Renal involvement usually follows a protracted course with periods of remissions and exacerbations (On & Off) immunosuppressive therapy
Lupus nephritis
* In situ Immune Complex (Ag-Ab) formation
Fixed antigens ( intrinsic)/ anti GBM nephritis) Planted antigens (exogenous/ endogenous)
*Conditions associated with IgA nephropathy
Hepatic cirrhosis - Gluten enteropathy - HIV infection - Minimal change disease -Others: membranous, Wegener’s, Ankylosing spondylitis, small cell Ca
*75% of all bladder tumor
Urothelial carcinoma
Papillary carcinoma
-Dysuria, frequency, urgency -Low back/ pelvic or genital pain -Fever, Chills & leukocytosis -Loss of sex drive,
- painful erections / ejaculation *DRE: enlarged tender prostate
Prostatitis
1-Hematuria or proteinuria discovered on urinalysis 2-Acute nephritic syndrome with hematuria HTN and edema 3-Recurrent episodes of gross hematuria 4-Insidious onset of edema and nephrotic syndrome - Most progress to ESRD within 10-15 yearsa
Type II Membranoproliferative glomerulonephritis
1-Renal ( primary kidney diseases)
Congenital - Acquired (glomerular / tubulointerstitial)
2 major causes of Acute Tubular Necrosis
ischemic & toxic
2-Pre-renal (inadequate blood supply) causes of dz
Heart failure - low cardiac out put - Low renal perfusion - Volume depletion - Sepsis - Severe bleeding
3- Post-renal (bilateral urinary obstruction) causes of dz
Tumors, BPH ( prostate)
: hematuria, proteinuria, hypertension
Acute nephritic syndrome:
AA (secondary) amyloid:
Amyloid precursor protein is an apolipoprotein produced by the liver as an acute phase reactant in response to long standing infection or inflammation
AA ( secondary amyloid ) seen in
Rheumatoid arthritis Behçet syndrome Crhon’s disease Osteomyelitis Tuberculosis Renal cell carcinoma Hodgkin’s disease
A group of disorders associated with rapid decline in renal function with associated severe oliguria & if untreated death from renal failure within weeks to months
Rapidly progressive glomerulonephritis (RPGN)/ crescentic glomerulonephritis
Acute caues of Tubulointerstitial nephritis
Drugs(71%)
(antibiotics)
- Infection(15%)
- Idiopathic(8%)
- Sarcoidosis (1%)
Acute Drug Induced Interstitial Nephritis (AIN)
Pathogenesis:
Allergic type reaction ....manifested by
Interstitial infiltration of (eosinophils, lymphocytes, macrophages)
Acute Drug Induced Interstitial Nephritis
(AIN)Clinical presentations
Onset usually 2 weeks after start medication (first exposure) or
3-5 days if second exposure
Symptoms & Signs: ( allergic – type reaction) - Fever (27%)
- Rash (15%)
- Eosinophilia (23%)
- Triad of all (10%) or
- ARF / oliguria
- Asymptomatic
Acute injury to renal tubules, causing cell death (necrosis).....acute renal failure
Acute Tubular Necrosis (ATN)
Acute pyelonephritis complications
- Papillary necrosis
- Pyonephrosis
- Perinephric abscess
Acute pyelonephritis infections
Acute pyelonephritis
pathogenesis:
Pathways of entry into kidney
1- Bloodstream: seeding of kidney from distant source
bacterial endocarditis, septicemia)
2- Ascending infection from lower urinary tract ( most common)
Acute pyelonephritis
Pathogenesis
Ascending infection:
Bacteria has to get into bladder first
Women:
Bacterial colonization of introitus & distal urethra....entry into bladder ( short urethra, foley's catheterization, sexual intercourse
Men:
entry into bladder ..BPH, catheterization, urine stasis...bacterial colonization...
Bacteria travel retrograde up the ureters to the kidneys ( vesicoureteral reflux)
Acute Pyelonephritis
laboratory findings
Elevated BUN, Creatinine (volume depletion) Elevated WBC
Pyuria, bacteruria,
WBC casts
Acute vs Late Post-Streptococcal glomerulonephritis pathogenesis
Initially : subendothelial IC deposits (activation of complement, influx of inflammatory cells with resultant proliferative GN…decline in GFR (fast clearance) Later: characteristic subepithelial “HUMPS”…responsible for epithelial cell damage & proteinuria (slow clearance)
Advanced sclerosing lupus nephritis Global sclerosis of >90% of glomeruli Advanced interstitial fibrosis & tubular atrophy Represents healing of prior inflammatory injury, advanced stages of chronic Class III, IV, V lupus nephritis
Class VI lupus nephritis
AIN serum levels
** Blood Tests:
Increased BUN & creatinine
Increased eosinophils count
Tubular dysfunction: High K, low HCO3
AL (primary) amyloidosis
Amyloid precursor is light chain or fragment of light chain produced by abnormal clone of plasma cells Therefore, amyloid fibrils are composed of abnormal light chains Can occur alone or in association with multiple myeloma
AIN- laboratory assessment
Urine microscopy
Eosinophils
Sterile pyuria
WBC casts
Proteinuria (mild)
Alport Genetics
Mutations { COL4A4 & COL4A5 genes }
X-linked (80%) / AR & AD (20%)
Alport’s syndrome
Defects in
Collagen IV synthesis basement membrane
Alport sx
Nephritis ( hematuria, proteinuria, renal failure) Nerve deafness 55%
Eye disorders 15-30% (juvenile form) Hematologic disorders rare (thrombocytopenia)
an important prognostic indicator in FSGS
Protineria
Amyloid fibrils composition
b-pleated sheet structures
Antigens & disorders associated with membranous nephropathy
**Idiopathic **Endogenous Antigens { DNA “SLE”/ tumors} **Exogenous antigens: Hepatitis B Syphilis Malaria Captopril Mercury Gold Penicillamine
Arterioles “protected” from transmission of high pressure due to stenotic renal artery - Hypertensive arteriosclerosis in contra-lateral kidney due to increased systemic pressure
RAS Arterioles “protected” from transmission of high pressure due to stenotic renal artery - Hypertensive arteriosclerosis in contra-lateral kidney due to increased systemic pressure
Assessment of testis for male infirtility
Semen analysis:
Volume (normal 3-4ml)
Sperm count (30 million/ml)
Morphology (80% normal, motile)
U/S, CT scan
Hormones – Gonadotrophins, androgens, estrogens ***Testicular biopsy
ATN initiation phase sx (36 hours)
Acute decrease in GFR to very low levels Rapid increase in serum creatinine & BUN
ATN maintainance phase
-plateau of serum creatinine & BUN
