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1

Renal involvement usually follows a protracted course with periods of remissions and exacerbations (On & Off) immunosuppressive therapy

Lupus nephritis

2

* In situ Immune Complex (Ag-Ab) formation

Fixed antigens ( intrinsic)/ anti GBM nephritis) Planted antigens (exogenous/ endogenous)

2

*Conditions associated with IgA nephropathy

Hepatic cirrhosis - Gluten enteropathy - HIV infection - Minimal change disease -Others: membranous, Wegener’s, Ankylosing spondylitis, small cell Ca

2

*75% of all bladder tumor

Urothelial carcinoma

Papillary carcinoma

2

-Dysuria, frequency, urgency -Low back/ pelvic or genital pain -Fever, Chills & leukocytosis -Loss of sex drive,

- painful erections / ejaculation *DRE: enlarged tender prostate

Prostatitis

3

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

4

1-Renal ( primary kidney diseases)

Congenital - Acquired (glomerular / tubulointerstitial)

5

2 major causes of Acute Tubular Necrosis

ischemic & toxic

6

2-Pre-renal (inadequate blood supply) causes of dz

Heart failure - low cardiac out put - Low renal perfusion - Volume depletion - Sepsis - Severe bleeding

7

3- Post-renal (bilateral urinary obstruction) causes of dz

Tumors, BPH ( prostate)

8

: hematuria, proteinuria, hypertension

Acute nephritic syndrome:

8

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

8

AA ( secondary amyloid ) seen in

Rheumatoid arthritis Behçet syndrome Crhon’s disease Osteomyelitis Tuberculosis Renal cell carcinoma Hodgkin’s disease

8

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

9

Acute caues of Tubulointerstitial nephritis

Drugs(71%)

(antibiotics)

- Infection(15%)

- Idiopathic(8%)

- Sarcoidosis (1%)

10

Acute Drug Induced Interstitial Nephritis (AIN)

Pathogenesis:

Allergic type reaction ....manifested by

Interstitial infiltration of (eosinophils, lymphocytes, macrophages)

11

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

12

Acute injury to renal tubules, causing cell death (necrosis).....acute renal failure

Acute Tubular Necrosis (ATN)

13

Acute pyelonephritis complications 

- Papillary necrosis

- Pyonephrosis

- Perinephric abscess

14

Acute pyelonephritis infections 

15

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)

15

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)

15

Acute Pyelonephritis

laboratory findings

Elevated BUN, Creatinine (volume depletion) Elevated WBC

Pyuria, bacteruria,

WBC casts

16

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)

17

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

18

AIN serum levels 

** Blood Tests:

Increased BUN & creatinine

Increased eosinophils count

Tubular dysfunction: High K, low HCO3

19

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

19

AIN- laboratory assessment

Urine microscopy

Eosinophils

Sterile pyuria

WBC casts

Proteinuria (mild)

19

Alport Genetics

Mutations { COL4A4 & COL4A5 genes }

X-linked (80%) / AR & AD (20%)

20

Alport’s syndrome

Defects in

Collagen IV synthesis basement membrane

 

20

Alport sx 

Nephritis ( hematuria, proteinuria, renal failure) Nerve deafness 55%

Eye disorders 15-30% (juvenile form) Hematologic disorders rare (thrombocytopenia)

21

an important prognostic indicator in FSGS

Protineria

21

Amyloid fibrils composition

b-pleated sheet structures

22

Antigens & disorders associated with membranous nephropathy

**Idiopathic **Endogenous Antigens { DNA “SLE”/ tumors} **Exogenous antigens: Hepatitis B Syphilis Malaria Captopril Mercury Gold Penicillamine

23

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

24

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

25

ATN initiation phase sx (36 hours)

Acute decrease in GFR to very low levels Rapid increase in serum creatinine & BUN

26

ATN maintainance phase 

-plateau of serum creatinine & BUN

- Lasts for days to 3 weeks (oliguria)

- Uremic symptoms, fluid overload, metabolic acidosis, hyperkalemia....dialysis

27

ATN recovery phase 

Tubular function is restored Increasing GFR

Increase urine volume

Gradual decrease in creatinine & BUN

28

ATN – laboratory findings

Elevated serum Creatinine & BUN Metabolic acidosis ( low HC03 ) Hyperkalemia Hyperphosphatemia

