Learning Objectives

1) Describe the basic anatomy and physiology of the prostate

2) Locate and identify the structures  and zones

3) Describe how anatomy applies in clinical situations

4) Describe the physiology of time and aging

5) Describe the common diseases that affect the prostate

Introduction

The prostate is an accessory organ of the male reproductive system and is a member of the genitourinary system. It is part fibromuscular and part glandular and shaped like an inverted cone, often called chestnut in shape, sometimes walnut in shape and to some extent in size, yet sometimes described as a small plum or even a small kiwi fruit in size. It is far from a vital organ since removal does not affect life itself but radical prostatectomy results in infertility. Thus although it is not vital for one individual human, it is vital to the survival of the human race. A lofty attribute for a small kiwi fruit I would say!

Overview

Structurally, it is characterised by its shape, central position, relationship to the urethra, and its close relationship to the seminal vesicles and ejaculatory ducts. It is the only exocrine organ that has a symmetric and central location in the body. In the central portion of the gland the prostatic urethra acts as the repository of the 3 major components of the semen – the mysterious fluid that keeps our species going. Thus the prostatic urethra is the “mixing pot” where semen is formed.

The prostate is divided into concentric zones around the urethra. Zonal anatomy has been a more recent method of characterizing the parts of the prostate since it has embryological, histological and pathological implications. The prostate is found deep in the pelvis and not an obvious organ unless deep dissection is performed. It was therefore not obvious to early anatomists.

The function of the prostate is to secrete a milky fluid which combines with the secretions of the seminal vesicles, sperm from the testes and small contribution from Cowper’s gland to form semen. The fluid that the prostate produces provides nutrients for the semen, aids in the liquefaction of semen after deposition in the vagina, and also aids as a chemical buffer. The relatively alkaline secretion of the seminal vesicles and prostate protect the sperm from the relatively acidic environment of the vagina.

The prostate contributes about 20% of the volume to the seminal fluid.

Common diseases include prostatitis, benign prostatic hyperplasia (BPH) and prostate carcinoma.

Diagnostic evaluations include digital rectal examination (DRA), serum prostate specific antigen (PSA) level, and imaging, usually MRI while transrectal ultrasound is used for biopsy. CTscan, and bone scan are useful in staging.

Treatments include medical therapies, such as the use of hormonal agents, alpha adrenergic (smooth muscle) blockers, antibiotics, and chemo therapy although in cancer, surgery and radiation are commonly employed.

The term prostate is derived from Greek- prostates, which means “one who stands before”, “protector”, “guardian” owing to is position relative to the bladder.

The Mixing Pot Concept

It is important to understand the role of the prostate as a secondary sexual organ not only in that it secretes a portion of semen, but that semen is formed in the confines of the walls of the prostatic urethra which is of course within the confines of the prostate. This implies that if and when the prostate is removed in radical prostatectomy the mixing pot is removed, and there is no place for semen to be formed which results in infertility. The concept of the prostate acting as a mixing pot is a key, unappreciated, and central function of the prostate.

The prostatic urethra also acts as a conduit for urine. If the prostatic tissue around the urethra enlarges it can result in narrowing of the prostatic urethra. This concept is more easily understood and known and results in a clinical syndrome called prostatism and more recently called lower urinary tract syndrome or LUTS.

History

The history of the prostate is one of intermittent and repeated recognition followed by intermittent and repeated neglect. With our aging population and with the incidence of benign prostatic hypertrophy and prostate carcinoma common after 60 and almost universal in the octogenarian population and beyond, it is currently in focus and likely to stay there because of the associated morbidity of prostate disease.

Herophilus of Chalcedon often called the father of anatomy, was a Greek anatomist and physician (335BC -280BC) assigned the name prostate which means “one standing in front” because he saw it as standing before the testis. Herophilus was one of the founders of the Alexandrian school of medicine which was set up at the end of the 4th century. He probably identified the organ in animals eg monkeys whose prostate consists of two distinct parts.

Rufus of Ephesus was a renowned Greek physician who lived in the first century AD followed Hippocrates and preceded Galen. He noted that in some cases of bladder stone he was able to feel a soft swelling near the bladder neck but he failed to identify the swelling as the prostate gland.

Galen (131 -201 AD) acknowledged the naming of the prostate by Herophilus, and wrote of the prostate as the “spongy flesh at the side of the neck of the urinary bladder” (Murray).

The prostate was lost to follow up until the 16th century when Niccolo Massa a Venetian physician and anatomist is credited with the accurate identification of the prostate in 1526.

Da Vinci (1452- 1519) was not aware of the existence of the prostate. A drawing by Vesalius in 1538 in his medical treatise “De humani corporis fabrica.”, is the first known diagram of the prostate.

Jean Riolan the younger was a French anatomist (1577-1657) was the first to suggest that obstruction of the bladder could be surgically relieved through the perineum but it is not certain whether he made the association of the prostate with bladder obstruction (Deaver).

There was little medical interest in the enlarged prostate until the late 18th century.

