Renal Flashcards
What part of the nephron is most susceptible to toxin damage?
The PCT
Acute tubular necrosis
What part of the nephron has a brush border?
PCT
For maximal reabsorption
Potter Syndrome
Babies can’t pee in utero
P: pulmonary hypoplasia O: oligohydramnios T: Twisted face T: twisted skin E: extremity defects (club feet) R: renal failure in utero
**Caused by ARPKD, renal agenesis, obstructive uropathy
What is the hallmark of glomerular injury?
Proteinuria
What passes easier through the glomerulus: positive or negative charged particles?
Positive: the golmerular basement membrane carries a negative charge, which repels negatively charged particles
NSAID effects on kidney
Constriction of the afferent arteriole
Dec GFR
Dec RBF
ACE inhibitor effects on kidney
Dilation of the efferent arteriole
Dec GFR
Inc RBF
Ang II effects on the kidney
Constriction of the efferent arteriole
Inc GFR
Dec RBF
Where is glucose reabsorbed? How much is excreted in the urine?
100% is reabsorbed in the PCT
There should be no glucose in the urine – presence indicates diabetes
What section of the nephron is most permeable to water? Which sections are impermeable?
PCT = high permeability
TAL and DCT = no permeability
Electrolyte defect consequences of diabetes insipidus?
High excretion of water in the urine causes hypernatremia
Due to a problem with ADH (dec secretion or inc resistance)
What stimulates the release of renin from the JGA cells?
Low blood volume by baroreceptors
Low flow (dec Na in tubules)
Inc sympathetic activity (B1)
Acidosis and alkalosis effects on potassium levels
Acidosis causes hyperkalemia: H+ moves into cells to correct pH and K+ moves out of cells to maintain electroneutrality
Alkalosis causes hypokalemia: H+ moves out of cells to correct pH and K+ moves into cells to maintain electroneutrality
Insulin effects on potassium levels
Causes hypokalemia
Insulin activates Na/K ATPase which pumps K+ into cells
EKG changes: Hypokalemia
U waves
Flattened T waves
EKG changes: Hyperkalemia
Peaked T waves
What happens if you rapidly correct hypernatremia?
High to low your brain will blow
Cerebral edema
What happens if you rapidly correct hyponatremia?
Low to high your pons will die
Osmotic demyelination
Fanconi syndrome
PCT
Generalized reabsorptive defect: inc excretion of amino acids, glucose, HCO3 and phosphate
Bartter syndrome
TAL of loop of henle
Defect in NKCC2 cotransporter
Causes hypokalemia and metabolic alkalosis
Gitelman syndrome
DCT
Defect in Na/Cl cotransporter
Liddle syndrome
Collecting duct
Gain of function in ENaC channels
Causes hypokalemia and metabolic alkalosis
Treat with Amiloride
Black licorice effects
Contains glycyrrhetic acid – blocks the activity of 11B hydroxysteroid dehydrogenase
(normally 11B OHsteroid dehydrogenase breaks down cortisol before it can act on the mineralcorticoid receptor) – blocked activity causes inc mineralcorticoid receptor activity
Hypernatremia
Hypokalemia
Inc BP
Metabolic alkalosis
Metabolism of glutamine
In the PCT
Produces NH4 and HCO3 –> allows fro excretion of H+
Calculate anion gap
AG = Na - (Cl + HCO3)
Normal range: 8-12
Causes of metabolic acidosis with elevated anion gap
MUDPALES
Methanol Uremia DKA Propofol Alcoholic ketoacidosis Lactic acidosis Ethylene Glycol Salicylates
Patient has respiratory alkalosis and metabolic acidosis wit elevated anion gap…
Salicylate overdose
Acid base: Opioid overdose
Respiratory acidosis
Acid base: pulmonary embolism
Respiratory alkalosis
Acid base: spironolactone
Metabolic acidosis
Acid base: Loop/thiazide diuretics
Metabolic alkalosis
Acid base: High altitude/hypoxemia
Respiratory alkalosis
Differential for intraabdominal tumor in children
Nephroblastoma (Wilms tumor): Kidney
Neuroblastoma: adrenal gland
Hepatoblastoma: liver
Muddy brown casts in urine = ?
Caused by what?
What portions of the nephron are particularly susceptible?
Acute Tubular necrosis
Caused by ischemia or toxicity
Ischemia: PCT and TAL of loop of henle
Toxicity: PCT
What can rhabdomylolysis do to the kidney?
Acute Tubular Necrosis
myoglobin is nephrotoxic
How does anemia occur in patients with renal disease?