Anemia ( decrease erythropoietin )

29

ATN – Urinary findings

Muddy brown granular casts Epithelial cells casts

Free epithelial cells Proteinuria (mild) Microscopic hematuria (mild) No pyuria

29

ATN- diagnosis

Clinical history / lab & urinary sediment

Ischemic insult:

 

- Hypotension

- Vasodilatory (septic shock)systemic infection - Hemorrhagic shock: gastrointestinal bleeding - Hypovolemic shock: vomiting, diarrhea

29

ATN- diagnosis Nephrotoxic

*Exogenous:

Aminoglycosides Contrast media “CT/cardiac cath”

 

Endogenous:

Hemoglobinuria myoglobinuria

30

ATN

Physical exam findings:

Hypotension

- Low urine output ( oliguria / anuria )

- Uremic signs ( pericardial friction rub; confusion)

31

Autosomal dominant polycystic kidney disease

development of multiple fluid filled cysts...leading to increased kidney size

32

bacteruria, pyuria

Urinary tract infection

32

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

33

bacteruria, pyuria

Urinary tract infection:

34

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)

34

Benign hypertensive nephrosclerosis Diagnosis:

Clinically: long standing hypertension Bland urine sediment with mild proteinuria Other manifestations: - LVH ( left ventricular hypertrophy) - Retinopathy - Stroke

34

Benign Prostate Hyperplasia

Nomenclature

BPH- benign prostate hyperplasia NOT hypertrophy

Is non-neoplastic Not premalignant

35

Benign Prostate Hyperplasia

Treatment

TURP-transurethral resection

5- alpha reductase inhibitors - Fenastiride

36

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

37

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

37

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)

37

Bladder cancer – risk factors

* Smoking- greatest risk factor (2X)

* Drugs: Analgesic abuse (phenacetin)

Cyclophosphamide

*Chemicals in workplace: (Naphthylamine, rubber products)

* Infections: Schistosomiasis

38

Causes of Renal Failure

1-Renal ( primary kidney diseases) 2-Pre-renal (inadequate blood supply) 3- Post-renal (bilateral urinary obstruction)

38

Child Serum: low albumin, normal Creatinine - Urine: proteinuria, bland urine sediment *Physical exam: Normal BP, Edema (periorbital, pedal)

Minimal Change Disease

39

Childhood Polycystic kidney genetics 

Autosomal recessive

Genetically homogeneous

“Gene PKHD1 (chromosome 6p21-23)”

{Protein fibrocystin}

40

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

41

Chronic Pyelonephritis:

( 2 forms):

1- Chronic obstructive pyelonephritis:

Posterior urethral valves

Kidney stones

2- Reflux nephropathy ( more common):

Vesicoureteral reflux

41

Chronic obstructive pyelonephritis gross

diffuse dilatation of calyces & scarring

Microscopic: tubular atrophy, chronic interstitial inflammation, fibrosis in cortex and medulla

42

Chronic Pyelonephritis

clinical course

Reflux pyelonephritis...silent onset....patient present late in course of disease

Renal insufficiency & hypertension

Proteinuria (mild) / significant with FSGS

43

Chronic Tubulointerstitial nephritis causes 

Infection(pyelonephritis)

- Analgesicabuse (ASA, Tylenol)

- Uratenephropathy

43

Chylocele

accumulation of lymph in tunica

44

Circulating Immune Complex

Endogenous antigens ( DNA) Exogenous antigens ( infectious protein)

45

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

46

Classification: renal involvement 1- Hypertension:

Benign nephrosclerosis Malignant nephrosclerosis

47

Clinical syndrome characterized by: heavy proteinuria (>3.5gm/day) Hypoalbuminemia Edema Hyperlipidemia & lipiduria Normal complement levels

Nephrotic Syndrome

47

Clinical: hematuria/flank pain/ palpable mass

*Hematuria is most common sign *Frequently asymptomatic (incidental) on

abdominal imaging/ work up for hematuria

Renal cell carcinoma

48

Clinically: microvascular thrombi lead to ischemic injury to target organs: kidney, brain, heart Rare: affects 1-4 people in every 1 million

HUS/TTP

49

CNS involvement more pronounced , renal failure less severe Often associated with SLE, HIV, hematological malignancy

TTP

51

colic, hematuria

Nephrolithiasis

52

colic, hematuria

Nephrolithiasis

53

Common causes Obstructive Uropathy

- BPH

- Bladder cancer

- Kidney stone

- Retroperitoneal adenopathy

- Papillary necrosis (sloughed papillae)

54

Commonest solid tumor in children 90 %...

