Block 3 - Renal Flashcards
A congenital condition resulting in the absence or underdevelopment of the kidneys. Also presents with pulmonary hypoplasia, oligohydramnios (due to decreased fetal urine excretion and resulting in compression of the fetus), wrinkly skin, twisted fact, and limb defects.
Potter’s syndrome
The most common renal congenital condition presenting as fusion of the lower poles of both kidneys. It may rarely cause symptoms, unless compression or occlusion of nearby structures occurs.
Horseshoe kidney
A congenital anomaly that is usually unilateral (bilateral disease results in oligohydramnios and Potter sequence). Grossly, the kidneys appear enlarged, irregular, and multi-cystic. Micro: undifferentiated mesenchyme, cartilage, and immature collecting ducts. Not an inherited disease.
Multicystic renal dysplasia
An AR congenital disease that presents in both kidneys, resulting from a mutation in the PKHD1 gene. “Spongiform kidneys” and possible liver involvement, leading to congenital hepatic fibrosis (portal hypertension in a child). Multiple ectatic collecting ducts appear radially oriented from the center of the kidney to the surface. The corticomedullary junction is obliterated by the numerous abnormal ducts.
Autosomal Recessive polycystic kidney disease (ARPKD)
An AD malformation of both kidneys typically presenting in adults. Results from a mutation in the PKD1 or PKD2 genes. May have hepatic or splenic cysts, Berry aneurysms, colonic diverticulosis, and mitral prolapse. Malformation occurs throughout the entire renal tubule, not just the collecting ducts.
Autosomal dominant polycystic kidney disease (ADPKD)
Gene involved in autosomal recessive polycystic kidney disease (ARPKD)
PKHD1
Gene involved in autosomal dominant polycystic kidney disease (ADPKD)
(2)
PKD-1 (Polycystin-1) and PKD-2 (polycystin-2)
Kidney cysts can commonly be acquired from long-term ___ due to other kidney diseases. >5years. May progress to malignancy.
Acquired cystic disease
Single or multiple kidney diseases ranging from 1-10 cm in diameter. Usually present in the subcapsular renal cortex. Commonly an incidental finding at autopsy and they rarely produce symptoms.
simple cysts
Essential (primary) hypertension can cause ___ nephrosclerosis. Grossly shows granular, contracted kidneys. Microscopically shows hyaline atherosclerosis.
Benign
Malignant hypertension can cause ___ nephrosclerosis. Grossly appears as nodular or flea-bitten kidney. Micro: fibrinoid necrosis of the afferent arteriole and hyperplastic arteriolitis (onion-skinning).
accelerated
Secondary hypertension can arise from what renal disease? Increased RAA system results in vasoconstriction and blood volume –> HTN
renal artery stenosis (low BV going into kidney falsely tells body to increase RAA response)
___ infarct appears pale and is caused by a mural thrombus from an MI or A-fib, infected valves in endocarditis, complicated AS plaques in the aorta.
Renal infarcts present with sharp flank or abdominal pain and hematuria.
ischemic
____ infarct appears as red and is caused by renal vein thrombosis (severe dehydration in infants and septic thrombophlebitis in adults).
Renal infarcts present with sharp flank or abdominal pain and hematuria.
Hemorrhagic
Dx? Pale, widespread necrosis of tubular epithelium and calcification. Seen as a complication in obstetric emergencies and DIC.
Diffuse cortical necrosis
Key difference between nephritic and nephrotic syndrome?
Nephritic - hematuria
Nephrotic - proteinuria
Nephrotic disease with primary GN
Most common cause of nephrotic syndrome in children, due to immune dysfunction and excessive cytokine production, which also results in increased infections and Hodgkin lymphoma. Presents acutely with 4+ albumin, fatty casts in urine, and hematuria in 20% of cases. Responds to steroid treatment, but can progress to focal segmental GN (FSGN). Microscopically, see effacement of foot processes due to cytokine production, WITHOUT immune deposits.
