CHAPTER II BPH

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CHAPTER II

LITERATURE

2.1 ANATOMY AND PHYSIOLOGY OF PROSTATE GLAND2.1.1 Anatomy Prostate Gland

The prostate is a fibromuscular and glandular organ lying just inferior

to the bladder. The normal prostate weighs about 25 g and contains the

posterior urethra, which is about 2.5 cm in length. It is supported anteriorly

by the puboprostatic ligaments and inferiorly by the urogenital diaphragm.

The prostate is perforated posteriorly by the ejaculatory ducts, which pass

obliquely to empty through the verumontanum on the floor of the prostatic

urethra just proximal to the striated external urinary sphincter.

According to the classification of Lowsley, the prostate consists of 5

lobes: anterior, posterior, median, right lateral, and left lateral. According to

McNeal (1972), the prostate has a peripheral zone, a centralzone, and a

transitional zone, an anterior segment, and a preprostatic sphincteric zone.

Fig 1. Anatomy of the prostate gland and surrounding structures.

Zonal model of the prostate


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Fig 2. Anatomy of the prostate gland and surrounding structures. Fascial

planes around the prostate. A, artery; AFS, anterior fibromuscular stroma;

CZ, central zone; ED, ejaculatory duct; N, nerve; PZ, peripheral zone; TZ,

transition zone; U, urethra; V, vein.

The urethra that traverses the prostate gland is the prostatic urethra. It

is lined by an inner longitudinal layer of muscle (continuous with a similar

layer of the vesical wall). Incorporated within the prostate gland is an

abundant amount of smooth musculature derived primarily from the

external longitudinal bladder musculature. This musculature represents the

true smooth involuntary sphincter of the posterior urethra in males.

The prostate consists of a thin fibrous capsule under which are

circularly oriented smooth muscle fibers and collagenous tissue that

surrounds the urethra (involuntary sphincter). Deep in this layer lies the

prostatic stroma, composed of connective and elastic tissues and smooth

muscle fibers 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 the transitional epithelium of the prostatic urethra

lie the periurethral glands.


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The prostate gland receives arterial supply from the inferior vesical,

internal pudendal, and middle rectal (hemorrhoidal) arteries. The veins

from the prostate drain into the periprostatic plexus, which has connections

with the deep dorsal vein of the penis and the internal iliac (hypogastric)

veins. The prostate gland receives a rich nerve supply from the sympathetic

and parasympathetic nerve plexuses. The lymphatics from the prostate

drain into the internal iliac (hypogastric), sacral, vesical, and external iliac

lymph nodes.

2.1.2 Physiology Prostate GlandSecretions of the prostate gland is a milky fluid that together

secretions from the seminal vesicles are a major component of semen.

Semen contains citric acid so that a slightly acidic pH (6.5). Moreover, it

can be found fibrinolysin enzymes that act as a strong, acid phosphates,

other enzymes and lipids. Prostatic secretions released during ejaculation

through the contraction of smooth muscle.

2.2 BENIGN PROSTATE HYPERPLASIA2.2.1 Epidemiology

BPH is the most common benign tumor in men, and its incidence is age-

related. The prevalence of histologic BPH in autopsy studies rises from

approximately 20% in men aged 41-50, to 50% in men aged 51-60, and to

over 90% in men older than 80. Although clinical evidence of disease

occurs less commonly, symptoms of prostatic obstruction are also age-

related. At age 55, approximately 25% of men report obstructive voiding

symptoms. At age 75, 50% of men complain of a decrease in the force and

caliber of their urinary stream.

2.2.2 EtiologyThe etiology of BPH is not completely understood, but it seems to

be multifactorial and endocrine controlled. The prostate is composed of


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both stromal and epithelial elements, and each, either alone or in

combination, can give rise to hyperplastic nodules and the symptoms

associated with BPH..

