Monday, April 30, 2012

Acute Kidney Injury: Novel Biomarkers and Potential Utility for Patient Care in Urology


Recent improvements in our understanding of AKI have enabled us to better recognize and identify early changes within the spectrum of kidney injury. AKI is prevalent among urological patients and carries significant clinical and financial costs. The previous lack of consensus about the classification of ARF and limited diagnostic tools to identify early renal dysfunction impeded research and development of early prevention and treatment strategies for AKI. The longstanding need for earlier and more reliable detection of AKI has led to the discovery of promising biomarkers for AKI, such as NGAL, IL-18, cystatin C, and KIM-1, which have the potential to be analogous to troponins in the management of cardiac ischemia. In the future, these novel biomarkers will likely prove invaluable for the prevention and clinical management of AKI. Partial nephrectomy serves as an excellent paradigm for the potential use of these biomarkers, although there are several other urological disease processes that are often associated with AKI that will also likely be transformed by this new biotechnology. Although recent results have been robust, further validation of these biomarkers in a variety of clinical settings will be required before wider implementation.
UROLOGY 77: 5–11, 2011. © 2011 Elsevier Inc.

Sunday, April 29, 2012

Ten rules for the prevention of the risk of kidney stones


1. Keep an ideal weight and take regular moderate exercise in the open air.
2. Drink enough water to obtain a urinary volume of 2 L/d.
3. Restrict the intake of meat and poultry proteins to about 20 g/d.
4. Eat about 40 g of plant protein a day.
5. Eat fruits and vegetables every day, avoiding products rich in oxalate.
6. Eat milk and dairy products to achieve a calcium intake of about 1000 mg/d.
7. Follow the international guidelines on fat and carbohydrate consumption.
8. Use fresh and frozen food products, avoiding precooked and/or preserved foods.
9. Avoid do-it-yourself use of supplements and only take medicines and supplements under medical supervision.
10. Try to avoid stressful life events as far as possible.

Saturday, April 28, 2012

FDA Approves New Impotence Drug Stendra


FRIDAY April 27, 2012 — The U.S. Food and Drug Administration on Friday announced that it had approved Stendra, a new medication for erectile dysfunction.
Stendra (avanafil) joins Viagra, Cialis and Levitra, all from a class of drugs known as phosphodiesterase type 5 inhibitors that help boost blood flow to the penis.
According to the FDA, fast-acting Stendra is designed to be taken 30 minutes before sexual activity and at the lowest effective dose.
Whether the new drug adds any value to the existing range of impotence medications is unclear, one expert said.
Dr. Bruce Kava, acting chairman of urology at the University of Miami School of Medicine, said that “the only advantage Stendra may have is a more rapid onset of action over the other drugs. The question is whether there are any advantages to a more rapid onset.”
He noted that many patients don’t respond to one or another of these drugs. But there is no way right now of telling who will respond to which drug. “Sometimes it’s hit or miss,” he explained.
Men will have to try these drugs to find the one that best suits their lifestyle, Kava said. For example, for some men Cialis works best because its effects seem to last much longer than that of the other drugs, he said.
The FDA said Stendra’s approval means one more option for patients.
“This approval expands the available treatment options to men experiencing erectile dysfunction, and enables patients, in consultation with their doctor, to choose the most appropriate treatment for their needs,” Dr. Victoria Kusiak, deputy director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research, said in a statement.
Stendra comes with the same warnings as its companions in this drug class. It should not be taken by men who take nitrates — drugs used to treat chest pain (angina). This combination can cause a sudden drop in blood pressure, the FDA cautioned.
The agency also warned that these drugs can, in rare cases, cause color vision changes and in rare instances, men have also reported a sudden loss of vision in one or both eyes. Sudden loss or decrease in hearing has also been reported in patients taking these drugs. “Patients who experience a sudden loss of vision or hearing should stop taking PDE5 inhibitors, including Stendra, and call a doctor right away,” the FDA said.
The most common side effects reported with Stendra include headache, redness of the face and other areas, nasal congestion, cold-like symptoms and back pain.
In rare cases, patients taking these drugs may get an erection lasting four hours or longer that will not go away. “If this happens, patients should seek immediate medical care,” the agency said.
Erectile dysfunction occurs when a man has trouble getting or maintaining an erection. An estimated 30 million American men in are affected by erectile dysfunction, according to the FDA.
Stendra’s safety and efficacy were established in three double-blind, placebo-controlled clinical studies. A total of 1,267 patients were randomly assigned to take Stendra for up to 12 weeks at doses of 50 milligrams (mg), 100 mg or 200 mg, or a placebo as needed about 30 minutes before sexual activity.
Stendra is marketed by Mountain View, Calif.-based Vivus Inc.
More information
For more information on erectile dysfunction, visit the U.S. National Library of Medicine.

Friday, April 27, 2012

Proposed mechanism of action of botulinum toxin type A (BoNTA) injected into the overactive bladder wall.

It has been proposed that a complex system of interactions exists between the release of neurotransmitters and actions on respective receptors located on the urothelium and suburothelium, corresponding to pathways of bladder mechanosensation. All connections identified by arrows are thought to be upregulated in detrusor overactivity. BoNTA may exert a multimodal effect on those pathways via multiple inhibition of the vesicular release of neurotransmitters and neuropeptides by the urothelium and suburothelial nerves and reduction of the axonal expression of soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE)-complex–dependent proteins that are thought to be involved in bladder mechanosensation. 



bl = basal lamina of urothelium; mf = myofibroblast layer; det = detrusor muscle; TRPV1 = transient receptor potential vanilloid 1; P2X3 = ionotropic purinergic receptor type 3; P2Y = metabotropic purinergic receptors; M2/M3 = muscarinic acetylcholine receptors types 2 and 3; NK1 = neurokinin receptor type 1 (SP receptor); SP = substance P; NGF = nerve growth factor; ACh = acetylcholine; ATP = adenosine triphosphate.

Wednesday, April 25, 2012

HOUNSFIELD UNIT DENSITY IN THE DETERMINATION OF URINARY STONE COMPOSITION


No significant difference was noted between the HU values of calcium oxalate and calcium phosphate stones, and thus they were analyzed collectively as “calcium stones.” When the HU values of calcium , uric acid, struvite, and cystine stones were compared, the overlap of ranges precluded accurate identification, and the mean HU values were not significantly different from one another. There was less overlap noted when comparing the HU densities of the stones studied, and no noncalcium stone had an HU density greater than 76 HU/mm. Using one-way analysis of variance, significant differences were noted between the mean HU density of calcium (105 6 43) and uric acid (50 6 24) stones (P 5 0.006). A trend toward significance was found between the mean HU density of the calcium and struvite stones (53 6 28, P 5 0.073). No significant differences were found among the other stones.


HU density (HU value was divided by each stone’s largest transverse diameter in millimeters) compared with the HU value alone better characterized differences in radiodensities among urinary stones; calcium stones can be distinguished from uric acid stones on the basis of this value. However, neither the HU density nor the mean HU value was able to identify urinary stones in vivo. UROLOGY 58: 170–173, 2001. © 2001, Elsevier Science Inc.

