Renal pathology Flashcards

1
Q

Nephrotic vs Nephritic

A

Nephrotic

  • Heavy proteinuria (>3.5 gm/day)
  • Edema
  • Lipiduria & Hyperlipidemia (Oval fat bodies, free fat droplets)
  • Low serum proteins (albumin)
  • few cell elements
  • fatty casts

Nephritic

  • Proteinuria (<3.5 gm/day)
  • Azotemia
  • Hematuria
  • red cells casts
  • Granular casts
  • variable proteinuria
  • Oliguria
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2
Q

Nephrotic syndrome

A

Dx

  • heavy proteinuria (>3.5gm/day) Hypoalbuminemia
  • Cholesterol casts -> Maltese cross shape
  • Edema
  • Hypogammaglobulinemia -> infections
  • Hypercoagulable state due to loss of anti-thrombin III
  • Hyperlipidemia & lipiduria
  • Normal complement levels
  • incr Glomerular permeability capillaries to protein

Diseases include

  • immunoglonulin deposition: membranous nephropathy
  • no immunoglobulin deposition: minimal change, Focal segmental glomerulosclerosis (FSGS), diabetic nephropathy, amyloidosis
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3
Q
A

Minimal change disease

Most common disorder in children

  • 15% in adults
  • Idiopathic usually
  • assoc w Hodgkin lymphoma, or renal cell carcinoma
    • due to cytokine releasing causing foot process damage

Etiopath:

  • The primary target is the glomerular epithelial cells (podocyte)
  • Injury results in increased glomerular permeability & subsequent massive proteinuria
  • No immune-complex deposition,
  • Non –inflammatory injury to visceral epithelial cells by T cell-derived cytokines

Sx: Normal BP, Edema (periorbital, pedal)

Dx Labs:

    • Serum: low albumin, normal Creatinine
    • Urine: Selective proteinuria (subepithelial lesion), bland urine sediment
    • LM: nl
  • ***EM: Fusion of foot processes & effacement detachment of BM

C&C

  • no tendency to progress into CRF/ESRD
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4
Q
A

FSGS

  • Focal: some glomeruli are affected but not others
  • Segmental: affecting only a segment of each glomerulus
  • Glomerulo: of glomeruli
  • Sclerosis: pink scarring on H&E
  • 10-15% of idiopathic nephrotic syndrome in children
  • Higher in adults (African American & Hispanics)
  • Often idiopathic,
  • Secondary to: causes of renal mass reduction
    • - HIV,
      • Morbid obesity,
      • Chronic reflux nephropathy
    • - Heroin use,
      • Malignancies (lymphoma)
    • - Sickle cell

Sx

  • Present with insidious onset of asymptomatic proteinuria Progression to nephrotic syndrome with massive proteinuria & microscopic hematuria (both subepithelial and subendothelial lesions)
  • Many are hypertensive & have renal insufficiency
  • Degree of proteinuria is an important prognostic indicator
  • Most patients will have persistent proteinuria & progressive decline in renal function
  • ESRD by 5-20 years

Dx

  • LM: FSGS
  • *IF: negative/ or non specific granular deposits of IgM &C3
  • * EM: patchy fusion of the foot processes & effacement
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5
Q

Secondary FSGS

A

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

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6
Q
A

Membranous nephropathy

  • Present with nephrotic syndrome, microscopic hematuria (50%), HTN, renal insufficiency (late), renal vein thrombosis
  • 20 years follow up: 25% of patients have spontaneous remission, 50% persistent proteinuria and stable or only loss of renal function, 25% develop ESRD
  • Poor prognosis: male, > 50 age, >10 gm proteinuria

Etiopath:

  • IC Deposits in sub-epithelial zone (Heymann Nephritis animal model)
  • Complement activation
  • Activation of mesangial cells releasing proteases and degradative enzymes

Sx: Massive proteinuria -> hypercoagulable state due to loss to anti-thrombin-3

Assoc Disorders & Ag

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

Dx

  • 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 resulting in“spikes & domes” formation
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7
Q

Diabetic nephropathy

A
  • important cause of end-stage renal failure (ESRF)

Morphology

  • Ischemia: causes tubular atrophy, interstitial fibrosis
  • Hyaline arteriolosclerosis
  • ****Kimmelstiel-Wilson nodules {nodular glomerulosclerosis} nodules contain lipids & fibrin **-> Fibrin Cap & capsular drop ( plasma proteins )
  • basement membrane thickening and mesangial expansion
  • diffuse glomerulosclerosis

