Renal Answers

Developmental defects:

Oligohydramnios maybe a symptom of which congenital renal defect? What abnormalities would the child be born with?

·         Bilateral agenesis

·         Kidneys make amniotic fluid: the decreased amount of fluid  à increased pressure exerted on the fetus by the uterus

·         Depressed/flattened facies (Potters), low set ears, deformed lower extremities, pulmonary hypoplasia

If a child has unilateral renal agenesis will he be symptomatic (if so, what symptoms will be present) and what will the other kidney look like?

·         Typically asymptomatic – only one kidney is needed for renal function

·         Adaptive hypertrophy of remaining kidney

·         Women may have mullerian duct abnormalities à infertility

·         Adults may have HTN

How can a true hypoplastic kidney be differentiated from an acquired atrophic kidney at autopsy?

·         Very few will be true hypoplastic – most due to acquired scarring

·         True hypoplastic kidney will have no scars and a reduced number of renal lobes/pyramids (>6)

Why might a patient with horseshoe or ectopic kidneys be prone to UTIs?

·         Horseshoe: ureters have to cross over the central connecting area of the horseshoe àin some causes leading to an increased risk for obstruction and thus bacterial infection

·         Ectopic kidney: the abnormal position may lead to tortuosity of ureters à obstruction of flow and thus risk for bacterial infection

Cystic Diseases of the kidney:

Match the following:

A.       Cystic renal dysplasia

B.       ADPCKD

C.        ARPCKD

D.       Medullary sponge kidney

E.        Nephronophthisis

F.        Acquired cystic disease

G.       Simple cyst

         I.            Most common genetic cause of end stage renal disease in kids/young adults – E

        II.             Caused by abnormal gene on chromosome 16 –B

      III.            Caused by a mutation in PKHD1 gene (which encodes fibrocystin)- C

      IV.            Cysts in the medulla are typically concentrated at the corticomedullary junction - E

       V.            Failure in kidney development despite normally formed precursors- A

      VI.            Likely caused by obstruction to drainage -A

    VII.            Cysts contain clear fluid and often calcium oxalate crystals –F

   VIII.            Cysts are translucent and lined by single layer of cuboidal epithelium – these are a common postmortem finding -G

      IX.            Multiple cystic dilations of the collecting ducts in the medulla-D

       X.            Silent until adulthood when they classily present as: hematuria, HTN, abdominal mass - B

      XI.            Affected children present first with polyuria/polydypsia with terminal renal failure following in 5-10 years - E

    XII.            One of the variants of this disorder is associated with ocular lesions – E

   XIII.            Cortical and medullary cysts seen in patients following prolonged dialysis -F

  XIV.            This disease affects the kidneys/liver in inverse proportions – C

    XV.            bilateral and symmetric enlargement but otherwise looks normal externally- but upon cutting the specimen there are multiple radially arranged cysts involving only the collecting ducts – C

  XVI.            initially involves distal tubules with BM disruption which is followed by chronic and progressive tubular atrophy (medulla + cortex) à interstitial fibrosis à renal insufficiency - E

 XVII.            Kidneys are massively enlarged with multiple variably sized cysts which may affect any area of the nephron - B

XVIII.            Histologically shows: arrested development with simple ducts and often cartilage –A

  XIX.            Juvenile form is associated with NPH1,2,3 - E

    XX.            20% of patients with this disease develop cerebral artery aneurysms – B

Urolithiasis:

Most common (75-85%) form of stone is made of _________________

·         Calcium with the most common being calcium oxalate (1/3 of stones)

Which type(s) of stones are radiolucent? ________________uric acid

How are stones composed of magnesium ammonium phosphate are formed?

·         Post-infection with ura-splitting bacteria (proteus) which alkalizes the urine causing precipitation of magnesium ammonium phosphate

·         Largest stones = staghorn

This type of stones may be seen in a patient with gout or tumor lysis syndrome________________ uric acid

A patient with squamous cell carcinoma of the lung may be at risk for which type of stone?___________

·         Calcium containing stone due to paraneoplastic syndrome which secretes PTHr

Diseases of tubules/interstitium:

What is the most common cause of acute renal failure? ____________________ ATN

What are the two major causes of ATN? ___________+____________

·         Ischemic: decreased renal perfusion (many associated with hypovolemia and shock) – typically follow prolonged period of pre-renal azotemia

·         Toxic

Define Oliguria

·         Production of <400 mL of urine/day

What would you expect the pertinent labs to say in a patient suffering from ATN (UA/urine chemistry)?

