Lec 1

What role does the mesangium have?

What role does the juxtaglomerular apparatus have?

How does the JGA control this?

1. holds together the glomerular capillaries

2. place where immune complexes get deposited usually

1. controlls blood pressure, body homeostasis, renal blood flow, glomerular filtration

--blood pressure is controlled by renin containing cells in the afferent arteriole

Lec1

What special structure does the proximal tubule have to increase salt and water reabsorption?

What are the roles of the PT?

1. microvilli

2. absorb Na, regulate acid-base balance

Lec 1

What is the main role of the thin limb of henle?

What is the main role of the thick limb of henle?

What is the main role of the distal convoluted tubule?

1. countercurrent exchange with medulla to excrete concentrated urine

2. hypertonic extrusion of salt-- create a medullary concentration gradient (dilutes urine)

3. regulate acid-base balance

Lec1

What are collecting ducts used for?

Principal cells- respond to ADH to allow water inside

Intercalated cells- regulate acid-base via chloride-bicarbonate exchangers and proton ATPases

Lec 2

What can you diagnose with a urinalysis?

What does a positive nitrite show?

glomerulonephritis

UTI

Diabetic ketoacidosis

E. coli infection

First ask-- What do the RBCs look like?

Normal biconcave --> bleed in urinary tract

Spherical blebs--> injured capillary in kidney (=glomerular disease)

Upper UT disease: think KIDNEY

glomerular injury (glomerulonephritis), kidney injury, kidney malignancy, pyelonephritis

Lower UT disease: think BLADDER

bladder malingancy or infection, stone

Or it could just be a contaminant

Lec2

When do the following casts form?

 Hyaline

RBC

WBC

Tubular epithelial

Fatty

Granular

Broad-waxy

Hyaline- after excercise, dehydrated

RBC- nephrItic syndrome

WBC- acute pyelonephritis

Tublar epithelial- tubular necrosis

Fatty- nephrOtic syndrome

Granular- renal disease- nonspecific

Broad-waxy- chromic renal failure

Lec2

What 4 symptoms point to nephrotic syndrome?

What path/phys causes nephrotic syndrome?

Name 9 causes of nephrotic syndrome?

hyperlipidemia, hypoalbuminemia, edema, proteinuria

increased permeability of the glomerular capillary

Abbs: MCD, FSGS, MGN, MPGN

Systemic: Diabetes, Amyloidoses, Lupus

Other: NSAIDs, Infection (HIV + Hep B, C)

Lec2

Minimal change disease

More common in___

Presents with ___

Is the toxicity reversible?

What does the EM look like?

children

edema, SELECTIVE proteinuria

Yes

Diffuse effacement of visceral epithelial cell foot proceses

Lec2

Focal Segmental Glomerulosclerosis (FSGS)

More common in__

Presenting symptoms

Is it reversible?

EM

Immunofluorescence

Hispanics and African Americns

NONselective proteinuria, hematuria, hypertension

No

detachment of foot processes from BM (in addition to diffuse effacement of foot processes)

IgM, C3 in course clumps in sclerotic segments

Lec2

Membranous Nephropathy (MGN)

Presents with____

Immunofluorescence

Causes of secondary MGN

NONselective proteinuria, hematuria, mild hypertension

IgG, C3 granular in capillary loop pattern on GBM

Mesangial staining is negative in idiopathic MGN but positive in secondary MGN

Lupus, tumors, drugs, infection, metabolic disorders

Lec 3

What 6 symptoms point to nephrItic syndrome?

What is the hallmark of an inflamed glomerulus?

Name 8 types of nephritic syndromes:

hematuria, azotemia, oliguria, hypertension, edema, proteinuria

Hypercellular glomerulus

Primary- acute postinfectious glomerulonephritis, IgA nephropathy, RPGN

Systemic- Cryoglobulinemic glomerulonephritis, Henoch-schonlein purpura, RPGN (Goodpasture and wegener), lupus

Mixed- membranoproliferative glomerulonephritis I and II

Lec 3

Acute Poststreptococcal Glomerulonephritis

More common in___

IF studies:

Children

IgG and C3 lumpy-bumpy

Lec3

Membranoproliferative Glomerulonephritis MPGN

More common in___

Difference between type I and II

IF studies

Light microscopy

Older children

Type I- alternative + classic complement activated (C3 + C1q)= "broken curvilinear"