Etiopath

  • Kidney disease is a result of adverse effects of systemic hyperglycemia
  • Earliest lesions: expansion of mesangial matrix & thickening of GBM
  • Initially hyperglycemia leads to hyperfiltration ( increased GFR) & increased glomerular hydrostatic pressure
  • Later lesions: diffuse global glomerulosclerosis with:
    • Diffuse increase in mesangial matrix & diffuse thickening of GBM
  • After 7-13 years of disease: microalbuminuria (30-300mg/24h) appears- incipient nephropathy (reversible renal failure)
  • After 10-20 years: macroalbuminuria (>300mg/24h) - overt/established nephropathy
  • Afterward there is persistent & progressive proteinuria, HTN, highly variable decline in GFR 1-24 ml/min/year ( median 12 ml/min/year)
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8
Q

Amyloidosis in kidney

A

Etiopath

Renal involvement can be seen with either AL or AA amyloid

Difference bw AL (majority of amyloid) vs AA: kappa or lambda

LM: nodular, amorphous hyaline material in the mesangium & capillary loops, with resultant narrowing or closing of capillary lumens; Similar morphology in diabetic neph (DDx)

Congo Red Stain positive with polarizable apple green birefringence

EM: subendothelial & mesangial fibrils

Sx

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

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9
Q

AA secondary amyloidosis

A

Rheumatoid arthritis

Behçet syndrome: recurrent aphthous ulcers, genital ulcers, and uveitis

Crohn’s disease

Osteomyelitis

Tuberculosis

Renal cell carcinoma

Hodgkin’s disease

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10
Q

Nephritic disorders

A

Normal complement levels:

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

Low complement levels:

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

variable complement:

  • **Rapidly progressive glomerulonephritis

Dx

  • Salt retention w periorbital edema HPT
  • Azotemia
  • Hematuria
  • red cells casts
  • Granular casts
  • variable proteinuria
  • Oliguria
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11
Q
A

IgA nephropathy Mesangioproliferative glomerulonephritis aka Berger’s disease

  • Most common type of Glomerulonephritis
  • May present at any age ( peak 2nd/3rd) decades

Morphology

  • LM: Segmental areas of increased mesangial matrix & hypercellularity
  • IF: Mesangial and subendothelial deposits of IgA & C3 (+/- IgG, IgM)
  • EM: Mesangial and Subendothelial deposits

Etiopath

  • Greatest incidence in Asians & Caucasians; Rare in blacks
  • Production of IgA IC ( predominately polymeric IgA1 subclass, which is mainly derived from the mucosal immune system)
  • Supported by clinical observation that hematuria worsens during URI or GI infections
  • Unknown why? But predilection for mesangium
  • Most likely deposition of IgA on mesangial matrix -> complement activation
  • Incr endothelin, less NO

Sx

  • Episodes of gross hematuria (associated with viral respiratory illness or GI illness)
  • Persistent microscopic hematuria between these episodes
  • HPT
  • Azotemia
  • Proteinuria (<3.5gm/day)
  • Normal C3/C4

C&C

  • Generally a prolonged benign course, BUT:
  • 20% patients will progress to ESRD
  • Most cases of IgA nephropathy are clinically restricted to kidney
  • Or associated with arthritis, vasculitis, non- thrombocytopenic purpura -> Henoch-Schönlein- Purpura) {HSP}

Assoc disorders

    • Hepatic cirrhosis
    • Gluten enteropathy
    • HIV infection
    • Minimal change disease
    • Others: membranous, Wegener’s, Ankylosing spondylitis, small cell Ca
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12
Q
A

Post-strep Glomerulonephritis (PSGN)

Clinical

  • GN manifests usually 10 days following pharyngitis & 3 weeks following impetigo
  • More common in children (6-10year age)
  • Usually abrupt onset of nephritic syndrome with:
    • Proteinuria >2gm/day
    • Complement levels always low

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 showing subepithelial humps (deposits); (subendothelial usually cleared away w/in first 2 months)

Etiopath

  • Initially: IC subendothelial deposits and clearance
  • Later: characteristic subepithelial “HUMPS” responsible for epithelial cell damage & proteinuria. IC deposits cleared slowly (separated from circulation by GBM) limiting their clearance

Dx

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

Sx

  • hematuria (cola-colored urine)
  • oliguria
  • HPT
  • periorbital edema
  • usually seen in children
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13
Q
A