Minimal change disease
Nephrotic syndrome with primary GN
Disease frequent in Hispanics and blacks. Can be idiopathic or secondary type. Secondary type arises from viral infection, IV rug use, or sickle cell anemia. Presents with non-selective proteinuria, and 75% have hematuria. Prognosis is poor despite treatment and typically progresses to chronic renal failure. Microscopically shows effacement of foot processes and segmental involvement.
focal segmental glomerulosclerosis
HIV causes a subtype of focal segmental glomerulosclerosis (FSGS) called ____ glomerulopathy. EM shows collapse of glomerular tufts and tubuloreticular bodies in endothelial cells, which are modified ER.
collapsing
Nephrotic syndrome with primary GN
The most common cause of nephrotic syndrome in Caucasian adults. 75% idiopathic/Autoimmune due to Ag against Phospholipase Receptor A2 and IgG4 deposits. Secondary causes are chronic Ag stimulation (Hepatitis, Malaria, Syphilis), malignancy, medication, or systemic disease. Another possible etiology is MAC activation of glomerular cells –> proteases and oxidants –> capillary wall injury –> protein leakage with entrapment of Ab-Ag complexes in the membrane.
Presents as proteinuria >3.5 gm/24hr. 50% have hematuria.
Intermediate prognosis, but many progress to renal failure.
EM shows spikes and domes, subepithelial deposits and foot process efacement.
Membranous glomerulonephritis
Nephrotic syndrome with system disease
High serum glucose leads to non-enzymatic glycosylation of the vascular basement membrane leading to hyaline atheriolosclerosis. Glomerular efferent arterial is more affected than afferent, leading to increased filtration pressure, hyperfiltration, and microalbuminuria. ACE-inhibitors slow progression.
Most common cause of end-stage renal disease in the US.
EM shows GBM thickening and sclerosis, effacement of foot processes, and endothelial cell damage.
Diabetic nephropathy
glomerular nodules seen in diabetic nephropathy
Kimmelstiel-Wilson
Nephrotic syndrome with systemic disease
An uncommon disease that is seen in elderly patients. Associated with hepatomegaly, restrictive cardiomyopathy, multiple myeloma, and long-standing inflammatory diseases like TB, bronchiectasis, and RA. Presents as proteinuria. Very poor prognosis.
Types are AL - light chain - in multiple myeloma and lymphoproliferative diseases
AA- chronic infections
Amyloidosis
Nephrotic syndrome with systemic disease that is typically asymptomatic
SLE
Nephrotic syndrome with primary GN
Two types based on the location of deposits: subendothelial (Hepatitis or HIV) or intramembranous with C3 nephritic factor
Primary type: due to immune complex deposition
Secondary type: systemic conditions and malignancy
Membranoproliferative GN
Nephrotic syndrome with primary GN
Subtype of membranoproliferative GN
Due to the deposition of circulating immune complexes (SLE, etc), excessive complement activation, or inflammatory reaction.
Tx with steroid and immunosuppressives.
Most progress to chronic renal disease despite treatment
Subendothelial deposits - “railroad”
Mesangial proliferation
MPGN type 1, membranoproliferative
Subendothelial, mesangiocapillary
Nephrotic syndrome with primary GN
Subtype of membranoproliferative GN
abnormalities resulting in excessive activation of the alternate complement pathway, favoring persistent C3 activation by C3 convertase. Hypocomplementemia.
Lamina densa and subendothelial GBM are transformed into an irregular electron dense substance
(formerly )Type 2 MPGN
Dense-deposit type
Nephritic or nephrotic?
Glomerular hypercellularity, type of cell varies
Infiltration of inflammatory cells
Mild edema, HTN, azotemia due to BUN and creatinine retention, oliguria due to reduced GFR, hematuria (dysmorphic RBCs and RBC casts), proteinuria <3gm
Nephritic
Nephritic syndrome with primary GN
Follows group A B-hemolytic strep pharyngitis (strains with M protein)
Reduced serum C3 and C4, CRP elevated
Occasionally progresses to rapidly progressive GN, but has an excellent prognosis.
Also can be caused by staph, meningococci, pneumococci, Measles, mumps, or rubella.
Micro: diffuse endothelial and mesangial hypercellularity with neutrophilic (acute) infiltrate. Hump shaped immune complex deposits with extensive foot process effacement and endothelial cell proliferation.
Acute proliferative GN (post-infectious GN)
Nephritic syndrome with primary GN
Most common GN
Can be nephritic, nephrotic, or isolated
Immune complex deposition in the mesangium
Presents in childhood with hematuria, RBC casts, Coke colored urine and diarrhea, and usually follows mucosal infection.