Type II- ONLY alternative activated (C3)= "rings"

shows cauliflowers due to endocapillary proliferation and influx of inflammatory cells

silver stain shows duplicate GBM= tram-track

Lec3

Cryoglobulinemic Glomerulonephritis (CGN)

Type 1 vs Type 2 vs Type 3

Clinical features

EM

Type 1- monoclonal IgGk- multiple myeloma

Type 2- polyclonal IgG, mono IgMk

Type 3- polyclonal IgG, poly IfM

Both 2 and 3 caused by hepC, lupus, RA

skin purpura, arthralgias, low serum complement

Thumbprint appearance- due to microtubular structure of deposits

Lec3

Name 2 immune complex glomerulopathies associated with recurrent hematuria:

Hint-- they both usually follow an upper respiratory tract infection

IgA nephropathy (Berger's disease)

Henoch-Schonlein Purpura (HSP)

Lec3

IgA Nephropathy (Berger's Disease)

More common in___

What 2 diseases is secondary IgA nephropathy associated with?

IF studies

older children

celiac disease, chronic liver disease

IgA, C3 granular deposits

Lec3

Henoch-Schonlein Purpura (HSP)

More common in___

Name 5 Symtpoms

children

Purpuric skin rash, abdominal pain, melena, vomiting, arthralgias

Alport's syndrome

Thin basement membrane disease (TBMD) (Benign Familial Hematuria)

Lec3

Alport's syndrome

inheritence

4 symptoms

Which gene is mutated?

EM

x-linked

hematuria, proteinuria, nerve deafness, eye disorders

a5 chain of collagen type IV

GBM shows splitting and a "basket woven" appearance

Lec3

Thin Basement Membrane Disease (TBMD)

Inheritence

Mutated gene

EM

Autosomal dominant

a3 or a4 of collagen type IV

GBM thinning

Lec4

Rapidly Progressive Glomerulonephritis (RPGN)

Main feature

Name types I, II, and III RPGNs

Crescents in most glomeruli

I = Anti-GBM antibody- idiopathic, goodpasture

II = immune complex- idiopathic, postinfectious glomerulonephritis, lupus, Diffuse IgA nephropathy/Henoch Schonlein, membranoprolif. glom.

III= pauci-immune- idiopathic, microscopic polyangitis, Wegener's

Lec4

Type I RPGN

What's the main difference between goodpasture & idiopathic?

Goodpasture is most common in ____ and also causes ___ symptoms.

IF studies

Idiopathic is only in kidney, goodpasture is in lungs also

young men: hemoptysis, pulmonary hemorrhage

strong linear staining of IgG and C3

EM- NO immune complex deposits present

Lec4

Type II RPGN- immune complex mediated glomerulonephritis-- usually idiopathic

What's special about glomerulus (compared to type 1 & 3)

IF studies

it's hypercellular

granular staining - IgA & C3 for IgA nephropathy, full-house staining for lupus

Lec4

Type III RPGN- Pauci immune- idiopathic, microscopic polyangitis, wegener granulomatosis

What type of autoantibodies is made?

What other symptoms does microscopic polyangitis cause?

What does the skin biopsy show?

P-ANCA- myeloperoxidase-- microscopic polyangitis

C-ANCA- PR3-- Wegener's

skin purpura, hemoptysis, arthralgias, abdominal pain

necrotizing vasculitis

Lec4

What is the triad for Wegener Granulomatosis?

Most common in___

What other symptoms do they get?

necrotizing granulomas in lung, vasculature, glomerulus

50 year old males

pneumonitis and sinusitis

Lec5

Diabetic Glomerulosclerosis= Diabetic nephropathy (DN)

What are happens during the 5 stages of DN?

Which finding is diagnostic of DN?

1. GFR increases, kidney/glomerulus enlarges

2. GBM thickens

3. Microalbuminuria, selective proteinuria, hypertension, normal renal function

4. IRREVERSIBLE- kimmelstiel-wilson nodules (PAS+), dipstick +, nonselective proteinuria, nephrotic syndrome, decreased GFR, increased creatinine, retinopathy, CAD

5. End-stage renal disease

Hyalinization of afferent and efferent arterioles

Lec5

Amyloidoses

Diagnostic lab test?

Congo red+

Lec5

AL

Precursor Protein?

