week 4 kidney then degenerates
functions as interim kidney for 1st trimester and later contributes to the male genital system
permanent; first appears in the 5th week of gestation
derived from the caudal end of the mesonephric duct; gives rise to the ureter, pelvises, calyces and collecting ducts; fully canalized by 10th week
ureteric bud interacts with this tissue inducing differentiation and formation of the glomerulus through to the distal convoluted tubule
The ureteropelvic junction is the…
last area to canalize and the most common site of obstruction in the fetus.
Potter Sequence is…
oligohydramnios leading to compression of the developing fetus leading to limb deformities and facial anomalies (low set ears and retrognathia) and compression of the chest leading to pulmonary hypoplasia.
Causes of Potter sequence include…
ARPKD, posterior urethral valves and bilateral renal agenesis. (babies who can’t Pee develop Potter)
POTTER syndrome is associated with:
Pulmonary hypoplasia Oligohydramnios (trigger) Twisted face Twisted skin Extremity defects Renal failure (in utero)
the inferior poles of both kidneys fuse and as they ascend from the pelvis during fetal development, they get trapped under the inferior mesenteric artery and remain low in the abdomen
Horseshoe kidneys have increased risk for…
ureteropelvic junction obstruction, hydronephrosis, renal stones and renal cancer (Wilms tumor).
Horseshoe kidneys are associated with…
Multicystic dysplastic kidney is due to….
abnormal interaction between the ureteric bud and metanephric mesenchyme. This leads to a nonfunctional kidney consisting of cysts and CT.
If multicystic dysplastic kidney is unilateral (most common), then it is generally…
asymptomatic with compensatory hypertrophy of the contralateral kidney.
The kidney taken for donor transplantation is…
the left one becasue it has a longer renal vein.
The ureters pass….
under the uterine artery and under the ductus deferens.
The ureters may be damaged by gynecologic procedures involving…
ligation of the uterine vessels leading to ureteral obstruction or leak.
Plasma volume is measured by…
Extracellular volume is measured by…
Plasma osmolarity =
The glomerular filtration barrier is composed of…
- Fenestrated capillary endothelium (size barrier) 2. Fused basement membrane with heparan sulfate (negative charge barrier) 3. Epithelial layer consisting of podocyte foot processes
The charge barrier of the glomerular filtration barrier is lost in…
nephrotic syndrome, resulting in albuminuria, hypoproteinemia, generalized edema and hyperlipidemia.
Renal Clearance Equation
Cx = UxV/P
If Cx < GFR, then there is…
net tubular reabsorption of X.
If Cx > GFR, then there is…
net tubular secretion of X.
To calculate GFR, use…
inulin because it is freely filtered and is neither secreted or reabsorbed.
Normal GFR is about…
Creatine clearance is an approximate measure of…
GFR but it slightly overestimates GFR becasue creatine is moderately secreted by the renal tubules.
Effective renal plasma flow (ERFP) can be estimated using…
para-aminohippuric acid (PAH) clearance because it is both filtered and actively secreted in the proximal tubule. Nearly all PAH entering the kidney is excreted.
the true RPF by about 10%.
Filtered load =
GFR x plasma concentration
In the kidneys, prostaglandins normally…
dilate the afferent arteriole leading to: -increased RPF -increased GFR (FF remains constant) **NSAIDs block this.
In the kidneys, angiotensin II acts to…
constrict the efferent arteriole leading to: -decreased RPF -increased GFR -increased FF **ACE inhibitors block this.
Excretion rate =
V x Ux
Reabsorption rate =
filtered - excreted
Secretion rate =
excreted - filtered
At a normal plasma level, glucose is…
completely reabsorbed in the proximal tubule by Na/glucose costransport.
Glucosuria begins at…
about plasma glucose of 200. And at 375, all transporters are fully saturated.
Normal pregnancy decreases the reabsorption of…
glucose and amino acids in the proximal tubule leading to glucosuria and aminoaciduria.
Amino acids are reabsorbed by…
sodium-dependent transporters in the proximal tubule.
Hartnup disease is…
a deficiency of neutral amino acid (tryptophan) transporters in the proximal renal tubular cells leading to aminoaciduria.