Prostate cancer was first identified by British surgeon John Adams, and published in the “The Lancet” in 1853.

Medical science has been challenged by prostatic hyperplasia and prostatic cancer ever since. Of recent, there are multiple innovations in prostatic therapy the most sophisticated of which is robotic surgery innovated in Vancouver in 1983. The first FDA approved system used in prostatic surgery is called the da Vinci system – an odd association since Leonardo missed the prostate despite his genius. It was developed by the US army in the hope that skilled surgeons would be able to execute complex surgery from centralized regions on wounded soldiers in geographically remote regions.

Principles

There are universal principles that govern all biological structures.

The principles of structure are in part reflected in the adjectives used to describe them including size, shape, position, character. Biological structures are made of smaller parts and are usually surrounded by a protective capsule. Structures that connect the prostate to the rest of the body include the blood vessels, lymphatics, ducts and nerves. As a biological structure the prostate undergoes changes in time that include the changes that occur in its early development and then in aging.

Biological structures function by receiving raw products, processing and producing, and then exporting products that are useful to the organism.

Disease is the alteration of structure and or function, while diagnosis aims at identifying these structural and functional abnormalities, and treatment aimed at relieving the aberrances.

Histology

The prostate is comprised of approximately 30% glandular and 70% fibromuscular stromal elements.

There are two basic types of cells in the prostate; glandular or epithelial cells, and the stromal cells. Epithelial cells make up the glandular portion of the prostate and stromal cells make up the surrounding muscle and connective tissues. The interaction between the epithelial cells and stromal cells is relevant in the evolution of prostatic disease.

The epithelial cells take two forms;
The columnar cells are the secretory cells, and form 90% of the epithelial population. They are rich in acid phosphatase and prostate-specific antigen.
The other epithelial cell type is the basal cell which is a small, undifferentiated, keratin-rich pluripotential cell. Basal cells form less than 10% of the epithelial cell population. These cells are responsible for regeneration of the epithelium. When they are present they form a second cell layer creating a pseudostratified appearance to the epithelium.

The fibromuscular stroma consists of smooth muscle separated by strands of connective tissue rich in collagenous and elastic fibers. The muscle is scattered in the gland, and also forms a dense ring around the urethra. Muscle is also found beneath the capsule of the prostate.

The glandular elements are organized with tree like morphology and have a tubuloalveolar shape. A tubuloalveolar gland is named because it is a combination of a tube and a sphere meaning in essence that it is tear drop shaped.

The epithelium or lining of the glands is cuboidal or columnar which describes the shape of the individual cells as being either like a cube or like a column. It is usually a single layer of cells thick but may look pseudostratified and two layered when basal cells are present. The mucosa forms papillary projections into the lumen giving the alveoli an irregular shape.

A characteristic feature of the glands, especially in older patient are hyaline accumulations of thickened secretions that form in layers which are found in the lumen of the acinus or gland. These lamellated concretions are called corpora amylacea. The word corpus is derived from the Latin word corpus which means a body and amylacea is from the Latin word amylum which means starch or gruel. The clinical significance of the corpora amylacea is not known. They may also be found less commonly in the pulmonary alveoli.

The glandular elements comprise of about 30 – 50 tubuloalveolar glands, which empty into 15 – 25 independent excretory ducts. These ducts open into the urethra just lateral to the verumontanum where the ejaculatory ducts enter.

The largest component of stroma cells is the smooth muscle contribution. The smooth muscle cells are rich in actin and myosin. The smooth muscle is required for release of seminal secretions during ejaculation. The second major component of the stroma is fibroblastic tissue. The fibroblasts are rich in vimentin and fibronectin, and provide structural support to the gland.

Carcinoma of the prostate develops from the epithelial cells, but the interaction with the stromal cells is relevant to the prognosis and characteristics of prostate cancer.

BPH develops from the complex interactions between epithelial and stromal cells.

Testosterone interacts with both cell types.

Anatomy Introduction

The prostate is rather unique among exocrine glands since it is the only exocrine gland that occupies a symmetrical central location in the body. The pancreas has both endocrine and exocrine function and is centrally placed, but its parts are eccentrically positioned with less of the gland on the right and more of the gland on the left side of the body.

If one were to show the non inquisitive person the prostate gland of a bull, he or she might ask – “What is that?” The easiest answer would be – “It is a bull’s prostate,” and that could suffice as an answer. If on the other hand the same prostate was shown to a curious minded, or analytically minded person, they may counter with “How do you know?” or “Why is it a prostate?” The answer, based on the knowledge of the structure would include describing its unique and characteristic size, shape, position, and character. We may also speak to its parts, and its relationships to other structures its connections to other biological structures, how it changes with time and different cyclical events. The manner with which it functions in vivo would be its physiological characteristics.

The descriptors we used above are universal descriptors that can be applied to all biological structures whether it is the bull’s prostate, the glial cell of the brain or the pancreas of a mountain rat. We can use these descriptors to describe the cell, a tissue, an organ in both health and disease. We can also use these descriptors for clinical findings such as an enlarged prostate felt on transrectal examination that feels hard, nodular, soft, or rubbery.