Micro: mesangial expansion with segmental sclerosis. “Holly leaf” depositions.
IgA nephropathy aka Berger disease
Nephritic syndrome with primary GN that is a primary immune disease
Acute onset with hemoptysis and hematuria.
Normal serum complement
anti-GBM Ab in serum or tissue. Non-collagenous domain of the alpha 3 chain of collagen IV in lamina dense of GBM. Basement membrane breaks.
In situ production of immune complexes in kidney and lung with inflammatory reaction.
History of viruses and hydrocarbons
Goodpasture syndrome (a type I RPGN)
Genetic defect resulting in the defective assembly of collagen and the GBM. Absence of a-5 isoform of collagen IV (X-linked); a-3 or a-4 in autosomal inheritance. GM shows irregular thinning and thickening with a “basket-weave” appearance. Rare. Presents with hematuria, mild proteinuria, normal serum complement.
More common and severe in males who develop renal failure in early adulthood. Prognosis is variable in female carriers.
Nerve deafness and ocular disorders may occur.
Alport’s disease
Benign familial hematuria that is otherwise asymptomatic.
Genetic defect resulting in the defective assembly of collagen and the GBM. Absence of a-5 isoform of collagen IV (X-linked); a-3 or a-4 in autosomal inheritance. GBM shows thinning.
Prognosis is good and does not progress to chronic renal failure
Thin basement membrane nephropathy
acute tubular injury caused by what?
Presents with ballooning/hydropic degeneration of epithelium of PCT. Calcium oxalate crystals in tubules and urine.
Ethylene glycos
Acute ___ is typically caused by infection with the patient’s own fecal flora (gram - bacilli), ascending UTI or descending infective endocarditis.
Micro: small abscesses with interstitial inflammation and papillary, tubular necrosis.
Pyonephrosis, perinephric abscess, pyelonephritic scar
pyelonephritis
Chronic ____ is interstitial inflammation with scarring of the renal parenchyma, calyces, and pelvis.
Reflux nephropathy or chronic obstructive type
Marked blunting of calyces with hydronephrosis and hydroureter.
Micro: “thyroidization of the kidney.” Interstitial fibrosis and mononuclear infiltration. Glomeruli usually spared but some may be sclerotic.
Gross: irregular scarring: broad depressed areas of cortical fibrosis overlying a dilated calyx. Bilateral and asymmetrical.
pyelonephritis
acute ___ interstitial nephritis presents with fever, rash, rapidly increasing creatinine, and eosinophilia.
Urinalysis: proteinuria, hematuria, and pyuria with eosinophils
Tubulitis and tubular necrosis
drug-induced (non-specific)
aggressive renal tumor
80% of all renal tumors in adults
Generally asymptomatic. “The great mimic.” The classic triad: hematuria, palpable abdominal mass and dull flank pain. Initial presentation is usually due to metastasis.
Gross: hemorrhage, necrosis, vascular invasion. Invasion of renal veins.
Ectopic hormone production aka paraneoplastic syndrome causes varied presentations: polycythemia (EPO), HTN (renin), hypercalcemia (PTH-like), Cushing syndrome (ACTH), etc.
Many predisposing factors
40% of patients die
Types: clear cell (shown below), papillary, or other
Renal cell carcinoma
type of renal cell carcinoma
clear cell carcinoma
Type of renal cell carcinoma
papillary carcinoma
Aggressive renal tumor that occurs unilaterally in children.
Micro: primitive, dark, small blue round cells
Primitive glomeruli and tubules
Wilms tumor
____ epithelium
urothelial aka transitional
Aggressive tumor
Aggressive behavior increases with tumor size
Large and multiple, become less papillary and more sessile, more atypical, increased mitotic activity, invasive, and metastatic.
Invades muscularis propia, prostate, rectum, vagina, or retropreitoneum
Metastasizes by lymph or blood
Types: squamous cell, mixed, or adenocarcinoma
Urothelial (transitional) cell tumor
Infection that increases the risk of squamous cell urothelial carcinoma
Micro: parasite eggs
Schistosoma hematobium (schistosomiasis) in Japan and Egypt
