TUBULO-INTERSTITIAL TUBULO-INTERSTITIAL NEPHROPATHYNEPHROPATHY

Conf.Dr. Mircea PENESCUConf.Dr. Mircea PENESCU

Definition. ClassificationDefinition. Classification

Interstitial Nephropathies are acute or chronic renal pluriethyological Interstitial Nephropathies are acute or chronic renal pluriethyological disorders, histopathologically carracterised by the predominant involvement disorders, histopathologically carracterised by the predominant involvement of the renal interstitia and tubuli; glomerular and vascular lesions being of of the renal interstitia and tubuli; glomerular and vascular lesions being of minor importance.minor importance.

Ethyologic criteriaEthyologic criteria

- TIN microbian infections - TIN microbian infections

- Non specific- Non specific

- Specific- Specific

Ethyologic and morphologic criteriaEthyologic and morphologic criteria - Secondary to infections ITN- Secondary to infections ITN

- Tuberculosis ITN- Tuberculosis ITN

- Leprous ITN- Leprous ITN

- - ITN : - Infectious mononucleosisITN : - Infectious mononucleosis - Typhoyd fever - Typhoyd fever - Toxoplasmosis- Toxoplasmosis - Aspergilosis- Aspergilosis - Candidosis- Candidosis - Sarcoidosis ITN- Sarcoidosis ITN - Necrosante angeitis ITN:- Necrosante angeitis ITN: - Wegener granulomatosis- Wegener granulomatosis - Family chronic granulomatosis- Family chronic granulomatosis - Criptogenic granulomatosis- Criptogenic granulomatosis

Topographic criteriaTopographic criteria:: - unilateral NTI- unilateral NTI - bilateral NTI- bilateral NTI

Evolutive criteriaEvolutive criteria:: - acute- acute - chronic- chronic

Ethyopathogenic criteria:Ethyopathogenic criteria: - urologic cause- urologic cause - medical cause- medical cause - unknown ethiollogy - unknown ethiollogy

PathogenyPathogeny

The majority of TIN are determined by infectious or toxic factors, acting The majority of TIN are determined by infectious or toxic factors, acting directly on tubuli and interstitiadirectly on tubuli and interstitiaInvolved germs are acting either directly on renal structures, or through the Involved germs are acting either directly on renal structures, or through the endotoxines they are eliminating in the circulation.endotoxines they are eliminating in the circulation.Medication and toxic substances are acting on certain zones of the kidney, Medication and toxic substances are acting on certain zones of the kidney, so they have special tropism so they have special tropism The involvement of the immune mechanisms in the genesis of TIN is only The involvement of the immune mechanisms in the genesis of TIN is only partially demonstrated:partially demonstrated:

- induction through experimental patterns on animals through - induction through experimental patterns on animals through certain immunologic methodscertain immunologic methods - composition of the inflammatory infiltrate – limphocythes - composition of the inflammatory infiltrate – limphocythes plasmocythesplasmocythes - frequent translation from acute into chronic forms - frequent translation from acute into chronic forms - immunologic mechanism can perpetuate the inflammatory - immunologic mechanism can perpetuate the inflammatory response even in case the initial response was not immunologicresponse even in case the initial response was not immunologic

FisiopathologyFisiopathologyAnathomo functional particularities responsible for making kidneys Anathomo functional particularities responsible for making kidneys vulnerable to certain aggressions vulnerable to certain aggressions ::

- high blood flow- high blood flow - the capacity of the nephrocytes to decuplate proteic chains - the capacity of the nephrocytes to decuplate proteic chains

- substances that normally are not toxic to pH = 6,8-7,4 levels can - substances that normally are not toxic to pH = 6,8-7,4 levels can became very toxicbecame very toxic - fagocythosis is diminished in conditions of raised osmolarity- fagocythosis is diminished in conditions of raised osmolarity - high concentration of ammonia in the renal interstitia inhibits the - high concentration of ammonia in the renal interstitia inhibits the

activation of the complementactivation of the complement

FFunctional consequences of the involvement of medullar structures (Henle unctional consequences of the involvement of medullar structures (Henle ansa, vasa recta, interstitial cells and collecting tubulli) are :ansa, vasa recta, interstitial cells and collecting tubulli) are :

-- lowering of the concentration capacity of urinelowering of the concentration capacity of urine - lowering of the renal capacity of preserving sodium- lowering of the renal capacity of preserving sodium - renal acidosis- renal acidosis - reduced renal excretion of potassium- reduced renal excretion of potassium

Pathologic AnatomyPathologic AnatomyMacroscopyMacroscopy

- smaller kidneys, unequally - smaller kidneys, unequally dimensioned in shape and weight dimensioned in shape and weight - irregular surface, with profound scars- irregular surface, with profound scars - capsulla appears as tight, fibrosed, infiltrated - capsulla appears as tight, fibrosed, infiltrated - in transversal section white traces appear, going from the papilla to the - in transversal section white traces appear, going from the papilla to the cortexcortex

MicroscopyMicroscopy - - predominency of lesions in the renal interstitium, to be evidenced predominency of lesions in the renal interstitium, to be evidenced mostly in the cortical zone (area)mostly in the cortical zone (area) - alternation between inflammatory zones and healthy parenchyma- alternation between inflammatory zones and healthy parenchyma - dominant lesions are in the renal interstitium and secondary ones in the - dominant lesions are in the renal interstitium and secondary ones in the tubestubes - tubular lesions are of variable degrees, out of simple tumefaction of the - tubular lesions are of variable degrees, out of simple tumefaction of the tubular epithelial cells up to tubulo-necrosis and tubulo-rhexistubular epithelial cells up to tubulo-necrosis and tubulo-rhexis

Pathologic Anatomy (2)Pathologic Anatomy (2)

Glomeruli and vases frequently appear as normal or sometimes a Glomeruli and vases frequently appear as normal or sometimes a certain degree of ischemia can be evidencedcertain degree of ischemia can be evidencedRenal papilla is affected in certain ethyologic formes of TIN (analgetic, Renal papilla is affected in certain ethyologic formes of TIN (analgetic, diabetus melitus, obstruction of urinary tract, siclemya, etc…) going diabetus melitus, obstruction of urinary tract, siclemya, etc…) going up to papillar necrosisup to papillar necrosisThe IF examination can evidence different aspects:The IF examination can evidence different aspects:

- presence of anti-MBT antibodies- presence of anti-MBT antibodies - presence of immune complexes (Ig and C) alongside - presence of immune complexes (Ig and C) alongside the MBT and in the renal interstitium the MBT and in the renal interstitium - non-specific abnormalities, fibrin in the interstitia - non-specific abnormalities, fibrin in the interstitia linear or granular linear or granular CC33 alongside the MBT alongside the MBT

