A CASE FOR THE PROSTATIC SPECIFIC ANTIGEN (PSA) AS DIAGNOSTIC TOOL FOR PROSTATIC DISORDERS
ABSTRACT

Prostate-specific antigen (PSA), also known as gamma- seminoprotein or kallikrein-3 (KLK3), is a glycoprotein enzyme encoded in humans by the KLK3 gene. PSA is a member of the kallikrein-related peptidase family and is secreted by the epithelial cells of the prostate gland. PSA is produced for the ejaculate, where it liquefies semen in the seminal coagulum and allows sperm to swim freely. It is also believed to be instrumental in dissolving cervical mucus, allowing the entry of sperm into the uterus.  PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer or other prostate disorders.  PSA is not a unique indicator of prostate cancer, but may also detect prostatitis or benign prostatic hyperplasia. Only 30 percent of patients with high PSA have prostate cancer diagnosed after biopsy. PSA is normally present in the blood at very low levels. Increased levels of PSA may suggest the presence of prostate cancer. However, prostate cancer can also be present in the complete absence of an elevated PSA level, in which case the test result would be a false negative. PSA levels can be also increased by prostatitis, irritation, benign prostatic hyperplasia (BPH), and recent ejaculation, producing a false positive result. The normal reference ranges for prostate-specific antigen increase with age, as do the usual ranges in cancer
TABLE OF CONTENTS
CHAPTER ONE
1.0    INTRODUCTION    -    -    -    -    -    -    1
1.1    Description of the prostate    -    -    -        2
1.1.1 Structure of the prostate    -    -    -    -    -    4
1.2    Development of the prostate    -    -    -    -    8
1.3     Functions of the prostate    -    -    -    -    -    9
1.4    Regulation of the prostate     -    -    -    -    11

CHAPTER TWO
2.0    PROSTATITIS    -    -    -    -    -    -    -    12
2.1. Types of Prostatitis    -    -    -    -    -    -    12
2.2    Benign prostatic hyperplasia(BPH)     -    -    -    14
2.3    Prostate Cancer    -    -    -    -    -    -    16
2.3.1  Pathophysiology    -    -    -    -    -    -    18
2.3.2  Symptoms of prostate cancer    -    -    -    -    20
2.3.3 Risk factors    -    -    -    -    -    -    -    20

CHAPTER THREE
3.0    APPLICATIONS OF PROSTATE SPECIFIC
ANTIGEN (PSA) AS A DIAGNOSTIC TOOL    -    -    23
3.1 Medical Application     -    -    -        -    -    24
3.2 Histology of PSA    -    -    -    -    -    -    -    24
3.3 Mechanism of action of PSA    -    -    -    -    26
3.4 Biochemistry of PSA    -    -    -    -    -    -    27
3.5 Serum levels of PSA    -    -    -    -    -    -    28
3.6 Free PSA    -    -    -    -    -    -    -    -    29
3.7    Limitation of PSA as diagnostic tool    -    -    -    30


CHAPTER FOUR
4.0    ASSAY METHOD FOR SPECIFIC PROSTATE
ANTIGEN (PSA)    -    -    -    -    -    -    -    31
4.1  Summary and Explanation of the Test Procedure -    31    
4.3  Assay Procedure    -    -    -    -    -    -    33
4.4 Limitations of Test    -    -    -    -    -    -    34

CHAPTER FIVE
5.0    CONCLUSION AND RECOMMENDATION    -    -    36
5.1    Conclusion    -    -    -    -    -    -    -    36
5.2    Recommendation    -    -    -    -    -    -    38
References    -    -    -    -    -    -    -    39

CHAPTER ONE
1.0    INTRODUCTION
Prostatic disorder refers to any abnormality and disease that afflict the prostate gland in the male reproductive system. The prostate gland is dependent on the hormonal secretions of the testes for growth and development. When production of the male hormone (androgen) decreases, the prostate begins to degenerate. Boys who are castrated before reaching puberty do not develop an adult-sized or functioning prostate. Normally changes occur in the prostate as a man ages. Between the fourth and sixth decades there is atrophy of the smooth muscles and an increase in fibrous scar tissue, collagen fibres (protein strands), and numbers of lymph cells. When a man passes the age of 60 years, the organ is largely replaced by fibrous tissue (Myers, 2000).
      In men over the age of 60 years, enlargement (hyperplasia) of the prostate is relatively common. In the vast majority of cases it causes no symptomatic difficulties, though infection may occur, as may rupturing of blood vessels. Enlargement may cause compression of the urethra with progressive obstruction of the flow of urine, incomplete emptying, or inability to void; there may also be a constant dribbling of urine. The bladder is never totally emptied, the remaining urine becomes stagnant and infection sets in. The stagnant urine may cause the precipitation of stones in the bladder; the bladder muscle thickens to overcome this obstruction. If urine begins to back up in the kidney, progressive damage may ensue, which can lead to kidney failure and subsequent uremia (the toxic effects of kidney failure) (Myers, 2000).
1.1 Description of the prostate
The prostate is an exocrine gland of the male reproductive system, and exists directly under the bladder, in front of the rectum. An exocrine gland is one whose secretions end up outside the body e.g. prostate gland and sweat glands. It is approximately the size of a walnut.  The urethra - a tube that goes from the bladder to the end of the penis and carries urine and semen out of the body - goes through the prostate (Zeegers,2003).
There are thousands of tiny glands in the prostate - they all produce a fluid that forms part of the semen. This fluid also protects and nourishes the sperm. When a male has an orgasm the seminal-vesicles secrete a milky liquid in which the semen travels. The liquid is produced in the prostate gland, while the sperm is kept and produced in the testicles. When a male climaxes (has an orgasm), contractions force the prostate to secrete this fluid into the urethra and leave the body through the penis. The Prostate Produces Prostate-specific antigen (PSA). The epithelial cells in the prostate gland produce a protein called PSA (prostate-specific antigen) (Zeegers,2003). The PSA helps keep the semen in its liquid state. Some of the PSA escapes into the bloodstream. We can measure a man's PSA levels by checking his blood. If a man's levels of PSA are high, it might be an indication of either prostate cancer or some kind of prostate condition (Miller et al,2003).
 
