Urinary Bladder capacity, Acute and Chronic Urinary Retention causes, Benign Prostatic Hyperplasia factors and Alpha-1 blocker treatment

For the urine to exit the bladder, both the autonomically controlled internal sphincter and the voluntarily controlled external sphincter must be opened. Problems with these muscles can lead to incontinence.

The urinary bladder usually holds 300-350 ml of urine. As urine accumulates, the rugae flatten and the wall of the bladder thins as it stretches, allowing the bladder to store larger amounts of urine without a significant rise in internal pressure.

bladder picture

The urinary bladder is a muscular sac in the pelvis, just above and behind the pubic bone. When empty, the bladder is about the size and shape of a pear.

The internal sphincter is a continuation of the detrusor muscle and is made of smooth muscle, therefore it is under involuntary or autonomic control. This is the primary muscle for prohibiting the release of urine.

The external sphincter muscle of urethra  in males is a secondary sphincter to control the flow of urine through the urethra. Unlike the internal sphincter muscle, the external sphincter is made of skeletal muscle, therefore it is under voluntary control of the somatic nervous system.

share courtesy: wikipedia.org

Urine is made in the kidneys, and travels down two tubes called ureters to the bladder. The bladder stores urine, allowing urination to be infrequent and voluntary. The bladder is lined by layers of muscle tissue that stretch to accommodate urine. The normal capacity of the bladder is 400 to 600 mL.

During urination, the bladder muscles contract, and two sphincters (valves) open to allow urine to flow out. Urine exits the bladder into the urethra, which carries urine out of the body. Because it passes through the penis, the urethra is longer in men (8 inches) than in women (1.5 inches).

Urinary retention: Urine does not exit the bladder normally due to obstruction or suppressed bladder muscle activity. The bladder may swell to hold more than a quart of urine.

Causes of Urinary retention: There are two general types of urinary retention: obstructive and non-obstructive. If there is an obstruction (for example, kidney stones), urine cannot flow freely through the urinary track. Non-obstructive causes include a weak bladder muscle and nerve problems that interfere with signals between the brain and the bladder. If the nerves aren’t working properly, the brain may not get the message that the bladder is full.

Some of the most common causes of non-obstructive urinary retention are:

• Stroke
• Vaginal childbirth
• Pelvic injury or trauma
• Impaired muscle or nerve function due to medication or anesthesia
• Accidents that injure the brain or spinal cord

Obstructive retention may result from:

• Cancer
• Kidney or bladder stones
• Enlarged prostate (BPH) in men    

Acute and Chronic urine retention: Urine retention may be acute or chronic and occurs when something prevents the flow of urine from the bladder to the urethra and out of the body. 

In acute urine retention, but the person is unable to pass the urine, resulting in significant pain. 
Chronic urine retention is where a person is able to pass small quantities of urine with difficulty and the bladder never completely empties. It is usually painless. Symptoms of acute urine retention include lower abdominal pain, a sensation of fullness in the lower abdomen, and a painful urge and inability to pass urine. Chronic urine retention symptoms include swelling of the abdomen, a frequent need to urinate, difficulty in starting the urine flow, a weak urine flow, and dribbling at the end of urinating and between urinating. Treatment options include temporary or permanent catheterization, medication, treating the underlying cause, herbal therapies, and homoeopathy.

Acute urinary retention (AUR) is the sudden inability to pass urine. It is usually painful and requires emergency treatment with a urinary catheter. 

Causes: These are numerous and can be classified as:

• In men - benign prostatic hypertrophy (BPH), meatal stenosis, paraphimosis, penile constricting bands, phimosis, prostate cancer.
• In women - prolapse (cystocele, rectocele, uterine), pelvic mass (gynaecological malignancy, uterine fibroid, ovarian cyst), retroverted gravid uterus.
• In both - bladder calculi, bladder cancer, faecal impaction, gastrointestinal or retroperitoneal malignancy, urethral strictures, foreign bodies, stones.

Infectious and inflammatory:

• In men - balanitis, prostatitis and prostatic abscess.
• In women - acute vulvovaginitis, vaginal lichen planus and lichen sclerosis, vaginal pemphigus.
• In both - bilharzia, cystitis, herpes simplex virus (particularly primary infection), peri-urethral abscess, varicella-zoster virus.