Membranoproliferative Glomerulonephritis (MPGN)

  • Glomerular disease characterized by:
  • thickening of basement membrane, mesangial proliferation, infiltration of inflammatory cells
  • Can be primary (idiopathic) or secondary (underlying systemic disorder)
  • Same histological findings

3 major types

Type I: subendothelial deposits; C3 & IgG;

  • Idiopathic rare; Secondary forms are more common; Hep B & C
  • more often assoc w Tram tracks
  • Classical complement pathway

Type II: deposition of dense material along GBM (unknown composition; maybe C3 nephritic factor); 4 presentations

  • 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 10-15years
  • Alternative complement pathway involving C3 convertase stablized by Ab

Type III: subendothelial, mesangial, subepithelial deposits; C3 & IgG

Morphology

  • PAS stain showing splitting of GBM (tram-track appearance) due to mesangial cells
  • Silver stain showing gaps (arrow) & tram-track appearance
  • EM: ribbon-like extension of immune complexes; type 1 deposition -> subendothelial
  • Type I (bottom left): subendothelial deposits (lamina rera interna)
  • Only Type II: C3 decr due to C3 Nephritic factor = Ig (lamina densa deposits) -> Dense deposit disease
  • Dx: C3 Nephritic factor = Ig, nl C4 but C3 decr
    • LM cannot differentiate bw type I to III
  • C&C: poor prognosis
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14
Q
A

Rapidly progressive GN (RPGN)

associated severe oliguria & if untreated death from renal failure within weeks to months

** Renal biopsy & serologic analysis are indicated for diagnosis:
** sub classified in to 3 types ( I, II, III)

  • Type I: Goodpasture’s syndrome,
  • Type II: SLE, PSGN, IgA, Henoch-Schonlein Purpura, Diffuse Proliferative Glomerulonephritis
  • Type III: Wegner’s (no IF, hemoptysis, hematuria, sinusitis), PAN, Churg-Strauss

Morphology

  • LM: characterized by a proliferative GN with prominent “crescent” formation in 30-70% of glomeruli and +/- segmental necrosis
  • Crescent composed of fibrin and macrophages

Sx

  • severe glomerular injury:
  • Proteinuria (non-nephrotic), hematuria, red blood cell casts, hypertension, edema, variable degree of oliguria
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15
Q

Lupus nephritis

A
  • Fullhouse disease: +ve for multiple immunofluorescence (IgG, IgA, IgM, C3, and C1q) -> SLE
  • Based on histology:
  • I- minimal mesangial
    • LM: nl
    • IF & EM: mesangial immune deposits
  • II- mesangial proliferative
    • mesangial immune deposits resulting in expandion & hypercellularity
    • clinical: mild disease; microscopic hematuria, proteinuria, nephrotic syndrome/ renal insufficiency rare.
  • III- focal segmental proliferative
    • <50% glomeruli affected on LM
  • subendothelial & mesangial IC deposits; complement activation, influx of inflammatory cells
  • Clinical: hematuria, nephrotic syndrome, hypertension, renal failure
  • IV- diffuse proliferative
    • >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
  • V- membranous
    • 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

  • VI- 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

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16
Q
A

Benign hypertensive nephrosclerosis

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

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

Morphology

Vascular: medial & intimal thickening

* 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)

Etiopath

  • HTN -> large & small arteries medial & intimal thickening -> luminal narrowing -> ischemic injury to glomerulus, tubules, interstitium

Sx

long standing history of hypertension

Slowly progressive elevation in serum Creatinine

Mild proteinuria (<1 g/day) No microscopic hematuria, Bland urine sediment with mild proteinuria

C&C

  • LVH ( left ventricular hypertrophy)
  • Retinopathy
  • Stroke
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17
Q

ARF (Pathoma)

A

Prerenal azotemia:

  • due to decr blood flow to kidney; common cause of ARF
  • decr. GFR and oliguria
  • Rebasorption of fluid and BUN ensues (serum BUN: Cr>15)
  • Tubular fx remains intact (FENa <1%; urine osm>500 osm/kg)

Postrenal azotemia:

  • obstruction downstream of kidney
  • decr GFR and oliguria
  • Early stage: incr tubular pressure forces BUN into blood (serum BUN: Cr>15); Tubular fx remains intact (FENa
  • Long-standing obstruction: decr reabsorption of BUN (serum BUN: Cr<15; FENa>2% and urine osm<500 osm/kg)
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18
Q

