Pathology Flashcards
Horseshoe Kidney
Conjoined kidneys connected at lower pole
-#1 congenital abnormality
Gets stuck on root of enteric mesentery artery, it will be located low in abdomen
Renal Agenesis
Absence of formation
Unilateral: hypertrophy of existing kidney
-Problems exist later in life (renal failure)
Bilateral: Oligohydraminios
-lung hypoplasia, flat face, low set ears, developmental defects of extremities (Potter Sequence)
-Incompatible with life
Dysplastic Kidney
NON-inherited, congenital malformation of renal parenchyma.
- Cysts and abnormal tissue (CARTILAGE)
- Usually Unilateral, when bilateral MUST BE distinguished from inherited PKD (polycystic kidney disease)
- If a second child is born after a child who develops dysplastic kidney the chances of 2nd child developing is is LOW
PKD (polycystic kidney disease)
Inherited defect, BILATERALLY enlarged kidneys with cysts in RENAL CORTEX and MEDULLA Autosomal Recessive -Usually infants -Renal failure and HTN -Potters sequence -Associated with congenital hepatic bebrosis and hepatic cysts -PORTAL HYPERTENSION in a baby Autosomal dominant -Young adults (ADult) -HTN, hematuria, worening renal failure -Increased plasma renin -APKD1 or APKD2 gene -Associated with BERRY ANEURYSM (brain hemorrhage), hepatic cysts, mitral valve prolapse
Medullary Cystic Kidney Disease
Inherited Autosomal dominant defect
- Cysts in MEDULLARY collecting ducts
- Parenchymal fibrosis results in SHRUNKEN kidneys
- Presents as worsening renal failure
Acute Renal Failure
Severe decrease in renal function
-AZOTEMIA, often oliguria
Prerenal, postrenal, intrarenal
Azotemia
High levels of nitrogen products in blood (urea, creatinine)
Oliguria
Low output of urine
Prerenal Azotemia
Due to decreased blood flow to kidneys (common cause of ARF)
-Low GFR, Azotemia, Oliguria
-BUN and creatinine in blood rise
BUN:Creatinine > 20 (Creatinine cannot be resorbed, urea can and will be resorbed back into blood)
-Tubular function is intact so FENa is 500 so kidney can still concentrate urine
Postrenal Azotemia
Obstruction of the urinary tract downstream of kidney
- Increased pressure and DECREASED GFR
- Azotemia and Oliguria
- Increased pressure forces BUN back into blood so BUN:Cr > 20
- Tubular function intact so FENa < 1% and Urine osmolality is > 500
Post Renal Azotemia - LONG term
Tubule damage causes decreased resorption of BUN
- Thus BUN:Cr < 20
- Decreased resorption of Na (FENa > 2%)
- Inability to concentrate urine (Uosm < 500)
Acute Tubular Necrosis
Intrarenal Azotemia
-Injury and necrosis of tubular epithelial cells, MOST COMMON cause of ARF
-Necrotic cells plug tubules, obstruction: DECREASED GFR
-Brown, granular CASTS seen in urine (sloughed off epithelial cells, casted in shape of tubule)
-Decreased ability to resorb BUN so BUN:Cr < 20
-Decresed resorption of Na and inability to concentrate urine
FENa > 2%, Uosm < 500
FENa
Fractional excretion rate of sodium
-Normal about 1%
High FENa - more Na EXCRETED
Low FENa - more Na RESORBED
Ischemic ATN
Decreased blood supply results in necrosis of tubules, often PRECEDED by PRErenal azotemia
-Proximal tubule and medullary segment of TAL susceptible
Nephrotoxic ATN
Toxic agent results in necrosis of epithelial cells
-Proximal tubule
Agents: Aminoglycosides, heavy metals (lead), myoglobinuria (crush injuries), Ethylene glycol (antifreeze) OXYLATE CRYSTALS in urine, Radiocontrast dye, Urate (Tumor lysis syndrome, chemotherapy)
-Oliguria with brown granuler casts
-Elevated BUN and Cr
-Hyperkalemia with metabolic acidosis (decreased excretion of K and also WOA)