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. It is the only exocrine organ located in the midline in humans and similar animals. share courtesy: wikipedia.org

#BPH is by far the most common cause of urinary retention. Alpha-1 blockers given before catheter removal increase the chances of a successful TWOC.

Diagram illustrating normal prostate (left)
and benign prostatic hyperplasia (right).
 share courtesy: http://en.wikipedia.org

Benign Prostatic Hyperplasia: BPH involves hyperplasia of prostatic stromal and epithelial cells, resulting in the formation of large, fairly discrete nodules in the periurethral region of the prostate. When sufficiently large, the nodules compress the urethral canal to cause partial, or sometimes virtually complete, obstruction of the urethra, which interferes with the normal flow of urine. It leads to symptoms of urinary hesitancy, frequent urination, dysuria (painful urination), increased risk of urinary tract infections, and urinary retention. Although prostate specific antigen levels may be elevated in these patients because of increased organ volume and inflammation due to urinary tract infections, BPH does not lead to cancer or increase the risk of cancer.

BPH involves hyperplasia (an increase in the number of cells) rather than hypertrophy (a growth in the size of individual cells), but the two terms are often used interchangeably, even amongst urologists. 

Its prevalence is age dependent. Histological evidence of BPH is rarely observed in men under 50 years of age, but by age 80 virtually all men will have some histological evidence of the process. It is unclear what specific factors regulate the degree of hyperplasia, which ultimately dictates the size of the prostate gland, nor is there any consensus regarding the prostate size that qualifies for the diagnosis of benign prostatic enlargement (BPE).

Alpha blockers for the treatment of Benign Prostatic Hyperplasia:

The relative degree of stromal and epithelial hyperplasia is highly variable. Overall, approximately 80% and 20% of the hyperplastic volume is composed of stromal and epithelial elements, respectively. Half of the stromal hyperplasia is composed of smooth-muscle elements. For decades, it was assumed that the enlarged hyperplastic prostate caused BOO via both dynamic and static mechanisms. The dynamic obstruction was thought to be the result of smooth-muscle hyperplasia causing a functional obstruction and static obstruction arising from the bulk enlargement of the hyperplastic process encroaching upon the prostatic urethra.

Marco Caine demonstrated in 1975 that strips of human prostate contracted in response to norepinephrine.The norepinephrine-induced contractions were inhibited by pretreatment with phenoxybenzamine, a non-selective inhibitor of alpha adrenoceptor. These studies implicated the alpha adrenoceptor as the mediator of prostate smooth-muscle contraction. Lepor and Shapiro were the first investigators to characterize both alpha 1 and 2 adrenoceptors in the human prostate using radioligand binding studies.  

Tamsulosin was the third alpha 1 blocker to be approved for the treatment of BPH. Tamsulosin was brought to market as the first subtype selective alpha 1 antagonist for the treatment of BPH. Tamsulosin alpha 1 subtype selective was supported by binding studies, which showed that tamsulosin was approximately tenfold more selective for the alpha 1a versus alpha 1b subtype. There was no demonstrable subtype selectivity of tamsulosin for the alpha 1a versus alpha 1d subtypes. The modest receptor selectivity of tamsulosin is not sufficient to result in a clinically meaningful advantage. Typically, clinical advantages attributed to pharmacological selectivity require a receptor selectivity well beyond the tenfold difference observed with tamsulosin.

A case report:
Age: 86 years male,
Acute urinary retention 1400 ml,

Prostate enlarge, 65 gm in weight,

Chronic retention of urine

cause may be BPH with
Bladder Neck Obstruction.

#As seen in above sonograph 

picture

Two pivotal trials of tamsulosin supported the NDA for the treatment of symptomatic BPH. Both 0.4 and 0.8 mg of tamsulosin achieved clinically significant improvements in symptom scores and peak flow rate. The ability of the 0.4 mg tamsulosin dose to achieve a clinically significant effect without the requirement for dose titration represented a unique advantage over the other approved alpha blockers. Although a 0.8 mg daily dose was more effective than 0.4 mg, it did not gain popularity because it required both dose titration and taking 2 tablets of 0.4 mg. (A 0.8 mg tablet was not commercially available.) The primary reason tamsulosin was prescribed over terazosin and doxazosin was not due to greater efficacy or better tolerability, but simply the lack of dose titration. The prescribing community placed a greater value on eliminating the dose response at the expense of increasing the incidence of ejaculatory dysfunction, which was thought to be retrograde ejaculation as a result of relaxation of the bladder neck. Recent studies have demonstrated that tamsulosin causes anejaculation rather than retrograde ejaculation. The mechanism for the increased incidence of ejaculatory dysfunction associated with tamsulosin has been attributed to its affinity for dopaminergic and other central nervous system receptors. 