Hydronephrosis of pregnancy


Approximately 90% of pregnant women develop a degree of unilateral or bilateral dilatation of the renal pelvis and ureter by the third trimester. It usually begins at the end of the first trimester and increases as the pregnancy advances. Right-sided dilatation predominates in most patients and the ureters below the pelvic brim are spared. The main cause is partial obstruction by the enlarging uterus compressing the ureters against the iliac arteries as they enter the pelvis. Maternal hormones, which decrease ureteric tone, appear to play a relatively minor role. In most women, dilatation disappears postpartum, sometimes in a few days, but usually more gradually over several weeks.
Renal calculi need to be excluded in pregnant women with loin pain, haematuria, or infection of the urinary tract. Abdominal radiographs are of limited value because the gravid uterus and the fetal skeleton can obscure ureteric calculi.
US demonstrates the presence of calyceal dilatation but cannot differentiate dilatation caused by calculi from dilatation due to pregnancy.
MR urography is now widely available and can provide good anatomical images of the dilated urinary tract without the use of contrast agents or radiation. It should be the investigation of choice in pregnant patients with loin pain. A regular tapering appearance can be seen in extrinsic compression due to the gravid uterus while stones are visible as filling defects with a signal void at the level of the obstruction.
IVU can be performed if US is equivocal and MRI is unavailable but the number of images should be kept to a minimum. Although an image obtained 1h after injection of contrast medium is appropriate if the dilatation is mild on US examination, the interval should be increased to 4–6 hours in patients with marked dilatation.
CT should not be used to evaluate stone disease in pregnancy because of the high dose of radiation.

Non-contrast helical CT (NCHCT)


The unrivalled advantage of CT over all other techniques is its diagnostic accuracy. Over 99% of stones, including those that are radiolucent on plain radiographs, will be seen on NCHCT.

The exceptions are pure matrix stones and stones made of indinavir sulphate, an HIV protease inhibitor and similar medication. NCHCT has the highest diagnostic accuracy (approximately 95% compared to around 80% for IVU) for acute ureteric colic. NCHCT can provide almost all information required for management of a patient with a ureteric calculus, although it is often supplemented by KUB for follow-up purposes. As well as demonstrating the size and location of the calculus, measurement of stone density may be useful, as stones of greater than 1000HU appear to respond less well to ESWL.

NEOPLASTIC RENAL MASSES: BENIGN: Adenoma and oncocytoma


Small renal tumours (< 3 cm) have been regarded in the past as adenomas rather than carcinomas. Unfortunately, the size of a renal mass is not a valid criterion for differentiating a benign from a malignant mass. There are reports of tumours that have produced metastases when less than 3 cm, although this is uncommon. Needle biopsy of a small lesion is not helpful in differentiating benign from malignant tumours, as most solid masses are composed of a heterogeneous population of cells and sampling error is common.
Oncocytomas are tubular adenomas with a specific histological appearance characterized by the oncocyte. They have previously been considered benign, but it is now recognized that they can metastasize. Oncocytomas can occur at any age and are often asymptomatic at presentation. They can vary in size from 1 to 20 cm in diameter, but tend to be large. Although they are usually solitary and unilateral, they can be multiple (5%) and bilateral (3%). Ultrasound demonstrates a solid mass with internal echoes, which occasionally has a stellate hypoechoic centre. However, the echogenicity of the mass can be variable. Contrast-enhanced CT demonstrates a well-defined solid mass (Fig 1) which, when large, can contain a low attenuation central scar. Large lesions can extend into and engulf the perinephric fat, and can be mistaken for angiomyolipomas. There are no features on MRI that will differentiate an oncocytoma from renal carcinoma. Arteriography is also of limited value in discrimination between an oncocytoma and renal cell carcinoma.
Figure 40.12  Oncocytoma. CT demonstrates multiple well-defined enhancing masses in both kidneys which were confirmed by percutaneous biopsy to be oncocytoma. Follow-up examination at 12 months did not demonstrate any growth.

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what is the diagnosis?

CT OF THE URINARY TRACT: Anatomical relationships of the kidney


The kidneys lie in the retroperitoneum, surrounded by the perinephric fat between the anterior and posterior layers of the renal fascia (Fig. 1). They lie lateral to and roughly parallel with the lateral border of the psoas. The renal fossa is bounded medially by the psoas muscle, posteriorly by the quadratus lumborum muscle, laterally by the transversus abdominis muscles, and superiorly by the diaphragm. Anteromedially, the kidneys are covered by peritoneum; posteriorly the twelfth rib crosses the left kidney at a 45? angle, with approximately one third or more of the left kidney superior to the inferior margin of the thoracic cage. Organs related to the kidney include the adrenal glands, which are directly superior to the kidney on the right side and anteromedial to the kidney on the left. The upper poles of both kidneys approximate the diaphragm, and the posterior aspect from the medial to the lateral borders is related to the psoas, quadratus lumborum and the transversus abdominis muscle or fascia. Depending on the amount of retroperitoneal fat, the anterior surface of the right kidney may be in contact with the right adrenal gland, the right lobe of the liver, the second portion of the duodenum and the hepatic flexure of the colon. The organs related to the anterior aspect of the left kidney are, from above downwards, the left adrenal gland, the stomach, the pancreas and (on the extreme lateral margin) the spleen and splenic flexure of the colon. In thin subjects the spleen may affect the contour of the left kidney (splenic hump).

Figure 1  The renal fascia. (A) Axial CT section showing anterior and posterior layers of the renal fascia. (B) CT peritoneogram clearly depicting the outline of the layers of the anterior and posterior renal fascia on the right and the location of the perirenal space. (C) Coronal multiplanar reformation (MPR) CT image showing the location of the kidneys in the perirenal space surrounded by the renal fascia.

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comment on this immage

Tuesday, April 24, 2012

Interactions Between Cholinergic and Prostaglandin Signaling Elements in the Urothelium: Role for Muscarinic Type 2 Receptors


We have demonstrated that both ATP and PGE2 Can induce ACh release from the bladder urothelium. Therefore, the stretch-induced ACh release, previously described in the bladder, might be a part of the result of a more complex series of signaling interactions within the urothelium. This complexity is increased because ACh can also modulate PGE2 release. This complex mechanism might provide a rapid amplification of urothelial signal output. NO partially inhibits ACh-induced PGE2 release and therefore might play a role in downregulating the urothelial-derived signal release. This could be another part of a mechanism to fine tune urothelial signal output. The ACh-induced PGE2 release in the bladder urothelium has been demonstrated to be mediated by the M2 receptor. A schematic of the bladder wall detailing the proposed location for the production of urothelial signals and their proposed interactions is shown in Figure1. 



