Renal Flashcards
What is the divide of fluid compartments?
60 (TBW)-40 (ICF)-20 (ECF)-15 (interstitial)-5 (plasma)
% of total body weight
How is GFR estimated?
With inulin (freely filtered, not absorbed, not secreted) Estimate with creatinine (overestimate, secreted by tubules)
How is ERPF estimated?
With PAH (underestimate by 10%, both filtered and actively secreted, nearly all PAH entering kidney leaves first pass by excretion)
What effect do prostaglandins have on nephron?
Dilate afferent arteriole (increase RPF, GFR, FF stays constant)
What effect do NSAIDs have on nephron?
Inhibit prostaglandin production, prevent afferent arteriole dilation. Can induce acute renal failure.
What effect does angiotensin II have on nephron?
Constricts efferent arteriole (decreased RPF, increases GFR, FF increases)
What are some key roles of the PCT?
Brush border–carbonic anhydrase-bicarbonate recycling; reabsorbs all glucose/AAs/most ions; generates/secretes ammonia (buffer urine); 65-80% of Na reabsorbed
What are the hormones that act on the PCT? effects? Drugs?
PTH–inhibits Na/PO4 contransport–>phosphate excretion; Angiotensin II–stimultes Na/H exchange–>increases Na/H20/HCO3- reabsorption–>contraction alkalosis; Carbonic anhydrase inhibitors (acetazolamide) alkalinize urine.
What are some key roles of the thin descending loop of Henle?
Passive reabsorbs water via medullary hypertonicity. It is impermeable to Na+. Concentrating segment–>makes hypertonic urine.
What are some key roles of thick ascending loop of Henle?
Actively reabsorbs Na/K/Cl (via NaK2Cl transporter). Ion movement induces paracellular absorption of Mg and Ca (via K+ backleak). Impermeable to water–>dilutes urine as it ascends
What are drugs that act on thick ascending loop?
Loop diuretics (furosemide) act on NaK2Cl transporter.
What are some key roles of the early distal convoluted tubule?
Actively resorbs Na/Cl, makes urine hypotonic.
What hormones act on early distal convoluted tubule? What drugs?
PTH–increases Ca/Na exchange–>increasing Ca2+ reabsorption; Thiazide diuretics inhibit Na/Cl cotransporter
What are some key roles of the collecting tubule?
Reabsorbs Na in exchange for secreting K and H (regulated by aldosterone). Principal cell respond to aldosterone and ADH to regulate amount of water re-absorbed. Alpha/Beta intercalated cells secrete acid/bicarbonate respectively.
What hormones act on collecting tubule? Drugs?
Aldosterone on principal cells (inserts Na channel on luminal side–>increased Na reabsorption/potassium excretion; ADH acts at V2 receptor–>insertion of aquaporins on luminal side. Amiloride/triamterene inhibit luminal Na channels. Spironolactone/epleronone are aldosterone antagonists.
Where do fanconi syndrome, bartter syndrome, gitelmans and liddle syndrome occur?
FABulous Glittering Liquid: Fanconi (PCT) Bartters (thick ascending loop) Gitelman (DCT) Liddle (collecting tubule)
Increased excretion of nearly all amino acids
Fanconi syndrome (PCT reabsorption defect) can result in metabolic acidosis (proximal RTA)
Renal tubular defect resulting in hypokalemia, metabolic alkalosis with hypercalciuria
Bartter Syndrome (reaborptive defect in thick ascending loop), autosomal recessive, affects NaK2Cl cotransporter/like being on furosemide
Renal tubular defect resulting in hypokalemia, metabolic alkalosis, hypocalciuria
Gitelman Syndrome (autosomal recessive, resorptive defect in early DCT in Na/Cl contransporter), like being on thiazide diuretic
Renal tubular defect resulting in hypertension, hypokalemia, metabolic alkalosis, decreased aldosterone
Liddle Syndrome (autosomal dominant, increased Na re-absorption in collecting duct-mutant epithelial Na channel)
What is Tx for liddle syndrome?
Amiloride–K sparing diuretic that inhibits epithelial Na channel in collecting duct.
In PCT, describe Cl vs Na reabsorption. Which is faster?
Na re-absorption is faster. Cl concentration slower–relative concentration increases then plateaus.
What is ANP? Where does it come from/What does it do/MoA
Released from atria in response to increased volume. “check” against RAAS; relaxes vascular smooth muscle via cGMP, causing increased GFR and decreased renin. Natriuresis with no compensation. Net sodium and volume loss.
What triggers RAAS?
Decreased BP (sensed by JG cells which release renin). Decreased Na delivery sensed by macula densa. Increased sympathetic tone (B1 receptors).
