Case 1 Explaination

Difficult terms:

IPSS:  the international prostate symptom score is an 8 question (7 symptom questions and 1 quality of life question) written screening tool used to screen for, rapidly diagnose, track the symptoms of and suggest management of the symptoms of the disease benign prostatic hyperplasia (BPH).

Serum PSA: prostate specific antigen. Also known as gamma-seminoprotein or kallikrein-3 (KLK3), is a glycoprotein enzyme encoded in humans by the KLK3 gene. 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.

UFM report: Uroflowmetry is a simple, diagnostic screening procedure used to calculate the flow rate of urine over time. The test is noninvasive (the skin is not pierced), and may be used to assess bladder and sphincter function.

Phenomena:

Male of 65 years of age: majority of men develop BPH as they age. . By age 60, 50% of men will have some signs of BPH. By age 85, 90% of men will have signs of the condition. About one third of these men will develop symptoms that require treatment.

Complain of going to the toilet at least 8 times a day:  this is a symptom of a probable prostate enlargement in this case benign prostatic hyperplasia. The urethra passes through the prostate and enlargement of the prostate leads to constriction of the urethra thus incomplete emptying of the bladder which in turn increases the frequency of urination.

Nocturia: in BPH since the bladder never empties completely thus nocturia can result in recumbent position. Also during sleep as the CNS control over the bladder weaken this causes an increased urgency to urinate at night leading to nocturia.

Dribbling weak stream for past few months: An enlarged prostate applies pressure and squeezes the urethra, which is the tube that leads from the bladder, down the penis, and out of the body. The compression of the urethra alters the flow of urine out of the body. Men may experience difficulty when they attempt to urinate, dribbling during urination, a weak urine stream and urgency, as well as an increased frequency in urination.

No history of renal stones or urethral instrumentations: this means that the symptoms are not related to a past history of kidney problems. Also no instrumentation of the urethra means that the symptoms are not a result of damage to the urethra.

IPSS of 21: in IPSS 8 questions (7 symptom questions and 1 quality of life question) are asked. The 7 symptoms questions include feeling of incomplete bladder emptying, frequency, intermittency, urgency, weak stream, straining and nocturia, each referring to during the last month, and each involving assignment of a score from 1 to 5 for a total of maximum 35 points. The 8th question of quality of life is assigned a score of 1 to 6.

IPSS result of 7 symptoms questions Score   Correlation

0-7       Mildly symptomatic

8-19     Moderately symptomatic

20-35   Severely symptomatic

GPE:

Height 5.8:             the BMI of this patient is 26.81.

Weight 80kg:         the patient is overweight.

BP: 130/80: normal.

R/R 30:  high.

Pulse : normal

Temp: normal

FBS: 80mg/dl: normal range is 70 to 100. FBS is done to rule out diabetes. In diabetes, the body has an increased thirst for fluids, which produces a great deal of urine throughout the day and evening. The bladder deals with the fluid over load by emptying at night as well, causing frequent disruptions in sleep. But here as FBS is normal thus diabetes is ruled out.

UCE:

Urea: 20mg/dl: normal value is 10 tp 20 mg/dl.

S.Creatinine: 1mg/dl: 0.6 to 1.2 mg/dl.

Na: 135mEq/l: 135 to 145 mEq/l.

K: 3.5 mEq/l: 3.5 to 5 mEq/l.

Cl: 103 mEq/l: 98 to 108 mEq/l

Urine D/R:

Specific gravity: 1.025: 1.002 to 1.035.

pH: 6.1: 6 to 7.

Pus cells: 1-2/hpf: normally no pus cells should be present.

RBCs : nil:  normal

Serum PSA: 4 ng/ml: less than 4ng/ml is considered normal. elevated levels point towards prostatitis, BPH and prostate cancer.

DRE: digital rectal exam is important, both to help rule out prostate cancer (a smooth prostate accessible by rectal examination is less likely to be cancerous than one with hard nodules and irregularities) and to determine the size of the prostate. Classification of the prostate size as “normal,” “big,” and “very big” can help determine therapy.