ATN

A
  • most common cause of ARF
  • 2 major causes:
    • ischemic: preceded by pre-renal azotemia; PT and medullary segment of ThAL susceptible
    • nephrotoxic: PT susceptible
    • Acute Interstitial Nephritis: drug-induced Hypersensitivity Reaction (HSR) -> Eos; Ex. NSAIDS, PCN, and diuretics
  • necrotic cells plug tubule leading to *acute decline in GFR,
  • *oliguria/anuria,
  • *serum BUN & Creatinine increased
  • Metabolic acidosis ( low HC03 )
  • Hyperkalemia
  • Hyperphosphatemia
  • Anemia ( decrease erythropoietin from renal peritubular interstitial cells)

Clinical course

3 predictable phases:

**Initiation phase (36 Hrs):

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

  • ***Maintenance phase:**
  • plateau of serum creatinine & BUN
  • Lasts for days to 3 weeks (oliguria)
  • Uremic symptoms, fluid overload, metabolic acidosis, hyperkalemia requiring dialysis

**Recovery phase:
Tubular function is restored Increasing GFR
Increase urine volume
Gradual decrease in creatinine & BUN

**Dx **

  • Hypotension
  • Low urine output ( oliguria / anuria )
  • Uremic signs ( pericardial friction rub; confusion)
  • Vasodilatory (septic shock): systemic infection
  • Hemorrhagic shock: gastrointestinal bleeding
  • Hypovolemic shock: vomiting, diarrhea
  • Muddy brown granular casts
  • Epithelial cells casts
  • Free epithelial cells
  • Proteinuria (mild)
  • Microscopic hematuria (mild)
  • No pyuria
  • ** urine may be “normal” in less severe disease
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19
Q

ESRD

A
  • most common causes are diabetes, HPT, and glomerular disease

Uremia sx:

  • nausea
  • anorexia
  • pericarditis
  • PLT dysfunciton
  • encephalopathy w asterixis
  • urea crystal depositions
  • salt and H2O retention -> HPT
  • hyperkalemia w metabolic acidosis
  • anemia (EPO made up renal peritubular interstitial cells)

Complications

  • hypocalcemia
  • renal osteodystrophy (osteitis firbos cystica, osteomalacia, and osteoporosis
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20
Q

Malignant Hypertension

A

>180/120mmHg/(diastolic >130mmHg)

Develops in patients with pre-existing essential hypertension, secondary hypertension { pheochromocytoma, primary hyperaldosteronism)

Most common in young black males

Morphology

Gross: “flea-bitten appearance” -> Small, pinpoint petechial hemorrhages.

Microscopic:

Fibrinoid necrosis of arterioles -> homogenous, granular eosinophilic appearance

“Onion-skin appearance” -> proliferation of intimal cells -> hyperplastic arteriolosclerosis

Etiopath

Severe HTN -> breakthrough transmission of high pressure -> arterioles & capillaries -> endothelial wall injury -> release of fibrinogen, platelet deposition, plasma proteins -> fibrinoid necrosis & intravascular thrombosis

C&C: hypertensive crisis

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21
Q

Thrombotic Microangiopathies

Hemolytic uremic syndrome (HUS)

Thrombotic thrombocytopenic purpura (TTP)

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

SX

  • 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

HUS:

  • HUS/TTP: Clinical:
  • 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

TTP:

  • CNS involvement more pronounced , renal failure less severe
  • Often associated with SLE, HIV, hematological malignancy
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22
Q

RAS

A

Etiology

  • 75-90% due to occlusion by atheromatousplaque
  • 10-25% fibromuscular dysplasia
  • Others: Takayasu’s arteritis, aortic/renal artery dissection
  • Onset of HTN age<30 or >55
  • Sudden onset of uncontrolled HTN in previously well controlled patient
  • Accelerated/malignant hypertension
  • Intermittent pulmonary edema with normal LV function

Ischemic nephropathy

  • Diffuse ischemic atrophy in kidney of affected RA stenosis
    • Crowded glomeruli
    • Atrophic tubules
    • Interstitial fibrosis
  • No significant arteriolosclerosis in kidney of affected RA stenosis:
    • Arterioles “protected” from transmission of high pressure due to stenotic renal artery
    • Hypertensive arteriosclerosis in contralateral kidney due to increased systemic pressure.