Advancing the Structural Detail

The size of prostate is smaller than one would imagine. It has been compared to a small kiwi fruit, small plum, an almond and a chestnut. In fact, after a small experiment involving the purchase of these fine fruits and nuts it was found that the chestnut was closest in size in all dimensions.

By virtue of its small size, it does not allow it to store large amounts of secretions. A normal prostate gland weighs about 20g-30g in a 30-year-old male. The normal volume is between 20-30 ccs. The prostate normally measures 3 cm in length (height), 4 cm in width (transverse), and 2 cm in depth (anteroposterior dimension).

It remains relatively stable in size until the age of 50 when increasing weight of the gland is observed. By the age of 80, the average prostatic weight is 35-45g.

Advancing the Structural Detail : Prostate Volume Calculation

A simple prorated, ellipsoid formula is commonly used to calculate prostate volume: (anterior-posterior diameter) x (transverse diameter) x (superior-inferior diameter) x Π/6 (approximately 0.52) is accurate and reproducible.

From a practical point of view in imaging the gland is usually enlarged if the transverse dimension is greater than 4cm.

 Applied Biology

 Shape

The prostate has been likened to many structures including a cone, a chestnut, a walnut and a heart.

In the A-P projection it is seen as a cone-shaped organ with apex directed inferiorly and base in contact with the bladder superiorly.

The prostate has anterior, posterior, and lateral surfaces. The anterior surface is rounded, the posterior surface is slightly flattened and the lateral surfaces rounded as well. This shape fits quite accurately with the chestnut as well.

In the transverse dimension the prostate is seen at some levels as heart-shaped.

Advancing the Structural Detail : Position
The term prostate is derived from Greek- prostates, which means “one who stands before”, “protector”, “guardian” owing to its position relative to the bladder although it appears that Herophilus who named the organ implied that it lay before the testes.

It is cradled by the urinary bladder, and fits snugly between the bladder and the membranous and penile urethra. It provides passage both for urine, and semen but also acts as the mixing pot for semen, where the ingredients come together.

The prostate sits between the internal and external sphincters that control the urinary stream. At the bladder neck the detrusor muscle of the bladder becomes confluent with the internal sphincter while smooth muscle of the anterior fibromuscular zone contributes to the internal sphincter as well. On the inferior side, the external urethral sphincter is formed from skeletal muscle from the inferior aspect of the fibromuscular layer and the participation of the perineal membrane. The external sphincter surrounds the membranous urethra and the beginning of the penile urethra. Thus, it is interesting as well that the anterior zone of the prostate contains smooth muscle superiorly and skeletal muscle inferiorly. It shares this unique characteristic of having both smooth muscle and skeletal muscle with the esophagus.

Advancing the Structural Detail : Sagittal Projection

The anterior and posterior relationships of the prostate are appreciated in this projection. The prostate lies immediately behind the pubic symphysis. Between the prostate and the pubic symphysis is the retropubic space of Retzius in which the anterior venous plexus of Santorini is positioned.

Posteriorly, the Denonvilliers’ fascia is found and is made up of a combination of posterior prostatic and anterior rectal coverings. As we have noted in the coronal projection the prostate sits on the perineal membrane. The urethra runs through it, and extends through the membrane, after which it changes direction to enter the shaft of the penis. This change in direction of the urethra is best appreciated in the sagittal projection. Posterolaterally, the prostate is cradled between the levator ani muscles.

Advancing the Structural Detail : Applied Biology

The ideal route for examining the prostate is via the rectum, whether one is performing a digital examination or imaging with ultrasound or MRI, due to the proximity of the two organs.

The relationship to the prostate and the urethra is also intimate. When the transitional zone of the prostate enlarges due to hyperplasia it obstructs the urethra resulting in partial obstruction clinically manifesting in a progressively reduced force of the urinary stream. Post void residual increases and the patient then needs to void more frequently. In addition during micturition the bladder muscle tires as it tries to expel the full volume of urine but recovers a short time thereafter (a few seconds) and the patient usually will void an additional small volume after the short rest period. This clinical syndrome resulting from bladder obstruction is called prostatism or more recently referred to as LUTS – lower urinary tract symptoms.

Advancing the Structural Detail : Character

The character of the prostate is based on its feel on palpation. On clinical examination, the normal prostate gland is described as being smooth, elastic and “rubbery”. Galen described it as that “spongy flesh at the side of the neck of the urinary bladder”. Abnormalities of the prostate felt on direct clinical examination are nodules, induration, bogginess or fluctuance.

Ultrasound
The prostate gland on ultrasound is almost isoechoic and the gains have to be finely tuned on the ultrasound equipment in order to bring out the subtle differences in the texture of the gland and the surrounding tissue.

Computed Tomography (CT)
The normal prostate has non specific features on CT scan and demonstrates soft tissue density similar to the muscle surrounding it.  The distinction between the various zones of the prostate usually cannot be appreciated on the normal gland.