- Lasts for days to 3 weeks (oliguria)
- Uremic symptoms, fluid overload, metabolic acidosis, hyperkalemia....dialysis
ATN recovery phase
Tubular function is restored Increasing GFR
Increase urine volume
Gradual decrease in creatinine & BUN
ATN – laboratory findings
Elevated serum Creatinine & BUN Metabolic acidosis ( low HC03 ) Hyperkalemia Hyperphosphatemia
Anemia ( decrease erythropoietin )
ATN – Urinary findings
Muddy brown granular casts Epithelial cells casts
Free epithelial cells Proteinuria (mild) Microscopic hematuria (mild) No pyuria
ATN- diagnosis
Clinical history / lab & urinary sediment
Ischemic insult:
- Hypotension
- Vasodilatory (septic shock)systemic infection - Hemorrhagic shock: gastrointestinal bleeding - Hypovolemic shock: vomiting, diarrhea
ATN- diagnosis Nephrotoxic
*Exogenous:
Aminoglycosides Contrast media “CT/cardiac cath”
Endogenous:
Hemoglobinuria myoglobinuria
ATN
Physical exam findings:
Hypotension
- Low urine output ( oliguria / anuria )
- Uremic signs ( pericardial friction rub; confusion)
Autosomal dominant polycystic kidney disease
development of multiple fluid filled cysts...leading to increased kidney size
bacteruria, pyuria
Urinary tract infection
Autosomal dominant polycystic kidney disease EPI
Common: occurs in 1-400 to 1000 lives births
Often clinically silent
Less than 50% of cases will be diagnosed during the patient’ lifetime
Accounts for 4-6% of ESRD
bacteruria, pyuria
Urinary tract infection:
Benign hypertensive nephrosclerosis Pathology
* Vascular: medial & intimal thickening ( response to hemodynamic changes) * Hyaline arteriolosclerosis ( due to extravasation of plasma proteins through injured endothelium) *Glomerular: Global sclerosis (ischemic injury)…leading to nephron loss FSGS( adaptive injury), compensatory hyperfiltration due to nephron loss * Tubules & interstitium: Tubular atrophy Interstitial fibrosis (ischemic mediated)
Benign hypertensive nephrosclerosis Diagnosis:
Clinically: long standing hypertension Bland urine sediment with mild proteinuria Other manifestations: - LVH ( left ventricular hypertrophy) - Retinopathy - Stroke
Benign Prostate Hyperplasia
Nomenclature
BPH- benign prostate hyperplasia NOT hypertrophy
Is non-neoplastic Not premalignant
Benign Prostate Hyperplasia
Treatment
TURP-transurethral resection
5- alpha reductase inhibitors - Fenastiride
Benign tumor ( rarely malignant)
Involvement (lymph nodes, spleen, Renal vein)..not malg.
50% ...tuberous sclerosis ( 25ys)/ asymtomatic / small
Sporadic...45ys / flank pain, mass, hematuria, retroperitoneal hemorrhage
Triphasic ( muscle, fat, vessels)
Angiomyolipoma
C4 levels may be normal but C3 remains depressed for prolonged periods due to C3 nephritic factor (IgG molecule that binds to and stabilizes C3bBb convertase allowing for continuous degradation of C3) Usually presents before age 30
Type II Actiavation via alternative pathway
Best prognosis of RPGN
Best prognosis is seen in those with a treatable underlying disorder (such as SLE) or one that spontaneously remits (such as post-strep)
Bladder cancer – risk factors
* Smoking- greatest risk factor (2X)
* Drugs: Analgesic abuse (phenacetin)
Cyclophosphamide
*Chemicals in workplace: (Naphthylamine, rubber products)
* Infections: Schistosomiasis
Causes of Renal Failure
1-Renal ( primary kidney diseases) 2-Pre-renal (inadequate blood supply) 3- Post-renal (bilateral urinary obstruction)
Child Serum: low albumin, normal Creatinine - Urine: proteinuria, bland urine sediment *Physical exam: Normal BP, Edema (periorbital, pedal)
Minimal Change Disease
Childhood Polycystic kidney genetics
Autosomal recessive
Genetically homogeneous
“Gene PKHD1 (chromosome 6p21-23)”
{Protein fibrocystin}
Chronic Interstitial Cystitis
Unknown etiology
Middle age female
Clinically:
* Suprapubic pain
* Frequency / Urgency *Nocturia / Hematuria
Cystoscopic examination: edema, hemorrhage, ulceration
Pathological Exam: chronic inflammation, mast cells
Chronic Pyelonephritis:
( 2 forms):
1- Chronic obstructive pyelonephritis:
Posterior urethral valves
Kidney stones
2- Reflux nephropathy ( more common):
Vesicoureteral reflux
Chronic obstructive pyelonephritis gross
diffuse dilatation of calyces & scarring
Microscopic: tubular atrophy, chronic interstitial inflammation, fibrosis in cortex and medulla
Chronic Pyelonephritis
clinical course
Reflux pyelonephritis...silent onset....patient present late in course of disease
Renal insufficiency & hypertension
Proteinuria (mild) / significant with FSGS
Chronic Tubulointerstitial nephritis causes
Infection(pyelonephritis)
- Analgesicabuse (ASA, Tylenol)
- Uratenephropathy
Chylocele
accumulation of lymph in tunica
Circulating Immune Complex
Endogenous antigens ( DNA) Exogenous antigens ( infectious protein)
Classically seen in children (one week after episode of bloody diarrhea caused by enterohemorrhagic E. coli ( 0157:H7) More severe renal failure, less pronounced CNS involvement Associated with other infections: viral, Shigella, Salmonella Drug induced: Quinine (tonic water), Gemcitabine, Cyclosporine, Ticlopidine, Oral contraceptives
hus
Classification: renal involvement 1- Hypertension:
Benign nephrosclerosis Malignant nephrosclerosis
Clinical syndrome characterized by: heavy proteinuria (>3.5gm/day) Hypoalbuminemia Edema Hyperlipidemia & lipiduria Normal complement levels
Nephrotic Syndrome
Clinical: hematuria/flank pain/ palpable mass
*Hematuria is most common sign *Frequently asymptomatic (incidental) on
abdominal imaging/ work up for hematuria
Renal cell carcinoma
Clinically: microvascular thrombi lead to ischemic injury to target organs: kidney, brain, heart Rare: affects 1-4 people in every 1 million
HUS/TTP
CNS involvement more pronounced , renal failure less severe Often associated with SLE, HIV, hematological malignancy
TTP
colic, hematuria
Nephrolithiasis
colic, hematuria
Nephrolithiasis
Common causes Obstructive Uropathy
- BPH
- Bladder cancer
- Kidney stone
- Retroperitoneal adenopathy
- Papillary necrosis (sloughed papillae)
Commonest solid tumor in children 90 %...