Fig. 1Fig. 1.. .. Chronicpielonephritis is suggested by tubulo-interstitial fibrosis and glomerular Chronicpielonephritis is suggested by tubulo-interstitial fibrosis and glomerular scars, irregularly distributed, in alternance with healthy (intact) zones . There is to be scars, irregularly distributed, in alternance with healthy (intact) zones . There is to be

noted a disproportion between the tubul interstitial inflammation always evidenced and noted a disproportion between the tubul interstitial inflammation always evidenced and the discreet glomerular involvement (jones Silver coloration ; the discreet glomerular involvement (jones Silver coloration ; X 100 ) )

Fig. 2.Fig. 2. Glomerular scars evidenced with focal and segmental location in the course of a PNC throughGlomerular scars evidenced with focal and segmental location in the course of a PNC throughreflux-nephropathy. Signifiquant signs for the diagnosis of this …. Are the periglomerulal scars reflux-nephropathy. Signifiquant signs for the diagnosis of this …. Are the periglomerulal scars

fourrounding relativecy intacts glomeruliand the tighteness of the capsula Bowman. The increased fourrounding relativecy intacts glomeruliand the tighteness of the capsula Bowman. The increased

glomeruli can appear in this form of secondary GNFS the pattern of the tubulo-interstitial scarsis glomeruli can appear in this form of secondary GNFS the pattern of the tubulo-interstitial scarsis “regional” – geografic pattern (“regional” – geografic pattern (Jones Silver coloration; x 120)

Fig. 3.Fig. 3. PNA – Interstitial limfo-plasmocitar infiltrate – in ssociation with oedema. Glomeruli are , PNA – Interstitial limfo-plasmocitar infiltrate – in ssociation with oedema. Glomeruli are , generraly, preserved, eventualy with minimal alterations, especially in the nephritis … to anagestics generraly, preserved, eventualy with minimal alterations, especially in the nephritis … to anagestics

((Jones Silver coloration; X 100)

SymptomathologySymptomathology Clinic ExaminationClinic Examination AnamnesisAnamnesis - general (septicemias) or local proximity infections- general (septicemias) or local proximity infections - inflammatory diseases in the little basin (mainly to woman)- inflammatory diseases in the little basin (mainly to woman) - digestive disorders (constipation, intestinal dyspepsia - digestive disorders (constipation, intestinal dyspepsia enterocolitis, megadolicocolon)enterocolitis, megadolicocolon) - endocrine metabolic disorders- endocrine metabolic disorders - exaggerate intake of medication (antinevralgic, sulphamide, - exaggerate intake of medication (antinevralgic, sulphamide, antibiotics, etc…).antibiotics, etc…).

General Clinic SimptomathologyGeneral Clinic Simptomathology -- infectious syndrome – fever, asthenia, cephaleea, infectious syndrome – fever, asthenia, cephaleea, moderate perspirations, arthralgias, mialgias, loss of weighmoderate perspirations, arthralgias, mialgias, loss of weigh - digestive syndrome –anorexia, nausea , - digestive syndrome –anorexia, nausea , gastrointestinal disordersgastrointestinal disorders

Symptomathology (2)Symptomathology (2) Renal functional disordersRenal functional disorders - reno-urinary pains –leading up to a nephritic - reno-urinary pains –leading up to a nephritic colica, suprapubian pains, urinary incontinence or retention colica, suprapubian pains, urinary incontinence or retention of urine of urine - diuressis disorders, meaning polyuria or oliguria- diuressis disorders, meaning polyuria or oliguria - mictioning disorders meaning dysuria, polakiuria- mictioning disorders meaning dysuria, polakiuria Physic examinationPhysic examination - pallor and often hiperpigmentated skin- pallor and often hiperpigmentated skin - diminished subcutaneous cellular layer- diminished subcutaneous cellular layer - normal or high arterial pressure - normal or high arterial pressure - local nephro-urinary examination can evidence lumbar pains- local nephro-urinary examination can evidence lumbar pains unilateral or bilateral ptossys, costomuscular and costovertebral unilateral or bilateral ptossys, costomuscular and costovertebral

painpain full points/areas, positive unilateral or bilateral Giordano full points/areas, positive unilateral or bilateral Giordano

manoeuvre manoeuvre and sometimes even vesical globeand sometimes even vesical globe - rectal and vaginal tacts are compulsory- rectal and vaginal tacts are compulsory

Paraclinic investigationsParaclinic investigations

Urine examinationUrine examination

-- 24 hours urine volume is variable pending on the stage of 24 hours urine volume is variable pending on the stage of

the illnessthe illness

- urinary density is low- urinary density is low

- collour of the urine is pale with hydruric aspect- collour of the urine is pale with hydruric aspect

- proteinuria is ussually from discreet up to moderate- proteinuria is ussually from discreet up to moderate

- sediment shows leucocyturia, leucocytes, cylinders, “glitter cells”, haematuria- sediment shows leucocyturia, leucocytes, cylinders, “glitter cells”, haematuria

Tests for induced leucocyturia and cylinderuriaTests for induced leucocyturia and cylinderuria

-- Pears-Hutt-Wardener test provoqued through pyrogen injectionsPears-Hutt-Wardener test provoqued through pyrogen injections

- Test Katz-Wardener of provoqued leucocyturia and cylinderuria through - Test Katz-Wardener of provoqued leucocyturia and cylinderuria through

injections of 40 mg of hydrocortison hemisuccinateinjections of 40 mg of hydrocortison hemisuccinate

- Bacteriologic exam of urine and antibiogram of urine, in case they detect - Bacteriologic exam of urine and antibiogram of urine, in case they detect

germs have a high value (important for pielonephritis)germs have a high value (important for pielonephritis)

Paraclinic investigations (2)Paraclinic investigations (2)

Renal function testsRenal function tests - - urine concentration alterationsurine concentration alterations - urine acidity alterations- urine acidity alterations - natriuresis, going up to natrium diabetis aspect- natriuresis, going up to natrium diabetis aspect - bicarbonate lakes, leading to acidosys- bicarbonate lakes, leading to acidosys - in more advanced stages,diminished glomerullar filtrate- in more advanced stages,diminished glomerullar filtrate

Other laboratory investigationsOther laboratory investigations

- haemmogram shows normocytar normochrome anemia, moderate - haemmogram shows normocytar normochrome anemia, moderate leucocitosisleucocitosis - raised speed of sedimentation of haematias - raised speed of sedimentation of haematias - blood ionogramm evidences alterations, in cases of pyelonephrithis - blood ionogramm evidences alterations, in cases of pyelonephrithis - fibrinogen values are moderatly high, attesting the presence of inflammatory - fibrinogen values are moderatly high, attesting the presence of inflammatory process in the kidneyprocess in the kidney - electrophoresis may evidence hyper - electrophoresis may evidence hyper ββ and hyper and hyper γγ- globulinaemia- globulinaemia