Clinical Features?

mainly λ

1. primary amyloidoses- MGUS- NO bone lesions

2. myeloma assoc.- multiple myeloma- bone lesions etc

Lec5

AA

Precursor Protein?

Clinical Features?

SAA

(acute phase protein), precursor for fibrils

Secondary Amyloidosis-hepatosplenomegaly, renal insufficiency

due to inflammatory condition (Crohn's, RA), heroin

Lec5

ATTR

Precursor Protein?

Clinical Features?

Abnormal TTR--> Familial ATTR amyloidosis- midlife onset of peripheral neuropathy, cardiomyopathy, vitreous opacities

Normal TTR--> Senile Systemic Amyloidosis- heart & kidney

Lec5

Aβ2m

Precursor protein?

Clinical features?

Diagnostic study?

β2microglobulin

Hemodialysis- associated- β sheets deposited in tendons, joints, synovium

EM shows fibrils forming feathery spikes like "fringe on a rug"

Lec5

Monoclonal Immunoglobulin Light Chain Deposition Disease- LCDD

   - nephrotic syndrome which is Congo Red -

   - also in pt's w/ MGUS or MM

Where do the monoclonal light chains get deposited?

IF studies

EM

kidney, heart, liver

nodules are very PAS+

κ light chain in smooth linear pattern

nonfibrillar powdery punctuate deposits in mesangium (resembles a pencil line)

Lec6

Which 2 antibodies are diagnostic for SLE?

What type of study/lab/procedure is essential for classifying and treating lupus?

IF studies for SLE

What is the clinical course for SLE?

Which classes of lupus get treated?

dsDNA, Smith (Sm)

renal biopsy

"Full House" staining= IgG, A, M, C3, C1q

I > II > V > III > IV

3, 4, 5

Lec7

What's the difference between primary and secondary HTN?

What's the difference between benign and malignant HTN?

Secondary HTN has a known cause but primary doesn't

Benign is slow, malignant progresses rapidly

Lec7

What causes benign HTN?

What does the kidney look like in someone w/ benign HTN?

What are the 3 main histological changes that occur during benign HTN?

a renal lesion called benign nephrosclerosis

finely granular on outside

1. intimal thickening of arteries

2. hyalinization of arterioles

3. renal parenchyma ischemia

lec7

Which 4 events occur during intimal thickening due to benign HTN?

What symptoms are associated with benign HTN?

1. medial hypertrophy

2. myointimal cellular proliferation

3. reduplication of the internal elastic membrane

4. fibrosis

trick question! it's asymptomatic

Pic of benign HTN

notice granular surface

Lec7

Name 3 complications of benign HTN:

Name 3 groups that are at greatest risk of developing renal failure:

1. CHD= Coronary heart disease

2. Cerebrovascular accidents

3. Left ventricular hypertrophy

1. African Americans

2. super high blood pressure

3. diabetes

Lec7

What does the kidney look like in someone with malignant HTN?

Why?

What type of microscopic changes to arteries, arterioles, and glomeruli does malignant HTN cause in the kidney?

Flea-bitten pinpoint hemorrhages

Due to glomerular necrosis and rupture

narrow arteries due to layering of collagen and accumulation of proteoglycans= 'onion skinning'

arterioles + glomeruli show fibrinoid necrosis and thrombosis.

glomeruli also show neutrophilic infiltrate

Lec7

Name 4 clinical features of malignant HTN:

REDS

Retinopathy

Encephalopathy

Diastolic >130

Stroke

Lec7

What do HUS and TTP have in common?

What can cause thrombotic microangipathy?

both cause:

Microangiopathic hemolytic anemia

Thrombocytopenia

Acute renal failure

Identical renal lesions (same as malignant HTN)

Shiga-like toxin in E. coli, complement mutations, lupus anticoagulant, pregnancy complications, malignant HTN, TTP

Lec7

Is secondary HTN due to renal artery stenosis curable?

What are the 2 main causes of RAS?

Yes, if you have surgery

More common:

1. MEN- atheromatous plaque stenoses RA ostium- more likely in old diabetics

2. FEMALE- fribromuscular dysplasia- fibromuscular thickening, medial fibroplasia is most common- 30-40yo

Lec7

What causes the Goldblatt kidney?

What type of features does the Goldblatt kidney show?

secondary HTN due to renal artery stenosis

decreased: blood flow, BP, GFR

stimulates: renin-ang system

renal ischemia

Lec7

Which factors in renal artery stenosis cause vasoconstriction and hypertension?

