1.

Describe the differential diagnosis of the common

causes of hematuria based on either etiological or
anatomic considerations
DEFINITION OF HEMATURIA Hematuria is RBCs in urine, specifically > 3 RBCs
per high-power field on urine sediment examination. Urine may be red, bloody, or
cola-colored (gross hematuria) or not visibly discolored (microscopic hematuria).

Gross hematuria Gross hematuria is suspected because of the presence of red

or brown urine. The color change does not necessarily reflect the degree of blood
loss, since as little as 1 mL of blood per liter of urine can induce a visible color
change. In addition, the intermittent excretion of red to brown urine can be seen in a
variety of clinical conditions other than bleeding into the urinary tract. Gross
hematuria with passage of clots almost always indicates a lower urinary tract source.

The initial step in the evaluation of patients with red urine is centrifugation of the
specimen to see if the red or brown color is in the urine sediment or the supernatant

As contamination with blood is a possibility in menstruating and post-partum women,

urine for analysis is best obtained when the other cause of bleeding has ceased. If
this is not possible a tampon can be inserted, and urinalysis obtained after the
perineum is thoroughly cleansed.

Hematuria is responsible if the red to brown color is seen only in the urine
sediment, with the supernatant being clear. A rare exception is that lysis of red
blood cells in patients with gross hematuria and very dilute urine can result in a
red supernatant.

Isolated hematuria without proteinuria, other cells, or casts is often indicative

of bleeding from the urinary tract

If, on the other hand, it is the supernatant that is red to brown, then the supernatant
should be tested for heme (hemoglobin or myoglobin) with a urine dipstick.

A red to brown supernatant that is negative for heme (hemoglobin or

myoglobin) is a rare finding that can be seen in several conditions, including
porphyria, the use of the bladder analgesic phenazopyridine, and the ingestion
of beets in susceptible subjects.
A red to brown supernatant that is positive for heme is due to myoglobinuria
or hemoglobinuria. How these disorders can be distinguished is discussed
elsewhere.

Red urine is not always due to RBCs. Red or reddish brown discoloration may result
from the following:
o Hb or myoglobin in urine, bilirubin
o Porphyria (most types)
1
o Foods (eg, beets, rhubarb, blackberries, blueberries, paprika, beets, fava beans,
sometimes food coloring)
o Drugs (most commonly phenazopyridine, rifampicin, metronidazole,
Sulfonamides, but sometimes cascara, diphenylhydantoin, methyldopa,
phenacetin, phenindione, phenolphthalein, phenothiazine, and senna)

2
2. Describe findings on history and physical exam that
may help define the source of hematuria, specifically :
a.Upper tract vs Bladder vs Prostate vs Urethra

b. Genitourinary specific or systemic

Historical clues There are often clues from the history that point toward
a specific diagnosis. These include:

Concurrent pyuria and dysuria, which are usually indicative of a urinary tract
infection, but may also occur with bladder malignancy.

A recent upper respiratory infection raises the possibility of postinfectious

glomerulonephritis or IgA nephropathy or sometimes hereditary nephritis.

A positive family history of renal disease, as in hereditary nephritis, polycystic

kidney disease, or sickle cell disease.

Unilateral flank pain, which may radiate to the groin, suggests ureteral obstruction
due to a calculus or blood clot, but can occasionally be seen with malignancy. Flank
pain that is persistent or recurrent can also occur in the rare loin pain-hematuria
syndrome.

Symptoms of prostatic obstruction in older men such as hesitancy and dribbling.

The cellular proliferation in benign prostatic hyperplasia (BPH) is associated with
increased vascularity, and the new vessels can be fragile. There is some
controversy about whether hematuria is more common in these patients than in
age-matched controls. However, there is general agreement that the presence of
BPH should not dissuade the clinician from pursuing further evaluation of hematuria,
particularly since older men are more likely to have more serious disorders such as
cancer of the prostate or bladder. Among those with gross hematuria in whom no
other cause can be identified, finasteride usually suppresses the hematuria.

