Renal Pathology Dr Rotimi Adigun.

Renal Pathology Dr Rotimi Adigun

Renal Pathology Outline
Introduction Glomerular diseases Tubular and interstitial diseases Diseases involving blood vessels Cystic diseases Tumors

Introduction

Introduction Functions of the kidney: Diseases of the kidney
excretion of waste products regulation of water/salt maintenance of acid/base balance secretion of hormones Diseases of the kidney glomeruli tubules interstitium vessels

Introduction Azotemia:  BUN, creatinine
Uremia: azotemia + clinical disease -Pericarditis ,Skin lesions, Gastro intestinal symptoms, Peripheral neuropathy Acute renal failure: oliguria(urine output between mls/day Chronic renal failure: prolonged uremia

Introduction Massive proteinuria>3.5gm/day Hypoalbuminemia Edema
Hyperlipidemia/-uria Nephrotic syndrome Proteinuria<3.5gm/day Hematuria Oliguria Azotemia Hypertension Nephritic syndrome

Introduction Glomerular diseases

Normal glomerulus

Nephrin Nephrin molecules extend towards each other from neighbouring foot processes Within the cytoplasm of the foot processes,It forms molecular connections. Mutations in genes encoding these proteins gives rise to nephrotic syndrome.

Characteristics of Glomerular Filtration
Glomerular filtration allows for highly permeable molecules i.e. water and small solutes to pass through. This is known as glomerular barrier function The barrier is completely impermeable to solutes, which are close to the molecular size and molecular charge of albumin Cationic (positive) charged molecules are more permeable Podocytes contain the slit diaphragm which maintains the integrity by providing a diffusion barrier to the filtration of proteins

Glomerular Diseases Can be divided into :
1. Primary Glomerular Diseases Nephrotic syndrome Nephritic Idiopathic RPGN 2. Secondary Glomerular diseases Nephrotic RPGN 3. Hereditary disorders 4.Chronic GN.

Primary Glomerular Disease
Nephrotic Minimal change disease (MCD) Focal and segmental glomerulosclerosis Membranous nephropathy Membrano-proliferative Nephritic Acute postinfectious GN Membranoproliferative GN IgA nephropathy Idiopathic RPGN or CrGN Focal segmental glomerulosclerosis

Secondary glomerular disease
Nephritic Lupus nepritis- (SLE) Diabetic nephropathy Goodpasture syndrome Microscopic polyangiitis Wegener’s granulomatosis Henoch-Schonlein purpura Bacterial endocarditis related GN Thrombotic RPGN- FSGS Nephrotic: D/M Nephropathy Focal segmental glomerulosclerosis Amyloidosis Drugs Hodgkins disease other malignancies

Hereditary Disorders Alport syndrome Fabry disease
Podocyte/slit –diaphragm protein mutations

Pathogenesis of Glomerular Disease
Three mechanisms: Immunological Podocyte injury Nephron loss Immunological: Most forms of glomerulonephritis (GN) result from immunologic mechanisms .Three mechanisms of immunological damage: 1) circulating immune complexes ( type III hypersensitivity) 2) in situ immune complexes 3) cell mediated immune reaction ( hypothetical mainly)

Pathogenesis of Glomerular Disease
Circulating Immune Complexes These are Type III hypersensitivity reactions Endogenous ( associated with SLE) or exogenous (bacterial, viral, parasitic) are different antigens involved in the immunological process Immunofluorescence microscopy reveals a granular pattern in the glomerulus

Immunological Mechanisms
In situ immune complex Deposition: Intrinsic antigens Anti-GBM Disease (good pastures),Heymann antigen(membranous glomerulopathy) Planted antigens,Exogenous(drugs,NSAIDs) Endogenous(SLE,IGA nephropathy) 2. Circulating Immune complex(tumor antigens, infectious products) Cytotoxic antibodiesActivation 3. Activation of alternative complement(dense deposit disease) Cell mediated immune Injury Cytotoxic antibodiesActivation

( Ab’s are aimed at the fixed Ag in theGBM.)
In Situ Immune Complexes i. Anti- GBM Ab GN. ( Ab’s are aimed at the fixed Ag in theGBM.) Goodpasture syndrome ,anti-GBM Ab’s cross reacting with basement membranes of lung alveoli and kidney Severe glomerular damage i.e. RPGN Immunofluorescenc microscopy will create a linear pattern when these Ab’s deposit. Anti bodies can also react against antigens in other parts of the glomerulus.