What does a Goldblatt kidney look like?

What microscopic changes occur to a Goldblatt kidney?

What does the non-ischemic kidney look like?

Sodium retention

producing endothelin- a vasoconstrictor

losing NO- a vasodilator

smooth, small (due to ischemic atrophy)

Hyperplasia of the glomerular JGA

Increased renin granules

Interstitial fibrosis

granular or flea-bitten- depending on type of HTN

Lec7

Name 4 causes of vasculitis

1. Immune complex- lupus and croglobulinemia

2. Microscopic polyangitis- ANCA

3. Polyarteritis nodosa

Lec7

Where does polyarteritis nodosa NOT go?

What virus often causes polyarteritis nodosa?

During the acute phase of polyarteritis nodosa, what does the weakened arterial wall lead to?

Who usually gets PN?

pulmonary

hepB

Aneurysmal dilatation, thrombosis, rupture

Young adults

Lec7

Name 5 causes of diffuse cortical necrosis:

1. pregnancy

2. septic shock

3. pancreatitis

4. NSAIDS

5. wrong blood transfused

Extra-- ONLY Cortex in infarcted. Medulla, juxtamedullary cortex, and cortex under capsue is spared.

Scarring and calcification necessitates dialysis

Lec7

1. Where do most renal infarcts come from?

2. What's the difference between recent infarcts and healed infarcts?

3. Name 2 symptoms of renal infarction:

1. Mural thrombi- Left atrium (atrial fibrillation) or Right ventricle (myocardial infarction)

Septic infarcts- Infective endocarditis

2. recent ones show ischemic coagulation necrosis while healed infarcts show interstitial fibrosis and tubular atrophy

CVA tenderness and hematuria

Lec10

What are 3 signs that a tubule is defective?

1. can't concentrate urine (polyuria)

2. salt wasting

3. can't excrete acids- metabolic acidosis

Lec10

What are some clinical signs of Acute Kidney Injury (AKI)?

Is AKI reversible?

oliguria, rapid onset azotemia, dilute urine, hyaline or granular pigmented casts

Yes

Lec10

Name 3 types of ATN (acute tubular necrosis) and what can cause them:

1. Pre-renal ischemia= decr. blood to kidney due to hypotension, shock, malignant HTN

2. Direct toxic injury= nephrotoxicity due to drugs and dyes

3. Post-renal disease= obstruction, stones

Lec10

What 2 things cause ischemic and nephrotoxic ATN?

Name 3 things that lead to oliguria during acute tubular necrosis:

1. tubular cell injury- loss of polarity leads to activation of caspases which results in apoptotic cells (IRREVERSIBLE)

2. altered blood flow- due to renin from tubuloglomerular feedback, endothelic release and decreased vasodilators

incr. tubulogomerular feedback, incr. intratubular pressure, decr. tubular flow leading to decr. GFR

Lec10

What are the early features of ischemic ATN?

Name 3 toxins that can cause nephrotoxic ATN?

cell swelling, blebbing, and loss of brush border

Gentamycin, ethylene glycol, radiocontrast dye

Lec10

What happens during the 3 stages of nephrotoxic ATN?

1. initiation- decr. urine output, incr. BUN & Cr

2. maintenance- oliguria, salt/water overload, more BUN & Cr increase, metabolic acidosis

3. recovery- incr urine output, BUN & Cr normalize

Lec10

How does acute pyelonephritis present?

sudden CVA tenderness

pyuria and positive urine culture

leukocyte casts

big kidneys, abscesses

Lec10

What are the hallmarks of pyelonephritis due to reflux?

pelvic inflammation

patchy interstitial neutrophilic inflammation

neutrophils in collecting ducts

abscess formation

Lec10

Chronic pyelonephritis is an important cause of ______

What are the 2 types of chronic pyelonephritis?

end-stage kidney disease

1. chronic reflux nephropathy- in kids w/ a UTI and reflux

hallmark- polar scarring

2. chronic obstructive pyelonephritis- due to stones or anatomic anomalies

hallmark- scars all over

Extra-- hydronephrosis occurs in both types

Lec10

What type of casts occur in chronic pyelonephritis?

What does scarring from chronic pyelonephritis lead to?

hyaline casts (thyroidization)

focal segmental glomerulosclerosis

Lec10

When do people get polyoma virus?

