Renal Flashcards
Which kidney is usually taken during liver donor transplantation and why?
Left Kidney; because it has a longer renal vein
Where is the macula densa located?
Distal convoluted tubule
Where are JG cells located?
Afferent arteriole
ureterovesicular junction
narrowest part of the ureter; common site for stones to get stuck
nephrocalcinosis
calcification of the medullary periods; assoc w/hyperparathyroidism
passage of ureters in relation to the uterine artery and ductus deferens?
ureters pass under uterine artery and under ductus deferens (retroperitoneal)
- ->”water passes under the bridge”
- water=ureters
- bridge=uterine arteries and ductus deferens
60-40-20 rule (of total body weight):
60% = total body water 40% = ICF 20% = ECF
How to measure plasma volume?
radiolabeled albumin
how to measure extracellular volume?
Inulin
Glomerular Filtration barrier is composed of:
- Fenestrated Capillary Endothelium
- Fused basement membrane
- Epithelial layer
- What is each one’s role?
- Composition?
- What is lost in nephrotic syndrome? What’s the result?
- What is lost in Minimal Change disease?
- Fenestrated Capillary Endothelium:
- Size barrier
- Fused basement membrane:
- negative Charge barrier
- has heparin sulfate
- lose charge barrier in neprhotic syndrome; get: albuminuria, hypoproteinemia, generalized edema, hyperlipidemia
- Epithelial layer:
- consists of podocyte foot processes
- lose podocytes in MCD
What substances can be used to measure GFR?
- Inulin or Creatinine Clearance.
- Inulin is freely filtered, but is neither reabsorbed nor secreted.
- BUT: Creatinine clearance slightly overestimates GFR, b/c creatinine is moderately secreted by renal tubules
What substance can be used to meausre the ERPF (Effective Renal Plasma Flow)?
-PAH clearance; b/c all PAH entering kidney is secreted
ERPF vs true RPF?
ERPF underestimates true RPF by about 10%
RBF =?
RBF = RPF/(1-Hct)
Normal Filtration Fraction =?
20%
Effect of prostaglandings on kidney:
Effect of NSAIDs on kidney?
Prostaglandins dilate afferent arteriole –> so, get:
- increased RPF
- increased GFR
- constant FF
- NSAIDs–>inhibit PGs –> get constriction of Afferent Arteriole:
- decreased RPF
- decreased GFR
- constant FF
Effect of Angiotensin II on kidneys?
Acts on Efferent Arteriole; constricts EA:
- decreased RPF
- increased GFR
- increased FF
Effect of ACE-inhibitors on kidneys?
ACE-inhibitors–> inhibit Ang II –> dilate Efferent Arteriole:
- increased RPF
- decreased GFR
- decreased FF
*so, may have increased Creatinine levels in blood (b/c decreased GFR, and Creatinine clearance is a measure of GRF, so decreased Creatinine clearance –> more Creatinine in blood)
What is Creatinine in urine a measurement of?
Glomerular Filtration Rate
Where in kidney is glucose normally reabsorbed?
Proximal tubule by Na+/glucose cotransport
At what plasma glucose levels does glucosuria begin (threshold)?
At what glucose levels is Tm (all transporters fully saturated)?
- see glucosuria at plasma glucose levels of 160-200
- all transporters are fully saturated (Tm) at plasma glucose levels = 350 mg/dL
Hartnups disease:
deficiency of neutral amino acid (tryptophan) transporter in proximal tubule; so, can’t reabsorb tryptophan
-results in pellagra (niacin/B3 deficiency; b/c B3 is derived from Tryptophan)
Where in nephron is glucose, AAs, and most of bicarbonate, Na, Cl, and water reabsorbed?
Early proximal tubule
Where in kidney is there “isotonic absorption”?
Early proximal tubule
Which part of nephron generates and secretes ammonia?
Early proximal tubule
Which part of the nephron is the most hypertonic/concentrated urine?
Thin descending limb of loop of Henle
–>impermeable to sodium; passively reabsorbs water b/c sodium can’t get in, so the medulla is hypertonic –> water leaves nephron into medulla, making urine more concentrated.
Which part of nephron is impermeable to water?
Thick ascending limb of loop of Henle
Which part of nephron is the “diluting segment”, where urine has the lowest osmolality?
Early distal convoluted tubule
Where are Na, K, and Cl actively reabsorbed and Mg and Ca indirectly reabsorbed?