Imagistic examinationsImagistic examinations

-- Radiologic examinationRadiologic examination -- Simple renal radiography shows: Simple renal radiography shows: kidneys assimetric in shapes, difference being over 1,5 cmkidneys assimetric in shapes, difference being over 1,5 cm -- irregular contour-- irregular contour -- possible calcifications -- possible calcifications

- Urography- Urography -- renal papilas are modified, shaped as plates or knobs-- renal papilas are modified, shaped as plates or knobs -- hydrocalicosis-- hydrocalicosis -- reduced parenchimatous index-- reduced parenchimatous index -- polar segmental hypoplasia-- polar segmental hypoplasia - Global and selective renal arteriography- Global and selective renal arteriography -- reduced vascularisation-- reduced vascularisation -- delayed evidencing of the contrast substance-- delayed evidencing of the contrast substance - - Renal scintigraphiaRenal scintigraphia -- renal assymmetric dimensions-- renal assymmetric dimensions -- weak non-homogeneous interception of the radiopharmaceutical-- weak non-homogeneous interception of the radiopharmaceutical - - SonographySonography evidences dimensions of the kidneys, echostructures of the evidences dimensions of the kidneys, echostructures of the

parenchyma and the reno-urinary cavitiesparenchyma and the reno-urinary cavities

Renal BiopsyRenal Biopsy

To be combined, preferably, with microlombothomy:To be combined, preferably, with microlombothomy: - - inflammatory infiltrate in renal interstitiainflammatory infiltrate in renal interstitia

- radial interstitial sclerosis, beginning from the calices- radial interstitial sclerosis, beginning from the calices

- hypertrophy of the tubular epithaelia , with dilatation of the tubes- hypertrophy of the tubular epithaelia , with dilatation of the tubes

- presence of colloidal cylinders in the tubes, leading to a - presence of colloidal cylinders in the tubes, leading to a

pseudotyroidian aspectpseudotyroidian aspect

- periglommerular hyalinousis- periglommerular hyalinousis

- proliferative endarteritis- proliferative endarteritis

Main ethyopathogenyc and clinic forms of interstitial Main ethyopathogenyc and clinic forms of interstitial

nephropathiesnephropathies

Interstitial nephropathies through obstructive uropathyInterstitial nephropathies through obstructive uropathyTubulo-interstitial nephropathies of medical causesTubulo-interstitial nephropathies of medical causes

- infectious tubulo-interstitial nephropathies (pyelonephritis)- infectious tubulo-interstitial nephropathies (pyelonephritis) - toxic – medicinal induced TIN- toxic – medicinal induced TIN

Interstitial nephropathies of metabolic causesInterstitial nephropathies of metabolic causes [hyperurricemical, [hyperurricemical, hypercalcemical (nephrocalcinosis), oxalic, kalyopenic, renal cystinosis]hypercalcemical (nephrocalcinosis), oxalic, kalyopenic, renal cystinosis]Immunological interstitial nephropathiesImmunological interstitial nephropathiesGranulomatous tubulo-interstitial nephropathiesGranulomatous tubulo-interstitial nephropathiesTubulo-interstitial nephropathies in haemopathies or neoplasias Tubulo-interstitial nephropathies in haemopathies or neoplasias (infiltrative (infiltrative NTI)NTI)Tubulo-interstitial nephropathies in hereditary diseasesTubulo-interstitial nephropathies in hereditary diseasesInterstitial nephropathies of unknown causesInterstitial nephropathies of unknown causes (chronic primitive interstitial (chronic primitive interstitial nephropathies, xantogranulomatous pyelonephritis, balcanic endemic nephropathies, xantogranulomatous pyelonephritis, balcanic endemic nephropathy).nephropathy).

Interstitial nephropathy through obstructive Interstitial nephropathy through obstructive uropathyuropathy

Definition.Definition. Interstitial nephropathy through obstructive uropathy comprises Interstitial nephropathy through obstructive uropathy comprises functional disorders and structural alteration of the kidney as a result of the functional disorders and structural alteration of the kidney as a result of the existence of an inner obstacle , mechanic or functional, within the urinary existence of an inner obstacle , mechanic or functional, within the urinary tract.tract.Obstructive uropathy concept ,versus obstructive nephropathy and Obstructive uropathy concept ,versus obstructive nephropathy and hydronephrosis:hydronephrosis:

- obstructive nephropathy : alterations in the structure of the proximal - obstructive nephropathy : alterations in the structure of the proximal urinary tract, induced by an obstacle situated to this levelurinary tract, induced by an obstacle situated to this level - nephropathy through obstructive uropathy (obstructive nephropathy) :- nephropathy through obstructive uropathy (obstructive nephropathy) : functional alterations and structural changes of various intensity in functional alterations and structural changes of various intensity in the reno-urinary tractthe reno-urinary tract

Due to the urinary obstructions , there are 3 important consequences:Due to the urinary obstructions , there are 3 important consequences: - functional renal failure induces bypyelic hypertension- functional renal failure induces bypyelic hypertension - organic injuries up stream the obstacle , due to stasis- organic injuries up stream the obstacle , due to stasis - superinduced- superinduced urinary infection, worsening the lesions urinary infection, worsening the lesions

Main causes of obstructive uropathyMain causes of obstructive uropathy

Heterogenous Heterogenous (foreign) bodies: calculus, clots, necroused papillas (foreign) bodies: calculus, clots, necroused papillas

Inflammation –Inflammation – fibrosis installation : fibrosis installation :

- - urinary tuberculosis (renal pelvis, ureter , bladder, prostate urinary tuberculosis (renal pelvis, ureter , bladder, prostate urethra)urethra) - non-specific uretral strictures- non-specific uretral strictures - peryureteral retroperitoneal fibrosis- peryureteral retroperitoneal fibrosis - interstitial cystitis- interstitial cystitis - post-radiation retraction of the bladder (vesical sclerosis)- post-radiation retraction of the bladder (vesical sclerosis) - prostatic fibrosis, prostatitis- prostatic fibrosis, prostatitis - ureteral strictures- ureteral strictures - traumatic injuries of the ureter- traumatic injuries of the ureter - bilharioses- bilharioses

Congenital malformations :Congenital malformations : - - pyelo-uretheral dissectasia (disease of colet Syndrome)pyelo-uretheral dissectasia (disease of colet Syndrome) - cystic distention of the terminal ureter- cystic distention of the terminal ureter - retrocave ureters- retrocave ureters - compressions through an abnormal artery- compressions through an abnormal artery - megaureters- megaureters - bladder col dissease- bladder col dissease - urethral valves- urethral valves - urethral meatus abnormalies- urethral meatus abnormalies