What do the infected cells look like?

How do you diagnose it?

the virus gets reactivated in renal transplant patients by immunosuppression

enlarged nuclei with viral inclusions

immunostain shows parallel crystalline arrays of viral particles

Lec10

WHen do people get ATIN (Acute Drug-Induced Interstitial Nephritis)?

What is the ATIN triad of symptoms?

15 days after drug exposure

fever, eosinophilia, rash

Extra-- see eosinophils in urine, rising creatinine, acute renal failure with oliguria, increased IgE, + skin test for drug haptens, both kidneys swollen, inflammatory cell infiltrate

REVERSIBLE

Lec10

What cause analgesic nephropathy? Be specific

How does analgesic nephropathy present?

acetaminophen and aspirin

chronic tubulointerstitial nephritis, papillary necrosis, urinary infection, stones

Lec8

What is Potter syndrome?

decreased amniotic fluid results in lack of kidneys and pulmonary hypoplasia

oligohydramnios

bilateral agenesis

facies

results in stillbirth

Lec8

Name the different types of renal cysts:

1. Dysplasia

2. APKD

3. ARPKD- recessive

4. Dialysis-associated

5. Medullary sponge kidney

Lec8

Name 5 characteristics of cystic renal dysplasia (CRD):

sporadic

unilateral

irregular structure

cystic

cartilage islands

Lec8

Pic of cysts

Lec8

Cystic Diseases:

 Compare CRD, ADPKD, ARPKD

Lec8

What is the clinical presentation of medullary sponge kidney?

What is the clinical presentation of nephronophtisis?

What is the clinical presentation of dialysis assoc. cystic disease?

hematuria, UTI, stones

benign/asymptomatic, normal renal function,

smooth contours on cyst

in older adults

kid w/ polydypsia & polyuria

NPH1 gene makes nephrocystins

small kidneys w/ multiple cysts

asymptomatic, uremic, develop renal cell carcinoma

tubules obstructed by fibrosis or oxalate crystals

Lec8

What is the main pediatric renal tumor?

Name 1 other benign pediatric tumor and 2 malignant tumors.

Wilms' tumor (WT)

Mesoblastic nephroma- benign

Clear cell sarcoma & rhabdoid tumor- malignant

Lec8

Name 3 benign adult renal tumors and decribe them

Papillary adenoma- most common, so small that it can't metastasize

Angiomylolipoma- seen in pt's w/ tuberous sclerosis benign but has complications- hemorrhage, CNS (seizures), giant yellow tumor w/out capsule. 3 elements: fat, large vessels & muscle bundles. pt's can have angiofibromas, cysts in liver, kidney, cardiac rhabdomyomas

Oncocytoma- pink oncocytes due to lots of mitochondria- come from intercalated cells of collecting ducts

Lec8

Name the 4 types of adult renal cancers

1. renal cell carcinoma-"clear"=classic- most common

2. papillary carcinoma-

3. chromophobe carcinoma-

4. collecting duct carcinoma-

Lec8

Renal cell carcinoma

Type of pt___

What is the classical clinical triad?

What is the classic type of renal cell carcinoma?

What are the variants of renal cell carcinoma?

60+yo male

hematuria, CVA pain, flank mass

Clear cell carcinoma

papillary RCC, chromophobe carcinoma (prominent pink membrane), ductal renal carcinoma (channels lined by irregular cells, fibrosis, osteoblastic bone metastases)

Lec8

What is Von Hippel Lindau syndrome?

tumor suppressor VHL gene is inactivated- inherited

results in up-regulation of hypoxia-induced factor

metastases to 3 places ("Let's Buy Land")

Lungs, brain, liver

can lead to multifocal clear renal cell carcinoma

Lec8

Papillary renal carcinoma-

what kind of histo changes occur?

what causes it?

psammoma bodies (calcifications)

foam cells

trisomy 7

Lec8

Wilm's tumor

What do you know about it?

derived from nephrogenic blastema cells

presents as large abdominal mass (unilateral)

responds to treatment

triphasic combo- epithelium + stroma + blastema

nephrogenic rests -- precursors to Wilm's tumor

sometimes found in kids with WAGR genitourinary synd. (WT1), Beckwith wiedmann synd (WT2 mutation,NO anaplasia)

IGF2 overexpressed)

Lec8

things emphasized in cyst lecture

·         MCD

o   Puffy baby (legs and eyes!)

o   Normal LM

o   EM = effacement

o   Selective proteinuria

·         FSGS

o   IgM + C3 entrapment (NOT complex)

o   EM = effacement + detachment

o   Secondary = HIV (collapsed) or heroin?