·         When the tubular cells are no longer functioning properly

o    Decreased reabsorption of Na = >2% FENa

o    BUN is normally reabsorbed in the PT while Cr is not reabsorbed and just lost in urine (BUN:Cr~15)

§  Conditions that decrease GFR = increased reabsoption and thus BUN:Cr >15

§  Example: pre/post-renal azotemia (there maybe tubular damage in late stages of both of these conditions **remember that pre-renal azotemia is a common cause of ischemic ATN)

§  When there is tubular damage BUN will also be lost in the urine resulting in a BUN:Cr <15***

o    Tubular casts**

T/F: widespread necrosis of the tubules is present in ATN

·         F: necrosis of individual tubular cells with irregular spacing of epithelial cells and dropout of tubule cells = characteristic ATN

Toxic or Ischemic?

·         Which type of ATN is more common? – I

·         The straight segment of PCT in primarily affected (+thick ascending limb of loop of henle) and appears dilated with flattening of individual epithelial cells and loss of brush border (distilazation) –I

·         Typically affects entire proximal portion of nephron with patchy involvement of ascending limb (loop of henle) +/- distal tubule – T (toxins such as mercuric chloride are more severe and will also involve the distal tubule)

How is ATN treated? Is it permanent?

·         Remove causative event (ex: remove aminoglycoside Rx)

·         Supportive +/- peritoneal dialysis/hemodialysis

·         Renal failure typically lasts 1-2 weeks (likelihood of recovery diminishes >4-6wks)

What causes acute vs chronic pyelonephritis? What would you look for in the urine to support your diagnosis?

·         Acute: ascending bacterial infection

o    Bacteria introcusded to bladder will multiply in the presence of stasis (due to dysfunction of bladder/obstruction)

·         Chronic: repeated UTI/obstruction/vesico-ureteral reflux à scarring

·         WBC casts

What bacteria is the most common cause of UTIs?

·         E. coli (gram negative bacilli from intestinal tract – 85%)

Match the following:

A.       Acute pyelonephritis

B.       Chronic pyelonephritis

C.        Papillary necrosis

D.       Pyonephrosis

E.        Perinephric abscess

         I.            Irregularly scarred kidneys corticomedullary scar overlying dilated/deformed calyx – B

        II.            Patchy interstitial suppurative inflammation which begins as limited to the interstitim à destroys tubulesà extends along nephrons/Collecting tubules: A

      III.            Following complete obstruction a suppurative exudates fills the pelvicalyceal system - D

      IV.            A complication of acute pyelonphritis that is commonly seen in diabetic and urinary tract obstruction – C (usually bilatyeral, coagulative infarct with leykocytic response at junction of viable tissue)

       V.            Presents as pain at costovertebral angle, bladder symptoms, and evidence of infection - A

      VI.            Forms due to suppurative inflammation extending through the renal capsule à perinephric tissue – E

What are the two forms of chronic pyelonephritis?

·         Chronic obstructive

·         Chronic reflux

Tubulointerstitial nephritis can be induced by drugs/toxins: name 2+ ways injury is induced:

         I.             Interstitial immunologic rxn

        II.             Acute renal failure

      III.             Subtle cumulative injury to tubules (ex: chronic analgesic use)

Which drugs maybe associated with drug-induced interstitial nephritis?

·         Sulfonamides

·         Synthetic antibiotics

·         Penicillin

·         NSAID

Symptoms present 2 weeks post drug exposure and are associated with eosinophilia, rash, hematuria/proteinuria/leucocyturia

·         50% will have a rising Cr or acute renal failure

·         Interstitial edema, PMN, eosinophils, mononuclear infiltrate +/- granulomas/tubular necrosis

·         Rx: withdraw drug!

Neoplasms of Urinary Tract:

What is the number of layers of urothelium found in a “normal” bladder?

·         5-7: according to degree of distention

·         If urothelium is made of >7 layers = abnormal

All of the following are true except:

A.       Von brunns nests contain a large central lumen with colloid material

B.       Cystitis glandularis is considered a normal variant of urothelium

C.        Von brunns nest are an example of reactive proliferation of urothelium

D.       Cystitis glandularis contain a columnar, mucus secreting cell lining

A: Von Brunns nest are compact groups of urothelial cells in the LP of the bladder. When they contain a central lumen with colloid accumulation it is called “Cystitis cystic” and when the lumen is enlarged further and there are columnar/mucus secreting cells lining the space- then it is cystitis glandularis. These are all normal variants of urothelium which have undergone reactive proliferation due to noxious stimuli.