Main causes of obstructive uropathy (2)Main causes of obstructive uropathy (2)

TumoursTumours -- prostate adenomaprostate adenoma

- prostate cancer- prostate cancer - papillomatous tumours of the ureter or bladder- papillomatous tumours of the ureter or bladder - bladder cancer (carcinoma)- bladder cancer (carcinoma) - secondary retroperitoneal ganglione cancer- secondary retroperitoneal ganglione cancer - cancer infiltration of the little basin and of the retroperitoneal tissue- cancer infiltration of the little basin and of the retroperitoneal tissue

– – Neurological bladderNeurological bladder - post –traumatic paraplegia- post –traumatic paraplegia - tabes- tabes - diabetic polyneuritis- diabetic polyneuritis - vascular cerebral strokes- vascular cerebral strokes

Clinical forms of nephropathy through Clinical forms of nephropathy through

obstructive uropathiesobstructive uropathies Interstitial nephropathy through unilateral ureteral Interstitial nephropathy through unilateral ureteral

obstructionobstruction

Complete obstruction of the ureter Complete obstruction of the ureter induces the first 6 hours completely induces the first 6 hours completely reversible functional disorders and the first 6 days functional but also reversible functional disorders and the first 6 days functional but also structural disorders; but within 3 weeks the kidney being deeply impaired , structural disorders; but within 3 weeks the kidney being deeply impaired , the renal function is only slightly improved after removing the obstacle. the renal function is only slightly improved after removing the obstacle. Between 3 weeks and 3 months the complete destruction of the kidney is Between 3 weeks and 3 months the complete destruction of the kidney is achieved.achieved.

Uncomplete obstruction of the ureterUncomplete obstruction of the ureter, acute of chronic, leads to progressive , acute of chronic, leads to progressive destruction of the respective kidney within a longer period of time, destruction of the respective kidney within a longer period of time, pending on the degree of pyelic hipertension.pending on the degree of pyelic hipertension.

Interstitial nephropathy through unilateral uretheral Interstitial nephropathy through unilateral uretheral obstacleobstacle

FisiopathologyFisiopathology. . Unilateral uretheral obstruction is associated with a raise in renal Unilateral uretheral obstruction is associated with a raise in renal inflammatory infiltrate with macrophages, responsible for the accumulation of inflammatory infiltrate with macrophages, responsible for the accumulation of inflammatory cells being the adhesion molecules.inflammatory cells being the adhesion molecules.

Pathological anatomyPathological anatomy. Macroscopically, following alterations can be registered:. Macroscopically, following alterations can be registered:

- great distension of the pelvis and pyelocaliceal cavity accumulating - great distension of the pelvis and pyelocaliceal cavity accumulating

up to 3 L of urineup to 3 L of urine

- reduction of the renal parenchyma to a simple thin blade, with the - reduction of the renal parenchyma to a simple thin blade, with the

erasing of the difference between cortical and meduularerasing of the difference between cortical and meduular

- controlateral injuried kidney is hypertrophic- controlateral injuried kidney is hypertrophic

MicroscopicallyMicroscopically, there are tubular and glomerular injuries, vases and interstitium , there are tubular and glomerular injuries, vases and interstitium structure; there is also a diffuse extensive and rare fibrosis.structure; there is also a diffuse extensive and rare fibrosis.

Interstitial nephropathy through obstacle on the common Interstitial nephropathy through obstacle on the common urinary tract or through obstacle on the unique ureter.urinary tract or through obstacle on the unique ureter.

Complete obstruction leads to acute urine retention, if reduction is under the bladder or Complete obstruction leads to acute urine retention, if reduction is under the bladder or to anuria , if reduction is on unique ureter.to anuria , if reduction is on unique ureter.

It is possible that anuria should be the reflex of a spasm of the “Clara preglomerular It is possible that anuria should be the reflex of a spasm of the “Clara preglomerular sphincter”sphincter”

Clinically, biologically mechanic anuria induces the clinic aspect of an IRA.Clinically, biologically mechanic anuria induces the clinic aspect of an IRA.

- - Uncomplete obstructionUncomplete obstruction , with the maintenance of the diuresis. , with the maintenance of the diuresis.

Uncomplete obstruction on the common way leads to the progresive Uncomplete obstruction on the common way leads to the progresive

appearance of bilateral or unilateral hydronephrosis – in the case of appearance of bilateral or unilateral hydronephrosis – in the case of

unique ureter. unique ureter.

Reflux nephropathyReflux nephropathy

Reflux nephropathy means kidney inflammation due to retrograde urinary flux at Reflux nephropathy means kidney inflammation due to retrograde urinary flux at the level of the Bellini ductsthe level of the Bellini ducts

Subsequent to the intrarenal reflux, the epithelia breaks and allows the urine to Subsequent to the intrarenal reflux, the epithelia breaks and allows the urine to penetrate in the interstitia, with inflammatory response in case of sterile urine and penetrate in the interstitia, with inflammatory response in case of sterile urine and more ample response in case of infected urine, leading finaly to fibrose.more ample response in case of infected urine, leading finaly to fibrose.

Progressive fibrose and impairment of renal function after resolution of the reflux is Progressive fibrose and impairment of renal function after resolution of the reflux is a consequence of the renin-dependet-on HTA which is settling downa consequence of the renin-dependet-on HTA which is settling down

Treatment Treatment consists in :consists in :

- maintaining the urine sterile- maintaining the urine sterile

- avoiding constipation- avoiding constipation

- periodic emptying of the bladder- periodic emptying of the bladder

- “permictionales” cystographies- “permictionales” cystographies

Tubulo-interstitial nephropathy of medical causeTubulo-interstitial nephropathy of medical cause

Infectious tubulo-interstitial nephropatiesInfectious tubulo-interstitial nephropaties

Acute pyelonephritisAcute pyelonephritis - - DefinitionDefinition.. Acute pyelonephritis is an acute bacterial disease, both of the Acute pyelonephritis is an acute bacterial disease, both of the

renal interstitial tissue and of the pyelon, the infection being spreaded renal interstitial tissue and of the pyelon, the infection being spreaded

on ascendent or descendent (haematogen) pathon ascendent or descendent (haematogen) path..

