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293 Cards in this Set

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What are the functions of angiotensin II?
1) Vasoconstricts peripheral resistance arterioles and efferent arterioles
2) Stimulates the synthesis and release of aldosterone
Where does Renal-derived prostaglandin (PGE2) work? Where is EPO made?
1) Vasodilates the afferent arterioles
2) renal cortex by interstitial cells in peritubular capillary bed
What is the function of Vit D on bone?
Vitamin D promotes bone mineralization by stimulating the release of alkaline phosphatase from osteoblasts. Alkaline phosphatase hydrolyzes pyrophosphate and other inhibitors of calcium-phosphate crystallization.
What is most common upper urinary tract cause of hematuria?
renal stone
How does the kidney function in vit D synthesis? What part of kidney is involved?
1) 1-α-Hydroxylase is synthesized in the proximal renal tubule cells.
2) Converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol.
What is most common cause of lower urinary tract hematuria?
infection
How does glomerularnephritis characterized on UA?
Characterized by dysmorphic RBCs (irregular membrane)
What is the most common noninfectious cause of lower urinary tract hematuria?
TCC
What are drugs leading to hematuria?
1) Anticoagulants (warfarin, heparin)
2) Cyclophosphamide
a. Hemorrhagic cystitis
b. Risk factor for transitional cell carcinoma
How is proteinuria defined? What does persistent protein in urine suggest?
1) Protein > 150 mg/24 hours or >30 mg/dL (dipstick)
2) intrinsic renal disease
Qualitative tests include dipsticks and sulfosalicylic acid (SSA). What do they check for?
1) Dipsticks are specific for albumin.
2) SSA detects albumin and globulins
What is normal BUN range? Where does it come from?
1) 7-18mg/dL
2) End-product of amino acid and pyrimidine metabolism
3) Produced by the liver urea cycle
where does the kidney absorb most BUN? How is it effected by GFR?
(1) Partly reabsorbed in the proximal tubule
(2) Amount reabsorbed is flow dependent.
(a) Decreased glomerular filtration rate, more reabsorbed
(b) Increased glomerular filtration rate, less reabsorbed
What is the most common cause of increased serum BUN?
CHF
What is the normal range of creatinine? What is an increase in creatinine and BUN called? How does GFR affect creatinine?
1) 0.6 to 1.2 mg/dL.
2) azotemia
3) lower GFR = less excreted
What is the normal BUN:creatinine ratio? What is the ratio in prerenal azotemia? In renal azotemia what is ratio? In post renal?
1) 15
2) > 15
3) ≤15
4) > 15
What are causes of pre-renal azotemia?
(1) Caused by a decrease in cardiac output
(a) Hypoperfusion of the kidneys decreases GFR.
(b) There is no intrinsic renal parenchymal disease.
(2) Examples-blood loss, congestive heart failure
Based on how the kidneys work, how does prerenal azotemia result? What is the relation of BUN and creatinine?
(a) Decreased GFR causes creatinine and urea to back up in blood.
**Ratio remains unchanged, because of proportionate increase.
(b) After filtration, proportionately more urea is reabsorbed back into the blood due to the decreased flow rate
**All of the creatinine is excreted in the urine.
(c) Addition of proportionately more urea to blood increases the ratio to >15.
(d) Example-serum BUN 80 mg/dL, serum creatinine 4 mg/dL
BUN:Cr ratio is 20
How does renal azotemia (uremia) result?
(1) Caused by parenchymal damage to the kidneys
(2) Examples-acute tubular necrosis, chronic renal failure
(3) Serum BUN:Cr ratio ≤15
How are BUN and creatinine affected in the kidney to result in renal azotemia?
(a) Decreased GFR causes creatinine and urea to back up in blood; increased extrarenal loss of urea
**Ratio is already <15 due to extrarenal loss of urea
(b) After filtration, both urea and creatinine are lost in the urine.
**Proximal tubule cells are sloughed off in renal failure.
(c) Serum BUN:Cr ratio remains ≤15.
(d) Example-serum BUN 80 mg/dL, serum creatinine 8 mg/dL
**BUN:Cr ratio is 10.
Pathologically what is occurring with post renal azotemia? What can it lead to?
(a) Obstruction to urine flow decreases the GFR.
(b) Backup of urea and creatinine in the blood
**Proportionate increase at this point; ratio unchanged
(c) Increased tubular pressure causes back-diffusion of urea (not creatinine) into blood.
**Postrenal azotemia: obstruction behind kidneys; initially ratio > 15; ≤15 if obstruction persists
**Disproportionate increase in urea increases ratio to >15.
(4) Persistent obstruction damages tubular epithelium causing renal azotemia (ratio ≤ 15).
By how much does the GFR decrease with age?
Annual decrease in CCr of 1 mL/minute after age 50 years
How is the creatinine clearance tested?
Measured CCr = UCr (mg/dL) × V (mL/min) ÷ PCr (mg/dL)
(1) V = volume of a 24-hour urine collection in mL/minute, and UCr and PCr are the creatinine concentration of urine and plasma, respectively.
(2) CCr results are dependent on a correct 24-hour urine collection
What is the CCr in a normal adult? When is kidney failure said to have occurred?
97 to 137 mL/minute
(1) In general, CCr < 100 mL/minute is abnormal.
(2) CCr < 10 mL/minute indicates renal failure.
How is functional proteinuria defined? Is there renal disease?
1) Protein < 2 g/24 hr
2) no
3) caused by Fever, exercise, congestive heart failure
How is overflow proteinuria characterized?
1) Protein loss is variable
2) LMW proteinuria
3) Amount filtered > tubular reabsorption
What are causes of overflow proteinuria?
1) Multiple myeloma with BJ proteinuria
2) Hemoglobinuria: e.g., intravascular hemolysis
3) Myoglobinuria: crush injuries, McArdle's glycogenosis (deficient muscle phosphorylase); increase in serum creatine kinase
What are 2 types of glomerular proteinurea?
1) Nephritic syndrome: protein > 150 mg/24 hr, but <3.5 g/24 hr
2) Nephrotic syndrome: protein > 3.5 g/24 hr
What are causes of nephritic syndrome?
Damage of GBM: nonselective proteinuria with loss of albumin and globulins; example is post-streptococcal glomerulonephritis
What causes nephrotic syndrome?
Loss of negative charge on GBM: selective proteinuria with loss of albumin and not globulins; example is minimal change disease (lipoid nephrosis)
What is tubular proteinurea?
1) Protein < 2 g/24 hr
2) Defect in proximal tubule reabsorption of LMW proteins (e.g., amino acids at normal filtered loads
What are causes of tubular proteinurea?
1) Heavy metal poisoning: e.g., lead and mercury poisoning
2) Fanconi syndrome: inability to reabsorb glucose, amino acids, uric acid, phosphate, and bicarbonate
3) Hartnup disease: defect in reabsorption of neutral amino acids (e.g., tryptophan) in the gastrointestinal tract and kidneys
How does CHF effect GFR, BUN reabsorption and serum BUN?
↓ Cardiac output → ↓ GFR → ↑ proximal tubule reabsorption of urea → ↑ serum BUN
What causes Acute glomerulonephritis? How are BUN and GFR effected?
1) Poststreptococcal glomerulonephritis
2) ↓ GFR → ↑ serum BUN
What are causes of increased serum BUN?
1) Decreased cardiac output
2) Increased protein intake
3) Increased tissue catabolism
4) Acute glomerulonephritis
5) Acute or chronic renal failure
6) Postrenal disease
How is GFR and serum BUN affected during pregnancy? With SIADH?