Sx

  • Flank or epigastric bruit
  • ARF

Dx: Renal arteriogram is GS

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23
Q

Tubulointerstitial nephritis

A
  • Group of diseases characterized by interstitial inflammation, edema,/ fibrosis and normal glomeruli
  • Tubular dysfunction:
      • Impaired urinary concentration (polyuria, nocturia)
      • Salt wasting ( hyponatremia )
      • Metabolic acidosis ( decrease ability to excrete acid)
      • No significant proteinuria or hematuria

Causes

  • Acute: Drugs (AIN), infection, idiopathic, sarcoidosis
  • Chronic: Infection (pyelonephritis), analgesic abuse (ASA, tylenol), urate nephropathy

Etiopath of AIN

  • Interstitial infiltration of (eosinophils, lymphocytes, macrophages)
  • Most common drugs: Penicillins & Cephalosporins, NSAIDs

Sulfonamides (Bactrim, Furosemide, Thiazide diuretics), Ciprofloxacin, Rifampin, Cimetidine, Allopurinol, PPI

Sx: Onset usually 2 weeks after start medication (first exposure) or 3-5 days if second exposure

  • Fever (27%)
  • Rash (15%)
  • Eosinophilia (23%)
  • Triad of all (10%) or
  • ARF / oliguria
  • Asymptomatic

Dx

Urine microscopy:

  • Eosinophils
  • Sterile pyuria
  • WBC casts
  • Proteinuria (mild)

** Blood Tests:

  • Increased BUN & creatinine
  • Increased eosinophils count
  • Tubular dysfunction: High K, low HCO3