Figure 1    Summary of structural and functional complexity of urothelial signaling systems in guinea pig bladder. (A) Immunohistochemical staining. (a) Basal and intermediate cells expressing enzyme COX I (red), and umbrella cells express marker for exocytotic vesicles SV2 (green; Nile and Gillespie, unpublished observation): presumptive ACh- and ATP-producing cells. (b) Basal cell layer expresses neuronal NO synthase (green), and enzyme-producing ACh (choline-acetyl transferase [ChAT]; Nile and Gillespie, unpublished observation) found in SV2-positive umbrella cells (red). (c) Relationship between layers expressing neuronal NO synthase (green) and COX I (red). (d) Basal layer expressing neuronal NO synthase (red) and cells that respond to NO with increase in cyclic guanosine monophosphate (green): umbrella cells and suburothelial interstitial cells. (e) Cells of intermediate urothelium express COX I (blue) and suggest they are also positive for M2 receptors (red/colocalization seen as purple). Calibration bars = 15 μM. (B) Cartoon showing different cell layers of urothelium and different signals they can generate or respond to. (C) Interactions observed between urothelial signals reported previously. Reciprocal positive interactions found between ACh and PGE2, and ATP promotes PGE2 and ACh output. ATP stimulation of COX I occurs by way of P2X- and P2Y-mediated mechanisms. Potential inhibitory action of NO on PGE2 production also demonstrated. 

The proposed schematic highlights the complexity of signal interactions that occur within the bladder wall. An understanding of these mechanisms and their interactions might reveal novel aspects of the control of bladder function. It could also lead to a better understanding of the nature of bladder pathologic features and facilitate the development of new pharmacologic approaches to manipulate and treat bladder disease.
UROLOGY 79: 240.e17–240.e23, 2012. © 2012 Elsevier Inc.

Up-regulation of Plakophilin-2 and Downregulation of Plakophilin-3 are Correlated With Invasiveness in Bladder Cancer


We conclude that Pkp2 mRNA and protein expression levels are elevated in invasive bladder cancer cell lines, whereas Pkp3 mRNA and protein expression levels are decreased in invasive bladder cancer cell lines, relative to noninvasive cells. Moreover, Pkp2 and 3 do not appear to be recruited to the plasma membrane but persist undegraded in the cytoplasm of invasive bladder cancer cell lines and tissues. Based on these data, as well as knockdown experiments, Pkp2 and 3 are likely to be involved in invasiveness through the mediation of loose cell adhesion but are probably not involved in the modulation of cellular growth.
UROLOGY 79: 240.e1–240.e8, 2012. © 2012 Elsevier Inc.

Utility of Urothelial mRNA Markers in Blood for Staging and Monitoring Bladder Cancer


Gene expression analysis of bladder-specific mRNA markers in blood samples by preamplification RT-qPCR is different among the various tumor risk groups of patients with UCC but does not predict the development of metastases. We have also found that this method is not suitable for monitoring hematogenous UCC dissemination in patients who have undergone cystectomy to predict the UCC outcome. The clinical utility of these findings should be evaluated further.
UROLOGY 79: 240.e9 –240.e15, 2012. © 2012 Elsevier Inc.

A Chinese Herbal Formula, Shuganyiyang Capsule, Improves Erectile Function in Male Rats by Modulating Nos-CGMP Mediators


SGYY, a Chinese herbal formula, significantly improves the maximal intracavernous pressure in a rat arteriogenic ED model. The underlying mechanism of action of SGYY involves increasing the expression of nNOS, iNOS, eNOS, and cGMP, and reducing PDE5 expression. Therefore, the modulation of the NOS-cGMP pathway plays a major role in SGYY action for treating ED.
UROLOGY 79: 241.e1–241.e6, 2012. © 2012 Elsevier Inc

Monday, April 23, 2012

Clinical Evaluation of a Urologic Patient

Clinical Evaluation
& Decision Making
Ø    HISTORY
I-Overview:
A complete history can be divided into the chief complaint, history of the present illness, the patient's past history (medical or surgical), and a family history.
Chief Complaint and Present Illness: the chief complaint is a constant reminder to the urologist as to why the patient initially sought care.
In obtaining the history of the present illness; the duration, severity, chronicity, periodicity, and degree of disability are important considerations.

II-Pain:
Pain arising from the GU tract may be quite severe and is usually associated with either urinary tract obstruction or inflammation.

ü    Urinary calculi cause severe pain when they obstruct the upper urinary tract. Conversely, large, non-obstructing stones may be totally asymptomatic. Thus, a 2-mm-diameter stone lodged at the ureterovesical junction may cause excruciating pain whereas a large staghorn calculus in the renal pelvis or a bladder stone may be totally asymptomatic.

ü    Inflammation of the GU tract is most severe when it involves the parenchyma of a GU organ. This is due to edema and distention of the capsule surrounding the organ. Thus, pyelonephritis, prostatitis, and epididymitis are typically quite painful. Inflammation of the mucosa of a hollow viscous such as the bladder or urethra usually produces discomfort, but the pain is not nearly as severe.

N.B: Tumors in the GU tract usually do not cause pain unless they produce obstruction or extend beyond the primary organ to involve adjacent nerves. Thus, pain associated with GU malignancies is usually a late manifestation and a sign of advanced disease.

1-Renal Pain
Pain of renal origin is usually located in the ipsilateral costovertebral angle just lateral to the sacrospinalis muscle and beneath the 12th rib. Pain is usually caused by acute distention of the renal capsule, generally from inflammation or obstruction. The pain may radiate across the flank anteriorly toward the upper abdomen and umbilicus and may be referred to the testis or labium. A corollary to this observation is that renal or retroperitoneal disease should be considered in the differential diagnosis of any man who complains of testicular discomfort but has a normal scrotal examination. Pain due to inflammation is usually steady, whereas pain due to obstruction fluctuates in intensity. Thus, the pain produced by ureteral obstruction is typically colicky in nature and intensifies with ureteral peristalsis, at which time the pressure in the renal pelvis rises as the ureter contracts in an attempt to force urine past the point of obstruction.

Pain of renal origin may be associated with gastrointestinal symptoms because of reflex stimulation of the celiac ganglion and the proximity of adjacent organs (liver, pancreas, duodenum, gallbladder, and colon).
Renal pain may be confused with pain of intraperitoneal origin of pain of intercostal nerves irritation
·         Pain of intraperitoneal origin is seldom colicky, as with obstructive renal pain. Furthermore, pain of intraperitoneal origin frequently radiates into the shoulder because of irritation of the diaphragm and phrenic nerve; this does not occur with renal pain. Typically, patients with intraperitoneal pathology prefer to lie motionless to minimize pain, whereas patients with renal pain usually are more comfortable moving around and holding the flank.
·         Renal pain may also be confused with pain resulting from irritation of the costal nerves; most commonly T10-T12 the pain is not colicky in nature. Furthermore, the intensity of radicular pain may be altered by changing position; this is not the case with renal pain.

2-Ureteral Pain:
Ureteral pain is usually acute and secondary to obstruction. The pain results from acute distention of the ureter and by hyperperistalsis and spasm of the smooth muscle of the ureter as it attempts to relieve the obstruction.
Usually, ureteral pain is produced by a stone or blood clot. The site of ureteral obstruction can often be determined by the location of the referred pain:
·         Right Mid-Ureter Right lower quadrant of the abdomen (McBurney's point simulating appendicitis)
·         Left Mid-Ureter Left lower quadrant (resembles diverticulitis).
·         Also, the pain may be referred to the scrotum in the male or the labium in the female.
·         Lower ureteral obstruction frequently produces symptoms of vesical irritability, including frequency, urgency, and suprapubic discomfort that may radiate along the urethra in men to the tip of the penis.