Hartnup disease results in..
pellagra like symptoms.
Treat Hartnup disease with…
high-protein diet and nicotinic acid.
Fanconi syndrome is…
a reabsorptive defect in PCT
Fanconi is associated with…
increased excretion of nearly all amino acids, glucose, HCO3-, and PO43-.
Fanconi may result in…
Causes of Fanconi include…
Wilson disease, ischemia and nephrotoxins/drugs.
Bartter syndrome is…
a resorptive defect in the thick ascending loop of Henle that affects the Na/K/2Cl cotransporter.
Bartter syndrome results in…
hypokalemia and metabolic alkalosis with hypercalciuria.
Gitelman syndrome is…
a resorptive defect of NaCl in the DCT. Less severe than Bartter.
Gitelman syndrome leads to…
hypokalemia and metabolic alkalosis but without hypercalciuria.
Liddle Syndrome is…
increased Na+ reabsorption in the distal and collecting tubules (increased ENaC).
Liddle syndrome results in…
HTN, hypokalemia, metabolic alkalosis and decreased aldosterone.
Treatment for Liddle syndrome is…
-affects baroreceptor function -limits reflex bradycardia -helps maintain blood volume and pressure
ANP is released from…
atria in response to increased volume; may act as a “check” on the RAAS; relaxes vascular smooth muscle via cGMP causing increased GFR and decreased renin
ADH primarily regulates…
osmolarity; it responds tolow blood volume states
Aldosterone primarily regulates…
ECF Na content and volume; responds to low blood volume states.
Renin is released from the kidneys in response to…
-decreased BP (JG cells) -decreased Na+ delivery to the macula densa -increased sympathetic tone (Beta-1 receptors)
The juxtaglomerular apparatus consists of…
JG cells (smooth muscle of the afferent arteriole) and macula densa (NaCl sensor in the distal convoluted tubule).
JG cells secrete…
The juxtaglomerular apparatus defends….
GFR via RAAS.
Beta-blockers can decrease BP by…
inhibiting beta1 receptors of the JGA causing decreased renin release.
Erythropoietin is released by…
interstitial cells in the peritubular capillary bed in response to hypoxia.
The proximal tubule cells convert…
25-OH vitamin D to 1,25 (OH)2 vitamin D which is the active form. 1alpha-hydroxylase is the enzyme.
Things that shift K+ out of the cell causing hyperkalemia
Digitalis HyperOsmolarity Insulin deficiency Lysis of cells Acidosis Beta-adrenergic antagonis
Things that shift K+ into the cell
-hypoosmolality -insulin -alkalosis -beta-adrenergic agonist (Insulin INto cells)
Low Serum Na+
nausea malaise stupor coma
High Serum Na+
irritability stupor coma
Low Serum K+
U waves on ECG flattened T waves arrhythmias muscle weakness
High Serum K+
wide QRS peaked T waves arrhythmias muscle weakness
Low Serum Ca2+
tetany seizures QT prolongation
High Serum Ca2+
Stones (renal) Bones (pain) Graons (abdominal pain) Psychiatric overtones (anxiety, altered mental status)
Low Serum Mg2+
tetany torsades de pointes
High Serum Mg2+
decreased DTRs lethargy bradycardia hypotension cardiac arrest hypocalcemia
Low Serum Phosphate
bone loss osteomalacia
High serum phosphate
renal stones metastatic calcifications hypocalcemia
pH = 6.1 + log(HCO3-/.03PCO2)
The predicted respiratory compensation for a simple metabolic acidosis can be calculated using…
the Winters formula. PCO2 = 1.5[HCO3-] + 8 +/- 2 If the measured PCO2 differs significantly from the predicted PCO2, then a mixed acid base disorder is likely present.
