RENAL Flashcards
During what week does the metanephros first appear?
5th week of gestation
What structure is the ureteric bud derived from? Name 4 structures that the ureteric bud gives rise to.
Derived from caudal end of mesonephros.
Gives rise to ureter, pelvises, calyces, and collecting ducts
Most common site of obstruction in fetus
Ureteropelvic junction
Last to canalize!
An infant is born with holoprosencephaly, short arms, and short legs. In utero, you noted little amniotic fluid. What is the most likely cause of death, and what was the original cause of this disease?
This is Potter Syndrome. Oligohydramnios –> compression of the fetus –>limb deformities, facial deformities, and pulmonary hypoplasia (cause of death).
This was the failure of the ureteric bud to form.
Cause of horseshoe kidney and major association
Kidneys failed to ascend due to entrapment by inferior mesenteric artery. Associated with Turner syndrome.
What substance makes the basement membrane of the glomerulus negatively charged?
Heparan sulfate
Describe the pathogenesis of nephrotic syndrome.
The charge barrier is lost (heparan sulfate fused with basement membrane gives it a negative charge), resulting in albuminuria, hypoproteinemia, generalized edema, and hyperlipidemia.
2 substances used to calculate GFR
Inulin
Creatinine
Equation for Effective Renal Plasma Flow
ERPF = clearance of PAH
Equation for Renal Blood Flow
RBF = RPF/(1-hct)
Equation for filtration fraction
GFR/RPF
Normal = 20%
Equation for filtered load
GFR x Plasma concentration
Equation for excretion rate
V x Urine concentration
What is the maximal serum glucose concentration at which glucose can be absorbed in the tubules?
350 mg/dL
How does constriction of the AFFerent arteriole affect GFR, RBF, and FF?
GFR and RBF both decrease.
No change in FF.
How does constriction of the EFFerent arteriole affect GFR, RBF, and FF>?
Increase GFR
Decrease RBF
Increase FF
How does dilation of the AFFerent arteriole affect GFR, RBF, and FF?
Increased GFR and RBF
No change in FF
How does dilation of the EFFerent arteriole affect GFR, RBF, and FF?
Decreased GFR
Increased RBF
Decreased FF
How does an increase in serum protein affect GFR, RBF, and FF?
Decrease GFR
NO change in RBF
Decrease in FF
How does ureter stone obstruction affect GFR, RBF, and FF?
Decrease GFR
No change in RBF
Decrease FF
How do ACE inhibitors affect GFR, RBF, and FF?
Decrease GFR
Increase RBF
DEcrease FF
How do NSAIDs affect GFR, RBF, and FF?
Decrease GFR
Decrease RBF
No change in FF
What is the role of the principle cells in the collecting duct/distal tubule?
Reabsorb H20 and Na+
Secrete K+
What is the role of the intercalated cells in the collecting duct/distal tubule?
Secrete H+ or HCO3-
Reabsorb K+
What are the 2 types of intercalated cells?
H+ secreting cells
HCO3- secreting cells
What effect does aldosterone have on the intercalated cells and principle cells of the collecting duct?
Stimulates intercalated cells to secrete acid.
Increases Na+ reabsorption and K+ secretion in principle cells.
What are the critical steps involved in excreting dilute urine?
Dilution of fluid in thick asc segment as solute is reabsorbed and water remains in the lumen (d/t impermeability of water in the thick asc limb). The absence of ADH renders the distal tubule and cortical collecting duct impermeable to water. Tubular fluid is diluted even more as solute is removed from the tubular fluid in the distal tubule and cortical collecting duct but water remains. Because of the low fluid osmolality in the collecting duct and the slight permeability of the medullary collecting duct to urea, urea enters the tubule from the medullary interstitium thereby keeping the osmolality of the medullary interstitium low.
Which segment of the renal tubule is responsible for concentrating urine?
Collecting duct
Which segment of the renal tubule is responsible for diluting urine?
Thick ascending limb
Where does water reabsorption occur in the Loop of Henle?
Thin descending limb
Which part of the renal tubule is always impermeable to water?
Thick ascending limb
Equation for plasma osmolality
2[Na+] + [glucose]/18 + [BUN]/2.8
6 things that shift potassium out of cells causing hyperkalemia
Low insulin Beta blockers Acidosis Digoxin Cell lysis (e.g. leukemia) ACE inhibitors
4 things that shift potassium into cells causing hypokalemia
Insulin
Beta agonist
Alkalosis
Cell creation proliferation (e.g. tumor)
Peaked T waves on EKG fits what electrolyte disturbance?
Hyperkalemia
Which electrolyte disturbance can cause decreased DTRs?
Hypermagnesemia
Which electrolyte disturbance can cause flattened T waves, U waves on EKG?
Hypokalemia
Causes of increased anion gap acidosis
Methanol Uremia DKA Propylene glycol INH or iron tablets Lactic acidosis (cyanide, CO, hypoxia Ethylene glycol Salicylates or shock
Defining features of nephritic syndrome
Proteinuria < 3.5 g/day
Hematuria with RBC casts in urine
HTN, oliguria, azotemia
Which glomerular disease would you suspect with IF showing granular pattern of immune complex deposition and LM showing diffuse capillary thickening?