Magnetic Resonance Imaging (MRI) Characteristics
MRI is the imaging modality that best characterizes the prostate. The T2-weighted sequence optimizes the distinction between the peripheral, central, transitional zones and the anterior fibrous layer.

Parts

The parts that make up the extremes of the prostate as we have previously outlined are called the base and the apex. Because the superior aspect of the prostate is broader it is called the base and the since the inferior aspect is pointed aspect is called the apex. Note that the same orientation and nomenclature applies to the heart.

The prostate has anterior, posterior, and lateral surfaces. The anterior surface is rounded, the posterior surface is slightly flattened and the lateral surfaces rounded as well.

The internal parts of the prostate that contribute to the zonal anatomy have embryological, histological and pathological significance. Each zone participates uniquely to the functioning of the gland.

The prostate appears morphologically simple on the outside but is complex internally at both the macroscopic and microscopic levels. The current concepts of its morphology have only evolved since 1968 after the work of McNeal. He suggested that the prostate was composed of three concentric zones that surround the prostatic urethra, and a fourth anterior zone.

The zones of the prostate include the central, peripheral and transition zones as well as an anterior fibromuscular layer.

The peripheral zone accounts for approximately 70%, central zone 20%, the transition zone about 5% and the anterior fibromuscular layer (zone) about 5%.

In the 19th century the prostate was seen as having 4 lobes; 2 lateral lobes, a middle lobe and an inconstant anterior lobe. In 1912 an inconstant posterior lobe was added by Lowsley.

Parts: Zones

The peripheral zone is the outermost layer of the gland and comprises of the mostly glandular tissue. It has simple glands and loose stroma. It is the site of origin of adenocarcinoma of the prostate.

The central zone has both glandular elements and ductal elements and characteristically surrounds the ejaculatory ducts and stromal elements. The epithelial cells are slightly different and are composed of tall columnar cells with eosinophilic cytoplasm, and prominent basal cell layer.

The transitional zone surrounds the urethra and contains the ductal system that eventually terminates in the periprostatic urethra. It is the innermost layer of the prostate and is the region where benign prostatic hyperplasia (BPH) originates.

The anterior zone is composed of fibromuscular stroma. This zone, comprising almost one third of the prostate mass, though of a lesser volume, contains smooth muscle, some skeletal muscle and has no glandular elements.

The prostate contributes to both the structure of the internal and external sphincter. The anterior fibromuscular layer contributes smooth muscle to the internal sphincter and skeletal muscle from the inferior aspect of the anterior fibromuscular zone, and is part of the external sphincter. The internal sphincter is under autonomic control while the external sphincter is under voluntary control.

Parts: Applied Biology

When palpating the prostate during digital rectal examination, the most prominent part is the peripheral zone. It is the most common site of prostate cancer.

Benign prostatic hypertrophy/hyperplasia originates in the transitional zone and may also be palpable during digital rectal examination.

Parts: Capsule

The prostate is surrounded by a firm fibrous capsule that is structurally composed of collagen, elastin, and smooth muscle. These fibers blend with the fibers of the puboprostatic ligament, anchoring the prostate to the posterior aspect of each of the pubic bones. The capsule itself lies within the sheath for the endopelvic fascia, which surrounds it laterally, anteriorly and posteriorly. Under this capsule are circularly oriented smooth muscle fibers and collagen-rich tissue that surround the urethra. The prostatic capsule is not present at the apex (inferiorly) where it transitions into the external sphincter, and is also absent at its base superiorly, where it transitions into the detrusor muscle of the bladder.

Functionally, the capsule provides a protective barrier to the prostate. In addition, smooth muscle elements aid in the expulsion of prostatic secretions.

When prostate cancer spreads beyond the capsule it carries a poorer prognosis. Nevertheless, as the prostatic capsule is poorly defined at the apex and base, determining extension beyond the capsule at these levels makes this evaluation a challenging problem for the pathologist.

Treatment is rarely focused on the capsule itself, though attempt is made to resect the prostate with the capsule intact so that pathologic examination can determine if the disease is confined within the borders of the capsule.

Parts: Connections of the Prostate

The connections of the prostate to the rest of the genitourinary tract and the rest of the body are via the ducts vessels and nerves. The ductal systems are confluent in the prostatic urethra, its blood supply is via the anterior branch of the internal iliac artery along with the cystic artery, venous drainage via the cystic veins, and lymphatics via the iliac system. Parasympathetic and sympathetic systems connect it to the autonomic system, while the hormonal control is via dihydrotestosterone (DHT).

Parts: Ducts of the Prostate

The lower genitourinary system has dual responsibility for the transport of urine and semen. Urine is the product of the kidneys and semen is the product of the testes, seminal vesicles, prostate and bulbourethral glands (aka Cowper’s glands).

The sperm and fluid from the seminal vesicle are transported via the paired ejaculatory ducts into the verumontanum, which is a mound of tissue in the middle of the prostatic urethra. The prostatic fluid is brought to the urethra by 15-20 ducts.