1) decreased serum BUN
2) ↑ Plasma volume → ↑ GFR → ↓ serum BUN
What conditions lead to decreased BUN from nonfunctional urea cycle?
Cirrhosis, Reye syndrome, fulminant liver failure
What conditions cause a low BUN based on diet?
Kwashiorkor (↑ carbohydrate is protein sparer), starvation gluconeogenesis in kidneys
How is CCr effected during pregnancy? When is it most changed?
1) Normal increase in plasma volume causes an increase in the GFR leading to an increase in CCr;
2) highest at the end of the first trimester
How is CCr effected in early diabetic glomerular nephropathy?
1) Efferent arteriole becomes constricted due to hyaline arterioloclerosis causing an increase in the GFR and CCr
2) Increased GFR damages the glomerulus (hyperfiltration injury)
How is CCr affected with ARF due to acute tubular necrosis, CRF due to diabetic glomerulopathy?
decreased CCr
What can dark yellow urine be a sign of?
concentrated urine, bilirubinuria, ↑ UBG, vitamins
What can red or pink urine be a sign of?
1) hematuria, hemoglobinuria, myoglobinuria
2) drugs (e.g., phenazopyridine, a urinary anesthetic),
3) porphyria
Smoky-colored urine can be a sign of what?
1) acid pH urine converts Hb to hematin
2) common finding in nephritic type of glomerulonephritis
Black urine after exposure to light?
alkaptonuria (AR disease with deficiency of homogentisate oxidase) with an increase in homogentisic acid in the urine; turns black when exposed to light
Cloudy urine with alkaline pH is? Cloudy urine with acid pH is?
1) normal may be from increased phosphates
2) normal finding most often due to uric acid
What does specific gravity evaluate? Above what level does it exclude intrinisic renal disease?
1) Evaluates urine concentration and dilution
2) Specific gravity > 1.023 (UOsm 900 mOsm/kg) indicates urine concentration and excludes intrinsic renal disease
Hypotonic urine has a specific gravity of what?
<1.015 (∼ UOsm 220 mOsm/kg)
A fixed specific gravity of 1.008-1.010 indicates what?
CRF
With a dipstick urine test how would a vegan be different from a meat eater?
1) pure vegan usually has alkaline pH (citrate converted into bicarbonate)
2) meat eater usually has acid pH (organic acids in meat)
What does Alkaline pH + smell of ammonia indicate?
urease-producing pathogen (e.g., Proteus)
With which urinalysis method can BJ be determined?
sulfosalicylic acid
In what condition can there be Normal serum glucose + glucosuria?
1) normal pregnancy (normally have a low renal threshold for glucose),
2) benign glucosuria (low renal threshold for glucose)
microalbuminuria is the first sign of?
diabetic nephropathy
When is ketonuria present?
DKA, starvation, ketogenic diets, pregnancy (normal finding), isopropyl alcohol poisoning
Absent urine UBG, ↑ urine bilirubin indicates what?
obstructive jaundice
↑ Urine UBG, absent urine bilirubin indicates what?
extravascular hemolytic anemia (e.g., hereditary spherocytosis)
↑ Urine UBG, ↑ urine bilirubin indicates what?
hepatitis
Myoglobinuria indicates? Hemoglobinuria indicates?
1) crush injuries; ↑ serum creatine kinase
2) intravascular hemolytic anemia
Why are nitrites not sensitive for a UA?
Detects nitrites produced by nitrate reducing uropathogens (e.g., E. coli); test sensitivity and specificity is 30% and 90%, respectively; requires ∼ 4 hr for nitrate reducing uropathogens to convert nitrates to nitrites and patients with UTI frequently have increased frequency of urination, which explains the tests poor sensitivity
Leukocyte esterase is sensitive. What is it good for?
Detects esterase in neutrophils (pyuria); ∼ 80% sensitivity
Infections: urethritis, cystitis, pyelonephritis
what is sterile pyuria? What causes it?
1) neutrophils present but negative standard urine culture
2) Chlamydia trachomatis urethritis, tuberculosis, drug-induced interstitial nephritis
What does Dysmorphic RBCs indicate if in the urine?
hematuria of glomerular origin
What do Oval fat bodies indicate on UA?
renal tubular cells with lipid (nephrotic syndrome)
Describe hyaline casts? Is it significant?
acellular, ghost-like cast containing protein; no significance in the absence of proteinuria
When is an RBC cast seen?
nephritic type of glomerulonephritis (e.g., post-streptococcal glomerulonephritis)
When is a WBC cast seen?
acute pyelonephritis, acute tubulointerstitial nephritis
When is a renal tubular cell cast seen?
acute tubular necrosis
What is a fatty cast seen in?
contains lipid (e.g., cholesterol); sign of nephrotic syndrome (e.g., lipoid nephrosis)
What is a waxy cast and when is it seen?
refractile, acellular cast; sign of chronic renal failure
Calcium oxalate crystals develop in who?
pure vegan diet, ethylene glycol poisoning, calcium oxalate stone
Uric acid crystals develop in who?
hyperuricemia associated with gout or massive destruction of cells after chemotherapy
triple phosphate crystals develop in who?
may be a sign of urinary tract infection due to urease producing uropathogens (e.g., Proteus species)
Cystine crystals occur in who? How are they shaped?
hexagonal crystal seen in cystinuria
What is the effect of NSAIDs on the kidney?
inhibit production of PGE2; therefore, intrarenal blood flow is controlled by the efferent arterioles, whose blood flow is maintained by ATII, a vasoconstrictor. This increases the risk of ischemic damage to the medulla.
What does the afferent arteriole contain? What molecule is locally active here?
1. Contain the juxtaglomerular apparatus
* Produces the enzyme renin
2. Blood flow is controlled by renal-derived PGE2 (vasodilator).
3. Direct blood into the glomerular capillaries
What molecule acts on the efferent arteriole? What is effect?
Blood flow controlled by ATII (vasoconstrictor).
What type of capillary network is in the glomeruli?
Glomerular capillaries contain fenestrated epithelium
What is the GBM made up of?
a. Composed of type IV collagen
1) Heparan sulfate produces the negative charge of the GBM.
2) Cationic proteins of low molecular weight (LMW) are permeable.
3) Albumin has a strong negative charge and is not permeable.
What are causes of GBM thickening?
1) Deposition of immunocomplexes
o Example-membranous glomerulopathy
2) Increased synthesis of type IV collagen
o Example-diabetes mellitus
What is fusion of podocytes a sign of?
sign of nephrotic syndrome
What is the function of visceral epithelial cells in the glomeruli?
1) Primarily responsible for production of the GBM
2) Contain podocytes (foot-like processes) and slit pores between the podocytes
What is the function of mesangial cells in glomeruli?
1) Support the glomerular capillaries
2) Can release inflammatory mediators and proliferate
* Example-IgA glomerulopathy has mesangial immunocomplex deposit
Where are parietal epithelial cells found in the glomeruli? What does their proliferation cause?
1. Lining cells of Bowman's capsule
2. Proliferation causes "crescents" that encroach upon and destroy the glomerulus.
A maltese cross is identified in the urine. what type of cast is this?
1) oval fat body
2) The Maltese crosses are due to cholesterol, which is always increased in the nephrotic syndrome
What is the Most common congenital kidney disorder? What is it associated with?
1) horse shoe kidney
2) Turner's syndrome
Where are the majority of horseshoe kidneys fused? What structure is the kidney stuck behind?
1) lower pole
2) Kidney is trapped behind the root of the inferior mesenteric artery.
What are the clinical features of a horseshoe kidney?