Ureteral pathology that arises slowly or produces only mild obstruction rarely causes pain. Therefore, ureteral tumors and stones that cause minimal obstruction are seldom painful.

3-Vesical Pain:
Vesical pain is usually produced either by over-distention of the bladder as a result of acute urinary retention or by inflammation. Constant suprapubic pain that is unrelated to urinary retention is seldom of urologic origin. Furthermore, patients with slowly progressive urinary obstruction and bladder distention (e.g., diabetics with a flaccid neurogenic bladder) frequently have no pain at all despite residual urine volumes over I L.

Inflammatory conditions of the bladder usually produce intermittent suprapubic discomfort. Thus, the pain in conditions such as bacterial cystitis or interstitial cystitis is usually most severe when the bladder is full and is relieved at least partially by voiding. Patients with cystitis sometimes experience sharp, stabbing suprapubic pain at the end of micturition, and this is termed strangury.

4-Prostatic Pain
Prostatic pain is usually secondary to inflammation with secondary edema and distention of the prostatic capsule. Pain of prostatic origin is poorly localized.

5-Penile Pain:
Pain in the flaccid penis is usually secondary to inflammation in the bladder or urethra, with referred pain that is experienced maximally at the urethral meatus.

6-Testicular Pain:
Scrotal pain may be either primary or referred:
Primary pain arises from within the scrotum and is usually secondary to acute epididymitis or torsion of the testis or testicular appendices

Chronic scrotal pain is usually related to non-inflammatory conditions such as a hydrocele or a varicocele, and the pain is generally characterized as a dull, heavy sensation that does not radiate.
Because the testes arise embryologically in close proximity to the kidneys, pain arising in the kidneys or retroperitoneum may be referred to the testes.

III-Hematuria:
Definition: presence of blood in the urine; greater than three RBCs per high-power microscopic field (HPF) is significant.
ü  Is the hematuria gross or microscopic?
ü  Is the hematuria associated with pain?
ü  Is the patient passing clots?
ü  If the patient is passing clots, do the clots have a specific shape?

1-Gross versus Microscopic Hematuria:
The significance of gross versus microscopic hematuria is simply that the chances of identifying significant pathology increase with the degree of hematuria.
2-Timing of Hematuria:
The timing of hematuria during urination frequently indicates the site of origin.
Initial hematuria usually arises from the urethra; it occurs least commonly and is usually secondary to inflammation.
Total hematuria is most common and indicates that the bleeding is most likely coming from the bladder or upper urinary tracts.
Terminal hematuria occurs at the end of micturition and is usually secondary to inflammation in the area of the bladder neck or prostatic urethra. It occurs at the end of micturition as the bladder neck contracts, squeezing out the last amount of urine.

Pain in association with hematuria usually results from upper urinary tract hematuria with obstruction of the ureters with clots.

3-Presence of Clots:
The presence of clots usually indicates a more significant degree of hematuria (More Severe)
The presence of vermiform (wormlike) clots, particularly if associated with flank pain, identifies the hematuria as coming from the upper urinary tract (Taking the shape of the ureters)

The most common cause of gross hematuria in a patient older than age 50 years is bladder cancer. (Hematuria in older than 50 years is a bladder cancer till proved otherwise)

IV-Lower Urinary Tract Symptoms:
v Irritative Symptoms:
Frequency: The normal adult voids five or six times per day, with a volume of approximately 300 mL per void. Thus; Urinary frequency is due either to increased urinary output (polyuria) or to decreased bladder capacity (More voiding times or more voided volume).
Nocturia is night frequency. Normally, adults arise no more than twice at night to void. As with frequency, nocturia may be secondary to increased urine output or decreased bladder capacity.



N.Bs:
·         Frequency during the day without nocturia is usually of psychogenic origin and related to anxiety.
·         Nocturia without frequency may occur in the patient with congestive heart failure and peripheral edema in whom the intravascular volume and urine output increase when the patient is supine.
·         Renal concentrating ability decreases with age; therefore, urine production in the geriatric patient is increased at night, when renal blood flow is increased as a result of recumbency.

Dysuria is painful urination that is usually caused by inflammation. This pain is usually not felt over the bladder but is commonly referred to the urethral meatus. Pain occurring at the start of urination may indicate urethral pathology, whereas pain occurring at the end of micturition (strangury) is usually of bladder origin.

v Obstructive Symptoms:
1-Decreased force of urination (Weak Stream of Urine)
It is usually secondary to bladder outlet obstruction and commonly results from benign prostatic hyperplasia (BPH) or a urethral stricture. In fact, except for severe degrees of obstruction, most patients are unaware of a change in the force and caliber of their urinary stream.
2-Urinary hesitancy
It refers to delay in the start of micturition.
3-Intermittency
It refers to involuntary start-stopping of the urinary stream.
4-Postvoid dribbling
It refers to the terminal release of drops of urine at the end of micturition. This is secondary to a small amount of residual urine in either the bulbar or the prostatic urethra that is normally “milked back” into the bladder at the end of micturition. The problem is more readily solved by manual compression of the bulbar urethra in the perineum and blotting the urethral meatus with a tissue.
5-Straining
It refers to the use of abdominal musculature to urinate. Normally, it is unnecessary for a man to perform a “Valsalva maneuver” except at the end of urination.
N.Bs:
·         The urologist must be careful not to attribute irritative symptoms to BPH unless there is documented evidence of obstruction
·         The second important example is irritative symptoms resulting from neurologic disease, such as cerebrovascular accidents, diabetes mellitus, and Parkinson's disease. Most neurologic diseases encountered by the urologist are upper motor neuron in etiology and result in a loss of cortical inhibition of voiding with resultant decreased bladder compliance and irritative voiding symptoms.


ü    International Prostate Symptom Score

VI-Incontinence:
Urinary incontinence is the involuntary loss of urine.
1.     Continuous Incontinence:
Continuous incontinence is most commonly due to a urinary tract fistula that bypasses the urethral sphincter. The most common type of fistula that results in urinary incontinence is a vesicovaginal fistula usually secondary to gynecologic surgery, radiation, or obstetric trauma. Less commonly, ureterovaginal fistulas may occur from similar causes. A second major cause of continuous incontinence is an ectopic ureter that enters either the urethra or the female genital tract
2.     Stress Incontinence:
Stress urinary incontinence is difficult to manage pharmacologically, and patients with significant stress incontinence are usually best treated surgically.
3.     Urgency Incontinence:
Urgency incontinence may result from a secondary underlying pathologic process, which should be identified.
4.     Overflow Urinary Incontinence:
Overflow incontinence has been termed paradoxical incontinence because it can often be cured by relief of bladder outlet obstruction.
5.     Enuresis.
It refers to urinary incontinence that occurs during sleep. It occurs normally in children up to 3 years of age but persists in about 15% of children at age 5 and about 1% of children at age 15. Enuresis must be distinguished from continuous incontinence, which occurs in the day as well as night.

VII-Sexual Dysfunction:
It Refers to Impotence or erectile dysfunction.
1-Loss of Libido:
A decrease in libido may indicate androgen deficiency arising from either pituitary or testicular dysfunction. This can be evaluated directly by measurement of serum testosterone that, if abnormal, should be further evaluated by measurement of serum gonadotropins and prolactin. A decrease in libido may also result from depression and a variety of medical illnesses that affect general health and well-being.

