WeightLoss! the everyday struggle

I have givenup breakfast and lunch to try and ensure once aa day meal. I am no longer selective about what I eat. my weight is fluctuating around 106 kg and the blood pressure is not coming down. The struggle goes on!

Weightloss; a dilemma!

despite being cautious about my diet. the weight decline has pretty much halted, actually I have gained about 300 gms in the last one week. the exercise goes on. I am now going to slowly increase the strain and also will be investing into a heart rate monitor to maintain a fast hart rate during thirty minutes of exercise. will be updating shortly to log my progress.

Weightloss:: my struggle; a personal milestone

I have been trying to reach a balance where I can manage my diet and also be part of the family during the meal times.
this can be a real challenge when my wife is such a good cook and I am eating bland steamed vegetables with apple cider vinegar and resisting the appetizing, wonderful smell of the food for the family.
My solution has been to keep talking about how I was three months back and where I stand now. definitely not an engaging conversation on the table!
I am still continuing with Oat Milk to replace dairy milk and my with is slowly reducing around one KG every 10 days, the blood pressure is showing a response and my joint pain have gone down though they have not completely disappeared.



Weightloss: its a struggle everyday

I have been trying to get into a routine of fasting and strict vegetarian diet since the beginning of this month. But, there is always a but in these struggles! I have found it difficult not to CHEAT!
had to have a bit of delicious food cooked by Mrs for the children, in addition to the steamed greens.
this has slowed my weight loss.
I have not been regular with bicycle training on the turbo trainer also.
the couple of positive additions in this period of low will power have been the
1- replacement of dairy milk with almond milk; I have yet to notice a positive effect! though I have now lost my taste for Tea, thanks to this plant based milk alternative.
2- regular use of blade cut oats without boiling (raw) in warm water and almond milk. This quenches the hunger really well.
following is the record of my weight and blood pressure. the only positive note is that I have not gained any weight.

date	Sum of weight KG	Systolic	diastolic	Heart Rate
23/04/2020	124
01/05/2020	118
24/05/2020	114.8
05/06/2020	110.9
06/06/2020	112.2
07/06/2020	110.9	124	71	105
08/06/2020	111.2	135	83	117
09/06/2020	110.7	146	84	70
10/06/2020	110.2	165	94	70
11/06/2020	110.6	156	89	82
12/06/2020	110	144	91	60
14/06/2020	110.5	156	94	70
16/06/2020	109.7	140	75	119
18/06/2020	109.6	142	70	109
21/06/2020	109.9	152	87	81
28/06/2020	109.5	142	87	70
29/06/2020	108.9	112	69	108
02/06/2020	108.7	139	83	64
09/07/2020	108.1	123	75	118

Weightloss: A personal milestone!

Today I have crossed my personal target 109 Kg. my weight today turned out to be 108.9. the blood pressure turned out to be 116/ 65. either the machines need to be re-calibrated or I have achieved something.
I am still in the Morbidly obese zone but there is some silver lining today.
Cycling goes on.

My trusted bike on the Turbo trainer. I bought from Amazon and it was delivered from China. the Turbo trainer again was bought from Wish.com and delivered from China.
had to make space in the garage to start the regular exercise.
My waist is shrinking slowly but at least I am not gaining weight.
still sticking to once a day meal and only eating greens. no red meat or chicken except for yesterday when after one month of going Herbivore I had chicken and rice and it was wonderful!
From today back to greens for the next 30 days.

Weightloss; the challenge goes on! (5)

Weekend! always a challenge to conform to any plans!
and
my weight loss caloric management was no different.
wife is a wonderful cook and children in their teens have a taste for spicy food.
the above lethal combination was too much on my sense of smell!
after 4 weeks,  yesterday I ended up eating rice with minced meat.
I have just finished 30 minutes of cardio.
For all of today I have been fasting and will be having dinner at 9:30 pm,
The weight is stable at 109.9KG and blood pressure still high at 147/75.
will conitue with above plan for the month.

Weight Loss; my challenge and progress: An Update (4)--- not a good day

The struggle is on.

No Two days are the same.

Had some oats with milk at 7 am. I intended to fast till 9:30 pm with a target of 1500 calories in this 24 hours.

Came home early and felt suddenly idle and went for binge eating . had two slices of bread and two fried eggs.

later my youngest decided not to eat a fried egg and I had it with another slice  of bread.

So today has been a setback.

now I will be skipping dinner.

just finished my 30 minutes cycle training on the turbotrainer.

my weight remain stable at 109.6 kg but the blood pressure still showing no response with systolic 145 and diastolic 75.

Controlling my diet and keeping the focus is  challenging.

the struggle goes on.

will update tomorrow!

Weight Loss; my challenge and progress: An Update (2)

Weight Loss; my challenge and progress:    An Update

Diet:

I am sticking to one meal a day protocol. this has been an interesting experience. in the beginning I found the cravings to munch, have sweets etc quite a challenge, but now it is like a story of the past.

I am no longer feeling any headaches and have also lost craving for high carbohydrate stuff.

the change to a steamed vegetables is till a challenge every day!

Blood pressure is still not under control.

Joint Pains:

On positive side I am not experiencing the joint pains any more.

Exercise:

I had started half an hour of cycling using a turbo trainer but the for the last 3 days had to stop it due to pain in right buttock and back of leg.

below is the record suggesting a slow weight reduction but no improving in the blood pressure.