**Diagnosis confirmation by renal biopsy

24
Q

Types of cell casts

A
  • all cylindrical due to formation in renal tubules; if injury post-renal such as kidney stone -> cells (hematuria)
  • Hyaline cast: cylindrical casts accumulate in CD
    • Tamm-Horsefall proteins -> mucuoid protein made in Tubules -> tubule injury
    • Some myoglobin
    • Seen in dehydration; not always pathological
  • Granular cast: cigar-shaped
    • Epithelial cells and Ig light chains
    • ATN (epithelial shedding)
    • Nephritis
  • Waxy cast: broad-large w sharp edges due to oliguria
    • Low urine flow > chronic renal failure
  • Red cell casts: a type of hematuria
    • always pathological -> nephritis: Wegner’s, SLE, PSGN, Goodpasture
    • Never in kidney stones
  • WBC casts:
    • Acute pylonephritis
    • Acute interstitial nephritis
  • Urine sediments: showing hematuria & pyuria (WBC)
  • Oval fat bodies: bubbly appearance
    • Nephrotic syndromes -> due to high levels apolipoproteins -> epithelial cells absorb lipds -> tubule shedding of lipid-ladened epithelial
25
Alport syndrome * Nephritic syndrome (hematuria, proteinuria, renal failure) * Males 5 to 20 yo **Etiology**: * X-linked Mutation in col4A4 for type IV collagen * absence of globular region of alpha 3 chain of type IV collagen. (AD, AR and X-linked) * defective GBM synthesis **Morphology** – LM: Thinning, splitting and fragmentation of GBM; foam cells in glomeruli and tubules –IF: Negative –EM: Basket weave splitting of lamina densa **Clinically:** • Microscopic haematura **Sx** * isolated hematuria * Nerve deafness (esp. to high frequencies), * Eye disorders (cataracts and dislocated lens) * Disorders of skin * Disorders of platelets
26
Acute pyelonephritis * Gross: collection of abscess (whitish) * Microscopic: focal inflammation & necrosis **Sx** * Fever (high) * Dysuria * Flank pain * Nausea, vomiting * Costovertebral angle tenderness **Dx** * Elevated BUN, Creatinine (volume depletion) * Elevated WBC * Pyuria, bacteruria, * WBC casts **Etiopath:** * Intense interstitial edema -\> compress renal arterioles -\>Decr GFR * Predisposing factors: decr urine flow -\> UTI, endocarditis, diabetes, BPH, renal stones, catheters **C&C** * Papillary necrosis * Pyonephrosis * Perinephric abscess
27
Chronic pyelonephritis
* 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 **2 forms** 1- Chronic obstructive pyelonephritis: Posterior urethral valves Kidney stones 2- Reflux nephropathy ( more common): Vesicoureteral reflux (VUR) **Clinical course:** * Reflux pyelonephritis...silent onset....patient present late in course of disease * Renal insufficiency & hypertension * Proteinuria (mild) / significant with FSGS * \*\*Gross: * VUR – preferential **scarring** & calyceal dilatation at **poles** * Obstructive – diffuse dilatation of calyces & scarring * Microscopic: tubular atrophy, chronic interstitial inflammation, fibrosis in cortex and medulla * FSGS
28
Papillary necrosis
* 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)
29
Papillary necrosis: pyelonephritis
* Uncommon, but serious * Interstitial inflammation compress medullary vasculature ischemia & papillary necrosis * Treat underlying infection w IV antibiotics
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Obstructive Uropathy (OU) * Obstruction at any level of urinary tract from urethra to renal pelvis * Obstruction above the bladder can be unilateral or bilateral * Common causes: * - BPH * - Bladder cancer * - Kidney stone * - Retroperitoneal adenopathy * - Papillary necrosis (sloughed papillae) UO w 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
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Cystic kidney diseases Classification:
\*Genetic: - Adult autosomal dominant polycystic kidney disease - Autosomal recessive (childhood) polycystic kidney \*Acquired: - Benign simple cysts - Medullary sponge kidney \*Cysts associated with systemic diseases: - Von Hippel-Lindau Syndrome (VHLS) - Tuberous sclerosis (TS)
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Autosomal dominant polycystic kidney disease (ADPKD) **Etiology** * Characterized by development of multiple fluid filled cysts...leading to increased kidney size * Common: occurs in1-400 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 **Pathogenesis of renal failure** * Abnormal Chromosome 16p13.3 (APKD1 gene) **-\> Majority cases** * Abnormal Chromosome 4q21 (APKD2 gene) * \*\*Milder phenotype: * •Later onset of cysts •Fewer & smaller cysts •Slower progression * •Later age of ESRD * Possible mechanisms for cyst formation in PKD * mutations in polycystin 1,2 or fibrocystin * defects in cell-cell and cell-matrix interactions * altered tubular epithelial growth and differentiation leading to changes promoting cyst formation * abnormal ECM * cell proliferation * fluid secretion * Cystic growth leads to: * 1- Compression & destruction of normal adjacent parenchyma * 2- Glomeruli are overperfused BUT: * - Small number of nephrons \<5% involved * - No evidence of FSGS **Sx: Renal manifestations** * HPT due to Cysts lead to compression of renal vessels--\> renin, aldosterone * Hematuria due to Rupture of cysts in collecting system * Flank pain due to Stretching of renal capsule * Nephrolithiasis due to \>50% uric stones, calcium oxalate * Renal failure **Sx: Extra-renal manifestations** * **Hepatic cysts**: 80% over age 30, usually asx & mild, liver fx intact * **Cerebral aneurysms** * Pancreatic cysts * Cardiac valve disease (**MVP**, AR) Colonic diverticular disease Abdominal wall & inguinal hernia Image below * Left: Hepatic cysts * Right: Berry aneurysm * Cysts any where in kidne **Dx** * Renal Biopsy: Arteriolar sclerosis or Interstitial fibrosis