Type I Renal Tubular Acidosis
-defect in ability of alpha intercalated cells to secrete H+ -new HCO3- is not generated leading to metabolic acidosis -associated with hypokalemia -incresaed risk for calcium phosphate kidney stones
Causes of Type I Renal Tubular Acidosis
-amphotericin B toxicity -analgesic nephropathy -multiple myeloma -congenital anomalies of the urinary tract
Type II Renal Tubular Acidosis
-defect in proximal tubule HCO3- reabsorption leading to metabolic acidosis -associated with hypokalemia -increased risk for rickets
Causes of Type 2 Renal Tubular Acidosis
-Fanconi syndrome (wilson dz) -chemicals toxic to proximal tubule (lead, aminoglycosides) -carbonic anhydrase inhibitors
Type 4 Renal Tubular Acidosis
-hypoaldosteronism; aldosterone resistance; or K+ sparing diuretics -hyperkalemia impairs ammoniagenesis in the PT -decreased buffering capcity and decreased H+ secretion
Presence of casts in the urine indicates that hematuria/pyuria is of…
renal origin (vs. bladder).
-glomerulonephritis, ischemia or malignant HTN
-tubulointerstitial inflammation, acute pyelonephritis, transplant rejection
Fatty casts (oval fat bodies)
Granular (muddy brown) casts
acute tubular necrosis
advanced renal disease/chronic renal failure
Nephrotic Syndrome presents with…
massive proteinuria (> 3.5; frothy urine), hyperlipidemia, fatty casts and edema.
Nephrotic Syndrome is associated with…
thromboembolism (hypercoagulable state due to AT III loss in urine) and increased risk of infxn (loss of Igs).
Focal Segmental Glomerulosclerosis is the most common cause of…
nephrotic syndrome in African Americans and Hispanics.
Focal Segmental Glomerulosclerosis can be idiopathic or associated with…
HIV, sickle cell, heroin, obesity, interferon, and chronic kidney disease.
Labs of Focal Segmental Glomerulosclerosis
LM - segmental sclerosis and hyalinosis IF - negative EM - effacement of foot processes
Membranous nephropathy is the most common cause of…
primary nephrotic syndrome in caucasian adults.
Membranous nephropathy can be idiopathic or associated with…
Ab to phospholipase A2 receptor, drugs, infxns, SLE or solid tumors.
Labs of Membranous Nephropathy
LM - diffuse capillary and GBM thickening IF - granular as a result of immune complex deposition EM - “spike and dome” appearance with subepithelial deposits
Minimal Change Disease is most common in…
Minimal Change Disease may be triggered by…
recent infection, immunization or immune stimulus.
Minimal Change Disease may be associated with…
Focal segmental glomerulosclerosis response to steroids
inconsistent; may progress to chronic renal disease
Membranous nephropathy response to steroids
poor; may progress to chronic renal disease
Minimal Change Disease response to steroids
Minimal Change Disease Labs
LM - normal glomeruli IF - negative EM - effacement of foot processes
The most commonly involved organ with systemic amyloidosis is…
the kidney. It is associated with chronic conditions (multiple myeloma, TB, RA).
Labs for amyloidosis
LM - congo red stain shows apple-green birefringence under polarized light
Type I Membranoproliferative Glomerulonephritis
-subendothelial immune complex deposits with granular IF -“tram-track” appearance due to GBM splitting caused by mesangial ingrowth
Type II Membranoproliferative Glomerulonephritis
-intramembranous immune complex deposits (dense)
Type I Membranoproliferative Glomerulonephritis is associated with…
HBV and HCV.
Type II Membranoproliferative Glomerulonephritis is associated with…
C3 nephritic factor.
-nonenzymatic glycosylation of GBM leads to increased permeability and thickening -nonenzymatic glycosylation of efferent arterioles leads to increased GFR and mesangial expansion
Light microscope of diabetic glomerulonephropathy
-mesangial expansion -GBM thickening -eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesion)
an inflammatory process that can lead to hematuria and RBC casts in the urine. It is associated with azotemia, oliguria, HTN and proteinuria (<3.5 grams/day).
Acute poststreptococcal glomerulonephritis is most frequently seen in…
children adn occurs about 2 wks after group A streptococcal infxn of the pharynx or skin. Resolves spontaneously. Type III HSR.