Decreased production of EPO by the kidney
Nephrotic syndrome characterisitcs
Podocyte dysfunction
- Proteinura >3 g
- Hypoalbuminemia
- Edema
- Hyperlipidemia with lipiduria
Podocyte effacement seen on Electron Microscopy
Minimal change disease
Most common cause of nephrotic syndrome in kids
Minimal change disease - may be triggered by a recent infection, immunization or other immune stimulus
EM shows thickening of glomerular capillary loops with small spikes on the glomerular basement membrane
Membranous Nephropathy – immune complex deposition disease
Nephrotic presentation of SLE, can be associated with drugs or infections (hepatitis)
Glomerular nodules and hyalinosis of arterioles seen on LM
Diabetic nephropathy
Kimmelstiel-Wilson lesions
Starry night appearance on immunofluorescence
Post-strep glomerulonephritis (IgG, IgM, and C3)
Large hump like subepithelial deposits on EM
Post-strep glomerulonephritis (IgG, IgM, and C3)
What is the most common cause of glomerulonephritis?
IgA nephropathy
Usually presents following a URI
Mesangial immune deposits
IgA nephropathy
Tram track appearance of GBM
Membranoproliferative Glomerulonephritis
which nephritic syndrome is associated with Hep B or Hep C
which nephrotic syndrome is associated with hep B or hep C?
Membranoproliferative Glomerulonephritis
Membranous Nephropathy
Wire looping of capillaries seen on LM
Diffuse Proliferative Glomerulonephritis: SLE
“Wire lupus”
Full house immunofluorescence
SLE: Diffuse Proliferative Glomerulonephritis
IgM, IgG, IgA C3, C1q, deposition
What do horseshoe kidneys get trapped on during ascent?
Inferior mesenteric artery
Acute interstitial nephritis:
Causes and presentation
Acute interstitial renal inflammation
→ associated with drugs (PCNs, NSAIDs, Thiazides, Rifampin, sulfonamides, diuretics, etc)
patients present with fever, skin rash, and eosinophilia
What part of the nephron causes alkalinization of the urine when acted on by an antidiuretic?
PCT: Acetazolamide
Hartnup disease
Autosomal recessive
Deficiency of amino acid transporters in the PCT and in enterocytes – increased excretion and reduced absorption of amino acids
Deficiency of tryptophan causes niacin deficiency and symptoms of pellagra – dermatitis, diarrhea, and dementia
Most common kidney stone presentation
calcium oxalate stone in a patient with hypercalcuria and normocalcemia
Coffin lid shaped crystals
Ammonium magnesium sulfate (struvite)
Precipitates due to high pH (urease positive bugs like proteus mirabilis)
Rhomboid shaped crystals
Uric acid
Precipitates due to low pH
Hexagonal shaped crystals
Cysteine
Precipitates due to low pH
Envelope shaped crystals
Calcium oxalate
Precipitates due to hypocitraturia
What else should you see in someone with cystinuria?
AR defect in cysteine reabsorbing PCT transporter causing cytinuria –> leads to poor absorption of cysteine, ornithine, lysine, and arginine
(COLA)
Origin of renal cell carcinoma
PCT
Origin of renal oncocytoma
Collecting duct
Calculation of RPF and RBF
RPF = PAH clearance = (urine PAH x urine flow rate)/plasma PAH
RBF = RPF/(1 - Hct)
Macula densa
Patch of columnar epithelium that senses the composition of fluid in the DCT
Filtration fraction calculation
FF = GFR/RPF
What is the result of acute tubular necrosis?
Usually spontaneously resolves – re-epthelialization of the tubules
Acetazolamide
Carbonic anhydrase inhibitor
Acts on the PCT
What is the effect of loop diuretics on renal perfusion?
Loop diuretics (like Furosemide) induce the expression of COX and increase prostaglandin synthesis –> dilation of the afferent renal arteriole
What diuretic could you give to someone to relieve their hypercalcemia?
Loop diuretic like Furosemide (increases calcium excretion)
What diuretic can help promote bone strength and decrease kidney stone formation?
Thick ascending limb diuretics (thiazides)
Promote the uptake of calcium
Dec absorption of Na increases the positive charge gradient, so more calcium is absorbed
If a patient is has a sulfa allergy, what loop diuretic can you not give them? What should you give them instead?
Furosemide (sulfonamide loop diuretic)
Give them Ethacrynic Acid (nonsulfonamide loop diuretic)
Which diuretic can cause lithium toxicity?
Thiazides
What labs do thiazides increase?
hyperGLUC hyperglycemia hyperlipidemia hyperuricemia hypercalcemia
Where does ADH act? What is the mechanism of action?