2-Impotence:
Impotence refers specifically to the inability to achieve and maintain an erection sufficient for intercourse. A careful history will often determine whether the problem is primarily psychogenic or organic.

3-Failure to Ejaculate:
An-ejaculation may result from several causes:
(1)          Androgen deficiency (decreased secretions from the prostate and seminal vesicles causing a reduction or loss of seminal volume)
(2)         Sympathetic denervation: Sympathectomy or extensive retroperitoneal surgery, most notably retroperitoneal lymphadenectomy for testicular cancer, may interfere with autonomic innervation of the prostate and seminal vesicles, resulting in absence of smooth muscle contraction and absence of seminal emission at time of orgasm.
(3)         Pharmacologic agents: (particularly α-adrenergic antagonists) may interfere with bladder neck closure at time of orgasm and result in retrograde ejaculation.
(4)         Bladder neck and prostatic surgery: Most commonly TURP may interfere with bladder neck closure, resulting in retrograde ejaculation.
(5)         Finally, Retrograde ejaculation may develop spontaneously in diabetic men.

4-Absence of Orgasm:
Anorgasmia is usually psychogenic or caused by certain medications used to treat psychiatric diseases.

5-Premature Ejaculation:
It is common for men to ejaculate within 2 minutes after initiation of intercourse, and many men who complain of premature ejaculation in actuality have normal sexual function with abnormal sexual expectations. However, there are men with true premature ejaculation who reach orgasm within less than 1 minute after initiation of intercourse. This problem is almost always psychogenic


6-Hematospermia:
It refers to the presence of blood in the seminal fluid. It almost always results from nonspecific inflammation of the prostate and/or seminal vesicles and resolves spontaneously, usually within several weeks. It frequently occurs after a prolonged period of sexual abstinence. Hematospermia is rarely associated with any significant urologic pathology.

VIII-Pneumaturia
It is the passage of gas in the urine. In patients who have not recently had urinary tract instrumentation or a urethral catheter placed, this is almost always due to a fistula between the intestine and the bladder. Common causes include diverticulitis, carcinoma of the sigmoid colon, and regional enteritis (Crohn's disease).

IX-Urethral Discharge:
Urethral discharge is the most common symptom of venereal infection. A purulent discharge that is thick, profuse, and yellow to gray is typical of Gonococcal urethritis; the discharge in patients with non-specific urethritis is usually scant and watery. A bloody discharge is suggestive of carcinoma of the urethra.

X-Fever and Chills
Fever and chills may occur with infection anywhere in the GU tract but are most commonly observed in patients with pyelonephritis, prostatitis, or epididymitis.

When associated with urinary obstruction, fever and chills may portend septicemia and necessitate emergency treatment to relieve obstruction.

*   Medical History:
Previous Medical Illnesses with Urologic Sequelae:
Patients with diabetes mellitus frequently develop autonomic dysfunction that may result in impaired urinary and sexual function. A previous history of tuberculosis may be important in a patient presenting with impaired renal function, ureteral obstruction, or chronic, unexplained UTIs.

*   Family History:
For example, 8% to 10% of men with prostate cancer have a familial form of the disease that tends to develop about a decade earlier than the more common type of prostate cancer.

*   Medications:
 For example, most of the antihypertensive medications interfere with erectile function, and changing antihypertensive medications can sometimes improve sexual function.

*   Previous Surgical Procedures:
It is worthwhile obtaining as much information as possible before any intended surgery because most surprises that occur in the operating room are unhappy ones (varicocelectomy in previous hernia repair).

*   Smoking and Alcohol Use:
Cigarette smoking is associated with an increased risk of urothelial carcinoma, most notably bladder cancer, and it is also associated with increased peripheral vascular disease and erectile dysfunction.

*   Allergies:
All medicinal allergies should be marked boldly on the front of the patient's chart.

Ø    PHYSICAL EXAMINATION
A-General Observations
The visual inspection of the patient provides a general overview. The skin should be inspected for evidence of jaundice or pallor. The nutritional status of the patient should be noted. Cachexia is a frequent sign of malignancy, and obesity may be a sign of underlying endocrinologic abnormalities, edema of the genitalia and lower extremities may be associated with cardiac decompensation, renal failure, nephrotic syndrome, or pelvic and/or retroperitoneal lymphatic obstruction.

B-Kidneys
The kidneys are fist-sized organs located high in the retroperitoneum bilaterally. In the adult, the kidneys are normally difficult to palpate because of their position under the diaphragm and ribs with abundant musculature both anteriorly and posteriorly. Because of the position of the liver, the right kidney is somewhat lower than the left. In children and thin women, it may be possible to palpate the lower pole of the right kidney with deep inspiration. However, it is usually not possible to palpate either kidney in men, and the left kidney is almost always impalpable unless it is abnormally enlarged.


The best way to palpate the kidneys is with the patient in the supine position (Bimanual Examination). The kidney is lifted from behind with one hand in the costovertebral angle. On deep inspiration, the examiner's hand is advanced firmly into the anterior abdomen just below the costal margin. At the point of maximal inspiration, the kidney may be felt as it moves downward with the diaphragm. With each inspiration, the examiner's hand may be advanced deeper into the abdomen. In children, it is easier to palpate the kidneys because of decreased body thickness. In neonates, the kidneys can be felt quite easily by palpating the flank between the thumbs anteriorly and the fingers over the costovertebral angle posteriorly. Transillumination of the kidneys may be helpful in children younger than 1 year of age with a palpable flank mass.

Other diagnostic maneuvers that may be helpful in examining the kidneys are percussion and auscultation. Although renal inflammation may cause pain that is poorly localized, percussion of the costovertebral angle posteriorly more often localizes the pain and tenderness more accurately. Percussion should be done gently, because in a patient with significant renal inflammation this may be quite painful. Auscultation of the upper abdomen during deep inspiration may occasionally reveal a systolic bruit associated with renal artery stenosis or an aneurysm. A bruit may also be detected in association with a large renal arteriovenous fistula.

Every patient with flank pain should also be examined for possible nerve root irritation. The ribs should be palpated carefully to rule out a bone spur or other skeletal abnormality and to determine the point of maximal tenderness. Unlike renal pain, radiculitis usually causes hyperesthesia of the overlying skin innervated by the irritated peripheral nerve. This hypersensitivity can be elicited with a pin or by pinching the skin and fat overlying the involved area. Finally, the pain experienced during the pre-eruptive phase of herpes zoster involving any of the segments between T11 and L2 may also simulate pain of renal origin.
ª      Abnormal Findings:
The most common abnormality detected on examination of the kidneys is a mass.
In neonates and younger children, the distinction between cystic, benign, and solid malignant masses can often be made by transillumination.

C-Bladder:
A normal bladder in the adult cannot be palpated or percussed until there is at least 150 mL of urine in it. At a volume of about 500 mL, the distended bladder becomes visible in thin patients as a lower midline abdominal mass.

Percussion is better than palpation for diagnosing a distended bladder. The examiner begins by percussing immediately above the symphysis pubis and continuing cephalad until there is a change in pitch from dull to resonant. Alternatively, it may be possible in thin patients and in children to palpate the bladder by lifting the lumbar spine with one hand and pressing the other hand into the midline of the lower abdomen.


