Pathophysiology

By J. Garcia

Normal Physiology

McCance, Huether, Brashers, & Rote (2019) states the prostate with the other glands in the male internal genitalia are responsible for secreting nutritious alkaline fluids for survival, motility and vehicular transport of sperms. The prostate gland is about the size of a walnut with three zones (peripheral, central, transition) and surrounds the urethra. It is situated in the middle of the bladder and penis, in front of the rectum, and the urethra runs through the center of it from the urinary bladder to the penis where urine flows out.  It comprises of glandular alveoli and ducts that are fixed in fibromuscular tissue. Its growth, development, and function are regulated by androgens and the androgen receptor. Prostate-specific antigen (PSA), cytokeratins, prostate-specific membrane antigen (PSMA),  and prostate-specific acid phosphatase are prostate epithelial secretions that are part of the ejaculate.

(Benign Prostatic Hyperplasia. n.d. Retrieved October 24, 2019)

Altered Physiology of Benign Prostatic Hypertrophy

One alteration of the prostate gland presented by McCance, et. al. (2019) is that of benign prostatic hypertrophy (BPH).  BPH is prostatic enlargement due to hyperplasia. Thus, benign prostatic hyperplasia is the preferred term. Prostatic enlargement is due to nodular hyperplasia and glandular cells hypertrophy that affect the transition zone. As a result of the enlargement, compression of the urethra results in a spectrum of lower urinary tract symptoms (LUTSs). BPH prevalence among men in the United States occurs to 60 years and older for about 50% and men 70 years and older is 90%. BPH begins around 40 to 45 years of age and slowly continues until death.

Current Multifactorial Causative Theories of BPH involve the following (McCance, et. al., 2019):

  1. Levels and Ratios of Endocrine Factors – androgens, estrogens, gonadotropins, prolactin
    • Androgens-disrupts balance of growth factor signaling pathways and stromal/epithelial interactions create growth-promoting and tissue remodeling microenvironment
    • Estrogen-testosterone (primary circulating male androgen) metabolized through CYP19/Aromatase into potent estrogen (estradiol-17B) affects directly/indirectly the growth and differentiation of the prostate. Estrogen and selective estrogen receptor modulators promote or inhibit prostate proliferation.
  2. Changes in the balance between Autocrine/Paracrine growth-stimulatory and growth-inhibitory factors – insulin-like growth factors (IGF),  epidermal growth factor, nerve growth factor, fibroblast factor, IGF binding proteins, transforming growth factor-beta (TGF-B)
  3. Dihydrotestosterone (DHT) – necessary for normal prostatic development; its role for BPH unclear
    • 5 alpha-reductase (most powerful among androgen metabolizing enzyme in the prostate) correlates positively with DHT
    • 5 alpha-reductase and DHT decreases with age in the epithelium
    • Both remain relatively constant in the stroma of the prostate gland.
  4. Relationship with Aging and Prostate Enlargement
    • At birth, the prostate is pea-size.
    • Until puberty, the prostate has gradual growth.
    • In the third decade of life, the prostate has rapid development to adult size.
    • At 40 to 45 years old, benign hyperplasia of the prostate continues slowly until death.
  5. Remodeled Microenvironment 

The interactions of the above cause an increased volume of the prostate. All these interactions result in the newly remodeled stroma that promotes local inflammation. The enlarging prostate is characterized by the formation and growth of nodules (nodular hyperplasia) and glandular cells increasing in size (hypertrophy).  Eventually, prostatic tissues compress the urethra.

Clinical Manifestations of BPH (McCance, et. al., 2019)

Urethral compression manifests a spectrum of lower urinary tract symptoms (LUTSs). Initially, urinary urgency, urination initiation delay, and reduction in urinary stream force happen. After several years, bladder emptying challenges set in with increased volume that leads to long term urinary retention. Over a long period,  volume causes uncontrolled outflow incontinence with increase intraabdominal pressure, significant decrease force of urinary stream and increase time to initiate and complete voiding. Unresolved BPH then results in complications such as hematuria, bladder or kidney infection, bladder calculi, acute urinary retention (hydroureter), hydronephrosis, and renal insufficiency may result if left untreated.

Evaluation of BPH (McCance, et. al., 2019)

  1. Medical History
  2. Physical Examination
    • Digital Rectal Examination (DRE) is performed to determine hyperplasia. DRE is annually indicated for males 40 years old and above or sooner for high-risk men. DRE findings in BPH show a soft or firm enlargement, with smooth mucosal surface, no discernible distinction between lobes and asymmetry which is common. These findings do not always reflect the degree of BPH since a substantial portion of enlargement is intravesicular.
  3. Laboratory Tests
    • Prostate-Specific Antigen (PSA) may be increased in BPH and Prostate Cancer
    • Urinalysis – serum creatinine, BUN levels, uroflowmetry, post-void residual (PVR) urine, pressure flow study, cystometry, cystourethroscopy
  4. Procedure – Transrectal ultrasound (TRUS) is performed to determine bladder and prostate volume and residual urine.

Treatments of BPH (McCance, et. al., 2019)

  1. Medications
    • Alpha-adrenergic blockers (Prazosin and Tamsulosin) relax the smooth muscle of the bladder and prostate. These do not affect the PSA level and no effect on cancer risk.
    • Antiandrogen agents (Finasteride or Proscar) selectively block androgens at the prostate cellular level and cause it to shrink. These improve BPH related symptoms and reduces urinary retention symptoms as well as BPH related surgery.
  2. Minimally Invasive Procedures is where the hyperplastic tissue is removed to prevent urethral obstruction.
    • Interstitial laser therapy
    • Transurethral radiofrequency procedures (TUNA)
    • Cooled thermotherapy
    • Prostate artery embolization
  3.  Genetics
    • Techniques in genomics, proteomics, epigenetics, the discovery of aberrant signaling pathways, novel biomarkers, DNA methylation signatures, and potential gene-specific targets to address BPH are available.
  4. Permanent Indwelling Catheter is inserted if the patient is unable to tolerate surgery.