The challenge goes on and I will keep updating the Blog.

date	Sum of weight KG	Systolic	diastolic	Heart Rate
23/04/2020	124
01/05/2020	118
24/05/2020	114.8
05/06/2020	110.9
06/06/2020	112.2
07/06/2020	110.9	124	71	105
08/06/2020	111.2	135	83	117
09/06/2020	110.7	146	84	70
10/06/2020	110.2	165	94	70
11/06/2020	110.6	156	89	82
12/06/2020	110	144	91	60

 

Weight Loss; my challenge and progress: an update (3)

I am sticking to once a day green leafy vegetable meal, thus eating once every 24 hours.
my weight is slowly coming down but the blood pressure still remains elevated.
Have started doing exercises on a bicycle mounted on a turbortrainer and it is too early to comment on its impact.
will keep updating the blog regularly.

Weight Loss; my challenge and progress

Having struggled with high BMI for many years I has pretty much resigned to my eating habits and sedentary lifestyle.

Recent diagnosis of high blood pressure followed by lumbar disc prolapse and knee pains left me determined to reconsider my position.

Last month at the start of Ramadan I decided to bring about a change.

the targets set were as follows

1- loose weight from 124 Kgs to 100 Kgs in 60 days

2- Once 10Kgs have been lost start exercising to improve muscle tone.

3- start weight training once weight below 100 KGs

Over the last one month I have managed to loose 10kgs  and have started using a turbotrainer to cycle for half an hour.

I have not checked the impact on my blood pressure for I do not expect a change at the moment.

I am keen to create an online support group to help people like me pursue their health goals



Suprapubic Catheter; What to consider?

The catheters for urinary problems have been used for ages. They have come a long way from being stiff hollow tubes or bamboo reeds to modern day soft less irritating means to achieve short term urinary drainage or long term urinary diversion or control.
The catheters can either be introduced into the bladder from
urethral opening
or
Through the abdomen (Suprapubic catheter)
The catheter placement can be short-term as part of managing any medical or surgical condition or it can be long term when it is difficult for the patient and carer to manage the urinary continence related issues or if the patient cannot pass urine normally.
The catheter cannot be left in indefinitely and regular catheter changes are needed.
The bladder normally is sterile (free of bacteria) reservoir and gets colonised by bacteria once catheterised.

Various other issues with long term catheter are as below

Bacteriuria (100% cases) & UTI (10% cases)
• Haematuria (30% cases)
• Blocking (48% cases)
• Bypassing (37% cases)
• Expulsion (3% cases)
• Equipment failure
• Bladder stones (45% cases)
• Discomfort & Pain
• Urethral & bladder neck trauma
• Cancer EAU UTI guidelines say “patients with UC in place for ≥5 years
should be screened annually for bladder cancer”




Catheter care:

• Smallest catheter inserted aseptically with lubricating gel to minimize trauma.
• Silicon catheters least inflammatory & prone to encrustation.
• Closed gravity drainage system emptied 8 hourly.
• Urine output 100ml/hr
• Frequency of change depends on pt - No consensus
• Infection control principles.
• Prophylactic antibiotics for the routine catheter change are not
necessary (Polastri 1990).
• If bypassing, use smallest possible balloon + antimuscarinics (tablets to calm the bladder0.
• If blocking – treat UTI, acidify urine if good UO.
• Citric acid bladder washouts widely used, no good evidence

Interstitial cystitis

Introduction

a treatable but essentially incurable condition occurring in the absence of any known etiology
encompasses a major portion of the "painful bladder" disease complex, which includes a large group of patients with bladder and/or urethral and/or pelvic pain, irritative voiding symptoms (urgency, frequency, nocturia, dysuria), and sterile urine cultures
occurring predominantly in women (10:1), there are striking similarities between IC and the newly coined chronic pelvic pain syndrome in men, a poorly understood symptom complex that was formerly referred to as "nonbacterial prostatitis and prostatodynia
IC is truly a diagnosis of exclusion . It may have multiple causes and represent a final common reaction of the bladder to different types of insult.

Historical perspective

Skene (1887) used the term to describe an inflammation that has "destroyed the mucous membrane partly or wholly and extended to the muscular parietes”
Early in the 20th century, at a New England section meeting of the American Urological Association, Guy Hunner reported on eight women with a history of suprapubic pain, frequency, nocturia, and urgency lasting an average of 17 years. He drew attention to the disease, and the red, bleeding areas he described on the bladder wall came to have the pseudonym "Hunner's ulcer."
Hand (1949) wrote the first comprehensive paper about the disease, seminal
reviewing 223 cases.
three grades of disease, with grade 3 matching the small-capacity, scarred bladder described by Hunner.
Sixty-nine percent of patients were grade 1 and only 13% were grade 3
Messing and Stamey (1978) discussed the "early diagnosis" of IC
They turned attention from looking for an ulcer to make the diagnosis to the concepts that
symptoms and glomerulations found with the patient under anesthesia were the disease hallmarks and the diagnosis was primarily one of exclusion


Diagnostic criteria

NIDDK research criteria too stringent. Thus, IC remains a clinical syndrome defined by chronic symptoms of urgency, frequency, and/or pain in the absence of any other reasonable causation