In Situ Immune Complexes
ii. Antibodies against endogenous Proteins Heyman Nephritis is the experimental model Auto-antibodies against glomerular cell membrane protein in humans. The protein responsible is yet to be identified. Complements are activated and immune aggregates from the cell surface forms subepithelial deposits. The pattern of immunoflouresence is granular in all of these cases. Responsible for Membranous glomerulopathy.

Downloaded from: StudentConsult (on 2 November 2011 05:23 AM)
© 2005 Elsevier

Downloaded from: StudentConsult (on 2 November 2011 03:49 PM)
© 2005 Elsevier

Cell Mediated Immune Response
There is a proposed theory that cell mediated immune response plays a role in glomerular injury Not a proven method of glomerular injury

Mechanisms of Glomerular injury
II. Podocyte injury: Causes of podocyte injury includes: antibodies against podocyte antigens,Toxins or mutations affecting Nephrin or any of the components of the slit –diaphragm. Ab’s attach to podocyte Ag and cause effacement, detachment of epithelial cells, and leakage of proteins.

III. Nephron Loss: Any process that leads to nephron loss =>GFR reduction of between 30-50% leads to end stage renal disease. Adaptive changes in the remaining undamaged nephrons , such as, hypertrophy of glomeruli =>, hemodynamic changes and capillary hypertension. =>Will eventually lead to further destruction of epithelial and endothelial cells.

=>to proteinuria , glomerulosclerosis, Eventually, capillaries collapse and obliterate, and glomeruli undergo segmental or global sclerosis

Introduction Glomerular diseases Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy Membranoproliferative GN Nephritic syndrome Postinfectious GN IgA nephropathy

Introductory stuff Glomerular diseases Nephrotic syndrome

Symptoms of Nephrotic Syndrome
Massive proteinuria>3.5g/day Hypoalbuminemia Edema Hyperlipidemia, lipiduria

Introductory stuff Glomerular diseases Nephrotic syndrome Minimal change disease

Causes of Nephrotic Syndrome
Adults: systemic disease DM,SLE,Drugs,E.T.C, Hodgkins lymphoma other cancers Children: minimal change disease Characterized by loss of foot processes Response to steroids in 90% of children

Minimal Change Disease
#1 cause of nephrotic syndrome in children Loss of foot processes Selective proteinuria Pathogenesis unknown Good prognosis Minimal change is the pattern of nephrotic syndrome seen in Hodgkins disease

Minimal change disease

Normal glomerulus

MCD- light microscopy The glomeruli appear normal Lipid accumulation in proximal tubule cells may be present

Minimal change disease

Introductory stuff Glomerular diseases Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis

Focal Segmental Glomerulosclerosis
Primary or secondary Some (focal) glomeruli show partial (segmental) hyalinization Unknown pathogenesis. Continuum with MCD? Primary or Idiopathic :congenital disease, Genetics(mutation of nephrin). Secondary: HIV, Heroin, other nephropathies IgA nephropathy

Histology: The affected glomeruli exhibit increased mesangial matrix, obliterated capillary lumen, and deposition of hyaline masses (hyalinosis) and lipid droplets. Occasionally, glomeruli are completely sclerosed (global sclerosis). .

Electron microscopy: effacement of foot processes as in MCD. progression =>to global sclerosis of the glomeruli with pronounced tubular atrophy and interstitial fibrosis.

Clinical disease Commonest cause of nephrotic syndrome in adults the U.S(Hispanics, blacks) Presents with non selective proteinuria Hypertension and hematuria may be present (i.e may also give nephritic picture) Prognosis: end stage renal disease in 50% within 10 years. Worse in adults.

Focal segmental glomerulosclerosis

Introductory stuff Glomerular diseases Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy

Membranous Nephropathy
Summary: Peak age 30 and 50 years of age, Idiopathic in about 85% of cases Auto immune antibodies against a yet to be identified renal antigen. Slowly progressing disease

Morphology: sub epithelial deposits (that contains immunoglobulin's) along the GBM. Little or no inflammation Spike and dome Immunoflourescence: Granular pattern Glomeruli may appear normal by light microscopy initially => diffuse thickening with disease progression. Podocyte effacement may also be seen

Membranous nephropathy

secondary membranous nephropathy: Infections (chronic hepatitis B, syphilis, schistosomiasis, malaria) Malignant tumors, carcinoma of the lung , colon and melanoma SLE and other autoimmune conditions Exposure to inorganic salts (gold, mercury) Drugs (penicillamine, captopril, nonsteroidal NSAIDS).

