patho sheet (#3 of dr faisal urinary tract) - Haitham Alnoti

In the name of god


# RAPIDLY PROGRESSIVE (CRESCENTIC) GLOMERULONEPHRITIS
Rapidly progressive glomerulonephritis (RPGN) is a syndrome associated with severe glomerular injury and does not denote a specific etiologic form of glomerulonephritis. It is characterized clinically by rapid and progressive loss of renal function associated with severe oliguria and (if untreated) death from renal failure within weeks to months. Regardless of the cause, the classic histologic picture is characterized by the presence of crescents in most of the glomeruli (crescentic glomerulonephritis). As discussed earlier, these are produced in part by proliferation of the parietal epithelial cells lining Bowman capsule and in part by infiltration of monocytes and macrophages.

Classification and Pathogenesis
RPGN may be caused by a number of different diseases, some restricted to the kidney and others systemic. Although no single mechanism can explain all cases, there is little doubt that in most cases, the glomerular injury is immunologically mediated. Thus, a practical classification divides RPGN into three groups on the basis of immunologic findings . In each group, the disease may be associated with a known disorder, or it may be idiopathic.
About 12% of patients have Type I RPGN (Anti-GBM ( glomerular basement membrane) Antibody) with or without lung involvement . 44% of patients have Type II RPGN (Immune Complex) , and the last 44% have Type III RPGN (Pauci-Immune) …… all have sever glomerular injury .
The first type of RPGN is best remembered as anti-GBM antibody-induced disease and hence is characterized by linear deposits of IgG and, in many cases, C3 in the GBM, as previously described. In some of these patients, the anti-GBM antibodies cross-react with pulmonary alveolar basement membranes to produce the clinical picture of pulmonary hemorrhage associated with renal failure (Goodpasture syndrome ) .
……As you know Goodpasture syndrome is characterized by the presence of a peptide within the noncollagenous portion of the α3-chain of collagen type IV. Which triggers the formation of these antibodies ( is antigen is common in the basement membrane of both the kidney and lung so it cause pulmonary hemorrhage associated with renal failure ) .
We can find these antibodies in the patient serum so they are helpful in this disease diagnosis ………..so , we use Plasmapheresis to remove the pathogenic circulating antibodies is usually part of the treatment, which also includes therapy to suppress the underlying immune response.
morphology
The kidneys are enlarged and pale, often with petechial hemorrhages on the cortical surfaces. Depending on the underlying cause, the glomeruli may show focal necrosis ( or segmental necrosis ) and breaking of the GBM, diffuse or focal endothelial proliferation, and mesangial proliferation. …a proper ratio of (proliferation) of parietal epithelial cells in response to the oxidation of the plasma proteins include fibrin and obliterate Bowman space …. formation of distinctive crescents which is formed by the oxidation of proteins in the bowman space ( specially fibrin ) which induces the proliferation of parietal epithelial cells .
By immunofluorescence microscopy , this case is characterized by the presence of strong stain for linear granular immune deposits of IgG and C3 along the GBM ( we can not see them by the electron microscope ( - ve test ) but it may show distinct ruptures in the GBM … Fibrin strands are prominent between the cellular layers in the crescents and with time they become scraped ( at the beginning they are cellular and with time they undergo sclerosis ) .
Note : we can see in the book figures the presence of inflammatory cell around crescents ( we can find leukocytes, proteins, and inflammatory mediators into the urinary space, where they trigger the crescent formation ) .
The second type of RPGN is the result of immune complex-mediated disease. It can be a complication of any of the immune complex nephritides, including postinfectious glomerulonephritis, SLE, IgA nephropathy, and Henoch-Schönlein purpura. In all of these cases, immunofluorescence studies reveal a characteristic granular ( lumpynupy … check it please ) pattern of staining for the GBM (immune complex deposition ) and those mesangium (mesangial cell )for immune complex are called complement .
…… These patients cannot usually be helped by Plasmapheresis, and they require treatment for the underlying disease. ( coz it is an accumulation of immune complex in the kidney ) .
There is sever injury with segmental necrosis at GBM breaks with resultant crescents formation . in contrast to the Type I RPGN segments of the glomeruli without necrosis show evidence for the underlying immune complex glomerulonephritis ( in type 1 the segments of glomeruli without necrosis don't show pathologic effect .. this isn't true for type 2 which show evidence of the disease ) .
immunofluorescence microscopy show a characteristic granular pattern , while electron microscope show discreet deposits .