Ascendent acute pyelonephritisAscendent acute pyelonephritis

- - EthyopathogenyEthyopathogeny: : two categories of elements: microbian two categories of elements: microbian

determinants elements and favouring elementsdeterminants elements and favouring elements

- in 1/3 of the acute pyelitis urinary tract is normal- in 1/3 of the acute pyelitis urinary tract is normal

- infection is produced in ascendent path ureteral and less often, - infection is produced in ascendent path ureteral and less often,

through lymphatic path, localised initially in the medulla where there through lymphatic path, localised initially in the medulla where there

are proper conditions for developing an infectionare proper conditions for developing an infection

Acute pyelonephritisAcute pyelonephritis

Pathologyc anatomyPathologyc anatomy

Macroscopy:Macroscopy:

- - kidneys are edematous, of enlarged volume with multiple kidneys are edematous, of enlarged volume with multiple abscesses visible on the surface and that occasionally pierce the abscesses visible on the surface and that occasionally pierce the capsulecapsule - surface of the kidney shows plots of congestion and paleness- surface of the kidney shows plots of congestion and paleness - on section , can be noted triangular areas, grey, radially - on section , can be noted triangular areas, grey, radially arranged , with the pear in the papilla, as well as abscesses in thearranged , with the pear in the papilla, as well as abscesses in the corticalcortical - pyelo-caliceal branch shows dilationed congested and covered by - pyelo-caliceal branch shows dilationed congested and covered by purulent secretionspurulent secretions

Microscopic:Microscopic:

- - acute inflammation with interstitial edema and focal infiltration with acute inflammation with interstitial edema and focal infiltration with

polinuclear and little abscessespolinuclear and little abscesses

- necrosis of the tubular epithelia, granulose cylinders in the lumen- necrosis of the tubular epithelia, granulose cylinders in the lumen

- in severe forms, glomeruli invaded by PMN (invasive glomerulitis)- in severe forms, glomeruli invaded by PMN (invasive glomerulitis)

- thrombosis of the segmentary capillaries,sometimes accompanied by - thrombosis of the segmentary capillaries,sometimes accompanied by

breakes of the capsular and capillary basal membranes, with messangial breakes of the capsular and capillary basal membranes, with messangial

celullar proliferationcelullar proliferation

- in severe forms , can be seen the exclusion of the circulation through - in severe forms , can be seen the exclusion of the circulation through

obliteration of medium size arteries , surrounded by ischemiac areasobliteration of medium size arteries , surrounded by ischemiac areas

- lesions are plotted , explaining the discrepancy between clinic picture and - lesions are plotted , explaining the discrepancy between clinic picture and

results of the renal puncture biopsy.results of the renal puncture biopsy.

- if disease is not controlled , extended renal suppuration forms appear - if disease is not controlled , extended renal suppuration forms appear

leading to melting away the Bertin pyramid , with high deadly riskleading to melting away the Bertin pyramid , with high deadly risk

- healing is accompanied by the apparition of linear scars with retraction - healing is accompanied by the apparition of linear scars with retraction

in the medullain the medulla

Fig 4. Pielonefrita acuta este diagnosticata prin evidentiere agregarilor intratubulare de neutrofile polimorfonucleare, inconjurate de inflamatie interstitiala continand PMN, limfocite, plasmocite; inflamatia este predominanta la nivelul tubulilor. (Coloratia Jones Silver , marirea X 200).

Acute pyelonephritis. (2)Acute pyelonephritis. (2)

Symptomatology.Symptomatology.

BeginningBeginningPhisic examinationPhisic examinationParaclinic investigation:Paraclinic investigation:

- - urine – summation examination;urine – summation examination; - examination of the 24 hours urines;- examination of the 24 hours urines; - bacteriological examination (urinary culture, haemoculture);- bacteriological examination (urinary culture, haemoculture); - renal functional examination;- renal functional examination; - blood examination.- blood examination. - - radiologic examination:radiologic examination: -- renal simple radiography-- renal simple radiography -- urography-- urography - renal biopsy- renal biopsy

Acute pyelonephritis. (3)Acute pyelonephritis. (3)

Positive diagnosisPositive diagnosis - anamnesis evidencing the presence of favoring factors- anamnesis evidencing the presence of favoring factors - infectious syndrome- infectious syndrome - lumbalgias , nephretic colics- lumbalgias , nephretic colics - cystic syndrome- cystic syndrome - urine exam evidencing discreet proteinuria- urine exam evidencing discreet proteinuria - leucocyturia – pyuria, leucocytar cylinders, pozitives urinary - leucocyturia – pyuria, leucocytar cylinders, pozitives urinary culturescultures - enlarged kidney volume evidenced due to the radio-urography- enlarged kidney volume evidenced due to the radio-urography

Differentiation diagnosisDifferentiation diagnosis with: with: - cystitis, cystopyelitis, renal litiasis- cystitis, cystopyelitis, renal litiasis - renal tuberculosis- renal tuberculosis - feverish diseases (malaria, typhos fever, sepsis, meningitis)- feverish diseases (malaria, typhos fever, sepsis, meningitis) - basal pneumonia- basal pneumonia - acute pancreatitis- acute pancreatitis

Acute pyelonephritis. (4)Acute pyelonephritis. (4)Evolution and evaluation of APN.Evolution and evaluation of APN. Correctly treated, ascendant APN has a Correctly treated, ascendant APN has a favorable evaluation, as it can cure, spontaneous, but in this case it exists the risk favorable evaluation, as it can cure, spontaneous, but in this case it exists the risk of becoming chronic. All favorable factors must be removed, and the patient will be of becoming chronic. All favorable factors must be removed, and the patient will be closely supervised and controlled for 1-2 years, by regular urine examinations.closely supervised and controlled for 1-2 years, by regular urine examinations.

APN complications APN complications are:are:

- Pyonephrosis, - Pyonephrosis, usually secondary to obstructive elementsusually secondary to obstructive elements

- Perynephretic Phlegmon, - Perynephretic Phlegmon, appearing due to transspassing of appearing due to transspassing of

the cortical infective centers through the capsule into the the cortical infective centers through the capsule into the

perirenal space. perirenal space.

- Papillary Necrosis – - Papillary Necrosis – at the same time a complication and aat the same time a complication and a

clinical form clinical form

- Sepsis, - Sepsis, as a consequence of massive pouring of germs into as a consequence of massive pouring of germs into

the blood circulationthe blood circulation

- Acute Renal Failure,- Acute Renal Failure, due to the severe APN due to the severe APN

Hematogenous interstitial nephritis (hematogenous acute Hematogenous interstitial nephritis (hematogenous acute or descendent PN)or descendent PN)

Ethyopathogeny. Ethyopathogeny. Insemination of the renal parenchima is induced Insemination of the renal parenchima is induced through descendent hematogenous way, with germs originating through descendent hematogenous way, with germs originating either in infectious proximal centers, or in far distance ones .either in infectious proximal centers, or in far distance ones .