Acute poststreptococcal glomerulonephritis presents with…
peripheral and periorbital edema, dark urine and HTN. -increased anti-DNase B titers -decreased complement levels
Acute poststreptococcal glomerulonephritis labs
LM - glomeruli enlarged and hypercellulr IF - “starry sky” granular appearance “lumpy bumpy” due to IgG, IgM and C3 deposition along the GBM and mesangium EM - subepithelial immune complex humps
Rapidly progressive (cresenteric) glomerulonephritis results from several disease processes:
- Goodpasture syndrome: type II HSR, Abs to GBM and alveolar BM leading to linear IF 2. Granulomatosis with polyangiitis 3. microscopic polyangiitis
Rapidly progressive glomerulonephritis Labs
LM and IF - crescent-moon shape consisting of fibrin and plasma proteins with glomerular parietal cells, monocytes and macrophages
Rapidly progressive glomerulonephritis presents with…
hematuria/hemoptysis. -PR3-ANCA/c-ANCA -MPO-ANCA/p-ANCA
Diffuse proliferative glomerulonephritis is due to either…
SLE or MPGN. This is the most common cause of death in SLE.
Labs of diffuse proliferative glomerulonephritis
LM - “wire looping” of capillaries EM - subendothelial and sometimes intramembranous IgG based immune complexes often with C3 deposition IF - granular
IgA Nephropathy (Berger) often presents with…
a URI or acute gastroenteritis. Episodic hematuria with RBC casts. Seen with Henoch-Schonlein purpura.
IgA Nephropathy Labs
LM - mesangial proliferation EM - mesangial immune complex deposits IF - IgA based immune complex deposits in the mesangium
Alport Syndrome is due to…
a mutation in type IV collagen leading to thinning and splitting of the glomerular basement membrane; usually X-linked
Alport syndrome presents with…
glomerulonephritis, deafness and eye problems.
Kidney stones can lead to…
hydronephrosis and pyelonephritis.
Kidney stones present with…
unilateral flank tenderness colicky pain radiating to the groin hematuria
All kidney stones are radiopaque except…
Uric acid stones with are radiolUcent.
Calcium phosphate stones precipitate at…
Calcium oxalate stones precipitate at…
Calcium stones are promoted by…
Oxalate crystals can result from…
ethylene glycol (antifreeze), vitamin C abuse or Crohn’s.
Treatments for recurrent calcium stones includes…
thiazides and citrate.
Most common presentation of kidney stones:
calcium oxalate stone in a pt with hypercalciuria and normocalcemia
Urine crystals of calcium stones appear…
envelope or dumbell shaped.
Ammonium magnesium phosphate stones urine crystals appear….
as a coffin lid.
Ammonium magnesium phosphate stones area also known as…
Struvite stones are caused by…
infection with urease + bugs (Proteus mirabilis, Staph, Klebsiella) that hydrolyze urea to ammonia leading to urine alkalinization.
Ammonium magnesium phosphate stones can form…
staghorn calculi taht can be a nidus for UTIs.
Ammonium magnesium phoshpate stones precipitate at…
Uric acid stones precipitate at…
Risk factors for Uric acid stones
-decreaed urine volume -arid climates -acidic pH
Uric acid stones are visible on…
CT and ultrasound but not X-ray.
Uric acid stones have a strong association with….
hyperuricemia (gout). They are often seen in disease with increased cell turnover like leukemia.
Treatment of uric acid stones
alkalinization of the urine.
Uric acid stones urine crystals appear as…
rhomboid or rosettes.
Cystine stones precipitate at…
Cystine stones urine crystals appear….
Cystine stones are mostly seen in…
children secondary to cystinuria. Can form staghorn calculi. Positive sodium nitroprusside test.
Treatment for Cystine stones
alkalinization of urine and hydration
distention/dilation of the renal pelvis and calyces. Usually caused by urinary tract obstruction; other causes include retroperitoneal fibrosis and vesicoureteral reflux.
Hydronephrosis only impairs renal function if…
it is bilateral or the pt only has one kidney.
Hydronephrosis leads to…
compression atrophy of the renal cortex and medulla.
Renal cell carcioma originates from…
the proximal tubule cells leading to polygonal clear cells filled with accumulated lipids and carbs.
Renal cell carcinoma is most common in…
men 50-70 yrs old.