Recent vigorous exercise or trauma in the absence of another possible cause.

History of a bleeding disorder or bleeding from multiple sites due to excessive

anticoagulant therapy. However, it should not be assumed that hematuria alone can
be explained by chronic warfarin therapy. In one report of 243 patients prospectively
followed for two years, the incidence of hematuria was similar to that in a control
group not receiving warfarin. Furthermore, evaluation of patients who developed
hematuria revealed a genitourinary cause in 81 percent of cases. Infection was most
common, but papillary necrosis, renal cysts, and several malignancies of the
bladder were also found.

These observations indicate that hematuria in an anticoagulated patient should

generally be evaluated in the same fashion as in other patients unless there is
evidence of bleeding from multiple sites with markedly abnormal coagulation
studies.
 Cyclic hematuria in women that is most prominent during and shortly after
menstruation, suggesting endometriosis of the urinary tract. Contamination with
menstrual blood is always a possibility, and should be ruled out by repeating the
urinalysis when menstruation has ceased.

Medications that might cause nephritis (usually with other findings, typically with
renal insufficiency).

Black patients should be screened for sickle cell trait or disease, which can lead to
papillary necrosis and hematuria.

Travel or residence in areas endemic for Schistosoma haematobium or tuberculosis.

Sterile pyuria with hematuria, which may occur with renal tuberculosis, analgesic
nephropathy and other interstitial diseases.

Blood that appears with the onset of urination --- initial hematuria --- often indicates
a problem in the urethra or, in men, the prostate.
Blood which occurs at the end of urination --- terminal hematuria --- can reflect
disease of the bladder or prostate.
Bleeding that occurs throughout urination --- total hematuria --- suggests problems
in the bladder, ureter or kidneys.
In women, hematuria that occurs cyclically with menstruation denotes abnormal
tissue growth (called endometriosis) of the urinary tract.
Blood discovered between voidings, such as stains found in one's underwear, often
signifies bleeding in one or both ends of the urethra.

Hematuria-associated symptoms also can suggest the site and/or cause of bleeding:
Pain in the flank with hematuria usually suggests a problem in the kidney, caused
by trauma or a tumor.
Hematuria with irritative voiding symptoms --- urinary urgency, pain or increased
frequency --- is a common symptom of bladder cancer.
If decreased urinary force, hesitancy or incomplete voiding of the bladder are
present with hematuria, the problem likely is in the lower urinary tract, although an
enlarged prostate constricting the urethra also may be involved. The enlargement
may be caused by a tumor, but it also can result from benign prostatic hyperplasia
(BPH), a common condition in men over age 40.
Abdominal pain with bleeding can be caused by inflammation of the kidney or
ureter resulting from trauma, infection or a tumor.
Fever typically indicates the presence of infection, typically of the kidney or ureter.
3. Describe the most common findings on history or
exam (signs) and patient complains (symptoms) at
presentation of the following clinical problems :
a. Renal tumors flank pain
Korteks

o Jinak adenoma, lipoma, hamartoma, onkositoma

o Ganas adenokarsinoma, nefroblastoma/tumor wilm

Sistem saluran

o Jinak papilloma

o Ganas tumor pelvis renalis

Renal cell carcinoma / adenoa ca / tumor grawitz / hipernefroma The majority of small renal
masses are RCCs. However, patients diagnosed with small RCCs are unlikely to have metastases at
presentation or to develop metastases during follow-up.

Benign renal tumors Small renal masses can also represent benign renal lesions. These included
oncocytoma (75 percent), angiomyolipoma (11 percent), and metanephric adenoma (3 percent).

Oncocytoma Oncocytoma typically appears on computed tomography (CT) or magnetic resonance

imaging (MRI) as a homogeneous, well-circumscribed solid mass containing a central scar. However,
these features are not sufficiently specific to exclude RCC.