Some theories or hypotheses are suspected as the cause of prostatic

hyperplasia are:

1. Dihydrotestosterone

Testosterone is produced by the Leydig cells of the testis (90%) and a

portion of the adrenal gland (10%) in the blood circulation and 98% will

be bound by sex hormone binding globulin to globulin (SHBG). Being

only 2% in a state of free testosterone. Free testosterone is what can get

into the "target cell" that prostate cells directly through the cell

membrane into the cytoplasm, the cell, testosterone is reduced by the

enzyme 5-alpha reductase into 5-dihydrotestosterone were then met with

cytoplasmic receptors become "hormone receptor complex". Then

"hormone receptor complex" is undergoing transformation receptors, a

"nuclear receptor" that went into the core which is then attached to the

chromatin and lead to m-RNA transcription. RNA will cause protein

synthesis result in the growth of the prostate gland. This theory was

proven that the castration before puberty do not happen BPH, also the

regression of BPH when done castration.

2. Estrogen-testosterone imbalance

In addition to androgens (testosterone / DHT), estrogen also contributes

to the occurrence of BPH. With age will change the hormonal balance,

which is between testosterone and estrogen, as testosterone production

decreases and the conversion of testosterone to estrogen in peripheral

adipose tissue with the help of the enzyme aromatase, which is the

nature of estrogen will stimulate hyperplasia of the stroma, causing

notion that testosterone is necessary for the initiation of cell proliferation

but then estrogen which contribute to the development of the stroma.

Another possibility is that changes in the relative concentrations of


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testosterone and estrogen will cause the production and potentiation of

other growth factors that can lead to an enlarged prostate.

From various experimental and clinical findings concluded that under

normal circumstances would cause the pituitary gonadotropin production

of testicular androgens that will control the growth of the prostate. With

increasing age, there will be a decrease of testicular function

(spermatogenesis), which will lead to a progressive decline of androgen

secretion. This result will greatly stimulate gonadothropin hormone

estrogen production by the Sertoli cells. While the views of the

functional histological, prostate consists of two parts, namely a central

around the urethra that reacts to estrogen and peripheral parts that do not

respond to estrogen.

3. Interaction stroma- epitel

This theory is based on the interaction between the elements of prostate

stromal and epithelial elements that cause prostate hyperplasia. The

growth factor was made by stromal cells under the influence of

androgens. The existence of over-expression of the epidermal growth

factor (EGF) and or fibroblast growth factor (FGF) and or a decrease in

the expression of transforming growth factor- (TGF-) will cause an

imbalance of prostate growth and produce an enlarged prostate.

4. Decrease in cell death

The aging process can lead to blockade the process of maturation in stem

cells, prevent them from entering the stage of programmed cell death

(apoptosis). As a result of the aging process in animal studies appears to

be mediated through the estrogen synergism induces androgen receptor,

steroi disrupt metabolism, resulting in increased levels of DHT in the

prostate that inhibit cell death when given in conjunction with androgen

nd poduksi stimulate collagen stroma.

5. Stem Cell Theory (stem cell hypothesis)

As in other organs, prostate gland periuretral in this case in an adult is in

a state of equilibrium "steady state", between cell growth and cell death,


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the balance is due to the presence of certain levels of testosterone in the

prostate tissue that can affect the stem cells that can proliferate. In

certain circumstances the number of stem cells can be increased resulting

in more rapid proliferation. Abnormal stem cell proliferation leading to

the production or proliferation of stromal cells and epithelial cells

periuretral prostate gland becomes redundant.

2.2.3 PathophysiologyOne can relate the symptoms of BPH to either the obstructive

component of the prostate or the secondary response of the bladder to the

outlet resistance. The obstructive component can be subdivided into the

mechanical and the dynamic obstruction.

As prostatic enlargement occurs, mechanical obstruction may

result from intrusion into the urethral lumen or bladder neck, leading to a

higher bladder outlet resistance. Prior to the zonal classification of the

prostate, urologists often referred to the "3 lobes" of the prostate, namely,

the median and the two lateral lobes. Prostatic size on digital rectal

examination (DRE) correlates poorly with symptoms, in part because the

median lobe is not readily palpable.