- involved germs: Staphylococus Aureus, Enterococcus - involved germs: Staphylococus Aureus, Enterococcus Pseudomonas aeruginosa, leptospire, ricketsii, brucellePseudomonas aeruginosa, leptospire, ricketsii, brucelle - gram negative germs (Escherichia coli, Proteus, Klebsiela)- gram negative germs (Escherichia coli, Proteus, Klebsiela)

Pathologycal anatomyPathologycal anatomy. Lesions appear in 3-7 days from the . Lesions appear in 3-7 days from the localization of the germs, being similar to those found in localization of the germs, being similar to those found in ascendant APNascendant APN

Microscopy:Microscopy: - plotted acute inflammation centers, abscesses, tubes destructions - plotted acute inflammation centers, abscesses, tubes destructions or thickened tubes (tubullis) distended by the leucocytes or thickened tubes (tubullis) distended by the leucocytes

contents contents or the cylindersor the cylinders - in the medullar vesgels, the first 3 days appear thrombi,- in the medullar vesgels, the first 3 days appear thrombi, resulting in septic infections resulting in septic infections - the process diffuses radially towards the cortex.- the process diffuses radially towards the cortex.

Haematogen interstitial nephritis(2)Haematogen interstitial nephritis(2)

SymptomatologySymptomatology is marked by sepsis and only systematic examines of is marked by sepsis and only systematic examines of urines could evidence the presence of the germs in the kidneys.urines could evidence the presence of the germs in the kidneys. Evolution and prognostication:Evolution and prognostication:

- APT could be confused with one of the causal disease- APT could be confused with one of the causal disease - certain forms are regressing under appropriate treatment, - certain forms are regressing under appropriate treatment, others became complicated with IRAothers became complicated with IRA - others became chronic- others became chronic - evolutive straight is pending on the virulence of the germs and - evolutive straight is pending on the virulence of the germs and the presence of the favorable conditionsthe presence of the favorable conditions - main treatment is the one of the causal disease- main treatment is the one of the causal disease

Pyelonephritis due to “Candida albicans”Pyelonephritis due to “Candida albicans”

Causes: abuse of antibiotherapy , prolonged corticotherapyCauses: abuse of antibiotherapy , prolonged corticotherapyLocation. Children, pregnant women, aged patients with consumptive diseases or Location. Children, pregnant women, aged patients with consumptive diseases or immunitary deficienciesimmunitary deficienciesKidneys can be infected through two ways: hematogenous and ascendantKidneys can be infected through two ways: hematogenous and ascendantHistology Histology : interstitial nephritis in focus (centers) with granulomatous elements : interstitial nephritis in focus (centers) with granulomatous elements that may confluence and then produce fistula in the parenchyma or the perirenal that may confluence and then produce fistula in the parenchyma or the perirenal space, disseminating in the whole kidneys (cortical and medullar) abscesses with space, disseminating in the whole kidneys (cortical and medullar) abscesses with draining in the renal excretory ductdraining in the renal excretory ductSymptomatology Symptomatology could be dramatic, with respect to the aspect of unilateral or could be dramatic, with respect to the aspect of unilateral or bilateral APN with papillar necrosis.bilateral APN with papillar necrosis.

- Some other times, patients show prolonged sub feverishness - Some other times, patients show prolonged sub feverishness lumbagos or even repeated nephritic collics, leading to confusions lumbagos or even repeated nephritic collics, leading to confusions with renal tuberculosiswith renal tuberculosis

Pyelonephritis due to “Candida albicans” (2)Pyelonephritis due to “Candida albicans” (2)

Investigations:Investigations: - urine examinations: uroculture on Sabouraud medium is- urine examinations: uroculture on Sabouraud medium is evidencing white colonies with creamy aspectevidencing white colonies with creamy aspect - urography ; is evidencing confluent cavities and fistular - urography ; is evidencing confluent cavities and fistular trajectoriestrajectories - immune deficiencies : hypogammaglobulinaemias, - immune deficiencies : hypogammaglobulinaemias, lymphocytopenialymphocytopenia

Evolution. In the absence of a specific treatment, kidneys are destroyedEvolution. In the absence of a specific treatment, kidneys are destroyedTreatment must be established as soon as possible, aiming to eradicate infecting favorable Treatment must be established as soon as possible, aiming to eradicate infecting favorable circumstances:circumstances:

- well-balancing of an eventual diabetes- well-balancing of an eventual diabetes - stop to administrating antibiotics and corticoids- stop to administrating antibiotics and corticoids - suppressing proximity fungi infections (urethritis, vaginitis)- suppressing proximity fungi infections (urethritis, vaginitis) - selected antibiotic would be “Amphotericyn B”administrated as - selected antibiotic would be “Amphotericyn B”administrated as intravenous perfusion, suggested dose of 0,75-1 mg/kg/day, for 30 daysintravenous perfusion, suggested dose of 0,75-1 mg/kg/day, for 30 days - Nefrotoxicity of “Amphtericyn B” complies to its substitution with - Nefrotoxicity of “Amphtericyn B” complies to its substitution with another antifungi drug: stamicine or mycostatin or diflucan(fluconazol)another antifungi drug: stamicine or mycostatin or diflucan(fluconazol)

Treatment of acute pyelonephritisTreatment of acute pyelonephritis

General treatment managementGeneral treatment managementEssential principles of the therapy of APN :Essential principles of the therapy of APN :

- - Antibiotic treatmentAntibiotic treatment before the identification of the germs, 3- before the identification of the germs, 3- 4g/day of Ampicilin will be administrated, followed, for some 4g/day of Ampicilin will be administrated, followed, for some weeks, by the proper therapy according to antibiogrammweeks, by the proper therapy according to antibiogramm - Attack treatment: cephalosporine (ceftazidim, ceftriaxon, cefuroxim) - Attack treatment: cephalosporine (ceftazidim, ceftriaxon, cefuroxim) tetracycline, carbenicycilin (Pyopen), as single or combined medicationtetracycline, carbenicycilin (Pyopen), as single or combined medication - In severe cases, administration of parentheral antibiotics is recommended, - In severe cases, administration of parentheral antibiotics is recommended,

in order to obtain high level sanguine concentrationsin order to obtain high level sanguine concentrations - Maintenance treatment: quinolones or sulphamides with prolonged action- Maintenance treatment: quinolones or sulphamides with prolonged action

In recurrent APN , there are 2 possible treatments:In recurrent APN , there are 2 possible treatments: -- antibiotic treatments for each acute episode, for at least 10-15 days-- antibiotic treatments for each acute episode, for at least 10-15 days -- continous treatments: initially 3-4g/day of ampicylin as the attack therapy, -- continous treatments: initially 3-4g/day of ampicylin as the attack therapy,

followed by : cotrimoxazole, norfloxacyn,etc., – each morning and evening followed by : cotrimoxazole, norfloxacyn,etc., – each morning and evening Presence of a septicemia complies with administration of 2 antibiotics:ampicylin 3-Presence of a septicemia complies with administration of 2 antibiotics:ampicylin 3-4g/day x20 days plus gentamycin 80 mg/each 8 hours x 10 days4g/day x20 days plus gentamycin 80 mg/each 8 hours x 10 days

Treatament of acute pyelonephritis (2)Treatament of acute pyelonephritis (2)

APN in pregnancy. APN in pregnancy. In case of APN in pregnant women, ampicylin,certain In case of APN in pregnant women, ampicylin,certain cephalosporines and carbenicylin could be used, as well as furantoin, but cephalosporines and carbenicylin could be used, as well as furantoin, but paing great attention to its administration.paing great attention to its administration.