Angiomyolipoma Angiomyolipomas can be reliably distinguished on imaging as an enhancing

mass that contains macroscopic fat and no calcifications. RCC, particularly the clear cell subtype, can
contain microscopic fat, but this can reliably be distinguished from macroscopic fat on imaging. Small
angiomyolipomas with minimal fat are difficult to characterize on imaging and generally require further
evaluation.

When renal angiomyolipomas are bilateral, patients have an 80 to 90 percent chance of having
tuberous sclerosis. Patients with tuberous sclerosis also have an increased frequency of RCC, although
malignancies are less common than with other hereditary syndromes such as von Hippel-Lindau
disease .

Metanephric adenoma Metanephric adenomas are rare benign lesions that are more common in
women than men. Although many cases are initially identified incidentally, some patients present with
pain, hematuria, or a palpable mass. Metanephric adenomas are defined by a characteristic histology
but may be difficult to distinguish from chromophilic (papillary) RCC or epithelial predominant Wilms
tumor.

Metastatic disease In patients with a history of a non-renal cancer, a solitary lesion in the kidney
may represent metastatic disease or a primary renal tumor. In a series of 2340 patients with a primary
non-renal cancer, 36 (1.5 percent) had a renal lesion concomitantly diagnosed. Of these, 21 (58
percent) were due to metastatic disease to the kidney; in the remaining 15 (42 percent), there was a
concomitant RCC.

Xanthogranulomatous pyelonephritis Xanthogranulomatous pyelonephritis is an unusual

variant of chronic pyelonephritis. In two-thirds of cases, it is a complication of urinary obstruction from
infected renal stones. Clues to the presence of xanthogranulomatous pyelonephritis include a history
of urinary tract infections and the presence of pyuria and bacteriuria at presentation. CT can suggest
this diagnosis by demonstrating an obstructing kidney stone and several rounded, low-density areas
corresponding to dilated calyces lined with necrotic xanthomatous tissue extending into the renal
parenchyma.
b. Bladder tumors

CLINICAL PRESENTATION Patients with bladder cancer classically present with painless hematuria
(grossly visible or microscopic), although irritative voiding symptoms (frequency, urgency, dysuria) can
be the initial manifestation. The diagnosis is often delayed due to the similarity of these symptoms to
those of benign disorders (urinary tract infection, interstitial cystitis, prostatitis, passage of renal
calculi), and delays can lead to a worsened prognosis due to more advanced stage at diagnosis. There
is evidence to suggest that delayed diagnosis accounts for the poorer survival in women diagnosed
with bladder cancer compared with men. Furthermore, symptoms are often intermittent. In some
patients, metastases will cause the initial symptoms. Incidental bladder cancer is rare at autopsy,
suggesting that most cancers eventually become symptomatic.

Hematuria The most common presenting symptom is hematuria, which is typically intermittent,
gross, painless, and present throughout micturition.

The likelihood of bladder cancer increases when the hematuria is gross (visible) or microscopic, with
some studies diagnosing bladder cancer in 10 to 20 percent of patients with gross hematuria. In those
evaluated for microscopic hematuria, the reported incidence of bladder cancer ranges between 2 and
5 percent

However, 9 to 18 percent of apparently normal individuals have some hematuria, and hematuria is due
to benign causes in most patients. The number of red blood cells in the urine is not predictive of the
probability of cancer.

The importance of evaluating hematuria was illustrated by a study of 1930 patients, in which 61
percent had no abnormality diagnosed. Abnormalities that were found included bladder cancer (12
percent), urinary tract infections (13 percent), medical renal disease (10 percent), stone disease (4
percent), kidney cancer (0.6 percent), and prostate cancer (0.4 percent). Bladder cancer was much
more frequent in older patients, but seven patients with bladder cancer were younger than 40 years,
including one with microscopic hematuria.

The point at which gross hematuria is noted during urination can be helpful in localizing its source:

Hematuria occurring primarily at the beginning of urination is usually from a urethral source.
Blood that is only noticed as a discharge between voidings or as a stain on undergarments,
while the voided urine itself appears clear, indicates an origin at the urethral meatus or the
anterior urethra.
Terminal hematuria, with blood appearing towards the end of voiding, generally originates from
the bladder neck or prostatic urethra.
Hematuria occurring throughout voiding can originate from anywhere in the urinary tract,
including the bladder, ureters, or kidneys.