Epidemiology

In 1987, there were 43,500 (perhaps up to 90,000) diagnosed cases of IC in the United States, approximately twice the prevalence in Finland found by Oravisto 12 years earlier. Median age of onset is 40 years.
No reports have ever documented a relationship to suggest that IC is a premalignant lesion
A large-scale survey of 6783 individuals, diagnosed by their physicians as having IC, studied the incidence of associated disease in this population
Allergies were the most common disorder, with 41% diagnosed with allergies and 45% with allergic symptoms
30% had a diagnosis of irritable bowel syndrome
Fibromyalgia is overrepresented in the IC population
Inflammatory bowel disease was found in over 7% of the IC population (100X that in gen population)
Sjögren's syndrome

Aetiology
Infection
Mast cell involvement
Increased mucosal permeability
Neurogenic mechanisms
Hypoxia, Reflex Sympathetic Dystrophy
Urine abnormalities
Autoimmunity/inflammation
IC is a multifactorial syndrome
Elbadawi and Light (1996) have suggested such a pathogenesis based on a potentially self-perpetuating process of neurogenic inflammation that can trigger a biologically potent cascade of events, including a leaky urothelium and mast cell activation

Epithelial permeability: KCl
Potentially strong evidence for a population with mucosal leak has been reported by Parsons (1994) who showed that KCl provoked 4.5% of normals and 70% of IC patients. Intravesical administration of KCl has since been proposed as a diagnostic test for IC (Parsons et al, 1998).
KCl: Normal bladder epithelium is not absolutely tight, and there is always some leak, however small. The findings of pain with KCl may be due to a hypersensitivity of the sensory nerves in this condition, rather than to pathologic epithelial permeability, at least in some patients


Pathology
One can have pathology consistent with the diagnosis of IC, but there is no microscopic picture pathognomonic of this syndrome
Attempts to definitively diagnose IC by electron microscopy have also been very unsuccessful
The role of histopathology in the diagnosis of IC is primarily one of excluding other possible diagnoses
Johansson and Fall (1990) looked at 64 patients with ulcerative disease and 44 with nonulcerative IC.
Ulcerative group: mucosal ulceration and hemorrhage, granulation tissue, intense inflammatory infiltrate, elevated mast cell counts, and perineural infiltrates.
The nonulcer group had a relatively unaltered mucosa with a sparse inflammatory response, the main feature being multiple, small, mucosal ruptures and suburothelial hemorrhages that were noted in a high proportion of patients.
Because these specimens were almost all taken immediately after hydrodistention, how much of the admittedly minimal findings in the nonulcer group were purely iatrogenic is a matter of speculation
pathologically, the two types of IC may be completely separate entities
mast cell counts per se have no place in the differential diagnosis of this clinical syndrome.
Diagnosis
Frequency and pelvic pain of long duration unrelated to other known causes establish a working diagnosis
One must rule out
infection
carcinoma
eosinophilic cystitis
malakoplakia
schistosomiasis
scleroderma
detrusor endometriosis
Various gynecologic problems even when not directly involving the bladder like pelvic endometriosis, vulvodynia, pelvic infection, urogenital atrophy, and leiomyoma can mimic the pain of IC
Reports of successful treatment of IC symptoms by laparoscopic adhesiolysis or urethral diverticulum excision give credence to the fact that IC is a diagnosis of exclusion. Many drugs, including cyclophosphamide, NSAIDs, and allopurinol, have caused a nonbacterial cystitis that resolves with drug withdrawal

Cystoscopy (under anaesthesia with hydrodistention)
Pain on bladder filling which reproduces the patient's symptoms is very suggestive of IC, allows for sufficient distention of the bladder to afford visualization of either glomerulations or Hunner's ulcers. Glomerulations are not specific for IC and only when seen in conjunction with the clinical criteria of pain and frequency can the finding of glomerulations be viewed as significant. Bladder biopsy is indicated only if necessary to rule out other disorders that might be suggested by the cystoscopic appearance


Treatment:
Treatments are empirical, symptoms can be controlled with one of a variety of treatments in majority, and there is little evidence that treatment does more than improve symptoms, rather than cure the condition.
There is a 50% incidence of temporary remission unrelated to therapy, with a mean duration of 8 months

Hydrodistension
Hydrodistention of the bladder with the patient under anesthesia, although technically a surgical treatment, is frequently the first therapeutic modality employed, often as a part of the diagnostic evaluation
A therapeutic hydraulic distention for 8 minutes after inspection of bladder for glomerulations and ulceration.
Therapeutic responses in patients with a bladder capacity under anesthesia of less than 600 ml showed 26% with an excellent and 29% with a fair result compared with 12% excellent and 43% fair in patients with larger bladder capacities (Hanno and Wein, 1991). Most improvements lasted less than 6 months. A capacity under anesthesia of under 200 ml would not bode well for the likelihood of success of medical therapy.
Reassure patient that disease not life threatening
Explain chronicity of disease and that treatments may not be successful
Empower patients (self help groups, pamphlets)
Lifestyle measures (stress reduction, exercise)

Dietary restrictions
Unsupported by any literature. Many patients find avoiding certain foods helpful (caffeine, alcohol, urine acidifying beverages such as cranberry juice)
Timed voiding/bladder drill
Biofeedback to help relax pelvic floor

Tricyclics
Amitriptyline has become a staple of oral treatment for IC.
The tricyclics possess varying degrees of at least three major pharmacologic actions:
They have central and peripheral anticholinergic actions at some but not all sites
they block the active transport system in the presynaptic nerve ending that is responsible for the re-uptake of the released amine neurotransmitters serotonin and noradrenaline,
they are sedatives, an action that occurs presumably on a central basis but perhaps is related to their antihistaminic properties
Hanno and Wein (1987) first reported a therapeutic response to amitriptyline in one of their patients concurrently being treated for depression

Antihistamines
The use of antihistamines goes back to the late 1950s and stems from work by Simmons
Theoharides (1994) have been the major modern proponents of antihistamine therapy and have shown 30% improvement in symptoms.