1. Increased incidence with Turner's syndrome
2. Danger of infection and stone formation
What is the Most common cystic disease in children? What is the genetic component? Pathologically what is occurring?
1) renal dysplasia
2) No inheritance pattern
3) Abnormal development of one or both kidneys
*abnormal structures persist in the kidneys (e.g., cartilage, immature collecting ductules).
Clinically how does renal dysplasia present? What can it lead to?
1) Present as an enlarged, irregular, cystic, unilateral (bilateral) flank mass
2) Bilateral dysplastic kidneys may lead to renal failure; accounts for ∼ 20% of cases of CRF in children
Juvenile polycystic kidney disease has what genetic component? Pathologically what is occurring? Where else can cysts present? What is it associated with?
1) AR inheritance
2) Bilateral cystic disease; cysts in the cortex and medulla
3) Cysts also occur in the liver
4) Association with congenital hepatic fibrosis leading to portal hypertension
How does Juvenile polycystic kidney disease present at birth? What causes it?
1) Enlarged kidneys at birth; most serious types are incompatible with life
2) Maternal oligohydramnios (decreased amniotic fluid)
3) newborns have Potter's facies, a deformation due to oligohydramnios
4) findings include low-set ears, parrot beak nose, and lung hypoplasia
Is Adult polycystic kidney disease dominant or recessive? Which chromosome is involved? When does it present? What is it associated with?
1) AD inheritance; defect on chromosome 16
2) Bilateral cystic disease develops by 20-25 years of age; bilaterally palpable kidneys; cysts involve all parts of the nephron in the cortex and medulla
3) Cysts are present in the liver (50%), pancreas (10%), spleen (5%)
What are findings in Adult polycystic kidney disease?
1) Hypertension (>80% of cases);
2) associated with stroke due to rupture of intracranial berry aneurysms (aneurysms in 10-30% of cases), intracerebral hemorrhage, lacunar infarcts
What other conditions are associated with adult polycystic kidney disease?
1) sigmoid diverticulosis
2) hematuria
3) mitral valve prolapse
4) slight risk for developing renal cell carcinoma
When does CRF begin with polycystic kidney disease? How is it treated?
1) CRF begins at age 40-60; due to destruction of kidneys by slowly expanding cysts; accounts for ∼ 10% of cases of CRF; it is the most common cause of death
2) Treatment: renal transplantation
What are pathologic findings in Medullary sponge kidney?
1) No inheritance pattern
2) Most commonly discovered with an Intravenous pyelogram
3) striations are present in the papillary ducts of the medulla ("Swiss-cheese" appearance)
4) multiple cysts of the collecting ducts are present in the medulla
What are clinical findings in medullary sponge kidney?
Recurrent UTIs, hematuria, and renal stones
How is acquired polycystic kidney disease caused? What is there a small risk of developing?
1) Tubules are obstructed by interstitial fibrosis or oxalate crystals
2) Small risk for developing renal cell carcinoma
3) Most common cause is renal dialysis; occurs in ∼ 50% of patients on long-term dialysis
What is the Most common adult renal cyst? Why do they occur? What can they produce?
1) simple retention cysts
2) Derived from tubular obstruction
3) May produce hematuria
4) Requires needle aspiration to distinguish it from renal cell carcinoma
At autopsy how does renal dysplasia look?
multicystic deformed kidney and dilated ureter
An immunoflouresence stain is done and reveals linearly and evenly distributed antibodies to the GBM. What is the disease? Would electron microscopy be an effective confirmation?
1) Goodpasture syndrome
2) Cannot be detected by electron microscopy
A Granular ("lumpy-bumpy") pattern is seen with immunoflouresence in the kidney. What is it?
immunocomplex type of glomerulonephritis
How do Immuncomplexes that deposit in the kidney lead to damage?
activate complement → C5a produced → attracts neutrophils

Damage to the glomeruli by neutrophils, which occurs in nephritic types of glomerulonephritis.
What does the production of T-cell cytokines lead to in the glomeruli?
1. Cytokines cause the GBM to lose its negative charge.
2. Cytokines damage podocytes causing them to fuse.
3. Example-minimal change disease in the nephrotic syndrome
Nephritic syndrome is mostly due to what?
Glomerular injury is primarily due to neutrophils
Clinically how does someone with nephritic syndrome present?
1) Hypertension
* Due to salt retention
2) Periorbital puffiness
a. Due to salt retention in the loose skin in that area
b. In some cases, edema can be more generalized.
o Sodium retention increases plasma hydrostatic pressure
does edema distinguish nephritic from nephrotic syndrome?
no
What are UA findings in someone with nephritic syndrome?
1) Oliguria (∼400 mL urine/day)
a. Due to decreased GFR from inflamed glomeruli
b. Tubular function is intact.
2) Hematuria
a. Dysmorphic RBCs with irregular membranes (see Fig. 19-2A)
b. Due to inflamed glomeruli from IC deposition
3) Neutrophils in the sediment
a. Particularly in IC types
4) RBC casts are a key finding
a. Occasionally, WBC casts are also present.
5) Proteinuria > 150 mg/day, but <3.5 g/day
6) Azotemia with a BUN:Cr ratio > 15
a. Tubular function is intact in acute glomerulonephritis.
Nephritic syndrome is characterized how?
moderate proteinuria; dysmorphic RBCs, RBC casts
What is the cause of nephrotic syndrome?
1) Glomerular injury is due to cytokines not neutrophils.
a. Cytokines damage podocytes causing them to fuse together.
b. Cytokines destroy the negative charge of the GBM.
What is the key finding in nephrotic syndrome?
proteinuria > 3.5 g/24 hours; fatty casts
why is there generalized pitting edema in nephrotic syndrome? What is there increased risk of developing?
(1) Due to hypoalbuminemia
o Pitting edema in nephritic syndrome is due to sodium retention.
(2) Increased risk for developing spontaneous peritonitis
o Due to Streptococcus pneumoniae
What are lab findings in nephrotic syndrome?
1) Hypertension in some types
* Due to sodium retention
2) Hypercoagulable state due to loss of antithrombin III
* Potential for renal vein thrombosis
3) Hypercholesterolemia
* Hypoalbuminemia increases synthesis of cholesterol (unknown mechanism).
4) Hypogammaglobulinemia
* Due to the loss of γ-globulins in the urine
5) Fatty casts with maltese crosses and oval fat bodies
* Key finding of the nephrotic syndrome
Does nephrotic or nephritic syndrome have more inflammation?
nephritic syndrome
What is prescribed when microalbuminuria is first detected?
1) ACE inhibitor
2) It slows the progression of diabetic glomerulopathy and retinopathy in both types of diabetes mellitus
How does ACE inhibitor help with diabetes glomerularnephropathy?
One possible mechanism is by reducing pressure in the glomerular capillaries by decreasing ATII vasoconstriction of the hyalinized efferent arterioles. Angiotensin receptor blockers are also useful, particularly in type 2 diabetes mellitus. These changes are independent of the blood pressure lowering capabilities of both drugs.
ACE inhibitor/receptor blockers are useful for?
slow progression of nephropathy in type 1/type 2 diabetes
when does Kimmelstiel-Wilson disease occur? What is it also known as?
1) Diabetic glomerulopathy
2) Nodular glomerulosclerosis
Does nodular glomerulosclerosis occur in both type I and II diabetes?
Occurs more often in type 1 (35-45%) than type 2 diabetes (20%)
What is Most common cause of chronic renal failure in United States?
1) diabetic glomerulopathy
2) Type 1 > type 2 diabetes mellitus
What are risk factors for glomerulopathy?