-Increased ANION GAP
-Reversible, oliguria can persist for 2-3 weeks before recovery
Acute Interstitial Nephritis
Drug-induced hypersensitivity reaction of interstitial and tubules, results in ARF
- Common drugs: NSAIDS, Diuretics, and Penicillin
- Oliguria with fever and RASH that arises days to weeks after starting drugs
- EOSINOPHILIA
- Resolve after cessation of drug
- May progress to Renal papillary necrosis
Renal Papillary Necrosis
Necrosis of renal papillae -Gross hematuria and flank pain Causes: -Chronic analgesia abuse (Phenacetin or aspirin use) -Diabetes Mellitus -Sickle Cell trait or disease -Sever acute pyelonephritis
Nephrotic Syndrome
Glomerular disorder with proteinuria (>3.5g/day)
- Hypoalbuminemia (edema)
- Hypogammaglobulinemia (inc risk of infection)
- Hypercoagulable state (lose ATIII (anti-thrombin III))
- Hyperlipidemia and hypercholesterolemia (reaction of liver to thicken blood from loss of protein)
MCD (minimal change disease)
Most common cause of nephrotic syndrome in children
- Usually idiopathic, but can be associated with Hodgkin lymphoma (Loose foot processes in glomerulus, cytokine mediated, in Hodgkin lymphoma you get massive production of cytokines from Reed-Sternberg cells)
- Normal glomeruli on H&E stain, but on EM will have Effacement of foot processes*
- NO immune complex deposits, negative immunofluorescence
- Selective proteinuria (ONLY albumin)
- Excellence response to CorticoSTEROIDS***
Focal Segmental Glomerular Syndrome
Most common cause of nephrotic syndrome in Hispanics and Blacks
- Usually idiopathic, maybe HIV, Heroin, Sickle Cell**
- If there’s a patient on any of these and develop nephrotic syndrome it is FSGS
- Focal and segmental (pink) sclerosis on H&E
- Effacement of foot processes on EM
- Negative IF (immunofluorescence) NOT immune complex mediated
- DO NOT respond to steroids (may progress from MCD) progresses to CRF
Membranous Nephropathy
Most common cause of nephrotic syndrome in Caucasian adults
- Idiopathic but may be associated with Hep B or C, solid tumors or SLE**, drugs (NSAIDs, penicillin’s)
- A patient with SLE that develops nephrotic syndrome, it is membranous*
- On H&E thick basement membranes
- IS DUE to Immune Complex so it will be a Positive Immunofluorescence test (granular, grainy appearance)
- Spike and Dome appearance on EM
Membranoproliferative Glomerulonephritis. Type I or Type II
Thick capillary membranes on H&E, often with ‘tram-track’ appearance (due to proliferation of mesangial cells)
- Due to immune complex deposition so it is IF positive
- Types based on location of deposits
Membranoproliferative Glomerulonephritis. Type I
Deposits underneath the ENDOTHELIAL cells
- SUBendothelial
- Associated with HBV or HCV
- More often ‘tram track’ presentation
Membranoproliferative Glomerulonephritis. Type II
Deposition of immune complexes WITHIN the BASEMENT membrane
- Antibody called C3 nephritic factor (auto-antibody) that stabilizes the C3 convertase (converts C3 to C3a and C3b, it is usually destroyed rapidly)
- The stabilization of C3 convertase results in over activation of compliment resting in inflammation and damage to the basement membrane
Diabetes Mellitus
Hyperglycemia results in non enzymatic glycosylation of vascular basement membranes resulting in hyalin arteriolosclerosis (leaks protein into tunica media)
- Efferent arteriole is more effected than the afferent, thus increases pressure within the glomerulus
- This creates hyperfiltration initially resulting in miecroalbuminuria that eventually results in nephrotic syndrome
