RENAL PATH

 2 TYPES
o Primary glomerular lesions
 The kidney is the prime target.
o Secondary glomerular lesions
 The glomerular injury is secondary to events elsewhere in the body.
 CAUSES
o Immunological reactions
o Non-immunological disorders
 - Diabetes mellitus
 - Hypertension
 - SLE
 - Haemolytic uraemic syndrome

IMMUNE GLOMERULAR INJURY

 Most common type of glomerular damage

 Occurs due to
o Circulating immune complex deposition
 When Antigen antibody complexes formed elsewhere in the body can enter the glomeruli via the afferent
arterioles and gets deposited within glomerulus
o Insitu immune complex formation
 Antibodies react directly with planted or fixed antigens in the glomerulus
 Antibodies may react in situ with previously "planted" nonglomerular antigens, which may localize in the
kidney
 Planted antigens include DNA, bacterial products, large aggregated proteins (e.g. aggregated IgG) etc
 Anti-glomerular basement membrane antibody glomerulonephritis
 When autoantibodies react against fixed antigens in glomerular basement membrane
 When auto ab cross react with basement membrane of lungs = concurrent lungs and kidney
lesion = goodpasture syndrome

INVESTIGATIONS IN GLOMERULAR INJURY

 RENAL BIOPSY
 H AND E STAINING
 SPECIAL STAINS = PAS , SILVER AND MASSONS TRICHROME
 ELECTRON MICROSCOPY
o Shows deposited immune complexes = subepithelial, subendothelial ,mesangeal
 IMMUNOFLUORESCENCE
o Detects deposition of immunoglobulin

NOMENCLATURE OF GLOMERULAR INJURY

Diffuse : a lesion affecting all glomeruli

Focal : a lesion involving some glomeruli,

but leaving others unaffected

Global : affecting the whole glomerulus

Segmental : affecting only part of the glomerulus.


ADDITIONAL TERMS USED TO DESCRIBE LIGHT MICROSCOPY CHANGES

 PROLIFERATIVE
o Increased no of cells within glomerulus
 Due to proliferation of indigenous cells
 Recruitment of polymorphs and macrophage from circulation
 MEMBRANOUS CHANGE
o Peripheral loops thickened due to basement membrane expansion
 MEMBRANO-PROLIFERATIVE
o Proliferative + membranous changes with accentuation of lobular architecture
 CRESCENTIC
o Proliferation of cells including macrophages lining bowman’s capsule = compresses the glomerulus

PRESENTATION OF GLOMERULAR DISEASE

1. Recurrent painless haematuria

a. exercise haematuria
b. IgA nephropathy (Berger's disease)
c. Henoch-Schönlein purpura
d. bacterial endocarditis
e. systemic lupus erythematosus (SLE)
f. vasculitis-polyarteritis
2. Asymptomatic proteinuria= VARIES IN SEVERITY . AND DETECTED AT A ROUTINE EXAMINATION
a. Henoch-Schönlein purpura
b. SLE
c. polyarteritis
d. bacterial endocarditis
e. shunt nephritis
f. focal segmental glomerulosclerosis
g. mesangiocapillary glomerulonephritis (MCGN
h. idiopathic rapidly progressive glomerulonephritis (RPGN)
i. post-infectious RPGN
j. Goodpasture's syndrome (anti-glomerular basement membrane disease)
k. SLE
l. polyarteritis
m. Wegener's granulomatosis
n. Henoch-Schönlein purpura
o. essential cryoglobulinaemia.
3. Nephrotic syndrome= heavy proteinuria due to which hypoalbuminemia leading to severe edema. Hypercholesterolemia
a. MINIMAL –CHANGE DISEASE ( LIPOID NEPHROSIS)-relatively benign
i. Most frequent cause of nephrotic syndrome in children ( common in 1-7yrs)
ii. Characteristics = glomeruli have normal appearance by light microscopy but electron micscopy – diffuse
effacement of podocyte foot proceses
iii. Clinical course
1. Insidious onset in healthy child. / renal function preserved in most individuals & no htn
2. Selective proteinuria ( smaller serum proteins chiefly albumin)
3. Prognosis is good in children
a. More than 90% respond to short course of corticosteroid therapy. Kids more responsive
than adults and less relapse so important to diagnose since they can be treated
b. Proteinuria recurs in more than 2 thirds of initial responders some become steroid depende
4. Chronic renal failure
a. elevated blood urea (uraemia)
b. vague features including
i. anaemia, nausea, vomiting, gastrointestinal bleeding and itching.
c. There is often polyuria and nocturia
 5. Acute nephritis (Nephritic syndrome)=HEMATURIA , OLIGURIA AND HTN

