder is The prostate is a fibromuscular and glandular organ lying just
related to the posterior surface of the pubic symphysis, and, inferior to the bladder (Figures 1–6 and 1–7). The normal
when distended, it is in contact with the lower abdominal prostate weighs about 20 g and contains the posterior urethra,
wall. which is about 2.5 cm in length. It is supported anteriorly by
the puboprostatic ligaments and inferiorly by the urogenital
diaphragm (Figure 1–6). The prostate is perforated posteri-
▶▶Histology (Figure 1–10) orly by the ejaculatory ducts, which pass obliquely to empty
The mucosa of the bladder is composed of transitional epi- through the verumontanum on the floor of the prostatic ure-
thelium. Beneath it is a well-developed submucosal layer thra just proximal to the striated external urinary sphincter
formed largely of connective and elastic tissues. The mucosa (Figure 1–11).
may be considered as a single functional unit that consists The prostate can be subdivided into two ways: by lobe
of the epithelial layer, basement membrane, and lamina pro- or by zone. The lobe classification is often used in cystoure-
pria. Physical or chemical stress on the bladder elicits releases throscopic examinations and consists of five lobes: anterior,
of multiple factors that modulate afferent and efferent nerve posterior, median, right lateral, and left lateral. The zone clas-
activities (Fry and Vahabi, 2016). External to the submu- sification is often used in pathology. McNeal (1981) divides
cosa is the detrusor muscle that is made up of a mixture of the prostate into four zones: peripheral zone, central zone
smooth-muscle fibers arranged at random in a longitudi- (surrounds the ejaculatory ducts), transitional zone (sur-
nal, circular, and spiral manner without any layer formation rounds the urethra), and anterior fibromuscular zone (Myers
or specific orientation except for proximity to the internal et al, 2010) (Figure 1–12). The segment of urethra that tra-
meatus, where the detrusor muscle assumes three definite verses the prostate gland is the prostatic urethra. It is lined
layers: inner longitudinal, middle circular, and outer longitu- by an inner longitudinal layer of muscle (continuous with
dinal (John et al, 2001). a similar layer of the vesical wall). Incorporated within the

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ANATOMY OF THE GENITOURINARY TRACT CHAPTER 1 9

▲▲Figure 1–7. (A) Anatomic relationship between the bladder, prostate, prostatomembranous urethra, and root of
the penis. (B) Histology of the testis. Seminiferous tubules lined by supporting basement membrane for the Sertoli and
spermatogenic cells. The latter are in various stages of development. (C) Cross sections of the testis and epididymis.
(Images [A] and [C] reproduced with permission from Walsh PC, Campbell MF: Campbell’s Urology, 6th ed. Philadelphia, PA:
Saunders; 1992.)

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10 SMITH & TANAGHO’S GENERAL UROLOGY

▲▲Figure 1–8. Top: Relations between the bladder, prostate, seminal vesicles, penis, urethra, and scrotal contents.
Lower left: Transverse section through the penis. The paired upper structures are the corpora cavernosa. The single
lower body surrounding the urethra is the corpus spongiosum. Lower right: Fascial planes of the lower genitourinary
tract. (After Wesson.)

prostate gland is an abundant amount of smooth muscula- separated from the rectum by the two layers of Denonvilliers’
ture derived primarily from the external longitudinal bladder fascia, serosal rudiments of the pouch of Douglas, which
musculature. This musculature represents the involuntary once extended to the urogenital diaphragm (Raychaudhuri
smooth muscle sphincter of the posterior urethra in males. and Cahill, 2008) (Figure 1–8).

B. Relations ▶▶Histology (Figure 1–10)


The prostate gland lies behind the pubic symphysis. Located The prostate consists of a thin fibrous capsule under
closely to the posterosuperior surface are the vasa deferentia which lie circularly oriented smooth-muscle fibers and
and seminal vesicles (Figure 1–7). Posteriorly, the prostate is collagenous tissue that surrounds the urethra (involuntary

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ANATOMY OF THE GENITOURINARY TRACT CHAPTER 1 11

▲▲Figure 1–9. Anatomy and relations of the bladder, urethra, uterus and ovary, vagina, and rectum.

▲▲Figure 1–10. Left: Histology of the prostate. Epithelial glands embedded in a mixture of connective and elastic tissue
and smooth muscle. Right: Histology of the bladder. The mucosa is transitional cell in type and lies on a well-developed
submucosal layer of connective tissue. The detrusor muscle is composed of interlacing longitudinal, circular, and spiral
smooth-muscle bundles.

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12 SMITH & TANAGHO’S GENERAL UROLOGY

▲▲Figure 1–11. Section of the prostate gland shows the


prostatic urethra, verumontanum, and crista urethralis,
in addition to the opening of the prostatic utricle and
the two ejaculatory ducts in the midline. Note that the
prostate is surrounded by the prostatic capsule, which
is covered by another prostatic sheath derived from the
endopelvic fascia. The prostate is resting on the genitouri-
nary diaphragm. (Reproduced with permission from Walsh
PC, Campbell MF: Campbell’s Urology, 6th ed. Philadelphia,
PA: Saunders; 1992.) ▲▲Figure 1–12. Anatomy of the prostate gland. Prostatic
adenoma develops from the periurethral glands at the
site of the median or lateral lobes. The posterior lobe,
however, is prone to cancerous degeneration. (Adapted
sphincter). Deep in this layer lies the prostatic stroma,
with permission from McNeal JE: The zonal anatomy of the
composed of connective tissues and smooth-muscle fibers
prostate. Prostate 1981;2(1):35–49.)
in which are embedded the epithelial glands. These glands
drain into the major excretory ducts (about 25 in number),
which open chiefly on the floor of the urethra between
the verumontanum and the vesical neck. Just beneath ▶▶Lymphatics
the transitional epithelium of the prostatic urethra lie the The lymphatics from the prostate drain into the internal iliac
periurethral glands. (hypogastric), sacral, vesical, and external iliac lymph nodes
(Saokar et al, 2010).
▶▶Blood Supply
A. Arterial SEMINAL VESICLES
The arterial supply to the prostate is derived from the inferior
vesical, internal pudendal, and middle rectal (hemorrhoidal) ▶▶Gross Appearance
arteries. The seminal vesicles lie just cephalic to the prostate under
the base of the bladder (Figures 1–6 and 1–7). They are about
B. Venous 6 cm long and quite soft. Each vesicle joins its corresponding
vas deferens to form the ejaculatory duct (Kim et al, 2009).
The veins from the prostate drain into the periprostatic The ureters lie medial to each, and the rectum is contiguous
plexus, which has connections with the deep dorsal vein of with their posterior surfaces.
the penis and the internal iliac (hypogastric) veins.

▶▶Histology
▶▶Nerve Supply The mucous membrane is pseudostratified. The submu-
The prostate gland receives a rich innervation from the sym- cosa consists of dense connective tissue covered by a thin
pathetic and parasympathetic nerves of the inferior hypogas- layer of muscle that, in turn, is encapsulated by connective
tric plexus. tissue.

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ANATOMY OF THE GENITOURINARY TRACT CHAPTER 1 13

▶▶Blood Supply EPIDIDYMIS


The blood supply of the seminal vesicles is similar to that of
the prostate gland. ▶▶Gross Appearance
A. Anatomy
▶▶Nerve Supply The upper portion of the epididymis (globus major) is con-
The nerve supply is mainly from the sympathetic nerve nected to the testis by numerous efferent ducts from the testis
plexus. (Figure 1–7). The epididymis consists of a markedly coiled
duct that, at its lower pole (globus minor), is continuous with
▶▶Lymphatics the vas deferens. An appendix of the epididymis is often seen
on its upper pole; this is a cystic body that in some cases is
The lymphatics of the seminal vesicles are those that serve
pedunculated, but in others, it is sessile.
the prostate.
B. Relations
SPERMATIC CORD
The epididymis lies posterolateral to the testis and is nearest
▶▶Gross Appearance to the testis at its upper pole. Its lower pole is connected to
the testis by fibrous tissue. The vas lies posteromedial to the
The two spermatic cords extend from the internal ingui- epididymis.
nal rings through the inguinal canals to the testicles
(Figure 1–7). Each cord contains the vas deferens, the
internal and external spermatic arteries, the artery of
▶▶Histology
the vas, the venous pampiniform plexus (which forms The epididymis is covered by serosa. The ductus epididy-
the spermatic vein superiorly), lymph vessels, and nerves midis is lined by pseudostratified columnar epithelium
(Jen et al, 1999). The entire cord contents are enclosed in throughout its length.
investing layers of thin fascia. A few fibers of the cremaster
muscle insert on the cords in the inguinal canal (Bhosale ▶▶Blood Supply
et al, 2008; Kim et al, 2009). A. Arterial

▶▶Histology The arterial supply to the epididymis comes from the internal
spermatic artery and the artery of the vas (deferential artery).
The fascia covering the cord is formed of loose connective
tissue that supports arteries, veins, nerve, and lymphatics. B. Venous
The vas deferens is a small, thick-walled tube consisting of an
internal mucosa and submucosa surrounded by three well- The venous blood drains into the pampiniform plexus, which
defined layers of smooth muscle encased in a covering of becomes the spermatic vein.
fibrous tissue. Above the testes, this tube is straight. Its proxi-
mal 4 cm tends to be convoluted. ▶▶Lymphatics
The lymphatics drain into the external iliac and internal iliac
▶▶Blood Supply (hypogastric) lymph nodes.
A. Arterial
TESTIS
The external spermatic artery, a branch of the inferior epigas-
tric, supplies the fascial coverings of the cord. The internal ▶▶Gross Appearance
spermatic artery passes through the cord on its way to the
testis. The deferential artery is close to the vas. A. Anatomy
The average testicle measures about 4 × 3 × 2.5 cm
B. Venous (Figure 1–7). The volume can be measured by an orchidom-
The veins from the testis and the coverings of the spermatic eter or by a formula with ultrasonic measurement (length ×
cord form the pampiniform plexus, which, at the internal width × height × 0.71). The average volume is 18 mL (rang-
inguinal ring, unites to form the spermatic vein. ing from 12 to 30 mL). The testicle has a dense fascial cov-
ering called the tunica albuginea testis, which, posteriorly,
is invaginated somewhat into the body of the testis to form
▶▶Lymphatics the mediastinum testis. This fibrous mediastinum sends
The lymphatics from the spermatic cord empty into the fibrous septa into the testis, thus separating it into about
external iliac lymph nodes. 250 lobules.

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14 SMITH & TANAGHO’S GENERAL UROLOGY

The testis is covered anteriorly and laterally by the visceral SCROTUM


layer of the serous tunica vaginalis, which is continuous with
the parietal layer that separates the testis from the scrotal ▶▶Gross Appearance
wall (Bidarkar and Hutson, 2005). A small amount of fluid
normally exists within the tunica vaginalis sac. At the upper Beneath the corrugated skin of the scrotum lies the dartos
pole of the testis is the appendix testis, a small pedunculated muscle. Deep to this are the three fascial layers derived from
or sessile body similar in appearance to the appendix of the the abdominal wall at the time of testicular descent. Beneath
epididymis. these is the parietal layer of the tunica vaginalis (Kim et al,
2007).
B. Relations The scrotum is divided into two sacs by a septum of con-
nective tissue. The scrotum not only supports the testes but
The testis is closely attached posterolaterally to the epididy- also, by relaxation or contraction of its muscular layer, helps
mis, particularly at its upper and lower poles (Klonisch et al, to regulate their temperature.
2004).
▶▶Histology
▶▶Histology (Figure 1–7) The dartos muscle, under the skin of the scrotum, is nonstri-
Each lobule contains one to four markedly convoluted ated. The deeper layer is made up of connective tissue.
seminiferous tubules, each of which is about 60 cm long.
These ducts converge at the mediastinum testis, where ▶▶Blood Supply
they connect with the efferent ducts that drain into the A. Arterial
epididymis.
The seminiferous tubule has a basement membrane con- The arteries to the scrotum arise from the femoral, internal
taining connective and elastic tissue. This supports the semi- pudendal, and inferior epigastric arteries.
niferous cells that are of two types: (1) Sertoli (supporting)
cells and (2) spermatogenic cells. The stroma between the B. Venous
seminiferous tubules contains connective tissue in which the The veins are paired with the arteries.
interstitial Leydig cells are located.
▶▶Lymphatics
▶▶Blood Supply The lymphatics drain into the superficial inguinal and subin-
The blood supply to the testes is closely associated with that guinal lymph nodes.
to the kidneys because of the common embryologic origin of
the two organs. PENIS AND MALE URETHRA
A. Arterial
▶▶Gross Appearance
The arteries to the testes (internal spermatics) arise from the The penis is composed of two corpora cavernosa and the
aorta just below the renal arteries and course through the corpus spongiosum, which contains the urethra. The corpus
spermatic cords to the testes, where they anastomose with spongiosum enlarges distally and forms the glans penis. Each
the arteries of the vasa deferentia that branch off from the corpus is enclosed in a fascial sheath (tunica albuginea), and
internal iliac (hypogastric) artery. all three corpora are surrounded by a thick fibrous envelope
known as Buck’s fascia. A covering of skin, devoid of fat, is
B. Venous loosely wrapped these bodies. The prepuce forms a hood
The blood from the testis returns in the pampiniform plexus over the glans.
of the spermatic cord. At the internal inguinal ring, the Beneath the skin of the penis (and scrotum) and extend-
pampiniform plexus forms the spermatic vein. ing from the base of the glans to the urogenital diaphragm is
The right spermatic vein enters the vena cava just below Colles’ fascia, which is continuous with Scarpa’s fascia of the
the right renal vein; the left spermatic vein empties into the lower abdominal wall (Figure 1–8).
left renal vein. The proximal ends of the corpora cavernosa are attached
to the pelvic bones just anterior to the ischial tuberosities.
The ischiocavernosus muscles insert into the lateral surface
▶▶Lymphatics of the tunica albuginea at the proximal corpora cavernosa.
The lymphatic vessels from the testes pass to the lumbar Occupying a depression of their ventral surface in the midline
lymph nodes, which, in turn, are connected to the medias- is the corpus spongiosum, which is connected proximally to
tinal nodes. the undersurface of the urogenital diaphragm, below which

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ANATOMY OF THE GENITOURINARY TRACT CHAPTER 1 15

lies the urethral bulb. This portion of the corpus spongiosum FEMALE URETHRA
is surrounded by the bulbospongiosus muscle.
The suspensory ligament of the penis arises from the linea ▶▶Gross Appearance
alba and pubic symphysis and inserts into the fascial covering
of the corpora cavernosa. The adult female urethra is about 4 cm long and 8 mm in
diameter. It is slightly curved and lies beneath the pubic sym-
physis just anterior to the vagina.
▶▶Histology
A. Corpora and Glans Penis ▶▶Histology
The corpora cavernosa, the corpus spongiosum, and the The epithelial lining of the female urethra is squamous in
glans penis are composed of smooth muscles, intracaverno- its distal portion and pseudostratified or transitional in the
sal struts (corpus cavernosum only), and endothelium-lined remainder. The submucosa is made up of connective and
sinusoids. The sympathetic and parasympathetic (as well as elastic tissues and spongy venous spaces. Embedded in it are
the nonadrenergic, noncholinergic [NANC]) nerve termi- many periurethral glands, which are most numerous distally;
nals are often seen around the vessels and near the smooth the largest of these are the periurethral glands of Skene that
muscles. open on the floor of the urethra just inside the meatus.
External to the submucosa is a longitudinal layer of
B. Urethra smooth muscle continuous with the inner longitudinal
layer of the bladder wall. Surrounding this is a heavy layer
The urethral mucosa that traverses the glans penis is formed
of circular smooth-muscle fibers extending from the exter-
of squamous epithelium. Proximal to this, the mucosa is tran-
nal vesical muscular layer. This constitutes the involuntary
sitional in type. Underneath the mucosa is the submucosa that
internal urethral sphincter. Distal to this is the external stri-
contains connective and elastic tissue and smooth muscle. In
ated (voluntary) sphincter surrounding the middle third of
the submucosa are the numerous glands of Littre, whose ducts
the urethra composed of smooth and striated muscles within
connect with the urethral lumen. The urethra is surrounded by
the midurethra (Ashton-Miller and Delancey, 2009; Morgan
the vascular corpus spongiosum and the glans penis.
et al 2009; Thor and de Groat, 2010).

