Renal Review Flashcards
What artery prevents a horseshoe kidney from ascending in the abdomen?
IMA
What fundamental problem creates Potter sequence?
oligohydramnios
classically from B/L renal agenesis
What are the three stimuli that induce renin release?
- beta adrenergic stimulation
- increased Na+ sensed by the macula densa
- increased pressure in afferent arteriole
What cell type releases renin?
JG cells (juxtaglomerular)
Kidney embryology
pronephros, mesonephros, metanephros
Pronephros
week 4; then degenerates
Mesonephros
functions as interim kidney for 1st trimester; later contributes to male genital system
Metanephros
permanent; first appears in 5th week of gestation
Where does the ureteric bud come from? What does it give rise to?
Ureteric bud is derived from the caudal end of the mesonephric duct
Ureteric bud gives rise to the ureter, pelvises, calyces, collecting ducts
How and what does the metanephric mesenchyme form?
Metanephric mesenchyme interacts with the ureteric bud, which induces differential and formation of glomerulus through the DCT
What is the POTTER sequence?
P - pulmonary hypoplasia O - oligohydramnios (cause) T - twisted face T - twisted skin E - extremity defects R - renal failure (in utero)
What is the anatomical relationship between the ureters and the ureter artery? Vas deferens?
The ureter passes under the uterine artery and the vas deferens
How does constriction of the afferent arteriole affect GFR, RPF, and FF?
decrease GFR, decrease RPF, no change in FF
What is the FF?
FF = GFR/RPF
How does constriction of the efferent arteriole affect GFR, RPF, and FF?
increase GFR, decrease RPF, increase FF
What effect does angiotensin II have on the glomerulus?
angiotensin II preferentially constricts the efferent article -> increase GFR, decrease RPF, increase FF
What effect do prostaglandins have on the glomerulus? What inhibits this?
prostaglandins preferentially dilate the afferent arteriole -> increased GFR, increased RPF, no change in FF
NSAIDs inhibit this
How does dilation of the afferent article affect GFR, RBF, and FF?
increase GFR, increase RBF, no change in FF
How does dilation of the efferent arteriole affect GFR, RBF, and FF?
decrease GFR, increase RBF, decrease FF
How does an increase in serum protein affect the GFR, RBF, and FF?
decrease GFR, no change in RBF, decrease FF
How does a ureter stone obstruction affect the GFR, RBF, and FF?
decrease GFR, no change in RBF, decrease FF
How do ACE inhibitors affect the GFR, RBF, and FF?
decrease GFR, increase RPF, decrease FF
What is the 60,40,20 rule?
60% of body weight = total body water in L
40% of body weight = intracellular fluid
20% of body weight = extracellular fluid
How much of extracellular fluid is made up of plasma volume?
25%
A 40-year-old patient of yours weighs 100kg. What is her estimated plasma volume?
5L
20L x 0.25
At what glucose concentration is the tubular reabsorption of glucose maximized?
350 mg/dL
~160-200 -> start spilling glucose
What vitamin deficiency results from Hartnup disease?
niacin (Vit B3)
What are the symptoms of niacin deficiency?
pellagra 3D's diarrhea dermatitis dementia
What substances can be used to estimate GFR? What substitutes can be used to estimate renal plasma flow?
estimate GFR with inulin CL or Cr CL
estimate RPF with PAH CL
What is the equation for the renal clearance of any substance?
CL = urine conc. x urine flow rate/plasma conc
excretion rate = urine conc. x urine flow rate
Hartnup diesase
deficiency in transporter of neutral amino acids, such as tryptophan -> with no tryptophan, can’t make niacin -> 3 D’s of pellagra
What is filtered in the proximal tubule?
all glucose, all amino acids, 2/3 fluid, 2/3 electrolytes
What is reabsorbed in the first half of the proximal tubule? What kind of transporter do they use? What is it driven by?
glucose, amino acids, Pi, and lactate
Na+ cotransporter
driven by Na+ gradient, which is maintained by the Na+/K+ ATPase
How is bicarbonate reabsorbed in the first half of the proximal tubule?
HCO3- is broken down by carbonic anhydrase, and the H+, CO2, and H2O all cross into the tubular cell where carbonic anhydrase turns it back into HCO3- where it is transported via Na+ and Cl- cotransporters
What does TF/P < 1 signify?
reabsorbing more quickly than H2O
What does TF/P > 1 signify?
solute reabsorbed slower than H2O
If a substance filtered by the kidney has a TF/P > Cr, what does this mean?
the substance is being actively secreted by the kidney (such as PAH) because Cr and inulin are not reabsorbed, only filtered
What is reabsorbed in the second half of the proximal tubule?