Pathogenesis: Idiopathic forms are induced by antibodies reacting in situ to endogenous or planted glomerular antigens. Circulating immune complexes are responsible for secondary diseases.

Pathogenesis: Immune complex deposition activate the c5b-9 (MAC)=>direct podocyte and mesangial cell injury=>Proteases and Oxidant production. Spike and dome: Sub-epithelial deposits that are separated from each other by small, spike-like protrusions of GBM matrix that form in reaction to the deposits.

Clinical course: Slowly developing disease Non selective proteinuria/contrast with MCD(globulins as well as albumin lost) Poor steroid response Variable course, remission in 10-30% End stage renal disease in up to 40% within 2-20 years

Membranous nephropathy

Membranoproliferative GN (MPGN)
Characterized by alterations in the GBM and mesangium and proliferation of glomerular cells. 5% to 10% of cases of idiopathic nephrotic syndrome in children and adults. Some present only with hematuria or proteinuria in the non-nephrotic range(nephritic); others have a combined nephrotic-nephritic picture. Two major types of MPGN (I and II) Type I accounts for 80% of cases) Different pathogenetic mechanisms responsible for the two types of MPGN

Membranoproliferative GN
Type 1. Circulating immune complexes responsible for most cases. Inciting antigen is not yet known. Occurs in association with : Hepatitis B ,Hepatitis C and SLE

Type II Also known as dense deposit disease Pathogenesis unclear Excessive complement activation Some patients possess C3 nephritic factor which is an autoantibody against C3 convertase. -It stabilizes the enzyme and prolong its activity=>extensive alternative pathway complement activation.

Type II Mutations affecting regulatory protein such as factor H has also been described.=>excessive complement activation. Low complement level is a feature of type 2 disease. Due to excessive consumption of complements as well as reduced synthesis of factor 3 by the liver.

Type II How complement activation leads to glomerular injury is still not very clear.

Morphology: Similar appearance on light microscopy Large glomeruli ,lobular appearance with proliferation of mesangial and endothelial cells. There is increased cellularity(leucocytes,mesangial cells,) Mesangial proliferation and interposition causes apparent split in basement membrane => thickened basement membrane with tram track appearance

Electron microscopy and immunoflourescence studies would demonstrate the differences in the two conditions.

Morphology:E/M and Immunoflourescence
Type II E.M Intramembranous very electron dense deposit. Immunoflouresence: Linear pattern of C3,IgG, C1q-c4 absent C3 nephritic factor may be seen Type I E.M Subendothelial electron dense deposit Immunoflouresence: Granular pattern of C3.IgG, c1q-c4 seen.

PAS showing tram track

Membrano-proliferative GN

Type II MPGN Intramembranous dense deposit

Clinical Disease 50% as nephrotic syndrome Mixed presentation also possible Progression to end stage disease in 40% of cases in 10 years Prognosis worse for dense deposit disease.

Introductory stuff Glomerular diseases Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy Nephritic syndrome

Symptoms of Nephritic Syndrome
Again, Hematuria Oliguria, azotemia Hypertension Non Nephrotic proteinuria < 3.5g/day Characterized by proliferative changes and inflammation

Causes of Nephritic Syndrome
Post-infectious GN, IgA nephropathy Immunologically-mediated

Glomerular diseases Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy Nephritic syndrome Postinfectious GN

Post-Infectious Glomerulonephritis
Child ,1-4 weeks after strep throat Immune complexes Hypercellular glomeruli Subepithelial humps Hypo complementemia Increased ASO titres

Glomerular deposition of immune complexes Caused by certain "nephritogenic" strains of β-hemolytic streptococci Other exogenous antigens such as staph aureus,pneumococcus,mumps measles,chicken pox. Endogenous antigens from SLE may also cause it(but more likely to give a membranous pattern)

“Sore throat, swollen face , pee coke with hypertension”

Increased cellularity

Sub-epithelial hump

PSGN -IF The immune deposits are distributed in the capillary loops in a granular, bumpy pattern

Introduction Glomerular diseases Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy Nephritic syndrome Postinfectious GN IgA nephropathy

A 25-years-old woman presented with 10 days history of facial edema and no other symptoms. She relates that one-year ago she saw the doctor because of hematuria. She does not have fever, weight loss. There was no personal or family history of major medical problems. Physical examination : blood pressure: 190/100, t Otherwise normal. Urinalysis revealed 60 erythrocytes HPF, proteins 4.27 g/24 h; a complete blood count was normal. What are your differentials?

Renal biopsy, shows mesangial proliferation and matrix increase

Silver staining showing increase mesangial matrix.