MGN

o   IgG +C3 (immune complex)

o   Phospholipase A2R

o   Secondary = HBV

o   GBM thickening!

o   Spikes

·         Acute Post-Strep GN

o   Hypercellular (oat meal raisin cookie, extra raisins!)

o   IgG + C3 = Lumpy – bumpy – humpy

·         MPGN

o   Hypocomplimentemia!

o   Cauliflower! (glomerulus)

o   Tram – track (GBM)

o   Type I = IgG + C3 + C1q

§  Immune complex deposits

o   Type II = C3 only

§  Dense ribbon-like material (in btw tram track)

·         Cryoglobulinemic GN

o   3 types

o   Type II/III = SLE, RA, Hep C

o   Purpura + arthralgias!

o   EM = Thumbprint!

IgA Nephropathy – MOST COMMON!

o   Recurrent hematuria (often post infxn, like flu)

o   Deposits OR Complexes (IgA obvs)

o   IgA + C3 in mesangium

Henoch – Schonlein Purpura

o   Childhood!

o   LE pupura, abdominal pain, melena, vomiting, arthralgia

o   IgA!

Alport’s

o   X-linked = A5 chain of collagen IV!!!

o   AR = A3 & 4

o   5-20 y/o

o   Nerve deafness + eye probs!

o   IF = negative

o   EM = basket woven!

Thin BM Disease

o   AD = A3 & 4

o   Asymptomatic microscopic hematuria

o   IF = negative

o   EM = thin GBM!

·         RAPID! = crescents!

o   Type I

§  Anti-GBM @ A3

§  Goodpasture’s

§  Linear staining IgG + C3

§  Hemoptysis!

§  Young adult male

o   Type II

§  Immune complex-mediated!

§  Post-infectious GN, SLE (IV), IgA GN, HSP, MPGN

·         So…hypercellular!

·         IF specific to disease

o   Type III = Pauci! (negative IF)

§  Microscopic Polyangiitis

·         P-ANCA (myeloperoxidase)

·         Purpura, hemoptysis, arthralgia, abdominal pain

§  Wegener

·         C-ANCA (PR3)

·         Triad: lung/sinus, necrotizing/granulomatous vasculitis, crescenteric GN

·         Diabetic Nephropathy

o   5 stages

o   Stage I = increased GFR (Stage IV = decreased)

o   Stage II = GBM thickening

o   Stage III = Mesangial thickening; selective proteinuria

§  Capsular drop (diagnostic for II/III)

o   Stage IV

§  KW nodules

§  Hyaline caps = IgM + C3 entrapment

§  Non-selective proteinuria

§  HTN

§  10-20 yrs after DM diagnosis

o   Stage V (ESRD)

§  Globally sclerotic glomeruli, severe interstitial fibrosis, tubular atrophy

o   Hyalinization of Afferent AND Efferent arterioles

Amyloidosis

o   Insoluble non-branching fibrils!

o   Congo Red POSITIVE!

o   Fringe on a rug!

o   AL (primary)

o   AA (secondary)

§  Acute phase proteins

§  Chronic inflam conditions

o   ATTR

§  Transthyretin (TTR)

§  Familial = peripheral neuropathy

§  Senile = heart & kidney

o   AB2M

§  Hemodialysis >20 yrs!

Monoclonal Ig Light Chain Deposition Disease (LCDD)

o   Kidney, heart, liver

o   Congo red NEGATIVE!

o   Kappa rather than Lambda (AL)

§  Smooth LINEAR deposition

o   EM = pencil line

·         SLE

o   Wire loops = subendothelial deposits

§  Bright red!

§  Begin in Class III

§  Prominent in Class IV

o   Class IV à tubulointerstitial nephritis OR vascular probs.