Increased incidence of renal cell carcinoma with…
smoking and obesity.
Renal cell carcinoma manifests clinically with…
hematuria, palpable mass, secondary polycythemia, flank pain, fever and weight loss.
Renal cell carcinoma can invade…
the renal vein and then the IVC and spread hematogenously. Metastasizes to the lung and bone.
Renal cell carcinoma is associated with gene deletion on…
chromosome 3 (sporadic or inherited as von Hippel-Lindau syndrome).
Renal cell carcinoma is also associated with…
paraneoplastic syndromes (ectopic EPO, ACTH, PTHrP)
Renal cell carcinoma is resistant to…
chemo and radiation. Need to resect or use immunotherapy.
Renal oncocytoma is…
a benign epithelial cell tumor that has large eosinophilic cells with abundant mitochondria without perinuclear clearing
Renal oncocytoma presents with…
painless hematuria, flank pain and abdominal mass.
Treatment for renal oncocytoma
Wilms tumor (nephroblastoma)
most common renal malignancy of early childhood; contains embryonic glomerular structures
Wilms tumor presents with…
huge, palpable flank mass and/or hematuria
Mutations of Wilms tumor
loss of function mutations of tumor suppressor genes WT1 or WT2 on chromosome 11
Wilms tumor may be part of either…
Beckwith-Wiedemann syndrome or WAGR complex (Wilms tumor, Aniridia, GU malformation and mental Retardation)
The most common tumor of the urinary tract system is…
transitional cell carcinoma.
Transitional cell carcinoma presents with…
painless hematuria (no casts) which suggest bladder cancer.
Transitional cell carcinoma is associated with problems in your….
Pee SAC: P - phenacetin S - smoking A - aniline dyes C - cyclophosphamide
Chronic irritation of the urinary bladder leads to…
squamous metaplasia leads to dysplasia and squamous cell carcinoma. Presents with painless hematuria.
Risk factors for squamous cell carcinoma of the bladder include:
-Schistosoma haematobium infxn (middle east) -chronic cystitis -smoking -chronic nephrolithiasis
Acute infectious cystitis presents as…
suprapubic pain, dysuria, urinary frequency adn urgency.
Risk factors for acute infectious cystitis
-femal gender (short urethra) -sexual intercourse (“honeymoon cystitis”) -indwelling catheters
Causes of Acute Infectious Cystitis
-E. coli -Staph saprophyticus (seen in sexually active young women) -Klebsiella -Proteus mirabilis (urine has ammonia scent) -adenovirus (hemorrhagic cystitis)
Lab findings for acute infectious cystitis
-positive for leukocyte esterase -nitrates appear for gram-neg organisms -sterile pyuria and negative urine cultures suggest N. gonorrhea or Chlamydia
the cortex with relative sparin of glomeruli/vessels.
Acute pyelonephritis presents with…
dysuria, fever, CVA tenderness, nausea/vomiting. Often with white cell casts in urine.
Causes of pyelonephritis include:
-ascending UTI (E. coli often) -vesicoureteral reflux -hematogenous spread to the kidney
CT of pyelonephritis shows…
striated parenchymal enhancement.
Risk factors for pyelonephritis
-indwelling catheter -urinary tract obstruciton -DM -pregnancy
Complications of acute pyelonephritis
-chronic pyelonephritis -renal papillary necrosis -perinephric abscess
Chronic pyelonephritis is the result of…
recurrent episodes of acute pyelonephritis. Typically requires predisposition to infxn such as vesicoureteral refulx or chronic stones.
Findings of Chronic Pyelonephritis
-coarse, asymmetric corticomedullary scarring, blunted calyx -tubules can contain eosinophilic casts resembling thyroid tissue
Drug-induced interstitial nephritis is…
pyuria and azotemia occuring after administration of drugs that act as haptens inducing hypersensitivity. Nephritis typically occurs 1-2 wks after certain drugs (diruretics, penicillins, sulfonamides, rifampin) but months after NSAIDs.
Drug-induced interstitial nephritis is associated with…
fever, rash, hematuria adn CVA tenderness.
diffuse cortical necrosis is…
acute generalized cortical infarction of both kidneys likely due to a combination of vasospasm and DIC.