Contra-indicated medicines are:Contra-indicated medicines are: tetracycline tetracycline →severe risks both for mother (jaundice or ARI) and →severe risks both for mother (jaundice or ARI) and

child (drug being deposited in the bones tissues and dental buds)child (drug being deposited in the bones tissues and dental buds) sulphamides, cortimoxazole mostly, due to the antifolic and sulphamides, cortimoxazole mostly, due to the antifolic and

teratogene action of the trimetroprimteratogene action of the trimetroprim streptomycine and kanamycin for their toxic effects on the cranial streptomycine and kanamycin for their toxic effects on the cranial

nerves of the childnerves of the childRifampycin, toxic during the first quarter of pregnancyRifampycin, toxic during the first quarter of pregnancyquinolones that must be avoided both the first 3 monthes and after quinolones that must be avoided both the first 3 monthes and after

the 8 month; nalidixic acid induces fetal jaundice through the 8 month; nalidixic acid induces fetal jaundice through inhibiting glucuronyltransferaseinhibiting glucuronyltransferase

Cloramfenicol, is medullarly hematotoxic both for mother and Cloramfenicol, is medullarly hematotoxic both for mother and childchild

Chronic pyelonephritisChronic pyelonephritis

DefinitionDefinition.. Chronic pyelonephritis is a bacterial interstitial nephritis Chronic pyelonephritis is a bacterial interstitial nephritis

associated with the inflammation of the pelvis, where lesions are situatedassociated with the inflammation of the pelvis, where lesions are situated

predominantly in the renal interstitium and secondary in the tubules.predominantly in the renal interstitium and secondary in the tubules.

Epidemiology.Epidemiology. CPN represents the cause of at least 20 % of the CPN represents the cause of at least 20 % of the

chronic renal failure.chronic renal failure.

Aetiology.Aetiology.

Bacteriology in CPN according to various authorsBacteriology in CPN according to various authors

Germen (%) Sarre Kienitz Legrain UrseaEscherichia coli 32,8 35 60 68,5Enterococcus 32,6 17 10 4,6Streptococcus 9,3 - - 0,4Proteus mirabilis 7,2 15 10-20 3,6Klebsiella 4,2 7 5-10 12,3Pseudomonas aeruginosa 3,8 4 5-10 1,8Staphylococcus aureus 2,6 9 2,5 0,5Alkaligenes 2,2 - - 1,4Aerobacter cloacae 2,6 - - 1,6

Symptomatology of PNC Symptomatology of PNC Clinical evidences Clinical evidences

GeneralGeneral– feverfever – asthenia, adynamiaasthenia, adynamia– loss in weightloss in weight– headache, migraineheadache, migraine

CutaneousCutaneous– pseudo-addisonian pigmentationpseudo-addisonian pigmentation

Cardio-vascularCardio-vascular– HTAHTA– left ventricle hypertrophyleft ventricle hypertrophy– global cardiac hypertrophyglobal cardiac hypertrophy– pericarditispericarditis

Digestive:Digestive:– anorexia, vomitisanorexia, vomitis– sabural tonguesabural tongue– hepatosplenomegaliahepatosplenomegalia

Bones:Bones:

– osteopathyosteopathy

Nephro-urinary:Nephro-urinary:– lumbalgiaslumbalgias– nephritic colicsnephritic colics– polakiuriapolakiuria– dissuriadissuria– turbid, fetid urinesturbid, fetid urines

Symptomatology of CPNSymptomatology of CPNParaclinical investigationsParaclinical investigations

Urine examinationUrine examination: : – hipo-izo-subizostenuriahipo-izo-subizostenuria– Lowered urinary osmolarityLowered urinary osmolarity– Leucocyturia pyuriaLeucocyturia pyuria– Sternheimer-Malbin cellsSternheimer-Malbin cells– Leucocytar cylindruriaLeucocytar cylindruria– Macroscopical haemathuriaMacroscopical haemathuria– bacteriuriabacteriuria

Biochemical examinationBiochemical examination::– diselectrolithemiadiselectrolithemia– acidosisacidosis– azotemiaazotemia

Functional renal explorationFunctional renal exploration– Lowered clearancesLowered clearances– natriurezisnatriurezis– Deficient concentration testsDeficient concentration tests– Hyperchloremic acidozisHyperchloremic acidozis

Hematological:Hematological:- anemia, leucocytosis- anemia, leucocytosis– raised VSH raised VSH

RadiologicalRadiological::– Asimetrical reduced in shape Asimetrical reduced in shape

kidneyskidneys– Irregular appearancesIrregular appearances– Reduced parenchymatous indexReduced parenchymatous index– Calice distortionsCalice distortions

Izotopic + sonographyc explorationsIzotopic + sonographyc explorations::– Morphologycal and functional Morphologycal and functional

inequality between kidneysinequality between kidneys– Hypocapting areasHypocapting areas

Renal biopsyRenal biopsy::

– Inflammatory infiltrate and areas Inflammatory infiltrate and areas of sclerosis in the interstitium, of sclerosis in the interstitium, alternating with healthy areasalternating with healthy areas

– Distroyed tubules , with Distroyed tubules , with pseudothyroidian aspectpseudothyroidian aspect

Radio-urographyc characteristics of CPNRadio-urographyc characteristics of CPN

Renal parenchym abnomaliesRenal parenchym abnomalies

-- global reduction in the shapes of the kidneys, preserving the asymmetry global reduction in the shapes of the kidneys, preserving the asymmetry

between them (one being with over 1,5 cm smaller that the other)between them (one being with over 1,5 cm smaller that the other)

- irregular contour , as expressions of the renal scars- irregular contour , as expressions of the renal scars

- atrophy of a renal pole (segmentary hypoplasya)- atrophy of a renal pole (segmentary hypoplasya)

- reduced distance from the papilla to the bord (parenchymatous index) due to - reduced distance from the papilla to the bord (parenchymatous index) due to

cortical atrophycortical atrophy

- calcifications :lithyasis, nephrocalcinouzis- calcifications :lithyasis, nephrocalcinouzis