Wilms tumor

55

Course of lupus nephritis

Clinical involvement correlates well with the degree of glomerular involvement: IV: diffuse proliferative III: focal segmental proliferative II: mesangial

55

Complications bladder diverticula 

• urine stasis

• infection

• stone formation

• Carcinomas

56

Creatinine Clearance (CrCl) 24 – hour urine collection

CrCL= UCr/PCr X volume/time

56

Cryptorchidism pic

57

Cryptorchidism Undescended testis

Epidemiology

* 4% ..........term newborn * 30%....premature

* 1%.....age one year

57

Cryptorchidism

Complications

** Germ cell tumor (35X)...Intraabdominal

** Infertility

58

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

58

Cystitis- pathogenesis

Cystitis usually secondary to infection

- Bacteria - E. Coli, Proteus, Klebsiella, Enterobacter

- Fungus – Candida

- Parasites – Schistosoma hematobium Or:

Iatrogenic:

chemotherapy , radiation (hemorrhagic cystitis)

58

Cystitis- predisposing factors

More common in female – short urethra

Diabetes mellitus

Instrumentation ( catheter, cystoscopy) Bladder calculi

Bladder outlet obstruction (male –prostate hyperplasia)

58

Cryptorchidism

Prevention of complications

surgical - Orchiopexy...before age 5y .....tumors

- Orchiopexy...before age 2y....infertility

59

Cytotoxic antibodies

Direct cell injury Without immune complex deposits

59

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

60

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)

61

Diabetic nephropathy pathogenesis:

adverse effects of systemic hyperglycemia

61

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

61

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

62

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

64

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

64

Earliest lesions in diabetic nephropathy

expansion of mesangial matrix & thickening of GBM

65

Enlarged, cystic kidneys at birth Cysts arising from collecting ducts Hepatic fibrosis

Typical outcome: variable {death in infancy or childhood}

Childhood polycystic kidney disease 

66

Epi 

Renal Stone Disease

Nephrolithiasis/ Urolithiasis

5-10% of Americans in their lifetime Peak age of onset 20-30 years

Men > women

67

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

68

Epi alports 

 

1: 5-10,000 US

5-20 yr ( M>F)

70

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

71

Epispadias

Dorsal surface

72

Epi Renal cell carcinoma (RCCa)

>11,000 cases/year in USA

Incidence peaks in six decade of life

M:F 2:1

72

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

73

Etiology Testicular tumors

– Isochromosome i(12p)

- Cryptorchidism (10%)

- Testicular dysgenesis ( Klinefelter's syndrome) - Others: radiation

74

Etiology 

Renal Stone Disease

Nephrolithiasis/ Urolithiasis

idiopathic or specific disease (gout, cystinuria, hyperoxaluria)

74

Extra-renal manifestations of ADPKD

Hepatic cysts

Cerebral aneurysms

Pancreatic cysts

Cardiac valve disease (MVP, AR) Colonic diverticular disease Abdominal wall & inguinal hernia

74

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

75

Focal segmental proliferative lupus nephritis -

Class III Lupus nephritis

75

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

77

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

78

Genetics of ADPKD

Autosomal dominant inheritance

79

Genetics of ADPKD

Genetically heterogenous

80

Germ cell tumors ( GCTs)

• Seminoma

• Seminoma

* 30% of GCTs

* middle age

* pure pattern

Sheets of cells (fried egg) + lymphocytic infiltrate)

81

Germ cell Tumors Treatment:

* Non-seminoma......surgery +/chemotherapy

* Seminoma..... surgery +/ radiotherapy

82

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

84

GFR=

volume of fluid filtered from the kidney (Glomerular capillaries) into Bowman’s space / unit time {ml/min}

85

Gleason grading

87

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

87

Group of diseases characterized by interstitial inflammation, edema,/ fibrosis and normal glomeruli