Pain Pain associated with bladder cancer is usually the result of locally advanced or metastatic
tumors. Its distribution is related to the size and location of the primary tumor or its metastases:

Flank pain may result when a tumor obstructs the ureter at any level (bladder, ureter, or renal
pelvis). Although obstruction usually is associated with muscle-invasive disease, large noninvasive
tumors at the ureteral orifice may also cause symptoms. The pain is similar to that experienced
with the passage of urinary stones, and may or may not be associated with hematuria.
Suprapubic pain is usually a sign of a locally advanced tumor that is either directly invading the
perivesical soft tissues and nerves or obstructing the bladder outlet and causing urinary retention.
Hypogastric, rectal, and perineal pain can be signs of disease invading the obturator fossa,
perirectal fat, presacral nerves, or the urogenital diaphragm.
Abdominal or right upper quadrant pain may signal the presence of abdominal lymph node or
liver metastases.
Bone pain may indicate the presence of bone metastases.
Significant and persistent headache or disordered cognitive function may suggest the presence
of intracranial or leptomeningeal metastases.
 Voiding symptoms Voiding symptoms are most common in patients with carcinoma in situ
(CIS) of the bladder and may result from a functional decrease in the bladder capacity, detrusor
overactivity, invasion of the trigone, or obstruction of the bladder neck or urethra.

Irritative voiding symptoms (eg, daytime and/or nocturnal frequency, urgency, dysuria, or
urge incontinence) occur in approximately one-third of patients. The complex of dysuria,
frequency, and urgency in particular is highly suggestive of bladder CIS.
Obstructive voiding symptoms are less common and may be due to tumor location at the
bladder neck or prostatic urethra. Symptoms include straining, an intermittent stream,
nocturia, decreased force of stream, and a feeling of incomplete voiding. On occasion, gross
hematuria may result in "clot retention."

Constitutional symptoms Symptoms such as fatigue, weight loss, anorexia, and failure to
thrive are usually signs of advanced or metastatic disease and denote a poor prognosis. In rare
cases, patients may have constitutional symptoms due to renal failure caused by bilateral
ureteral obstruction.
Diagnosis
Palpasi Bimanual
Lab sel urotelium, antigen permukaan sel, flow cytometry
IPV filling defect
Tx
Reseksi vladder transurethra/TUR buli
Diversi urine

c.Prostate cancer

Symptoms Most men with early stage prostate cancer have no symptoms attributable to the
cancer. >50 tahun

Etiologi genetic, hormonal, diet lemak tinggi, lingkungan, infeksi, rokok dan kadmium

Urinary frequency, urgency, nocturia, and hesitancy are seen commonly but are usually related to
a concomitant benign prostate enlargement.

Hematuria and hematospermia are uncommon presentations of prostate cancer but their
presence in older men should prompt consideration of prostate cancer in the differential
diagnosis. These symptoms are also present in men with benign prostatic hyperplasia (BPH) and
are more likely to be caused by BPH than cancer.

Bone pain may be the presenting symptom in men with metastatic disease but an initial diagnosis
when bone metastases are present has become unusual.
Manfes PSA naik, colok dubur ada nodul keras, ultrasonografi transrektal (TRUS)
Tx observasi, prostatektomi, radiasi, hormonal (turunin androgen total)

d. Scrotal tumor

CLINICAL MANIFESTATIONS Testicular tumors usually present as a nodule or painless

swelling of one testicle, which may be noted incidentally by the patient or by his sexual partner.
Occasionally, a man with a previously small atrophic testis will note enlargement. Approximately
30 to 40 percent of patients complain of a dull ache or heavy sensation in the lower abdomen,
perianal area, or scrotum, while acute pain is the presenting symptom in 10 percent.