Sodium Pentosanpolysulfate (PPS)
Parsons' suggestion that a defect in the GAG layer contributes to the
pathogenesis of IC
synthetic sulfated polysaccharide (PPS) (Elmiron), a heparin analogue available in an oral formulation, 3% to 6% of which is excreted into the urine
100mg tds

Analgesics
The long-term, appropriate use of pain medications forms an integral part of the treatment of a chronic pain condition like IC
Most patients can be helped markedly with medical pain management using pain medications commonly employed for chronic neuropathic pain syndromes including antidepressants, anticonvulsants, and opioids
nonopioid analgesics including nonsteroidal anti-inflammatory drugs (NSAIDs) and even antispasmodic agents have a place in therapy
the use of long-term opioid therapy in the rare patient who has failed all forms of conservative therapy can be considered
Intravesical Therapy
Intravesical lavage with one of variety of preparations has remained a mainstay of treatment in the therapeutic armamentarium of IC
oldest of the intravesical therapies is silver nitrate (Mercier 1855)
DeJuana and Everett (1977) had a 50% response rate in 102 patients.
Clorpactin WCS-90 (O’Connor 1955) their success rate was 72% with an average 6-month duration of response (Messing and Stamey 1978)

DMSO
A mainstay of the intravesical treatment of IC is the instillation of DMSO
DMSO is a product of the wood pulp industry and a derivative of lignin
freely miscible with water, lipids, and organic agents.
Pharmacologic properties include membrane penetration, enhanced drug absorption, anti-inflammatory, analgesic, collagen dissolution, muscle relaxation, and mast cell histamine release.Stewart and associates (1968) were responsible for popularizing intravesical DMSO for IC.
Heparin has also been used, and Parsons advocates the use of 40,000 units of heparin in 20 ml sterile water, self-administered by the patient daily and held for 30 to 60 minutes. Reasonable improvement after 6 months
PPS, another GAG analogue, has been shown to have a modest benefit
Trials with hyaluronic acid have shown response rates of 30 to 70%
Intravesical BCG first reported by Zeidman 1994 showing a 60% response rate compared with a 27% placebo response (Peters et al, 1997)
Well tolerated
It is unclear how BCG achieved this result, but immunologic and/or anti-inflammatory mechanisms have been postulated (Peters et al, 1999).
A small Swedish study failed to substantiate BCG efficacy (Haghsheno et al, 2000; Peeker et al, 2000).

Other intravesical agents
Other possible treatements intravesically include oxybutinin, capsaicin.
TENS has been shown to be helpful. Fall (1980:14 women treated successfully with long-term intravaginal stimulation or TENS)
Sacral neuromodulation of S3 may prove to be effective.

Surgery
The surgical therapy of IC is an option after all trials of conservative treatment have failed
IC is a nonmalignant process with a temporary spontaneous remission rate of 50% that does not directly result in mortality
Transurethral resection of Hunner's ulcer, as initially reported by Kerr (1971), can provide symptomatic relief.
Disappearance of pain and decreased frequency in 21/30 pts (Fall 1985)
Similar results have been attained with the Nd:YAG laser
Extreme caution required
Substitution cystoplasty
Urinary diversion
Substitution cystoplasty

Supratrigonal cystectomy and the formation of an enterovesical anastomosis with bowel segments has been a popular surgical procedure for intractable IC (Worth and Turner-Warwick, 1972)
Flood (1995) reviewed 122 augmentation procedures, 21 of which were done for IC.
Patients with IC had the poorest results of any group, with only 10 having an "excellent" outcome
Webster and Maggio (1989) reviewed their data in 19 patients, and concluded that only patients with a bladder capacity less than 350 ml under anesthesia should undergo substitution cystoplasty
Some advocate diversion and/or total cystourethrectomy if the trigone is "affected" by IC (on biopsy, although biopsy findings are not pathognomonic, and IC tends to affect the whole of the bladder)
There has been a controversy over whether the IC process can occur in a transposed bowel patch. Urinary diversion with or without cystourethrectomy is the ultimate surgical answer to the dilemma of IC. Cystourethrectomy is certainly indicated in patients who not only have failed all other therapies but also have demonstrated chronicity such that remission is considered extremely unlikely.

Risks of failure peculiar to IC include both the development of phantom pain in the pelvis that persists despite the fact that the stimulus that initially activated the nociceptive neurons (diseased bladder) has been removed. Despite all of the problems, many patients will do well after major surgery, and quality of life can measurably improve. The surgical route needs to be persued with extreme amount caution and patient motivation has to be taken into account.

Vasectomy: What's worth knowing?