IgA Nephropathy/Berger Disease
Commonest cause of nephritic syndrome Child with hematuria after URI,UTI or GI infection Typically recurrent hematuria even years after the primary episode IgA in mesangium Variable prognosis May also cause nephrotic range proteinuria(less common)

IgA Nephropathy Abnormality in IgA production and clearance.
IgA, is at low levels in normal serum but increased in 50% of patients with IgA nephropathy due to increased production in the marrow. In addition, circulating IgA-containing immune complexes are present in some individuals.

IgA Nephropathy The prominent mesangial deposition of IgA suggests entrapment of IgA immune complexes in the mesangium, increased frequency in celiac disease and in liver disease Clinical Course. Common in children and young adults. Nephritic-Nephrotic picture or typical nephritic syndrome Slow progression to chronic renal failure in 25% to 50% of cases over 20 years.

IgA nephropathy- E/M Electron dense deposits in the mesangial area

Immunofloursecence IGA shows mesangial deposits
IgA nephropathy

Alport Syndrome (Hereditary Nephritis)
Caused by mutations in GBM proteins. X linked disorder Along with nephritis, Alport syndrome is associated with nerve deafness, lens dislocation, cataract, and corneal defects Mutations in any one of the alpha chains of collagen type IV result in defective assembly of these chains

Alport Syndrome Clinical findings in a female carrier will result in asyptomatic hematuria. Male with the disease would present with hematuria, proteinuria and eventual renal failure Microscopy : foam cells, which are due to accumulation of fat and mucopolysaccharides in interstitial cells. E/M: The GBM develops irregular foci of thickening or attenuation with pronounced splitting and lamination of the lamina densa, yielding a "basket-weave" appearance.

Rapidly Progressive (Crescentic) GN (RPGN)
Rapid decrease in GFR and loss of renal function in weeks to several months Major pathologic finding :extensive glomerular crescent formation within Bowman’s space due to proliferation of the parietal epithelial cells of Bowman’s capsule These crescents are composed of parietal epithelial cells, macrophages, monocytes, and fibrin It may be associated with other diseases or it may be idiopathic

RPGN Three main types of RPGN, based upon the immunological process:
1)Type I- Anti-GBM Ab- Goodpasture syndrome 2)Type II-Immune complex-poststreptococcal, SLE, HSP, IgA nephropathy 3)Type III- Pauci immune –ANCA associated- Wegener granulomatosis, microscopic angiitis On immunofluorescence, granular or linear deposits of immunoglobulins may be present +/- complement Electron microscopy may show GBM disruption

RPGN Clinical findings includes: nephritic syndrome severe oliguria Poor prognosis with rapid progression to renal failure Long term dialysis or transplantation may be required

RPGN – M/E There are epithelial crescents squashing the glomerular tufts from all sides.

Type I RPGN This is characterized deposits of IgG and C3 on the GBM .
Note: anti-GBM Ab’s also deposit on the pulmonary alveolar basement membrane => pulmonary hemorrhage and renal failure- known as Goodpasture syndrome In idiopathic cases, there is only renal involvement. Treatment: plasmapheresis

Type I RPGN- Goodpasture syndrome- IF
There is strong linear reactivity for IgG along the glomerular basement membranes.

Type II RPGN These are characterized by the presence of immune complexes An underlying cause i.e. poststreptococcal GN, IgA nephropathy,etc. may be present Immunofluorescence reveals a granular (“lumpy bumpy”) pattern on the GBM or mesangium

Type III RPGN This is also known as pauci immune RPGN
No significant immune complex or anti-GBM Ab deposition seen on immunofluorescence or electron microscopy There is the presence of ANCA in the serum of these individuals Vasculitides i.e. Wegener granulomatosis and microscopic angiitis play a role in the pathogenesis of renal disease Severe segmental necrosis may be seen in the glomeruli

Chronic GN Important cause of end stage renal disease (ESRD) characterized by chronic renal failure and uremia Clinical features: Hypertension, Proteinuria, Azotemia, Anemia, Nephritic or Nephrotic syndrome The glomeruli get obliterated and the degree of proteinuria decreases with disease progression. Treatment with renal dialysis and transplantation . Prognosis is poor .

Chronic GN-gross In ESRD, the kidneys are small and shrunken bilaterally, as shown here.