Bimanual examination, best done with the patient under anesthesia, is invaluable in assessing the regional extent of a bladder tumor or other pelvic mass. The bladder is palpated between the abdomen and the vagina in the female or the rectum in the male. In addition to defining areas of induration, the bimanual examination allows the examiner to assess the mobility of the bladder; such information cannot be obtained by radiologic techniques such as CT and MRI, which convey static images.
ª      Abnormal Findings:
The most common palpable abnormality involving the urinary bladder is a full bladder resulting from over-distention. This may occur in men with bladder outlet or urethral obstruction due to BPH or urethral stricture disease
Tenderness over the suprapubic area may indicate cystitis.

D-Penis:
 Most penile cancers occur in uncircumcised men and arise on the prepuce or glans penis.
ª      Abnormal Findings:
1.             Phimosis.: Inability to retract the prepuce, In males younger than 4 years old it is normal for the foreskin to be unretractable.
2.            Paraphimosis: is a condition in which the foreskin has been retracted and left behind the glans penis (Not Returned).
3.            Peyronie's Disease: Peyronie's disease is a common condition that results in fibrosis of the tunica albuginea,
4.            Priapism.
5.            Hypospadias.

E-Scrotum and Contents:
Because the scrotum, unlike the penis, contains both hair and sweat glands, it is a frequent site of local infection and sebaceous cysts.

The testes should be palpated gently between the fingertips of both hands. The testes normally have a firm, rubbery consistency with a smooth surface. Abnormally small testes suggest hypogonadism or an endocrinopathy such as Klinefelter's disease. A firm or hard area within the testis should be considered a malignant tumor until proved otherwise. The epididymis should be palpable as a ridge posterior to each testis. Masses in the epididymis (spermatocele, cyst, epididymitis) are almost always benign.

To examine for a hernia, the physician's index finger should be inserted gently into the scrotum and invaginated into the external inguinal ring. The scrotum should be invaginated in front of the testis, and care should be taken not to elevate the testis itself, which is quite painful. Once the external ring has been located, the physician should place the fingertips of his or her other hand over the internal inguinal ring and ask the patient to bear down (Valsalva's maneuver). A hernia will be felt as a distinct bulge that descends against the tip of the index finger in the external inguinal ring as the patient bears down. Although it may be possible to distinguish a direct inguinal hernia arising through the floor of the inguinal canal from an indirect inguinal hernia prolapsing through the internal inguinal ring, this is seldom possible and of little clinical significance because the surgical approach is essentially identical for both conditions.

ª      Abnormal findings:
1-Testicular Cancer:
The most common physical finding in the testis is a mass. A useful guideline is that most masses arising from the testis are malignant, whereas almost all masses arising from the spermatic cord structures are benign. Testicular tumors usually present as painless, firm, irregular masses on the surface of the testis.
2-Torsion:
Torsion is the twisting of the testis on the spermatic cord, resulting in strangulation of the blood supply and infarction of the testis. Torsion occurs most commonly between the ages of 12 and 20 years, although it does occur less frequently during the first year of life. The patient usually presents with the sudden onset of pain and swelling of the involved testis. The pain may radiate into the groin and lower abdomen; thus, it may be confused with appendicitis unless the physician examines the genitalia carefully. On physical examination, it is difficult to distinguish the testis from the epididymis because of localized swelling. For this reason, the condition is frequently misdiagnosed as epididymitis. Age is the most useful criterion in distinguishing torsion from epididymitis, because torsion usually occurs around puberty whereas epididymitis more often occurs in sexually active males, usually after age 20 years.
3-Hydrocele:

4-Varicocele:
Patients with the sudden onset of a varicocele, a right-sided varicocele, or a varicocele that does not reduce in size in the supine position should be suspected of having a retroperitoneal neoplasm with obstruction of the spermatic vein.

E-Rectal and Prostate Examination in the Male
Digital rectal examination (DRE) should be performed in every male after age 40 years and in men of any age who present for urologic evaluation. Prostate cancer is the second most common cause of male cancer deaths after age 55 years and the most common cause of cancer deaths in men older than 70 years. Many prostate cancers can be detected in an early curable stage by DRE, and about 25% of colorectal cancers can be detected by DRE in combination with a stool guaiac test.

DRE should be performed at the end of the physical examination. It is done best with the patient standing and bent over the examining table or with the patient in the knee-chest position. In the standing position, the patient should stand with his thighs close to the examining table. The feet should be about 18 inches apart, with the knees flexed slightly. The patient should bend at the waist 90 degrees until his chest is resting on his forearms. The physician should give the patient adequate time to get in the proper position and relax as much as possible. A few reassuring words before the examination are helpful. The physician should place a glove on the examining hand and should lubricate the index finger thoroughly.
Before performing the DRE, the physician should place the palm of his other hand against the patient's lower abdomen. This provides subtle reassurance to the patient by allowing the physician to make gentle contact with the patient before touching the anus. It also allows the physician to steady the patient and provide gentle counterpressure if the patient tries to move away as the DRE is being performed.

1-Inspecting the anus for pathology, usually hemorrhoids, but, occasionally, an anal carcinoma or melanoma may be detected. The gloved, lubricated index finger is then inserted gently into the anus. Only one phalanx should be inserted initially to give the anus time to relax and to easily accommodate the finger.

2-Estimation of anal sphincter tone is of great importance; a flaccid or spastic anal sphincter suggests similar changes in the urinary sphincter and may be a clue to the diagnosis of neurogenic disease. If the physician waits only a few seconds, the anal sphincter will normally relax to the degree that the finger can be advanced to the knuckle without causing pain.

3-prostate (Size, Consistency, Surface, Sulcus)
The index finger then sweeps over the prostate, the entire posterior surface of the gland can usually be examined if the patient is in the proper position. Normally, the prostate is about the size of a chestnut and has a consistency similar to that of the contracted thenar eminence of the thumb (with the thumb opposed to the little finger).
The index finger is extended as far as possible into the rectum, and the entire circumference is examined to detect an early rectal carcinoma.
ª      Abnormal Findings:
1-Acute Prostatitis:
Acute prostatitis most commonly occurs in sexually active men between the ages of 20 and 40 years. Symptoms include fever, malaise, perineal and rectal discomfort, urinary frequency, urgency, dysuria, and sometimes urinary retention. When acute prostatitis is suspected, rectal examination should be performed carefully. Examination reveals the prostate to be warm, tender, and sometimes fluctuant or boggy in consistency. A localized fluctuant, tender region within the prostate may indicate a prostatic abscess for which surgical drainage is required. The prostate should never be massaged for secretions in men with acute prostatitis. Massage of the acutely infected prostate is not only unnecessary but also extremely uncomfortable for the patient. In addition, massage may disseminate bacteria through the vas deferens, causing secondary epididymitis or, more significantly, may disseminate bacteria into the bloodstream, producing gram-negative septicemia.