Wilms tumor
Course of lupus nephritis
Clinical involvement correlates well with the degree of glomerular involvement: IV: diffuse proliferative III: focal segmental proliferative II: mesangial
Complications bladder diverticula
• urine stasis
• infection
• stone formation
• Carcinomas
Creatinine Clearance (CrCl) 24 – hour urine collection
CrCL= UCr/PCr X volume/time
Cryptorchidism pic
Cryptorchidism Undescended testis
Epidemiology
* 4% ..........term newborn * 30%....premature
* 1%.....age one year
Cryptorchidism
Complications
** Germ cell tumor (35X)...Intraabdominal
** Infertility
Cystic kidney diseases changes to kidney
*Renal cysts increase in size & number (age)
*Enlarged kidneys up to 40 cm & 18Ibs
Cysts arising from different areas of tubules
Cystitis- pathogenesis
Cystitis usually secondary to infection
- Bacteria - E. Coli, Proteus, Klebsiella, Enterobacter
- Fungus – Candida
- Parasites – Schistosoma hematobium Or:
Iatrogenic:
chemotherapy , radiation (hemorrhagic cystitis)
Cystitis- predisposing factors
More common in female – short urethra
Diabetes mellitus
Instrumentation ( catheter, cystoscopy) Bladder calculi
Bladder outlet obstruction (male –prostate hyperplasia)
Cryptorchidism
Prevention of complications
surgical - Orchiopexy...before age 5y .....tumors
- Orchiopexy...before age 2y....infertility
Cytotoxic antibodies
Direct cell injury Without immune complex deposits
Cytogenetic{2 tumor supp.Genes short arm 11}
Single, well circumscribed, encapsulated soft, fleshy, grey-white / tan
Gross examination is critical ...staging Triphasic pattern (blastema, stroma,epithelial) Anaplasia { nuclear size ( 3X) & abn. mitosis
Wilms tumor
Diabetic nephropathy Clinical& outcome
Initially hyperglycemia leads to hyperfiltration ( increased GFR) & increased glomerular hydrostatic pressure After 7-13 years of disease: microalbuminuria (30-300mg/24h) appears- incipient nephropathy After 10-20 years: macroalbuminuria (>300mg/24h) - overt nephropathy Afterward there is persistent & progressive proteinuria, HTN, highly variable decline in GFR 1-24 ml/min/year ( median 12 ml/min/year)
Diabetic nephropathy pathogenesis:
adverse effects of systemic hyperglycemia
Diffuse proliferative lupus nephritis - >50% glomeruli affected on LM - Marked deposition of IC in subendothelial & mesangium - Crescents & necrotizing lesions - Clinical: most common & most severe form; hematuria, proteinuria, nephrotic syndrome, renal failure, low complements, high anti-DNA levels
Class IV lupus nephritis
Disorders characterized by abnormal platelet aggregation leading to thrombosis in arterioles & capillaries throughout the body Thrombosis in small vessels results in mechanical injury to circulating RBCs with resultant“ microangiopathic hemolytic anemia”
HUS/TTP
Diverticula bladder
Congenital : due to defect in the development of the muscle wall of bladder
Acquired : due to increase intravesical pressure secondary to obstruction of urine outflow ( BPH )
Definition: pouch like eversion or evagination of bladder wall
Electron microscopy good to visualize
1. Irregularities in GBM 2. Expansion of mesangium 3. Electron dense deposits Location * Mesangium * GBM (subendothelial / subepithelial/intramembrane) * Mixed Pattern : dense granular / fibrillary
Earliest lesions in diabetic nephropathy
expansion of mesangial matrix & thickening of GBM
Enlarged, cystic kidneys at birth Cysts arising from collecting ducts Hepatic fibrosis
Typical outcome: variable {death in infancy or childhood}
Childhood polycystic kidney disease
Epi
Renal Stone Disease
Nephrolithiasis/ Urolithiasis
5-10% of Americans in their lifetime Peak age of onset 20-30 years
Men > women
Epi ADPKD
Prevalence increases with age 80% over age 30
Usually asymptomatic & mild Synthetic liver function intact
May cause pain due to distension on liver capsule
Epi alports
1: 5-10,000 US
5-20 yr ( M>F)
Episodes of gross hematuria (associated with viral respiratory illness or GI illness) Persistent microscopic hematuria between these episodes Usually non-nephrotic range proteinuria (
IgA nephropathy
Epispadias
Dorsal surface
Epi Renal cell carcinoma (RCCa)
>11,000 cases/year in USA
Incidence peaks in six decade of life
M:F 2:1
esticular tumor- epidemiology
Trimodal age distribution:
Infant & children : Teratomas & yolk sac
15-30 years – mixed germ cell tumor
30-50 years- seminoma
> 60 year - lymphomas
Etiology Testicular tumors
– Isochromosome i(12p)
- Cryptorchidism (10%)
- Testicular dysgenesis ( Klinefelter's syndrome) - Others: radiation
Etiology
Renal Stone Disease
Nephrolithiasis/ Urolithiasis
idiopathic or specific disease (gout, cystinuria, hyperoxaluria)
Extra-renal manifestations of ADPKD
Hepatic cysts
Cerebral aneurysms
Pancreatic cysts
