Batool Hasanatpathology 2 – sheet #1 17/Feb/2014

Urinary Tract Pathology- 1

The subject of urinary tract pathology will discussed in the first 4 lectures of this semester .

Basic four histological structures of kidney :

glomerulus Renal tubules Renal interstitial Blood vessels

Any one of those can effect of any disease ; we will discuss the glomerulus nephritis, tubulointerstitial nephritis and inflammation, renal stones, and renal tumors .

First topic will be about URINARY OUTFLOW OBSTRUCTION

Causes :

Renal tumors Foreign body Renal stones (the most common ) it’s called urolithiasis - lithiasis came from stone -

Renal stone – urolithiasis – is calculus formation at any level in the urinary collecting system; starting from the renal pelvis(kidney) > ureters > urinary bladder > urethra but most often the calculi arise in the kidney and at any level the stone can form and lodge there cuz an obstruction and related symptom .

it can be seen in 1% of all autopsies (the specimen that taken after death).

Symptomatic urolithiasis is more common in men than in women , female could have renal stone without any symptoms for long period of time . but in male the problem is usually symptomatic .

A familial tendency toward stone formation has long been recognized , but nothing is recommended.

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Batool Hasanatpathology 2 – sheet #1 17/Feb/2014

Type of renal stone :1. Calcium ( 80% most commen) composed of either calcium oxalate or calcium oxalate mixed

with calcium phosphate.2. Struvite ; magnesium ammonium phosphate ( 10% ) 3. uric acid stones ( 6%-7% ) , rare 4. cystine stones ( 1%-2% ) , rare

In all cases ( in any stones type ) there are a cores of mycoprotein ; organic matrix that help in the aggregation of the ions ( Calcium , magnesium ammonium phosphate ,…) above them and form the stones .it’s makes up about 2.5% of the stone by weight .

The cause is often obscure (unknown ) , especially in calcium-containing stones. It’s not necessary to have patient with hypercalcemia or hypercalciuria to get the calcium stones .So most the time the stones are formed but the causes are unknown , probably multifactorial causes ; familial causes ,environmental causes ,… .

Pathogenesis (the way the stones form ):

1. increased urine concentration of the stone's constituents (the most important cause ) so that it exceeds their solubility in urine (supersaturation : high concentrated ions in the urine, one of them calcium) . so the hypercalciuria is consider as cause of stone formation - not the only cause - .

50% of patients who develop calcium stones have hypercalciuria that is not associated with hypercalcemia. But only 5% -10% of the patients have hypercalcemia associated with hypercalciuria.

Hypercalciuria : increase calcium concentration in the urine

It’s causes :

Excessive absorption of calcium from the gut (absorptive hypercalciuria) and promptly excrete it in the urine.

Primary renal defect of calcium reabsorption (renal hypercalciuria).

Hypercalcemia : increase calcium concentration in the blood

It’s causes :

Hyperparathyroidism .. parathyroid hormones ;secreted from parathyroid gland; increase calcium absorption from gut and calcium mobilization from the bone marrow so the net result increase the calcium level in the blood .

vitamin D intoxication .. the people who take high amount of vitamin D will lead to hypercalcemia cuz it’s help in calcium absorption .

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Batool Hasanatpathology 2 – sheet #1 17/Feb/2014

sarcoidosis .. autoimmune disease one of it’s feature is hypercalcemia .

In 20% of patients with hypercalcemia there is excessive excretion of uric acid in the urine which favors calcium stone formation.

As we said before there are uric acid stones and cystine stones which are rarely happen, but in order to form the calcium stones they need uric acid nidus .

In 5% of patients who develp stone they have hyperoxaluria (oxalate in urine ) or hypercitraturia (citrate in urine )

2. PH of the urine All the stones except uric acid and cystine stone(they need acidic urine to form ) espically cacium stone required high PH; alkaline urine ; to be formed berceuse the high urine PH favourable the crystallization of calcium and magnesium ions and stone deposition .The causes of alkaline urine is urinary tract infection.

3. Infection The people who have recurrent infection favourable to form renal stone . one of the suggestion mechanism is that bacteria which cause the urinary tract infection (urea-splitting bacteria ) such as Proteus vulgaris and the staphylococci, predisposed the patient to have alkaline urine that predisposed the stone formation (urealithlasis ).