Thick ascending limb of loop of Henle (this is the part that is also impermeable to H20; so, have reabsorption of electrons + water cannot leave (nor enter) –> so this portion of the loop makes the urine less concentrated as it ascends; eventually, it has the lowest osmolality at the early distal convoluted tubule)
Where in nephron does PTH act?
Early proximal tubule: PTH inhibits Na/P cotransport –> get increased phosphate excretion
Early distal convulted tubule: increased Ca/Na exchange –> get increased Ca reabsorption
Where in nephron does Angiotensin II act?
Early proximal tubule –> AT II stimulates Na/H exchange –> increased Na and water reabsorption
ADH vs Aldosterone:
ADH primarily regulates osmolarity; but, also responds to low blood volume, when necessary (b/c low volume takes precedence over osmolarity)
Aldosterone primarily regulates blood volume
Juxtaglomerular Apparatus:
- JG cells in AA
- Macula densa = Na sensor –> in distal convoluted tuule
*JGA defends GFR via the RAAS system: JG cells secrete renin in response to low renal BP, low Na delivery to distal tubule, and increased sympathetic tone (beta-1 receptors)
Which cells secrete renin?
JG cells (in Afferent Arteriole)
How may NSAIDs cause acute renal failure?
NSAIDs inhibit the renal production of prostaglandins, which normally keep the afferent arterioles vasodilated and maintain GFR
-NSAIDS–>constrict AA–>decrease both RPF and GFR
4 endocrine functions of the kidneys:
1) Erythropoietin production
2) 1,25-(OH)2-vitamin D production –> in proximal tubule; convert vit D to active form
* Note: vitamin D–> increases Ca and P absorption in intestines
* note: PTH acs directly on the kidney to reabsorb P, but not reabsorb P
* note: PTH also stimulates formation of active Vitamin D, which increases absorption of both Ca and P in intestines!
3) Renin –> beta-1 effect
4) Prostaglandins –> vasodilates AA to increase GFR
Hormones that act on the kidney:
1) ANP
2) PTH
3) AT II
4) Aldosterone
5) ADH
ANP = Atrial Natriuretic Peptide
- secreted in response to increased atrial pressure (ie high preload or high blood volume)
- causes: increased GFR and increased Na filtration, but not increased Na reabsorption
- NET effect: Na+ loss and volume loss
PTH:
-secreted in response to low plasma Ca, high plasma P, or low plasma vitamin D
-causes: increased Ca reabsorption in DCT, decreased P reabsorption in PCT, and increased vit D production
Also causes: increased Ca and P absorption from gut (b/c of effects of Vitamin D)
AT II = Angiotensin II
-Causes EA constriction –> decreased RPF, increased GFR and increased FF; also get compensatory Na reabsorption in proximal and distal nephron (b/c goal is to increase BP!)
Aldosterone:
- secreted in response to low blood volume (via Ang II) and elevated plasma K
- causes: increased Na reabsorption, increased K secretion, and increased H secretion
ADH/Vasopressin
- secreted in response to elevated plasma osmolarity and decreased blood volume
- causes increased # of water channels and increased water reabsorption
6 situations that shift K+ out of cells –> causing HYPERkalemia:
- decreased insulin (like in DKA)
- beta-blockers
- acidosis/severe exercise
- hyper-osmolarity
- digitalis
- cell lysis
4 situations that shift K+ into cells –> causing HYPOkalemia:
- insulin
- beta-agonists (ie albuterol)
- alkalosis
- hypo-osmolarity
Too rapid correction of Hyponatremia?
get Central Pontine Myelinosis (irreversible; acute paralysis, dysarthria, dysphagia, diplopia, loss of consciousness)
U waves on ECG, flattened T waves, arrhythmias and paralysis?
low serum K+
Peaked T waves, wide QRS, arrhythmias:
high serum K+
effects of low serum Ca?
- Tetany
- Neuromuscular irritability
effects of high serum Ca?
“stones, bones, groans, moans”
- delirium
- renal stone
- abdominal pain
effects of low serum Phosphate?
bone loss and osteomalacia
effectsof high serum Phosphate?
renal stones, metastatic calcifications
Compensatory response to respiratory acidosis or alkalosis?
- -> kidneys!
- if respi acidosis –> kidneys increase renal HCO3 reabsorption
- if respi alkalosis –> kidneys decrease renal HCO3 reabsorption
–> these compensatory mechanisms take time, are delayed! (unlike compensation of metabolic acidosis/alkalosis, which can be done quickly by breathing more/less!)
Causes of metabolic acidosis with a high anion gap?
MUDPILES!