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Childhood Polycystic kidney: AR PCKD * Enlarged, cystic kidneys at birth * newborns may present w Potter sequence (Pathoma) * Cysts arising from collecting ducts * Assoc w Congenital Hepatic fibrosis -\> liver fx intact but can present w portal HPT * Typical outcome: variable {death in infancy or childhood}
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Simple renal cysts
* Can be single or multiple * Do not predispose to CRF or cancer * More common with older age
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Renal tumor types
Benign * Renaladenoma * Renaloncocytoma * Medullaryfibroma * Angiomyolipoma Malignant * Renal cell carcinoma 90% * Urothelial carcinoma * Children: Wilms tumor
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Renal cortical papillary adenoma
* Autopsy series (7-23%) * Pathology “safe criteria”: * size (\< 5mm) * tubulopapillary /papillary * basophil cell type * no clear cells
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Angiomyolipoma
* 50% **tuberous sclerosis** ( 25ys)/ asymtomatic / small * Sporadic @ 45ys / flank pain, mass, hematuria, retroperitoneal hemorrhage * Triphasic **hamartoma** composed of muscle, fat, vessels
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Renal cell carcinoma (RCCa) * Gross: solitary large yellow mass on upper pole due to tumour * Microscopic: * High vascularization * Polygonal cells with very **clear cytoplasms** * Malignant tumor of renal tubular epithelial cells * Majority sporadic/ unilateral/ single * Clear cell carcinoma: * **Etiopath** * males more than females * Tobacco, obesity, HPT * Renal vein invasion -\> poor prognosis * Sporadic or hereditary​: both involving **VHL gene** * Autosomal dominant RCCa * Von-Hippel-Lindau (**VHL**) disease: Von Hippel Lindau syndrome (renal, CNS, retina) * incr IGF-1 and * incr HIF which in turn VEGF & PDGF * Hereditary papillary RCCa: ( multiple, bilateral, younger age group) **Clinical** * Incidence peaks in six decade of life * M:F 2:1 * SX: **hematuria/flank pain/ palpable mass** \<10% of patients * \*Hematuria is most common sign \*Frequently asymptomatic (incidental) on * abdominal imaging/ work up for hematuria **Assoc. w Paraneoplastic syndrome** **Dx** * Renal ultrasound * CT scan * IV pyelograph * biopsy * Urine cytology useless
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Wilms tumour
* Commonest solid tumor in children 90 %...\<6 ys * Cytogenetic{2 tumor supp.Genes short arm 11} * Single, unilateral well circumscribed, encapsulated soft, fleshy, grey-white / tan * Gross examination is critical for staging * Triphasic pattern: **blastema (key component)**, stroma,epithelial * Anaplasia { nuclear size ( 3X) & abn. mitosis * Sx: WAGR
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Horseshoe kidney
–Fusion of kidney during developing –Usually asx -\> maybe obstructions, UTI, and renal stones
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Diverticula of the 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 * Complications: * urine stasis * infection * stone formation * Carcinomas
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Cystitis
**Etiopath** * Cystitis usually secondary to infection or iatrogenic (chemo, radiation/hemorrhagic cystitis) **Predisposing factors** * More common in female – short urethra * Diabetes mellitus * Instrumentation ( catheter, cystoscopy) * Bladder calculi * Bladder outlet obstruction (male –prostate hyperplasia) * Malacoplakia due to chronic bacterial infection, commonly E. coli or Proteus. **Sx** * Urinary frequency (up to 20 times/day) * Dysuria – pain or burning micturition * Pain over bladder / suprapubic * Fever and chills (usually absent; Pathoma) * Microhematuria **Dx Labs (Pathoma)** * urinalysis: cloudy urine w \>10 WBCs/hpf * Dipstick: +ve leukocyte esterase (due to pyuria) and nitrites * Culture: \> 1e5 CFU * Sterile pyuria suggests C. trachomatis or N. gonorrhoeae
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Nephrolithiasis compositions & causes
See table below (Pathoma) * AMP stone -\> stag horn caliculus in adults * Uric acid -\> seen in Pt w leukemia and myeloproliferative * Cysteine -\> stag horn caliculus in children
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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
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Urothelial carcinoma * Jagged edges obstructing bladder lumen **Etiology** * 50 to 80 yo males * Risk factor: * Smoking- greatest risk factor (2X) * Drugs: Analgesic abuse (phenacetin) * Cyclophosphamide * Chemicals in workplace: (Naphthylamine, rubber products) **Pathogenesis** * assoc w p53, Rb,p16 gene mutations * Squamous cell carcinoma: Schistosoma haematobium; worse prognosis * Classification * Flat type * Papilllary type **Sx:** * painless hematuria * Dysuria (20%) * Urgency & frequency * Flank pain * Metastatic disease (up to 20% ) **Rx:** TUR, chemo, radio, surgery, **Flat vs Papillary type** Papillary type * 75% of all bladder tumor * \* Exophytic tumor * \* Low grade tumor * \* Superficial invasion * \* Multiple recurrence * \* Multifocal ( urinary tract) * \*\*Tumor progression ( 5-10%) * \* high grade 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