The presenting manifestations of testicular cancer are attributable to metastatic disease in

 approximately 10 percent of patients. Symptoms vary with the site of metastasis:

A neck mass (supraclavicular lymph node metastasis)

Cough or dyspnea (pulmonary metastasis)
Anorexia, nausea, vomiting, or gastrointestinal hemorrhage (retroduodenal metastasis)
Lumbar back pain (bulky retroperitoneal disease involving the psoas muscle or nerve roots)
Bone pain (skeletal metastasis)
Central or peripheral nervous system symptoms (cerebral, spinal cord, or peripheral root
involvement)
Unilateral or bilateral lower extremity swelling (iliac or caval venous obstruction or
thrombosis)

Gynecomastia, which occurs in about 5 percent of men with testicular germ cell tumors (GCTs), is
a systemic endocrine manifestation of these neoplasms. It also occurs in 20 to 30 percent of
patients with the less common (2 percent of testicular tumors) Leydig cell tumors of the testes.
These tumors are found in 6- to 10- year-old boys who present with precocious puberty and in 26-
to 35-year-old men who present with a testicular mass, gynecomastia, impotence, and loss of
libido.

Gynecomastia is usually associated with production of human chorionic gonadotropin (hCG) by

foci of choriocarcinoma or trophoblastic cells in the tumor. However, the relationship between
gynecomastia, testicular tumor morphology, and endocrine abnormalities remains incompletely
defined. In individual patients, gynecomastia may or may not be associated with elevated serum
concentrations of hCG, human chorionic somatomammotropin, prolactin, estrogens, or androgens.

Patients with marked overproduction of hCG can develop another endocrine complication,
paraneoplastic hyperthyroidism. Thyroid-stimulating hormone and hCG have a common alpha-
subunit and a beta-subunit with considerable homology. As a result, hCG has weak thyroid-
stimulating activity.

Patients with testicular cancer also may develop a paraneoplastic limbic encephalitis. Most of
these patients have anti-Ma2 (also called anti-Ta) antibodies. The Ma2 antigen is selectively
expressed in the neuronal nucleoli of normal brain tissue and the testicular tumor of the patient.

Testicular examination Physical examination of the testes should begin with bimanual
examination of the scrotal contents, starting with the normal contralateral testis. This permits
the examiner to appreciate the relative size, contour, and consistency of the normal testis as a
baseline for comparison of the suspected gonad. The testis should be carefully palpated between
the thumb and first two fingers of the examining hand.

The normal gonad is homogeneous in consistency, freely movable, and separable from the
epididymis. Any firm, hard, or fixed area within the substance of the tunica albuginea should be
considered suspicious until proven otherwise. Further evaluation of the affected side should be
directed toward possible involvement of the spermatic cord, scrotal investments, or skin.

Testicular tumors tend to remain ovoid, being limited by the tough investing tunica albuginea.
However, spread to the epididymis or spermatic cord occurs in 10 to 15 percent of patients. In
general, a seminoma tends to expand within the testis as a painless, rubbery enlargement, while
an embryonal carcinoma or teratocarcinoma forms an irregular mass with indiscrete borders.
However, this distinction is not always easily appreciated.

A hydrocele may be present and can make evaluation of a suspected testicular tumor more
difficult. In such cases, ultrasonography of the scrotum is a rapid, reliable technique to exclude a
hydrocele or epididymitis; it is indicated in any man with a suspected testicular tumor.

Physical examination should also include palpation of the abdomen for evidence of nodal disease
or visceral involvement. Routine assessment of the supraclavicular lymph nodes may reveal
adenopathy in men with advanced disease. Examination of the chest may disclose gynecomastia
or raise suspicion for thoracic involvement.

Cryptorchidism Men with a history of cryptorchidism and a prior orchiopexy are at increased
risk for testicular cancer in both testes (greater in the undescended one), although the
magnitude of increased risk compared with men in the general population is poorly quantified.
Regardless, testicular self-examination is an important part of the routine evaluation. Because of
the rarity of such tumors, surveillance scrotal ultrasound (in the absence of clinical exam
findings) is not indicated.