Cardiac valve disease (MVP, AR) Colonic diverticular disease Abdominal wall & inguinal hernia
Failure of a testis to descend completely into its normal position within the scrotum
More common on right side
Unilateral in majority but 25% cases – B/L
Cryptorchidism – undescended testis
Focal segmental proliferative lupus nephritis -
Class III Lupus nephritis
Forms of PSA
PSA in the serum occurs in both free & bound forms
Bound to various protease inhibitors like: “Alpha 1 anti-chymotrypsin & alpha 2- macroglobulin”
Both free & total PSA are measured
FSGS pathogenesis
Anything causing a reduction in renal mass will result in compensatory hyperfiltration in remaining glomeruli leading injury pattern {FSGS} *Renal ablation nephropathy (partial nephrectomy) ** Glomerulonephritis ** Congenital unilateral renal agenesis or aplasia
Genetics of ADPKD
Autosomal dominant inheritance
Genetics of ADPKD
Genetically heterogenous
Germ cell tumors ( GCTs)
• Seminoma
• Seminoma
* 30% of GCTs
* middle age
* pure pattern
Sheets of cells (fried egg) + lymphocytic infiltrate)
Germ cell Tumors Treatment:
* Non-seminoma......surgery +/chemotherapy
* Seminoma..... surgery +/ radiotherapy
Germ cell tumors: Prognosis
** Seminoma...excellent prognosis (95% cure with radiotherapy)
* spread through lymphatic
** Non-seminoma, mixed tumor....good prognosis (Up to 90% cure with chemotherapy)
* spread through blood vessels & lymphatic
GFR=
volume of fluid filtered from the kidney (Glomerular capillaries) into Bowman’s space / unit time {ml/min}
Gleason grading
GN manifests usually 10 days following pharyngitis & 3 weeks following impetigo {late period of antibody formation} More common in children (6-10year age)
Post-streptococcal GN
Group of diseases characterized by interstitial inflammation, edema,/ fibrosis and normal glomeruli
Tubulointerstitial Nephritis
Hematocele
blood in tunica vaginalis, trauma
hematuria, proteinuria, hypertension
Acute nephritic syndrome
Heyman has deposition where
subepithelium deposition
Higher in adults (African American)
FSGS-
Histologically (LM): characterized by a proliferative GN with prominent “crescent” formation in 30-70% of glomeruli and +/- segmental necrosis “The histological picture is the same regardless of the cause” The crescents evolve from cellular to fibrocellular to fibrous crescents
Rapidly progressive glomerulonephritis (RPGN)/ crescentic glomerulonephritis
history, - clinical presentation, - elevated titers of anti-streptolysin O Ab or anti-DNAase B in association with low complement
Post-streptococcal GN
HUS/TTP: Diagnosis
Clinical ground and laboratory findings: Microangiopathic hemolytic anemia ( schistocytes in peripheral blood smear) Thrombocytopenia Purpuric rash Acute renal failure (mild to moderate proteinuria, hematuria) Neurological abnormalities: headache, confusion, seizure, stroke Fever
Hydrocele
accumulation of fluid in the tunica
Hypospadias
Ventral surface of penis
IF of RPGN
Check notes for graph
IgA Nephropathy Pathogenesis:
deposition of circulating IgA ICs with subsequent activation of complement { supported by finding of granular deposits of IgA and complement (C3) in the glomerular mesangium on IF
Immunofluorescence studies good to see
Stains for antigens as Immunoglobulin deposits: ( IgG, IgA, IgM, C3, Kappa, Lambda) Distribution: Along GBM / Mesangium/ Both Patchy / diffuse Pattern: Fine or coarse granular / linear
Inflammation
Epididymo-orchitis caused by
Children: gram negative bacilli
C. trachomatis
>35 year – UTI-E. Coli, Pseudomonas
Is there inflammation in amyloidosis?
No
known to be key in the progression of many glomerular diseases
sensitized T cells (cell mediated )
Late lesions in diabetic nephropathy
diffuse global glomerulosclerosis with: - Diffuse increase in mesangial matrix & diffuse thickening of GBM - **Kimmelstiel-Wilson nodules{nodular glomerulosclerosis} nodules contain lipids & fibrin Fibrin Cap & capsular drop ( plasma proteins ) - Ischemia: causes tubular atrophy, interstitial fibrosis - Hyaline arteriolosclerosis
Light microscopy good visualize
1Cellular proliferation * Endothelial cells * Epithelial cells * Mesangial cells * Parietal cells (crescent) 2- Leukocytic infiltration 3- Necrosis 4- Thrombi (fibrin) 5- GBM thickening 6- Hyalinization ( segmental / global) glomerulosclerosis 7- deposits (amyloidosis)
LM: * Hypercellular glomeruli (neutrophils + monocytes) * Proliferation of mesangial, endothelial, epithelial cells. * Process is diffuse (entire lobules of all glomeruli) Closure of capillary loops due to: proliferation & swelling of endothelial cells & leukocytes infiltration IF: granular deposits of IgG & C3 in the mesangium & along capillary walls EM: electron dense deposits in subepithelial space “ humps”.