The dynamic component of prostatic obstruction explains the

variable nature of the symptoms experienced by patients. The prostatic

stroma, composed of smooth muscle and collagen, is rich in adrenergic

nerve supply. The level of autonomic stimulation thus sets a tone to the

prostatic urethra. Use of alpha-blocker therapy decreases this tone,

resulting in a decrease in outlet resistance.

The irritative voiding complaints of BPH result from the

secondary response of the bladder to the increased outlet resistance.

Bladder outlet obstruction leads to detrusor muscle hypertrophy and

hyperplasia as well as collagen deposition. Although the latter is most

likely responsible for a decrease in bladder compliance, detrusor

instability is also a factor. On gross inspection, thickened detrusor muscle


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bundles are seen as trabeculation on cystoscopic examination. If left

unchecked, mucosal herniation between detrusor muscle bundles ensues,

causing diverticula formation (so-called false diverticula composed of

only mucosa and serosa).

2.2.4 Clinical FindingsSymptoms

The symptoms of BPH can be divided into obstructive and

irritative complaints. Obstructive symptoms include hesitancy, decreased

force and caliber of stream, sensation of incomplete bladder emptying,

double voiding (urinating a second time within 2 hour of the previous

void), straining to urinate, and post-void dribbling. Irritative symptoms

include urgency, frequency, and nocturia.

The self-administered questionnaire developed by the American

Urological Association (AUA) is both valid and reliable in identifying the

need to treat patients and in monitoring their response to therapy. The

AUA Symptom Score questionnaire is perhaps the single most important

tool used in the evaluation of patients with BPH and is recommended for

all patients before the initiation of therapy.


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Fig 4. The AUA Symptom Score questionnaire

This assessment focuses on 7 items that ask patients to quantify the

severity of their obstructive or irritative complaints on a scale of 0-5. Thus,

the score can range from 0 to 35. A symptom score of 0-7 is considered

mild, 8-19 is considered moderate, and 20-35 is considered severe.

Physical Examination

Digital Rectal Examination (DRE) is examination to determine the

size and consistency of the prostate is noted, even though prostate size.

BPH usually results in a smooth, firm, elastic enlargement of the prostate.

Induration, if detected, must alert the physician to the possibility of cancer

and the need for further evaluation.


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On physical examination, when upper urinary tract abnormalities

occurs sometimes kidney may be palpable and when pyelonefritis happens

it will be accompanied by pain and percussion pain on the waist.

Gallbladder may be palpable urinary retention occur when it is total, the

inguinal area should begin to be considered to determine the hernia.

External genitalia should also be checked to see if there are other possible

causes that can lead to micturition disorders such as stones or urethral

fossa navicularis anterior, urethral fibrosis area, phimosis, condiloma

meatus area.

Laboratory Findings

A urinalysis to exclude infection or hematuria and serum creatinine

measurement to assess renal function are required. BSS to find possibility

of diabetes that can cause neurological gallbladder. Serum PSA is

considered optional, if suspicious of carcinoma prostate.

Imaging

a. Plain abdominal (BNO)

This examination use to look for the opaque stones in the urinary tract,

the presence of stones and sometimes may show a shadow of

gallbladder that filled with urine which is the sign of a urinary retention.

And also to know presence of bone metastases of prostate carcinoma.

b. Pyelography Intravenous (IVP)

Enlargement of the prostate can be seen as a filling defect / prostate

indentation at the base of the bladder or ureter distal end turned up

shaped like the eye of the hook (hooked fish). Can also be aware of any

abnormalities in the kidneys or ureters or hydronephrosis hidroureter

form and complications (trabeculation or diverticular). Photos after

micturition residual urine can be seen there.

c. Ultrasonography


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Ultrasound can be either trans abdominal or trans rectal. Its use to find

an enlarged prostate, this examination can also determine abnormalities

in the bladder (mass, stone, blood clot), measuring residual urine and

kidney damage caused by prostatic obstruction. In TRUS prostate

malignancy likely hypoechoic area.

2.2.5 Differential DiagnosisOther obstructive conditions of the lower urinary tract, such as

urethral stricture, bladder neck contracture, bladder stone, or prostate

cancer must be entertained when evaluating men with presumptive BPH. A

history of previous urethral instrumentation, urethritis, or trauma should be

elucidated to exclude urethral stricture or bladder neck contracture.