Chronic GN- micro There is interstial fibrosis, the glomeruli are sclerotic, and there are scattered chronic inflammatory cell infiltrates

Diabetes Nephropathy Glomerular lesions are the commonest cause of end stage renal disease in Diabetes Three major patterns of Glomerular disease: -Non Nephrotic Proteinuria -Nephrotic syndrome Chronic renal failure Diabetes also affects the arterioles. Characteristically involving both the afferent and efferent arterioles. Efferent arterioles are not affected in non diabetics.

Diabetes Glomerulonephritis
Pathogenesis D/M Microangiopathy (small vessel disease)is responsible. 1.Metabolic effect=>Hyperglycemia=> None enzymatic glycosylation of proteins=>AGE. => Increased type IV collagen in the GBM and decreased Heparan sulfate=>thickened GBM, increased mesangial matrix. 2.Hemodynamic effects. Initial GFR increase=>glomerular hypertrophy=>glomeruloscleorsosis

Morphology:3 main lesions 1. Capillary Basement Membrane Thickening:Thickening of basement membrane occurs in all diabetics. Starts from 2 – 5 years of D/M onset Detectible only by E/M. 2. Diffuse Mesangial Sclerosis: Diffuse progressive increase in mesangial matrix The mesangial depositions are PAS positive May also be seen in old age and hypertension.

3.Nodular sclerosis otherwise known as Kimmelstiel-Wilson Disease Ball like deposits of PAS positive laminated matrix located in the periphery of the glomerulus. Usually contained trapped mesangial cells. Seen in 15-30% of long term diabetics More Pathognomonic of D/m than diffuse sclerosis.

Exudative lesions in D/m Fibrin Cap
Exudative lesions in D/m Fibrin Cap.Hyaline deposits in the peripheral tufts of capillaries.

Exudative Lesions of D/M. capsular drop
Exudative Lesions of D/M. capsular drop.Hyalin deposits in bowmans capsule.

Introductory stuff Glomerular diseases Tubular and interstitial diseases Tubulo-interstitial Nephritis pyelonephritis drug-induced interstitial nephritis Toxic/ischemic lesions Acute tubular necrosis

Tubulointerstitial nephritis
Kidney diseases that involve structures in the kidney apart from the glomerulus. Two main categories: Pyelonephritis Interstitial Nephritis

Introductory stuff Glomerular diseases Tubular and interstitial diseases Inflammatory lesions pyelonephritis

Pyelonephritis Invasive suppurative infection of the kidneys and the renal pelvis. Usually ascends from UTI Fever, flank pain Hematogenous spread is also possible in the immuno-compromised, severe sepsis and debilitated patients. Organisms: E. coli, Proteus, enterobacter ,Pseudomonas Urinary tract mainipulations, anomalies of the lower urinary tract

Acute Pyelonephritis Pathogenesis
Bacteria can reach the kidneys via two pathways: the bloodstream or the lower urinary tract (ascending infection) Ascending infection from the lower urinary tract (most important route) : bacteria adhere to the mucosa colonize distal urethra (introitus in females) gain bladder accessmove upstream against flow of urine ascend ureters and enter pelvis of kidney

Predisposing factors for infection include: VUR (vesicoureteral reflux)- most important. Others access to bladder via instrumentation i.e. catheterization and cystoscopy females :short urethra, urethral trauma during intercourse, outflow obstruction or bladder dysfunction may lead to stasis and lead to multiplication of bacteria congenital or acquired -

Congenital- defective ureterovesical valve Acquired- - Bladder atony due to spinal cord injury and neurogenic bladder in diabetics.

Acute Pyelonephritis- gross
There is a variable number of small , yellowish abscesses scattered over the renal surface The kidney may be normal sized or enlarged

Acute Pyelonephritis Clinical findings: fever, chills, malaise
costovertebral tenderness urinary symptoms: dysuria, frequency, and urgency urinalysis: pyuria and WBC casts Complications: chronic pyelonephritis papillary necrosis perinephric abscess

Acute pyelonephritis-micro
Numerous PMN's are seen filling renal tubules

Acute pyelonephritis

WBC cast

White cell cast differentiates between pyelonephritis and a mere UTI.