Post-Streptococcal glomerulonephritis
LM: diffuse thickening of the glomerular basement membrane with little increase of cellularity IF: Fine granular deposits of IgG, C3 along the basement membrane – subepithelial EM: subepithelial immune complex deposits and proliferation & growth of new GBM “ spikes” formation
Membranous nephropathy
LM: FSGS *IF: negative/ or non specific granular deposits of IgM &C3 * EM: patchy fusion of the foot processes & effacement
FSGS
LM: normal ( glomeruli, tubules, vessels) IF: no immunoglobulin deposits EM:Fusion of foot processes & effacement, detachment of basement membrane
Minimal change disease
LM: nodular, amorphous hyaline material in the mesangium & capillary loops, with resultant narrowing or closing of capillary lumens Congo Red Stain positive with polarizable apple green birefringence EM: subendothelial & mesangial fibrils
Amyloid
LM: Segmental areas of increased mesangial matrix & hypercellularity IF: Mesangial and subendothelial deposits of IgA & C3 (+/- IgG, IgM) EM: Mesangial and Subendothelial deposits
IgA Nephropathy
LM: Variation of the thickness of BM & FSGS
IF: negative & ** negative / Segmental stain for alpha 3, 4, 5 collagen GBM
EM:
- Thin BM (
Alports
long standing history of hypertension Slowly progressive elevation in serum Creatinine Mild proteinuria (
Benign hypertensive nephrosclerosis clinical presentation
Lupus Nephritis pathogenesis
Abnormal excess production of antibodies against “endogenous” nuclear antigens {dsDNA, ANA, Sm., RNA, Ro, La}
Male infertility Definition
failure to conceive after one year of regular coitus without contraception”
-59% testicular failure -37% obstruction -25% genetic
-2% endocrinopathy
Male infertility
Causes
Pre-testicular: hypopituitarism, estrogen excess
Testicular: agonadism, atrophy, germ cell aplasia, maturation arrest
Post-testicular: B/L obstruction, infections, immotile cilia syndrome
May present at any age ( peak 2nd/3rd) decades Greatest incidence in Asians & Caucasians Rare in blacks
IgA nephropathy
Membranoproliferative glomerulonephritis 3 major types all look same in LM, but EM and IF can help tell difference
LM: mesangial expansion & hypercellularity “Thickening of the peripheral capillary loops due to double contour formation “ tram track” = duplication of GBM”
Membranoproliferative glomerulonephritis Electron microscopic (EM): differing types
Type I: subendothelial deposits Type II: deposition of dense material along GBM (unknown composition) Type III: subendothelial, mesangial, subepithelial deposits
Membranous lupus nephritis - Subepithelial immune complex deposits - Diffuse thickening of GBM - Clinical: same as idiopathic membranous: nephrotic syndrome, “bland” urine sediment, mild renal insufficiency, normal C3/C4, negative anti-DNA * IC deposits in blood vessels
CLass V lupus nephrits
Membranous nephropathy pathogenesis
Localization of ICs in sub-epithelial zone as result of IC formation in situ or the deposition of circulating ICs
mesangial proliferative lupus nephritis - Mesangial immune deposits resulting in expansion & hypercellularity - Clinical: mild disease; microscopic hematuria, proteinuria, nephrotic syndrome/ renal insufficiency rare
Class II lupus nephritis
Urothelial Neoplasms Mesenchymal tumors
benign or malignant (sarcoma)
Method to gleason scoring
Select the most predominant patterns Grade each of them (grade 1-5)
Add the two numeric figures = score
example: (grade2 + grade3)= 5/10
Better idea of the aggressiveness because the pattern varies in the same tumor in different areas
(heterogenous tumor)
Score 8/10 bad prognosis
minimal mesangial lupus nephritis - LM…normal - IF & EM: mesangial immune deposits
CLass I Lupus nephritis
Most common cancer in Men in USA
2nd most common cause of cancer related deaths in men over 50years
Prostate carcinoma
Most common cancer of kidney (90%)
Renal cell carcinoma (RCCa)
Most common disorder in children
Minimal Change Disease
Most common type of Glomerulonephritis
IgA nephropathy
most common type of membranoproliferative glomerulonephritis Idiopathic rare Secondary forms are more common Evaluate patient for underlying diseases Classical Pathway activation
Type I
Nephritic disorders w/ Low complement levels:
Post-streptococcal glomerulonephritis *Membranoproliferative glomerulonephritis *SLE ( class III, IV) *Bacterial endocarditis/ infected ventriculoatrial shunt *Cryoglobulinemia
Narrowing of one or both renal arteries 75-90% due to occlusion by atheromatous plaque 10-25% fibromuscular dysplasia Others: Takayasu's arteritis, aortic/renal artery dissection
Renal artery stenosis (RAS)
Nephritic disorders w/ normal complement levels
IgA nephropathy/ Henoch-Schönlein Purpura Alport’s syndrome (hereditary nephritis) SLE ( class I, II, V) Benign hematuria
Nephritic disorders w/ variable complement
Rapidly progressive glomerulonephritis
Nephritic: urine sediment
1- red blood cells and/or red blood cell casts 2- granular casts 3- variable proteinuria 4- possibly WBC
Nephrotic dz that has No immunoglobulin deposition:
minimal change -FSGS -Diabetic nephropathy -Amyloidosis
Non-seminoma Testicular Germ cell tumor
Embryonal carcinoma (3% pure)/ more in mixed Teratoma (children ( B) / adult (M)
Yolk sac tumor (serum AFP) (children/adult) Choriocarcinoma (serum B-HCG)- rare
Mixed germ cell tumor (60%) {seminoma& non seminoma} **Peak 3rd decade
**Ill defined hemorrhagic mass, cystic, solid
Obstructive Uropathy & Hydronephrosis
Dilatation of renal pelvis & calyces
As a result of continued glomerular filtration, but unable to be excreted due to obstruction..