What shifts potassium out of cell causing hyperkalemia?
DO Insulin LAB: Digitalis, HyperOsmolarity, Insulin deficiency, Lysis cells, Acidosis, Beta-adrenergic antagonist
Nausea, malaise, stupor, coma
hyponatremia
irritability, stupor, coma
hypernatremia
U waves, flat T waves, arrhythmias, muscle weakness
hypokalemia
Wide QRS, peaked T waves, arrhythmias, muscle weakness
hyperkalemia
Tetany, seizures, QT prolongation
hypocalcemia
Tetany, torsades de pointes
hypomagnesmia
Decreased DTRs, lethargy, bradycardia, hypotension, cardiac arrest, hypocalcemia
hypermagnesemia
Bone loss, osteomalacia
hypophosphatemia
Renal stones, metastatic calcifications, hypocalcemia
hyperphosphatemia
Defect in ability of alpha-intercalated cells to secrete H+
Type 1 RTA (distal, urine pH > 5.5); new HCO3 for plasma not generated–>nonAG metabolic acidosis. Hypokalemia. Increased risk for calcium phosphate kidney stones. Caused by amphotericin B toxicity, analgesic nephropathy, urinary tract congenital obstructions
Defect in proximal tubule HCO3- reabsorption
Type 2 RTA (proximal, urine pH < 5.5); HCO3 excretion is acidified by distal alpha-intercalated cells. Hypokalemia. Increased risk for hypophosphatemic rickets. Caused by Fanconi syndrome (Wilson disease), lead, aminoglycosides, carbonic anhydrase inhibitors, multiple myeloma light chains
Hypoaldosteronism, mild acidosis, hyperkalemia
Type 4 RTA (hyperkalemic, urine pH < 5.5); caused by hypoaldo/aldosterone resistance/K sparing diuretics. Hyperkalemia inhibits ammoniagenesis in PCT–>decreased buffering capacity and decreased ability to excrete H+ via urine.
How can you distinguish between Type 1/2/4 RTA?
Type 1/2 are hypokalemia. Type 4 is hyperkalemia. Type 1 has high urine pH > 5.5 (too distal to be acidified) and has severe acidosis.
Segmental sclerosis and hyalinosis, negative IF, effacement of foot process
Focal segmental glomerulosclerosis–most common cause of nephropathy in blacks and hispanics
diffuse capillaryand GBM thickening, granular (IC) complex deposition on IF, spike and dome appearance with sub-epithelial deposits
Membranous nephropathy–most common cause in caucasion adults
Normal glomeruli, negative IF, effacement of foot processes
Minimal change disease–most common in children
Congo red stain showing apple-green birefringence under polarized light
Amyloidosis (kidney most common organ involved), associated w/ chronic conditions (multiple myeloma, TB, rheumatoid arthritis)
subendothelial IC deposits with granular IF; “tram track” appearance due to GBM splitting caused by mesangial ingrowth
Mebranoproliferative glomerulonephritis Type 1. Ass with HBV, HCV, idiopathic.
intramembranous IC deposits “dense deposits”
Membranoproliferative glomerulonephritis Type 2. Associated with C3 nephritic factor (stabilizes C3 convertase to decrease serum C3 levels)
Mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis
Diabetic glomerulonephropathy (kimmelstiel wilson lesion). Nonenzymatic glycosylation of GBM increases permeability and thicking. Nonenzymatic glycosylation of efferent arterioles increases GFR–>mesangial expansion.
Glomeruli enlarged and hypercellular. “Starry sky” granular appearance “lumpy bumpy” along GBM and mesangium. Subepithelial IC humps.
Acute post-streptococcal glomerulonephritis (IgG IgM C3 deposition along GBM/mensagium. Type 3 hypersensitivity.
Crescent moon shape
RPGN. Crescents consist of fibrin and plasma proteins (C3b) with glomerular parietal cells, monocytes, macrophages. Goodpasture, Wegener, MPA.
Goodpasture syndrome
Type 2 hypersensitivity, antibodies to GBM and alveolar basement membrane, linear IF
Wegener (granulomatosis with polyangiitis)
PR3-ANCA/c-ANCA
Microscopic polyangiitis
MPO-ANCA/p-ANCA
Wire looping of capillaries, subendothelial and sometimes intramembranous ICs, granular IF appearance
Diffuse proliferative glomerulonephritis due to SLE or MPGN. Most common cause of death in SLE (nephrotic + nephritic). IgG, C3 deposition.