Diagram of the location of the prostate gland and nearby organs (Miller et al,2003).
1.1.1 Structure of the prostate
A healthy human prostate is classically said to be slightly larger than a walnut. The mean weight of the normal prostate in adult males is about 11 grams, usually ranging between 7 and 16 grams. It surrounds the urethra just below the urinary bladder and can be felt during a rectal exam. The secretory epithelium is mainly pseudostratified, comprising tall columnar cells and basal cells which are supported by a fibroelastic stroma containing randomly orientated smooth muscle bundles. The epithelium is highly variable and areas of low cuboidal or squamous epithelium are also present, with transitional epithelium in the distal regions of the longer ducts. Within the prostate, the urethra coming from the bladder is called the prostatic urethra and merges with the two ejaculatory ducts. The prostate can be divided in two ways: by zone, or by lobe.  It does not have a capsule, rather an integral fibromuscular band surrounds it.  It is sheathed in the muscles of the pelvic floor, which contract during the ejaculatory process (Verhamme etal., 2002).
The zone classification is more often used in pathology. The idea of zones was first proposed by McNeal in 1968. McNeal found that the relatively homogeneous cut surface of an adult prostate in no way resembled lobes and thus led to the description of zones. The prostate gland has four distinct glandular regions, two of which arise from different segments of the prostatic urethra:
Table 1: – Structure/fractions of the prostate gland (Verhamme et al., 2002)
Name    Fraction of gland    Description
Peripheral zone (PZ)    Up to 70% in young men    The sub-capsular portion of the posterior aspect of the prostate gland that surrounds the distal urethra. It is from this portion of the gland that constitute 70–80% of prostatic cancers originate.

Central zone (CZ)    Approximately 25% normally    This zone surrounds the ejaculatory ducts. The central zone accounts for roughly 2.5% of prostate cancers although these cancers tend to be more aggressive and more likely to invade the seminal vesicles.
Transition zone (TZ)    5% at puberty    ~10–20% of prostate cancers originate in this zone. The transition zone surrounds the proximal urethra and is the region of the prostate gland that grows throughout life and is responsible for the disease of benign prostatic enlargement.

Anterior fibro-muscular zone (or stroma)    Approximately 5%    This zone is usually devoid of glandular components, and composed only, as its name suggests, of muscle and fibrous tissue.


 
Lobes
The lobe classification is more often used in anatomy.
Table 2:- Classification of Prostate lobes (Verhamme et al., 2002).
Anterior lobe (or isthmus)    roughly corresponds to part of transitional zone
Posterior lobe    roughly corresponds to peripheral zone
Lateral lobes    spans all zones
Median lobe (or middle lobe)    roughly corresponds to part of central zone

1.2    Development of the prostate
The prostatic part of the urethra develops from the pelvic (middle) part of the urogenital sinus (endodermal origin). Endodermal outgrowths arise from the prostatic part of the urethra and grow into the surrounding mesenchyme. The glandular epithelium of the prostate differentiates from these endodermal cells, and the associated mesenchyme differentiates into the dense stroma and the smooth muscle of the prostate. The prostate glands represent the modified wall of the proximal portion of the male urethra and arises by the 9th week of embryonic life in the development of the reproductive system. Condensation of mesenchyme, urethra and Wolffian ducts gives rise to the adult prostate gland, a composite organ made up of several glandular and non-glandular components tightly fused (Verhamme etal., 2002).
1.3 Functions of the prostate
The function of the prostate is to secrete a slightly alkaline fluid, milky or white in appearance, that usually constitutes 50–75% of the volume of the semen along with spermatozoa and seminal vesicle fluid.  Semen is made alkaline overall with the secretions from the other contributing glands, including, at least, the seminal vesicle fluid. The alkalinity of semen helps neutralize the acidity of the vaginal tract, prolonging the lifespan of sperm. The alkalinization of semen is primarily accomplished through secretion from the seminal vesicles. The prostatic fluid is expelled in the first ejaculate fractions, together with most of the spermatozoa. In comparison with the few spermatozoa expelled together with mainly seminal vesicular fluid, those expelled in prostatic fluid have better motility, longer survival and better protection of the genetic material. The prostate also contains some smooth muscles that help expel semen during ejaculation (Anderson etal.,2006).
During male ejaculation, sperm is transmitted from the ductus deferens into the male urethra via the ejaculatory ducts, which lie within the prostate gland. It is possible for men to achieve orgasm solely through stimulation of the prostate gland, such as prostate massage or receptive anal intercourse.
Secretions
Prostatic secretions vary among species. They are generally composed of simple sugars and are often slightly acidic. In human prostatic secretions, the protein content is less than 1% and includes proteolytic enzymes, prostatic acid phosphatase, beta-microseminoprotein, and prostate-specific antigen. The secretions also contain zinc with a concentration 500–1,000 times the concentration in blood (Verhamme etal., 2002).
1.4    Regulation of the prostate
To function properly, the prostate needs male hormones (testosterones), which are responsible for male sex characteristics. The main male hormone is testosterone, which is produced mainly by the testicles. Some male hormones are produced in small amounts by the adrenal glands. However, it is dihydrotestosterone that regulates the prostate (Verhamme etal.,2002).