a. post-infectious/streptococcal glomerulonephritis
i. More commonly occurring = due to deposition of immune complex leading to diffuse proliferative GN
ii. Other causative organisms = pneumococcal infections, staph, viral like mumps, measles , chicken pox, hep b
and c
iii. Common scenario /classic
1. In a child 1-4 weeks after recovery from a group A streptococcal infection ( initial infection = skin or
pharynx)
iv. Clinical course
1. Abrupt onset = malaise, slight fever, nausea and nephritic syndrome
2. Mild –moderate= oliguria , azotemia and htn
3. Characteristics = gross hematuria with smoky brown urine rather than bright red
4. Constant feature = some proteinuria. Might be severe enough to produce nephrotic syndrome
5. Serum anti-streptolysin O antibody titers are elevated in post streptococcal cases
v. MOrpholgy
1. Diffuse glomerular involvement
2. Increased cellularity due to
a. Proliferation and swelling of endothelial and mesangial cells
b. Neutrophilic and monocyctic infiltrate
vi. RECOVERY
1. Occurs in most children
2. Some develop rapidly progressive GN due to severe injury with crescents or chronic renal disease
due to secondary scarring

Tubulointerstitial

 Tubular injury involving interstitium characterized by

o INFLAMMATORY INVOLVEMENT OF TUBULES AND INTERSTITIUM ( INTERSTITIAL NEPHRITIS)
o ISCHEMIC OR TOXIC TUBULAR INJURY
 Acute tubular injury / acute kidney injury

TUBULOINTERSTITIAL NEPHRITIS

 Involves interstitium and tubules. Glomeruli can be spared or affected late

 Cause of TIN = mostly bacterial
 Interstitial nephritis = TIN which of noon bacterial origin
o Example = drugs, metabolic disorders like hypokalemia irradiation and viral infection
ACUTE PYELONEPHRITIS = to infection of the kidney by pyogenic organisms.