Another mechanism , the urea-splitting bacteria by itself form a nidus ( center of the stone ) like mycoprotein , which help the aggregation of ions over the bacteria itself ending by stone formation .

4. Avitaminosis A , commen in female High level of vitamin A that lead to Desquamation which mean that the lining of the urinary bladder in some area specially in the female trigone of the bladder(The trigone is a smooth triangular region of the internal urinary bladder formed by the two ureteral orifices and the internal urethral orifice)

lined by squamous epithelium rather than the normal transitional epithelium that line the urinary tract (in female normally the trigone have squamous metaplasia ) this squamous cells when they desquamate from the metaplastic epithelium of the collecting system act as nidus for renal stone formation .

5. Gout and diseases involving rapid cell turnover, such as the leukemias Susceptible for uric acid stone rather than calcium and magnesium stones . gout and rapid turnover make progressive damaged to the cells which have a uric acid as one of the DNA component so it will lead to high uric acid level in the urine .

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Batool Hasanatpathology 2 – sheet #1 17/Feb/2014

50% of the individuals with uric acid stones, however, have neither hyperuricemia nor increased urine urate but an unexplained tendency to excrete a persistently acid urine (under pH 5.5).

This low pH favors uric acid stone formation in contrast to the high pH that favors formation of stones containing calcium phosphate.

It’s the same as calcium stone ; not necessary to associated with hyperuricemia , so the gout disease increase the risk of uric acid stone by increase the uric acid concentration in the urine . 50% dosen’t have hyperuricemia ( high uric acid in the blood ) or hyperuricosuria ( uric acid elevation in the urine .

6. Cystine stonesare almost invariably associated with a genetically determined defect in the renal transport of certain amino acids, including cystine. More likely to form when the urine is relatively acidic .

7. lack of substances that normally inhibit mineral precipitation.

Inhibitors of crystal formation in urine (anti-urelithiasis ; prevent the crystallization and stone formation ) include :

Tamm-Horsfall protein osteopontin pyrophosphate mucopolysaccharides diphosphonates a glycoprotein called nephrocalcin

So logically any deficiency of those will susceptible to the stone formation ; however no deficiency of any of these substances has been consistently demonstrated in individuals with urolithiasis but it’s still a suggested mechanism .

Clinical course ( clinical consequences ) Female in most time have asymptomatic renal damage

1-Stones may be present without producing either symptoms or significant renal damage -silent - .

Especially with large stones lodged in the renal pelvis ( where the calyces are met to join with the ureter) . if this large stone stay there may be disposed symptoms but most of the time it’s won’t produce symptom because the urine pathway still open and the urine can flow and go outside .

The highly symptomatic cases when the stone found in the ureter or the opening of the ureter to the urinary bladder (narrower areas) or in the urethra .

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Batool Hasanatpathology 2 – sheet #1 17/Feb/2014

2-Smaller stones may pass into the ureter ( which make sense ), producing a typical intense pain known as renal or ureteral colic الكلوي . المغص

It is characterized by paroxysms of flank pain radiating toward the groin and intermittent in attacks (berceuse the pain felt when the stone move from it’s place to another ).

3-Hematuria (Blood in the urine)

the stone produce ulceration and irritation of the urinary mucosa end by presence of the blood in the urine (hematuria ) ; which can be

gross hematuria : visual change in the urine color to cola color urine due to the acidity / alkalinity of the urine which effect it’s color

microscopic hematuria : only identified in urine analysis by noticed the presence of RBCs in the urine .

Complications of stone formation :

• obstruction of urine flow (renal colic ) or to produce sufficient trauma to cause ulceration and bleeding ( hematuria )

• predispose the sufferer to bacterial infection ; because of the stagnation of urine which is the result of presence of stones that preduce good media for bacterial growth

• renal damage ; people who have a stone and ledge for long period of time, with time they will get hydronephrosis ( the calyceal system and pelvis of the kidney will be dilated and cause pressure on the renal cortex ( they will have atrophy ) and by the time it will lead to infection and scares so the renal damage is ultimate result .

Morphology• Stones are unilateral in about 80% of patients. Unlikely to be bilateral .

• Common sites of formation are renal pelvis and calyces, and the bladder , form there and can be transmitted to the ureter from the renal pelvis and calyces and to urethra and urinary bladder . sometime in the bladder they can impinge to the opening orifice of the ureter bilaterally and cause obstruction there and leading to consequence of obstruction, renal damage , infection ,and pain .