64 000 per yr in UK

Irreversible
Consider alternatives

Complications

EARLY
-Bleeding 3.6% (Philp)
-Bruising
-Wound D/C 1% (Philp)
-Wound infection 4%(Randall)
-Haematoma 1%
-Failure 0.36 (Philp) - 0.6% (early recanalisation, duplication, wrong structure)

LATE

-Chronic scrotal pain 13-16%
16% 1 yr, 13% 10 yrs
severe in 5%
(Stepping Hill: 460 pts in each group)
NB. Some evidence less if testicular end left open: (6% vs 2%, Moss, 1992, Contraception)

-Sperm granuloma 15-40%

-Non motile sperm (2-30%) 'special clearance' after 7mths/25 ejaculates <10000 NMS/ml
2% in Philp series from Oxford. 150 pts given special clearance, but only 51 followed up. 50/51 azoospermic, but no pregnancies attributable to vasectomy failure

-Failure 1/2500 Philp (recanalisation)

-CaP, testicular ca, IHD...no evidence in large trials

Need 2 clear SA before using as sole form of contraception at 12 &14 weeks OR 1 at 16 weeks
45% do not submit any samples (Chwala Urology 2004)
20 ejaculations probably needed (this is recommended in third world)
93% azoospermic by 20 weeks


SA Technique
Masturbation into a non-toxic container after 48hr abstinence; maintained at body temperature
Examine within 4hr
Assess within 1hr for persistent non-motile sperms
Germ cells, epithelial cells & leucocytes often seen in semen up to 16 weeks after vasectomy
Store between 20 & 40 °C and await liquefaction (within 4 hours)
Count 10 µl in a 20 µm chamber to allow sperm movement
Phase-contrast microscopy
If no sperms seen, centrifuge @ 3000g for 15 min and re-suspend in 100 µl autologous seminal plasma


Sivardeen, Annals RCS Eng 2001
75% of UK urologists send vas for histology.
95% request at least 2 semen samples.

Philp BJU 1984, from Oxford
16000 pts
1970-1983
Most diathermy, no fascial interposition
Vas not routinely sent
Semen analysis 4 and 41/2 months
Special clearance given if 2 consecutive semen analyses of under 10000 semen/ml, non motile, and >7 months post vasectomy. 2.2% in series
800 men sent questionnaire: 67% response rate
7.7% sought post op advice for pain
3.6% for bleeding
1% scrotal haematoma
Early failure 0.43%
12/69: vas not tied
57/69: early recanalisations (0.36%), 0.51% following ligation, and 0.28% after diathermy
6 late recanalisations (1 in 2000)
Failures lower in more experienced surgeons

Davies, Cranston et al, BJUI 1990, Oxford

6000pts
1980-85
2.5% men given special clearance (151)
Criteria as above
Follow up semen analysis after 3 yrs in 50
49/50 azoospermic, no attributable pregnancies

Vasectomy Reversal
1-3 per 1000 vasectomised men will request reversal (Swingl and Guess)
Testic biopsies show normal spermatogenesis up to 10yrs post vasectomy

NB Rx post vasectomy epididymal pain
Good prognostic indicators
· <8yrs since vasectomy
· Partner <40yo
· Fluid from epididymal end at time of reversal
Vasovasostomy/epididymovasostomy
2 layers
Use magnification - microscope a little better
Alternatives - ICSI, DI, Adoption

Physiology of Sperm production and Erection

Spermatogenesis

• germinal cells divide to become spermatogonia which divide to become spermatocytes
• Type A spermatocytes undergo meiosis to become secondary spermatocytes
• spermatocytes divide and give rise to mature cell lines (spermatids)
• spermatids (haploid) undergo a transformation into a spermatozoa
• There are six stages of seminiferous epithelium development
• 16 days required for a mature sperm to develop from early spermatogonia
• 72 days until ejaculation
• 1 spermatogonium becomes 215 spermatids

• testosterone and FSH are the hormones that are directed at the seminiferous tubule epithelium
• LH effects spermatogenesis indirectly in that it stimulates endogenous testosterone production
• The physical proximity of the Leydig cells to the seminiferous tubules and the elaboration by the Sertoli cells of androgen-binding protein, cause a high level of testosterone to be maintained in the microenvironment of the developing spermatozoa (i.e. 50X peripheral levels)

Epididymis: involved with maturation, storage and transport of spermatozoa.
• Testicular spermatozoa are non-motile
• Spermatozoa gain progressive motility and fertilizing ability after passing through the epididymis
• The epididymis consists of a fragile single convoluted tubule that is 5-6 meters in length. The epididymis is divided into the head, body, and tail
• Although epididymal transport time varies with age and sexual activity, the estimated transit time is four days.
• In epididymis, sperm develops the increased capacity for progressive motility and also acquire the ability to penetrate oocytes during fertilization
• The epididymis also serves as a reservoir or storage area for sperm

• The extragonadal sperm reservoir
• Is 440 million spermatozoa
• more than 50% of these are located in the tail of the epididymis.
• The sperm that are stored in the tail of the epididymis enter the vas deferens which is a muscular duct 30-35 cm in length
• The contents of the vas are propelled by peristaltic motion into the ejaculatory duct
• Sperm are then transported to the outside of the male reproductive tract by emission and ejaculation.







Erection:

Parasympathetic stimulation leads to penile erection (Eckhard, 1863, in the dog)
Sympathetic pathways important for detumescence and play a role in psychogenic erections (via inhibition of these pathways)

Reflex erection: afferent stimulation via S2-4, with efferent impulses via the same level sacral roots
Psychogenic erections: due to audiovisual, olfactory stimuli, or fantasy, and require the long tracts to be intact.