The ejaculatory ducts are a paired system that forms by the confluence of the duct of the seminal vesicle and vas deferens. They enter into the prostatic urethra in the verumontanum just below the prostatic utricle (when present).

Parts: Prostatic Urethra

The prostatic urethra is part of the urinary system, structurally characterized by its position in the anterior part of the prostate surrounded by the transitional zone. It is widest in its midportion where the confluence of prostatic ducts, ejaculatory ducts and prostatic utricle are concentrated. It is a multifunctional conduit for the transport of urine and semen, and in fact is the mixing pot where the major ingredients of semen are combined. The prostatic urethra forms semen from three main structures that include the seminal vesicles, vasa deferens and prostate.

Blood Supply

The primary blood supply of the prostate comes from the prostatic artery which is a branch of the inferior vesical artery which is s a branch (direct or indirect) of the anterior division of the internal iliac artery. Some accessory vessels to the prostate are supplied from the middle hemorrhoidal (rectal) and internal pudendal arteries.

 

Venous Drainage

Structurally, the venous drainage of the prostate is through the prostatic plexus. The plexus surrounds the prostate like a net and joins the venous drainage of the penis (deep dorsal vein) in Santorini’s plexus.

The periprostatic plexus consists of the anterior plexus called Santorini’s plexus that lies behind the pubic symphisis in the retropubic space of Retzius and the paraprostatic plexus called the pudendal plexus (vesicoprostatic plexus) which drains both the inferior aspect of the bladder as well as the prostate.

The usual drainage of the prostate is via the internal pudendal vein which drains into the anterior branch of the internal iliac vein. The plexus however does collateralize with the external pudendal vein which drains into the external iliac system, and the vertebral venous system or Batson’s plexus, which is the valveless system that drains the spinal cord and vertebral column. The intervertebral veins and the epidural venous plexus, collateralize at all levels of the spinal canal and vertebral bodies and also drains into the azygos system. Thus venous drainage goes three ways; internal iliac, external iliac, and azygos via the collateral systems of Santorini’s plexus, vesicoprostatic plexus and Batson’s plexus.

Blood Supply: Applied Anatomy

Diseases, such as infection and cancer may spread through the venous drainage to the distant organs.

Radiation seeds, used in the treatment of prostate cancer, may also embolize through the venous drainage system either via the iliac or via the azygos system.

The most usual method is via the internal iliac system and into the IVC and then pulmonary circulation.

It is not unusual for metastatic prostate cancer to affect the vertebral column and it does this by it connection with Batson’s plexus which is the valveless system that drains the vertebral bodies and the cord.

The venous plexus is of particular importance in treatment during radical prostatectomy, when division of the dorsal venous complex can result in significantly increased risk of blood loss.

Phleboliths or calcifications within the prostatic veins are common in older patients and may be seen on CT. They have no clinical significance other than causing some difficulties in differentiating ureteric stones from phleboliths.

Lymphatic Drainage

Lymphatic drainage from the prostate is via the internal iliac, sacral, vesical, and external iliac nodes.

Nerve Supply

The autonomic nervous system helps to control the function of the prostate gland. The parasympathetic division of the autonomic nervous system regulates erection, whereas ejaculation is triggered by sympathetic impulses (Ventura).

The hypogastric nerve (sympathetic) join the pelvic splanchnic nerves (parasympathetic S2-S4) to form the pelvic plexus.

During prostatectomy, the portions of the hypogastric plexus that go to erectile tissues of the penis pass through the prostatic plexus. If these nerves are sacrificed, impotence can develop.

Embryology

The prostate is derived from the urogenital sinus. The prostate develops as 30-50 distinct glands which grow in confluence and gradually fuse. These tubuloalveolar glands originate from the uroepithelium and grow into the surrounding wall of the developing urethra and enlarge. After birth, the size of the prostate remains relatively unchanged for 10-12 years, until puberty. Increased production of androgens stimulates an increase in gland size.

The prostate will attain a mass of approximately 20 grams by the end of puberty, which will again remain stable for several decades.

The prostate first appears during the third month of embryonic development. Five epithelial buds form in a paired manner on the posterior side of the urogenital sinus on both sides of the verumontanum, and they then invade the mesenchyme to form the prostate. The top pairs of buds form the inner zone of the prostate and appear to be of mesodermal origin; the lower buds form the outer zone of the prostate and appear to be of endodermal origin. This is of potential importance since the inner zone gives rise to benign prostatic hyperplasia (BPH) tissue, whereas the outer zone contains the primary origin of cancer. Much of the development, growth, invasion, budding, and branching are genetically controlled and influenced by dihydrotestosterone, which is produced from testosterone in the urogenital sinus. By its 4th month, the fetal prostate is well-developed.