Diffuses back in to renal interstitium
High pressure in pelvis is transmitted through collecting tubules into renal cortex...causing renal atrophy
Renal function fully recovered if relieved fast
Irreversible damage & renal failure if obstruction not relieved by 2-3 weeks
Often asymptomatic – 50% (early stage)
Symptoms may include:
Hematuria
Bone pain - usually back pain (late stage/ metastasis)
Weight loss
Nodular hyperplasia like:
Dysuria, weak interrupted urine flow, ..
Prostate carcinoma
oliguria / anuria / azotemia
Acute renal failure
oliguria / anuria / azotemia
Acute renal failure
Overall prognosis in RPGN
Overall 75% die or are placed on dialysis within 2 years of diagnosis
Pathology “safe criteria”: size (< 5mm) tubulopapillary /papillary basophil cell type
no clear cells
Renal cortical papillary adenoma
Paraphimosis
when a phimotic prepuce is forcibly retracted over the glans penis, causing marked constriction & swelling.
(Painful, urethral constrictions, urinary tract infection)
patients are asymptomatic Usually normal or slight reduced GFR Clinical paradox: HTN ( 25% in patients with ESRD)
Benign nephrosclerosis
Penile carcinoma in situ (CIS) all associated with HPV infection
Penile congenital anomalies etiology
Malformations of the urethral groove & urethral canal may create abnormal openings
Penile congenital anomalies May be associated with
Failure of normal descent of testis (9%)
Inguinal hernia (9%),
Other malformations of urinary tract
Urinary tract obstruction
Recurrent infections Infertility
Penile Squamous Cell Carcinoma
Clinical course
slow growing locally invasive tumors
Penile Squamous Cell Carcinoma
Etiology / pathogenesis:
Carcinogens in smegma HPV 16,18
Cigarette smoking Bowen’s disease ( CIS)
Maximum incidence between the ages of 40-70 years
Penile Squamous Cell Carcinoma
Incidence:
wide variation in different populations
Rare in Jews & Muslims
( protective effects of circumcision)
Phenacetin, ASA, caffeine, acetaminophen, codeine
Ingestion of large quantities
Papillary damage due to direct toxic effect
(acetaminophen) & ischemic effect of ASA (inhibit PG)
Chronic tubulointerstitial nephritis
Excretion of necrotic papilla...gross hematuria, renal colic (ureter obstruction)
Progressive renal failure Urothelial carcinoma (rare)
Papillary Necrosis
& Chronic Analgesic Abuse
Phimosis
the orifice of the prepuce is too small to permit normal retraction
Due to: development anomalies or infection and scarring of the preputial ring.
Physical Exam/Labs: Flank or epigastric bruit ARF History: - Onset of HTN age 55 - Sudden onset of uncontrolled HTN in previously well controlled patient - Accelerated/ malignant hypertension - Intermittent pulmonary edema with normal LV function “ flash pulmonary edema” – acute pulmonary venous congestion / volume overload
Renal artery stenosis clinical:
Poor prognosis of Membranous nephropathy
male, > 50 age, >10 gm proteinuria
Possible mechanisms for cyst formation in PKD
Post-Streptococcal glomerulonephritis pathogenesis
Patient is infected with nephritogenic strain of B-hemolytic streptococci (strep- pharyngitis, skin infection- impetigo) Antibody formation against streptococcal antigenic component (? circulating or planted in glomeruli)
Post-streptococcal GN clinical/outcome/prognosis
Children: almost always renal function recovered {irreversible renal failure in
Present with nephrotic syndrome, microscopic hematuria (50%), HTN, renal insufficiency (late), renal vein thrombosis
Membranous nephropathy
Primary Glomerular Diseases Pathogenesis
A- Immune Mechanisms B- Nonimmune Mechanisms
Primary Glomerular Diseases Pathophysiology
1. Ideopathic immglob 2. exogenous/endogenous antigens Formation of complement
Penile Squamous Cell Carcinoma Prognosis
related to “stage of the tumor” Without metastasis to regional lymph nodes:
(66%) 5 year survival rate)
With metastasis: (27%) 5 year survival rate)
Prognosis of AIN
Complete recovery or
Incomplete (40%) – persistent elevation of creatinine
prognosis of amyloidosis
Poor
Prognosis of IgA nephropathy
Generally a prolonged benign course, BUT: 20% patients will progress to ESRD Most cases of IgA nephropathy are clinically restricted to kidney Arteritis, vaculitis Henoch-Schönlein- Purpura
Progression to nephrotic syndrome with massive proteinuria & microscopic hematuria Many are hypertensive & Have renal insufficiency
FSGS
prolonged symptoms of uremia
Chronic renal failure
prolonged symptoms of uremia
Chronic renal failure:
Prostate cancer – diagnosis
DRE: 70% of the tumors are in the
peripheral zone & easily palpable
(50% detected by DRE )- 2/3 outside of the capsule Transrectal ultrasound:
-Evaluation for abnormal DRE or PSA
- Biopsies( 6-12 biopsies from multiple areas ( right & left lobe apex, base, mid zone, transition zone)
Prostate carcinoma Risk factors
- Age – (8 to 10X) >65 year
- Race: African, Caribbean African American
are at higher risk (low in Asians)
- High fat diet
- Familyhistoryincreasesrisk
Prostate carcinoma- risk factors genetic link
ereditary form in 9% of all cases & up to 40% of early onset disease
Hereditary prostate cancer gene
“1 or HPC1”
Linked in prostate cancer families to the RNASEL gene
Prostate carcinoma- screening:
Annual screening of men over age 50:
PSA screening
Digital Rectal Exam (DRE) Transurethral Ultrasound & possible biopsies
Prostate Carcinoma
Treatment:
STAGE dependent