ADH binds to V2 receptor (G coupled protein) → inc cAMP and activation of PKA → PKA activation stimulated AQP2 that is stored in vesicles to shuttle it to the apical membrane → inc AQP2 causes inc H2O reuptake → concentrated urine
Patient presents with hematuria, proteinuria, oliguria, inc BUN and hypertension. What do they have?
Nephritic syndrome
Immune complex mediated disease
60-40-20 rule of distribution of water
o Total body water = 60%
o Intracellular fluid = 40%
o Extracellular fluid = 20%
Renal cell carcinoma is associated with which gene mutation?
Deletion on chromosome 3 (VHL)
Von Hippel Lindau
Von Hippel Lindau
Mutation or deletion of VHL gene on chromosome 3
Characterized by cerebellar hemangioblastoma, renal cell carcinomas, and pheochromocytomas
Renal cell carcinoma is the major cause of death
Where do uric acid crystals precipitate during tumor lysis syndrome? Why here?
These crystals precipitate in an acidic environment and the lowest pH along the nephron is found in the distal tubules and collecting ducts – these segments of the nephron can be obstructed
Renal biopsy shows crescent formation in glomeruli?
Rapidly progressive glomerulonephritis
ANCA positive
What are the two most important buffers in urine? What is their function?
NH3 and HPO4^2-
o The kidney utilizes acid buffers to trap H+ and allow the excretion of much larger amounts of acid without markedly lowering urinary pH
o HPO4^2- is a titratable acid that combines with H+ to form H2PO4^-
o NH3 is generated by the proximal tubular cells via metabolism of glutamine and combines with H+ to form NH4+
o These are elevated during DKA! Allows for excretion of acid
What diuretic can cause ototoxicity?
Furosemide (loop diuretics)
Usually resolves after med discontinuation
c-ANCA vs p-ANCA
c-ANCA: target antigen is proteinase 3
p-ANCA: target antigen is MPO
Patient presents with history of vision problems, glomerulonephritis, and deafness. What do you suspect?
Inheritance?
Mechanism of action?
Alport Syndrome
X linked dominant
Mutation in type IV collagen –> thinning and splitting of glomerular basement membrane
Generally have eye and ear problems as well
Renal Osteodystrophy: caused by?
Calcium
Phosphate
PTH
Calcitriol
Complication of chronic kidney disease
Calcium: dec
Phosphate: inc (less is filtered due to dec GFR)
PTH: inc (due to dec calcium)
Calcitriol: dec (injured kidney cannot activate vitamin D)
Effects of citrate on calcium oxalate stone formation
Citrate will bind to free (ionized) calcium and prevent it from precipitating
Give citrate or thiazide diuretics in the tx of calcium stones
Acid Base: Vomiting
Metabolic alkalosis (due to loss of gastric H+)
Acid-base: diarrhea
Metabolic acidosis ( due to loss of GI HCO3-)
Chronic kidney hypoperfusion results in hyperplasia and hypertrophy of which cells?
The juxtaglomerular cells (modified smooth muscle cells that are part of the afferent arteriole)
Blood supply to different parts of the ureter
o Proximal: renal artery
o Middle: multiple anastamoses
o Distal: superior vesicle artery
Non lactose fermenting cause of UTI
Pseudomonas
What should you consider in a patient who has been taking Naproxen daily for 3+ months?
Chronic interstitial necrosis – NSAIDs can cause damage over time to the kidneys
What do positive nitrates in urine indicate?
Presence of gram negative bacteria, like E coli
What is the most common site of obstruction (hydronephrosis) in fetus?
The uteropelvic junction, as this is the last area to canalize during development
Which cells in the kidney are responsible for activation of vitamin D? Using what enzyme?
The PCT cells
1a hydroxylase
renal disease in paroxysmal nocturnal hemoglobinuria is caused by?
Lysis of iron-containing RBCs leads to inc iron deposition in the kidney (hemosiderosis) which can interfere with PCT function and cause interstitial scarring and cortical infarcts
Precipitate in high or low pH? Calcium Uric acid Ammonium magnesium (struvite) Cysteine
Calcium: high pH
Uric acid: low pH
Ammonium magnesium (struvite): high pH
Cysteine: low pH
Patient presents with signs of ATN (proximal tubular cell ballooning and vacuolar degeneration in a patient with acute renal failure) and is found to have oxalate crystals in the tubular lumen
Indicative of ethylene glycol poisoning (seen as suicide – antifreeze – or due to alcohol abuse)
How does renal artery stenosis lead to HTN?
Renal artery stenosis causes decreased perfusion to the kidney. This causes the kidney to release more renin, which is then used to eventually form Ang II –> inc BP