An Egyptian woman presents with squamous cell carcinoma of the bladder. What infectious agent are you suspicious she was exposed to?

·         Schistosoma hematobium

What is the most common bladder sarcoma in adults vs kids?

·         Adults: leiomyosarcoma

·         Rhabdomyosarcoma: kids

Bladder cancer may occur due to direct extension from ___________+__________+_________

·         Rectum

·         Cervix

·         Prostate

Fill in the chart:

	description	Hyperplasia	Pleomorphism	chromatin	mitoses
Grade1
Grade2
Grade3

	description	Hyperplasia	Pleomorphism	chromatin	mitoses
Grade1	Well differentiated +/- atypia	Cell layers maybe slightly increased	None	Fine/regular	Uncommon
Grade2	Still recognizable as originating from urothelial but more disorganized	Variable increased in cell layers	Greater loss of polarity Greater variability in size/shape	Fine/regular	Common
Grade3	Difficult to recognize as transitional epithelial	Prominent increase	Extreme!	Coarse	prominent

·         NOTE: all transitional cell carcinomas have a tendency to recur post excision (may recur at higher stage)

·         High correlation between grade/stage = infiltrating tumors tend to be grade 3

Match the following: answers maybe reused/multiple

A.       Renal papillary adenoma

B.       Renal oncocytoma

C.        Angiomyolipoma

D.       Renal fibroma

                                 I.            Epithelial neoplasm in which cells have abundant eosinophilic cytoplasm and small round nuclei. They have a high concentration of mitochondria – B

                                II.            Typically are very small and present within the renal medulla and have no malignant potential. Neoplasm shows fibroblast proliferation. – D

                              III.            Benign – A,B,C,D

                              IV.            Irregular and admixed proliferation of blood vessels, smooth muscle, fat – C

                               V.            Small (<1cm) – if larger than this generally considered RCC – A

                              VI.            Grossly: homogenous and brown with a central scar –B

                            VII.            Do not misdiagnose a granular RCC or chromophobe RCC as this! –B

                           VIII.            Composed of branching papillary fronds with fibrovascular cores – A

                              IX.            25% patients with tuberous sclerosis have this neoplasm – C

All of the following are true about RCC except:

A.       85% of all renal cancers are RCC

B.       There is a male predominance

C.        Tumors typically occur 40-50’s

D.       Unopposed estrogen therapy is a risk factor

E.        Most cases are sporadic

C: most occur between 60-70

The three classic diagnostic deatures of RCC are: ___________+_____________+_________

·         Costovertebral pain

·         Palpable mass

·         Hematuria

·         Fq asymptomatic until large!

·         May also see signs of paraneoplastic syndromes such as:

o    Polycythemia

o    Hypercalcemia

o    HTN

o    Hepatic dysfunction

o    Feminization/msaculinization

o    Cushings

o    Amyloid

Match the type of RCC with the description:

A.       Clear cell

B.       Papillary

C.        Chromophobe

D.       Collecting duct

         I.            Maybe associated with sickle cell trait – if so it is termed “medullary carcinoma” and is rapidly fatal - D

        II.            80% of all RCC- A

      III.            composed of pale eosinophilic cells with distinct cell borders and perinuclear clearing - C

      IV.            May see psammoma bodies when these tan tumors are examined histologically - B

       V.            These bright yellow tumors have a high propensity for venous invasion – A

RCC  is associated with  a loss of part of ______ chromosome in 98% of tumors. What syndrome is associated with this loss (resulting in a high co-incidence).

·         Chromosome 3 – VHL gene (TSG)

·         Von hippel landau syndrome

All of the following concerning urothelial carcinoma of the renal pelvis are true except:

A.       These tumors become symptomatic late in their course

B.       Patients may have gross hematuria and renal colic

C.        Up to 50% of patients have a pre-existing/concomitant bladder cancer

D.       Poorer prognosis than bladder carcinoma

A: these tumors sit right in the collecting system so they are more likely to present with hematuria when they fragment à prompting earlier discovery. These tumors typically infiltrate the pelvic/calcyceal walls so therefore have a poorer prognosis than bladder cancer

What is the most common renal neoplasm of childhood? Wilms = nephroblastoma

This tumor has been linked to abnormalities with a TSG located on chromosome ___ 11

This tumor is (histologically) composed of three main components

1.         

2.         

3.         