Tubulointerstitial Nephritis

87

Hematocele

blood in tunica vaginalis, trauma

89

hematuria, proteinuria, hypertension

Acute nephritic syndrome

90

Heyman has deposition where

subepithelium deposition

92

Higher in adults (African American)

FSGS-

94

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

95

history, - clinical presentation, - elevated titers of anti-streptolysin O Ab or anti-DNAase B in association with low complement

Post-streptococcal GN

96

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

96

Hydrocele

accumulation of fluid in the tunica

97

Hypospadias

Ventral surface of penis

99

IF of RPGN

Check notes for graph

100

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

101

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

102

Inflammation

Epididymo-orchitis caused by

Children: gram negative bacilli

C. trachomatis 

>35 year – UTI-E. Coli, Pseudomonas

104

Is there inflammation in amyloidosis?

No

106

known to be key in the progression of many glomerular diseases

sensitized T cells (cell mediated )

107

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

108

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)

109

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

111

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

112

LM: FSGS *IF: negative/ or non specific granular deposits of IgM &C3 * EM: patchy fusion of the foot processes & effacement

FSGS

113

LM: normal ( glomeruli, tubules, vessels) IF: no immunoglobulin deposits EM:Fusion of foot processes & effacement, detachment of basement membrane

Minimal change disease

113

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

115

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

116

LM: Variation of the thickness of BM & FSGS

IF: negative & ** negative / Segmental stain for alpha 3, 4, 5 collagen GBM

EM:

- Thin BM (

Alports 

118

long standing history of hypertension Slowly progressive elevation in serum Creatinine Mild proteinuria (

Benign hypertensive nephrosclerosis clinical presentation

119

Lupus Nephritis pathogenesis

Abnormal excess production of antibodies against “endogenous” nuclear antigens {dsDNA, ANA, Sm., RNA, Ro, La}

120

Male infertility Definition

failure to conceive after one year of regular coitus without contraception”

-59% testicular failure -37% obstruction -25% genetic

-2% endocrinopathy

121

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

123

May present at any age ( peak 2nd/3rd) decades Greatest incidence in Asians & Caucasians Rare in blacks

IgA nephropathy

125

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”

127

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

129

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

130

Membranous nephropathy pathogenesis

Localization of ICs in sub-epithelial zone as result of IC formation in situ or the deposition of circulating ICs

131

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

132

Urothelial Neoplasms Mesenchymal tumors

benign or malignant (sarcoma)

133

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

135

minimal mesangial lupus nephritis - LM…normal - IF & EM: mesangial immune deposits

CLass I Lupus nephritis

136

Most common cancer in Men in USA

2nd most common cause of cancer related deaths in men over 50years

Prostate carcinoma

137

Most common cancer of kidney (90%)

Renal cell carcinoma (RCCa)

138

Most common disorder in children

Minimal Change Disease

140

Most common type of Glomerulonephritis

IgA nephropathy

141

most common type of membranoproliferative glomerulonephritis Idiopathic rare Secondary forms are more common Evaluate patient for underlying diseases Classical Pathway activation

Type I

142

Nephritic disorders w/ Low complement levels:

Post-streptococcal glomerulonephritis *Membranoproliferative glomerulonephritis *SLE ( class III, IV) *Bacterial endocarditis/ infected ventriculoatrial shunt *Cryoglobulinemia

142

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)

143

Nephritic disorders w/ normal complement levels

IgA nephropathy/ Henoch-Schönlein Purpura Alport’s syndrome (hereditary nephritis) SLE ( class I, II, V) Benign hematuria

144

Nephritic disorders w/ variable complement

Rapidly progressive glomerulonephritis

146

Nephritic: urine sediment

1- red blood cells and/or red blood cell casts 2- granular casts 3- variable proteinuria 4- possibly WBC

148

Nephrotic dz that has No immunoglobulin deposition:

minimal change -FSGS -Diabetic nephropathy -Amyloidosis

149

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

151

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

152

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

153

oliguria / anuria / azotemia

Acute renal failure

155

oliguria / anuria / azotemia

Acute renal failure

156

Overall prognosis in RPGN

Overall 75% die or are placed on dialysis within 2 years of diagnosis

156

Pathology “safe criteria”: size (< 5mm) tubulopapillary /papillary basophil cell type

no clear cells

Renal cortical papillary adenoma

156

Paraphimosis

when a phimotic prepuce is forcibly retracted over the glans penis, causing marked constriction & swelling.