An episode of acute urinary retention is no longer an absolute indication for surgical intervention. Alpha blockers are a very reasonable initial option for managing acute urinary retention.

Following sites referred thankfully and reference for further detail:

http://en.wikipedia.org

http://www.webmd.com

http://www.medtronic.com

http://www.naturaltherapypages.com.au/glossary/Urine_Retention#ixzz2T2pDuWCp 

http://www.patient.co.uk/doctor/acute-urinary-retention

NCBI journal Rev Urol. 2007 Fall; 9(4): 181–190

file:///E:/Alpha%20Blockers%20for%20the%20Treatment%20of%20Benign%20Prostatic%20Hyperplasia.htm

Some abbreviations used:

Food and Drug Administration (FDA)

lower urinary tract symptoms (LUTS)

bladder outlet obstruction (BOO)

benign prostatic enlargement (BPE)

benign prostatic hyperplasia (BPH)

Medical Therapy of Prostatatic Symptoms (MTOPS)

The American Urological Association Symptoms Index (AUASI)

International Prostate Symptom Index Score (IPSS)

new drug application (NDA)

Three subtypes of the alpha 1 adrenoceptor (alpha 1a, alpha 1b, alpha 1d) have been cloned and  pharmacologically characterized.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Drinking too much water can lead to hyponatremia, water intoxication, water poisoning and death

Liquid H₂O is the sine qua non of life.  
Making up about 66 percent of the human body, water runs through the blood, inhabits the cells, and lurks in the spaces between. At every moment water escapes the body through sweat, urination, defecation or exhaled breath, among other routes. Replacing these lost stores is essential but rehydration can be overdone. There is such a thing as a fatal water overdose.  

The poison is the dose

Water can cause the brain to swell 

share courtesy: http://news.bbc.co.uk

Drinking several litres over a relatively short period of time could be enough to cause water intoxication. Those most at risk include people taking ecstasy, as the drug increases thirst and facilitates the release of anti-diuretic hormones so more water is taken in but cannot be excreted. Also, elderly people because their kidney function may be impaired. 

Strange but true; drinking too much water can kill.

In a hydration-obsessed culture, people can and do drink themselves to death. 

As long as you are healthy and equipped with a thirst barometer unimpaired by old age or mind-altering drugs, follow Verbalis's advice, "drink to your thirst. It's the best indicator." 

Beware of mindlessly drinking several glasses of water per day without considering your diet, exercise habits, climate, and sense of thirst. And when you do find yourself in need of water, remember that you can get it from liquids and/or whole foods that are rich in water.

Forcing your body to accept a large amount of water within a short period of time - say, an hour or two - can be fatally dangerous to your health. Here's why:

If you force large amounts of water into your system over a short period of time, your kidneys will struggle to eliminate enough water from your system to keep the overall amount at a safe level.

As your circulatory system becomes diluted with excess water, the concentration of electrolytes in your blood will drop relative to the concentration of electrolytes in your cells. In an effort to maintain an equal balance of electrolytes between your blood and your cells, water will seep into your cells from your blood, causing your cells to swell.

If this swelling occurs in your brain, you'll experience increased intracranial pressure i.e. your brain will get squeezed because the flat bones that make up your skull don't provide much give. Depending on how much water your drink in a short period of time, you could experience a wide variety of symptoms, ranging from a mild headache to impaired breathing. As occurred in the tragic water-drinking contest, it's quite possible to die if you drink enough water in a short period of time. 

Water intoxication, also known as water poisoning or dilutional hyponatremia, is a potentially fatal disturbance in brain functions that results when the normal balance of electrolytes in the body is pushed outside safe limits by over-hydration.