(a) Poor glycemic control
(b) Hypertension
(c) Diabetic retinopathy
o High correlation with coexisting glomerulopathy
Pathologically what is occurring in nodular glomerulosclerosis?
(1) Nonenzymatic glycosylation (NEG) of the GBM
(2) NEG of the afferent and efferent arterioles
a. Produces hyaline arteriolosclerosis
b. Involves efferent arterioles before afferent arterioles
(3) Osmotic damage to glomerular capillary endothelial cells
a. Glucose is converted by aldose reductase into sorbitol.
b. Sorbitol is osmotically active.
c. Water enters the cells causing damage.
(4) Hyperfiltration damage to the mesangium
a. Selective hyaline arteriolosclerosis of efferent arterioles
b. Increases the GFR, which damages mesangial cells
(5) Diabetic microangiopathy; increased deposition of type IV collagen
a. GBM, tubular cell basement membranes, mesangium
Hyaline arteriolosclerosis of efferent arteriole leads to what?
↑ GFR producing hyperfiltration injury
What does electron microscopy show in nodular glomerularsclerosis?
fusion of podocytes
What are microscopic findings in nodular glomerulosclerosis?
(1) Afferent and efferent hyaline arteriolosclerosis
o When the afferent arteriole becomes hyalinized, the GFR decreases.
(2) Nodular masses develop in the mesangial matrix.
o Due to increased type IV collagen synthesis and trapped proteins
What happens to GFR when the afferent arteriole has hyaline arteriosclerosis?
GFR decreases
Laboratory findings in someone with nodular glomerulosclerosis show what?
(1) Microalbuminuria
a. Initial laboratory manifestation of diabetic glomerulopathy
b. Usually begins after ∼10 years of poor glycemic control
c. Microalbuminuria dipsticks detect albumin levels in the range of 1.5 to 8 mg/dL.
What is the first laboratory sign of diabetic glomerulopathy?
microalbuminuria
Besides nodular glomerulosclerosis what are other renal diseases associated with diabetes mellitus?
Renal papillary necrosis, acute and chronic pyelonephritis
What is Alports syndrome?
1) Autosomal dominant disease; perhaps X-linked recessive
2) Autoantibodies to type IV collagen in GBM
What is seen under the microscope and electron microscope in Alports?
1) No specific immunofluorescence or electron microscopic findings
2) Lipid accumulation in VECs producing foam cells under microscope
How is alports syndrome characterized?
hereditary nephritis, sensorineural hearing loss, ocular defects
What is Thin basement membrane disease?
1) "Benign familial hematuria"
2) Autosomal dominant disorder
3) Extremely thin GBMs
a. Normal renal function
4) Mild proteinuria, persistent microscopic hematuria
List causes in descending order of chronic glomerularnephritis?
1. Rapidly progressive glomerulonephritis (RPGN; 90%)
2. Focal segmental glomerulosclerosis (80%)
3. Type I membranoproliferative glomerulonephritis (40%)
4. Membranous glomerulopathy (20-30%)
5. Type IV diffuse proliferative glomerulonephritis in SLE (20%)
6. IgA glomerulopathy (10%)
What is seen in chronic glomerulonephritis?
1. Shrunken kidneys
2. Glomerular sclerosis and tubular atrophy
Proliferative glomerulonephritis means what? Membranous glomerulopathy means what? Membranoproliferative glomerulonephritis means what?
1) >100 nuclei in affected glomeruli
2) Thick GBM, no proliferative change
3) Thick GBM, hypercellular glomeruli
What does Crescentic glomerulonephritis mean?
1) Proliferation of parietal epithelial cells around glomerulus
List diseases that are primarily result in nephritic syndrome?
1) IgA glomerulopathy (Berger's disease)
2) Post-streptococcal glomerulonephritis
3) Diffuse proliferative glomerulonephritis (SLE)
4) Rapidly progressive crescentic glomerulonephritis
Who does Berger's disease occur in? What else is it called? What is increased and Why?
1) IgA glomerulopathy
2) majority are nephritic (5% nephrotic)
3) Affects children and adults
4) Increased mucosal synthesis and decreased clearance of IgA; increased serum IgA (50%)
Is Berger's focal or global? What is occurring pathologically? Is hematuria continuous or intermittent? What other symptom is present and how is it treated?
1) Focal proliferative glomerulopathy
2) Mesangial IgA IC deposits with granular IF
a. ICs activate alternative complement pathway
3) Episodic bouts of hematuria (microscopic or gross) usually following an upper respiratory infection
4) hypertension
5) Slow progression to CRF (40-50%)
6) Treatment: corticosteroids decrease proteinuria; treat hypertension
When does Post-streptococcal glomerulonephritis occur? What cells get activated?
1) Usually follows group A streptococcal infection of skin (e.g., scarlet fever) or pharynx
Subepithelial IC deposits with granular IF
2) ICs activate alternative complement pathway
3) Diffuse proliferative pattern with neutrophil infiltration
Clinically how does someone with Post-streptococcal glomerulonephritis present?
1) Hematuria 1-3 weeks following group A streptococcal infection by a nephritogenic strain (never produces acute rheumatic fever)
2) periorbital edema (sodium retention)
3) edema can occasionally be more extensive but is related to sodium retention not hypoalbuminemia
4) hypertension (usually transient; sometimes severe)
What are lab tests for Post-streptococcal glomerulonephritis? Does it progress to chronic failure? How is it treated?
1) Increased anti-DNase B titers
2) ASO is degraded by oil in the skin and is not increased
3) streptozyme test is positive (can detect anti-DNase B, ASO, anti-AH, and anti-NAD antibodies)
4) Usually resolves; CRF is uncommon
5) Treatment: supportive; penicillin G or V if cultures are positive for Streptococcus pyogenes; treat hypertension
Diffuse proliferative glomerulonephritis occurs in SLE. Is it diffuse or localized? Can it be nephrotic? What occurs pathologically?
1) Diffuse proliferative GN is most common subtype of glomerular disease in SLE
2) other types can have a nephrotic presentation
3) Subendothelial IC deposits with granular IF
4) DNA-anti-DNA ICs activate classical complement pathway
"Wire looping" of capillaries is characteristic of what glomerular disease?
1) SLE
a. corresponds with subendothelial ICs
2) neutrophil infiltration with hyaline thrombi in capillary lumens
What is major target organ in SLE? What antibodies are present? What is death from? How is it treated?
1) Kidneys (∼ 90%)
2) Serum ANA test usually has a rim pattern, which corresponds with the presence of anti-dsDNA antibodies
3) Evolves into CRF in most cases; common cause of death in SLE
4) Treatment: corticosteroids + cyclophosphamide
Is Rapidly progressive crescentic glomerulonephritis a primary or secondary disease? How does it progress? What is it associated with?
1) may be primary or secondary
2) Rapid loss of renal function progresses to ARF over days to weeks; very poor prognosis
3) May or may not be associated with crescent formation (crescentic GN)
4) Clinical associations: Goodpasture's syndrome, microscopic polyarteritis (p-ANCA), Wegener's granulomatosis (c-ANCA)
Who does Goodpasutures occur in? What is genetic association? What organs are affected? What is seen with electron microscope?
1) Male dominant disease; 80% HLA-BR2 positive
2) Anti-basement membrane antibodies against collagen in glomerular and pulmonary capillaries
3) Linear IF; EM has no electron-dense deposits; crescentic GN (accounts for 5% of all cases)
Which symptoms are present initially in goodpastures? How does it end? How is it treated?