(Painful, urethral constrictions, urinary tract infection)

158

patients are asymptomatic Usually normal or slight reduced GFR Clinical paradox: HTN ( 25% in patients with ESRD)

Benign nephrosclerosis

159

Penile carcinoma in situ (CIS) all associated with HPV infection

160

Penile congenital anomalies etiology

Malformations of the urethral groove & urethral canal may create abnormal openings

161

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

162

Penile Squamous Cell Carcinoma

Clinical course

slow growing locally invasive tumors

163

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

164

Penile Squamous Cell Carcinoma

Incidence:

wide variation in different populations

Rare in Jews & Muslims

( protective effects of circumcision)

166

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

167

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.

169

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:

170

Poor prognosis of Membranous nephropathy

male, > 50 age, >10 gm proteinuria

171

Possible mechanisms for cyst formation in PKD

172

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)

173

Post-streptococcal GN clinical/outcome/prognosis

Children: almost always renal function recovered {irreversible renal failure in

174

Present with nephrotic syndrome, microscopic hematuria (50%), HTN, renal insufficiency (late), renal vein thrombosis

Membranous nephropathy

176

Primary Glomerular Diseases Pathogenesis

A- Immune Mechanisms B- Nonimmune Mechanisms

177

Primary Glomerular Diseases Pathophysiology

1. Ideopathic immglob 2. exogenous/endogenous antigens Formation of complement

178

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)

179

Prognosis of AIN 

Complete recovery or

Incomplete (40%) – persistent elevation of creatinine

180

prognosis of amyloidosis

Poor

181

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

182

Progression to nephrotic syndrome with massive proteinuria & microscopic hematuria Many are hypertensive & Have renal insufficiency

FSGS

183

prolonged symptoms of uremia

Chronic renal failure

184

prolonged symptoms of uremia

Chronic renal failure:

185

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)

186

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

187

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

188

Prostate carcinoma- screening:

Annual screening of men over age 50:

PSA screening

Digital Rectal Exam (DRE) Transurethral Ultrasound & possible biopsies

189

Prostate Carcinoma

Treatment:

STAGE dependent

* Radical prostatectomy * Radiotherapy

* Hormonal therapy

* Cryosurgery

190

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

191

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)

193

proteinuria / hematuria / both

Asymptomatic nephritic

194

proteinuria / hematuria / both

Asymptomatic:

195

Proteinuria >2gm/day - Complement levels always low Young children

Post-streptococcal GN

196

proteinuria, edema, lipiduria, hypoalbuminemia, hyperlipidemia

Nephrotic syndrome

198

proteinuria, edema, lipiduria, hypoalbuminemia, hyperlipidemia

Nephrotic syndrome

200

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

201

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%

202

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%

203

PSA-screening levels

Normal (10ng/ml...high Levels 4-10ng/ml (gray zone) Results don’t provide diagnosis 46% sensitivity,

specificity varies with age

204

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

205

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)

207

Renal cell carcinoma Clinical picture

Paraneoplastic syndrome:

* Polycythemia (erythropoietin)

* Hypertension (renin)

* Hypercalcemia (PTH)

* Cushing’s syndrome (ACTH)

* leukemoid reaction *Amyloidosis

208

Renal cell carcinoma

Investigations

• Renal ultrasound

• CT scan

• IV pyelograph

• biopsy

* Urine cytology is not good

209

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%)

210

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

210

Renal cell carcinoma

Treatment

Surgical – nephrectomy (Radical or partial)

211

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

212

Renal manifestations of polycystic kidney

213

Renal normal functions

Convert 1700 L of blood /day into 1L of urine Excretion of nitrogenous wastes Erythropoietin synthesis Renin synthesis Vit. D activation

214

Renal stone disease is usually superimposed with what infection

UTI

215

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)

217

Renal Stone: treatment

IV antibiotic,

Urological intervention, surgery

218

Renal tumors overview

219

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

221

Risk factors for ESRD in benign nephrisclerosis

- Blacks ( 8- fold) - Higher blood pressure - Second underlying CKD (diabetes)

222

Scrotal cancer risks

Chimney sweepers

Coal tar

Skin cancer

224

Secondary FSGS

HIV, - Morbid obesity, - Chronic reflux nephropathy - Heroin use, - Malignancies (lymphoma)

225

Sex cord / stromal tumors

* Rare..3% of all testicular tumors

* Leydig cells / Sertoli cells/ Granulosa cells

* benign

227

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)

229

Simple renal cysts do they predispose you to CRF or cancer? 