Water, just like any other substance, can be considered a poison when over-consumed in a specific period of time. Water intoxication mostly occurs when water is being consumed in a high quantity without giving the body the proper nutrients it needs to be healthy.

One of the many Risk factors, is  Psychogenic polydipsia is the psychiatric condition in which patients feel compelled to drink large quantities of water, thus putting them at risk of water intoxication. This condition can be especially dangerous if the patient also exhibits other psychiatric indications (as is often the case), as the care-takers might misinterpret the hyponatremic symptoms.

Following sites referred thankfully and reference for further detail:

wikipedia.org

http://www.scientificamerican.com

http://news.bbc.co.uk

http://drbenkim.com/drink-too-much-water-dangerous.html

Human brain: Hypothalamus as control center for ageing identified but risk lies in follow up

Hypothalamus region of the brain is the control centre of ageing. Dongsheng Cai from the Albert Einstein College of Medicine in New York has discovered yet another vital duty on the hypothalamus’ already impressive CV—it’s a command centre that coordinates the ageing process across the entire body. By manipulating proteins within it, Cai managed to speed up or slow down the pace of ageing in mice. 

The brain's mechanism for controlling ageing
has been discovered – and manipulated to
shorten and extend the lives of mice.
Drugs to slow ageing could follow

share courtesy:
http://www.newscientist.com/section/science-news

Cai’s team found that the ageing hypothalamus builds up more microglia—a dedicated brand of inflammatory immune cells in the brain, which destroy infectious microbes and vacuum up debris. They also produce NF-kB, which tells neighbouring neurons to do the same. This flood of NF-kB switches off the gene for a hormone called GnRH.

That’s a surprise—GnRH is best known as a reproductive hormone. It controls the development of our sexual organs and the making of eggs and sperm. 

Human hypothalamus 

(animation, shown in red)

share courtesy: wikipedia.org

Howard Chang from Stanford University says, “If reproduced by others, this work provides further evidence that aging is a regulated rather than a [random] process.” 

But let’s recap what we already know, just to appreciate how bizarre this chain of results is. You have a life-support centre in the brain, a protein that coordinates the immune system, and a hormone that controls our sex organs, all working together to influence… the pace of ageing?

This research follow up may bring some serious consequences as: 

Given the pathway, we would not be surprised if a large experiment showed a significant increase of cancer risk. NF-kB is a well known cancer pathway, lower levels of NF-kB1 allow cancer cells to avoid cell death (apoptosis). I imagine this works along the same lines.  

Following sites referred thankfully and reference for further detail:

http://phenomena.nationalgeographic.com/2013/05/01/almond-sized-brain-region-is-control-centre-for-ageing/

mb, may1, 2013 on http://phenomena.nationalgeographic.com/2013/05/01/almond-sized-brain-region-is-control-centre-for-ageing/

http://www.newscientist.com/section/science-news

wikipedia.org

Images of a molecule

"Nobody has ever taken direct, single-bond-resolved images of individual molecules, right before and immediately after a complex organic reaction," says Felix Fischer of the U.S. Department of Energy's Lawrence Berkeley National Laboratory. 

(The researchers report their results in the June 7, 2013 edition of the journal Science, available in advance on Science Express.)

Almost as clearly as textbook diagram, this image made by a noncontact atomic force microscope reveals the positions of individual atoms and bonds, in a molecule having 26 carbon atoms and 14 ydrogen atoms structured as three connected benzene rings. Credit: Lawrence Berkeley national Laboratory and University of California at Berkeley

The original reactant molecule, resting on a flat silver surface, is imaged both before and after the reaction, which occurs when the temperature exceeds 90 degrees Celcius. The two most common final products of the reaction are shown. The three-angstrom scale bars (an angstrom is a ten-billionth of a meter) indicate that the reactant and product molecules are about a billionth of a meter across. Credit: Lawrence Berkeley national Laboratory and University of California at Berkeley

The single-atom tip of the noncontact atomic force microscope "feels" changes in the strength of electronic forces as it moves across the surface at a constant height. Resulting movements of the stylus are detected by a laser beam to compute images. Credit: Lawrence Berkeley national Laboratory and University of California at Berkeley

#thankfully shared from: http://phys.org
May 30, 2013