The third type of RPGN, also called pauci-immune type, is defined by the lack of anti-GBM antibodies or immune complexes by immunofluorescence and electron microscopy. Most patients with this type of RPGN have antineutrophil cytoplasmic antibodies (ANCA), of cytoplasmic (C) or perinuclear (P) patterns, in the serum, which, as we have seen , play a role in some vasculitides. Hence, in some cases, this type of RPGN is a component of a systemic vasculitis such as Wegener granulomatosis or microscopic polyarteritis. In many cases, however, pauci-immune crescentic glomerulonephritis is isolated (restricted to the kidney ) and hence idiopathic.
And here again we can see a segmental necrosis … GBM breaks ( like type 1 we don't see the disease changes on the un affected segments of glomeruli as in type 2 ) .
immunofluorescence microscopy doesn't show a characteristic granular pattern ( for immunoglobulins and complements , also electron microscope doesn't show discreet deposits ( both are – ve so we call it pauci ) .
the onset of (RPGN) is much similar to that of NEPHROTIC SYNDROME but Polyurea and azotemia are not pronounced . proteinurea reaching NEPHROTIC SYNDROME sometimes occurs ,some of these patients may become anuric and require long term dialysis or transplantation . the prognosis may be built on the number of crescents ( patients with crescents in less than 80 % of their glomeruli have better prognosis ).
Plasma exchange manifest some individuals particularly those with (Anti-GBM Antibody) RPGN and Goodpasture syndrome .

CHRONIC GLOMERULONEPHRITIS is a chronic glomerular disease . irrespective of their reasons ….. (patients) receiving glumeruloinflammatory injury … it is an important cause of end stage renal disease that is presenting as chronic renal failure.
Among all individuals how require renal hemo dialysis or renal transplantation 50 % have the diagnosis of CHRONIC GLOMERULONEPHRITIS .
By the time CHRONIC GLOMERULONEPHRITIS is discovered , the glomerular changes has occurred (that is difficult to determine the nature of the original lesion ).a proper Varity of entities represented at this stage among which crescentic glomerulonephritis , focal segmental sclerosis , membranous nephropathy ,IgA nephropathy , membrane proliferative glomerulonephritis .( so we look to it as an end stage disease ).
It has been estimated that about 20 % of cases arise with no history of symptomatic renal disease ( they represent for the first time as CHRONIC GLOMERULONEPHRITIS .

Morphology
Classically, the kidneys are symmetrically contracted and have diffusely granular ,and their surfaces are red- brown diffuse granular . microscopically the features are a band scaring of glomeruli and sometimes a degree ( rarely to great) sclerosis .. there is also interstitial fibrosis associated with atrophy of the tubules . the small and medium size arteries are thick walls and narrow secondary to hypertension ,and in (plus) cases it is difficult to assure if the primary lesion is glomerular , tubular , vascular or interstitial . such markedly damage kidney is refer to as end stage kidney .
Most often CHRONIC GLOMERULONEPHRITIS develops seriously and discovered late in scares ( proteinurea ,microscopic hematuria , hypertension are usually present ). without treatment the prognosis is poor ,and progression to renal failure is the rule . renal dialysis , renal transplantation alter the course in these patients . (A Masson trichrome preparation \ stain is used to give the blue color for the fibrous tissue )

# Diseases Affecting Tubules and Interstitium
It refer to a group of inflammatory diseases of the kidney that primarily involve the tubules and interstitium the glomeruli may be spared or affected late in the course of the disease .
Most cases of Tubular and Interstitial diseases are caused by bacterial infection …. The renal pelvis is prominently involve ( in these cases ) ,hence the more descriptive term is pyelonephritis.
The term interstitial nephritis is generally reserved to the tubular interstitial nephritis that are not bacterial in origin …. These include tubular injury due to drug , vascular injury, minor infection, metabolic disorder ,immune reactions.

Acute Pyelonephritis
Acute pyelonephritis is an acute suppurative inflammation of the kidney and pelvis caused by bacterial infections . the great majority of these cases are associated with infection of lower urinary tract infection which mainly remain localized without the involvement of the kidney .
The principle causative agent is the gram – ve rod bacteria E- coli ( most common one …. Others include proteus , klebsiella , Pseudomonas , enterobacter . these are most commonly associated with recurrent infection especially in urinary manipulated individuals ( urinary instrumentation )or Persons have (congenital or acquired) lower urinary tract anomalies .

