Description
CHAPTER ONE
INTRODUCTION
This project is on Biochemical changes associated with benign prostatic hyperplasia (BPH) in ageing men attending clinic at university of Nigeria teaching hospital (UNTH), ituku-ozalla, Enugu state of Nigeria.
Benign prostatic hyperplasia (BPH) is the nonmalignant enlargement of the prostate gland. It refers to stromal and glandular epithelial hyperplasia that occurs in the periurethral transition zone of the prostate that surrounds the urethra. BPH clinically manifest as lower urinary tract symptoms (LUTS) consisting of irritative (urgency, frequency, nocturia) and obstructive symptoms (hesitancy, a weak and interrupted urinary stream, straining to initiate urination, a sensation of incomplete bladder emptying) (Miller and Tarter, 2009). Prolonged obstructions may eventually lead to acute urinary retention (AUR), recurrent urinary tract infection (UTI), hematuria, bladder calculi, and renal insufficiency (Curtis, 2006). The prevalence of LUTS due to BPH increases with increasing age. Moderate to severe symptoms occur in 40 and 80% of men after the age 60 and by 80 years, respectively. Nearly all men develop microscopic BPH by the age of 90 years (Ogunbiyi and Shittu, 1999). It is also described as quality of life disorder, affecting man’s ability to initiate or terminate urine flow stream (the symptoms interfere with the normal activities), and reduces the feeling of well being. The causes of BPH are not fully known, but the overgrowth of smooth muscle tissue and glandular epithelial tissue is attributed to a number of different causes such as aging, late activation of cell growth, genetic factors, and hormonal changes (Wang and Jicun, 2015).
- Epidemiology
Benign prostatic hyperplasia (BPH) is a histological diagnosis associated with unregulated proliferation of connective tissue, smooth muscle and glandular epithelium within the prostatic transition zone (Auffenberg et al., 2009). Prostate tissue is composed of two basic elements: A glandular element composed of secretory ducts and acini; and a stromal element composed primarily of collagen and smooth muscle. In BPH, cellular proliferation leads to increased prostate volume and increased stromal smooth muscle tone. McNeal, (1984) describes two phases of BPH progression. The first phase consists of an increase in BPH nodules in the periurethral zone and the second a significant increase in size of glandular nodules (McNeal, 1984).
BPH may cause physical compression of the urethra and result in anatomic bladder outlet obstruction (BOO) through two distinct mechanisms: First, an increase in prostate volume, termed the static component; second, an increase in stromal smooth muscle tone, termed the dynamic component (McVary, 2006). BOO, in turn, may present clinically as lower urinary tract symptoms (LUTS), urinary tract infections, acute urinary retention (AUR), renal failure hematuria, and bladder calculi (Stroup et al., 2012).
Notably, two factors complicate the natural history and clinical presentation of BPH, BOO and LUTS; first, prostate volume does not linearly correlate with the severity of BOO or LUTS; and second, progressive BPH and BOO can lead to primary bladder dysfunction, which in turn can exacerbate the severity of LUTS independently of BOO(McVary, 2006). Collectively, BPH, BOO and LUTS are associated with increased risks of mortality, depression, falls and diminished health-related quality-of-life as well as with billions of US dollars in annual health expenditures (Tailor et al., 2006).
In the last decade, epidemiological models of BPH and BOO have evolved substantially. Although age and genetics play important roles in the etiology of BPH and BOO, recent data have revealed novel, modifiable risk factors that present new opportunities for treatment and prevention. These risk factors appear to potentially influence the natural history of BPH and BOO throughout the different stages of clinical progression (Tailor et al., 2006).
- Prostate Anatomy and Histology
The human prostate is a compact walnut-sized musculo–glandular organ in contact with the inferior surface of the bladder, weighs about 20 gm in adult males and forms part of the males’ reproductive system. The gland is made up of two lobes or region, enclosed by an outer layer of tissue and is located in front of the rectum and just below the bladder. It also surrounds the urethra (Leissner and Tisell, 1979).