 Suppurative inflammation of the kidney and renal pelvis

 Cause = bacterial infection (UTI)= can involve the lower ( cystititis , prostatitis , urethritis)or upper or both
 Causative organism
COMPLICATION
o Principle = enteric gram negative rod
 Ecoli = most common 1. Renal papillary necrosis = due
 Proteus to inflammation medullary
 Klebsiella blood supply gets
 Enterobacter compromised leading to this
 Pseudomonas a. One or more or all
 Clinical features affected
o Fever, chills, pain , malaise and tenderness in loins b. apical two-thirds of
o Dysuria and urgency = associated infection in lut the pyramids ( renal
 Lab findings papillae ) show
o Pus cells in the urine (pyuria) sharply defined gray-
o White cell casts (provides unequivocal evidence of pyelonephritis) white to yellow areas
o Urine culture ( significant when excess of 10 culture-forming units/ml )
5 of suppurative
 Predisposing factors necrosis.
o Urinary obstruction ( congenital / acquired ) c. Microscopy =
o Instrumentation of the urinary tract ( especially catheterization ) coagulative necrosis
o Vesicoureteral reflux with surrounding
o Pregnancy neutrophilic infiltrate
o Sex and age
 1-40 year = females
 With increasing age = incidence increase in males due to BPH and frequent instrumentation
o Pre existing renal lesion = intrarenal scarring and obstruction
o DM = increased susceptibility to infection and neurogenic bladder dysfuction PYONEPHROSIS = complete
o Immune suppression and immunodeficiency obstruction high in urinary tract
 PATHOGENESIS near kidney. Stagnant fluid in
o HEMATOGENOUS SPREAD pelvis and calyceal system
 In IE, bacteremia from other sources suppurates. Eventually kidney
 Bacteria , fungi , rickettsia and viruses becomes grossly distended with
 Previous renal damage or structural abnormality increases risk pus .
o RETROGRADE URETERIC SPREAD /ASCENDING INFECTION
 More common / specially young women
 Occurs due to reflux of urine
 Causative organism = gram neg ( ecoli,proteus, enterobacter) from pts faecal flora
 Risk factors = short urerthra, pregnancy , instrumentation in both sex
 MORPHOLOGY
PERINEPHRIC ABCESS
o One or both kidneys. Normal size or increased in size
o Abscesses or Infection breach the renal
 Throughout the cortex and medulla capsule and extend into
 Wedge shaped confluent areas of suppuration perirenal tissues
o Differentiate between hematogenous and urinary reflux
 Minute abscesses are randomly distributed in = hematogenous
 Lesions = located at upper and lower poles = urinary reflux
 HISTOLOGY
o Intratubular polymorphs together with interstitial oedema and inflammation
o With healing, fibrosis occurs in the interstitium and the inflammatory infiltrate becomes dominated by
lymphocytes and plasma cells
o Glomeruli are not affected
 2 TYPES
o Obstructive
o Reflux associated
 OBSTRUCTIVE
o Obstruction  lead to infection recurrent infection recurrent bouts of inflammation and scarring -> chronicp
o Either
 Bilateral = congential anormalies of urethra ( posterior urethral valves)
 Unilateral = calculi and unilateral obstructive lesions of ureter
 REFLUX ASSOCIATED PYELONEPHRITIS
o More common form of chronic pyelonephritic scarring / can be unilateral or bilateral
o results from superimposition of a UTI on congenital vesicoureteral reflux and intrarenal reflux
 vur enables organisms to gain access to kidney from bladder
 In patients with VUR, the terminal portion is short and orientated at approximately 90° to the
mucosal surface.Contraction of the bladder tends to hold the ureteric orifice open. This facilitates
reflux of urine
 In the mid-zone papillae, the ducts open obliquely onto the surface of the papilla.
In the event of urinary reflux from the bladder, these duct orifices will close under the increased
pressure in the pelvicalyceal system.
 In the polar papillae, the terminal ducts open on to the surface at right angles
Therefore , they have no valve effect and remain widely patent.This will allow the refluxed urine
and any bacteria within it to be transmitted into the parenchyma of the kidney. SO REFLUXING
PAPILLA ARE MAINLY AT THE POLES AND DAMAGE IS SEEN HERE THE MOST
 primary abnormality = angle at which terminal ureteric segment traverses bladder wall
o clinical features
 gradual onset renal insufficiency
 hypertension
o INVESTIGATIONS
 US= size and shape of kidney
 Pyelogram = for appearances. Asymmetrically contracted , blunting and deformity of calyceal system
o MORPHOLOGY
 Unilaterally or bilaterally asymmetrically contracted kidney
 Deep irregular scars at the poles
 HALLMARK = scarring involving the pelvis or calyces or both leading to papilarry blunting and marked
calyceal deformity
o MICROSCOPY = largely non specific
 Uneven interstitial fibrosis and an inflammatory infiltrateof lymphocytes, plasma cells, and occasionally
neutrophils
 Dilation or contraction of tubules, with atrophy of the lining epithelium. Many of the dilated tubules
contain pink to blue, glassy-appearing PAS-positive casts, known as colloid casts, that suggest the
appearance of thyroid tissue—hence the descriptive term thyroidization. Often, neutrophils are seen
within tubules.
 Chronic inflammatory cell infiltration and fibrosis involving the calyceal mucosa and wall
 Arteriolosclerosis caused by the frequently associated hypertension
 Glomerulosclerosis that usually develops as a secondary process caused by nephron loss
 Presents as a chronic interstitial nephritis, often associated with renal papillary necrosis.
 RISK FACTORS
o consume mixtures containing some combination of phenacetin & aspirin for a long period of time
 acetaminophen = coavalent binding and oxidative damage – toxic effects
 aspirin = inhibits vasodilatory effects of pg = ischemic effects
 PATHOGENESIS
o Not clear
o Papillary necrosis is the initial event. Interstitial nephritis in the overlying renal parenchyma is the next
 MORPHOLOGY
o Necrotic papillae appears yellowish brown due to break down products off phenacetin . and later papilla may be
slouged off into pelvis
 MICROSCOPY
o Coagulative necrosis of papilla
o Foci of dystrophic calcification may occur in necrotic areas
o cortex drained by the necrotic papillae shows tubular atrophy, interstitial scarring, and inflammation
 when analgesic is stopped kidney function can return to normal but maybe in months
 Complications
o Transitional-cell carcinoma of the renal pelvis or bladder