There are two routes by which bacteria can be transferred ( disseminate to the target tissue :
- blood stream ( hematogenous )
- ascending urinary tract infection ( urinary tract infection )

although the hematogenous is the less common of them , Acute Pyelonephritis may be caused by seeding of the kidney by bacteria originates from bacterial septicemia or infective endocarditis .
ascending infections of the urinary tract are the most common route by which ( bacteria ) affect the kidney in a several steps process ( pathogenesis ):
_ the adhesion of bacteria to the mucosal surface of the kidney followed by colonization of the distal urinary tract .
Genetically determined property of both the uricelium and the bacterial pathogen may facilitate the adhesion to the urinary lining by bacterial tympani common in appetite to the infection ( so factors related to the host and the bacteria have a role in the occurrence of urinary tract infection and the recurrence in other persons ) .
Travenza must be an access to the bladder by expressive growth of the colony and moving against the flow of urine . this may occur during urine instrumentation including catheterization and (the soft copy ) which are important predisposing factor for the pathogenesis of urinary tract infection . n the absence of instrumentation , urinary tract infection most commonly affect females because the close proximity of the urethra to the rectum and the short urethra in females . also the trauma to the urethra during sexual intercourse which facilitate the entry of bacteria to urinary bladder .
Normally , bladder urine is sterile and remain so as a result of flushing action associated with periodic voiding of urine . when outflow obstruction or bladder dysfunction , the natural defense mechanisms are overlong ( seven ) stages for urinary tract infection .
With obstruction at the level of bladder , incomplete emptying and increase of urine lead to increase in the cases of bacterial infections . accordingly UTI is frequent in patient with benign prostatic hyperplasia and uterine prolapse ( in females ) .
UTI increase in patient with diabetes as a result of a neurological dysfunction of the bladder and increase appetite to infections .
Although obstruction is a common predisposing factor for infection , it is the incompetence of ureter orifice ( vesicoureteral junction ) that allow bacterial ascending to the through the ureter into the pelvis .
# note : normally the ureter meet the bladder at acute angle . at the time of bladder emptying , the contraction of the bladder cause obstruction of the ureter orifice …… so urine can not return to the kidney . some people with congenital abnormality in the insertion of the ureter in the bladder have lager angle ….. so contraction of the bladder doesn't prevent the urine reflux to the ureter ….. this condition occurs in patient with vesicoureteral reflux congenital anomaly . these patient are more susceptible to:
- the ascending UTI infection (Pyelonephritis )
- transmission of diseases from the bladder to the pelvis through ureter .
reflux presents in 20- 40 % of young children with UTI , it is usually congenital defect that cause the ureterovesical junction to be incompetence . it may be acquired in persons with spinal cord injury or (bladder) dysfunction in the ureter .
one of the kidney may be involved . affected kidney may be normal in size or enlarged ……discrete abscesses are grossly visible on the kidney surface . the characteristic histologic features of Acute Pyelonephritis are suppurative necrosis or abscesses formation in the renal parenchyma , large masses of inter tubular neutrophil exist in the infected nephron and extend to reach collecting duct giving rise to charcterstic white cells present in the urine …. Typically the glomeruli are not affected . a second form of Acute Pyelonephritis is necrosis of the renal papillae known as papillary necrosis . it is seen mainly in diabetics and in those with urinary tract obstruction . it is also seen in patient with analgesic abuse . it is a combination of ischemic and suppurative necrosis in the tips of the pyramid in the renal papillae . the pathgnomanic gross features of the papillary necrosis is sharply defined ganular necrosis of the apical 2\ 3 of the renal pyramid . Acute Pyelonephritis is often associated with predisposing factors include :
urinary obstruction , instrumentation , vesicoureteral reflux .
in pregnancy 4 -6 % develop bacterurea in pregnancy . 40 % of these develop symptomatic UTI if not treated . in the first years of age , infections are more common in females . after that ( older age ) the infection rate increase in males due to benign prostatic hyperplasia and instrumentation . ( so generally speaking … before the age of 40 UTI are more common in females …. But after 40 it is more common in males due to ……… ) .
plzzzzzz be careful ….
In the first year of age specially the UTI are more common in boys because the congenital abnormalities are more common in boys .
Pre existing renal lesion cause intra renal scaring , diabetes mellitus , immuno deficiency \ suppression is also seen . ( these are the pre disposing factor for the renal infection ) .

The onset of disease is sudden , with pain at costovertbral angle …. Chills , fever and malaise …. Urinary finding include biurea ( WBCs in urine ) , bacterurea usually with bladder and urethral irritation symptoms like dysurea ( pain with urination ) , agency ( patient feels that he must urinate quickly ) frequency ( increase rate of urination ) . even without antibiotic treatment , disease tends to be benign and self limited …… the disease is usually unilateral so patient doesn't develop renal failure .
Development of papillary necrosis is associated with poorer prognosis . the diagnosis is established by the finding of neutrophil in urine and urine culture ( it is important (before antibiotic treatment) to take urine sample and make urine culture to detent the presence of specific micro organism ….. to make hypersensitivity test to choose the best treatment ) .
Notes :
Abscesses on the kidney surface contain neutrophil
The tip of the papillae in the papillary necrosis contain suppurative puss
The best marker in the Acute Pyelonephritis is the presence of the neutrophil infiltrate in kidney ……. WBCs in urine .

#3 from urinary tract