                                                               i.       Blastema

                                                              ii.       Epithelial (primitive tubules/glomerular structures/rosettes-rare)

                                                            iii.       stromal

Glomerular renal disease:

Although albumin is small enough to fit through the fenestrated epithelium of the glomeruli capillaries it is not found in high concentration in the urine of a patient with a functioning kidney. Why is this?

·         The job of the glomerulus: keep proteins in and allow water/solute to pass out

·         The glomerulus is composed of:

o     capillaries (fenestrated epithelium)

o     basement membrane (major barrier to protein passage because it contains strong negative charge which repels the proteins)

o     podocytes (exact function is not known – appear to trap proteins and have pinocytotic functions)

o    mesangial cells SMC which support capillary loops – these are highly responsive to hormones + have the ability to regulate glomerular blood flow via contraction /expansion

Match the following – there maybe multiple :

A.       nephrotic syndrome

B.       nephritic syndrome

C.        low grade proteinuria

         I.            Associated with red cell casts – B

        II.            minimal basement membrane damage that results in a urine protein excretion of <150 mg and normal serum protein concentration because the liver is able to compensate: C

      III.            mild-moderate diffuse glomerular inflammation that is associated with a drop in GFR-B

      IV.            moderate to severe basement membrane injury resulting in protein loss that exceeds the livers ability to compensate à drop in serum albumin à drop in oncotic pressure and thus edema: A

       V.            Associated with hypercholesterolemia A

What causes crescent formation in RPGN?

·         This is the most severe form of glomerular inflammation

·         Capillary loops are disruptedà cytokines/chemokines leak into bowmans space à activation/proliferation of parietal epithelial cells with associated inflammatory cells à crescent formation à if untreated - sclerosis

·         The excess cellularity may compress the glomeruslus

What will happen to C3 + C4 in the following scenarios:

·         Activation of classic complement pathway: decrease C3+ C4

·         Activation of the alternative pathway: decrease C3 only (ex: membranoproliferative GN)

What does the term “membranous” refer to?

·         Involvement of the capillary basement membrane leading to an increase in loop thickness

What causes a “granular” appearance on IF?

·         Antigen-antibody complexes àgranular

·         Antibodies that bind directly to antigen (ex: goodpastures: anti-GBM) à linear

What is EM used for when evaluating glomerular diseases?

·         Localize immune complex location

·         Provides extreme detail of BM structure

In adults, MCD may occur secondary to _______ or _________

·         NSAIDs

·         Hodgkin lymphoma

Match the following:

A.       Minimal change disease

B.       Membranous nephropathy

C.        Diabetic glomerular damage

D.       Amylodosis

E.        FSGN

F.        Membranoproliferative GN

         I.            Corticosteroid response generally good: A

        II.            Capillary loops are pushed to the edge of tufts creating kimmelsteil-wilson – C

      III.            Subepithelial deposits seen on EM create “spike and dome” pattern: B

      IV.            Subendothelial deposits are seen with this condition- F (T1)

       V.            C3 convertase leads to overactivation of complement à low C3 circulating – F(T2)

      VI.            Associated with HIV - E

    VII.            Widespread podocyte effacement with normal LM – A

   VIII.            Most common cause of nephritic syndrome in kids: A

      IX.            Associated with sickle cell – E

       X.            Congo red with apple green birefringence - D

      XI.            Thick glomerular basement membrane appears as “tram tracks” because divided by mesangium - F

    XII.            Earliest evidence is microscopic albuminuria: C

   XIII.            IF: thickened mesangium, no immune complexes, thickened capillary loops: C

  XIV.             Most common cause of nephrotic syndrome in Caucasian adults: B

    XV.            Maybe seen in patients with multiple myeloma: D

  XVI.            Associated with HBV : B

 XVII.            Most common nephrotic syndrome in African Americans - E

XVIII.            Granular deposits of IgG and C3 seen in even line along GBM on IF: B

  XIX.            Circulating serum proteins are deposited in the tissues as B-pleated sheets: D

Postinfectious glomerulonephritis: Which of the following are not true?

·         Typically follows a skin or less commonly a throat infection with group B strep

o    F: group A

·         Infection seen >1-2 weeks after infection as coca-cola colored urine, periorbital edema, HTN, oliguria

·         LM: increase PMN in the glomerulus and tubulointerstitial compartment (F: TI spared!)

·         Biopsies are only preformed for persistent proteiuria

·         May progress to RPGN

·         Better Px in kids

IgA in Berger disease deposits in which part of the glomerulus? Mesangium - #1 nephropathy worldwide!

What disease presents as hematuria, sensory hearing loss and ocular disturbances? Alports (IV collagen defect – X linked)