“The prostate gland is dependent on the hormonal se cretion of the testes for growth and development (Ball and Risbridger, 2003). The prostate growth accelerates at sexual maturity due to androgen action on both stromal and epithelia cells (Verhamme et al., 2002). Between the ages of 31 and 50 years the prostate doubles in size every 4-5 years. Between 51 and 70 years doubling time increased to 10 years and over 70 it reaches 100 years. In other words, after the age of 70 years the prostate may have almost attained its possible maximum size (Verhamme et al., 2002).
The human prostate is divided into three anatomically distinct-zones: peripheral, transitional and central zones which are surrounded by a dense and continue fibro-muscular stroma (McNeal, 1984). BPH, a non malignant overgrowth found in older men mainly develop in the transitional zone while prostate cancer (PCA) arises primarily in the peripheral zone (Abate and Shen, 2000). At histological level human prostate contains mainly two types of cell that are called epithelial and stroma cells and in ratio of 2:1 in human (Mayers and Robert, 2000). The epithelial cell layer is composed of four differential cell types known as basal, secretary, luminal neuroendocrine (NE) and transitional amplifying cells that are identified by their morphology, location and distinct marker expression. The basal cells form a layer of flattened to cuboidal shaped cells above the basement membrane and express p63, a homology of tumor suppressor genes (p53), an antiapoptic factor, cluster designation (CD44), hepatocytes growth factor (HGF) and higher molecular weight cytokeratins (CK5and14) (Mayers and Robert, 2000). The expression of androgen receptor (AR) is lower or undetectable in the basal cells which makes the basal cell independent of androgens for their survival (Mayers and Robert, 2000). The Lumina cells are the major cell types of prostate that form a layer of columnar – shaped cells above the basal layer and constitute the exocrine compartment of the prostate, secreting prostate- specific antigen (PSA) and prostatic acid phosphatase (pap) into the lumen. They are terminally differentiated and is not androgen dependant and non proliferating cells expressing low molecular weight CK8 and 18, CD 57 and P27kipl (a cell cycling inhibitor). Neuroendocrine cells are rare cells scattered in the basal and Lumina layer of the prostate and terminally differentiated and is not androgen insensitive cells, expressing chromogranin A, synaptophysin and Neuro-specific enolase (NSE). Additionally, there is small group of intermediate cells referred to as transitional amplifying cells (TA) that express both basal as well as luminal cell markers and PSA (Ball and Risbridger,2003). The epithelial layer is surrounded by a stromal layer, which forms a peripheral boundary of the prostate gland. The stromal cell layer consist of several types of cell that include smooth muscle cells, (the most abundant cell type in stromal) fibroblasts and myofibroblasts. The stromal cells express mesenchymal markers such as CD34, CD44, CD117 and CD90 (McNeal, 1984). Prostate epithelium is structurally and functionally, a highly complex tissue composed of multiple differentiated cell types, including basal, luminal and neuroendocrine cells with small population of relatively undifferentiated cells generally known stem cells that are endowed with self renewal and differentiation (Pece et al., 2010).
- Functions of the Prostate
The prostate makes some of the fluid for semen, may keep urine out of the semen probably because of presence of the internal urethral sphincter complex within the prostate gland (Rosenthia, 2012). The prostate gland secretion contain, milky fluid that contains calcium citrate, phosphate ion, a clothing enzyme and profibrinolysin. During emission, the capsule of the prostate gland contract simultaneously with the contraction of the vas deference so that the thin milky fluid of the prostate add further to the bulk of the semen which may be slightly alkaline. The alkaline nature of this semen is quite important for successful fertilization of the ovum (De Jong et al., 2014). The fluid of the vas deference is relatively acidic owing to the presence of citric acid and metabolic end product of the sperms and consequently, help to inhibit sperm fertility and probably the slightly alkaline prostatic fluids help to neutralize the acidity of the seminal fluids during ejaculation and thus enhance the motility and fertility of the sperm. The prostatic fluid also contains prostatic specific antigen (PSA) which liquefies semen in seminal coagulum and allows sperm to swim freely (Morgan et al., 2011). The fluid also contains some metals such as magnesium, zinc, calcium, selenium which are needed for prostate function (Morgan et al., 2012).