- Kimmelstiel-Wilson Nodules* (dense sclerosis)
- ACE Inhibitors help this
Systemic Amyloidosis
Kidney is MOST commonly involved organ
- Amyloid deposits in mesangium resulting in nephrotic syndrome
- Characterized by apple-green birefringence under polarized light
Nephritic Syndrome
Glomerular inflammation and BLEEDING (hematuria)
- Limited proteinuria
- Oliguria and azotemia
- Salt retention with periorbital edema and HTN
- RBC casts and dysmorphic RBC’s in urine
- Biopsly: Hypercellular inflamed glomeruli, immune complex deposition activates compliment (C5a)
Post Strep Glomerular Nephritis
Nephritic syndrom post group A beta-hemolitic strep infection (M PROTEIN)
- 2-3 weeks after infection (usually seen in children - hematuria (cola colored), oliguria, HTN, periorbital edema)
- Hallmark - granular IF, SUB-EPITHELIEAL HUMP on EM**
- TX is supportive
- Adults can progress to RPGN
RPGN - Rapidly progressive glomerular nephritis
Nephritic syndrome that progresses to renal failure in weeks to months
- Biopsy - CRESCENTS in bowman space made up of FIBRIN* AND MACROPHAGES*
- IF: linear = basement membrane attachment (Goodpasture syndrome), granular = PSGN, negative = pauci-immune = test for ANCA (Wegeners c-ANCA)
Goodpasture Syndrome
Antibody against glomerular and alveolar basement* membranes - hematuria and hemoptysis
-Young adult males
Wegeners
c-ANCA
- Lung, kidney, and ENT involvement
- Hemoptysis, hematuria, and nasopharyngeal symptoms (sinusitis) - must differentiate from Goodpasture
Churg-Straus
p-ANCA
-Eosinophilia, granulomatous inflammation, ASTHMA
IgA Nephropathy
Most common cause world wide
- IgA deposits in MESANGIUM of glomeruli
- Gross or microscopic hematuria, RBC casts, following mucosal infections
- May progress to RF
Alport Syndrome
Inherited defect of type IV collagen, X-linked
- Thinning and splitting of glomerular basement membrane
- Isolated Hematuria**
- Hearing loss and ocular disturbances, FAMILY history
UTI
Usually ascending
-Risk- sexual intercourse, urinary stasis, gender, catheters
Cystitis
Pyonephritis
Cystitis
Bladder infection
-Urinary pain (dysuria), urgensy/frequency, suprapubic pain
-NO systemic signs (fever, night sweats, etc)
Urinalysis - cloudy urin with < 10 abc/hpf
Dipstick- positive leukocyte esterase and nitrites
Goldstandard: CULTURE (over 100,000 CFU)
-E coli #1
-Staphylococcus Saprophyticus (young sexually active women)
-Klebsiella pneumoniae
-Proteus Mirabilis (alkaline urine)
-Enterococcus faecalis
Sterile Pyuria
Pyuria with NEGATIVE culture
-suggests URETHRITIS due to Chlamydia Trachomatis or Neisseria gonorrhoeae
Pyelonephritis
Kidney infection
- Usually caused by ascending infection, increaseased risk with vesicoureteral reflux
-Liver failure, flank pain, WBC casts, Leukocytosis, in addition of sx of cystitis
E Coli #1
Klebsiella
Enterococcus
Chronic Pyelonephritis
Interstitial fibrosis and atrophy of tubules
- CHILDREN, due to vesicoureteral reflux (VUR) or obstruction (adults)
Leads to cortical scarring and blunted calyces, scarring at upper and lower poles indicate VUR
-Thyroidization of kidney
Nephrolithiasis
Precipitation of urinary solute as a STONE
- Risk: high concentration of solute or low urine volume
- COLICKY pain with hematuria and UNILATERAL flank tenderness
Calcium Oxylate or Phosphate stone
Most common type of stone*
-Check for hypercalcemia (think about Crohn disease) also form idiopathic hypercalciuria**
TX: Hydrochlorothiazide
Ammonium magnesium Phosphate stone
Second most common type - due to alkalization of urine (stag horn calliculi)