• They tend to be small (average diameter 2-3 mm) and may be smooth or jagged outer surface .

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Batool Hasanatpathology 2 – sheet #1 17/Feb/2014

• Occasionally, the staghorn calculi ( large stone ) will form ,which branching structures development due to progressive accretion of salts that create a cast of the renal pelvis and calyceal system (take the shape of them ). These massive stones are usually composed of magnesium ammonium phosphate . but the small stones are composed of calcium .

Hydronephrosis important consequence of renal stone .

hydro : water , nephrosis : dilatation

• Hydronephrosis refers to dilation of the renal pelvis and calyces ( in severe cases the ureter will effected ; dilate and tortuous ), with accompanying atrophy of the parenchyma, caused by

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Abnormal kidney

The renal calyces and renal pelvis large in size which is abnormal

Atrophy of renal cortex because of the pressure that produce due to hydronephrosis

Renal pelvis = where the urine collect after get out from kidney

Calyces = usually 7 in number , met to form renal pelvis

Renal cortex and medulla = tissue of

the kidney

Batool Hasanatpathology 2 – sheet #1 17/Feb/2014

obstruction (related to stone formation ) to the outflow of urine. So if there is stone at the ureter, the urine will accumulate above the renal pelvis ,the urine can’t pass the result will be dilation of the renal pelvis and calyces .

• The obstruction may be sudden or insidious (slowly accumulate until the kidney size became large and form a mass that can palpate by the physician) , and it may occur at any level of the urinary tract, from the urethra to the renal pelvis .

Causes of hydronephrosis : all of them lead to obstruction then hydronephrosis as consequences

Congenital: discover immediately after birth ; kidney very large and dilated o Atresia ( close ) of the urethra ; the lumen full of fibrous tissue o valve formations in either ureter or urethra ( normally should not be a valve in

both )o aberrant ( abnormal ) renal artery compressing the ureter from outside o kinking ( إلتواء) of the ureter

Acquired:o Foreign bodies: Calculi (stone).o Tumors:

Benign prostatic hyperplasia, carcinoma of the prostate. bladder tumors (papilloma and carcinoma). contiguous malignant disease (retroperitoneal lymphoma, carcinoma of

the cervix or uterus)

o Inflammation: Prostatitis, ureteritis, urethritis. ( edema = obstruction = hydronephrosis )

o Neurogenic: Spinal cord damage with paralysis of the bladder( no contraction = stagnation of urine = accumulation of urine =dilatation )

o Normal pregnancy: Mild and reversible ( common cause , the pregnancy uterus will compress on the urinary bladder . after delivery everything back to normal.

Bilateral hydronephrosis occurs only when the obstruction is below the level of the ureters (ex : prostatic hyperplasia ). If blockage is at the ureters (cuz they are 2 in number ) or above, the lesion is unilateral.

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Batool Hasanatpathology 2 – sheet #1 17/Feb/2014

Clinical course ( hydronephrosis ) : Unilateral bilateral “ complete , incomplete “

Bilateral complete , out sudden obstruction produces anuria ( no urine output ) the kidneys will be non functional which is soon brought to medical attention. Emergency situation if it not treated = renal damage .

When the obstruction is below the bladder, the dominant symptoms are those of bladder distention.

Paradoxically, incomplete bilateral ( one of the kidneys is normal and functional so it will compensate the reduction of the effected kidney ) obstruction causes polyuria(increase urine output ) rather than oliguria( reduction of urine output ), as a result of defects in tubular concentrating mechanisms because of the atrophy of renal cortex .

Unfortunately, unilateral hydronephrosis may remain completely silent for long periods unless the other kidney is for some reason not functioning.

Often the enlarged kidney is discovered on routine physical examination..

Sometimes the basic cause of the hydronephrosis, such as renal calculi or an obstructing tumor, produces symptoms that indirectly draw attention to the hydronephrosis. So as we said before hydronephrosis may remain completely silent for long periods but what make it appear is the causes of it such as renal calculi or an obstructing tumor cause hematuria , the patient came because of one of them , not because the enlarged kidney (mass) or hydronephrosis .

Removal of obstruction within a few weeks usually permits full return of function; however, with time the changes become irreversible.

Done By : Batool Mohammad

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