▶▶Blood Supply ▶▶Blood Supply


A. Arterial The arterial supply to the female urethra is derived from the
The penis and urethra are supplied by the internal pudendal inferior vesical, vaginal, and internal pudendal arteries. Blood
arteries. Each artery divides into a cavernous artery of the from the urethra drains into the internal pudendal veins.
penis (which supplies the corpora cavernosa), a dorsal artery
of the penis, and the bulbourethral artery. These branches ▶▶Lymphatics
supply the corpus spongiosum, the glans penis, and the ure- Lymphatic drainage from the external portion of the urethra
thra. Accessory pudendal arteries originate from inferior is to the inguinal and subinguinal lymph nodes. Drainage
vesical, obturator, or other arteries may also supply the penis from the deep urethra is into the internal iliac (hypogastric)
(Henry et al, 2017). lymph nodes.

B. Venous BIBLIOGRAPHY
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35–49. Ashton-Miller JA, Delancey JO: On the biomechanics of vaginal birth
Myers RP et al: Making anatomic terminology of the prostate and and common sequelae. Annu Rev Biomed Eng 2009;11:163–176.
contiguous structures clinically useful: Historical review and sug- Delancey JO: Why do women have stress urinary incontinence?
gestions for revision in the 21st century. Clin Anat 2010;23:18–29. Neurourol Urodyn 2010;29(Suppl 1):S13–S17.
Raychaudhuri B, Cahill D: Pelvic fasciae in urology. Ann Roy Coll Morgan et al: Urethral sphincter morphology and function with and
Surg Engl 2008;90:633–637. without stress incontinence. J Urol 2009;182(1):203–209.
Saokar A et al: Detection of lymph nodes in pelvic malignancies with Thor KB, de Groat WC: Neural control of the female urethral and
computed tomography and magnetic resonance imaging. Clin anal rhabdosphincters and pelvic floor muscles. Am J Physiol
Imaging 2010;34:361–366. Regul Integr Compar Physiol 2010;299:R416–R438.

McAninch_CH01_p001-p016.indd 16 07/02/20 9:58 AM


17

2
Embryology of the
Genitourinary System

Emil A. Tanagho, MD; Hiep T. Nguyen, MD;


& Michael DiSandro, MD

At birth, the genital and urinary systems are related only in nearby primary nephric duct as it grows caudally to join
the sense that they share certain common passages. Embryo- the cloaca (Figure 2–1). This primary nephric duct is now
logically, however, they are intimately related. Because of the called the mesonephric duct. After establishing their con-
complex interrelationships of the embryonic phases of the nection with the nephric duct, the primordial tubules elon-
two systems, they are discussed here as five subdivisions: gate and become S-shaped. As the tubules elongate, a series
the nephric system, the vesicourethral unit, the gonads, the of secondary branches increase their surface exposure,
genital duct system, and the external genitalia. thereby enhancing their capacity for interchanging material
with the blood in adjacent capillaries. Leaving the glomeru-
NEPHRIC SYSTEM lus, the blood is carried by one or more efferent vessels that
soon break up into a rich capillary plexus closely related to
The nephric system develops progressively as three distinct
the mesonephric tubules. The mesonephros, which forms
entities: pronephros, mesonephros, and metanephros.
early in the 4th week, reaches its maximum size by the end
of the second month.
▶▶Pronephros
The pronephros is the earliest nephric stage in humans, and ▶▶Metanephros
it corresponds to the mature structure of the most primitive
The metanephros, the final phase of development of the
vertebrate. It extends from the 4th to the 14th somites and
nephric system, originate from both the intermediate meso-
consists of 6–10 pairs of tubules. These open into a pair of
derm and the mesonephric duct. Development begins in the
primary ducts that are formed at the same level, extend cau-
5–6-mm embryo with a budlike outgrowth from the meso-
dally, and eventually reach and open into the cloaca. The pro-
nephric duct as it bends to join the cloaca. This ureteral bud
nephros is a vestigial structure that disappears completely by
grows cephalad and collects mesoderm from the nephro-
the 4th week of embryonic life (Figure 2–1).
genic cord of the intermediate mesoderm around its tip. This
mesoderm with the metanephric cap moves, with the grow-
▶▶Mesonephros ing ureteral bud, more and more cephalad from its point of
The mature excretory organ of the larger fish and amphib- origin. During this cephalic migration, the metanephric cap
ians corresponds to the embryonic mesonephros. It is becomes progressively larger, and rapid internal differentia-
the principal excretory organ during early embryonic life tion takes place. Meanwhile, the cephalic end of the ureteral
(4–8 weeks). It, too, gradually degenerates, although parts bud expands within the growing mass of metanephrogenic
of its duct system become associated with the male repro- tissue to form the renal pelvis (Figure 2–1). Numerous out-
ductive organs. The mesonephric tubules develop from the growths from the renal pelvic dilatation push radially into
intermediate mesoderm caudal to the pronephros shortly this growing mass and form hollow ducts that branch and
before pronephric degeneration. The mesonephric tubules rebranch as they push toward the periphery. These form the
differ from those of the pronephros in that they develop a primary collecting ducts of the kidney. Mesodermal cells
cuplike outgrowth into which a knot of capillaries is pushed. become arranged in small vesicular masses that lie close to
This is called Bowman’s capsule, and the tuft of capillaries the blind end of the collecting ducts. Each of these vesicular
is called a glomerulus. In their growth, the mesonephric masses will form a uriniferous tubule draining into the duct
tubules extend toward and establish a connection with the nearest to its point of origin.

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18 SMITH & TANAGHO’S GENERAL UROLOGY

▲▲Figure 2–1. Schematic representation of the development of the nephric system. Only a few of the tubules of the
pronephros are seen early in the 4th week, while the mesonephric tissue differentiates into mesonephric tubules that
progressively join the mesonephric duct. During this time, the first sign of the ureteral bud from the mesonephric duct is
seen. At 6 weeks, the pronephros has completely degenerated and the mesonephric tubules start to do so. The ureteral
bud grows dorsocranially and has met the metanephrogenic cap. At the 8th week, there is cranial migration of the differ-
entiating metanephros. The cranial end of the ureteric bud expands and starts to show multiple successive outgrowths.
(Data from several sources.)

As the kidney grows, increasing numbers of tubules are the ends of the anterior pronephric tubules; (4) this pronephric
formed in its peripheral zone. These vesicular masses develop duct serves subsequently as the mesonephric duct and as such
a central cavity and become S-shaped. One end of the S gives rise to the ureter; (5) the nephric duct reaches the cloaca
coalesces with the terminal portion of the collecting tubules, by independent caudal growth; and (6) the embryonic ureter
resulting in a continuous canal. The proximal portion of the is an outgrowth of the nephric duct, yet the kidney tubules dif-
S develops into the distal and proximal convoluted tubules ferentiate from adjacent metanephric blastema.
and into Henle’s loop; the distal end becomes the glomeru-
lus and Bowman’s capsule. At this stage, the undifferentiated
mesoderm and the immature glomeruli are readily visible on ▶▶Molecular Mechanisms of Renal and
microscopic examination (Figure 2–2). The glomeruli are
Ureteral Development
fully developed by the 36th week or when the fetus weighs The kidney and the collecting system originate from the
2500 g (Osathanondh and Potter, 1964a, b). The metaneph- interaction between the mesonephric duct (Wolffian duct)
ros arises opposite the 28th somite (fourth lumbar segment). and the metanephric mesenchyme (MM). The uretic bud
At term, it has ascended to the level of the first lumbar or (UB) forms as an epithelial outpouching from the meso-
even the twelfth thoracic vertebra. This ascent of the kidney nephric duct and invades the surrounding MM. Reciprocal
is due not only to actual cephalic migration but also to differ- induction between the UB and MM results in branching
ential growth in the caudal part of the body. During the early and elongation of the UB from the collecting system and in
period of ascent (7th–9th weeks), the kidney slides above the condensation and epithelial differentiation of MM around
arterial bifurcation and rotates 90°. Its convex border is now the branched tips of the UB. Branching of the UB occurs
directed laterally, not dorsally. Ascent proceeds more slowly approximately 15 times during human renal development,
until the kidney reaches its final position. generating approximately 300,000 and 1 million nephrons
Certain features of these three phases of development must per kidney (Nyengaard and Bendtsen, 1992).
be emphasized: (1) the three successive units of the system This process of reciprocal induction is dependent on the
develop from the intermediate mesoderm; (2) the tubules at all expression of specific factors. Glial cell-derived neurotrophic
levels appear as independent primordia and only secondarily factor (GDNF) is the primary inducer of ureteric budding
unite with the duct system; (3) the nephric duct is laid down (Costantini and Shakya, 2006). GDNF interacts with sev-
as the duct of the pronephros and develops from the union of eral different proteins from the MM (eg, Wt1, Pax2, Eyal,

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EMBRYOLOGY OF THE GENITOURINARY SYSTEM CHAPTER 2 19

▲▲Figure 2–2. Progressive stages in the differentiation of the nephrons and their linkage with the branching collecting
tubules. A small lump of metanephric tissue is associated with each terminal collecting tubule. These are then arranged
in vesicular masses that later differentiate into a uriniferous tubule draining into the duct near which it arises. At one
end, Bowman’s capsule and the glomerulus differentiate; the other end establishes communication with the nearby
collecting tubules.

Six1, Sall1) and from the UB itself (Pax2, Lim1, Ret) result- termination and tubule maintenance (hepatocyte growth fac-
ing in outgrowth of the UB (reviewed by Shah et al, 2004). tor, transforming growth factor-α, epidermal growth factor
Proper activation of the Ret/GDNF signaling pathway in receptor) (reviewed by Shah et al, 2004). BMP7, SHH, and
the tip of UB epithelium appears to be essential in the pro- Wnt11 produced from the branching ureteric bud induce the
gression of branching morphogenesis (reviewed by Michos, MM to differentiate. These factors induce the activation of
2009). B-catenin and Gata3 are important regulators of Ret Pax2, α-8-integrin, and Wnt4 in the renal mesenchymal cells,
expression, and correct activity of Ret is regulated by posi- resulting in condensation of the MM and the formation of
tive (Wnt11 from MM) and negative (Sprouty1 from the UB) pretubular aggregate and primitive renal vesicle (reviewed by
feedback signaling. Additional specific factors are required for Burrow, 2000). With the continued induction from the UB
(1) early branching (eg, Wnt4 and Wnt11, fgf 7–10); (2) late and the autocrine activity of Wnt4, the pretubular aggregates
branching and maturation (bmp2, activin); and (3) branching differentiate into comma-shaped bodies. Platelet-derived

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20 SMITH & TANAGHO’S GENERAL UROLOGY

growth factor α-β and vascular endothelial growth factor ureter and is most commonly associated with an accessory
expression are required for initiating the migration of endo- ureteral bud in a duplicated system, but it also can be seen in
thelial cells into the cleft of the comma-shaped bodies to a single system. The migration and insertion of the ureteric
form rudimentary glomerular capillary tufts (reviewed by bud into the bladder depend on Ret gene activity and Ret
Burrow, 2000). Wt1 and Pod1 may have important functions gene expression and is mediated by the action of the retinoic
in the regulation of gene transcription necessary for the dif- acid and Gata3 gene (Schultza, 2016).
ferentiation of podocytes (Ballermann, 2005).
Fibroblast growth factors (FGF) are also important for
VESICOURETHRAL UNIT
early metanephric development, especially the receptors
Fgfr1 and Fgfr2. A loss of both these receptors leads to kid- The blind end of the hindgut caudal to the point of origin of
ney agenesis. Other signaling proteins include Six1 and Sall1. the allantois expands to form the cloaca, which is separated
Six1 is a homeobox protein essential for early kidney devel- from the outside by a thin plate of tissue (the cloacal mem-
opment. Sall1 is a transcription factor that is important for brane) lying in an ectodermal depression (the proctodeum)
the development of the metanephros. Lack of Sall1 leads to under the root of the tail. At the 4-mm stage, starting at the
renal agenesis (Krause, 2015). cephalic portion of the cloaca where the allantois and gut
meet, the cloaca progressively divides into two compartments
by the caudal growth of a crescentic fold, the urorectal fold.
ANOMALIES OF THE NEPHRIC SYSTEM
The two limbs of the fold bulge into the lumen of the cloaca
Failure of the metanephros to ascend leads to an ectopic kidney. from either side, eventually meeting and fusing. The division
An ectopic kidney may be on the proper side but low (simple of the cloaca into a ventral portion (urogenital sinus) and a
ectopy) or on the opposite side (crossed ectopy) with or with- dorsal portion (rectum) is completed during the 7th week.
out fusion. Failure to rotate during ascent causes a malrotated During the development of the urorectal septum, the cloacal
kidney. Fusion of the paired metanephric masses leads to vari- membrane undergoes a reverse rotation, so that the ectoder-
ous anomalies—most commonly a “horseshoe” kidney. mal surface is no longer directed toward the developing ante-
The ureteral bud from the mesonephric duct may bifur- rior abdominal wall but gradually is turned to face caudally
cate, causing a bifid ureter at various levels depending on and slightly posteriorly. This change facilitates the subdivision
the time of the bud’s subdivision. An accessory ureteral bud of the cloaca and is brought about mainly by development of
may develop from the mesonephric duct, thereby forming the infraumbilical portion of the anterior abdominal wall and
a duplicated ureter, usually meeting the same metaneph- regression of the tail. The mesoderm that passes around the
ric mass. Rarely, each bud has a separate metanephric mass, cloacal membrane to the caudal attachment of the umbilical
resulting in supernumerary kidneys. cord proliferates and grows, forming a surface elevation, the
If the double ureteral buds are close together on the meso- genital tubercle. Further growth of the infraumbilical part
nephric duct, they open near each other in the bladder. In of the abdominal wall progressively separates the umbilical
this case, the main ureteral bud, which is the first to appear cord from the genital tubercle. The division of the cloaca is
and the most caudal on the mesonephric ducts, reaches the completed before the cloacal membrane ruptures, and its two
bladder first. It then starts to move upward and laterally and parts therefore have separate openings. The ventral part is the
is followed later by the second accessory bud as it reaches the primitive urogenital sinus, which has the shape of an elon-
urogenital sinus. The main ureteral bud (now more cranial gated cylinder and is continuous cranially with the allantois;
on the urogenital sinus) drains the lower portion of the kid- its external opening is the urogenital ostium. The dorsal part
ney. The two ureteral buds reverse their relationship as they is the rectum, and its external opening is the anus.
move from the mesonephric duct to the urogenital sinus. Traditionally, it is believed that the urogenital sinus
This is why duplicated ureters always cross (Weigert–Meyer receives the mesonephric ducts. The caudal end of the meso-
law). If the two ureteral buds are widely separated on the nephric duct distal to the ureteral bud (the common excre-
mesonephric duct, the accessory bud appears more proximal tory duct) is progressively absorbed into the urogenital sinus.
on the mesonephric duct and therefore ends in the bladder By the 7th week, the mesonephric duct and the ureteral bud
more distal than usual, with an ectopic orifice lower than the have independent opening sites. This introduces an island of
normal one. This ectopic orifice could still be in the bladder mesodermal tissue amid the surrounding endoderm of the
close to its outlet, in the urethra, or even in the genital duct urogenital sinus. As development progresses, the opening
system (Figure 2–3). A single ureteral bud that arises more of the mesonephric duct (which will become the ejaculatory
proximal than normal on the mesonephric duct can also end duct) migrates downward and medially. The opening of the
in a similar ectopic location, although this is less common. ureteral bud (which will become the ureteral orifice) migrates
Lack of development of a ureteral bud results in a solitary upward and laterally. The absorbed mesoderm of the meso-
kidney and a hemitrigone. The ureteral bud may also develop nephric duct expands with this migration to occupy the area
or migrate into the bladder, abnormally leading to a uretero- limited by the final position of these tubes (Figure 2–3).
cele. A ureterocele is a cystic dilation of the distal intramural This will later be differentiated as the trigonal structure,