1) Begins with hemoptysis and ends with renal failure
2) Treatment: plasma exchange; immunosuppressive therapy with corticosteroids and cyclophosphamide; renal transplantation
Minimal change disease (lipoid nephrosis) occurs in who? What occurs pathologically and what is lost?
1) Most common cause of nephrotic syndrome in children
2) more common in girls than boys
3) occurs in ∼ 15% of adults with nephrotic syndrome
4) T-cell cytokines cause the GBM to lose its negative charge
a. selective proteinuria (albumin not globulins)
What changes occur in the glomeruli of Minimal change disease (lipoid nephrosis)? What does EM and IF show?
1) Structurally normal glomeruli
2) positive fat stains in glomerulus and tubules
3) Negative IF
4) EM shows fusion of podocytes and no deposits
What is a secondary cause of Minimal change disease (lipoid nephrosis)? What precedes it? Are they hypertensive? How is it treated?
1) Hodgkin's lymphoma
2) Often preceded by respiratory infection or routine immunization
3) Usually normotensive (90%), unlike other types of nephrotic syndrome
4) children respond well to steroid therapy; CRF is rare
Does Focal segmental glomerulosclerosis caused by primary or secondary disease? What does IF and EM show?
1) Primary or secondary disease
2) secondary causes-HIV (most common glomerular disease) and intravenous heroin abuse
3) Negative IF; EM focal damage of VECs
How does Focal segmental glomerulosclerosis present? Is it progressive?
1) Nonselective proteinuria, microscopic hematuria (60-80%)
2) Hypertension early (20%)
3) Poor prognosis; commonly progresses to CRF
4) Treatment: corticosteroids (only 15-20% response)
What is the Most common cause of nephrotic syndrome in adults?
1) Diffuse membranous glomerulopathy
2) Primary and secondary types
What are secondary causes of Diffuse membranous glomerulopathy?
1) Drugs: e.g., captopril, gold therapy
2) Infections: HBV, Plasmodium malariae, syphilis
3) Malignancy: carcinomas, Hodgkin's lymphoma
4) Autoimmune disease: SLE (nephrotic presentation)
microscopically what is seen in Diffuse membranous glomerulopathy? What does silver stain show? How is it treated?
1) Diffuse thickening of membranes
2) silver stains show "spike and dome" pattern beneath VECs (subepithelial deposits)
3) Subepithelial ICs with granular immunofluoresence
4) Treatment: corticosteroids may slow progression
What is the Most common type of MPGN? Is it nephrotic or nephritic? What is it associated with?
1) MPGN I
2) nephrotic presentation (60%)
3) some cases have a nephritic presentation
4) Associated with HBV, HCV (more common), or cryoglobulinemia
What is seen histologically in MPGN I? What is seen with immunoflouresence and EM?
1) Subendothelial ICs with granular IF
2) ICs activate classical and alternative complement pathways
3) EM shows tram tracks caused by splitting of the GBM by an ingrowth of mesangium
How does MPGN I present? How is it treated?
1) Hypertension (35%); majority have hematuria
2) Majority progress to CRF
3) Treatment: response to corticosteroids not established
What is MPGN II associated with? What remains at low levels?
1) Associated with the C3 nephritic factor (C3NeF), an autoantibody that binds to C3 convertase (C3bBb)
2) prevents degradation of C3 convertase causing sustained activation of C3 resulting in very low C3 levels
What is seen on EM in MPGN II? What are presenting symptoms? How is it treated? What does it progress to?
1) Diffuse intramembranous deposits ("dense deposit disease")
2) EM shows tram tracks
3) Hypertension (35%); majority have hematuria
Majority progress to CRF
4) Treatment: response to corticosteroids not established
Who is at risk for developing ARF?
1) Greater than 10% of intensive care unit patients develop acute renal failure (ARF).
2) Greater than 40% of hospital ARF is iatrogenic (doctor-induced).
3) ARF occurs in 20% of patients with sepsis.
4) ARF develops in >50% of patients with septic shock.
How is ARF defined? What the most common cause?
(1) Acute suppression of renal function developing in 24 hours
(2) Accompanied by anuria or oliguria (∼400 mL/24 hours)
(3) ATN is the most common cause of ARF.
a. Subdivided into ischemic and nephrotoxic types
Besides ATN what are causes of ARF?
(1) Postrenal obstruction
o Examples-prostate hyperplasia; invasive cervical cancer
(2) Vascular disease
o Example-malignant hypertension
(3) RPGN, drugs, disseminated intravascular coagulation (DIC), urate nephropathy
What is the most common cause of ischemic ATN?
Most often caused by prerenal azotemia due to hypovolemia
How does ischemic ATN effect the endothelial cells?
(1) Causes decrease in vasodilators
o Examples-nitric oxide, PGI2
(2) Increase in vasoconstrictors
o Example-endothelin
(3) Net effect is vasoconstriction of afferent arterioles, which decreases GFR.
How does ischemic ATN affect the tubule cells? What is net effect?
(1) Causes detachment of tubular cells into the lumen causing obstruction
a Produces pigmented renal tubular cell casts
(2) Casts obstruct the lumen causing an increase in intratubular pressure.
a. Decreases GFR
b. Pushes fluid into the interstitium
c. Net effect is oliguria
What is the key cast of ATN?
Renal tubular cell cast
Where are sites of tubular damage with ischemia?
(1) Straight segment of proximal tubule
a. Part of the nephron most susceptible to hypoxia
(2) Medullary segment of the thick ascending limb (TAL)
b. Location of the Na+-K+-2 Cl- cotransporter
(3) Tubular basement membranes are disrupted at these sites.
a. Interferes with renal tubular cell regeneration
What are causes of nephrotoxic ATN?
(1) Aminoglycosides most common cause (e.g., gentamicin)
(2) Radiocontrast agents
(3) Heavy metals (e.g., lead and mercury)
What are microscopic findings in nephrotoxic ATN?
(1) Primarily damages the proximal tubule cells
(2) Tubular basement membrane is intact.
Common laboratory findings in ATN are what?
1. Oliguria, in most cases
a. Some cases have polyuria (∼800 mL/24 hours).
2. Pigmented renal tubular cell casts
3. Hyperkalemia, increased anion gap metabolic acidosis
4. Increased serum BUN and creatinine (ratio ≤ 15)
5. Hypokalemia (diuresis phase) and infection are common problems
renal tubular cell casts are seen in what? What other lab features do they have?
1) ATN
2) BUN: creatinine ratio ≤15; hyperkalemia, metabolic acidosis
How is ATN treated?
1. Treat prerenal azotemia
a. Volume expansion if hypovolemic; increase renal blood flow
2. Low dose dopamine
3. Fenoldopam (dopamine α-1-receptor agonist)
4. Dialysis
How should patients with disseminated cancer be treated before aggressive chemotherapy? Why?
1) allopurinol, an xanthine oxidase inhibitor
2) This prevents urate nephropathy (tumor lysis syndrome) and acute renal failure.
What are causes of both acute or chronic TIN?
1.Acute pyelonephritis (APN; most common)
2. Drugs
3. Infections
a. Examples-legionnaires' disease, leptospirosis
4. SLE, lead poisoning
5. Urate nephropathy, multiple myeloma
What is the most common cause of TIN? Who does it occur more in? Why?
1) acute pyelonephritis
2) women
3) E. coli infections, also enterococcus
What are risk factors for acute pyelonephritis?
(a) Indwelling urinary catheter
(b) Urinary tract obstruction
(c) Medullary sponge kidney
(d) Diabetes mellitus, pregnancy
(e) Sickle cell trait/disease
How does vesicoureteral reflux lead to acute pyelonephritis?