Afferent impulses via the dorsal penile nerves through pudendal nerves to dorsal roots of S2-4.
Upwards transmission via spinothalamic tracts to the thalamus and sensory cortex

Coordinated in medial pre-optic nucleus, contiguous with the hypothalamus

Efferent impulses via the medial forebrain bundle to the spinal cord. Parasympathetic fibres pass in intermediate lateral bundle and outflow through S2-4 in preganglionic pelvic nerves (nervi erigentes) to the pelvic plexus and then to the erectile tissue via the cavernous nerves

Sympathetic outflow from the spinal cord leads to flaccidity. Coordination in medial pre-optic nucleus, with outflow via T11-L4 via the hypogastric plexus, and thence to the pelvic plexus

Following spinal cord injuries higher than T9, erections can occur due to the reflex arc, and with lower lesions erections may occur as a result of efferent impulses through the thoracic sympathetic outflows, even though sympathetic stimulation normally leads to flaccidity (this is via a negative effect on the sympathetic outflow).

LMN pts unable to obtain a reflex erection, but 25% can get psychogenic erections

6 phases of erection (FFTFRD):
1: flaccid
contracted smooth muscle
2: filling
relaxation of arterial and cavernosal smooth muscle
3: tumescence
continued inflow
4: Full erection
compression of subtunical venous plexuses
decreased venous outflow via emissary veins
5: rigid erection
contraction of ischiocavernosus smooth muscle
6: detumescence
sympathetic stimulation and relaxation of ischiocavernosus smooth muscle
release of NA leads to stimulation of a1 receptors, an increase in intracellular calcium and contraction of cavernous smooth muscle


Ejaculation

Emission: sympathetic control (T10-L2)
Secretions from the seminal vesicles and prostate are deposited into the posterior urethra via contraction of epididymes and vasa and seminal vesicles
Bladder neck closure occurs under sympathetic nervous control.
Ejaculation: parasympathetic control (S2-4): the bladder neck tightens and the external sphincter relaxes with the semen being propelled through the urethra via rhythmic contractions of the perineal and bulbocavernosus and ischiocavernosus muscles.


The seminal vesicles provide 65% of volume fructose, prostaglandins and coagulating substrates.
A recognized function of the seminal plasma is its buffering effect on the acidic vaginal environment.
The coagulum formed by the ejaculated semen liquefies within 20 to 30 minutes as a result of prostatic proteolytic enzymes.
The prostate (30% volume) also adds zinc, phospholipids, spermine, and phosphatase to the seminal fluid.
The first portion of the ejaculate characteristically contains most of the spermatozoa and most of the prostatic secretions, while the second portion is composed primarily of seminal vesicle secretions and fewer spermatozoa.

What is Prostate?

The Prostate Gland and BPH. Basic Science



Function

Secretory
Produces 30% of the volume of seminal fluid
Provides nutrients for sperm
Proteases such as PSA (chymotrypsin) maintain semen fluidity by acting as an anticoagulant
Neutralises acidity of vagina
Antibiotic function of some secretions from the central zone.

Muscular pump
Smooth muscle surrounding the glands forces ejection of prostatic fluid to mix into seminal fluid during ejaculation


Development

Wk 7 male and female identical.
Mullerian ducts degenerate in male
Wolffian ducts differentiate - ejaculatory ducts, SV, vas and central zone of prostate
Wk 10-15 prostate derived from urogenital sinus (UGS) (peripheral zone)
Prostatic utricle is remnant of Mullerian or paramesonephric duct
3rd trimester gland quiescent till puberty


Structure

70% glandular / 30% fibromuscular


Zonal anatomy (McNeal 1968)

TZ - 5-10% glandular tissue

CZ - 25% glandular tissue structurally / immunohistochemically distinct from other zones.

Possibly originated from Wolffian duct

PZ - 70% glandular tissue

Derived from urogenital sinus


Transition zone BPH, 20% cancers
Central zone, 1-5% cancers
Peripheral Zone, 70% cancers


Blood supply: Inferior vesical and middle rectal arteries - branches of internal iliac artery
Venous drainage:
Prostatic venous plexus - sides & base of prostate
Located between capsule + fascial sheath
Drain to internal iliac veins
Communicate with vesical venous plexus, vertebral venous plexus

Innervation

Via cavernosal nerves which follow arterial supply
Parasympathetic fibres arise from pelvic splanchnic nerves S2, S3, & S4, promote secretions
Sympathetic fibres derived from inferior hypogastric plexuses, contraction of SM of capsule & stroma

Sphincters:

Rhabdosphincter (distal sphincter/urethral sphincter mechanism)
Three components: smooth muscle, then striated muscle, then periurethral component of levator ani (pubourethral sling)
Under conscious control
Signet ring shaped, deficient posteriorly

Bladder Neck
Both sexes, at bladder neck, cholinergic innervation, continence mechanism

Preprostatic sphincter
Males, supraverumontanal, adrenergic innervation, genital sphincter
Separate from rhabodosphincter
Smooth mucle, not under conscious control



Lymphatic drainage:
Lymph vessels terminate mainly in internal iliac and obturator lymph nodes
Some travel to external iliac lymph nodes & presacral nodes