Mesangial proliferation, mesangial IC deposits, IgA based IC deposits in mesangium
IgA nephropathy (Berger disease), seen with Henoch-Schonlein purpura, presents/flares with URI/gastroenteritis
Thinning and splitting of glomerular basement membrane
Alport Syndrome–mutatation in Type 4 collage, X linked; glomerulonephritis/deafness/eye problems
Calcium kidney stones. Precipitate pH/Appearance/Tx
calcium phosphate: increased pH/envelope or dumbellshaped/Thiazides and citrate; calcium oxalate/low pH/caused by ethylene glycol, vitamine C abuse, Crohn’s Disease
Most common kidney stone presentation?
Patient with calcium oxalate stone; hypercalciuria, normocalcemia
Ammonium magnesium phosphate kidney stones
Struvite. increased pH. Coffin lids. Infection with urease + bugs (Proteus, Staphylococcus, Klebsiella hydrolyze urea to ammonia and alkalinize urine), staghorn caliculi–>UTI nidus; Tx infection and remove stone
Uric acid kidney stone
Radiolucent, decreased pH, rhomboid/rosettes; strong association with hyperuricemia (gout). Seen in leukemia, increased cell turnover. Tx by alkalinizing urine
Cystine kidney stone
Decreased pH. Hexagonal. Cystinuria, staghorn caliculi. Sodium nitroprusside test positive. Tx by urine alkalinization and hydration.
polygonal clear cells filled with accumulated lipids and carbohydrates
Renal cell carcinoma, proximal tubule cells, hematogenous spread to lung/bone, most common renal malignancy, Chromosome 3 deletion (VHL syndrome), paraneoplastic syndromes: EPO/ACTH/PTHrP; silent cancer often presents with mets
Well circumscribed mass with a central scar and large eosinophilic cells with abundant mitochondria without perinuclear clearing
Renal oncocytoma. Benign epithelial cell tumor
Wilms tumor
most common renal malignancy of early childhood, LOF mutations of tumor supressors WT1/2 on chromosome 11
Wilms tumor, aniridia, genitourinary malformation, mental retardation
Beckwith Wiedemann syndrome (WAGR)
Papillary growth lined by transitional epithelium with mild nuclear atypia and pleomorphism, painless hematuria
Transitional cell carcinoma, most common tumor of urinary tract, ass with Phenacetin/Smoking/Aniline dyes/Cyclophosphamide (Pee SAC)
Chronic irritation of bladder, painless hematuria
Squamous cell carcinoma of bladder–RFs include schistosoma haematobium (middle east), chronic cystitis, smoking, chronic nephrolithiasis,
Causes of cystitis? Most common? Sexually active young women? Ammonia scent? hemorrhagic?
E coli is most common. Staph saprophyticus in sexually active young women (e coli still more common). Proteus mirabilis has ammonia scent. Adenovirus has hemorrhagic.
Nitrite positive urine
Gram-negative (E coli, Klebsiella, proteus) infection
Sterile pyuria and negative urine cultures
urethritis by N gonorrhea or Chlamydia trachomatis
White casts in urine, fever, CVAT, striated parenchymal enhancement on CT
acute pyelonephritis
Lymphocytic infiltrate, eosinophilic casts within tubules
Chronic pyelonephritis caused by recurrent kidney stones, vesicoureteral reflux
eosinophilic pyuria, azotemia
Drug induced interstitial nephritis (tubulointerstitial nephritis) caused by drugs that act like haptens–>hypersensitivity (Type 3). Typically 1-2 weeks after drug started (diuretics, penicillins, sulfonamides, rifampin) but can occur months later
ARF after obstetric catastrophe (abruptio placentae) or septic shock
Diffuse cortical necrosis (combo of vasospasm and DIC)
In ischemia, which parts of nephron are most susceptible to injury?
PCT and thick ascending limb.
Causes of renal papillary necrosis
diabetes mellitus, acute pyelo, chronic acetaminophen use, sickle cell anemia/trait
Consequences of renal failure
MAD HUNGER: Metabolic acidosis, Dyslipidemia, Hyperkalemia/Hyperphosphatemia, Uremia, Na/H2O retention, Growth retardation, EPO failure, Renal osteodystrophy
ADPKD
PKD1 (ch16) PKD2 (ch4), death from CKD or hypertension. Berry aneurysms, mitral valve prolapse, benign hepatic cysts.
ARPKD
autosomal recessive. Congenital hepatic fibrosis, can cause potter syndrome via in utero renal failure,
Simple vs complex cyst
complex cyst is septated with solid components that require followup for risk of renal cell carcinoma
shrunken kidneys on US, tubulointerstitial fibrosis
medullary cystic disease, progressive inability to concentrate urine,