(1) Vesicoureteral reflux (VUR) with ascending infection (most common)
a. Intravesical portion of the ureter is normally compressed with micturition.
** Prevents reflux of urine into the ureter(s)
b. In VUR, the intravesical portion of the ureter is not compressed during micturition.
** Urine refluxes into the ureter(s).
c. Should be corrected by reimplantation of the ureters/stents
What organism is suspected if hematogenous spread is the route of acute pyelonephritis?
1) S aureus
2) note: uncommon cause
What are gross and microscopic findings in acute pyelonephritis?
(1) Grayish white areas of abscess formation are in the cortex and medulla.
(2) Microabscess formation occurs in the tubular lumens and interstitium
Clinically how does someone with acute pyelonephritis present?
(1) Spiking fever, flank pain
(2) Increased frequency of urination
(3) Painful urination (dysuria)
What are lab findings in acute pyelonephritis?
(1) WBC casts (key finding)
(2) Pyuria, bacteriuria (usually E. coli)
(3) Hematuria
What are Findings in APN and not lower UTIs?
fever, flank pain, WBC casts in urine
What are complications of acute pyelonephritis?
(1) Chronic pyelonephritis
(2) Perinephric abscess
(3) Renal papillary necrosis
(4) Septicemia with endotoxic shock
How is acute pyelonephritis treated?
(1) Ciprofloxacin given orally if uncomplicated
(2) Ciprofloxacin IV if hospitalized
(3) Repair VUR
What are causes of chronic pyelonephritis?
(1) VUR starting in young girls
(2) Lower urinary tract obstruction
a. Produces hydronephrosis
b. Examples-prostate hyperplasia, renal stones
What are gross findings in chronic pyelonephritis?
(1) Reflux type of CPN
a. U-shaped cortical scars overlying a blunt calyx
b. Visible with an intravenous pyelogram (IVP)
(2) Obstructive type CPN
a. Uniform dilation of the calyces
b. Diffuse thinning of cortical tissue
What are microscopic findings in chronic pyelonephritis?
1) Chronic inflammation
a. Secondary scarring of the glomeruli
2) Tubular atrophy
a. Tubules contain eosinophilic material resembling thyroid tissue ("thyroidization")
What are clinical and lab findings in chronic pyelonephritis?
(1) Usually a history of recurrent APN
(2) May cause hypertension
a. Reflux nephropathy is a cause of hypertension in children.
(3) May cause chronic renal failure (CRF)
What is a cause of hypertension in children?
reflux nephropathy
Which drugs can lead to acute drug induced TIN?
1) Penicillin, particularly methicillin
2) Rifampin, sulfonamides
3) NSAIDs, diuretics
When does acute drug induced TIN begin? What type of hypersensitivity is it?
(1) Combination of type I and type IV hypersensitivity
(2) Occurs ∼2 weeks after beginning a drug
How does someone present with acute drug induced TIN? What are lab findings?
(1) Abrupt onset of fever, oliguria, and rash
a. Withdrawal of the drug causes reversal of the disease.
(2) Laboratory findings
a. BUN:Cr ratio ≤15
b. Eosinophilia and eosinophiluria (highly predictive)
Who does analgesic nephropathy occur?
(1) Common cause of chronic drug-induced TIN
(2) More common in women than men
(3) Usually occurs in patients with chronic pain
Pathologically what occurs in analgesic nephropathy?
(1) Chronic use of acetaminophen plus aspirin for 3 or more years
(2) Acetaminophen free radicals damage renal tubules in medulla
(3) Aspirin inhibits renal synthesis of PGE2 leaving ATII unopposed.
a. Decreased blood flow to the renal medulla
Analgesic nephropathy is a combination of what? Leads to?
acetaminophen + aspirin; renal papillary necrosis
What are complications of analgesic nephropathy?
(1) Renal papillary necrosis
a. Sloughing of renal papillae
b. Produces gross hematuria, proteinuria, and colicky flank pain
c. An IVP shows a "ring defect" where one or more papillae used to reside.
2) Hypertension, CRF
(3) Renal pelvic and bladder transitional cell carcinomas
What are causes of renal papillary necrosis?
1) analgesic nephropathy
2) SCD
3) diabetes
4) APN
where does urate nephropathy develop? What are causes? What can it lead to?
1. Deposition of urate crystals in the tubules and interstitium
2. Causes
a. Massive release of purines (precursor of uric acid)
** Usually following aggressive treatment of disseminated cancer (e.g., leukemia)
b. Lead poisoning, gout
3. May produce ARF
How does lead effect the kidney's?
(1) Decreases excretion of uric acid (urate nephropathy)
a. Can also decrease uric acid secretion producing gout
(2) Direct toxic effect produces TIN
What are histologic findings in chronic lead poisoning?
proximal tubules with nuclear acid-fast inclusions
How do BJ proteins effect the kidneys?
(1) BJ protein produces tubular casts.
a. Light chains are toxic to renal tubular epithelium.
(2) Casts obstruct the lumen and incite a foreign body giant cell reaction.
a. Reaction involves tubules and interstitium leading to renal failure.
What are 3 ways multiple myeloma effects the kidney?
1) Bence Jones protein
2) Nephrocalcinosis
a. Due to hypercalcemia
b. Metastatic calcification of the basement membrane of collecting tubules
c. Causes polyuria and renal failure
3) Primary amyloidosis producing nephrotic syndrome
a. Light chains are converted to amyloid
How is oliguria defined?
urine output < 400 mL/day or <20 mL/hour
What are lab tests that are used for differentiating causes of oliguria?
1) urine osmolality (UOsm)
2) fractional excretion of sodium (FENa+)
3) random urine sodium (UNa+)
4) the serum BUN:Cr (blood urea nitrogen/creatinine) ratio
A UOsm > 500 mOsm/kg indicates what? <350 mOsm/kg?
1) good concentrating ability
2) poor concentrating ability and tubular dysfunction
What does the FENa+ mean?
The FENa+ represents the amount of sodium excreted in the urine divided by the amount of sodium that is filtered by the kidneys
What does a FENa+ of <1% mean? >2%?
1) An FENa+ < 1% indicates good tubular function and excludes acute tubular necrosis (ATN) as a cause of oliguria.
2) An FENa+ > 2% indicates tubular dysfunction and is highly predictive of ATN as the cause of oliguria
What does a random UNa+ < 20 mEq/L mean? UNa+ > 40 mEq/L?
A random UNa+ < 20 mEq/L indicates intact tubular function, while a random UNa+ > 40 mEq/L indicates tubular dysfunction
In prerenal azotemia and acute glomerulonephritis (nephritic type) is tubular function preserved? How can these two conditions be distinguished?
1) yes
2) urine sediment: pre-renal has none, but glomerulonephritis has RBCs casts and hematuria
How is it possible to distinguish ATN from postrenal azotemia as a cause of tubular dysfunction and oliguria?