Seminal vesicle
Pear shaped structure, 5cm long
Lies between fundus of bladder and rectum / (ureter enters bladder medial to tip of SV)
Provide majority of volume of seminal fluid, does not store sperm
Join vas deferens to form ejaculatory duct, opens posterior wall of prostatic urethra
Blood supply - sup / inf vesical arteries



Ejaculation
Emission of semen into urethra: peristalsis of vas / seminal vesicles, contraction of smooth muscle in prostate - sympathetic
Ejaculation clonic spasm bulbospongiosus muscles – parasympathetic
Sequence:
Bladder neck tightens
Emission of vasal ampullary sperm
Contraction of bulbospongiosus
Contraction of prostatic smooth muscle
Urethral sphincter mechanism overcome
Further contraction of prostate and seminal vesicle contraction




Seminal plasma

2ml seminal vesicle secretion, 0.5ml prostatic secretion, 0.1ml Cowper’s glands and glands of Littré

Role of seminal plasma
Optimise fertilisation
(ejaculated sperm v aspirated sperm)
protective effect
enhance motility and survival directly
Protective effect on urinary tract
biological esp. Zn, spermine, Ig
mechanical washing
Lubrication


Prostatic secretions

o Proteins: Acid phosphatase, PSA, Leucine aminopeptidase, Diamine oxidase, Β Glucuronidase, Plasminogen activator, Complement C3 and C4, transferrin, transferritin, Growth factors, annexin 1

o Non-proteins: Citrate (240-1300x conc elsewhere), Spermine, Spermidine, Putrescine, Zinc (high concentrations), Myoinositol, Cholesterol

o Functions: zinc for the structure of sperm chromatin and antibacterial. PSA for semen liquefaction. Cholesterol may stabilize sperm against temperature and environmental shock Citrate is important for electrochemical neutrality in combination with zinc and polyamines


Fructose

§ From seminal vesicles
§ Patients with congenital absence of seminal vesicles don’t have fructose in ejaculate [Barak 1994]
§ Concentration has some androgenic regulation but also depends on nutritional status and frequency of ejaculation
§ Provides anaerobic and aerobic energy source for sperm
§ Indirectly linked to forward sperm motility through prostasome function [Fabiani et al 1995]

Prostaglandins

§ Seminal vesicles are richest source in body (originally thought to be from prostate – hence the name) many types
§ Very potent pharmacological actions
§ Erection, ejaculation, sperm motility and transport
§ Effects on cervical mucus and vaginal secretions

Cell biology

Cellular organization is of a complex ductal system of epithelial cells embedded in a
stromal matrix

Epithelial: Exocrine and neuroendocrine cells
3 types: basal, luminal and neuroendocrine
Have different functions but are believed to originate from a common progenitor stem cell
Separated from stromal cells by the basement membrane
DHT formed mainly in these cells, and DHT then diffuses to stroma (where there are most of the androgen receptors)
Stromal nuclei produce growth factors, which then drive epithelial cells

Stroma: smooth muscle cells and fibroblasts
Has most of the androgen receptors
DHT diffuses from stromal cells, which produce growth factors, and these factors then work in an autocrine and paracrine fashion, stimulating epithelial cells

Cell type Function
Basal cells Proliferation
Luminal cells Secretion of prostatic fluid
Neuroendocrine Unknown - control growth and secretion?

Fibroblast Secrete growth factors (androgen dep)
Smooth muscle Contraction to eject prostatic fluid


Cellular organisation in the glandular prostate

Epithelial Cells

Neuroendocrine
Morphologically found in two forms
Open ended flask shaped cells with long extension towards the glandular lumen.
Closed cells without dendrite luminal extensions but with occasional horizontal processes.
Prostate has largest number of NE cells of any urogenital organ.
Function: Unknown but may play a role in the regulation of the normal growth and gland development (paracrine and autocrine) and may be important in the development of disease.

Basal cells
Spindle shaped, lying parallel to the basement membrane
Cigar shaped nuclei and high nucleus to cytoplasm ratio
81% of all proliferation occurs in the basal layer
Ratio of basal cells to luminal is 1:3 in normal and BPH tissue and 1:6 in hyperplastic situations
Major function: Proliferation
Includes stem cells

Luminal cells
Tall, columnar cells high in cytoplasm
Secretory cells contributing to the seminal fluid
PSA - Prostate specific antigen
PAP - Prostatic acid phosphatase
Only 1/10 the proliferative index of basal cells
Function - secretory - androgen dependent, as is survival
These cells most abundantly express the adrenoreceptor in BPH, cf basal cells

Cytokeratins:
Prostate: K5/14 basal cells and K8/18 in luminal cells

Stromal cells

Smooth muscle cells and fibroblasts
Little information about stromal cell types
Fibroblasts appear to initiate glandular growth and then differentiate into smooth muscle cells.
In cancer loss of muscle and gain of fibroblasts is associated with increased epithelial cell division
In culture a cell type called myofibroblasts appears and this may be an intermediate cell type
Both cell types express andrenoreceptors in BPH
98% of all α-adrenoreceptors in the prostate (90% α1 (60% α1a), 10% α2)