Ultrasound pre and post void volume: a post void residual baldder volume of less than 80 ml is considered normal.

Ultrasound prostate: Ultrasound has become the standard first line investigation after the urologist's finger. Typically there is an increase in volume of the prostate with a calculated volume exceeding 30cc ( (A x B x C)/2 ). The central gland is enlarged, and is hypoechoic or of mixed echogenicity. Calcification can be seen both within the hypertrophied gland as well as in the pseudocapsule (representing compressed peripheral zone).

Decrease fluid intake at night: in order to decrease nocturia.

UFM report: Uroflowmetry is performed by having a person urinate into a special funnel that is connected to a measuring instrument. The measuring instrument calculates the amount of urine, rate of flow in seconds, and length of time until completion of the void. This information is converted into a graph and interpreted by a physician. The information helps evaluate function of the lower urinary tract or help determine if there is an obstruction of normal urine outflow.

During normal urination, the initial urine stream starts slowly but almost immediately speeds up until the bladder is nearly empty. The urine flow then slows again until the bladder is empty. In persons with a urinary tract obstruction, this pattern of flow is altered, and increases and decreases more gradually. The uroflowmeter graphs this information, taking into account the person’s gender and age.

Pathology:

Benign protatic hypertrophy a time honored synonym for the nodular hyperplasia of the prostate, is both a redundant and a misnomer, because all hypertrophies are benign and the fundamental lesion is hypreplastic rather than hypertrophic.

Nodular hyperplasia is an extremely common abnormality of the prostate that is present in a significant number of men by age 40 and is in 90% of men by the 8^th decade. Androgen have a central role in the development of nodular hyperplasia. Dihydrotestosterone (DHT) an androgen derived from testosterone through the action of  5 alpha reductase and its metabolite 3 alpha androstanediol are major hormonal stimuli for the stromal and glandular proliferation in men with nodular hyperplasia.

The prostate has many distinct regions which are 1) peripheral zone 2) central zone 3) transitional zone and 4) periurethral zone. It is the periurethral glands that are mostly affected and the transitional and central region mostly contain the nodularity. These hyperplasitic nodules usually compress the urethra to a slit like orifice..

Pharmacology:

Finasteride: It is a type II 5α-reductase inhibitor. 5α-reductase is an enzyme that converts testosterone to dihydrotestosterone (DHT).

MOA: Testosterone in males is produced primarily in the testicles, but also in the adrenal glands. The majority of testosterone in the body is bound to sex hormone-binding globulin (SHBG), a protein produced in the liver that transports testosterone through the bloodstream, prevents its metabolism, and prolongs its half-life. Once it becomes unbound from SHBG, free testosterone can enter cells throughout the body. In certain tissues, notably the scalp, skin, and prostate, testosterone is converted into 5α-dihydrotestosterone (DHT) by the enzyme 5α-reductase. DHT is a more powerful androgen than testosterone (as it has approximately 3-10x the potency at the androgen receptor, the site of action of the androgen hormones), so 5α-reductase can be thought to amplify the androgenic effect of testosterone in the tissues in which it's found.

Finasteride, a 4-azasteroid and analogue of testosterone, works by acting as a potent and specific, competitive inhibitor of one of the two subtypes of 5α-reductase, specifically the type II isoenzyme. In other words, it binds to the enzyme and prevents endogenous substrates such as testosterone from being metabolized. 5α-reductase type I and type II are responsible for approximately one-third and two-thirds of systemic DHT production, respectively.

S/E: impotence (1.1% to 18.5%), abnormal ejaculation (7.2%), decreased ejaculatory volume (0.9% to 2.8%), abnormal sexual function (2.5%), gynecomastia (2.2%), erectile dysfunction (1.3%), ejaculation disorder (1.2%), testicular pain, increased risk of high-grade prostate cancer, depression and anxiety.

Contraindications:  teratogenic. ( Women who are or who may become pregnant must not handle crushed or broken finasteride tablets, because the medication could be absorbed through the skin).

Indications: male pattern baldness.