In ATN, the sediment has pigmented renal tubular cell casts, but in postrenal azotemia, the sediment is usually normal
What are the following values for pre-renal azotemia:
1) FENa+ %
2) BUN:Cr
3) UNa+
4) UOsm
5) Urinalysis
1) <1
2) >15
3) <20
4) >500
5) Normal sediment or hyaline casts
What are the following values for Acute glomerulonephritis:
1) FENa+ %
2) BUN:Cr
3) UNa+
4) UOsm
5) Urinalysis
1) <1
2) >15
3) <20
4) >500
5) RBC casts, hematuria
What are the following values for Acute tubular necrosis:
1) FENa+ %
2) BUN:Cr
3) UNa+
4) UOsm
5) Urinalysis
1) >2
2) ≤15
3) >40
4) <350
5) Renal tubular cell casts
What are the following values for Postrenal azotemia (prolonged obstruction):
1) FENa+ %
2) BUN:Cr
3) UNa+
4) UOsm
5) Urinalysis
1) >2
2) ≤15
3) >40
4) <350
5) Normal sediment
The renal cortex shows deep U-shaped scars. Sections through this scar would have revealed a blunt calyx. What is it?
chronic pyelonephritis
multiple brownish necrotic papillae are seen with what?
analgesic nephropathy
At what GFR does someone have CRF? How doe the kidney's appear?
1) <10 ml/min
2) Bilateral, small shrunken kidneys
What are causes of CRF in descending order?
1. Diabetic mellitus (37%)
2. Hypertension (30%)
3. Chronic glomerulonephritis (12%)
a. Particularly due to RPGN and focal segmental glomerulosclerosis
4. Cystic renal disease
a. Renal dysplasia in children, adult polycystic kidney disease
What are hematologic findings in CRF?
1) Normocytic anemia with corrected reticulocyte count < 3%
a. Primarily due to decreased erythropoietin
2) Qualitative platelet defects
How does CRF affect the bone?
1) Osteitis fibrosa cystica
2) osteomalacia
3) osteoporosis
What causes Osteitis fibrosa cystica? How is it characterized?
1) Due to hypovitaminosis D seen in CRF
a. Causes hypocalcemia, which stimulates production of parathyroid hormone (PTH)
b. Called secondary hyperparathyroidism (HPTH)
2) Secondary HPTH increases bone resorption.
a. Causes cystic lesions in bone (e.g., jaw)
b. Hemorrhage into cysts causes a brown discoloration
Why is there osteomalacia in CRF?
1. Decreased mineralization of the organic bone matrix (osteoid)
2. In CRF, it is due to hypovitaminosis D.
a. Causes hypocalcemia, leading to decreased bone mineralization
3. Produces fractures and bone pain
Why does osteoporosis result in CRF?
1. Loss of organic bone matrix and minerals
a. Causes an overall reduction in bone mass
2. In CRF, it is due to chronic metabolic acidosis.
a. Excess H+ ions are buffered by bone.
3. Produces fractures and bone pain
How does CRF effect the cardiovascular system?
1. Hypertension from salt retention
2. Hemorrhagic fibrinous pericarditis
3. Congestive heart failure, accelerated atherosclerosis
What are two unusual findings in CRF?
1. Hemorrhagic gastritis
2. Uremic frost (urea crystals deposit on skin)
How are electrolytes and acid base balance effected by CRF?
1. Hyperkalemia and increased anion gap metabolic acidosis
2. Sodium is usually normal except in salt-losing types of CRF.
How are Ca2+ and phosphorous effected by CRF?
1) Hypovitaminosis D
a. Due to decreased synthesis of 1-α-hydroxylase
b. Decreased reabsorption of calcium from the small intestine
2) Hyperphosphatemia
a. Due to decreased renal excretion
b. Drives calcium into bone and soft tissue
o Metastatic calcification
How are the CBC and coag effected by CRF?
Normocytic anemia; prolonged bleeding time
What is a biomarker of kidney function?
Cystatin C
Why is Cystatin elevated in CRF? What is the function/purpose of the molecule?
1. Cysteine protease inhibitor produced by all nucleated cells
2. Filtered by glomerulus but not secreted
3. Less dependent on age, sex, race, and muscle mass than creatinine
4. May be superior to creatinine in assessing severity of renal function
* Biomarker of kidney function
UA finding in someone with CRF may show what?
1. Fixed specific gravity
a. Tubular dysfunction causes lack of concentration and dilution.
b. Free water clearance is zero
2. Waxy/broad casts

Waxy casts: sign of CRF
What is the free water clearance in CRF?
zero
What are waxy casts a sign of?
CRF
How is CRF treated without meds?
1. Restrict sodium
2. Low-protein diet
3. Adjust drug doses to renal clearance
4. Kidney transplantation
How is CRF treated with medical intervention?
1. ACE inhibitors
a. Reduce proteinuria and disease progression
b. Treat hypertension
2. Dialysis
3. Erythropoiesis stimulating agents
4. Calcium supplementation and vitamin D (calcitriol)
a. Treat renal osteodystrophy
5. Phosphate binder (e.g., sevelamer)
What is the Most common renal disease in essential hypertension?
Benign nephrosclerosis (BNS)
Pathologically how does benign nephrosclerosis occur?
1. Hyaline arteriolosclerosis of arterioles in the renal cortex.
2. Causes tubular atrophy, interstitial fibrosis, glomerular sclerosis
How doe the kidney's appear in benign nephrosclerosis? What are lab findings?
1) Small kidneys with a finely granular cortical surface
2) Laboratory findings
a. Mild proteinuria
b. Hematuria (no RBC casts)
c. Renal azotemia
In who does malignant hypertension occur? Is it rapid or progressive?
1) Sudden onset of accelerated hypertension
a. May occur in normotensive individuals
b. May occur in those with BNS (most common)
c. May occur as a complication of various disorders
What are risk factors for malignant hypertension?
(1) Pre-existing BNS (most common)
(2) Hemolytic-uremic syndrome
(3) Thrombotic thrombocytopenic purpura
(4) Systemic sclerosis
What is the pathogenesis of malignant hypertension? What are gross and microscopic findings?
1. Vascular damage to arterioles and small arteries
2. Fibrinoid necrosis and necrotizing arteriolitis and glomerulitis
3. Pinpoint hemorrhages on the cortical surface ("flea-bitten" kidneys)
4. Hyperplastic arteriolosclerosis ("onion skin" lesion)
a. Smooth muscle hyperplasia and reduplication of basement membrane
What are clinical findings in malignant hypertension?
1. Rapid increase in blood pressure to ≥210/120 mm Hg
2. Hypertensive encephalopathy
a. Cerebral edema
b. Papilledema
**Loss of the normal optic nerve disk margin
c. Retinopathy
** Flame hemorrhages, exudates
d. Potential for an intracerebral bleed
3. Oliguric acute renal failure
What are lab findings in malignant hypertension? How is it treated?
1) Azotemia with BUN:Cr ratios ≤15
2) Hematuria with RBC casts
3) Proteinuria
Treatment: IV nitroprusside
What are causes of renal infarction?
1. Embolization from thrombi in the left side of the heart (most common)
2. Atheroembolic renal disease
3. Vasculitis, particularly polyarteritis nodosa
What are gross and microscopic findings in renal infarction?
1) Irregular, wedge-shaped pale infarctions in the cortex
2) Old infarcts have a V-shaped appearance due to scar tissue.
How does renal infarction present?
Sudden onset of flank pain and hematuria
How does sickle cell nephropathy present?
1. Asymptomatic hematuria (most common)
a. Due to infarctions in the medulla
2. Loss of concentrating ability
3. Renal papillary necrosis
4. Pyelonephritis
NOTE: occurs with sickle trait or disease
When does diffuse cortical necrosis occur?
1) preeclampsia
2) abruptio placentae
3) DIC limited to renal cortex
What is are gross and microscopic findings in someone with DIC limited to the renal cortex?
1) Fibrin clots in arterioles and glomerular capillaries
2) Bilateral, diffuse, pale infarct of the renal cortex
diffuse cortical necrosis in pregnant woman initially results in what? and leads to what?
1) anuria
2) goes to ARF
What are some causes of hydronephrosis?