Na+ and Cl-
How are organic anions secreted in the proximal tubule?
in exchange for alpha ketoglutarate
How are organic cations secreted in the proximal tubule?
in exchange for H+
What is true of the thin descending limb in relation to water/Na+ reabsorption?
impermeable to Na+
Thin descending limb is responsible for water reabsorption
H2O follows osmotic gradient into hypertonic medulla -> luminal fluid becomes more concentrated
What important cotransporter is located in the thick descending limb? What is true of H2O reabsorption here?
Na+/2Cl-/K+ cotransporter
TAL is impermeable to water
How are Ca2+ and Mg2+ reabsorbed in the TAL?
between cells
What is true of the concentration of the filtrate in the TAL?
TAL is impermeable to water, but the filtrate is still becoming less concentrated because all the cations are leaving
Where does PTH act in the kidney?
early distal tubule
What is true of H2O reabsorption in the early distal tubule?
impermeable to water
What two types of cells compose the collecting duct and the last segment of the distal tubule? What do they do?
- principal cells -> reabsorb H2O and Na+; secrete K+
2. intercalated cells -> secrete H+ or HCO3-; reabsorb K+
What are the two types of intercalated cells? What do they each do?
- alpha cells (A cells) -> secrete H+
2. beta cells (B cells) -> secrete HCO3-
What determines how much water is reabsorbed in the distal tubules and the collecting ducts?
ADH (vasopressin)
What drug inhibits aquaporins at the collecting tubule?
lithium
What class of diuretic directly affects the principal cells?
potassium-sparing diuretics
Inhibit epithelial Na+ channels in collecting tubules -> triamterene, amiloride
Aldosterone antagonists -> spironolactone & eplerenone
What effect does aldosterone have on the principal cells and intercalated cells of the collecting duct?
principal cells - reabsorption of Na+, secretion of K+
intercalated cells - stimulates secretion of H+
What causes K+ to shift out of the cells (hyperkalemia)?
low insulin (hyperglycemia) beta blockers acidosis digoxin cell lysis (leukemia)
What causes K+ to shift inside the cells (hypokalemia)?
insulin
beta-agonists
alkalosis
cell creation/proliferation
What is the treatment for hyperkalemia?
IV bicarb
beta-agonist (albuterol)
IV insulin + dextrose
IV Ca2+ to prevent arrhythmias (always do this first)
What electrolyte disturbance may result in central pontine myelinolysis if corrected too rapidly?
hyponatremia
What electrolyte disturbance results in peaked T waves?
hyperkalemia
What electrolyte disturbance results in tetany?
hypocalcemia
What electrolyte disturbance results in arrhythmias?
hyper/hypokalemia and hypomagnesemia
What electrolyte disturbance results in decreased tendon reflexes?
hypermagnesemia
What electrolyte disturbance results in flattened T waves and the presence of U waves on ECG?
hypokalemia
What are the diagnostic features of diabetes insipidus?
polyuria
polydipsia
very dilute urine
water deprivation test -> urine osmolarity does not increase
What do the results of the desmopressin test tell you in regards to diabetes insipidus?
If desmopressin results in concentrated urine -> central diabetes insipidus
If desmopressin fails to concentrate urine -> nephrogenic diabetes insipidus
What is the treatment for central DI?
ADH (desmopressin)
What is the treatment for nephrogenic DI?
HCTZ, indomethacin, amiloride
What is the treatment for Lithium-induced nephrogenic DI?
amiloride
What can cause SIADH?
ectopic ADH (small cell lung cancer)
CNS disorders/head trauma
Pulmonary disease (COPD, pneumonia)
Drugs (cyclophosphamide)
What are the normal gas values for pH, HCO3-, and pCO2?
pH = 7.35-7.45 HCO3- = 22-28 pCO2 = 35-45
What is the main cause of respiratory acidosis?
hypoventilation
Possible causes: airway obstruction and air trapping
lung Dz
weak respiratory muscles
opioids
What are the main causes of metabolic acidosis?
adding acid -> HAGMA; MUDPILES
Losing HCO3 -> diarrhea, renal tubular acidosis, spironolactone, acetazolamide
What is MUDPILES?
causes of HAGMA M - methylene glycol U - uremia D - DKA P - polyethylene glycol I - iron, isoniazid L - lactic acid E - ethylene glycol S - salicylates (aspirin) (late)
If pH goes up, what should HCO3- and pCO2 do?
pH and HCO3- move in the same direction
pH and pCO2 move in opposite directions
Henderson-Hasselbach: pH is relatively equal to HCO3-/pCO2
What is the main cause of respiratory alkalosis?
hyperventilation
Possible causes: psychogenic (panic attack), increased altitude, hypoxia (PE), aspirin toxicity (early)
What are possible causes of metabolic alkalosis?
excessive vomiting, diuretics, hyperaldosteronism
How do you calculate anion gap?