Usually from UTI Proteus or Klebsiella
Uric Acid Stone
Radiolucent (cannot see on X-ray)
Risk: Hot arid climates, low urine volume, acidic pH
GOUT patients*, hyperuricemia, leukemia, myeloproliferative disorders
Tx: hydration and alkalization of urine (potassium bicarbonate) or ALLOPURINOL
Cystine Stone
Rare but most common in CHILDREN
-Staghorn calliculi
TX: hydration or alkalization of urine
End-stage Kidney Failure
Results from glomerular, tubular, inflammatory or vascular insults
Most common cause: DM, HTN, Glomerular disease
Tx of ESRF
Dialysis or renal transplant or renal transplant (cysts develop within SHRUNKEN kidneys)
-Increased risk for renal cell carcinoma*
Symptoms of ESRF
UREMIA - increased nitrogenous waste in blood, nausea, anorexia, pericarditis, encephalopathy, urea crystals in skin
- Salt and water retention (HTN), hyperkalemia, metabolic acidosis (anion gap)
- Anemia (EPO from renal peritubular interstitial cells)
- Hypocalcemia (decreased 1 alpha hydroxylation of vitamin D in kidney or due to hyperphosphatemia)
- Renal osteodystrophy (damage to bone due to renal failure) osteitis fibrous cystic, osteomalacia, osteoporosis)
Angiomyolipoma
Hamartoma comprised of blood vessels, smooth muscle, and adipose tissue
-Pts with TUBEROUS SCLEROSIS
Renal Cell Carcinoma
Malignant epithelial tumor of the renal tubules
- TRIAD - hematuria, palpable mass, and flank pain
- Feber, weight loss, paraneoplastic syndrome** (could release EPO, renin, PRHrP, or ACTH)
- May present with left sided varicocele (rare)
- Yellow Mass* - clear cytoplasm (clear cell carcinoma)
- involves LOSS of VHL which is a tumor suppressor gene
Paraneopastic Syndrome
wer
Sporatic pathway of Renal Cell Carcinoma
Hereditary pathway
Adult smoker** in upper pole of kidney
Multiple and bilateral tumors
Von Hippel-Lindau Disease
Autosomal dominant disorder associated with loss of VHL gene
- Predisposes patients for RCC***
- also increased risk for hemangioblastoma of cerebellum and renal cell carcinoma
Staging of RCC
T - based on tumor size and involvement of renal vein
N - based on spread to retroperitoneal lymph nodes
Wilms Tumor
Most common renal tumor in CHILDREN**
- Comprised of blastema**, primitive glomeruli, and tubules, and stromal cells
- Present with large unilateral flank mass, HTN, and hematuria
- WT1 mutation
WAGR Syndrome
Wilms Tumor
Aniridia
Genetal abnormalities
Mental and motor Retardation
Beckwith-Widemann Syndrome
Wilms Tumor
Neonatal hypoglycemia
Muscular Hemihypertrophy
Organomegaly (tongue)
Urothelial Carcinoma
Risk. Papillary vs Flat pathway.
Malignant tumor arising from urothelial lining of renal pelvis, ureter, bladder, or urethra
-MOST COMMON type flower urinary tract cancer (bladder)
-Smoking*
-Napthylamine (in cigarette smoke)
-Azo dyes (hair dressers)
-Long term cyclophosphamide or phenacetin
Usually seen with PAINLESS HEMATURIA in elderly
Papillary pathway** (tumor starts low grade, progresses to high grade and invades)
Flat (starts as high grade and invades) associated with early p-53 mutations**
Field defect - MULTIFOCAL tumors that reoccur
Renal Squamous Cell Carcinoma
Malignant proliferation of squamous cells; usually in the bladder**
-Arises in a background of squamous metaplasia
Risk: Chronic cystitis, Schistosoma Hematobium** (middle eastern male), Long-standing nephrolithiasis
Renal Adenocarcinoma
Malignant proliferation of glands usually in the bladder*
-Arises from URACHAL REMNANT** (then tumor would be present at dome of bladder), cystitis glandularis, bladder exstrophy