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BPH **Gross image:** –Prostate larger than 4 cm –Slit like urethra –Bumpy (vs smooth in adenocarcinoma) **Microscopic:** - large glands producing serine proteases, stroma thickening, - 2 layers lining glands (outer cuboidal or innner transitional): suggesting nl or hyperplasia - Peri-urethral or transitional zone -\> BPH **Signs & Symptoms:** Only 10% are symptomatic * \*\*Urethral compression: * - Difficultystarting&stoppingurination * - Frequency/Dribbling * - Nocturia,Dysuria * \*\*Urine retention: due in part to inability to completely empty the bladder leading to infections, obstruction -\> **dribbling** **Etiopath:** * Etiopath: proposed to involve increased DHT-R and estrogen **C&C:** * non-neoplastic & Not premalignant * diverticulum inside bladder * UTI due to stasis * Bladder stones * Obstructive uropathy **Rx:** * TURP-transurethral resection * 5- alpha reductase inhibitors - Fenastiride
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Prostatitis
Clinical diagnosis: * -Dysuria, frequency, urgency * -Low back/ pelvic or genital pain * -Fever, Chills & leukocytosis * -Loss of sex drive, * - painful erections / ejaculation * \*DRE: enlarged tender prostate
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Prostatitc adenocarcinoma **Microscopic:** * Single layer surround glands -\> Less stroma to parenchyma **Etiopath:** * 7th or 8th decade * Race: African, Caribbean African American are at higher risk (low in Asians) * High fat diet * Family hx increases risk * Hereditary prostate cancer gene: 1 or HPC1 -\> RNASEL gene **Sx** * Often asymptomatic – 50% (early stage) * Hematuria * Bone pain - usually back pain (late stage/ metastasis) * Weight loss * Nodular hyperplasia like: * Dysuria, weak interrupted urine flow **Dx:** * PSA velocity: rate of incr. \> 0.75ng/ml/year suggestive of adenocarcinoma * PSA density (PSA levels: prostate vol. ratio) * DRE: Posterior-lateral (periphery) zone enlargement -\> adenocarcinoma * Transurethral Ultrasound & possible biopsies * Bound to various protease inhibitors like: Alpha 1 anti-chymotrypsin & alpha 2- macroglobulin * Both free & total PSA are measured * PSA \> 10 ng/ml -\> HIGH
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Cryptorchidism
* More common on right side * Unilateral in majority but 25% cases – B/L **Microscopic** * More intestitium and Leydig cell in bw * Thickening of BM * Seminiferous tubules: atrophy and less cells, more eosinophilic * Sparing of Leydig and Sertoli cells * Spermatogonia destruction **Etiopath​** •Failure of Gubernaculum •Hormonal dysfunction •Other congenital abnl ex. Hypospadias •Incr cancer risk even in descended testes **C&C:** * Intra-abdominal germ cell tumour (3 to 5x) * Infertility * Orchidopecsy before 5 yo to prevent cancer risk * Orchidopecsy before 2 yo to prevent infertility
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Epididymo-orchitis- etiology varies with age
* Children: gram negative bacilli * \<35 year – STD – Gonorrhea,C. trachomatis * \>35 year – UTI-E. Coli, Pseudomonas
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Seminoma **Microscopic** * Sheets of Fried egg appearance cells w clear cytoplasm w prominent cytoplasm (similar to dysgerminoma ovaries & medullary carcinoma of breast) * Lymphocytic infiltrates in interstitium **Etiopath:** •Males 30 to 50 yo •Germinal cell tumour •Isochr12p •Risks: Testicular dysgenesis & Klinefelter disease, cryptoorchdism **Sx** * 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 **Investigations:** beta-HCG **C&C:** good prognosis with radiotherapy •Risk of metastasis to para-aortic LN via lymphatic spread
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Non-seminona
* 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 * **Rx:** surgery + chemo * **C&C:** both hematogenous & lymphatic spread
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Inflammation (Balanitis) & Phimosis and paraphimosis
* 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. * Paraphimosis: when a phimotic prepuce is forcibly retracted over the glans penis, causing marked constriction & swelling.
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Penile carcinoma in situ (CIS)
* all associated w HPV 16 & 18 infections Bowen's disease: Old people * Solitary * Shaft * Plaque (scaly) * Associated visceral malignancies; * Progress to invasive Erythroplasia of Queyrat * Solitary or multiple * Glans & perpuce * Red patch, shiny plaque * Progress to invasive SCca (Penile Squamous Cell Carcinoma) Bowenoid papulosis: middle age * multiple * Shaft (glans/foreskin) * Papular * doesn’t progress to invasive SCca Penile Squamous Cell Carcinoma * Protective effect of circumcision * **Etiopath:** * Carcinogens in smegma HPV 16,18 * Cigarette smoking Bowen’s disease ( CIS) * Maximum incidence between the ages of 40-70 years * **C&C:** slow growing locally invasive tumors
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Scrotal lesions
Hematocele: blood in tunica vaginalis, trauma Hydrocele: accumulation of fluid in the tunica Chylocele: accumulation of lymph in tunica Varicocele: dilatation of congested blood vessels in spermatic cord Spermatocele: dilatation of epididymis with semen (sperms) \*\*Therapy: surgical