McAninch_CH02_p017-p030.indd 20 07/02/20 10:00 AM


EMBRYOLOGY OF THE GENITOURINARY SYSTEM CHAPTER 2 21

▲▲Figure 2–3. Development of the ureteral bud from the mesonephric duct and the relationship of both to the urogenital
sinus. The ureteral bud appears at the 4th week. The mesonephric duct distal to this ureteral bud is gradually absorbed
into the urogenital sinus, resulting in separate endings for the ureter and the mesonephric duct. The mesonephric tissue
that is incorporated into the urogenital sinus expands and forms the trigonal tissue.

which is the only mesodermal inclusion in the endodermal supported by more recent studies that suggest the trigone is
vesicourethral unit. formed mostly from bladder smooth muscle and less so from
More recent studies suggest an alternative path of devel- the ureters. Condensation of myoblasts in the region between
opment (reviewed by McInnes and Michaud, 2009). The the openings of the ureters and Wolffian ducts at 12 weeks of
right and left common excretory ducts appear to undergo gestation gives rise to the trigone, as a single circular muscu-
gradual programmed cell death; the elimination of the com- lar layer and the muscles from the distal ureters cross midline
mon excretory ducts brings the distal ureters into immediate to form the interureteral fold (Oswald et al, 2006).
contact with the urogenital sinus epithelium. Concurrently, The urogenital sinus can be divided into two main seg-
the ureters undergo a 180° rotation around the axis of the ments. The dividing line, the junction of the combined
mesonephric duct (also known as the Wolffian duct). The Müllerian ducts with the dorsal wall of the urogenital sinus, is
distal segment of the ureters then also undergoes apoptosis. an elevation called Müller’s tubercle, which is the most fixed
As a result, this process generates a new ureteral connection reference point in the whole structure and is discussed in a
point in the urogenital sinus region that will give rise to the subsequent section. The segments are as follows:
bladder, while the Wolffian duct remains in the region giving 1. The ventral and pelvic portion forms the bladder, part of
rise to the urethra. Further growth of the bladder and ure- the urethra in males, and the whole urethra in females.
thra moves the ureteral orifices cranially, while those to the This portion receives the ureter.
Wolffian ducts move caudally. This pattern of development is

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22 SMITH & TANAGHO’S GENERAL UROLOGY

2. The urethral, or phallic, portion receives the mesonephric The part of the urogenital sinus caudal to the opening of
and the fused Müllerian ducts. This will be part of the ure- the Müllerian duct forms the vaginal vestibule and contrib-
thra in males and forms the lower fifth of the vagina and utes to the lower fifth of the vagina in females (Figure 2–5).
the vaginal vestibule in females. In males, it forms the inframontanal part of the prostatic
During the 3rd month, the ventral part of the urogenital urethra and the membranous urethra. The penile urethra
sinus starts to expand and forms an epithelial sac whose apex is formed by the fusion of the urethral folds on the ventral
tapers into an elongated, narrowed urachus. The pelvic por- surface of the genital tubercle. In females, the urethral folds
tion remains narrow and tubular; it forms the whole urethra remain separate and form the labia minora. The glandular
in females and the supramontanal portion of the prostatic urethra in males is formed by canalization of the urethral
urethra in males. The splanchnic mesoderm surrounding the plate. The bladder originally extends up to the umbilicus,
ventral and pelvic portion of the urogenital sinus begins to where it is connected to the allantois that extends into the
differentiate into interlacing bands of smooth-muscle fibers umbilical cord. The allantois usually is obliterated at the level
and an outer fibrous connective tissue coat. By the 12th week, of the umbilicus by the 15th week. The bladder then starts to
the layers characteristic of the adult urethra and bladder are descend by the 18th week. As it descends, its apex becomes
recognizable (Figure 2–4). stretched and narrowed, and it pulls on the already obliterated

▲▲Figure 2–4. Differentiation of the urogenital sinus in males. At the 5th week, the progressively growing urorectal
septum separates the urogenital sinus from the rectum. The former receives the mesonephric duct and the ureteral
bud. It retains its tubular structure until the 12th week, when the surrounding mesenchyme starts to differentiate into
the muscle fibers around the whole structure. The prostate gland develops as multiple epithelial outgrowths just above
and below the mesonephric duct. During the 3rd month, the ventral part of the urogenital sinus expands to form the
bladder proper; the pelvic part remains narrow and tubular, forming part of the urethra. (Reproduced with permission
from Tanagho EA, Smith DR: Mechanism of urinary continence. I. Embryologic, anatomic and pathologic considerations, J Urol.
1968 Nov;100(5):640–646.)

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EMBRYOLOGY OF THE GENITOURINARY SYSTEM CHAPTER 2 23

▲▲Figure 2–5. Differentiation of the urogenital sinus and the Müllerian ducts in the female embryo. At 9 weeks, the
urogenital sinus receives the fused Müllerian ducts at Müller’s tubercle (sinovaginal node), which is solidly packed with
cells. As the urogenital sinus distal to Müller’s tubercle becomes wider and shallower (15 weeks), the urethra and fused
Müllerian duct will have separate openings. The distal part of the urogenital sinus forms the vaginal vestibule and the
lower fifth of the vagina (shaded area), and that part above Müller’s tubercle forms the urinary bladder and the entire
female urethra. The fused Müllerian ducts form the uterus and the upper four-fifths of the vagina. The hymen is formed at
the junction of the sinovaginal node and the urogenital sinus.

allantois, now called the urachus. By the 20th week, the blad- anterior lobe tubules are large and show multiple branches,
der is well separated from the umbilicus, and the stretched they gradually contract and lose most of the branches. They
urachus becomes the middle umbilical ligament. continue to shrink so that at birth, they show no lumen and
appear as small, solid embryonic epithelial outgrowths. In
contrast, the tubules of the posterior lobe are fewer in num-
PROSTATE ber yet larger, with extensive branching. These tubules, as
The prostate develops as multiple solid outgrowths of the they grow, extend posterior to the developing median and lat-
urethral epithelium both above and below the entrance of the eral lobes and form the posterior aspect of the gland, which
mesonephric duct. These simple tubular outgrowths begin to may be felt rectally.
develop in five distinct groups at the end of the 11th week and Prostate development results from complex interaction
are complete by the 16th week (112-mm stage). They branch between urogenital sinus epithelium and mesenchyme in
and rebranch, ending in a complex duct system that encoun- the presence of androgens (reviewed by Cunha et al, 2004,
ters the differentiating mesenchymal cells around this seg- and Thomson, 2008). Early in development, the androgen
ment of the urogenital sinus. These mesenchymal cells start receptors are solely expressed in the urogenital sinus mesen-
to develop around the tubules by the 16th week and become chyme. Under the influence of androgen, the mesenchyme
denser at the periphery to form the prostatic capsule. By the induces epithelial bud formation, regulates the growth and
22nd week, the muscular stroma is considerably developed, branching of epithelial bud, promotes differentiation of a
and it continues to increase progressively until birth. secretory epithelium, and specifies differential expression
From the five groups of epithelial buds, five lobes are eventu- of prostatic secretory proteins. Genome-wide analyses have
ally formed: anterior, posterior, median, and two lateral lobes. revealed critical molecular events in prostate development.
Initially, these lobes are widely separated, but later they meet, These include Nkx3.1, Sox, and homeobox genes for ductal
with no definite septa dividing them. Tubules of each lobe do morphology development; sonic hedgehog, fibroblast growth
not intermingle with each other but simply lie side by side. factor and the Wnt5a gene for bud development; and bone
The anterior lobe tubules begin to develop simultaneously morphogenic protein and notch genes for branching (Meeks,
with those of the other lobes. In the early stages, although the 2011). Other factors such as activin A serve to inhibit ductal

McAninch_CH02_p017-p030.indd 23 07/02/20 10:00 AM


24 SMITH & TANAGHO’S GENERAL UROLOGY

branching in order to maintain tissue homeostasis and regu- mesonephros is converted into a gonadal mesentery known
lated growth in the prostate. as the mesorchium. The cells of the germinal epithelium
grow into the underlying mesenchyme and form cordlike
ANOMALIES OF THE VESICOURETHRAL UNIT masses. These are radially arranged and converge toward the
mesorchium, where a dense portion of the blastemal mass
Failure of the cloaca to subdivide is rare and results in a
is also emerging as the primordium of the rete testis. A net-
persistent cloaca. Incomplete subdivision is more frequent,
work of strands soon forms that is continuous with the testis
ending with rectovesical, rectourethral, or rectovestibular
cords. The latter also split into three to four daughter cords.
fistulas (usually with imperforate anus or anal atresia).
These eventually become differentiated into the seminifer-
Failure of descent or incomplete descent of the blad-
ous tubules by which the spermatozoa are produced. The rete
der leads to a urinary umbilical fistula (urachal fistula),
testis unites with the mesonephric components that will form
urachal cyst, or urachal diverticulum depending on the
the male genital ducts, as discussed in a subsequent section
stage and degree of maldescent.
(Figure 2–6).
Development of the genital primordia in an area more
If the gonad develops into an ovary, it (like the testis) gains
caudal than normal can result in formation of the corpora
a mesentery (mesovarium) and settles in a more caudal posi-
cavernosa just caudal to the urogenital sinus outlet, with the
tion. During the 9th week the internal blastema differentiates
urethral groove on its dorsal surface. This defect results in
in the into a primary cortex beneath the germinal epithelium
complete or incomplete epispadias depending on its degree.
and a loose primary medulla. A compact cellular mass bulges
A more extensive defect results in bladder exstrophy. Failure
from the medulla into the mesovarium and establishes the
of fusion of urethral folds leads to various grades of hypospa-
primitive rete ovarii. At 3–4 months of age, the internal cell
dias. This defect, because of its mechanism, never extends
mass becomes young ova. A new definitive cortex is formed
proximal to the bulbous urethra. This is in contrast to epi-
from the germinal epithelium as well as from the blastema
spadias, which usually involves the entire urethra up to the
in the form of distinct cellular cords (Pflüger’s tubes), and a
internal meatus.
permanent medulla is formed. The cortex differentiates into
ovarian follicles containing ova.
GONADS
Genetically, in the presence of a Y chromosome, SRY (as
Most of the structures that make up the embryonic genital sys- known as testis determining factor [TDF]) induces the upreg-
tem have been taken over from other systems, and their read- ulation of Sox9 in the undifferentiated gonad (reviewed by
aptation to genital function is a secondary and relatively late Sekido, 2010). This in turn upregulates the expression of FGF9
phase in their development. The early differentiation of such and increases PGD2 synthesis, both helping to maintain Sox9
structures is therefore independent of sexuality. Furthermore, expression. Sox9 directs the differentiation of cells into Sertoli
each embryo is at first morphologically bisexual, possessing all cell by activating several downstream genes such as Amh,
the necessary structures for either sex. The development of one Cbln4, FGF9, and Ptgds. In the absence of a Y chromosome
set of sex primordia and the gradual involution of the other are and SRY, Rspo1 is upregulated in the undifferentiated gonads
determined by the sex of the gonad. (reviewed by Nef and Vassalli, 2009). Rspo1 is required for
The sexually undifferentiated gonad is a composite struc- Wnt4 expression, and together they activate β-catenin, which,
ture. Male and female potentials are represented by specific in turn, suppresses the formation of the testis cords by inhibit-
histologic elements (medulla and cortex) that have alterna- ing Sox9 and FGF9. A second pathway involving the upregu-
tive roles in gonadogenesis. Normal differentiation involves lation of Foxl2 also serves to inhibit Sox 9 and FGF9 activity,
the gradual predominance of one component. contributing to the development of the ovary.
The primitive sex glands appear during the 5th and 6th New genetic data on human sex determination from
weeks within a localized region of the thickening known as modern gene sequencing will create opportunities for the
the urogenital ridge (this contains both the nephric and the development of mechanistic models and should lead to
genital primordia). At the 6th week, the gonad consists of better understanding of this complex process (reviewed by
a superficial germinal epithelium and an internal blastema. Bashamboo, 2017).
The blastemal mass is derived mainly from proliferative
ingrowth from the superficial epithelium, which comes loose ▶▶Descent of the Gonads
from its basement membrane.
A. Testis
During the 7th week, the gonad begins to assume the
characteristics of a testis or ovary. Differentiation of the In addition to its early caudal migration, the testis later leaves
ovary usually occurs somewhat later than differentiation of the abdominal cavity and descends into the scrotum. By the
the testis. 3rd month of fetal life, the testis is located retroperitoneally
If the gonad develops into a testis, the gland increases in in the false pelvis. A fibromuscular band (the gubernacu-
size and shortens into a more compact organ while achiev- lum) extends from the lower pole of the testis through the
ing a more caudal location. Its broad attachment to the developing muscular layers of the anterior abdominal wall

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EMBRYOLOGY OF THE GENITOURINARY SYSTEM CHAPTER 2 25

▲▲Figure 2–6. Transformation of the undifferentiated genital system into the definitive male and female systems.