2-Benign Prostatic Hyperplasia:
The physical findings in BPH are usually limited to the prostate. In BPH, the prostate remains rubbery in consistency, but may be variably enlarged from normal chestnut size to the size of a lemon, or, occasionally, even as large as an orange. There is only a general correlation between prostatic size and degree of symptoms.
Because BPH affects almost all men older than age 50 years, the finding of an enlarged prostate on physical examination is not a reason per se to initiate further urologic evaluation. The severity of the disease and the need for treatment are best determined by the patient's symptoms as well as the results of further urologic testing, such as measurement of a urinary flow rate and postvoid residual urine.
3-Carcinoma of the Prostate:
Prostate cancer usually arises in the posterior peripheral region of the prostate and, therefore, is frequently palpable in its early stages on rectal examination. On physical examination, prostatic carcinomas are palpable as firm, indurated nodules or regions within the prostate. These areas of induration are characterized by having a woodlike consistency. As prostatic carcinomas progress, the entire gland becomes firmer than usual. Eventually, these tumors may progress beyond the capsule of the prostate, extending cephalad into the seminal vesicles and laterally toward the pelvic side wall.
It should be emphasized that men with early, localized carcinoma of the prostate are almost always asymptomatic. Therefore, a patient should never be allowed to dissuade the urologist from performing a rectal examination simply because he is asymptomatic. Urinary obstructive symptoms and skeletal pain are symptoms of advanced, incurable disease.

Detection of early prostatic carcinoma on rectal examination takes practice and has been greatly facilitated by the discovery of PSA. An elevated PSA value should raise the suspicion of prostatic carcinoma, regardless of the findings on rectal examination. Conversely, a normal PSA test does not exclude the possibility of early prostate cancer, and, in fact, 30% of men with early prostate cancer will have a normal serum PSA test.
A prostatic biopsy should be performed for any palpable lesion within the prostate. In one study, the detection rate of prostate cancer was 18% among men with an abnormal DRE and a PSA less than 4.0 ng/mL. In contrast, 56% of men with palpable abnormalities and a PSA greater than 4.0 ng/mL were found to have malignancy. Other causes of prostatic induration besides cancer include calculi (which are typically harder than tumors), inflammation, fibrous BPH, and infarction. Biopsies are now done easily using topical anesthesia under transrectal ultrasound guidance (TRUS). There is no excuse for delaying a prostatic biopsy in an otherwise healthy younger man with either an abnormal DRE or an elevated PSA level. It serves no purpose to have the patient return in 6 months for a repeat examination to see whether the nodule has changed, because prostate cancers usually grow very slowly; the fact that a nodule does not change appreciably with time is of no clinical significance.

F-Pelvic Examination in the Female:
The patient is then asked to perform a Valsalva maneuver and is carefully examined for a cystocele (prolapse of the bladder) or rectocele (prolapse of the rectum). The patient is then asked to cough, which may precipitate stress urinary incontinence.
Bimanual examination of the bladder, uterus, and adnexa should then be performed with two fingers in the vagina and the other hand on the lower abdomen. Any abnormality of the pelvic organs should be evaluated further with a pelvic ultrasound or CT scan.

G-Neurologic Examination
There are a variety of clinical situations in which the neurologic examination may be helpful in evaluating urologic patients. In some cases, the level of neurologic abnormalities can be localized by the pattern of sensory deficit noted during physical examination using a dermatome map. Sensory deficits in the penis, labia, scrotum, vagina, and perianal area generally indicate damage or injury to sacral roots or nerves. In addition to sensory examination, testing of reflexes in the genital area may also be performed.
The most important of these is the bulbocavernosus reflex (BCR), which is a reflex contraction of the striated muscle of the pelvic floor that occurs in response to a variety of stimuli in the perineum or genitalia. This reflex is most commonly tested by placing a finger in the rectum and then squeezing the glans penis or clitoris. If a Foley catheter is in place, the BCR can also be elicited by gently pulling on the catheter. If the BCR is intact, tightening of the anal sphincter should be felt and/or observed. The BCR tests the integrity of the spinal cord mediated reflex arc involving S2-S4 and may be absent in the presence of sacral cord or peripheral nerve abnormalities
The cremasteric reflex can be elicited by lightly stroking the superior and medial thigh in a downward direction. The normal response in males is contraction of the cremasteric muscle that results in immediate elevation of the ipsilateral scrotum and testis. There is limited clinical utility for testing superficial reflexes such as the cremasteric when investigating neurologic dysfunction. However, there may be a role for testing this reflex when assessing patients with suspected testicular torsion or epididymitis.

Ø    Investigations (URINALYSIS):
ª      Common Causes of Abnormal Urine Color
1-Turbidity:
Freshly voided urine is clear. Cloudy urine is most commonly due to phosphaturia.
Pyuria, usually associated with a UTI, is another common cause of cloudy urine. The large numbers of white blood cells cause the urine to become turbid.
2-Specific Gravity and Osmolality:
In general, specific gravity reflects the state of hydration but also affords some idea of renal concentrating ability.

·         Conditions that decrease specific gravity (Diluted Urine) include:
 (1) Increased fluid intake
 (2) Diuretics
 (3) Decreased renal concentrating ability.
 (4) Diabetes insipidus.
·         Conditions that increase specific gravity (Concentrated Urine) include:
 (1) Decreased fluid intake.
(2) Dehydration owing to fever, sweating, vomiting, and diarrhea.
 (3) Diabetes mellitus (glucosuria).
(4) Inappropriate secretion of antidiuretic hormone.


3-Urinary pH
It varies from 4.5 to 8; the average pH varies between 5.5 and 6.5. A urinary pH between 4.5 and 5.5 is considered acidic, whereas a pH between 6.5 and 8 is considered alkaline.
In general, the urinary pH reflects the pH in the serum. In patients with a presumed UTI, alkaline urine with a pH greater than 7.5 suggests infection with a urea-splitting organism, most commonly Proteus. Urinary pH is usually acidic in patients with uric acid and cystine stones. Alkalinization of the urine is an important feature of therapy in both of these conditions.

4-Chemical Examination of Urine
·         Urine Dipsticks:
The abnormal substances commonly tested for with a dipstick include:
 (1) Blood.
 (2) Protein.
 (3) Glucose.
 (4) Ketones
 (5) Urobilinogen and bilirubin.
 (6) White blood cells.

1-Hematuria:
Hematuria can be distinguished from hemoglobinuria and myoglobinuria by microscopic examination of the centrifuged urine; the presence of a large number of erythrocytes establishes the diagnosis of hematuria. If erythrocytes are absent, examination of the serum will distinguish hemoglobinuria and myoglobinuria.

Differential Diagnosis and Evaluation of Hematuria:
Hematuria may reflect either significant nephrologic or urologic disease. Hematuria of nephrologic origin is frequently associated with casts in the urine and almost always associated with significant proteinuria. Even significant hematuria of urologic origin will not elevate the protein concentration in the urine into the 100 to 300 mg/dL or 2+ to 3+ range on dipstick, and proteinuria of this magnitude almost always indicates glomerular or tubulointerstitial renal disease.

Morphologic evaluation of erythrocytes in the centrifuged urinary sediment also helps localize their site of origin. Erythrocytes arising from glomerular disease are typically dysmorphic and show a wide range of morphologic alterations. Conversely, erythrocytes arising from tubulointerstitial renal disease and of urologic origin have a uniformly round shape; these erythrocytes may or may not retain their hemoglobin (“ghost cells”), but the individual cell shape is consistently round.