[Na+] - [Cl-] - [HCO3-]
What is RTA Type 1?
Distal renal tubular acidosis
defect in ability of alpha intercalated cells to secrete H+ -> no new HCO3- is generated -> metabolic acidosis
urine pH > 5.5
hypokalemia
increased risk for calcium phosphate kidney stones
(H+ prob, H = 1 letter, type 1)
What is RTA Type 2?
Proximal renal tubular acisois
defect in PCT HCO3- reabsorption -> increased excretion of HCO3- -> metabolic acidosis
urine pH < 5.5
hypokalemia
increased risk for hypophosphatemic rickets
(bi carb, bi = 2, type 2)
What is RTA Type 4?
Hyperkalemic renal tubular acidosis
impaired NH4+ excretion
hypoaldosteronism -> hyperkalemia -> decreased NH3 synthesis in PCT -> decrease NH4+ excretion
“Aldo” (4 letters, type 4)
Acute poststreptococcal glomerulonephritis
LM - glomeruli enlarged and hypercellular
IF - “lumpy bumpy” due to IgG, IgM, and C3 deposition along GBM and mesangium
EM - sub epithelial immune complex humps
Most frequently seen in children; occurs 2-4 weeks after group A strep infection of pharynx or skin; resolves spontaneously
Type 3 HS (immune complex damage)
presents with peripheral and periorbital edema, coca-cola colored urine with increased anti-DNase B and increase anti-streptolysin O Abs; decreased complement (C3) due to consumption
Rapidly progressive (cresenteric) glomerulonephritis
LM and IF - crescent moon shape consisting of fibrin and plasma proteins
poor prognosis; rapidly deteriorating renal function
Goodpasture syndrome
form of rapidly progressive glomerulonephritis
Type II HS; Abs to GBM and alveolar basement membrane -> linear IF
hematuria/hemoptysis
What are two other causes of RPGN besides good pasture, and what Abs would you see?
- granulomatosis with polynagiitis (Wegener) -> PR3-ANCA/c-ANCA (also affects lungs and upper respiratory tract)
- microscopic polyangiits -> MPO-ANCA/p-ANCA
can also be caused by lupus
Diffuse proliferative glomerulonephritis
often due to SLE
LM - wire looping of capillaries (wire lupus)
IF - granular
common cause of death in SLE
Anti-dsDNA Abs in mesangium and subendothelially
IgA nephropathy (Berger disease)
LM - mesangial proliferation
IF - IgA-based IC deposits in mesangium
renal pathology of henoch-schonlein purport
episodic gross hematuria that occurs concurrently with respiratory or GI tract infections
What is Henoch-Schonlein purpura?
palpable purpura on buttocks and legs
arthralgia
abdominal pain from intestinal hemorrhage
renal Dz (IgA nephropathy/Berger)
Alport syndrome
mutation in type 4 collage -> thinning and splitting of basement membrane X-linked dominant eye problems (lens dislocation), glomerulonephritis, sensorineural deafness (can't see, can't pee, can't hear a high C)
Membranoproliferative glomerulonephritis
type 1 - sub endothelial immune complex deposits with granular IF “tram track” appearance (due to basement membrane splitting)
MPGN is nephritic syndrome that often presents with nephrotic syndrome also
Can be caused by: Hep B, Hep C, lupus, and subacute bacterial glomerulonephritis
Which glomerular disease would you suspect with a linear pattern of IgG deposition on IF?
Goodpasture Dz
Which glomerular disease would you suspect with lumpy-bumpy deposits of IgG, IgM, and C3 in the mesangium?
post streptococcal glomerulonephritis
Which glomerular disease would you suspect with deposits of IgA in the mesangium?
IgA nephropathy/Berger Dz
Which glomerular disease would you suspect with Anti-GBM antibodies, hematuria, hemoptysis?
goodpasture
Which glomerular disease would you suspect with crescent formation in the glomeruli?