Chronic pyelonephritis
Renal injury induced by recurrent or persistent renal infection. Associated with progressive renal scarring, which can lead to end-stage renal disease (ESRD) Continuous damage and scarring of renal parenchyma=>ESRD There are two types:1) chronic obstructive pyelonephritis- recurrent infections, due to obstruction, lead to renal failure 2) reflux nephropathy- this is due to VUR, which causes chronic renal damage

Chronic Pyelonephritis con’t
Hallmark of chronic pyelonephritis is scarring of pelvis or calyces, which leads to papillary blunting and an asymmetrically contracted kidney Clinical findings and diagnosis: hypertension ultrasound-looks at size and shape of kidney

Chronic pyelonephritis

Drug-Induced Interstitial Nephritis
Antibiotics, NSAIDS IgE and T-cell-mediated immune reaction Fever, eosinophilia, hematuria Patient usually recovers Analgesic nephritis is different (bad)

Drug Induced Nephritis
Injury to the kidney can be caused by a number of drugs, which include: penicillin (ampicillin, methicillin) rifampin NSAIDS Pathogenesis: - Type I (eosinophilia and rash) and Type IV hypersensitivity reactions ( granulomatous reaction) -drugs act as haptens, which bind tubular cells and become immunogenic Microscopically, there is infiltration by lymphocytes, neutrophils and eosinophils. Granulomas may be present.

Drug Induced Nephritis
Clinical findings include: fever eosinophila rash hematuria proteinuria +/- Note: complete recovery of renal function is the rule following cessation of drug intake

Drug-induced interstitial nephritis

Analgesic Nephropathy
Chronic usage of analgesic mixtures leads to papillary necrosis. Drugs implicated include: Aspirin inhibits the vasodilatory action of PGE2 and causes ischemia Acetaminophen causes free radical formation that damage renal tubules. Pathogenesis: papillary necrosis followed by interstitial nephritis Clinical findings: gross hematuria , proteinuria Increased risk of transitional cell carcinoma of the renal pelvis in survivors

Acute Tubular Necrosis
The most common cause of ARF! Reversible tubular injury Many causes: ischemic (shock), toxic (drugs) Most patients recover

Acute Tubular Necrosis (ATN)
ATN is a renal disorder involving damage to the tubular epithelial cells. It is the most common causes of acute renal failure, which is manifested by anuria or oliguria( < 400 ml/24hrs) ATN usually occurs after an acute ischemic or toxic event. Examples include: septicemia, acute pancreatitis, hemorrhage, trauma, etc.

ATN Hypovolemia and shock are the most common causes of ischemic ATN
There are two types of patterns seen in ATN: Ischemic ATN Nephrotoxic ATN Hypovolemia and shock are the most common causes of ischemic ATN Ischemia damages endothelial cells. Causes decrease in vasodilators i.e. nitric oxide, PGI2 Increase in vasoconstrictors i.e endothelin These effects lead to vasoconstriction of afferent arterioles, which decrease GFR.

ATN Nephrotoxic type Causes include: Aminoglycosides i.e. gentamicin
Radiographic contrast agents Heavy metals (i.e. lead and mercury) Organic solvents ( carbon tetrachloride)

ATN Pathogenesis: Toxins or anoxia causes shedding of tubular cells into the urine  continual injury leads to further damage of tubules tubular debris (casts) accumulates leads to increased intra-tubular pressure fluid is pushed into interstitium GFR is reduced Final result: oliguria Note: necrosis of tubular segments leads to the production of proteinaceous casts- brown colored granular casts

ATN Clinical findings: Well-defined sequence of events.
Initiation phase- (first 36 hours) Acute decrease in GFR (and oliguria) Sudden increase in serum creatinine and blood urea nitrogen (BUN) concentrations. The maintenance phase (first week) Sustained severe reduction in GFR, continues for a variable length of time(about 1-2 weeks.) Oliguria and increased BUN/creatinine persists

ATN The recovery phase, Tubular function is restored,
Increase in urine volume (up to a few liters a day) there is an increased susceptibility to infection thus, a higher mortality rate Renal function is restored and urine output returns to normal. Some kidney abnormalities may persist for several months. With appropriate therapy, there is a good prognosis

Acute tubular necrosis

Urinary Tract Infection
Women, elderly Patients with catheters or malformations Dysuria, frequency Organisms: E. coli, Proteus

UTI: Common Bugs E. coli uncomplicated complicated

Urinary catheter colonized by Proteus

Introduction Glomerular diseases Tubular and interstitial diseases Diseases involving blood vessels Benign nephrosclerosis Malignant nephrosclerosis

Benign Nephrosclerosis
Found in patients with benign hypertension Hyaline thickening of arterial walls Leads to mild functional impairment Rarely fatal Affects only afferent arterioles When seen in diabetes affects both afferent and efferent arterioles

Benign nephrosclerosis

Malignant Nephrosclerosis
Arises in malignant hypertension Hyperplastic vessels Ischemia of kidney “Flea beaten”kidney on gross appearance Medical emergency