Membranous glomerulonephritis
Most common nephrotic syndrome in adults
Membranous glomerulonephropathy
Which nephrotic syndrome is associated with hepatitis B and HCV?
Membranoproliferative glomerulonephritis Type I
Which glomerular disease would you suspect with EM showing subendothelial humps and tram-track apperance?
Membranoproliferative glomerulonephropathy
Which glomerular disease would you suspect with EM showing spiking of the GBM due to electron dense subepithelial deposits?
Membranous glomerulonephropathy
Glomerular histology reveals multiple mesangial nodules. This lesion is indicative of what disease?
Diabetic glomerulonephritis (these are Kimmelstiel-Wilson nodules).
3 glomerular diseases that decrease serum complement levels
Post-Streptococcal glomerulonephritis
Membranoproliferative glomerulonephritis type II
Lupus nephritis
Which glomerular disease would you suspect with deposition of IgG, IgM, IgA, and C3 in the mesangium?
IgA nephropathy
Which glomerular disease would you suspect with granular pattern of immune complex deposition and LM displaying hypercellular glomeruli?
Acute Post Streptococcal Glomerulonephritis
This disease is characterized by nephritis, deafness, and cataracts.
Alport Syndrome
A tumor in the kidney is found to be actually a hamartoma comprised of blood vessels, smooth muscle, and adipose tissue. What associated d/o does this patient most likeyl have?
Angiomyolipoma assoc with tuberous sclerosis
Rare presentation of renal cell CA
Left-sided varicocele due to involvement of left renal vein by CA blocking drainage of left spermatic vein –> varicocele.
4 paraneoplastic syndromes seen with Renal Cell CA
EPO (polycythemia)
Renin –> HTN
PTHrP (hypercalcemia)
ACTH
Pathogenesis of Renal Cell CA
Loss of VHL (3p) tumor suppressor gene which leads to increased IGF-1 (promotes growth) and increased HIF transcription factor (increases VEGF and PDGF)
Deletion of WT1
WT1 = tumor suppressor gene
This results in WAGR syndrome – Wilms Tumor + Aniridia + Genital abnormalities + mental/motor retardation.
WT1 is located at 11p13
Mutations of WT1
Denys-Drash syndrome – Wilms tumor + progressive renal (glomerular) dz + male pseudohermaphroditism
CHROMOSOME 11
Composition of Wilm’s Tumor
Malignant tumor comprised of blastema (immature kidney mesenchyme), primitive glomeruli and tubules, and stromal cells
Mutations in WT2 gene cluster particularly IGF-2
Beckwith Wiedemann syndrome – Wilms tumor + neonatal hypoglycemia + muscular hemihypertrophy + organomegaly (including tongue)
Imprinted genes at 11p15.5
4 risk factors for transitional cell CA
Smoking
Phenacetin (from acetaminophen)
Aniline Dyes
Cyclophosphamide
What are the classic features of drug-induced Acute Interstitial Nephritis?
Acute renal failure caused by NSAIDs, penicillin, diuretics
Fever, rash, eosinophilia*, azotemia
May progress to renal papillary necrosis
4 causes of renal papillary necrosis
Chronic analgesic abuse
DM
Sickle cell trait or disease
Severe acute pyelonephritis
In what disease are brown, granular casts seen in the urine?
Acute Tubular Necrosis
BUN:Cr ratio, FENa, and urine osmolarity in ATN
BUN:Cr < 15
FENa>2%
Urine osm<500 mOsm/kg
Which segments of the kidney tubule are particularly susceptible to ischemic damage?
Proximal tubule
Medullary segment of thick ascneding limb
Need a ton of ATP
Which segment of the renal tubule is most susceptible to nephrotoxic damage?
Proximal tubule
6 causes of nephrotoxicity
Aminoglycosides Heavy metals Myoglobinuria Ethylene glycol Radiocontrast dye Urate (e.g. tumor lysis syndrome -- > rapid death of cells -- > increased [uric acid])
What should you think of when you see oxalate crystals in the urine?
Ethylene glycol
BUN:Cr, FENa, and urine osmolality in prerenal azotemia
BUN:Cr > 15 (reabsorption of fluid and BUN ensues since low blood flow activates RAS, which increases reabsorption of H2O and a causing additional BUN to be reabsorbed)
FENa < 1% (tubular function remains intact)
URine osmolality > 500 mOsm/kg
Early post-renal azotemia values for BUN:Cr, FENa, and urine osmolality
BUN:Cr > 15
FENa < 1%
Urine osmolality > 500mOsm/Kg
Long-standing post-renal azotemia values for BUN:Cr, FENa, and urine osmolality
BUN:Cr < 15
FENa>2%
Urine osm < 500 mOsm/kg
3 associations with ADPKD
Berry aneurysm
Hepatic cysts
Mitral valve prolapse
Histological appearance of renal cell CA
Polygonal clear cell CA
Histological appearance of chronic pyelonephritis
Atrophic tubules containing eosinophilic proteinaceous material resemble thyroid follicles
Waxy casts in urine
When are fatty casts seen in urine?
Nephrotic syndrome
When are epithelial cell cast seen in urine?
Renal tubular damage
When are waxy casts seen in urine?
End stage renal disease