RPGN
Which glomerular disease would you suspect with wire loop appearance on LM?
diffuse proliferative glomeruloneprhitis
lupus nephritis
What are the defining features of nephrotic syndrome?
Have to have: proteinuria > 3.5, hypoalbuminemia, peripheral edema
Can also have: hyperlipidemia, hypercoagulable state, increased risk of infection
Minimal change disease
nephrotic syndrome
LM - normal glomeruli
EM - effacement of foot processes
Most common cause of nephrotic syndrome in children; often primary and triggered by recent infection, immunization, immune stimulus; excellent response to corticosteroids
Focal segmental glomerulosclerosis (FSGS)
nephrotic syndrome
LM - segmental sclerosis and hyalinosis
IF - may be positive for nonspecific focal deposits of IgM, C3, C1
EM - effacement of foot process similar to minimal change disease
most common cause of nephrotic syndrome in US (and African Americans and Hispanics); associated HIV; may progress to chronic renal disease
Membranous nephropathy
nephrotic syndrome
LM - diffuse capillary and GBM thickening
IF - nephrotic presentation of SLE
EM - “spike and dome” appearance with sub epithelial deposits
most common cause of primary nephrotic syndrome in caucasians
associated with SLE and multiple myeloma
may progress to chronic renal disease
Amyloidosis
LM - congo red stain shows apple-green birefringence due to amyloid in mesangium
Diabetic glomerulonephropathy
nephrotic
LM - mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions)
nonenzymatic glycosylation of GBM -> increase permeability, thickening
non enzymatic glycosylation of efferent arterioles (hyaline arteriosclerosis) -> increase GFR -> mesangial expansion
Most common cause of end-stage renal disease in the US
glomerular histology reveals multiple mesangial nodules. This lesion is indicative of what disease?
diabetic nephropathy
Kimmelstiel-Wilson nodules
most common nephrotic syndrome in children
minimal change disease
most common nephrotic syndrome in adults
FSGS
What glomerular disease would you suspect with EM: effacement of epithelial foot processes?
minimal change disease
nephrotic syndrome associated with HepB?
membranoproliferazive glomerulonephritis
nephrotic syndrome associated with HIV?
FSGS
What glomerular disease would you suspect with EM: sub endothelial humps and tram-track appearance?
membranoproliferative glomerulonephritis
What glomerular disease would you suspect with LM: segmental sclerosis and hyalinosis?
FSGN
What glomerular disease would you suspect with purport on backs of arms and legs, abdominal pain, and IgA nephropathy?
Henoch-Schonlein (IgA nephropathy/Berger Dz)
What glomerular disease would you suspect with EM: spiking of the GBM due to electron-dense sub epithelial deposits?
membranous nephropathy
What are causes of prerenal azotemia?
hypovolemia, portal HTN, CHF, cardiac arrest, NSAID use (excessive constriction of afferent arteriole)
What are the causes of intrinsic renal disease?
acute tubular necrosis, acute glomerulonephritis (RPGN, HUS), acute interstitial nephritis
What are the causes of post renal azotemia?
outflow obstruction (stones, BPH, neoplasia, congenital anomalies)
What is the urine Na+ in prerenal azotemia versus intrinsic renal disease?
prerenal azotemia - urine Na+ <20 mEq/L
intrinsic renal Dz - urine Na+ >40mEq/L
What is the fractional excretion of Na+ normally? in prerenal azotemia vs intrinsic renal Dz?
normal = 1%
prerenal azotemia = <1%
intrinsic renal disease = >2%
What is the BUN:Cr in prerenal azotemia vs intrinsic renal disease?
prerenal azotemia - BUN:Cr = >20:1
intrinsic renal disease - BUN:Cr = 10-15:1
What happens to potassium levels with kidney failure? phosphate levels?
hyperkalemia, hyperphophatemia
What are causes of acute tubular necrosis?
ischemia -> prolonged hypotension, sepsis, blood loss, surgery
nephrotoxins -> drugs (ahminoglycosides, cisplatin), radio contrast, myoglobin (rhabdomyolysis), synthetic cannbanioids
What would you see in the urine of someone with acute tubular necrosis?