McAninch_CH02_p017-p030.indd 25 07/02/20 10:00 AM


26 SMITH & TANAGHO’S GENERAL UROLOGY

to terminate in the subcutaneous tissue of the scrotal swell- the 4-mm stage) joins the ventral part of the cloaca, which
ing. The gubernaculum also has several other subsidiary will be the urogenital sinus. This duct gives rise to the ureteral
strands that extend to adjacent regions. Just below the bud close to its caudal end. The ureteral bud grows cranially
lower pole of the testis, the peritoneum herniates as a and meets metanephrogenic tissue. The part of each meso-
diverticulum along the anterior aspect of the gubernacu- nephric duct caudal to the origin of the ureteric bud becomes
lum, eventually reaching the scrotal sac through the ante- absorbed into the wall of the primitive urogenital sinus so
rior abdominal muscles (the processus vaginalis). The testis that the mesonephric duct and ureter open independently.
remains at the abdominal end of the inguinal canal until the This is achieved at the 15-mm stage (7th week). During this
7th month. It then passes through the inguinal canal behind period, starting at the 10-mm stage, the Müllerian ducts start
(but invaginating) the processus vaginalis. Normally, it to develop. They reach the urogenital sinus relatively late—at
reaches the scrotal sac by the end of the 8th month. the 30-mm stage (9th week); their partially fused blind ends
producing the elevation called Müller’s tubercle. Müller’s
B. Ovary tubercle is the most constant and reliable point of reference
in the whole system.
In addition to undergoing an early internal descent, the ovary If the gonad starts to develop into a testis (17-mm stage,
becomes attached through the gubernaculum to the tissues 7th week), the Wolffian duct will start to differentiate into
of the genital fold and then attaches itself to the developing the male duct system, forming the epididymis, vas deferens,
uterovaginal canal at its junction with the uterine (fallopian) seminal vesicles, and ejaculatory ducts, when the Müllerian
tubes. This part of the gubernaculum between the ovary and duct proceeds toward its junction with the urogenital sinus
uterus becomes the ovarian ligament; the part between the and immediately starts to degenerate. Only its upper and
uterus and the labia majora becomes the round ligament lower ends persist, the former as the appendix testis and the
of the uterus. These ligaments prevent extra-abdominal latter as part of the prostatic utricle.
descent, and the ovary enters the true pelvis. It eventually lies If the gonad starts to differentiate into an ovary (22-mm
posterior to the uterine tubes on the superior surface of the stage, 8th week), the Müllerian duct system forms the uter-
urogenital mesentery, which has descended with the ovary ine (fallopian) tubes, uterus, and most of the vagina. The
and now forms the broad ligament. A small processus vag- Wolffian ducts, aside from their contribution to the urogeni-
inalis forms and passes toward the labial swelling, but it is tal sinus, remain rudimentary.
usually obliterated at full term.
MALE DUCT SYSTEM
GONADAL ANOMALIES
The gonad may either (1) not develop (agenesis), (2) develop ▶▶Epididymis
incompletely (hypogenesis), (3) develop incorrectly (dysgen- Because of the proximity of the differentiating gonads and the
esis), or (4) develop correctly, but then suffer an embryologic nephric duct, some of the mesonephric tubules are retained
injury (eg, intrauterine torsion). Supernumerary gonads are as the efferent ductules, and their lumens become continu-
rare. The commonest anomaly involves descent of the gonads, ous with those of the rete testis. These tubules, together with
especially the testis. Retention of the testis in the abdomen or the part of the mesonephric duct into which they empty, will
arrest of its descent at any point along its natural pathway form the epididymis. Each coiled ductule makes a conical
is called cryptorchidism, which may be either unilateral or mass known as the lobule of the epididymis. The cranial end
bilateral. If the testis does not follow the main gubernacular of the mesonephric duct becomes highly convoluted, com-
structure but follows one of its subsidiary strands, it will end pleting the formation of the epididymis. This is an example of
in an abnormal position, resulting in an ectopic testis. direct inclusion of a nephric structure into the genital system.
Failure of union between the rete testis and mesonephros Additional mesonephric tubules, both cephalad and caudal
results in a testis separate from the male genital ducts (the to those that were included in the formation of the epididy-
epididymis) and azoospermia. mis, remain as rudimentary structures, that is, the appendix
of the epididymis and the paradidymis.
GENITAL DUCT SYSTEM
Alongside the indifferent gonads, there are, early in embry- ▶▶Vas Deferens, Seminal Vesicles, and
Ejaculatory Ducts
onic life, two different yet closely related ducts. One is pri-
marily a nephric duct (Wolffian duct), yet it also serves as a The mesonephric duct caudal to the portion forming the
genital duct if the embryo develops into a male. The other epididymis forms the vas deferens. Shortly before this duct
(Müllerian duct) is primarily a genital structure from the joins the urethra (urogenital sinus), a localized dilatation
start. (ampulla) develops, and the saccular convoluted structure
Both ducts grow caudally to join the primitive urogenital that will form the seminal vesicle is evaginated from its wall.
sinus. The Wolffian duct (known as the pronephric duct at The mesonephric duct between the origin of the seminal

McAninch_CH02_p017-p030.indd 26 07/02/20 10:00 AM


EMBRYOLOGY OF THE GENITOURINARY SYSTEM CHAPTER 2 27

vesicle and the urethra forms the ejaculatory duct. The whole tubes (fallopian tubes, oviducts) are the cephalic two-thirds
mesonephric duct now achieves its characteristic thick of the Müllerian ducts (Figure 2–6).
investment of smooth muscle, with a narrow lumen along
most of its length. ANOMALIES OF THE GONADAL DUCT SYSTEM
Both above and below the point of entrance of the meso-
Nonunion of the rete testis and the efferent ductules can
nephric duct into the urethra, multiple outgrowths of ure-
occur and, if bilateral, causes azoospermia and sterility.
thral epithelium mark the beginning of the development of
Failure of the Müllerian ducts to approximate or to fuse com-
the prostate. As these epithelial buds grow, they meet the
pletely can lead to various degrees of duplication in the geni-
developing muscular fibers around the urogenital sinus,
tal ducts. Congenital absence of one or both uterine tubes or
and some of these fibers become entangled in the branch-
of the uterus or vagina occurs rarely.
ing tubules of the growing prostate and become incorporated
Arrested development of the infratubercular segment of
into it, forming its muscular stroma (Figure 2–4).
the urogenital sinus leads to its persistence, with the urethra
and vagina having a common duct to the outside (urogenital
FEMALE DUCT SYSTEM sinus).
The Müllerian ducts, which are a paired system, are seen
alongside the mesonephric duct. It is not known whether EXTERNAL GENITALIA
they arise directly from the mesonephric ducts or separately During the 8th week, external sexual differentiation begins
as an invagination of the celomic epithelium into the paren- to occur. Not until 3 months, however, do the progressively
chyma lateral to the cranial extremity of the mesonephric developing external genitalia attain characteristics that can
duct, but the latter theory is favored. The Müllerian duct be recognized as distinctively male or female. During the
develops and runs lateral to the mesonephric duct. Its open- indifferent stage of sexual development, three small protu-
ing into the celomic cavity persists as the peritoneal ostium berances appear on the external aspect of the cloacal mem-
of the uterine tube (later it develops fimbriae). The other brane. In front is the genital tubercle, and on either side of the
end grows caudally as a solid tip and then crosses in front of membrane are the genital swellings.
the mesonephric duct at the caudal extremity of the meso- With the breakdown of the urogenital membrane (17-mm
nephros. It continues its growth in a caudomedial direction stage, 7th week), the primitive urogenital sinus achieves a
until it meets and fuses with the Müllerian duct of the oppo- separate opening on the undersurface of the genital tubercle.
site side. The fusion is partial at first, so there is a tempo-
rary septum between the two lumens. This later disappears,
leaving one cavity that will form the uterovaginal canal. The
MALE EXTERNAL GENITALIA
potential lumen of the vaginal canal is completely packed The urogenital sinus opening extends on the ventral aspect
with cells. The solid tip of this cord pushes the epithelium of the genital tubercle as the urethral groove. The primitive
of the urogenital sinus outward, where it becomes Müller’s urogenital orifice and the urethral groove are bound on either
tubercle (33-mm stage, 9th week). The Müllerian ducts fuse side by the urethral folds. The genital tubercle becomes elon-
at the 63-mm stage (13th week), forming the sinovaginal gated to form the phallus. The corpora cavernosa is indicated
node, which receives a limited contribution from the uro- in the 7th week as paired mesenchymal columns within the
genital sinus (this contribution forms the lower fifth of the shaft of the penis. By the 10th week, the urethral folds start
vagina). to fuse from the urogenital sinus orifice toward the tip of the
The urogenital sinus distal to Müller’s tubercle, originally phallus. At the 14th week, the fusion is complete and results
narrow and deep, shortens, widens, and opens to form the in the formation of the penile urethra. The corpus spongio-
floor of the pudendal or vulval cleft. This results in separate sum results from the differentiation of the mesenchymal
openings for the vagina and urethra and brings the vaginal masses around the formed penile urethra.
orifice to its final position nearer the surface. At the same The glans penis becomes defined by the development of a
time, the vaginal segment increases appreciably in length. circular coronary sulcus around the distal part of the phallus.
The vaginal vestibule is derived from the infratubercular seg- The urethral groove and the fusing folds do not extend
ment of the urogenital sinus (in males, the same segment will beyond the coronary sulcus. The glandular urethra develops
form the inframontanal part of the prostatic urethra and the as a result of canalization of an ectodermal epithelial cord that
membranous urethra). The labia minora are formed from the has grown through the glans. This canalization reaches and
urethral folds (in males they form the pendulous urethra). communicates with the distal end of the previously formed
The hymen is the remnant of the Müllerian tubercle. The penile urethra. During the 3rd month, a fold of skin at the
lower fifth of the vagina is derived from the portion of the base of the glans begins growing distally and, 2 months later,
urogenital sinus that combines with the sinovaginal node. surrounds the glans. This forms the prepuce. Meanwhile, the
The remainder of the vagina and the uterus are formed from genital swellings shift caudally and are recognizable as scrotal
the lower (fused) third of the Müllerian ducts. The uterine swellings. They meet and fuse, resulting in the formation of

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28 SMITH & TANAGHO’S GENERAL UROLOGY

the scrotum, with two compartments partially separated by Michos O: Kidney development: From ureteric bud formation
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FEMALE EXTERNAL GENITALIA
Nef S, Vassalli JD: Complementary pathways in mammalian female
Until the 8th week, the appearance of the female external geni- sex determination. J Biol 2009;8:74.
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urethral groove is shorter. The genital tubercle, which becomes to age, kidney weight, and body surface in normal man. Anat Rec
bent caudally and lags in development, becomes the clitoris. As 1992;232(2):194–201.
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Urol Clin North Am 1998;25:171.
shortens and widens, forming the vaginal vestibule. The urethral
folds do not fuse but remain separate as the labia minora. The Sekido R: SRY: A transcriptional activator of mammalian testis deter-
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Shah MM et al: Branching morphogenesis and kidney disease.
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on either side of the vestibule and form the labia majora.
Stephens FD: Embryopathy of malformations. J Urol 1982;127:13.
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ANOMALIES OF THE EXTERNAL GENITALIA ger, New York, 1983.
Absence or duplication of the penis or clitoris is very rare. Tanagho EA: Embryologic development of the urinary tract. In: Ball
More commonly, the penis remains rudimentary or the cli- TP (ed): AUA Update Series. American Urological Association,
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Tanagho EA: Developmental anatomy and urogenital abnormalities.
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In: Raz S (ed): Female Urology. 2nd ed. Saunders, Philadelphia,
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Failure or incomplete fusion of the urethral folds results Differentiation 2008;76(6):587–598.
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31

3
Symptoms of Disorders of
the Genitourinary Tract

Benjamin N. Breyer, MD, MAS, FACS

In the workup of any patient, the history is of paramount General malaise may be noted with tumors, chronic
importance; this is particularly true in urology. It is neces- pyelonephritis, or renal failure. The presence of many of
sary to discuss here only those urologic symptoms that are these symptoms may be compatible with human immunode-
apt to be brought to the physician’s attention by the patient. ficiency virus (HIV; see Chapter 17).
It is important to know not only whether the disease is acute
or chronic but also whether it is recurrent, since recurring LOCAL AND REFERRED PAIN
symptoms may represent acute exacerbations of chronic
disease. Two types of pain have their origins in the genitourinary
Obtaining the history is an art that depends on the skill organs: local and referred. The latter is especially common.
and methods used to elicit information. The history is only Local pain is felt in or near the involved organ. Thus, the
as accurate as the patient’s ability to describe the symptoms. pain from a diseased kidney (T10–T12, L1) is felt in the cos-
This subjective information is important in establishing an tovertebral angle and in the flank in the region of and below
accurate diagnosis. the 12th rib. Pain from an inflamed testicle is felt in the gonad
itself.
SYSTEMIC MANIFESTATIONS Referred pain originates in a diseased organ but is felt at
some distance from that organ. The ureteral colic (Figure 3–1)
Symptoms of fever and weight loss should be sought. The
caused by a stone in the upper ureter may be associated with
presence of fever associated with other symptoms of urinary
severe pain in the ipsilateral testicle; this is explained by the
tract infection may be helpful in evaluating the site of the
common innervation of these two structures (T11–T12).
infection. Simple acute cystitis is essentially an afebrile dis-
A stone in the lower ureter may cause pain referred to the
ease. Acute pyelonephritis or prostatitis is apt to cause high
scrotal wall; in this instance, the testis itself is not hyperes-
temperatures (≤40°C [104°F]), often accompanied by violent
thetic. The burning pain with voiding that accompanies
chills. Infants and children who have acute pyelonephritis
acute cystitis is felt in the distal urethra in females and in the
may have high temperatures without other localizing symp-
glandular urethra in males (S2–S3).
toms or signs. Such a clinical picture, therefore, invariably
Abnormalities of a urologic organ can also cause pain in
requires bacteriologic study of the urine.
any other organ (eg, gastrointestinal, gynecologic) that has a
A history of unexplained attacks of fever occurring even
sensory nerve supply common to both (Figures 3–2 and 3–3).
years before may otherwise represent asymptomatic pyelo-
nephritis. Renal carcinoma sometimes causes fever that may
reach 39°C (102.2°F) or more. The absence of fever does not ▶▶Kidney Pain (Figure 3–1)
by any means rule out renal infection, for it is the rule that Typical renal pain is felt as a dull and constant ache in the
chronic pyelonephritis does not cause fever. costovertebral angle just lateral to the sacrospinalis muscle
Weight loss is to be expected in the advanced stages of and just below the 12th rib. This pain often spreads along
cancer, but it may also be noticed when renal insufficiency the subcostal area toward the umbilicus or lower abdominal
due to obstruction or infection supervenes. In children who quadrant. It may be expected in the renal diseases that cause
have “failure to thrive” (low weight and less than average sudden distention of the renal capsule. Acute pyelonephritis
height for their age), chronic obstruction, urinary tract infec- (with its sudden edema) and acute ureteral obstruction (with
tion, or both should be suspected. its sudden renal back pressure) both cause this typical pain.

McAninch_CH03_p031-p040.indd 31 07/02/20 10:01 AM


32 SMITH & TANAGHO’S GENERAL UROLOGY

▲▲Figure 3–1. Referred pain from kidney (dotted areas) and ureter (shaded areas).

It should be pointed out, however, that many urologic renal The physician may be able to judge the position of a ure-
diseases are painless because their progression is so slow that teral stone by the history of pain and the site of referral. If the
sudden capsular distention does not occur. Such diseases stone is lodged in the upper ureter, the pain radiates to
include cancer, chronic pyelonephritis, staghorn calculus, the testicle, since the nerve supply of this organ is simi-
tuberculosis, polycystic kidney, and hydronephrosis due to lar to those of the kidney and upper ureter (T11–T12).
chronic ureteral obstruction. With stones in the midportion of the ureter on the right side,
the pain is referred to McBurney’s point and may therefore
▶▶Ureteral Pain (Figure 3–1) simulate appendicitis; on the left side, it may resemble diver-
ticulitis or other diseases of the descending or sigmoid colon
Ureteral pain is typically stimulated by acute obstruction (pas-
(T12, L1). As the stone approaches the bladder, inflamma-
sage of a stone or a blood clot). In this instance, there is back
tion and edema of the ureteral orifice ensue, and symptoms
pain from renal capsular distention combined with severe col-
of vesical irritability such as urinary frequency and urgency
icky pain (due to renal pelvic and ureteral muscle spasm) that
may occur. It is important to realize, however, that in mild
radiates from the costovertebral angle down toward the lower
ureteral obstruction, as seen in the congenital stenoses, there
anterior abdominal quadrant, along the course of the ureter.
is usually no pain, either renal or ureteral.
In men, it may also be felt in the bladder, scrotum, or testicle.
In women, it may radiate into the vulva. The severity and col-
icky nature of this pain are caused by the hyperperistalsis and ▶▶Vesical Pain
spasm of this smooth-muscle organ as it attempts to rid itself The overdistended bladder of the patient in acute urinary
of a foreign body or to overcome obstruction. retention causes agonizing pain in the suprapubic area. Other

McAninch_CH03_p031-p040.indd 32 07/02/20 10:01 AM


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Figure. 6.
Wagner’s Digestion Apparatus for Slags.