§  Vascular probs = non-inflam (complexes), inflam, or thrombotic microangiopathy (onion skinning!)

o   Class V = membranous = spikes

·         Primary Benign HTN

o   Old, black, DM

o   Grain leather surface

o   Arterionephrosclerosis

§  Internal elastic membrane squiggly trichrome/elastic stain

o   V-shaped scars

·         Primary Malignant

o   Flea-bitten

o   Onion skinning

o   Fibrinoid necrosis = acute damage

o   Black males

o   Retinopathy, encephalopathy, stroke

o   Fucking absurd BP

·         Thrombotic Microangiopathy - HUS/TTP

o   Renal lesions identical to malignant HTN

·         Secondary HTN (due to Renal Artery Stenosis)

o   Goldblatt kidney = problem child!

§  Decreased blood flow

§  Decreased BP

§  Decreased GFR

§  Stim’d ARS

§  Smooth & tiny

§  Not affected by HTN

o   Other kidney

§  Leather grain or flea bitten (benign or malignant)

§  Vessels manifest FULL EFFECT of HTN

·         Vasculitis – Polyarteritis Nodosa

o   Small & medium sized muscular arteries!

o   Hep B!

o   Acute = inflam cells + aneurysmal dilatation + lots of rupturing

o   Chronic = fibrous/nodular thickening of vessel wall

o   Young adults!

·         Diffuse Cortical Necrosis

o   Pregnancy

o   Shock, etc.

o   Pancreatitis

o   NSAIDS, contrast, poisons, snake bites

o   Arteriolar + glomerular thrombosis and necrosis

o   Cortical scarring + calcification = dialysis!

Agenesis

o   Characteristic facies, limb defects, hypoplastic lungs

·         Cystic Renal Dysplasia

o   Histo = cartilage and immature collecting ducts

o   Assoc. w/ UPJ obs.

o   Flank mass?

·         ADPKD (adult)

o   Crunch grapes!

o   Bilateral, enlarged

o   Liver cysts! (also spleen, pancreas, lung)

o   Berry aneurysms

o   Mitral valve prolapse

·         ARPKD (childhood)

o   Sponge!

o   Dead babies

o   Bilateral, enlarged

o   Hepatic fibrosis!

·         Dialysis associated cystic disease

o   Can lead to RCC (papillary)

·         Wilms’ Tumor (WT)

o   2-5 y/o

o   Solitary tan tumor

o   Triphasic: blastema (small blues), stroma, epithelium

o   Large abdominal mass

o   WAGR

§  Wilms’, Aniridia, GU abnorms, Retardation

o   Beckwith-Wiedemann Syndrome (BWS)

§  Large organs, macroglossia, renal cysts, adrenal cytomegaly

o   Nephrogenic rests (NR)

§  Precursors!

Angiomyolipoma

o   Huge, hemorrhagic

o   Assoc. w/ tuberous sclerosis (retarded/seizing)

Oncocytoma

o   Large pink epithelial cells (from intercalated cells of CD)

o   Packed with mitochondria!

Brown tumor

Renal Cell Carcinoma (RCC)

o   Hematuria, CVA pain, flank mass

o   Unilateral solitary yellow tumor (w/ hemorrhage or necrosis)

o   LUNG BONE LIVER

o   Clear Cell

§  VHL (3p)

o   Papillary

§  Foam cells

§  Trisomy 7 and 17

§  Assoc. w/ dialysis

o   Chromophobe

§  Hot pink plant cell w/ perinuclear halo

§  From intercalated cells (like oncocytoma)

o   Collecting duct = AGGRESSIVE. BONE. DIE.

·         UPJ

o   Hydronephrosis in babies/kids

·         Vesicoureteral reflux

o   Most common cause of pyelonephritis

·         Hemorrhagic cystitis

o   Cyclophosphamide

o   Adenovirus

·         Interstitial (Hunner ulcer)

o   No bacterial infxn.

o   Inflam only

·         Malacoplakia

o   Raised yellow plaques!

o   Foam cells!

o   Michaelis Gutmann bodies (bulls-eye)

o   Neg. urine culture + not responding to tx + woman (immunosuppressed transplant pt)

·         Urothelial (Transitional Cell) Neoplasm

o   Tobacco, dyes, arylamines, schisto (Egypt), long term analgesic, cyclophosphamide, radiation

o   Painless hematuria

o   Flat = CIS if no invasion

§  Tx. w/ BCG if invasion

o   Papillary

§  High grade: severe atypia, anaplasia, frequent mitoses, lack of polarity!!!