muddy brown casts
Acute interstitial nephritis
Classic presentation -> fever, eosinophilia, azotemia, rash (diffuse, maculopapular) (FEAR)
most common cause is drugs -> NSAIDs, penicillins and cephalosporins, ciprofloxacin, rifampin, sulfonamides, diuretics, proton pump inhibitors, cimetidine, allopurinol
renal papillary necrosis
ischemia -> necrosis and sloughing of renal papillae
presentation: -> gross hematuria +/- flank pain, azotemia, hypertension
Causes: pyelonephritis, analgesics (acetaminophen, possibly NSAIDs), diabetes, sickle cell disease
Where could you see hyaline casts?
normal patients with concentrated urine
Where could you see RBC casts?
glomerular bleeding (glomerulonephritis, vasculitis)
Where could you see WBC casts?
tubular interstitial Dz, acute pyelonephritis
Where could you see epithelial cell casts?
acute tubular necrosis, acute interstitial nephritis, glomerulonephritis
Where could you see granular casts?
form from the breakdown of RBC or WBC casts; muddy brown casts
see in acute tubular necrosis
Where could you see fatty casts?
nephrotic syndrome
Where could you see waxy casts?
end-stage renal Dz
What changes would be seen in a basic metabolic panel in a patient with renal failure?
increased BUN & Cr
increase potassium
decreased Ca2+
decreased HCO3- (metabolic acidosis)
Autosomal dominant polycystic kidney disease (ADPDK)
typically presents in adulthood
mutation in the PDK1 genet (chromosome 16) or PKD2 (chromosome 4)
numerous B/L renal cysts with massive enlargement of the kidneys
Presentation:
-HTN
-progressive renal insufficiency -> ESRD
-hemorrhage into the cysts -> flank pain +/- hematuria
increased risk of kidney stones and UTI
associated with hepatic cysts, intracranial aneurysms, and mitral valve prolapse
Autosomal recessive polycystic kidney disease (ARPKD)
mutation in the gene PKHD1 (chromosome 6)
typically presents in infancy
B/L renal cysts, enlarge and echogenic kidneys
presentation:
-oliguria -> oligohydramnios -> potter sequence
-HTN, renal insufficiency, hepatomegaly
Autosomal dominant tubulointerstitial kidney disease
autosomal dominant inheritance
small, shrunken kidneys and interstitial fibrosis
rarely produces cysts int he renal medulla
progressive renal failure
Calcium oxalate stones
Associations: hypercalciuria, hyperoxaluria (ethylene glycol ingestion), Crohn’s Dz, hypocitraturia, Vit C ingestion
X-ray: radiopaque
Crystal shape: envelope
Prevention: thiazide diuretic
Struvite (NH4MgPO4) stones
Associations: urease-positive bacteria (proteus mirabilis (pH >/= 8), Klebsiella, S. saprophyticus)
X-ray: radiopaque staghorn calculi
Crystal shape: coffin lid
Prevention: eradicate infection
Cystine stones
Associations: hereditary impairment of cystine reabsorption -> cystinuria, presents in childhood
X-ray: radiolucent staghorn calculi
Crystal shape: hexagon
Prevention: alkalinize the urine
Uric acid stones
Associations: hyperuricemia and gout
X-ray: radiolucent
Crystal shape: rhombus/rosette
Prevention: allopurinol
Renal cell carcinoma
most common primary renal malignancy
arises from PCT in the cortex
risk factors: men ages 50-70, smoking, obesity, HTN
deletions on chromosome 3 (can be part of VHL)
Presentation:
- often asymptomatic; usually found incidentally
- classic triad: flank pain, hematuria, palpable abdominal mass
- paraneoplastic syndromes (polycythemia -> increased EPO, anemia, hypercalcemia -> PTHrP)
Pathology: solid tumor with clear cells full of lipids/carbs
Wilms tumor (nephroblastoma)
most common renal malignancy of early childhood (2-4 years)
presentation
- palpable abdominal/flank mass
- possible abdominal pain or hematuria
Mutation of tumor suppressor gene WT1 or WT2 (chromosome 11)
WAGR complex
- wilms tumor
- aniridia
- GU malformations (cryptorchidism or bicornate uterus)
- mental retardation
Transitional cell carcinoma (urothelial carcinoma)
most common malignancy of the urinary tract
can occur in the renal calyces or pelvis, ureters, and urinary bladder
Presentation: painless hematuria
Major risk factors: smoking, aniline dyes, naphthylamine dyes, cyclophosphamide (cancer Tx)
Squamous cell bladder cancer
smoking, chronic/recurrent UTIs, bladder stones, cyclophosphamide, schistosome haematobium