The chief objection to this method of Wagner lies in the failure to control the temperature at
which the digestion with citrate solution is made. Huston has shown, as will be described further
on, that the temperature exercises a great influence in digestion with citrate. Since the laboratory
temperature, especially in this country, may vary between 10° and 35°, it is evident that on the
same sample the Wagner method would give very discordant results at different seasons of the
year.
82. Solutions Employed in the Wagner Method.—1. Ammonium Citrate.—In one liter there
should be exactly 150 grams of citric acid and 27.93 grams of ammonia, equivalent to twenty-three
grams of nitrogen. The following example illustrates the preparation of ten liters of the solution: In
two liters of water and three and a half liters of eight per cent ammonia, 1,500 grams of citric acid
are dissolved and the cooled solution made up exactly to eight liters. Dilute twenty-five cubic
centimeters of this solution to 250 cubic centimeters and treat twenty-five cubic centimeters of this
with three grams of calcined magnesia and distill into forty cubic centimeters of half normal sulfuric
acid. Suppose the ammonia nitrogen found correspond to twenty cubic centimeters of fourth
normal soda-lye. Then in the eight liters are contained

(20.0 × 0.0035 × 8000)


————————— = 224 grams
2.5
of ammonia nitrogen. Then in order to secure in the ten liters the proper quantity of ammonia there
must be added two liters of water containing 230 - 224 = six grams of nitrogen or seven and three-
tenths grams ammonia; viz., ninety-four cubic centimeters of 0.967 specific gravity.
2. Molybdate Solution.—Dissolve 125 grams of molybdic acid in dilute two and five-tenths per
cent ammonia, avoiding a large excess of the solvent. Add 400 grams of ammonium nitrate, dilute
with water to one liter and pour the solution into one liter of nitric acid of 1.19 specific gravity. Allow
the preparation to stand for twenty-four hours at 35° and filter.
3. Magnesia Mixture.—Dissolve 110 grams of pure crystallized magnesium chlorid and 140
grams of ammonium chlorid in 700 cubic centimeters of eight per cent ammonia and 130 cubic
centimeters of water. Allow to stand several days and filter.
83. Estimation of Lime.—When the lime is to be determined in basic slags some difficulty
may be experienced by reason of danger of contamination of the oxalate precipitate with iron and
especially manganese, which is often present in slags.
Holleman[68] proposes to estimate the lime in basic slag by a modification of the methods of
Classen and Jones. The manipulation is as follows: Fifty cubic centimeters of the solution of slag,
equivalent to one gram of substance, are evaporated to a small volume, twenty cubic centimeters
of neutral ammonium oxalate solution (one to three) added to the residue and heated on a water-
bath with frequent stirring, until the precipitate is pure white and free from lumps. The time
required is usually about ten minutes. The precipitate is collected on a filter and washed with hot
water until the filtrate contains no oxalic acid. The precipitated calcium oxalate must be snow-
white. The filter is broken and the calcium oxalate washed through, first with water and finally with
warm, dilute hydrochloric acid (one to one). The calcium oxalate is dissolved by adding fifteen
cubic centimeters of concentrated hydrochloric acid, the solution evaporated to a volume of about
twenty-five cubic centimeters and ten cubic centimeters of dilute sulfuric acid (one to five), and 150
cubic centimeters of ninety-six per cent alcohol added. After standing three hours or more the
precipitate is separated by filtration and washed with ninety-six per cent alcohol until the washings
show no acid reaction with methyl orange. The calcium sulfate precipitated is dried to constant
weight. This method gives a pure precipitate of calcium sulfate, containing only traces of
manganese.
84. Estimation of Caustic Lime.—The lime mechanically present in basic slags is likely to be
found as oxid or hydroxid, especially when the sample is of recent manufacture. In the form of oxid
the lime may be determined by solution in sugar. In this process one gram of the fine slag meal is
shaken for some time with a solution of sugar, as suggested by Stone and Scheuch.[69] The
dissolved lime is separated as oxalate by treatment of the solution with the ammonium salt. The
calcium oxalate may be determined by ignition in the usual way or volumetrically by solution in
sulfuric acid and titration of the free oxalic acid with potassium permanganate solutions. The
standard solution of permanganate should be of such a strength as to have one cubic centimeter
equivalent to about 0.01 gram of iron. The iron value of the permanganate used multiplied by 0.5
will give the quantity of calcium oxid found.
85. Detection of Adulteration of Phosphatic Slags.—The high agricultural value of
phosphatic slags has led to their adulteration and even to the substitution of other bodies. Several
patents have also been granted for the manufacture of artificial slags of a value said to be an
approximation to that of the by-products of the basic pig iron process.
(1) Method of Blum.—One of the earliest methods of examining basic slag for adulterations is
the method of Blum.[70] This method rests upon the principle of the determination of the carbon
dioxid in the sample. The basic phosphatic slag is supposed to contain no carbon dioxid. This is
true only in case it is freshly prepared. The tetrabasic phosphate, after being kept for some time,
gradually absorbs carbon dioxid from the air. As high as nineteen per cent of carbon dioxid have
been found in slags which have been kept for a long while. When the slag has absorbed so much
of carbon dioxid and water from the air as to be no longer profitable for market, it can be restored
to its original condition by ignition.
(2) Method of Richter-Forster.—One of the common adulterants of tetrabasic phosphate is
aluminum phosphate. The method of detecting this when mixed with the slag is described by
Richter-Forster.[71] The method depends on the fact that soda-lye dissolves the aluminum
phosphate, although it does not dissolve any calcium phosphoric acid from the slag. Two grams of
the sample to be tested are treated with ten cubic centimeters of soda-lye of from 7° to 8° C. in a
small vessel with frequent shaking for a few hours at room temperature. After filtration the filtrate is
made acid with hydrochloric and afterwards slightly alkaline with ammonia. With pure basic slag
there is a small trace of precipitate produced, but this is due to a little silica which can be dissolved
in a slight excess of acetic acid. If, however, the basic slag contain aluminum phosphate, a dense
jelly-like precipitate of aluminum phosphate is produced.
(3) Method of Jensch.—Edmund Jensch[72] determines the tetrabasic phosphate in slags by
solution in organic acids, and prefers citric acid for this purpose. This method was also
recommended by Blum[73].
It is well known that the tetrabasic phosphate in slags is completely soluble in citric acid while
the tribasic phosphate is only slightly, if at all, attacked. The neutral ammonium salts of organic
acids do not at first attack the tribasic phosphate at all, and they do not completely dissolve the
tetrabasic phosphate. The solution used by Jensch is made as follows: Fifty grams of crystallized
citric acid are dissolved in one liter of water. A weaker acid dissolves the tetrabasic phosphate too
slowly and a stronger one attacks the tribasic phosphate present.
Schucht recommends the following method of procedure:[74] One gram of the slag, finely
ground, is treated in a beaker glass with about 150 cubic centimeters of Jensen’s citric acid
solution and warmed for twelve hours in an air-bath at from 50° to 70° with frequent shaking.
Afterwards it is diluted with 100 cubic centimeters of water, boiled for one minute and filtered. The
filter is washed thoroughly with hot water and the phosphoric acid is estimated in the filtrate in the
usual way. With artificial mixtures of basic slags and other phosphates the quantity of basic slag
can be determined by the above method.
(4) Method of Wrampelmeyer.—According to Wrampelmeyer the most convenient method for
discovering the adulteration of basic slag is the use of the microscope.[75] All finely ground natural
phosphates are light colored and with a strong magnification appear as rounded masses. In basic
slags the particles are mostly black but there are often found red-colored fragments having sharp
angles which refract their light in a peculiar way so that, with a very little experience, they can be
recognized as being distinctive marks of pure basic slag.
In artificial mixtures of these two phosphates, which we have made in our laboratory, we have
been able to detect with certainty as little as one per cent of added mineral phosphate.
One form of adulterating natural mineral phosphates has been mixing them with finely
pulverized charcoal or soot to give them the black appearance characteristic of the basic slags.
This form of adulteration is at once disclosed by simple ignition or by microscopic examination.
(5) Loss on Ignition.—If all doubts cannot be removed by the use of the microscope, the loss
on ignition should be estimated. Natural phosphates all give a high loss on ignition, ranging from
eight to twenty-four per cent, while a basic slag gives only a very slight loss on ignition, especially
when fresh. A basic slag which has stood for a long while and absorbed carbon dioxid and
moisture, may give a loss on ignition approximating, in a maximum case, the minimum loss on
ignition from a natural phosphate.
In experiments made in this laboratory in testing for loss on ignition, we have uniformly found
that natural mineral phosphates will lose from nearly one to two and one-half times as much on
ignition as a basic slag which has been kept for two years. A basic slag in the laboratory more
than two years old gave, as loss on ignition, 4.12 per cent. Several samples of finely ground
Florida phosphates gave the following percentages of loss on ignition, as compared with a sample
of slag.
Odorless phosphate 4.12.
Florida phosphates 8.06, 6.90, 9.58, 6.40, 10.38, and 10.67 respectively.
There are some mineral phosphates, however, which are ignited before being sent to the
market. We have one such sample in our laboratory from Florida which gave, on ignition, a loss of
only one and four-tenths per cent. In this case it is seen that the application of the process of
ignition would not discriminate between a basic slag and a mineral phosphate.
It may often be of interest to know what part of the loss, on ignition, is due to water in form of
moisture. In such cases the sample should first be dried to constant weight in a steam-bath and
then ignited. In the following data are found the results obtained here with samples treated as
above indicated and also ignited directly. Number one is a basic slag two years old and the others
Florida phosphates.
Heated to 100° C. then ignited. Ignited directly.
Loss at Loss on Total Loss on
100° C. ignition. loss. ignition.
No. 1 (Slag) 2.57 1.77 4.34 4.12
No. 2 (Rock) 2.61 5.19 7.80 8.06
No. 3 “ 1.09 5.77 6.86 6.90
No. 4 “ 0.42 9.20 9.62 9.58
No. 5 “ 1.81 4.83 6.64 6.40
No. 6 “ 4.36 6.52 10.88 10.83
No. 7 “ 3.31 7.01 10.32 10.67
(6) Presence of Sulfids.—Another point noticed in this laboratory is that the basic slags
uniformly contain sulfids which are decomposed upon the addition of an acid with an evolution of
hydrogen sulfid.
(7) Presence of Fluorin.—In applying the test for fluorin, it has been uniformly found here that
the mineral phosphates respond to the fluorin test while the basic slags, on the contrary, respond
to the hydrogen sulfid test. This test, however, was applied only to the few samples we have had
and may not be a uniform property.
The absence of fluorin might not prove the absence of adulteration, but its presence would, I
believe, certainly prove the fact of the adulteration in that particular sample.
The fluorin test is applied by Böttcher in the following manner:[76] From ten to fifteen grams of
the slag are placed in a beaker ten centimeters high and from five to six centimeters in diameter,
with fifteen cubic centimeters of concentrated sulfuric acid, stirred with a glass rod, and covered
with a watch-glass on the under side of which a drop of water hangs. If there be formed upon the
drop of water a white murky rim, it is proof that a mineral phosphate containing fluorin has been
added. After from five to ten minutes you can notice on the clean watch-glass the etching
produced by the hydrofluoric acid. According to Böttcher an adulteration of ten per cent of raw
phosphate in slag can be detected by this method.
(8) Solubility in Water.—Solubility in water is also a good indication, natural phosphates being
totally insoluble in water, while a considerable quantity of the basic slag will be dissolved in water
on account of the calcium oxid or hydroxid which it contains. If the loss on ignition is low, and the
volume-weight and water-solubility high, the analyst may be certain that the sample is a pure slag.
In comparative tests made in our laboratory with a sample of basic slag and seven samples of
Florida phosphate, the percentages of material dissolved by water and by a five per cent solution
of citric acid were found to be as follows:
Sol. in
five per cent
Water-soluble. citric acid.
Per cent. Per cent.

Odorless phosphate 0.97 16.10


Florida phosphate 0.01 4.15
“ “ 0.09 4.66
“ “ 0.02 3.43
“ “ 0.08 3.61
“ “ 0.02 3.79
“ “ 0.05 4.46
“ “ 0.02 4.24
From the above data it is seen that the solvent action of water especially would be of value
inasmuch as it dissolves only a mere trace of the mineral phosphates, approximating one per cent
of the amount dissolved from basic slag. In the case of the citric acid it is found that the amount of
materials soluble in this solvent for basic slag is fully four times as great as for the mineral
phosphates. Both of these processes, therefore, have considerable value for discriminating
between the pure and adulterated article of basic slag.
(9) Specific Gravity.—The estimation of the volume specific gravity is also a good indication for
judging of the purity of the slag. This is best done by weighing directly a given volume. Basic slag
will have a volume-weight of about one and nine-tenths, while natural phosphates will have about
one and six-tenths.
(10) Conclusions.—From the above résumé of the standard methods which are in use for
determining the adulteration of basic slag, it is seen that there are many cases in which grave
doubt might exist even after the careful application of all the methods mentioned. If we had only to
consider the adulteration of basic slag with certain of the mineral phosphates, that is, tricalcium
phosphate, the problem would be an easy one, but when we add to this the fact that iron and
aluminum phosphates are employed in the adulteration, and that artificial slags may be so used,
the question becomes more involved.
In doubtful cases one after another of the methods should be applied until there is no doubt
whatever of the judgment which should be rendered.

VOLUMETRIC DETERMINATION
OF PHOSPHORIC ACID.
86. Classification of Methods.—The time required for a gravimetric determination of
phosphoric acid has led analysts to try the speedier if less accurate processes, depending on the
use of volumetric methods. The chief difficulty with these methods has been in securing some
sharp method of distinguishing the end reaction. In most cases it has been found necessary to
remove a portion of the titrated solution and prepare it for final testing by subsidence or filtration.
As is well known, this method of determining the end reaction is less accurate and more time-
consuming than those processes depending on a change of color in the whole mass. All the
volumetric processes now in general use may be divided into two classes; viz., (1) the direct
precipitation of phosphoric acid and the determination of the end reaction by any appropriate
means, and (2) the previous separation of the phosphoric acid, usually by means of a citro-
magnesium or molybdenum mixture, and in the latter case the subsequent titration of the yellow
ammonium phosphomolybdate either directly or after reduction to a lower form of oxidation. In
respect of extent of application by far the most important volumetric method is the one depending
on titration by a uranium salt after previous separation by ammoniacal magnesium citrate. A
promising method after previous separation by molybdenum is the one proposed by Pemberton,
but it has not yet come into general use. For small quantities of phosphoric acid or of phosphorus,
such as are found in steels and irons, the method of Emmerton, either as originally proposed or as
modified by Dudley and Noyes, is in frequent use. Where volumetric methods are applied to
products separated by molybdic solution, the essential feature of the analytical work is to secure a
yellow precipitate of constant composition. If this could be uniformly done such methods would
rival the gravimetric processes in accuracy. Hence it is highly important in these methods that the
yellow precipitate should be secured as far as possible, under constant conditions of strength of
solution, duration of time, and manner of precipitation. In these cases, and in such only, can the
quicker volumetric methods be depended on for accurate results.
The direct volumetric precipitation of the phosphoric acid by a uranium salt or otherwise is
practiced only when the acid is combined with the alkalies and when iron and alumina are absent
and only small quantities of lime present. This method has therefore but little practical value for
agricultural purposes. In all volumetric analyses the accuracy of the burettes, pipettes, and other
graduated vessels should be proved by careful calibration. Many of the disagreements in
laboratories where the analytical work is conducted equally well can be due to no other cause than
the inaccuracy of the graduated vessels which are found in commerce. Burettes should not only
be calibrated for the whole volume but for at least every five cubic centimeters of the graduation.