Developmental Abnormalities

Developmental abnormalities are rare. Aplasia and hypoplasia represent incomplete development. This is usually due to a deficiency of androgen production. Cystic changes may occur proximally or distally or in neighboring structures. These changes may lead to infertility but are otherwise asymptomatic. Mesonephric remnants represent incomplete obliteration of these primordial embryological structures.

Aging

At birth the prostatic acini are lined with squamous epithelia.

Stimulation of further development of the gland is dependent on maternal steroids, namely estrogens. As the levels of these hormones decrease, an involutional phase ensues during the first 5 months. Large transient surges of serum androgen, estrogen, and progesterone normally occur very early in postnatal life. This is usually between 2 to 3 months of age. At this time, levels may reach upward of 60 times normal prepubertal levels, approaching adult serum testosterone levels.

The prostate increases rapidly in size at puberty. During the fifth decade, it starts to show the effects of aging either resulting in atrophy but more commonly hyperplasia.

The prostatic age is the period in a mans life when he starts to experience the clinical manifestations of the aging prostate which in the past was called prostatism but is now referred to as lower urinary tracts symptoms (LUTS). These symptoms include frequency, urgency, hesitancy, poor emptying, nocturia, and dribbling.

Function

The prostate is present in all mammals and its function, though still not completely understood, has importance in reproductive physiology. The most obvious function is to participate in the production of semen, but it also has a function in the ejaculatory process by acting as a mechanical pump, and acts as a one way conduit for the semen by clamping off the internal sphincter and opening the external sphincter during ejaculation. Interestingly, it also participates in the pleasurable feeling of the orgasm, with its female counterpart, the Skene’s glands which are purportedly considered the erogenous G spot that brings pleasure to the female during sexual intercourse. Skene’s glands lie lateral to the female urethra.

The process of ejaculation and the transport and life cycle of semen is a marvel and we will take you through this chronologically.

Function: Show Time

The components of semen are continually produced and during intercourse the seminal vesicles, seminiferous tubules, and prostatic glands are overflowing with their products.

The diagram below by da Vinci exemplifies coitus.

Preparation for the Event

As the climax is approached the three major organs that produce the semen are all revved up and in full production, and finally ejaculation takes place.

During ejaculation the anterior fibromuscular zone of the prostate plays its part by assisting in closing the internal sphincter with smooth muscle, thus prevents the forward flow of urine into the ejaculate and preventing the ejaculate from going backward into the bladder. The anterior fibromuscular zone also assists in opening the external sphincter using the skeletal muscle allowing the gate to open for the semen to be released. Lastly by contractions of the fibromuscular layer in the central zone the prostate helps to expel the semen.

The prostate, in addition, participates at a higher level in that it enhances the pleasurable sensations during orgasm.

The initial ejaculate is a heterogeneous mixture. The first portion of the ejaculate, about 1-2% of it, is made up of secretions from the Cowper (bulbourethral) and Littre glands that lubricate the urethra and buffer any acidic urine than may be present in the urethra. The second portion derives from the prostate and contributes from 15% to 30% to the ejaculate. It is a milky white to gray in color. Thereafter, sperm from the testes via the vasa deferentia (2-5%) follow and, finally, the contribution of the seminal vesicles, which accounts for the majority of the ejaculate (65-70%), arrives. The normal PH of semen is between 7.05 and 7.8 and normal sperm count should be more than 20 million per mls and is usually closer to more than 40 million per ml and even up to 250 million per ml. It boggles the mind to think of the number of “hopefuls” looking for the one Miss Right, and only one of which will be successful.

1-2ccs of prostatic fluid is secreted in the urine per day in the absence of ejaculation.

The vaginal environment is acidic (PH about 4), and as such is a protective environment for the vagina against bacteria. On the other hand sperm are also sensitive to the acid environment. Nature has solved this problem by creating a two step process in the safe delivery of sperm. The first step is the deliver the sperm in coagulated form and protected from the acid, and the second step is to liquefy the coagulated form and free the sperm into a safe environment.

Function: Chemical Components of the Prostatic Secretion

The prostate gland produces and stores a fluid that has a high buffering capacity when mixed with other components of semen. The PH of semen is close to body PH and is used to buffer the acidity of the vagina ensuring a safer chemical environment for the sperm which survive longer and have greater motility within the environment of prostatic secretions (Owen).

As the PH is buffered the chemical environment becomes safer for the sperm.

The prostate is also responsible for the production of many other components that comprise semen. It is a milky fluid contains acid phosphatase, citric acid, inositol, calcium, zinc, and magnesium. Enzymes, such as proteases, esterases, phosphatases, prostate specific antigen, amylases, pepsinogen and hyaluronidase are also present.

The concentration of citric acid in prostatic secretion is the highest found in the body (Kandeel) by an order of 100 times. This latter fact adds one more mystery about the prostate. One hypothesis is that the citrate serves to chelate calcium and thus aids the PSA enzyme in liquefying the coagulated semen that initially forms and attaches itself to the cervix.

The presence of zinc from the secretion presumably is an antiseptic. When the semen initially enters the vagina it clots, which glues the semen and trapped sperm to the cervix. The PSA enzyme will lyse this clot and releasing the sperm which will find their way into the uterus and then the Fallopian tube.