* Radical prostatectomy * Radiotherapy
* Hormonal therapy
* Cryosurgery
Prostate hyperplasia: pathogenesis
Problem:
* BPH is common in old age when testosterone levels are low
*Treatment with testosterone doesn’t aggravate BPH
**Possible role of Estrogen - increased receptors for DHT on prostatic cells
Prostate specific antigen
(PSA)
33Kd protein (serine protease)
Normally produced by prostatic glandular
epithelium
Functions on seminal liquefaction
PSA is produced in larger quantities by malignant cells
( 75% of the cancers are associated with elevated serum PSA value)
proteinuria / hematuria / both
Asymptomatic nephritic
proteinuria / hematuria / both
Asymptomatic:
Proteinuria >2gm/day - Complement levels always low Young children
Post-streptococcal GN
proteinuria, edema, lipiduria, hypoalbuminemia, hyperlipidemia
Nephrotic syndrome
proteinuria, edema, lipiduria, hypoalbuminemia, hyperlipidemia
Nephrotic syndrome
Proteinuria, edema, most common renal presentation, nephrotic syndrome Renal insufficiency is present in 50% at time of Diag. Electrolyte abnormalities (Fanconi’s syndrome) Systemic disease: Include: Heart: CM/ CHF, arrhythmias, heart block GI: hepatomegaly, malabsorption, bleeding Neuro: ischemic stroke, neuropathy, orthostatic hypotension Skin: easy bruising, purpura
Amyloidosis
PSA density (PSAd)
PSAd= ratio of the serum PSA to the volume of the prostate as determined by TRUS
PSAd of >0.125 is associated with an 80% likelihood of detecting cancer
Not as accurate as fPSA Sensitivity = 68% Specificity =75%
PSA Velocity
**The change in serum PSA over time
- Required serial sampling
- There is high degree of suspicion when the serum PSA increases more than 0.75ng/ml/year
- Sensitivity =72% - Specificity =95%
PSA-screening levels
Normal (10ng/ml...high Levels 4-10ng/ml (gray zone) Results don’t provide diagnosis 46% sensitivity,
specificity varies with age
Recurrent or persistent renal infection
Chronic tubulointerstitial nephritis
Associated with progressive renal scarring
Decline renal function...end-stage renal disease
Occurs in patients with anatomical abnormalities
Chronic Pyelonephritis
Renal cell carcinoma (RCCa)
Malignant tumor of renal tubular epithelial cells Majority sporadic/ unilateral/ single
(only 5% inherited):
- Autosomal dominant RCCa -Von-Hippel-Lindau (VHL) disease -Hereditary papillary RCCa
( multiple, bilateral, younger age group)
Renal cell carcinoma Clinical picture
Paraneoplastic syndrome:
* Polycythemia (erythropoietin)
* Hypertension (renin)
* Hypercalcemia (PTH)
* Cushing’s syndrome (ACTH)
* leukemoid reaction *Amyloidosis
Renal cell carcinoma
Investigations
• Renal ultrasound
• CT scan
• IV pyelograph
• biopsy
* Urine cytology is not good
Renal cell carcinoma
prognosis stages
Stage clinical ( I – IV ):
* Stage I: Confined to kidney ( 5ys:60- 80%)
* Stage II: perirenal fat ( 5ys:40- 70%)
* Stage III: lymph node & IVC ( 5ys:10- 40%)
* Stage IV: Adjacent organs/metas.( 5ys:5%)
Renal disease associated with marked increases in blood pressure generally >180/120mmHg/(diastolic >130mmHg) Develops in patients with pre-existing essential hypertension, secondary hypertension { pheochromocytoma, primary hyperaldosteronism) Most common in young black males
Malignant hypertensive nephrosclerosis
Renal cell carcinoma
Treatment
Surgical – nephrectomy (Radical or partial)
Renal failure + other organs involved: Brain, eye, heart, lungs, large vessels Organ damage develops over hours or days True medical emergency requiring prompt institution of intravenous anti-hypertensive medications to avoid irreversible organs damage In the past ( >50% mortality within 3 months)
Malignant hypertensive CRISIS
Renal manifestations of polycystic kidney
Renal normal functions
Convert 1700 L of blood /day into 1L of urine Excretion of nitrogenous wastes Erythropoietin synthesis Renin synthesis Vit. D activation
Renal stone disease is usually superimposed with what infection
UTI
Renal Stone Disease Prevention
Decreasing urinary concentration of the causing substances:
- Increased fluid intake (2L/day)
- Low sodium diet..decrease urinary calcium excretion CA reabsorbed in PCT with Na)
- Alkalinization of urine to (increase solubility of uric acid)
Renal Stone: treatment
IV antibiotic,
Urological intervention, surgery
Renal tumors overview
Renal US: asymmetrical kidney size (small kidney on side of RA stenosis) Renal artery Doppler: measurement of blood flow velocities in renal arteries compared to aorta { renal aortic ratio >3.5= hemodynamically significant RAS} MRA renal arteries: anatomical CT angiogram: anatomical Renal arteriogram – GOLD STANDARD
DX of Renal artery stenosis
Risk factors for ESRD in benign nephrisclerosis
- Blacks ( 8- fold) - Higher blood pressure - Second underlying CKD (diabetes)
Scrotal cancer risks
Chimney sweepers
Coal tar
Skin cancer
Secondary FSGS
HIV, - Morbid obesity, - Chronic reflux nephropathy - Heroin use, - Malignancies (lymphoma)
Sex cord / stromal tumors
* Rare..3% of all testicular tumors
* Leydig cells / Sertoli cells/ Granulosa cells
* benign
Signs & Symptoms: Only 10% are symptomatic
**Urethral compression:
- Difficulty starting & stopping urination - Frequency/ Dribbling
- Nocturia, Dysuria
**Urine retention: due in part to inability to completely empty the bladder...infections, obstruction, ect...
Benign Prostate Hyperplasia (BPH)
Simple renal cysts do they predispose you to CRF or cancer?