 Important cause of AKI

 Atn is fully recoverable if pt is given adequate supportive fluid and electrolyte therapy
 Clinical course
o Affected patients often present with manifestations of acute kidney injury, including oliguria and decreased
GFR. Not all patient may manifest oliguria; some will have anuria, while in others, particularly if the injury is
milder, the ATI may be non oliguric.
 CAUSES
o ISHCEMIC
 Following shock= trauma,burns and infections
 Profound hypotension= hypoperfusion of peritubular circulation
 MORPHOLOGY
 Kidney = pale and swollen
 Interstitium edematous
 Epithelial cell injury with flattening and vacuolation through out entire length of tubules
 Casts composed of cellular debris and protein, including Tamm-Horsfall protein occur
frequently in the distal tubules and collecting ducts
o ATN resulting from a crush injury, myoglobin is present in the casts.
o Following a mismatched blood transfusion haemoglobin would be present

o TOXINS
 Causes = heavy metals organic solvents glycol therapeutic substances ( antibiotics, nsaids, diuretics,
anesthesics, paraquat, phenol , pesticides
 Morphology
 Red and swollen
 SAME AS ISCHEMIC BUT damage is more in proximal tubular cells and distal tubule spared
RENAL STONES

 Risk factors
o Men
o Familial tendency
 Occurs anywhere in tract = commonest = renal pelvis
 CALCULI FORMS EITHER DUE TO
o Substances in excess= supersaturation
o Lack of substances that normally inhibit mineral precipitation
 Substances in urine that normally inhibit precipitation of crystals = tamm horsfall protein ,
pyrophosphates, citrates
o PH OF URINE
 HIGH PH = calcium phosphate and struviate stones
 LOW = uric acid
 Types of stones
o CALCIUM OXALATE / CALCIUM PHOSPHATE ( 80% stones)
 Idiopathic hypercalciuria (50%)
 Hypercalcemia and hypercalciuria (10%)
 Hyperoxaluria (5%)
 Hyperuricosuria (20%)
 No known metabolic abnormality (15% to 20%)
o STRUVITE ( Mg, NH3, Ca, PO4)
 Renal infection
o URIC ACID
 Hyperuricemia
 Hyperuricosuria
 Idiopathic (50% of uric acid stones)
o CYSTINE
 Clinical features
o Asymptomatic
o Dull ache in the loins
o Renal colic (due to the passage of a small stone along the ureter)
o Recurrent urinary tract infection.
 MORPHOLOGY
o Stones are unilateral in about 80% of patients
o Common sites
 Renal pelvis and calyces
 Bladder
o Staghorn calculi = cast of renal pelvis and calyces
 Made up of magnesium ammonium phosphate

HYDRONEPHROSIS = dilation of renal pelvis and calyces with

accompanying atrophy of parenchyma

 Due to obstruction to outflow of urine

o Sudden or insidious
o Complete or partial
o Can occur at any level of ut
CAUSES Clinical Course
• Complete bilateral obstruction anuria.
 CONGENITAL
o Atresia of urethra
• Incomplete bilateral obstruction polyuria
o Valve formations in either ureter or urethra
(due to defects in tubular concentrating
o Kinking of ureter mechanisms)
 ACQUIRED
o FB= calculi, necrotic papilla • Obstruction is below the bladder bladder
o Tumors = BPH , CA prostate , bladder, cervix,uterus distention.
o Inflammation: Prostatitis, ureteritis, urethritis,
o Neurogenic: Spinal cord damage with paralysis of the
bladder • Unilateral hydronephrosis may remain
o Normal pregnancy completely asymptomatic for long periods.

PROGNOSIS • Symptoms of the cause of hydronephrosis

(e.g. tumour, calculi )
 Removal obstruction and after few weeks = full return of function
• Enlarged kidney on physical examination.
 With time = changes become irreversible

MORPHOLOGY

 Bilateral = renal failure and alters natural course of lesion ON MICROSCOPY

 Unilateral = full range of morphologic changes
• The early lesions show tubular dilation,
 Subtotal or intermittent obstruction
followed by atrophy and fibrous
o Kidney maybe massively enlarged
replacement of epithelium.
o consists almost entirely of the distended pelvicalyceal
system. • Relative sparing of the glomeruli.
o The renal parenchyma is compressed and atrophied,
o There is obliteration & flattening of the papillae • In severe cases the glomeruli are also
 Sudden and complete obstruction atrophic and disappear converting the
o Glomerular filtration is compromised relatively early. entire kidney into a thin shell of fibrous
o Therefore, renal function may cease while dilation is still tissue
comparatively slight.
o Depending on the level of the obstruction, one or both
ureters may be dilated(hydroureter
o COAGULATIVE NECROSIS OF RENAL PAPILLAE