1. Renal stone (most common)
2. Retroperitoneal fibrosis
3. Cervical cancer, benign prostatic hyperplasia
What are gross findings in hydronephrosis? What may it lead to? How is it treated?
1. Dilated ureter and renal pelvis
2. Compression atrophy of the renal medulla and cortex
3.May produce postrenal azotemia
4. treat with Catheter (most often); nephrostomy tube; cystoscopy
Who do stones occur more in? What time of year?
1. Stones occur in males more often than females.
2. Incidence is greater during the summer.
a. Insufficient fluid intake
What is the most common metabolic abnormality causing calcium stones? What is cause?
1) Hypercalciuria in the absence of hypercalcemia
2) Due to increased gastrointestinal reabsorption of calcium
a. Called absorptive hypercalciuria
What is the role of citrate in urine?
1) normally chelates calcium
2) if low can get calcium stones
What endocrine problem can lead to calcium stone formation? Diet?
1) Primary HPTH (10% of cases)
2) Diets high in dairy products (contain phosphate) or oxalates
What are the 2 types of calcium stones?
(1) Calcium oxalate stone (>50%) is the most common type in adults.
a. Increased incidence in pure vegans and those with Crohn's disease
(2) Calcium phosphate stones (10-20%) are the most common type in children.
a. Associated with dairy products and distal renal tubular acidosis
Magnesium ammonium phosphate results in what type of crystal? How are they produced? What are characteristics of the urine?
(1) "Staghorn calculus" or struvite stone (15%)
(2) Associated with urease producers (e.g., Proteus)
(3) Urine is alkaline and smells like ammonia
What are 2 types of stones that are least common?
Uric acid (8%), cystine (3%)
Clinically how does someone with kidney stones present?
1. Sudden onset of flank tenderness
2. Nausea and vomiting
3. Colicky pain radiating into groin
4. Patient constantly moving to try to relieve pain
5. Gross hematuria may be evident.
What are lab findings with the different types of kidney stones?
1. Hematuria
2. May find crystals in urine
3. Hypercalcemia
* Consider primary HPTH
What percent of kidney stones are radiopaque? What technique is most effective for diagnosing kidney stones? Is ultrasound more sensitive or specific?
1) 80% stones radiopaque
2) Unenhanced spiral (helical) CT
a. Sensitivity 96%, specificity 100%
3) Ultrasound (sensitivity 15%, specificity 90%)
What percent of stones pass in first 48 hours? What is risk of recurrence?
(1) Greater than 50% pass stone within 48 hours.
(2) Recurrence occurs in ∼50% of patients
What can be given to treat calcium stones?
(1) Hydrochlorothiazide
a. Increases renal tubule reabsorption of calcium
(2) Cellulose phosphate
a. Binds calcium in intestine
How can uric acid stones be treated?
(1) Allopurinol
(2) Increase urinary pH
o Makes uric acid soluble in urine
How can struvite stone be treated?
(1) Surgical removal because of size
(2) Antibiotic to eliminate urease producer
What is an Angiomyolipoma? What is it associated with in the kidney?
1. Hamartoma composed of blood vessels, smooth muscle, and adipose cells
2. Associated with tuberous sclerosis
a. Mental retardation
b. Multisystem hamartomas
Renal cell carcinoma is also known as?
1) Grawitz tumor
2) clear cell carcinoma
3) hypernephroma
Who does renal cell carcinoma occur in?
1) Sporadic (most common) and hereditary types
2) Occurs in men more frequently than women
a. Occurs in the sixth to seventh decades
What are risk factors for renal cell carcinoma?
(1) Smoking (most common)
(2) Von Hippel-Lindau disease (VHL)
(3) Adult polycystic kidney disease
(4) Obesity, asbestos exposure, exposure to lead
(5) Exposure to gasoline and petroleum products
How does VHL present? What is it?
(a) Autosomal dominant
(b) Chromosome 3 relationship
(c) Hemangioblastomas of cerebellum and retina
(d) Bilateral renal cell carcinoma (50-60%)
What type of genetic aberration occurs in VHL?
Translocations with loss of von Hippel-Lindau suppressor gene
Which part of the kidney does renal cell carcinoma derive from?
derives from proximal tubule cell
What is the most common type of renal cell carcinoma? How does it look?
1) clear cell carcinoma
2) Upper pole mass with cysts and hemorrhage
3) Tumor is a bright yellow mass larger than 3 cm (75-80%).
4) Composed of clear cells that contain lipid and glycogen
If a renal clear cell carcinoma invades the IVC what can happen?
Yellow tumor may invade inferior vena cava and extend to right side of heart.
Where does renal cell carcinoma metastisize?
1) Lungs are the most common site (50-60%)
a. Often hemorrhagic, "cannonball" appearance on radiographs
2) Bone (lytic lesions; 30-40%)
3) Regional nodes (15-30%)
4) Hemorrhagic nodules in the skin
a. Due to increased vascularity in the tumor
an x-ray shows cannon balls. What is suspected?
renal cell carcinoma
Clinically how does renal cell carcinoma present?
1) Hematuria (50-60%)
2) Abdominal mass (25-45%)
3) Flank pain (35-40%)
4) Hypertension (20-40%)
5) Triad-hematuria, abdominal mass, flank pain (5-10%)
6) Weight loss (30-35%)
7) Fever (5-15%)
8) Left-sided varicocele
What are lab findings with a renal cell carcinoma?
1. Elevated erythrocyte sedimentation rate (50-60%)
2. Normocytic anemia (20-40%)
3. Ectopic secretion of hormones
a. Erythropoietin (EPO)
o Produces secondary polycythemia (4%)
b. PTH-related protein
o Produces hypercalcemia (3-6%)
c. prolactin
What is the prognosis of renal cell carcinoma?
1. Characteristically has late metastases
a. May recur 10 to 20 years after the tumor has been removed
2. Average 5-year survival rate is 45% with metastasis.
b. Up to 70% of cases do not have metastasis.
3. Extension into the renal vein or through the renal capsule has a poor prognosis
c. 10% to 15% 5-year survival rate
What are risk factors for developing a renal TCC?
(1) Smoking (most common)
(2) Phenacetin abuse
(3) Aromatic amines (aniline dyes)
(4) Cyclophosphamide
What are risk factors for renal SCC?
renal stones and chronic infection.
What is the Most common primary renal tumor in children? When does it occur? What are causes?
1) Wilms tumor
2) Occurs between 2 and 5 years of age
3) Sporadic type (most common)
4) Genetic type
What is the genetic causes of wilms tumor?
Autosomal dominant inheritance (chromosome 11)
What is WAGR syndrome?
1) Wilms' tumor
2) aniridia (absent iris)
3) genital abnormalities
4) retardation
What is Beckwith-Wiedemann syndrome?
1) Wilms' tumor
2) enlarged body organs
3) hemihypertrophy of extremities
How does Wilms tumor appear grossly and microscopically? What embryonic layer is it derived from?
1) Large, necrotic, gray-tan tumor
a. Derived from mesonephric mesoderm
b. Contains abortive glomeruli and tubules, primitive blastemal cells, and rhabdomyoblasts
what are clinical findings in a child with wilm's tumor? Where is primary metastisis? survival rate?
1) Unilateral palpable mass in a child with hypertension
a. Hypertension due to renin secretion
2) Lungs are the most common site of metastasis.
3) With combined therapies 2-year survival rate is >90%
A large, yellow upper pole mass with multifocal areas of hemorrhage extends into the renal pelvis is seen. What is it?
renal cell carcinoma