The semen coagulates due to a fibrinogen like agent secreted by the seminal vesicles. The semen is also sticky allowing it to become adherent to the cervix. The sperm needs temporary cocoon type protection from the acidic environment of the vagina. The sperm are housed in the coagulum and are nourished by other components of the semen eg fructose produced by the seminal vesicles.

Following ejaculation and formation of the coagulated semen, between about 5-20 minutes is needed for liquefaction to occur that will allow the release of the sperm. This period allows the PH of the acidic vaginal environment to be buffered by the semen in order for the sperm survive.

Liquefaction occurs as a result of proteolytic enzymes within the prostatic secretion that include pepsinogen, amylase, hyaluronidase and prostate specific antigen. The citric aid as stated appears to assist the process by chelating calcium.

The prostate is unique as an androgen-receptor expressing organ in that it remains sensitive to androgens throughout life. This occurs through a process of differential gene expression known as imprinting and may be of importance in the development of benign prostatic hyperplasia (BPH).

Diseases

The most common diseases that affect the prostate are benign prostatic hyperplasia (BPH) and prostate carcinoma. Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer death in men second to lung cancer. Prostate hyperplasia is an aging phenomenon that can give rise to significant morbidity in the aging male. Prostatitis and prostatic abscess are two other relatively common diseases.

Diseases: Prostate Carcinoma

Prostate carcinoma is a malignant disease usually originating in the secretory cells of the prostate glands. It is the most commonly diagnosed cancer in men and the second leading cause of cancer death in men second to lung cancer.

Tumors of the prostate are estimated to be found in about half of the men in their 70’s and almost all men in their 90’s. The incidence of prostate cancer differs among different ethnicities. The incidence is highest among African Americans and lowest among Asian Americans.

Structurally, it can present with a focal thickening in the peripheral zone, along with irregularities in the prostate contour.

Functionally, there is limited impairment, and diagnosis is often made incidentally or during screenings.

Complications include early spread to the regional nodes and spread to distal areas, such as the skeleton.

Clinically, the patient is usually asymptomatic with localized disease. With progression patients may experience bony pain, urinary symptoms from obstruction, or hematuria. Survival rates vary depending on how aggressive the disease is at the time of diagnosis.

The diagnosis is suspected by digital rectal examination (DRE) showing a nodule or induration, as well as and elevated serum prostate specific antigen (PSA), but is often found incidentally at autopsy. As such it is a highly heterogeneous disease with varying degrees of impact on morbidity and mortality. Biopsy is the gold standard for diagnosis. It is believed that screening has played a significant role in reducing mortality from prostate cancer. Screening utilizes various measurements of PSA levels.

From an imaging standpoint, ultrasonography can reveal a hyperechoic, hypoechoic, or isoechoic nodule or region. Endorectal T2-weighted MRI may be more specific. CT is of little use in the diagnosis of the primary disease, though contrast-enhanced CT may demonstrate enhancement in tumors. It is best used in the evaluation of nodal disease and systemic spread. Bone scintigraphy is sensitive and useful for the evaluation of osseous metastases.

Treatment of prostate cancer depends on several factors, namely the grade and stage of the tumor, life expectancy of the patient, and the ability to ensure disease-free survival. Surgical treatment provides the only opportunity for cure and is indicated in the presence of aggressive disease (Gleason 7-10), and is dependent on the age at diagnosis. Gleason 6 is considered by many to be non-operative but should undergo close surveillance. The role of neoadjuvant therapy prior to surgery is indicated in patients with T3 disease, followed by external beam radiotherapy. If a resection results in positive tumor margins, adjuvant radiotherapy may also be indicated.

 

Diseases: Prostate Specific Antigen (PSA)

PSA or Prostate Specific Antigen plays a role in liquefying the semen that is formed after ejaculation. It has a half biologic half-life of approximately 2-3 days.

There is considerable debate regarding the role of PSA in screening for prostate cancer. PSA can be elevated in a variety of situations, including prostate cancer, BPH, and prostatitis. The sensitivity of PSA is about 80%, but the specificity of PSA in detecting prostate cancer is only 65%.

Diseases: Metastasis

Prostate metastasis spreads primarily by contiguous spread locally via lymphatic vessels to regional lymph nodes, as well as hematogenously to distant sites. Initially spread to distant sites is mostly within the axial skeleton. In later stages of disease spread to the lungs, liver, and kidneys may also occur.

 Regional Spread

Diseases: Nodal metastases

Metastatic Disease Bone

Spread to bones is common, and spread of disease to the bones is often monitored via bone scintigraphy. The association of a common venous drainage via the valveless Batson’s plexus, enables the early spread of the disease to the spine. While new foci of disease may be appreciated, the resulting blastic activity is not particularly effective in demonstrating a response to therapy.

 

Diseases: Benign Prostatic Hyperplasia (BPH)

Benign prostatic hyperplasia or BPH is a benign process of the prostate whose cause is uncertain, but is dependent on androgens to evolve.