URANIUM METHOD AS PRACTICED


BY THE FRENCH CHEMISTS.
87. The Uranium Method.—Since the phosphoric acid of practical use for agricultural
purposes is nearly always combined with lime, alumina, and iron, its volumetric estimation by
means of a standard solution of a uranium salt is to be preceded by a preliminary separation by
means of an ammoniacal magnesium citrate solution. The principle of the method was almost
simultaneously published by Sutton,[77] Neubauer,[78] and Pincus.[79] The phosphoric acid may
also be separated by means of molybdic solution or by tin or bismuth.[80] In practice, however, it
has been found that when the uranium method is to be used the magnesium citrate separation is
the most convenient. Since this is the method practiced almost universally in France, the method
there used will be given in detail. It is based essentially on the process described by Joulie.[81]
88. Preparation of Sample.—(1) Incineration.—Since the organic matters present in a
phosphatic fertilizer often interfere with the employment of uranium as a reagent, it is necessary to
incinerate the sample taken for analysis.[82]
(2) Solution of the Material.—All phosphates, with the exception of certain aluminum
phosphates, amblygonite for example, are easily dissolved in nitric and hydrochloric acids more or
less dilute, especially on ebullition. The best solvent, however, for calcium phosphates for the
uranium method is incontestably hydrochloric acid which also very easily dissolves the iron and
aluminum phosphates, which are often found present with calcium phosphates.
(3) Nitric Acid.—In many laboratories nitric acid is preferred in order to avoid, in part, the
solution of ferric oxid which interferes with the determination of phosphoric acid in certain
processes. Since it does not act in this way for the citro-magnesium uranium method, it is
preferable to employ hydrochloric acid, especially because it dissolves the iron completely and
permits thus the operator to judge of the success of the solvent action by the completely white
color of the residue.
(4) Pyritic Phosphates.—Certain phosphates contain pyrites which hydrochloric acid does not
dissolve, and there is left consequently, a residue more or less colored. In this case it is necessary
to add some nitric acid and to prolong the boiling until the pyrite has disappeared, since it might
retain a small quantity of phosphoric acid in the state of iron phosphate.
(5) Sulfuric Acid.—Some chemists decompose the phosphates by means of dilute sulfuric acid.
This method, which is certainly able to give good results for certain products and for certain
processes, presents numerous inconveniences which tend to render its use objectionable for
volumetric purposes. The calcium sulfate which is formed, requires prolonged washings which
lead to chances of fatal error.
If an aluminum phosphate be under examination, containing only very little or no lime, sulfuric
acid is to be preferred to hydrochloric and nitric acids, since it attacks amblygonite, which, as has
been before stated, resists the action of the other two acids. But these are cases which are met
with very rarely, and which can always be treated by the general method by previously fusing the
material with a mixture of sodium and potassium carbonate.
In the great majority of cases the decomposition by hydrochloric acid is very easily
accomplished by simply boiling in a glass vessel, and without effecting the separation of the silica.
This operation is only necessary after the substance has been fused with alkaline carbonates, or,
in case of substances which contain decomposable silicates giving gelatinous silica with
hydrochloric acid.
There are two methods [see (6) and (7)] of securing a solution of the sample taken which
varies from one to five, and even ten grams, according to the apparent homogeneity of the
material to be analyzed.
(6) Solution by Filtration and Washing.—The ordinary method can be employed consisting in
decomposing the substance by an acid, filtering, and washing the residue upon the filter, and
combining all the wash-waters to make a determinate volume. Afterwards an aliquot fraction of the
whole is taken for the precipitation. This method is long, and presents some chances of error,
when the insoluble residue is voluminous and contains silica which obstructs the pores of the
paper and renders the filtration difficult.
(7) Volumetric Solution.—It is advisable to substitute volumetric solution for solution by filtration
and washing, which is accomplished by decomposing the substances in a graduated flask, the
volume being afterwards made up to the mark with distilled water after cooling. The solution is
then filtered without washing, and by means of a pipette an aliquot part of the original volume is
taken for precipitation. Thus all retardations in the process are avoided, and likewise the chances
of error from washing on the filter. It is true that this method may lead to a certain error due to the
volume of the insoluble matter which is left undecomposed, but since this insoluble matter is
usually small in quantity, and since it is always possible to diminish the error therefrom by
increasing the volume of the solution, this cause of error is much less to be feared than those due
to the difficulties which may occur in the other method. Let us suppose, in order to illustrate the
above, that we are dealing with a phosphate containing fifty per cent of insoluble sand which may
be considered as an extreme limit. In working on four grams of the material in a flask of 100 cubic
centimeters capacity, there will be an insoluble residue of two grams occupying a volume of about
one cubic centimeter, the density of the sand being generally nearly two. The one hundred cubic
centimeter flask will then contain only ninety-nine cubic centimeters of the real solution, and the
error at the most would be 0.01. This error could be reduced to one-half by dissolving only two
grams of the material in place of four, or by making the volume up to 200 instead of 100 cubic
centimeters.
In general it may be said that the errors which do not exceed 0.01 of the total matter under
treatment, are negligible for all industrial products. The method of volumetric solution does not
present any further inconvenience. It deserves to be and has been generally adopted by reason of
its rapidity in all the laboratories where many analyses are to be made. In the volumetric method
great care should be taken not to make up to the volume until after the cooling to room
temperature, which may be speedily secured by immersing the flask in cold water. Care should
also be exercised in taking the sample for analysis by means of the pipette immediately after
filtration, and filtration should take place as soon as the volume is made up to the standard. By
operating in this way the possible variations from changes of volume due to changes of
temperature are avoided.
(8) Examination for Arsenic Acid.—When the sample examined contains pyrites, arsenic is
often present. When the decomposition has been effected by means of nitric acid, arsenic acid
may be produced. This deports itself in all circumstances like phosphoric acid, and if it is present
in the matter under examination it will be found united with the phosphoric acid and determined
therewith afterwards. It is easy to avoid this cause of error by passing first a current of sulfurous
acid through the solution, carrying it to the boiling-point in order to drive out the excess of
sulfurous acid, and afterwards precipitating the arsenic by a current of hydrogen sulfid. After
filtration, the rest of the operation can be carried on as already described.
89. Precipitation of the Phosphate by Magnesium Citrate.—By means of an accurate
pipette a quantity of the solution representing from 0.125 to 0.250 gram or more is taken,
according to the presumed richness of the product to be examined. In order that the following
operations may go on well, it is necessary that the quantity of phosphoric acid contained in the
sample should be about fifty milligrams. The sample being measured is run into a beaker, and
there are added, first, ten cubic centimeters of magnesium citrate solution, and second, a large
excess of ammonia. If the quantity of the magnesium citrate solution be sufficient, the mixture
should at first remain perfectly limpid and only become turbid at the end of some moments and
especially after the mixture is stirred.
If there should be an immediate turbidity produced it is proof that the quantity of magnesium
citrate solution employed has been insufficient, and it is necessary to begin again by doubling its
amount. Good results cannot be obtained by adding a second portion of the magnesium citrate
solution to the original, since the iron and aluminum phosphates which are once formed are
redissolved with difficulty. Many chemists at the present time abstain from using the magnesium
citrate solution and replace it by a solution of citric acid and one of magnesium sulfate, which they
pour successively into the sample under examination. This is a cause of grave errors which it is
necessary to point out. Joulie has indeed recognized the fact that the precipitation of the
phosphoric acid is not completed in presence of ammonium citrate except it is employed in
conjunction with a sufficient excess of magnesia. But the foreign matters which accompany the
phosphoric acid require different quantities of ammonium citrate in order to keep them in solution,
and it is important to increase the magnesium solution at the time of increasing the citric acid in
order to maintain them always in the same proportion. This is easily accomplished by measuring
the two solutions, but it is much more easily done by uniting them and adding them together.
90. The Magnesium Citrate Solution.—The formula originally proposed by Joulie, and
modified by Millot, and adopted by the French Association of Chemists, is as follows: Citric acid,
400 grams; pure magnesium carbonate, forty grams; caustic magnesia, twenty grams; distilled
water, half a liter. After solution, add enough of ammonia to render strongly alkaline, requiring
about 600 cubic centimeters. Make the volume up with distilled water to one and a half liters. If the
solution be turbid, it is proof that the magnesia or the carbonate employed contains some
phosphoric acid which is to be separated by filtration, and the solution can then be preserved
indefinitely.
91. Time of Subsidence.—When the phosphoric acid is precipitated by the mixture above
mentioned, it is necessary to allow it to subside for a certain time under a bell jar in order to avoid
the evaporation of the ammonia. In order to give plenty of time for this subsidence, it is well to
make the precipitations in the afternoon and the filtrations the following morning. There are thus
secured twelve to fifteen hours of repose, which is time amply sufficient for all cases.
92. Filtration and Washing.—Filtration is performed easily and rapidly upon a small filter
without folds placed in a funnel with a long stem of about two millimeters internal diameter. Placed
in a series of six or eight, they allow the filtration to take place in regular order without loss of time,
the first filter being always empty by the time the last one is filled. The supernatant liquid from the
precipitate should first be decanted on the filter, avoiding the throwing of the filtrate on the filter
which would greatly retard the process, especially if it should contain a little silica, as often
happens.
When the clear liquid is thus decanted as completely as possible, the rest of the precipitate is
treated with water to which one-tenth of its volume of ammonia has been added, and the washing
is continued by decantation as at first, and afterwards by washing upon the filter until the filtered
solution gives no precipitate with sodium phosphate. Four washings are generally sufficient to
attain this result.
If the operations which precede have been well-conducted, the total phosphoric acid contained
in the material under examination is found upon the filter-paper, except the small portion which
remains adhering to the beaker in which the precipitation has been made. The determination of
the phosphoric acid comprises the following operations: First, solution of the ammonium
magnesium phosphate and second, titration by means of a standard solution of uranium.
93. Solution of the Ammonium Magnesium Phosphate.—The phosphate which has been
collected upon the filter is dissolved by a ten per cent solution of pure nitric acid. This solution is
caused to pass into the beaker in which the precipitation was made in order to dissolve the
particles of phosphate which remain adherent to its sides; and this solution is then thrown upon
the filter. The filtrate is then received in a flask of about 150 cubic centimeters capacity, marked at
seventy-five cubic centimeters. After two or three washings with the acidulated water, the filter
itself is detached from the funnel and introduced into the vessel which contains the solution.
The whole of the filtrate being collected in the flask it is saturated by one-tenth ammoniacal
water until a slight turbidity is produced. One or two drops of dilute nitric acid are now added until
the liquor becomes limpid, and the flask is placed upon a sand-bath in order to carry the liquid to
the boiling-point. After ebullition there are added five cubic centimeters of acid sodium acetate in
order to cause the free nitric acid to disappear and immediately the titration, by means of a
standard solution of uranium, is undertaken.
94. Acid Sodium Acetate.—The acid sodium acetate is prepared as follows: Crystallized
sodium acetate, 100 grams; glacial acetic acid, fifty cubic centimeters; distilled water, enough to
make one liter.
95. Standard Solution of Uranium.—A solution of uranium is to be prepared as follows: Pure
uranium nitrate, forty grams; distilled water, about 800 cubic centimeters. Dissolve the uranium
nitrate in the distilled water and add a few drops of ammonia until a slight turbidity is produced,
and then a sufficient amount of acetic acid to cause this turbidity to disappear. The volume is then
completed to one liter with distilled water.
The uranium nitrate often contains some uranium phosphate and some ferric nitrate. It is
important that it be freed from these foreign substances. This is secured by dissolving it in distilled
water and precipitating it by sodium carbonate, which redissolves the uranium oxid and
precipitates the iron phosphate and oxid.
The filtered liquor is saturated with nitric acid, and the uranium oxid reprecipitated by ammonia.
It is then washed with distilled water by decantation and redissolved in nitric acid, as exactly as
possible, evaporated, and crystallized.
The crystals are taken up with ether, which often leaves still a little insoluble matter. The
solution is filtered, and the ether evaporated. The salt which remains is perfectly pure. It frequently
happens when the uranium nitrate has not been properly purified that the solution prepared as has
been indicated above, deposits a light precipitate of phosphate which alters its strength and
affords a cause of error. Only those solutions should be employed which have been prepared
some days in advance, and which have remained perfectly limpid.
The solution of uranium thus obtained contains uranium nitrate, a little ammonium nitrate, a
very small quantity of uranium acetate, some ammonium acetate, and a little free acetic acid. Its
sensibility is the more pronounced as the acetates present in it are less in quantity. It is important,
therefore, never to prepare the solution with uranium acetate.
96. Typical Solution of Phosphoric Acid.—In order to titrate a solution of uranium, it is
necessary to have a standard solution of phosphoric acid; that is to say, a solution containing a
precise and known quantity of that acid in a given volume. This solution is prepared by means of
acid ammonium phosphate, a salt which is easily obtained pure and dry. Sometimes as it may
contain a small quantity of neutral phosphate which modifies the relative proportions of phosphoric
acid and ammonia, and it is indispensable to have its strength verified. The titer of the typical
solution should be such that it requires for the precipitation of the phosphoric acid which it
contains, a volume of the solution of uranium almost exactly equal to its own, in order that the
expansions or contractions which the two liquors undergo, by reason of changes in the
temperature of the laboratory, should be without influence upon the results.
The solution of uranium prepared as has been indicated above, precipitates almost exactly five
milligrams of phosphoric acid per cubic centimeter; the typical solution of phosphoric acid is
prepared with eight and one-tenth grams of acid ammonium phosphate pure and dry, which is
dissolved in a sufficient quantity of distilled water to make one liter.
The acid ammonium phosphate containing 61.74 per cent of anhydrous phosphoric acid, the
quantity above gives exactly five grams of that acid in a liter, or five milligrams in a cubic
centimeter.
97. Verification of the Strength of the Standard Solution of Phosphoric Acid.—The
strength of the standard solution of phosphoric acid is verified by evaporating a known volume,
fifty cubic centimeters for example, with a solution of ferric hydroxid containing a known quantity of
ferric oxid. The mass having been evaporated to dryness, and ignited in a platinum crucible, gives
an increase in the weight of the iron oxid exactly equal to the amount of anhydrous phosphoric
acid contained therein, both the nitric acid and ammonia being driven off by the heat.
To prepare the solution of ferric hydroxid, dissolve twenty grams of iron filings in hydrochloric
acid. The solution is filtered to separate the carbon, and it is converted into ferric nitrate by nitric
acid, and the solution diluted with distilled water, and the ferric oxid precipitated by a slight excess
of ammonia. The precipitate, washed by decantation with distilled water until the wash-water no
longer gives a precipitate with silver nitrate, is redissolved in nitric acid, and the solution is
concentrated or diluted, as the case may be, to bring the volume to one liter.
In order to determine the quantity of ferric oxid which it contains, fifty cubic centimeters are
evaporated to dryness, ignited, and weighed.
A second operation like the above is carried on by adding fifty cubic centimeters of the
standard solution of phosphoric acid, and the strength of the solution thus obtained is marked
upon the flask.
If the operation have been properly carried on, three or four duplicates will give exactly the
same figures. If there are sensible differences, the whole operation should be done over from the
first.
98. Titration of the Solution of Uranium.—In a 150 cubic centimeter flask marked at seventy-
five cubic centimeters, are poured ten cubic centimeters of the standard solution of phosphoric
acid measured with an exact pipette; five cubic centimeters of the acid sodium acetate are added,
and distilled water enough to make about thirty cubic centimeters, and the whole carried to the
boiling-point. The titration is then carried on by allowing the solution of uranium to fall into the flask
from a graduated burette, thoroughly shaking after each addition of the uranium, and trying a drop
of the liquor with an equal quantity of a ten per cent solution of potassium ferrocyanid upon a
greased white plate. Since the quantity of the uranium solution present will be very nearly ten
cubic centimeters at first, nine cubic centimeters can be run in without testing. Afterwards, the
operation is continued by adding two or three drops at a time until the test upon the white plate
with the potassium ferrocyanid shows the end of the reaction. When there is observed in the final
test a slight change of tint, the flask is filled up to the mark with boiling distilled water and the
process tried anew. If in the first part of the operation the point of saturation have not been passed,
it is still usually necessary to add a drop or two of the uranium solution in order to produce the
characteristic reddish coloration, and this increase is rendered necessary by the increase in the
volume of the liquid. Proceeding in this manner two or three times allows the attainment of
extreme precision, inasmuch as the analyst knows just when to look for the point of saturation.
Correction.—The result of the preceding operation is not absolutely exact. It is evident indeed
that in addition to the quantity of uranium necessary for the exact precipitation of the phosphoric
acid, it has been necessary to add an excess sufficient to produce the reaction upon the
potassium ferrocyanid.
This excess is rendered constant by the precaution of operating always upon the same
volume; namely, seventy-five cubic centimeters. It can be determined then once for all by making
a blank determination under the same conditions but without using the phosphoric acid.
The result of this determination is that it renders possible the correction which it is necessary to
make by subtracting the quantity used in the blank titration from the preceding result in order to
obtain the exact strength of the uranium solution.
The operation is carried on as follows: In a flat-bottomed flask of about 150 cubic centimeters
capacity and marked at seventy-five cubic centimeters, by means of a pipette, are placed five
cubic centimeters of the solution of sodium acetate; some hot distilled water is added until the
flask is filled to the mark, and it is then placed upon a sand-bath and heated to the boiling-point. It
is taken from the fire, the volume made up to seventy-five cubic centimeters with a little hot
distilled water, and one or two drops of the solution of uranium are allowed to flow into the flask
from a graduated burette previously filled exactly to zero. After each drop of the solution of
uranium the flask is shaken and the liquid tried upon a drop of potassium ferrocyanid, as has been
previously indicated. For a skilled eye, four to six drops are generally necessary to obtain the
characteristic coloration; that is from two-tenths to three-tenths of a cubic centimeter. Beginners
often use from five-tenths to six-tenths, and sometimes even more.
The sole important point is to arrest the operation as soon as the reddish tint is surely seen, for
afterwards the intensity of the coloration does not increase proportionally to the quantity of liquor
employed.
It is well to note that at the end of some time the coloration becomes more intense than at the
moment when the solutions are mixed, so that care must be taken not to pass the saturation-point.
This slowness of the reaction is the more marked as there is more sodium or ammonium acetate
in the standard solutions. This is the reason that it is important to introduce always the same
quantity; namely, five cubic centimeters. This is also the reason why the uranium acetate should
not be employed in preparing the standard solution of uranium which ought to contain the least
possible amount of acetate in order that the necessary quantity which is carried into each test
should be as small as possible and remain without appreciable influence. If it were otherwise, the
sensibility of the reaction would be diminished in proportion as a larger quantity of uranium
solution was employed, giving rise to errors which would be as much more important as the
quantities of phosphoric acid to be determined were greater. The correction for the uranium
solution having been determined it is written upon the label of the bottle containing it.
Causes of Errors.—In the work which has just been described, some causes of error may
occur to which the attention of analysts should be called.
The first is the error which may arise from the consumption of the small quantity of uranium
phosphate which is taken with a stirring rod when the liquid is tested with potassium ferrocyanid. It
is very easy to be assured that the end of the reaction has really been reached. For this purpose it
is only necessary to note the quantity of the solution already employed and to add to it afterwards
four drops; shake, and make a new test with a drop of the potassium ferrocyanid placed near the
spot which the last one occupied. If a decidedly reddish tint does not appear at the moment of
removing the glass rod, it is to be concluded that the first appearance was an illusion, and the
addition of uranium is to be continued. If, on the contrary, the coloration appear of a decided tint,
the preceding number may be taken for exact. It is then always beneficial to close the titration by
this test of four supplementary drops which will exaggerate the coloration and confirm the figure
found.
The second cause of error, and one moreover which is the most frequently met with, consists
in passing the end of the reaction by adding the uranium too rapidly. In place of giving then a
coloration scarcely perceptible, the test with the drop of potassium ferrocyanid gives a very
marked coloration. In this case the analysis can still be saved. For this purpose the analyst has, at
his disposal, a tenth normal solution prepared with 100 cubic centimeters of the standard solution
of phosphoric acid diluted to one liter with distilled water. Ten cubic centimeters of this tenth
normal solution are added, and the titration continued. At the end, the amount of additional
phosphoric acid used is subtracted from the total.
A third cause of error is found in the foam which is often found in the liquid, due to the shaking.
This foam may retain a portion of the last drops of the solution of uranium which fall upon its
surface and prevent its mixture with the rest of the liquid. If the glass stirring rod in being removed
from the vessel pass through this froth charged with uranium, the characteristic coloration is
obtained before real saturation is reached. Consequently it is necessary to avoid, as much as
possible, the formation of the foam, and especially to take care never to take the drop for test after
agitation except in the middle of the liquid where the foam does not exist.
Suppose the titration has been made upon ten cubic centimeters of the normal solution of
phosphoric acid in the conditions which we have just indicated, and the figure for the uranium
obtained is 10.2 cubic centimeters; if now the correction, which may be supposed to amount to
two-tenths cubic centimeter, be subtracted there will remain ten cubic centimeters of the uranium
solution which would have precipitated exactly fifty milligrams of phosphoric acid.
The quantity of phosphoric acid which precipitates one cubic centimeter of the solution will be
consequently expressed by the proportion ⁵⁰/₁₀ = five milligrams, which is exactly the strength
required. In the example which has just been given, the inscription upon the flask holding the
standard solution would be as follows: Solution of uranium, one cubic centimeter equals five
milligrams of phosphorus pentoxid; correction, two-tenths cubic centimeter.
99. Titration of the Sample.—The strength of the solution of uranium having been exactly
determined, by means of this solution the strength of the sample in which the phosphoric acid has
been previously prepared as ammonium magnesium phosphate is ascertained. In this case the
quantity of phosphoric acid being unknown, it is necessary to proceed slowly and to duplicate the
tests in order not to pass beyond the point of saturation. From this there necessarily results a
certain error in consequence of the removal of quite a number of drops of the solution of the
sample before the saturation is complete. It is therefore necessary to make a second
determination in which there is at once added almost the quantity of the solution of uranium
determined by the first analysis. Afterwards the analysis is finished by additions of very small
quantities of uranium until saturation is reached. Suppose, for instance, that the sample was that
of a mineral phosphate, five grams of which were dissolved in 100 cubic centimeters, and of which
ten cubic centimeters of the solution prepared as above required 15.3 cubic centimeters of the
standard solution of uranium. We then would have the following data:
Mineral phosphate, five grams of the material dissolved in twenty cubic
centimeters of hydrochloric acid.
Water, sufficient quantity to make 100 cubic centimeters.
Quantity taken, ten cubic centimeters = 0.50 gram of the sample taken.
Solution of uranium required 15.3 cubic centimeters.
Correction 0.2 “ “
Actual quantity of uranium solution 15.1 “ “
Strength of the solution of uranium, one cubic centimeter =
fivemilligrams P₂O₅.