- Methanol (formic acid)
- Uremia
- DKA
- Paraldehyde or Phenformin
- Iron tablets or INH (Isoniazid)
- Lactic acidosis, hypoxia
- Ethylene glycol (oxalic acid)
- Salicylates (ie aspirin)
Causes of normal anion gap metabolic acidosis?
- Diarrhea
- Glue sniffing
- Renal tubular acidosis (RTA)
- Hyperchloremia
Causes of Respiratory alkalosis:
- Hyperventilation (early high-altitude exposure)
- Initially after aspirin ingestion (then becomes anion-gap metabolic acidosis)
Causes of metabolic alkalosis with compensation (Hypoventilation):
- Diuretics
- Vomiting
- Antacids
- Hyperaldosteronsim (increases H+ secretion)
***These are all cases where get rid of acid!
Causes of Respiratory Acidosis:
- any time can’t get rid of CO2!
- airway obstruction
- acute lung disease
- chronic lung disease
- opiods, narcotics, sedatives
- weakened respiratory muscles
How to calculate anion gap:
Anion gap = Na - (Cl + HCO3) = Na - Cl - HCO3
3 types of RTA (Renal Tubular Acidosis)
- Type 1 = “distal”: defect in CT’s ability to excrete H+ (so increased urinary pH)
- associated with hypokalemia and risk for calcium kidney stones
- Type 2 = “proximal”: defect in PT HCO3 reabsorption
- associated with hypokalemia and hypophosphatemic rickets
- Type 3 = “hyperkalemic”: Hypoaldosteronism or lack of Ct response to aldosterone
- associated with hyperkalemia and can’t excrete ammonium in PT
- decreased urinary pH d/t decreased buffering capacity
RBC casts
Glomerulonephritis
-Also: ischemia, malignant HTN
WBC casts
- Acute pyelonephritis
- Tubulointerstitial inflammation
- Also: transplant rejetion
“muddy brown”/Granular casts
Acute tubular necrosis
Waxy casts
advanced/chronic renal disease
Hyaline casts
nonspecific
What does the presence of casts in urine indicate?
- ->casts indicate that hematuria/pyuria is of renal origin
- so, with bladder cancer, kidney stones –> have hematuria, but no casts
- with acute cystitis –> have pyuria (WBCs), but no casts
Nephritis vs Nephrotic syndromes:
- Nephritic–> Inflammatory; hematuria and RBC casts in urine
- ->have azotemia (increased BUN and increased Creatinine), oliguria, HTN (d/t salt retention), and mild proteinuria ( Proteinuria (>3.5g/day), frothy urine, hyperlipidemia, fatty casts, edema
- ->associatd with thromboemolism and increased risk of infection (b/c loss of immunglobulins)
***lose charge barrier (fused basement membrane) of glomerular filtration barrier in nephrotic syndrome
Lumpy bumby appearance of glomeruli on LM?
Acute PSGN
child with peripheral and periorbital edema, dark urine, elevated anti-ASO, elevated anti-DNAse B, decreased C3 and total complement levels
Acute PSGN
supepithelial humps on EM
Acute PSGN
Wegener’s vs Goodpasture
both cause Crescentic/RPGN
- ->Goodpastures only affects lung and kidneys (hematuria + hemoptysis)
- ->Wegener’s: c-ANCA; and can also affect upper airways, so may present with sinusitis, nasal perforation, as well as hematuria, hemoptysis
subendothelial and maybe intramembranous IgG-based immune complexes, often with C3 deposition seen on EM
Diffuse Proliferative GN
wire looping of capillaries on LM
Diffues Proliferative GN
–>see in SLE or MPGN (Membranoproliferative GN)
most common cause of death in SLE?
- Diffuse Proliferative GN (associated with anti-dsDNA marker)
- -> can present as nephrotic and nephritic syndrome concurrently
Nephritis + IgA immune complexes in mesangium + URI or acute gastroenteritis
Berger’s disease = IgA nephropathy
–>related to Henoch-Schonlein disease (vasculitis, also have IgA immune complexes)
Nephritis with mutation in type IV collagen –> split Basement membrane, X-linked
Alport syndrome = “can’t see, can’t pee, can’t hear”
–>have nerve disorders, ocular disorders, deafness
most common glomerular disease in HIV pts?
Focal Segmental Glomerulosclerosis
Most common cause of adult nephrotic syndrome?
Membranous GN
Spike and dome appearance on EM with subepithelial deposits
Membranous GN
Foot process effacement on EM
Minimal Change Disease
Treatment for Minimal Change Disease?