A-Glomerular Hematuria:
Glomerular hematuria is suggested by the presence of dysmorphic erythrocytes, red blood cell casts, and proteinuria.
IgA Nephropathy (Berger's Disease) is the most common cause of glomerular hematuria, accounting for about 30%.
B-Nonglomerular Hematuria
1-Medical:
The urinalysis in nonglomerular hematuria is distinguished from that of glomerular hematuria by the presence of uniform circular erythrocytes and the absence of erythrocyte casts. Like glomerular hematuria, nonglomerular hematuria of renal origin is frequently associated with significant proteinuria. Papillary necrosis as a cause of hematuria should be considered in diabetics.

Medications may induce hematuria, particularly anticoagulants. Anticoagulation at normal therapeutic levels, however, does not predispose patients to hematuria. Thus, anticoagulant therapy per se does not appear to increase the risk of hematuria unless the patient is excessively anticoagulated.
Exercise-induced hematuria is being observed with increasing frequency. It typically occurs in long-distance runners (>10 km).
Vascular disease may also result in nonglomerular hematuria. Renal artery embolism and thrombosis, arteriovenous fistulas, and renal vein thrombosis may all result in hematuria.

2-Surgical:
Nonglomerular hematuria or essential hematuria includes primarily urologic rather than nephrologic diseases. Common causes of essential hematuria include urologic tumors, stones, and UTIs.

The urinalysis in both nonglomerular medical and surgical hematuria is similar in that both are characterized by circular erythrocytes and the absence of erythrocyte casts. Essential hematuria is suggested, however, by the absence of significant proteinuria usually found in nonglomerular hematuria of renal parenchymal origin. It should be remembered, however, that proteinuria is not always present in glomerular or nonglomerular renal disease.
And here is an algorithm for the evaluation of essential hematuria.
2-Proteinuria:
Although healthy adults excrete 80 to 150 mg of protein in the urine daily, the qualitative detection of proteinuria in the urinalysis should raise the suspicion of underlying renal disease. Proteinuria may be the first indication of renovascular, glomerular, or tubulointerstitial renal disease, or it may represent the overflow of abnormal proteins into the urine in conditions such as multiple myeloma. Proteinuria also can occur secondary to non-renal disorders and in response to various physiologic conditions such as strenuous exercise.
The protein concentration in the urine obviously depends on the state of hydration, but it seldom exceeds 20 mg/dL. In patients with dilute urine, however, significant proteinuria may be present at concentrations less than 20 mg/dL. Normally, urine protein is about 30% albumin, 30% serum globulins, and 40% tissue proteins, of which the major component is Tamm-Horsfall protein.
Pathophysiology: Most causes of proteinuria can be categorized into one of three categories: glomerular, tubular, or overflow.
·                     Glomerular proteinuria is the most common type of proteinuria and results from increased glomerular capillary permeability to protein, especially albumin
·                     Tubular proteinuria results from failure to reabsorb normally filtered proteins of low molecular weight such as immunoglobulins. In tubular proteinuria, the 24-hour urine protein loss seldom exceeds 2 to 3 g and the excreted proteins are of low molecular weight rather than albumin.
·                     Overflow proteinuria occurs in the absence of any underlying renal disease and is due to an increased plasma concentration of abnormal immunoglobulins and other low-molecular-weight proteins.

Protein electrophoresis is particularly helpful in distinguishing glomerular from tubular proteinuria. In glomerular proteinuria, albumin makes up about 70% of the total protein excreted, whereas in tubular proteinuria, the major proteins excreted are immunoglobulins with albumin making up only 10% to 20%. Immunoassay is the method of choice for detecting specific proteins such as Bence-Jones protein in multiple myeloma.
Evaluation: Proteinuria should first be classified by its timing into transient, intermittent, or persistent.

·                     Transient proteinuria occurs commonly, especially in the pediatric population, and usually resolves spontaneously within a few days
·                     Proteinuria may also occur intermittently, and this is frequently related to postural change.
·                     Persistent proteinuria requires further evaluation, and most cases have a glomerular etiology.
A patient in who total protein excretion is 300 to 2000 mg/day, of which the major components are low-molecular-weight globulins, further qualitative evaluation with immunoelectrophoresis is indicated. qualitative evaluation reveals abnormal proteins in the urine, this establishes a diagnosis of overflow proteinuria.

3-Glucose and Ketones:
This so-called renal threshold corresponds to serum glucose of about 180 mg/dL; above this level, glucose will be detected in the urine.
4-Bilirubin and Urobilinogen:
Conjugated (Direct) bilirubin has a low molecular weight, is water soluble, and normally passes from the liver into the small intestine through the bile ducts, where it is converted to urobilinogen. Therefore, conjugated bilirubin does not appear in the urine except in pathologic conditions in which there is intrinsic hepatic disease or obstruction of the bile ducts.
Indirect bilirubin is of high molecular weight and bound in the serum to albumin. It is water insoluble and, therefore, does not appear in the urine even in pathologic conditions.
Leukocyte esterase activity indicates the presence of white blood cells in the urine. The presence of nitrites in the urine is strongly suggestive of bacteriuria.
5-Urinary Sediment:
The urinary sediment should be examined microscopically for
(1)          Cells.
(2)         Casts
(3)         Crystals
(4)         Bacteria
(5)         Yeast.
(6)         Parasites.
(1)-Casts:
A cast is a protein coagulum that is formed in the renal tubule and traps any tubular luminal contents within the matrix. Tamm-Horsfall mucoprotein is the basic matrix of all renal casts; it originates from tubular epithelial cells and is always present in the urine. When the casts contain only mucoproteins, they are called hyaline casts and may not have any pathologic significance.
Hyaline casts may be seen in the urine after exercise or heat exposure but may also be observed in pyelonephritis or chronic renal disease.
Red blood cell casts contain entrapped erythrocytes and are diagnostic of glomerular bleeding, most likely secondary to glomerulonephritis.
White blood cell casts are observed in acute glomerulonephritis, acute pyelonephritis, and acute tubulointerstitial nephritis.
Casts with other cellular elements, usually sloughed renal tubular epithelial cells, are indicative of nonspecific renal damage. Granular and waxy casts result from further degeneration of cellular elements. Fatty casts are seen in nephrotic syndrome, lipiduria, and hypothyroidism.
(2)-Crystals:
The identification of cystine crystals establishes the diagnosis of cystinuria.
(3)-Bacteria:
Normal urine should not contain bacteria; and in a fresh uncontaminated specimen, the finding of bacteria is indicative of a UTI. As each HPF views between 1/20,000 and 1/50,000 mL, each bacterium seen per HPF signifies a bacterial count of more than 20,000/mL. Therefore,5 bacteria/HPF reflects colony counts of about 100,000/mL
(4)-Yeast:
The most common yeast cells found in urine are Candida albicans.
(5)Parasites:
Trichomonas vaginalis is a frequent cause of vaginitis in women and occasionally of urethritis in men.
Schistosoma hematobium is a urinary tract pathogen that is not found in the United States but is extremely common in countries of the Middle East and North Africa. Examination of the urine shows the characteristic parasitic ova with a terminal spike.

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