§  LUNG BONE LIVER

o   Squamous Cell

§  Egypt

§  Schistosomiasis

§  Invasive

§  Abundant keratin

o   Adenocarcinoma

§  Urachal remnants

§  Intestinal metaplasia

·         Acute Tubular Necrosis (ATN)

o   Oliguria

o   Dilute urine, mild proteinuria, microhematuria, hyaline, granular or pigmented casts

o   Pre-renal, renal, post-renal

o   RAS, endothelin (vasoconstrictor), decreased NO, PGI2

o   Pre-renal (ischemic)

§  Patchy tubular necrosis

§  Normal glomeruli and vessels

§  Blebbing!

§  Loss of brush border!

§  Dilated tubules!!!

·         w/ necrotic epithelial cells

§  Regeneration

o   Renal (nephrotoxic)

§  Extensive, uniform tubular necrosis

§  3 stages

·         Osmotic diuresis in recovery stage

·         Acute Pyelonephritis

o   CVA pain, fever, chills, dysuria, frequency, pyuria, WBC casts

o   LM = inflammation of renal pelvis

·         Chronic Pyelonephritis

o   Reflux

§  Child, UTI, congenital VUR

§  Upper and lower poles only

o   Obstructive

§  Poles and midzones

o   Hydronephrosis in both

o   Hyaline casts à thyroidization

o   Globally sclerotic glomeruli + thickened vessels (from HTN)

o   Polyuria; nocturia

·         Polyoma Virus (PV) Nephropathy

o   Immunosuppressed pt!

o   Inflam, epi cell necrosis, tubulitis, enlarged nuclei w/ viral inclusions

o   Immunostains red!

·         Acute Drug-Induced Interstitial Nephritis (ATIN)

o   Triad: fever, eosinophilia, rash

o   IgE + T-cell mediated

o   HUGE SWOLLEN KIDNEYS!

Analgesic Nephropathy

o   Papillary necrosis

o   Tubular atrophy

o   No inflam cells

o   Chronic tubulointerstitial nephritis

·         Granulomatous prostatitis

From BCG used to tx bladder cancer

·         BPH

o   Old dudes

o   5-alpha-reductase à DHT

o   Transitional zone (periurethral)

o   Increased PSA!!!

o   Nocturia, dysuria, start/stop probs.

·         Prostate cancer!

o   Familial

o   Black dudes

o   Peripheral part of posterior zone

o   Adenocarcinomas w/ good gland formation; LACK BASAL CELLS!

o   Perineural invasion

o   Gleason!

o   BONE!

o   PIN = precursor lesion; HAS BASAL CELLS!

o   PSA > 4ng/ml might be bad maybe?

o   Free PSA >25% lowers risk of cancer

Seminoma

§  + PLAP, c-KIT, OCT4

§  Sometimes + BHCG

§  Pale, soft, fleshy

§  30s-40s

§  Big clear cells w/ big nuclei

§  Fibrous septa!

Spermatocytic Seminoma

§  Old dude

§  Small, Medium, Giant cells

§  Does NOT metastasize

Embyronal Carcinoma

§  20s-30s

§  Hemorrhage, necrosis

§  Blue sheets (undifferentiated cells)

o   Yolk Sac (endodermal sinus)

§  Babies! = pure

§  Adults = mixed (w/ embryonal)

§  Lacelike network of flat/cuboidal cells

§  Schiller Duval bodies = Saturn

§  AFP!!!

Choriocarcinoma

§  Cytotrophoblast + Syncitiotrophoblast

§  BHCG!!!

§  Most aggressive! (Syncitio’s invade!!!)

§  Hemorrhage, necrosis

§  LUNG BRAIN

§  Aphrodite = orchiectomy

§  Athena = metastasis

o   Teratoma

§  >1 germ layer

§  Mature elements = muscle, cartilage, squamous and glandular epithelium, brain (brain balls!)

o   Leydig

§  Big balls and big boobs

§  Brown tumor

§  Pink granular cells

§  Reinke crystalloids

Sertoli

§  Firm white nodules

o   Condyloma accuminatum

·         Penis Tumors?

§  HPV 6, 11

§  Koilocytes

CIS

Penis Tumors

§  HPV 16

oPenis Tumors  Carcinoma

§  HPV 16, 18

§  Tobacco hurts!

§  Circumcision helps!

§  40s-70s

§  Squamous carcinomas

·         Papillary or flat

·   

o   Verrucous

Penis Tumors

§  Giant

§  HPV 6, 11

§  Verrucous eats the penis!