No
Spermatocele
dilatation of epididymis with semen (sperms)
Systemic Lupus Erythematosus
25-50% of lupus patients have clinical renal disease at onset 60% of adults with SLE develop renal disease during course
Testicular Germ cell tumor:
classification (cell differentiation )
*Seminiferous differentiation- seminoma OR
*Other differentiation -Non seminoma group:
- Minimally differentiated- embryonal Ca
- Somatic differentiation- teratoma
- Trophoblastic differentiation- chorioca.
- Yolk sac differentiation- yolk sac ca
*Mixed germ cell tumor
Testicular tumor- clinical
Unilateral testicular mass
Feeling of heaviness in the scrotum
Dull ache in the groin or abdomen
Hydrocele
Testicular pain
Breast enlargement
Metastatic disease in lymph nodes
Testicular tumors- CLASSIFICATION: Cell of origin
Germ cell tumor: (95%) (Seminoma & non seminoma)
Sex cord/ stromal tumor:
sertoli cell, leydig cell/ granulosa cell tumors
Others: lymphoma, sarcoma, metastatic tumors
Testicular tumors:Epidemiology
- 1% of all cancer death
More common in white male as compared to Asians & Africans
Testicular Tumors
Diagnosis:
** clinical picture
** serum levels of ( AFP, B-HCG)
- for diagnosis
- monitoring after treatment
The leading cause of end stage renal diseases in USA (1/3 of all patients)
Diabetic nephropathy
The primary target in minimal change
glomerular epithelial cells (podocyte)
thickening of basement membrane, mesangial proliferation, infiltration of inflammatory cells Can be primary (idiopathic) or secondary (underlying systemic disorder
Membranoproliferative glomerulonephritis (MPGN)
Tubular dysfunction
Impaired urinary concentration (polyuria, nocturia) - Salt wasting ( hyponatremia )
- Metabolic acidosis ( decrease ability to excrete acid) - No significant proteinuria or hematuria
Tx for Minimal Change Disease
Steroids
Type I underlying dz
* lupus * Hepatitis C * Cryoglobulinemia * Endocarditis * Parasitic infection
Types of renal stones:
1- Calcium containing 75%
- Calcium oxalate
- Calcium phosphate
2- Struvite (Mg/Ammonium phosphate)- 10-15% 3- Uric acid 5% 4- Cystine 1-2%
Urachus
Tubular Structure - persistent
(bladder dome to umbilicus)
Cystic * draining sinus * carcinoma
Surgical Excision
Urinary frequency (up to 20 times/day)
Dysuria – pain or burning micturition
Pain over bladder / suprapubic
Fever and chills
Microhematuria
Cystitis
Urothelial Carcinoma
(Transitional cell carcinoma- TCCa) epi
50,000 new cases/year 13,000/year estimated deaths Common, Mean age 50-80 years Male : female = 3: 1
Urothelial Carcinoma- prognosis
**57% overall survival rate (5years)
* Up to 98% -10 years with low grade tumors
* 40%- 10 years with high grade tumors
* 20% - 5 years with deeply invasive tumors
Urothelial Carcinoma:
Flat Carcinoma
Invasive carcinoma
* Deeply invasive at diagnosis
* Infrequently papillary (10%)
* Usually high grade tumor ( poorly differentiated)
* Metastases to: regional nodes/ liver/lung/bone
* Poor prognosis
Urothelial Carcinoma
Clinical features:
*Painless hematuria (70 – 90%) * Dysuria (20%)
* Urgency & frequency
* Flank pain
* Metastatic disease (up to 20% )
Urothelial Carcinoma
Natural History
Classification: (morphology – biopsy)
* Flat lesion: noninvasive / invasive
* Papillary lesion: noninvasive / invasive
Urothelial Carcinoma
Prognostic Factors:
Stage:
* Depth of invasion of bladder wall * Nodal metastases
* Distant metastases
Grade: based on (architecture & cytology) * low grade
* high grade
Urothelial Carcinoma
Treatment:
Stage:
*Ca in situ: * TUR (localize)
* Chemotherapy (multifocal)
*Noninvasive Papillary: * TUR
*Invasive Ca: * TUR (superficial)
*Surgical (cystectomy) - deep * Radiotherapy
**Metastatic CA: * Chemotherapy
Urothelial Neoplasms
*Epithelial tumors
Benign - Urothelial papilloma
Malignant:
- Urothelial carcinoma (90%)
- Squamous cell carcinoma ( 7% ) - Adenocarcinoma (1-2%)
Urothelial Neoplasm
Squamous cell carcinoma
• 5% of primary carcinoma
• Schistosoma Hematobium
• Worse prognosis
Urothelial tumors - gross features pic
Varicocele
dilatation of congested blood vessels in spermatic cord
Vascular lesions
• Testicular torsion
- Twisting of spermatic cord
- Obstructionofvenous drainage
- Venouscongestion
- Infarction
Vesicoureteral reflux Gross
preferential scarring & calyceal dilatation at poles
What causes injury in minimal change
Injury results in increased glomerular permeability & subsequent massive proteinuria
What mutations associated with Urothelial Carcinoma
Associated with mutations (p53, Rb,p16 genes)
What nephrotic dz has Immunoglobulin deposition
Membranous nephropathy
When not to take a kidney bx
Young kid End-stage renal dz orthostatic protinuria Sx are definitive for a certain dz Normal BP, Low loss of protein, normal complement, normal creatinine
WHO classification of Lupus nephritis
I- minimal mesangial II- mesangial proliferative III- focal segmental proliferative IV- diffuse proliferative V- membranous VI- advanced sclerosing lupus nephritis
Why is there edema in nephrotic dz
Loss of oncotic pressure, fluid escapes from cells, Body determines loss of volume increases aldosterone secretion to retain fluids
Why is there hyperlipidemia in nephrotic dz
Compensatory production of ApoE to replace lost proteins
with polyuria, nocturia, electrolyte disorders
Renal tubular defects
with polyuria, nocturia, electrolyte disorders
Renal tubular defects