Diffuse cortical necrosis is associated with…
obstetric catastrophes and septic shock.
The most common cause of intrinsic renal failure is…
acute tubular necrosis. Death most often occurs during the initial oliguric phase.
Key finding of acute tubular necrosis
-granular “muddy brown” casts
3 stages of Acute Tubular Necrosis
- inciting event 2. maintenance phase - oliguric; lasts 1-3 wks; risk of hyperkalemia; metabolic acidosis 3. recovery phase - polyuric; BUN adn serum creatinine fall; risk of hypokalemia
Ischemic acute tubular necrosis is secondary to…
decreased RBF (hypotension, shock, sepsis, hemorrhage, CHF). Results in death of tubular cells that may slough into tubular lumen.
Nephrotoxic Acute Tubular Necrosis is secondary to…
injury resultin gfrom toxic substances (aminoglycosides, radiocontrast, lead, cisplatin), crush injury (myoglobinuria), hemoglobinuria.
Pathogenesis of renal papillary necrosis
sloughing of renal papillae leads to gross hematuria and proteinuria; may be triggered by
Renal papillary necrosis is associated with…
DM acute pyelonephritis chronic phenacetin use sickle cell anemia/trait
In the normal nephron, BUN is…
reabsorbed (for countercurrent multiplication) but creatitine is not.
Acute kidney injury is defined as…
an abrupt decline in renal function with increased creatinine and increased BUN over a period of several days.
Prerenal azotemia occurs as a result of…
decreased RBF leading to decreased GFR. Na/water and urea are retained by the kidney in an attempt to conserve volume so BUN/creatinine ratio is increased.
Intrinsic renal failure is generally due to..
acute tubular necrosis or ischemia/toxins; less commonly due to acute glomerulonephritis.
Intrinsic renal failure demonstrates…
patchy necrosis leading to debris obstructing the tubule and fluiud backflow across the necrotic tubule. This decreases GFR. BUN reabsorption is impaired (decreased BUN/creatinine ratio).
Urine in intrinsic renal failure has…
Postrenal azotemia is due to..
outflow obstruction (stones, BPH, neoplasia, congenital anomalies). Develops only with bilateral obstruction.
Consequences of Renal Failure
MAD HUNGER MA: Metabolic Acidosis D: Dyslipidemia H: Hyperkalemia U: Uremia N: Na/H20 retention G: Growth retardation/developmental delay E: Erythropoietin failure (anemia) R: Renal osteodystrophy
Uremia is a clinical syndrome marked by:
increased BUN and creatinine -nausea/anorexia -pericarditis -asterixis -encephalopathy -platelet dysfunction
Renal Osteodystrophy is…
failure of vitamin D hydroxylation, hypocalcemia, and hyperphosphatemima leading to secondary hyperparathyroidism. Causes subperiosteal thinning of bones.
Within renal osteodystrophy, hyperphosphatemia also independently…
decreases serum calcium by causing tissue calcifications.
Autosomal dominant polycystic kidney disease
-innumerable cysts causing bilateral enlarged kidneys ultimately resulting in destruction
ADPKD presents with…
flank pain, hematuria, HTN, urinary infxn and progressive renal failure; typically in adults.
ADPKD has mutation in either…
PKD1 (on chr 16) or PKD 2 (on chr 4).
ADPKD is associated with…
berry aneurysms, mitral valve prolapse and hepatic cysts.
Autosomal recessive polycystic kidney disease
infantile presentation; significant renal failure in utero can lead to Potter sequence
ARPKD is associated with…
congenital hepatic fibrosis.
Concerns of ARPKD beyond the neonatal period include…
HTN, portal HTN, and progressive renal insufficiency.
Medullary cystic disease is…
an inherited disease causing tubulointerstitial fibrosis and progressive renal failure with the inability to concentrate urine. Shows shrunken kidneys on ultrasound.
Simple renal cysts are typically found in…
the outer cortex filled with ultrafiltrate. Verry common/majority of all renal masses; found incidentally.
Complex renal cysts have…
solid components as seen on CT and require follow-up/removal due to increased risk of RCC.