Alterations of the excretory cavities (which appear modified)Alterations of the excretory cavities (which appear modified)

- little calice appears closer , pushed, but preserving its contour- little calice appears closer , pushed, but preserving its contour

- pyelocaliceal ”fan” with “withered dropping flowers” aspect- pyelocaliceal ”fan” with “withered dropping flowers” aspect

- papillas shaped as” plate” , “bludgeon”, “mush room”- papillas shaped as” plate” , “bludgeon”, “mush room”

- papillar necrousis shapped as “ ring” or “crab tongs”- papillar necrousis shapped as “ ring” or “crab tongs”

- pelvis can be hypotonic, with irregular contour, - pelvis can be hypotonic, with irregular contour,

- urethers are hypotonic- urethers are hypotonic

Urinary obstruction : hydronephrosis, hydroureter, bladder residueUrinary obstruction : hydronephrosis, hydroureter, bladder residue

Associated signs: lythiasis, vesico-ureteral refluxAssociated signs: lythiasis, vesico-ureteral reflux

CPN treatmentCPN treatmentPrinciples:Principles:

- treatment of the urinary infection – antiinfectious treatment- treatment of the urinary infection – antiinfectious treatment - treatment of the arterial hypertension - treatment of the arterial hypertension - correction of the favourable conditions for infecting of the renal - correction of the favourable conditions for infecting of the renal parenchym- the urological approachparenchym- the urological approach - correction of the renal function disorders – fiziopathologycal and - correction of the renal function disorders – fiziopathologycal and symptomatical treatmentssymptomatical treatments

General attitudeGeneral attitudeAntibiotherapy requirementsAntibiotherapy requirements

- identification of the infectious germs and of their sensitivity to - identification of the infectious germs and of their sensitivity to appropriate medicationappropriate medication - elimination of the favourable conditions promoting the infections- elimination of the favourable conditions promoting the infections - antiinfectious treatment will not be administrated untill at least two - antiinfectious treatment will not be administrated untill at least two urocultures and one haemoculture would have been taken overurocultures and one haemoculture would have been taken over - initial administration of an attack treatment protocole for about 3-4 weeks, - initial administration of an attack treatment protocole for about 3-4 weeks, followed by a long term treatment that could be continously administrated in reduced followed by a long term treatment that could be continously administrated in reduced dosage given between several monthes up to 1 year, or intermitently 7-10 days / dosage given between several monthes up to 1 year, or intermitently 7-10 days / monthly in high doses.monthly in high doses.

CPN treatment (2)CPN treatment (2)

In selecting appropriate antiinfectious medication some principles must be In selecting appropriate antiinfectious medication some principles must be observed:observed:

-- to have a proper spectrum, as much as possible , against -- to have a proper spectrum, as much as possible , against

the infectious agent found in the urinethe infectious agent found in the urine

-- to be eliminated mostly through the urine, under active -- to be eliminated mostly through the urine, under active

metabolits formmetabolits form

-- not to precipitate in the urine, irrespectively of the pH-- not to precipitate in the urine, irrespectively of the pH

-- to be properly tollerated-- to be properly tollerated

-- to induce the lowest possible microbial resistance-- to induce the lowest possible microbial resistance

Drug medicine – induced toxic tubulli-interstitial Drug medicine – induced toxic tubulli-interstitial nephropathynephropathy. . AAnalgesicsnalgesics n nephropathy ephropathy

DefinitionDefinition. . Nephropathy to analgesics is a chronic interstitial nephropathy, Nephropathy to analgesics is a chronic interstitial nephropathy, associated with papillar necrosis due to excessive and prolonged intake of associated with papillar necrosis due to excessive and prolonged intake of analgetics.analgetics.

Pathogenesis. Papillar necrosis is the result of 2 categories of aggressive factors: Pathogenesis. Papillar necrosis is the result of 2 categories of aggressive factors: toxic and ischemiactoxic and ischemiac

Prototype- nephropathy due to phenacethyn (Prototype- nephropathy due to phenacethyn (ZollingerZollinger and and SpuhlerSpuhler).). - hypothesis of the toxic action of associated ingredients to - hypothesis of the toxic action of associated ingredients to phenacethynphenacethyn - hypothesis of the decreased resistance to renal infections- hypothesis of the decreased resistance to renal infections - hypothesis of immuno-allergycal reaction of the delayed - hypothesis of immuno-allergycal reaction of the delayed hypersensitivityhypersensitivity Pathologyc anathomyPathologyc anathomy: : bilateral interstitial nephropathy, being characterised by the bilateral interstitial nephropathy, being characterised by the

compulsory presence of the papillar necrosiscompulsory presence of the papillar necrosis Macroscopy:Macroscopy:

o Kidneys are reduced in shapes, with adherent capsula, wrinkled by Kidneys are reduced in shapes, with adherent capsula, wrinkled by whitish stripeswhitish stripes

o The surface of the kidneys appears as irregular with retractile scarsThe surface of the kidneys appears as irregular with retractile scarso Cysts , papillar necrosis ,calcifications, papillar scars Cysts , papillar necrosis ,calcifications, papillar scars

Analgesyc induced NEPHROPATHYAnalgesyc induced NEPHROPATHYPathologyc anathomy (2)Pathologyc anathomy (2)

Microscopy:Microscopy:Papillar necrosis and poor inflammatory infiltrate in the interstitiaPapillar necrosis and poor inflammatory infiltrate in the interstitiaBrown-golden pigment, intracytoplasmatic,very similar to Brown-golden pigment, intracytoplasmatic,very similar to

lipofuscinalipofuscinaNecrosis of the interstitial cells, of Henle ansas and of capillariesNecrosis of the interstitial cells, of Henle ansas and of capillariesBrown-black pigment in the necrotic papillas and other tissues such Brown-black pigment in the necrotic papillas and other tissues such

as cartilages, representing a metabolyte of phenacetyn, 3-amino-7 as cartilages, representing a metabolyte of phenacetyn, 3-amino-7 etoxi-phenasoneetoxi-phenasone

Slender calcification of MB thickening of the Henle ansasSlender calcification of MB thickening of the Henle ansasExistent healthy areas and necrotic areas the lasts containing Existent healthy areas and necrotic areas the lasts containing

acicular birefringent crystalsacicular birefringent crystals Important thickening of the capillaries situated under the pyelic and Important thickening of the capillaries situated under the pyelic and

uretheral endothelium,as well as in the bladderuretheral endothelium,as well as in the bladderAlterations of the renal cortex appear only in more advanced or Alterations of the renal cortex appear only in more advanced or

more severe stages. more severe stages.

Fig 5. Fragment de papila medulara necrozata prezent in urina

Fig 6. Necroza papilara in nefropatia la analgetice.