Then P₂O₅ in 0.50 gram of the material = 5 × 15.1 = 75.50 milligrams.


75.5 x 100
Then the per cent of P₂O₅ = = 15.10.
50
The sample under examination ought always to be prepared in duplicate, either by making a
single precipitation and re-solution of the ammonium magnesium phosphate which is made up to a
certain volume and an aliquot portion of which is taken for the analysis, or by making two
precipitations under the conditions previously described. When the content of phosphoric acid in
the material under examination is very nearly known, the double operation may be avoided,
especially if it be required to have rapid and only approximate analyses, such as those which are
made for general control and for the conduct of manufacturing operations. But when analyses are
to be used to serve as the basis of a law or for the control of a market, they should always be
made in duplicate, and the results ought not to be accepted when the numbers obtained are
widely different, since the agreement of the two numbers will show that the work has been well
executed.
This method of analysis, much longer to describe than to execute, gives results perfectly exact
and always concordant when it is well carried out, provided that the standard solutions, upon
which it rests for its accuracy, are correctly prepared and frequently verified in the manner
indicated.
The strength of the solution of uranium ought to be verified every three or four days. The
strength of the standard solution of phosphoric acid should be verified each time that the
temperature of the laboratory undergoes any important change. A solution prepared, for example,
in winter when the temperature of the laboratory is from 15° to 18° would no longer be exact in
summer when the temperature reaches 28° or 30°.
100. Condition of Phosphoric Acid in Superphosphates.—Superphosphates are the
products of the decomposition of phosphates by sulfuric or hydrochloric acid. They contain
phosphoric acid combined with water, with lime, with magnesia, and with iron and alumina in
various proportions.
These combinations may be classed in three categories: First, those compounds soluble in
water; second, those insoluble in water, but very soluble in ammoniacal salts of the organic acids
such as the citrate and oxalate; and third, phosphates not soluble in any of the above-named
reagents.
In the products soluble in water are met free phosphoric acid, monocalcium phosphate, acid
magnesium phosphate, and the iron and aluminum phosphates dissolved in the excess of
phosphoric acid. In the products insoluble in water but soluble in the ammonium citrate are found
bicalcium phosphate and iron and aluminum phosphates, which together constitute the
phosphates called reverted.
These compounds reduced to a very fine state of division in the process of manufacture are
considered to contain phosphoric acid of the same economic value.
101. Determination of the Total Phosphoric Acid in Superphosphates and Fertilizers.—
The process is carried on exactly as for an ordinary phosphate, and with all the care indicated in
connection with the sampling, the incineration, the solution by means of hydrochloric acid, and the
separation of the phosphoric acid in the state of ammonium magnesium phosphate, and finally in
the titration by uranium.
102. Determination of Soluble and Reverted Phosphoric Acid.—To make this
determination a method unique and applicable to all cases consists in extracting, at first, the
soluble constituents in distilled water, and following this operation by digestion in the ammonium
citrate. The products soluble in water can be determined either separately or at the same time as
the products soluble in the ammonium citrate according to the taste of the people interested,
without its being necessary to modify very greatly the method of operation.
The determination of the soluble phosphoric acid comprises first, the solution of the soluble
constituents in distilled water; second, the solution of the reverted phosphates in ammonium
citrate; third, the precipitation of the phosphoric acid dissolved in the two preceding operations,
and its determination.
103. Preparation of the Sample for Analysis.—The sample sent to the chemical expert is
prepared as has been indicated; that is to say, it is poured on a sieve of which the meshes have a
diameter of one millimeter, and sifted upon a sheet of white paper. The parts which do not pass
the sieve are broken up either by the hand or in a mortar and added, through the sieve, to the first
portions. The product is well mixed and, in this state, the mass presents all the homogeneity
desirable for analysis.
Some fertilizers are received in a pasty state which does not permit of their being sifted. It is
necessary in such a case to mix them with their own weight either of precipitated calcium sulfate
dried at 160° or with fine sand washed with hydrochloric acid and dried, which divides the particles
perfectly and permits of their being passed through the meshes of the sieve.
104. Extraction of the Products Soluble in Distilled Water.—The substance having been
prepared as has just been indicated, one and a half grams are placed in a glass mortar. Twenty
cubic centimeters of distilled water are added, and the substance gently suspended therein. After
standing for one minute, the supernatant part is decanted into a small funnel provided with a filter-
paper and placed in a flask marked at 150 cubic centimeters. This operation is repeated five times
and is terminated by an intimate breaking up of the matter with distilled water. When the volume of
100 cubic centimeters of the filtrate has been obtained, the residue in the mortar is placed on the
filter, and the washing is continued until the total volume reaches 150 cubic centimeters. The
filtrate is shaken in order to render the liquor homogeneous, and is transferred to a precipitating
glass of about 300 cubic centimeters capacity.
105. Solution of the Reverted Phosphates by Ammonium Citrate.—The filter from the
above process is detached from the funnel and is introduced into a flask marked at 150 cubic
centimeters together with sixty cubic centimeters of alkaline ammonium citrate prepared in the
following manner:

Pure citric acid, 400 grams.


Ammonia of 22°, 500 cubic centimeters.
The ammonia is poured upon the citric acid in the form of crystals in a large dish. The mass
becomes heated, and the solution takes place rapidly. When it is complete and the solution is cold
it is poured into a flask of one liter capacity, and the flask is filled up to the mark with strong
ammonia. It is preserved for use in a well-stoppered bottle. The solution must be strongly alkaline.
The flask in which the filter-paper is introduced, together with the ammonium citrate, is
stoppered and shaken violently in order to disintegrate the filter-paper and put the reverted
phosphates in suspension. There are added then about sixty cubic centimeters of distilled water,
and the flask is shaken and left for twelve hours at least, or at most for twenty-four hours. The
volume is made up to 150 cubic centimeters with distilled water, and, after mixture, the solution is
filtered.
There are thus obtained two solutions which can be precipitated together or separately
according to circumstances. The most usual process is to combine the two equal volumes of
twenty-five, fifty, or one hundred cubic centimeters, representing one-quarter, one-half, or one
gram of the material according to its presumed richness, in a precipitating flask to which are added
from ten to twenty cubic centimeters of the solution of magnesia made up as follows:
Magnesium carbonate, 50 grams.
Ammonium chlorid, 100 “
Water, 500 cubic centimeters.
Hydrochloric acid, 120 “ “
After complete solution of the solid matters in the above, add 100 cubic centimeters of
ammonia of 22° strength, and distilled water enough to make one liter.
The solutions are thoroughly mixed in a precipitating glass, an excess of ammonia added, and
allowed to stand for twelve hours under a bell jar. The phosphoric acid contained in the liquor is
separated as ammonium magnesium phosphate. It is collected upon a small filter, washed with a
little ammoniacal water, redissolved, and titrated with the uranium solution in the manner already
indicated.
Example: The following is an example of this kind of a determination:
(1) One and one-half grams of the superphosphate and distilled water
enough to make 150 cubic centimeters.
(2) Filter-paper with reverted phosphates, sixty cubic centimeters of
ammonium citrate, and a sufficient quantity of distilled water to make 150
cubic centimeters.
Aqueous solution (1) 25 cc
= 0.25 grams of the sample.
Citrate solution (2) 25 cc
Add magnesium solution twenty cubic centimeters and ammonia in
excess, and allow from twelve to twenty-four hours of digestion, then filter
and wash, dissolve and titrate.
Required of solution of uranium 8.55 cubic centimeters (1 cubic
centimeter = 5 milligrams P₂O₅).
Correction 0.20.
Remainder 8.35 × 0.005 = 0.04175 gram P₂O₅ for 0.25 gram of the
sample. Then 0.04175 ÷ 0.25 = 16.7 per cent.
From the above data there would be 16.7 per cent of phosphoric acid
soluble in water and in ammonium citrate.
If it be desirable to have separately the phosphoric acid soluble in water, a separate
precipitation is made of the aqueous solution alone by means of the magnesium citrate solution.
The precipitate washed with ammoniacal water is redissolved and titrated in the manner indicated.
In subtracting from the figures obtained with the two solutions together the number obtained for
the phosphoric acid soluble in water, the number representing the phosphoric acid soluble in
ammonium citrate alone, is obtained.
It is to be noted that the determinations with uranium require always two successive titrations.
It would therefore be an advantage in all operations to precipitate a weight of ammonium
magnesium phosphate sufficient for allowing this precipitate to be dissolved and made up to 100
cubic centimeters on which amount it would be possible to execute two, three, or four
determinations, and thus to obtain a figure absolutely incontestable.
106. Conclusions.—It has been seen from the above data that the French chemists have
worked out the uranium volumetric method with great patience and attention to detail. Where
many determinations are to be made it is undoubtedly possible for an analyst to reach a high
degree of accuracy as well as to attain a desirable rapidity, by using this method. For a few
determinations, however, the labor of preparing and setting the standard solutions required would
be far greater than the actual determinations either by the molybdate or citrate gravimetric
methods. For control work in factories and for routine work connected with fertilizer inspection, the
method has sufficient merit to justify a comparison with the processes already in use by the official
chemists of this country.
The use of an alkaline ammoniacal citrate solution, however, for the determination of reverted
acid renders any comparison of the French method with our own impossible. On the other hand
the French method for water-soluble acid is based on the same principle as our own; viz., washing
at first with successive small portions of water, and thus avoiding the decomposition of the soluble
phosphates, which is, likely to occur when too great a volume of water is added at once.
In the matter of the temperature and time as affecting the solubility of reverted acid, the French
method is also distinctly inferior to our own. The digestion is allowed to continue from twelve to
twenty-four hours, at the pleasure of the analyst, and meanwhile it is subjected to room
temperature. It is not difficult to see that this treatment in the same sample would easily yield
disagreeing results between twelve hours at a winter temperature and twenty-four hours at
summer heat.