Corticosteroids
Selectively lose albumin, but not globulins:
Minimal Change Disease
What conditions are associated with nephrotic syndrome caused by Amyloidosis (have amyloid deposits in mesangium)?
Associated w/chronic conditions:
- multiple myeloma
- TB
- Rheumatoid arthritis
Tram-track appearance on LM with GBM splitting
Type I Membranoproliferative GN
Glomerulonephritis associated with HBV, HCV
Type I Membranoproliferative GN
“dense deposits” on EM
Type II Membranoproliferative GN
Pathology behind Diabetic Glomerulonephropathy:
Non-enzymatic glycosylation of GBM –> increased permeability and thickening
Also: nonenzymatic glycosylation of efferent arterioles –> increased GFR –> mesangial expansion
***see GBM thickening on LM! and mesangial expansion..
Kimmelstein-Wilson lesion:
-Diabetic glomerulonephropathy
Most common type of kidney stones?
Calcium (Calcium oxalate, Calcium phosphate, or both)
Calcium kidney stones:
- ph they precipitate at?
- x-ray appearance?
- what conditions may cause them?
- most common type of kidney stones; may be calcium oxalate or calcium phosphate or both
- precipitate at neutral or decreased pH
- radiopaque on x-ray
- conditions that cause hypercalcemia (like cancer, elevated PTH) can lead to hypercalciuria and stones
- may get oxalate crystals from ethylene glycol (antifreeze) or vitamin C abuse
Vitamin C abuse may lead to what type of kidney stones?
Calcium oxalate crystals
Ethylene glycol (anti-freeze) may lead to what kind of kidney stones?
Calcium-oxalate kidney stones
Staghorn calculi
Get these with ammonium-magnesium-phosphate kidney stones (caused by infection with urease-positive bugs…)
Ammonium-Magnesium-Phosphate kidney stones:
- ph precipitate at?
- X-ray appearance?
- Caused by?
- precipitates at elevated pH
- radio-opaque or radiolucent on xray
- caused by infection with urease positive bugs (ie proteus, klebsiella) that form ammonium cation that binds to Mg and P and forms stones
Uric acid kidney stones:
- precipitates at what pH?
- x-ray appearance?
- associated with?
- low pH
- radio-lucent
- assoc with hyperuricemia (ie gout); also diseases with high cell turnover, like leukemia
Cystine kidney stones:
- precipitate at what pH?
- x-ray appearance?
- causes?
- treatment?
- low pH
- radioopaque
- usually secondary to cystinuria
- treat by alkalinizing urine
What causes hydronephrosis?
Results for complete or partial obstruction of urinary tract
polygonal clear cells on histology
Renal cell carcinoma
–>cells are filled with lipids and carbohydrates
2 main sites of metastasis of renal cell carcinoma?
lung and bone
Most common renal malignancy of childhood?
Wilm’s tumor = Nephroblastoma
–>2-4 yo
huge, palpable flank mass and/or hematuria in child 2-4 yo?
Wilm’s tumor = Nephroblastoma
WAGR complex:
- Wilm’s tumor
- Aniridia (no iris)
- Genitourinary malformation
- mental-motor Retardation
- d/t deletion on chromosome 11
- often obese too
Squamous cell cancer of the bladder associated with?
Schistosomiasis
Painless hematuria, no casts:
Bladder cancer –> Transitional cell carcinoma
most common tumor of urinary tract system?
Transitional cell cancer (can occur in renal calyces, pelvis, ureters, bladder…)
Problems associated with Transitional Cell Carcinoma?
Pee SAC:
- Phenacetin (analgesic; acetaminophen=phenacetin derivative)
- Smoking
- Aniline dyes
- Cyclophosphamide (alkylating agent, used to treat cancers/immunosuppressant)
Histology of Acute vs Chronic Pyelonephritis?
- Acute –> neutrophil infiltration ito renal interstitium
- Chronic –> lymphocytic invasion with fibrosis
Thyroidization of kidney (eosinophilic casts in tubules)
Chronic pyelonephritis
fever + rash + hematuria + flank tenderness 1-2 weeks after taking certain drugs
Drug-induced / Acute Interstitial Nephritis
What causes Acute Interstitial Nephritis?
- DRUGS!:
- NSAIDs
- diuretics
- penicillins
- sulfonamides
- rifampin
- get interstitial renal inflammation, pyuria, azotemia, 1-2 weeks after taking meds
- also: fever, rash, hematuria, flank pain
Most common cause of acute renal failure in hospital?