Hematuria and pain are commonly associated with bladder stones. Prostate

cancer may be detected by abnormalities on the DRE or an elevated PSA.

A urinary tract infection, which can mimic the irritative symptoms

of BPH, can be readily identified by urinalysis and culture. However, a

urinary tract infection can also be a complication of BPH. Although

irritative voiding complaints are also associated with carcinoma of the

bladder, especially carcinoma in situ, the urinalysis usually shows evidence

of hematuria. Likewise, patients with neurogenic bladder disorders may

have many of the signs and symptoms of BPH, but a history of neurologic

disease, stroke, diabetes mellitus, or back injury may be present as well. In

addition, examination may show diminished perineal or lower extremity

sensation or alterations in rectal sphincter tone or the bulbocavernosus

reflex. Simultaneous alterations in bowel function (constipation) might also

alert one to the possibility of a neurologic origin.

2.2.6 TreatmentAfter patients have been evaluated, they should be informed of the

various therapeutic options for BPH. Specific treatment recommendations

can be offered for certain groups of patients. For those with mild symptoms


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(symptom score 0-7), watchful waiting only is advised. On the other end of

the therapeutic spectrum, absolute surgical indications include refractory

urinary retention (failing at least one attempt at catheter removal), recurrent

urinary tract infection from BPH, recurrent gross hematuria from BPH,

bladder stones from BPH, renal insufficiency from BPH, or large bladder

diverticula (McConnell et al, 1994).

A. Watchful Waiting

As mentioned above, watchful waiting is the appropriate management of

men with mild symptom scores (0-7). Men with moderate or severe

symptoms can also be managed in this fashion if they so choose. Neither

the optimal interval for follow-up nor specific endpoints for intervention

have been defined.

B. Medical Therapy

1. Alpha blockers

The human prostate and bladder base contains alpha-1-

adrenoreceptors, and the prostate shows a contractile response to

corresponding agonists. The contractile properties of the prostate and

bladder neck seem to be mediated primarily by the subtype a1a

receptors. Alpha blockade has been shown to result in both objective and

subjective degrees of improvement in the symptoms and signs of BPH in

some patients. Examples of alpha inhibition include prazosin, terazosin,

doxazosin and newer tamslosin (selective blockade of receptors 1a).

Side effects include hypotension APHA inhibitors ortostatik, dizziness,

fatigue, retrograde ejaculation, rhinitis and headache. This side effect is

less on the use of a more selective inhibition 1a.

2. 5a-Reductase inhibitors

This drug is a 5a-reductase inhibitor that blocks the conversion of

testosterone to dihydrotestosterone. This drug affects the epithelial


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component of the prostate, resulting in a reduction in the size of the

gland and improvement in symptoms. Six months of therapy are required

to see the maximum effects on prostate size (28% reduction) and

symptomatic improvement. Side effects include decreased libido,

decreased ejaculate volume and impotence.

3. Phytotherapy

Phytotherapy refers to the use of plants or plant extracts for medicinal

purposes. The use of phytotherapy in BPH has been popular in Europe

for years, and its use in the United States is growing as a result of

patient-driven enthusiasm. Several plant extracts have been popularized,

including the saw palmetto berry, the bark of Pygeum africanum, the

roots of Echinacea purpurea and Hypoxis rooperi, pollen extract, and the

leaves of the trembling poplar. The mechanisms of action of these

phytotherapies are unknown, and the efficacy and safety of these agents

have not been tested in multicenter, randomized, double-blind, placebo-

controlled studies.

C. Conventional Surgical Therapy

1. Transurethral Resection of The Prostate (TURP)

Ninety-five percent of simple prostatectomies can be done

endoscopically. Most of these procedures involve the use of a spinal

anesthetic and require 1 to 2 day hospital stay. Risks of TURP include

retrograde ejaculation (75%), impotence (5-10%), and incontinence (

CHAPTER II BPH

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