THE DETERMINATION OF PHOSPHORIC ACID


BY TITRATION OF THE YELLOW PRECIPITATE.
107. Pemberton’s Volumetric Method.—In order to shorten the work of determining the
phosphoric acid, numerous attempts have been made to execute the final determination directly
on the yellow precipitate obtained by treating a solution of a phosphate with ammonium molybdate
in nitric acid. The composition of this precipitate appears to be somewhat variable, and this fact
has cast doubt on the methods of determination based on its weight. Its most probable
composition is expressed by the following formula, (NH₄)₃PO₄(MoO₃)₁₂. For convenience in
writing reactions this formula should usually be doubled. Pemberton has described a volumetric
determination of phosphoric acid in the yellow precipitate which has the merit of being rapid.[83]
In this laboratory the method has not given very satisfactory results when compared with the
molybdate gravimetric process. It has however attracted so much attention from analysts as to
merit description, and the details of the process are therefore given.
108. The Process.—One gram of phosphate rock, or from two to three grams of phosphatic
fertilizer, are dissolved in nitric acid, and, without evaporation, diluted to 250 cubic centimeters.
Without filtering, twenty-five cubic centimeters are placed in a four-ounce beaker and ammonia
added until a slight precipitate begins to form. Five cubic centimeters of nitric acid of one and four-
tenths specific gravity are then added, and afterwards ten cubic centimeters of saturated solution
of ammonium nitrate and enough water to make the volume about sixty-five cubic centimeters.
The contents of the beaker are boiled, and while still hot, five cubic centimeters of the aqueous
solution of ammonium molybdate added. Additional quantities of the molybdate are added, if
necessary, until the whole of the phosphorus pentoxid is thrown-out.
After allowing to settle for a moment the contents of the beaker are poured upon a filter seven
centimeters in diameter. The precipitate is thoroughly washed with water, both by decantation and
on the filter. The filter with its precipitate is transferred to a beaker and titrated with standard alkali,
in the presence of phenolphthalein. Each cubic centimeter of alkali employed should correspond to
one milligram of phosphorus pentoxid, (P₂O₅).
The reagents employed have the composition indicated below:
Ammonium Molybdate.—Ninety grams of the crystals of ammonium molybdate are placed in a
large beaker and dissolved in a little less than one liter of water. The beaker is allowed to stand
over night and the clear liquor decanted. Any undissolved acid is brought into solution in a little
ammonia water and added to the clear liquor. If a trace of phosphoric acid be present a little
magnesium sulfate is added and enough ammonia to produce a slight alkaline reaction. The
volume of the solution is then made up to one liter. Each cubic centimeter of this solution is
capable of precipitating three milligrams of phosphorus pentoxid.
Standard Potassium Hydroxid.—This solution is made of such strength that one cubic
centimeter is equivalent to one milligram of phosphorus pentoxid. Treated with acid of normal
strength, 100 cubic centimeters are required to neutralize 32.37 cubic centimeters thereof.
Standard Acid.—This should have the same strength, volume for volume, as the standard
alkali solution. It is made by diluting 323.7 cubic centimeters of normal acid to one liter.
Indicator.—The indicator to be used is an alcoholic solution of phenolphthalein, one gram in
100 cubic centimeters of sixty per cent alcohol, and half a cubic centimeter of this should be used
for each titration.
Thomson has shown[84] that of the three hydrogen atoms in phosphoric acid two must be
saturated with alkali before the reaction with phenolphthalein is neutral. Therefore, when the
yellow precipitate is broken up by an alkali, according to the reaction to follow, only four of the six
molecules of ammonium are required to form a neutral ammonium phosphate as determined by
the indicator employed. The remaining two molecules of ammonium unite with the molybdenum
forming also a salt neutral to the indicator.
Phenolphthalein is preferred because, as has been shown by Long, its results are reliable in
the presence of ammonium salts unless they be present in large quantity, and if the solution be
cold and the indicator be used in sufficient quantity.[85] To prepare the indicator for this work, one
gram of phenolphthalein is dissolved in 100 cubic centimeters of sixty percent alcohol. At least
one-half of a cubic centimeter of the solution is used for each titration.
The advantages claimed for the method are its speed and accuracy. Much time is saved by
avoiding the necessity for the removal of the silica by evaporation. The results of analyses with
and without the removal of the silica are practically identical. When the silica is not removed it is
noticed that the filtrate from the yellow precipitate has a yellow tint.
The reaction is represented by the following formula:
(NH₄)₆(PO₄)₂(MoO₃)₂₄ + 46KOH = (NH₄)₄(HPO₄)₂ + (NH₄)₂MoO₄
+ 23K₂MoO₄ + 22H₂O.
From this reaction it is seen that the total available acidity of one molecule of the yellow
precipitate titrated against phenolphthalein is equivalent to twenty-three molecules of potassium
hydroxid.
Calculation of Results.—The standard alkali is of such strength that one cubic centimeter is
equal to one per cent of phosphoric acid when one gram of material is employed and one-tenth of
it taken for each determination. In a given case one gram of a sample was taken and one-tenth of
the solution used. Fifty cubic centimeters of alkali were added to the yellow precipitate. It required
thirty-two cubic centimeters of standard alkali to neutralize the excess.
The alkali consumed by the yellow precipitate was 50 - 32 = 18. The sample therefore
contained eighteen per cent of phosphoric acid.
Comparison with Official Method.—A comparison of the Pemberton volumetric with the official
method of the Association of Agricultural Chemists has been made by Day and Bryant.[86] The
comparisons were made on samples containing from 1.45 to 37.28 per cent of phosphoric acid
and resulted as follows:
Per cent Per cent
Substance. P₂O₅, P₂O₅,
Official. Pemberton.
No. 1. Florida rock 1.45 1.32
“ 2. “ “ 4.40 4.53
“ 3. Sodium phosphate 19.78 19.99
“ 4. “ “ 19.72 19.73
“ 5. Florida rock 37.28 37.22
This near agreement shows the reliability of the method. The comparison of the Pemberton
volumetric method with the official gravimetric method was investigated by the reporter of the
Association of Official Agricultural Chemists in 1894.[87] The individual variations were found to be
greater than in the regular method but the average results were nearly identical therewith. The
method works far better with small percentages of phosphoric acid than with large. Where the
average of the results by the official methods gave 12.25 per cent, the volumetric process gave
11.90 per cent, whereas in the determination of a smaller percentage the results were 2.72 and
2.73 per cent, respectively. Kilgore proposes a variation of the method which differs from the
original in two principal points.[88] First the temperature of precipitation in the Pemberton process
is 100°; but in the modified form from 55° to 60°. At the higher temperature there is danger of
depositing molybdic acid.
The second difference is in the composition of the molybdate solution employed. The official
molybdate solution contains about sixty grams of molybdenum trioxid in a liter while the
Pemberton solution contains sixty-six grams. There is therefore not much difference in strength.
The absence of nitric acid, however, from the Pemberton solution favors the deposition of the
molybdic acid when heat is applied. Kilgore, therefore, conducts the analysis as follows: The
solution of the sample is made according to the official nitric and hydrochloric acid method for total
phosphoric acid. For the determination, twenty or forty cubic centimeters are taken, corresponding
to two-tenths or four-tenths gram of the sample. Ammonia is added until a slight precipitate is
produced and the volume is then made up, with water, to seventy-five cubic centimeters. Add
some ammonium nitrate solution, from ten to fifteen cubic centimeters, but this addition is not
necessary unless much of the nitric acid has been driven off during solution. Heat in water-bath to
60° and precipitate with some freshly filtered official molybdate solution. Allow to stand for five
minutes, filter as quickly as possible, wash four times by decantation using from fifty to seventy-
five cubic centimeters of water each time, and then wash on a filter until all acid is removed. The
solution and titration of the yellow precipitate are accomplished as in the Pemberton method. The
agreement of the results obtained by this modified method was much closer with the official
gravimetric method than those obtained by the Pemberton process.
109. Estimation of Phosphoric Acid as a Lead Compound.—In the volumetric lead method,
as described by Wavelet, the phosphoric acid is precipitated by the magnesium citrate solution as
in the uranium method of Joulie, as practiced by the French chemists, and the washing of the
precipitate and its solution in nitric acid are also conducted as in that method.[89] After solution in
nitric acid ammonia is added to neutrality and the solution is then made acid with acetic. The
phosphoric acid is precipitated in the acid solution by a standard solution of lead nitrate, the
precipitate having the formula P₂O₅3PbO.
The end reaction is determined by placing a drop of the titrated mixture on a white greased
dish in contact with a drop of a five per cent solution of potassium iodid. When all the phosphoric
acid is precipitated the least excess of the lead salt is revealed by the characteristic yellow
precipitate of lead iodid.
The author of the process claims that the lead phosphate is insoluble in the excess of acetic
acid and that the phosphate itself does not give any yellow coloration with potassium iodid. The
process is quite as exact as the uranium method and the end reaction is far sharper and the
standard reagents are easily made and preserved.[90] The method described merits, at least, a
comparative trial with the uranium process, but cannot be recommended as exact until further
approved by experience.
The reagents employed have the following composition:
(1) Disodium phosphate solution containing 10.085 grams per liter
(2) Sodium acetate “ “ 50.000 “ “ “
(3) Lead nitrate “ “ 40.000 “ “ “
(4) Potassium iodid “ “ 50.000 “ “ “
The titrations should be conducted in the cold.

110. Water-Soluble Phosphoric Acid.—Glaser has modified the volumetric method of


Kalmann and Meissels for the volumetric estimation of water-soluble phosphoric acid so as to
avoid the double titration required by the original method.[91] If methyl orange be used as an
indicator in the original method, the determination does not at once lead to the tricalcium salt, but
the liquid still contains, after neutralization, some monocalcium phosphate, which is determined by
a further titration with phenolphthalein. In the modified method the total phosphoric acid is
estimated in one operation as a tricalcium salt. This is secured, by adding, at the proper time, an
excess of calcium chlorid. Two grams of the superphosphate are shaken with water several times,
and, after settling, filtered, and the insoluble residue finally washed on the filter until the total
volume of the filtrate is a quarter of a liter. Of this, fifty cubic centimeters are taken and titrated with
tenth normal soda-lye, with addition of two drops of methyl orange, until the acid reaction has
entirely disappeared. There is then added some neutral calcium chlorid solution in excess. If iron
and alumina be present, a precipitate is produced of which no account need be made. The acid
reaction is thus restored. Five drops of the phenolphthalein solution are added and the titration
continued until the alkaline reaction is noted throughout the whole mass. Each cubic centimeter of
the soda-lye corresponds, in the first titration, to 7.1, and in the second to 3.55 milligrams of
phosphoric acid.
111. Estimation of Phosphoric Acid in the Presence of a Large Excess of Iron.—The
method given below, due to Emmerton, depends upon the precipitation of a phosphomolybdate, of
constant composition, in the presence of a large excess of iron, as in the analysis of iron and steel
and iron ores.[92] The molybdenum trioxid obtained is reduced by zinc to Mo₁₂O₁₉. The action of
permanganate on this compound is shown in the following equation:

5Mo₁₂O₁₉ + 17(K₂OMn₂O₇) = 60MoO₃ + 17K₂O + 34MnO.


Seventeen molecules of permanganate are equal to sixty molecules of molybdenum trioxid.
The iron or steel is dissolved in nitric acid, evaporated to dryness, heated, and redissolved in
hydrochloric acid, then treated again with nitric acid and evaporated until a clear and concentrated
solution is obtained free from hydrochloric acid.
The solution obtained is diluted to forty cubic centimeters with water and washed into a 400
cubic centimeter flask, making the total volume about seventy-five cubic centimeters. Add strong
ammonia, shaking after each addition, until the mass sets to a thick jelly from the ferric hydroxid.
Add a few more cubic centimeters of ammonia and shake thoroughly, being sure the ammonia is
present in excess. Add next nitric acid gradually, with shaking, until the precipitate has all
dissolved; add enough more nitric acid to make the solution a clear amber color. The volume
should now be about 250 cubic centimeters. Bring the solution to 85° and add, at once, forty cubic
centimeters of molybdate solution of the following strength: Dissolve 100 grams of molybdic acid in
300 cubic centimeters of strong ammonia and 100 cubic centimeters of water, and pour the
solution into 1,250 cubic centimeters of nitric acid (1.20); close the flask with a rubber stopper,
wrap it in a thick cloth, and shake violently for five minutes. Collect the precipitate on a filter, using
pump, and wash with dilute nitric acid (1 HNO₃ : 50 H₂O). If a thin film of the precipitate should
adhere to the flask it can be removed by the ammonia in the next operation. Wash the molybdate
precipitate into a 500 cubic centimeter flask with dilute ammonia (1 H₃N : 4 H₂O), using about
thirty cubic centimeters. Add hot dilute sulfuric acid (1 H₂SO₄ : 4 H₂O) and cover the flask with a
small funnel. Add ten grams of granulated zinc and heat until rapid action begins, and then heat
gently for five minutes. The reduction is then complete. During the reduction the colors, pink, plum,
pale green, and dark green, are seen in the molybdate solution, the latter color marking the end of
the reaction.
To remove the zinc, pour through a large folded filter, wash with cold water, and fill up the filter
once with cold water. But little oxidation takes place in this way. A port-wine color is seen on the
filter, but this does not indicate a sufficient oxidation to make an error.
In titrating, the wine color becomes fainter and finally the solution is perfectly colorless and
shows a single drop in excess of the permanganate. The permanganate solution, for convenience,
is made so that one cubic centimeter is equal to 0.0001 gram of phosphorus. With iron its value is
one cubic centimeter equals 0.006141 gram of iron; and one cubic centimeter equals 0.005574
gram of molybdenum trioxid.
112. Variation of Dudley and Noyes.—The method of Emmerton to determine small
quantities of phosphoric acid, or of phosphorus in presence of a large excess of iron, has been
modified by Dudley and Pease,[93] and by Noyes and Royse.[94] As modified, the method is not
intended for fertilizer analysis, but the principle on which it rests may some time, with proper
modifications, find application in fertilizer work. The reduction is accomplished in a Jones’ tube,[95]
much simplified, so as to render it suitable for common use. The molybdic acid is reduced to a
form, or series of forms, corresponding to molybdenum sesquioxid, as in the Emmerton method,
and subsequently as in that method, titrated by a set solution of potassium permanganate.
The iron or steel filings, containing phosphorus, are brought into solution by means of nitric
acid. For this purpose two grams of them are placed in a half liter flask together with fifty cubic

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