Malignant Hypertension
5% of cases of hypertension Super-high blood pressure, encephalopathy, heart abnormalities First sign often headache, scotomas Decreased blood flow to kidney leads to increased renin, which leads to increased BP! 5y survival: 50% Histology:Necrotising arteriolitis, onion skinning,

Malignant nephrosclerosis

Introductory stuff Glomerular diseases Tubular and interstitial diseases Diseases involving blood vessels Cystic diseases Adult polycystic kidney disease Childhood polycystic kidney disease

Adult Polycystic Kidney Disease
Autosomal dominant Huge kidneys full of cysts Usually no symptoms until 30s Associated with berry aneurysms and Hypertension,hematuria Germline mutation affecting PKD1 gene on chromosome 16(85-90%). or PKD2 gene on chromosome 4(15%)

ADPKD Cysts can be formed anywhere in the kidney i.e. tubules, collecting ducts, bowman’s space, etc. Expanding cysts cause pressure on the surrounding tissues and lead to ischemic changes

Adult polycystic kidney disease

ADPKD Clinical findings:
- Most patients remain asymptomatic until middle age - Abdominal mass – massive bilateral kidney enlargement - Flank pain - Hypertension - Gross hematuria - Berry aneurysms, liver cysts are extrarenal findings Diagnosis: ultrasound Most patients develop end stage renal failure

Childhood Polycystic Kidney Disease
Autosomal recessive Numerous small cortical cysts Associated with liver cysts Patients often die in infancy

Autosomal Recessive (Childhood) Polycystic Kidney disease
This rare disease has a autosomal recessive pattern, which result from a mutation in the PKHD1 gene-codes for the fibrocystin gene on chromosome 6 It presents bilaterally as small cysts, which are usually found in the cortex and medulla and give a sponge-like appearance Cysts may be found in the liver There is a high mortality rate associated with neonates or young infants. In the surviving patient, liver cirrhosis will ensue

Childhood polycystic kidney disease

Urinary Outflow Obstruction
Renal stones -passage of a urinary stone is a frequent cause of obstruction to urinary tract -calculus (stone formation) can occur anywhere along the urinary tract The first phenomenon is supersaturation of the urine by stone-forming constituents, including calcium, oxalate, and uric acid. Crystals or foreign bodies can act as nidi, upon which the supersaturated urine form microscopic crystalline structures -

Composition of renal stones: 1. calcium oxalate or calcium oxalate + calcium phosphate (approximately 80 %) 2. magnesium ammonium phosphate (struvite stones) (approximately 10 %) 3. Uric acid (approximately 6 -7%) 4. Cystine stones (approximately 1-2%)

Pathogenesis Calcium containing stones (calcium oxalate, calcium phosphate) - Idiopathic hypercalciuria occurs in more than one half of patients with calcium oxalate stones. Most causes of hypercalciuria are absorptive -Increased absorption in individuals after a normal diet causes an elevation of serum calcium levels -Hypercalcemia due to hyperparathyroidism, sarcoidosis, vitamin D intoxication -The presence of uric acid , oxalates, and citrates in the urine provide a conducive environment for calcium deposition - Crystallization of calcium phosphate stones occurs in a high pH

Urinary Outflow Obstruction con’t
Magnesium ammonium phosphate (struvite stones) - Urinary tract infections provide an alkaline environment, which naturally cause urea splitting bacteria i.e. Proteus vulgaris to flourish -deposition in the kidney creates a cast in the renal pelvis and calyces, which is known as staghorn calculi Uric acid stones Hyperuricemia due to gout or leukemias The most important determining factor in uric stone production the presence of acidic urine-

Cystine stones -there is a defect in renal transport of cystine - Inborn errors of cystine metabolism

Clinical findings in renal Stones
-The patient may remain asymptomatic until a small stone passes out into the ureter. This typically causes a colicky pain, which radiates to the groin -Gross hematuria -Obstruction caused by stones leads to infection - Xray shows radiopaque calcium stones

Urolithiasis-CXR Radiopaque stones can be seen in this xray These are are composed of calcium

Staghorn calculi This is an x-ray of staghorn calculi

Hydronephrosis Hydronephrosis is defined as a dilation of the renal pelvis and calyces, due to the interruption of urine outflow The obstruction can be anywhere along the urinary tract Causes include: congenital- urethral atresia, kinked ureter, etc. acquired- stones, carcinoma prostate, BPH, spinal cord damage, prostatitis, ureteritis