Acute tubular necrosis
–>can be reversible, but fatal if left untreated
3 stages of Acute Tubelar Necrosis:
1) Inciting event(ie renal ischemia from shock, sepsis, or crush injury like myoglobinuria)
2) Maintenance phase –> oliguric; 1-3 weeks; risk of hyperkalemia; have muddy brown casts
3) Recovery –> polyuric, risk of hypokalemia; get decreased levels of BUN and serum creatinine
Definition of Acute Renal Failure = Acute Kidney Injury:
–>abrupt decline in renal function with elevated Creatinine and elevated BUN (so, Azotemia) over several days
Pre-Renal Azotemia: Acute Renal Failure
- -> not enough blood to kidney: so decreased RBF (ie hypotension) –> decreased GFR
- Na, H20, and urea are retained by the kidney (not excreted in urine) to conserve volume
- So: get elevated BUN/Creatinine ratio
Intrinsic Renal: Acute Renal Failure
usually d/t acute tubular necrosis or ischemia/toxins
- ->have necrosis or something that obstructs the tubule, so get fluid backflow across the necrotic tubule –> decreases GFR
- Also: BUN reabsorption impaired –> decreased BUN/Creatinine ratio
Postrenal: Acute Renal Failure
- ->d/t outflow obstruction (ie stones, BPH, neoplasia, congenital anomalies)
- ->only have bilateral obstruction with postrenal…
2 most common causes of chronic renal failure?
- Hypertension
- Diabetes
Renal Osteodystrophy:
- get this with chronic renal failure
- failure of vitamin D hydroxylation –> Calcium wasting and Phosphate retention –> secondary hyperparathyroidism
- causes subperiosteal thinning of bones
Autosomal dominant mutation in PKD1 or PKD2 gene?
ADPKD
What conditions are associated with ADPKD?
- polycystic liver disease
- berry aneurysms
- mitral valve prolapse
bilaterally enlarged kidneys + oligohydramnios + small/absent bladder in-utero (by US)?
–>ARPKD
Thin, nonenhancing, cortical, fluid filled cysts in kidney?
Benign simple cysts; incidental finding in elderly
***don’t confuse these with medullary cystic disease –> medullary cysts, fibrosis, progressive renal insufficiency, can’t concentrate urine, small kidney –> poor prognosis!
Osmotic diuretic
Mannitol
–>increased tubular fluid osmolarity, so helps excrete free H2O)
Diuretic with Pulmonary edema side effect?
Mannitol
Diuretic used to treat altitude sickness?
Acetazolamide
- ->Carbonic anhydrase inhibitor –> helps get rid of HCO3
- ->can also be used for glaucoma
- ->may cause hyperchloremic metabolic acidosis….
Diuretics used to treat Glaucoma?
- Acetazolamide –> for long-term treatment
- Mannitol –> for emergencies
Diuretic of choice to treat edematous states (ie CHF, cirrhosis, nephrotic syndrome, pulmonary edema…)?
Furosemide (loop diuretic)
Side effects of Furosemide?
“OH DANG”
- Ototoxicity
- Hypokalemia
- Dehydration
- Allergy (sulfa)
- Nephritis (Acute Interstitial Nephritis)
- Gout
NSAIDs inhibit the effect of which type of diuretic? Why?
NSAIDs inhibit Furosemide
–>Furosemide/Loop diuretics stimulate Prostaglandin release; so, if give NSAIDs + loop diuretics together –> get decreased diuretic response
Drugs that are both Ototoxic and Nephrotoxic?
- Aminoglycosides
- Loop diuretics (Furosemide)
- Cisplatin and Carboplatin (anti-cancer drugs)
- Vancomycin
Ethacrynic acid
Loop diuretic, works the same way as Furosemide. But, not a sulfonamide (unlike furosemide)
–>give to pts with sulfa allergy
K+ sparing diuretics:
“K+ STAES”
- Spironolactone
- Triamterene
- Amiloride
- Eplerenone
Which diuretics lead to increased urinary K+ (decreased blood K+)?
–>all, EXCEPT for K+sparing
Which diuretics may lead to decrease pH –> acidemia?
- ->Carbonic anhydrase inhibitors
- ->K+ sparing diuretics
Which diuretics may lead to increase pH –> alkalemia?
- ->Loop diuretics
- ->Thiazides
Why should ACE-inhibitors NOT be given to pts with renal artery stenosis?
- ->pts with renal artery stenosis depend on EA constriction to maintain renal perfusion; but, ACE inhibitors cause EA dilation –> decreased GFR, decreased FF
- ->so, ACE inhibitors can cause acute renal failure or complicate an existing renal disease in pts with renal artery stenosis