Structurally, the disorder is characterized by a proliferation of the epithelial and stromal cells in the periurethral area of the prostate.

Functionally, this disorder may contribute to neurogenic changes in the bladder contractility. As a result of proliferation and hypertrophy, pressure exerted on the urethra obstructs bladder outflow. The increased filling of the bladder results in urgency. Since greater pressure is required to overcome the obstruction, incomplete voiding of the bladder is common. This elevated post-void residual leaves the bladder little additional capacity for urine produced, resulting in frequency and nocturia. As the bladder overflows, dribbling may also result.

Clinically, this process contributes to the majority of lower urinary tract symptoms in men. The long term clinical consequences of BPH are uncertain, as the natural history is poorly understood.

Imaging is not routinely performed for the evaluation of BPH, however, ultrasound and  MRI are useful. Determination of prostatic size may also be estimated using digital rectal examination As it is technically a histologic diagnosis, confirmation usually requires examination of tissue from biopsy, surgery or autopsy. The greatest impact of BPH is on quality of life, related to urinary symptoms, and thus severity is most usefully measured using the American Urological Association Symptom Index (AUASI), developed in 1992. This is a questionnaire of 7 questions pertaining to urinary symptoms, i.e. frequency, urgency, hesitancy. Alternatively, urinary flow rates, and measurements of Prostate Specific Antigen may be used as adjuncts.

Treatment may span from pharmacologic, such as androgen deprivation therapy, minimally invasive surgical therapy, and transurethral resection of the prostate (TURP). Medical therapy includes alpha adrenergic blockers that inhibit smooth muscle contraction and relax prostatic smooth muscle and smooth muscle of the bladder receptors causes relaxation of smooth muscles in the bladder neck and prostate.

Benign Prostatic Hyperplasia (BPH): Diagnosis

A general approach to evaluation of the prostate is that the first line of diagnosis is usually physical examination, via the digital rectal examination. An experienced practitioner can characterize the various zones, and their composition, in addition to a gross assessment of size, shape, and symmetry.

Prostate specific antigen levels is a blood test that aids in the diagnosis of prostate cancer.

The most important disease processes where imaging is used as an aid is in prostate cancer. Although no imaging modality is reliable in diagnosing or ruling out malignancy, imaging serves as an adjunct in the diagnosis and staging.

Biopsy is performed with ultrasound guidance. MR, usually with the aid of endorectal coils and transrectal ultrasound are useful in staging local disease.

Clinical Examination
A normal prostate gland feels smooth and “rubbery”. Abnormalities of the prostate felt on DRE are nodules, induration, bogginess or fluctuance.

Benign Prostatic Hyperplasia (BPH): Labs

Urine analysis to look for hematuria or signs of infection.
BUN and Creatinine level to look for ureteral obstruction.
PSA is controversial because it lacks specificity to detect prostate cancer, however in combination with a physical exam it is still the best test we have to screen for prostate cancer.
Voided sample after prostatic massage to look for prostatitis

Benign Prostatic Hyperplasia (BPH): Imaging

The most important disease processes where imaging is used as an aid is in prostate cancer. Although no imaging modality is reliable in diagnosing or ruling out malignancy, imaging serves as an adjunct in the diagnosis and staging.

Biopsy is performed with ultrasound guidance. MR, usually with the aid of endorectal coils and transrectal ultrasound are useful in staging local disease.

Finally CT and MR are useful in staging in the presence of nodal or distant metastases. PET-CT does not have a well-defined role in the evaluation of prostate cancer, as areas of disease do not typically have significantly elevated metabolic rates. CT is also useful in radiation treatment planning. T2-weighted endorectal MRI has the unique ability to consistently identify the zonal anatomy of the gland .

Bone scintigraphy is often useful for assessing the spread of prostate cancer to bony areas, usually within the axial skeleton.

Diseases: Conclusion

The prostate is a remarkable organ that is situated deep in the pelvis in a central location. Although it was identified and named by Herophilus (335BC -280BC) it was neglected and ignored for many centuries. With the aging population, this small, chestnut sized and chestnut shaped organ has become central to morbidity and mortality.

From a structural aspect, seminal work by Mcneal in 1988 enhanced the understanding of the embryology, histology, anatomy and disease of the gland. Functionally it is more than just an exocrine gland, since it acts as a mixing pot for the semen, inhibits backflow of the semen into the bladder, favors forward flow by opening the external sphincter, protects the sperm from acid environment of the vagina, participates in the emancipation of the sperm from its coagulated cocoon, and enhances the physical pleasure of the sexual acts… all tied up (and probably more) in this one chestnut shaped organ.

MRI has the ability to identify the zonal anatomy of the gland, but accurate and satisfying diagnosis and management of BPH and prostate cancer is elusive at this time. Many technical innovations have evolved recently including robotic surgery, but all challenged by real and potential pitfalls of removing the gland including incontinence, impotence and infertility.