Hydronephrosis Can be unilateral or bilateral. It is bilateral if the obstruction is below the level of the urethra; and, it is unilateral if it is above the bladder. Pathogenesis: If the flow of urine is obstructed, urine backs up behind the point of blockage, eventually reaching the small tubes of the kidney and renal pelvis Continued filtration (GFR) and back pressure (due to the obstruction) cause compression of the renal vasculature Obstruction leads to tubular dysfunction and reduction in GFR

Hydronephrosis Bilateral hydronephrosis leads to renal failure. In contrast, unilateral hydronephrosis causes an enlarged kidney There is atrophy and compression of renal parenchyma, along with loss of papillae and flattening of the pyramids Hydroureter may result depending upon the level of obstruction On M/E: tubular dilation/ atrophy and fibrosis of tubular epithelium/ loss of glomeruli (late finding), papillary necrosis eventually, cortical atrophy progresses to the point at which only a thin rim of parenchyma is present

Hydronephrosis Clinical findings:
-obstruction bilaterally leads to anuria -obstruction unilaterally may be asymptomatic -with acute obstruction, patients may present with pain, which is usually described as severe, intermittent, and dull

Hydronephrosis- gross
The cut surface shows a very thin rim of cortex The area of the pelvis and calyx are distended, and large cystic spaces occupy the pyramids. The ureter is dilated.

Introductory stuff Glomerular diseases Tubular and interstitial diseases Diseases involving blood vessels Cystic diseases Tumors Renal cell carcinoma Bladder carcinoma

Renal Cell Carcinoma Renal cell carcinoma accounts for 3 % of all malignancies.Most of these cancers arise from the proximal renal tubular epithelium Risk factors include: smoking, hypertension, cadmium exposure, and obesity. The classification of the three most common types of tumors is based upon genetic predisposition.

2. Papillary renal cell carcinoma 3. Chromophobe renal carcinoma
RCC con’t The three most common types of RCC : 1. Clear cell carcinoma 2. Papillary renal cell carcinoma 3. Chromophobe renal carcinoma

RCC Clear cell carcinoma -This is the most common type ( 70-80%) -As the name suggests, it is made up of cells with clear or granular cytoplasm -There may be an association with von Hippel Lindau (VHL) disease -VHL is an autosomal dominant disease that is characterized by cerebellar or retinal hemangioblastomas - Presents as bilateral multiple cysts

RCC Clear cell carcinoma
-VHL gene (tumor suppressor gene) is present on chromosome 3 (3p25) and an individual inherits the germ line mutation. -Somatic “hit” or somatic mutation causes the loss of the second allele. This leads to clear cell mutation, by uncontrolled tumor growth and angiogenesis -The tumor invades the renal vein, as it enlarges and extends through the kidney to reach other parts of the body- IVC penetration and invade the heart -they can metastasize to lungs (most frequent) and bone (causes lytic lesions)

RCC Papillary Renal Cell Carcinoma
- They make up % of all renal cancers - These tumors are multifocal and bilateral with a papillary growth pattern -Associated with the MET- proto-oncogene, which is located on chromosome 7 (7q31) - Grossly, they appear as a yellow mass, but to a lesser degree than clear cell carcinoma (due to lower lipid content)

RCC Chromophobe Renal Carcinoma
- These tumors represent 5 % of all renal cell carcinomas -They are made up of intercalated cells of the collecting duct. -Grossly, the tumor appears tan brown. Microscopically, nuclei are surrounded by clear cytoplasm - Missing chromosomes ( chromosomes 1,2 6, 10, 13, 17, and 21)=> hypodiploidy -This tumor has a good prognosis

This photograph shows the cut surface of a kidney
There is a large renal cell carcinoma in the upper pole with bright yellow areas, areas of hemorrhage, and tan and white areas They appear as spherical masses

RCC (clear cell carcinoma)- M/E
The malignant cells have abundant clear or empty appearing cytoplasm The tumor may appear vacuolated or solid

RCC Clinical findings: -triad of : painless hematuria, palpable abdominal mass, and dull flank pain -fever -polycythemia-erythropoiesis -paraneoplastic syndrome: hypertension, hypercalcemia, Cushing syndrome

Renal cell carcinoma

Renal Pathology Dr Rotimi Adigun.

Similar presentations

Presentation on theme: "Renal Pathology Dr Rotimi Adigun."— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Renal Pathology Dr Rotimi Adigun.

Similar presentations

Presentation on theme: "Renal Pathology Dr Rotimi Adigun."— Presentation transcript:

Similar presentations

About project

Feedback