No 

230

Spermatocele

dilatation of epididymis with semen (sperms)

232

Systemic Lupus Erythematosus

25-50% of lupus patients have clinical renal disease at onset 60% of adults with SLE develop renal disease during course

233

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

234

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

235

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

236

Testicular tumors:Epidemiology

- 1% of all cancer death

More common in white male as compared to Asians & Africans

237

Testicular Tumors

Diagnosis:

 

** clinical picture

** serum levels of ( AFP, B-HCG)

- for diagnosis

- monitoring after treatment

239

The leading cause of end stage renal diseases in USA (1/3 of all patients)

Diabetic nephropathy

241

The primary target in minimal change

glomerular epithelial cells (podocyte)

243

thickening of basement membrane, mesangial proliferation, infiltration of inflammatory cells Can be primary (idiopathic) or secondary (underlying systemic disorder

Membranoproliferative glomerulonephritis (MPGN)

245

Tubular dysfunction

 Impaired urinary concentration (polyuria, nocturia) - Salt wasting ( hyponatremia )

- Metabolic acidosis ( decrease ability to excrete acid) - No significant proteinuria or hematuria

247

Tx for Minimal Change Disease

Steroids

248

Type I underlying dz

* lupus * Hepatitis C * Cryoglobulinemia * Endocarditis * Parasitic infection

249

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%

250

Urachus

Tubular Structure - persistent

(bladder dome to umbilicus)

Cystic * draining sinus * carcinoma

Surgical Excision

251

Urinary frequency (up to 20 times/day)

Dysuria – pain or burning micturition

Pain over bladder / suprapubic

Fever and chills

Microhematuria

Cystitis

252

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

 

253

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

254

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

255

Urothelial Carcinoma

Clinical features:

*Painless hematuria (70 – 90%) * Dysuria (20%)

* Urgency & frequency

* Flank pain

* Metastatic disease (up to 20% )

257

Urothelial Carcinoma

Natural History

Classification: (morphology – biopsy)

* Flat lesion: noninvasive / invasive

* Papillary lesion: noninvasive / invasive

258

Urothelial Carcinoma

Prognostic Factors:

Stage:

* Depth of invasion of bladder wall * Nodal metastases

* Distant metastases

Grade: based on (architecture & cytology) * low grade

* high grade

259

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

260

Urothelial Neoplasms

*Epithelial tumors

Benign - Urothelial papilloma

Malignant:

- Urothelial carcinoma (90%)

- Squamous cell carcinoma ( 7% ) - Adenocarcinoma (1-2%)

261

Urothelial Neoplasm

Squamous cell carcinoma

• 5% of primary carcinoma

• Schistosoma Hematobium

• Worse prognosis

262

Urothelial tumors - gross features pic

263

Varicocele

dilatation of congested blood vessels in spermatic cord

264

Vascular lesions

• Testicular torsion

- Twisting of spermatic cord

- Obstructionofvenous drainage

- Venouscongestion

- Infarction

265

Vesicoureteral reflux Gross

preferential scarring & calyceal dilatation at poles

266

What causes injury in minimal change

Injury results in increased glomerular permeability & subsequent massive proteinuria

267

What mutations associated with Urothelial Carcinoma

 

Associated with mutations (p53, Rb,p16 genes)

268

What nephrotic dz has Immunoglobulin deposition

Membranous nephropathy

269

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

270

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

271

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

272

Why is there hyperlipidemia in nephrotic dz

Compensatory production of ApoE to replace lost proteins

273

with polyuria, nocturia, electrolyte disorders

Renal tubular defects

274

with polyuria, nocturia, electrolyte disorders

Renal tubular defects