Stromal epithelial interaction theory

Interation between the stroma and the epithelium is important in growth and maintenance of the prostate
Reischauer suggested this first in 1925, and the theory was adopted by Cunha (1973)
Cunha showed that murine embryonic prostatic stroma could induce adult bladder epithelial cells to replicate and form prostate like glandular structures from the bladder cells. This effect does not occur in castrated animals, thus indicating the importance of androgens.
This interaction is thought to be the driving factor in the development of BPH, with androgens stimulating the local production of growth factors. These factors are responsible for the abnormal proliferation of the prostatic stroma and the appearance of micronodules and macronodules

Other Theories for BPH development

Embryonic reawakening: McNeal suggests that the initial abnormality in nodule genesis is a spontaneous reversion of a clone of stromal cells to the embryonic state

Oestrogen hypothesis: oestradiol modulates the action of androgens by altering the sensitivity of the prostate to androgens. A small increase in oestradiol concs results in an increased number of androgen receptors and prostate size. A large increase in oestradiol has the opposite effect. With aging, the oestrogen to androgen ratio increases, and these changes mimic those seen in BPH. Glandular BPH has been induced in castrated dogs by oestrogen and androgen administration (Walsh and Wilson, 1976)

Stem cell hypothesis: Isaacs and Coffey 1989. Number of stem cells, which is the rate limiting factor in prostate growth, slowly increases over time.


Growth Factors


FGF
IGF
TGFα all stimulatory (TGFα accounts for 20% of stimulatory factors)
EGF

TGFβ inhibitory

They all regulate the epithelial and mesenchymal interactions responsible for prostate development.
TGFβ inhibits prostate epithelial growth, but stimulates prostatic mesenchymal cells.

Following androgen withdrawal, there is decreased production of EGF, IGF and FGF, and an increase in expression of TGFβ1 and 2 receptors. This leads to prostatic involution.

Growth Factors in BPH:

bFGF stromal/epithelial autocrine/paracrine stimulatory
KGF stromal paracrine stimulatory
TGFβ1 stromal autocrine/paracrine inhibitory
TGFβ2 epithelial autocrine/paracrine inhibitory
IGF stromal paracrine stimulatory

In BPH there is no change in EGF, a large increase in FGF2, and keratinocyte growth factor and IGF appear.


Apoptosis and programmed cell death

Apoptosis is important in the development of BPH.
Activation of endonucleases occurs relatively early in the apoptotic pathway. This results from the hydrolysis of DNA, and the endonucleases are Ca2+/Mg2+ dependent.
Prostate stroma expresses α1a receptors, and pts treated with terazosin and doxasosin show induction of apoptosis, without affecting proliferation. Apoptitic index is higher in pts treated with an α blocker and proscar. Expression of TGFβ1 is increased with all therapies. However, α blocker treatment is not associated with a decrease in size of the prostate clinically.




BPH
LUTS
Urodynamic obstruction
BPE


LUTS, anatomical hyperplasia and urodynamic obstruction are interrelated.
Some pts have all three.
However, a large number have anatomical hyperplasia and urodynamic obstruction without LUTS.
Other have LUTS and urodynamic obstruction without anatomical hyperplasia, such as with bladder neck obstruction or a urethral stricture.
The last group have anatomical hyperplasia and symptoms of LUTS without urodynamic obstruction, and such pts may have a slow stream when voiding, but this is due to detrusor failure.

Anatomical hyperplasia
BPH consists of a mixture of glandular tissue and stromal components developing in a nodular fashion.
Glandular tissue that participates in BPH nodule formation is derived exclusively from branches of the few small ducts that join the urethra at or near its point of angulation at the base of the veru.
Nodules develop either in TZ or in periurethral stroma
Very different histologically: periurethral nodules are purely stromal in character or show only a few small glands. (TZ nodules are a proliferation of glandular (epithelial) tissue with a reduction in the relative amount of stroma ? correct)
In BPH stromal to glandular (epithelial) tissue is 5:1, while normally it is 2:1 in normal prostates
BPH has been described as primarily a stromal process
Causes obstruction in 2 ways
Static obstruction from increased tissue mass
Dynamic obstruction from contraction of the bladder neck, prostatic fibromuscular stroma and capsule
This sympathetic mediated obstruction may be responsible for upto 40% of bladder outflow obstruction




Natural History and Epidemiology

Initial development of BPH starts age 25-30 yrs, with a prevalence of 10% in that age range (data from autopsies involving 1075 prostates, Berry et al, J Urol 1984)
6th decade prevalence is >50%
by age 85, 90% affected
Data from Berry showed normal prostates weigh 20 +/- 6g in men 20-30 yrs, and remains constant throughout life
In pts with LUTS aged 60-80 yrs average weight is 40-50g


Risk factors and androgens

Age
Functioning testes leading to production of testosterone
BPH develops when test levels are on the decline
Role of androgens likely to be facilitative rather than causative

Intracellular androgens:
Testosterone metabolized to DHT, by 5 alpha reductase
Types 1 5a red (skin and liver) and type 2 (intraprostatic)
DHT: testosterone in prostate is 5:1
Both DHT and test bind to androgen receptors, DHT > testosterone, leading to greater subsequent intracellular changes of DNA activation and mRNA production
Males with 5a reductase def have no prostates

Androgen control:

Gene encoding 5a red enzyme type 1 found on Chr 5: expressed in nongenital skin and liver (inhibited by dutasteride)
Gene encoding 5a red enzyme type 2 found on Chr 2: expressed in prostate (stroma and basal epithelial cells) and genital skin (inhibited by finasteride and dutasteride)