Renal Flashcards
Pronephros, mesonephros, and metanephros
Pronephros: Present at week 4; later degenerates
Mesonephros: interim kidney for first trimester; later contributes to male genital system
Metanephros: appears in 5th wk gestation, forms permanent kidney. ureteric bud form mesonephric duct gives rise to ureter, pelvises, calyces, collecting ducts. metanephric mesenchyme gives rise to glomerulus through distal convoluted tubule
Potter sequence
Oligohydramnios causes compression of developing fetus leading to limb deformities and facial anomalies, compression of chest, lack of aspiration of fluid into fetal lungs leading to pulmonary hypoplasia
Causes: ARPKD, obstructive uropathy, bilateral renal agenesis
Horseshoe kidney
Inferior poles of kidneys fuse; gets trapped under inf mesenteric artery as kidneys ascend
Multicystic dysplastic kidney
Caused by abnormal interaction between ureteric bud and metanephric mesenchyme. Nonfunctional kidney of cysts and connective tissue
Duplex collecting system
bifurcation of ureteric bud creating bifid ureter; associated iwth vesicoureteral feflux, ureteral obstruction, UTIs
Path of ureters
Under uterine artery and under ductus deferens (water under the bridge)
Fluid breadkwon of body
60% of body made of water
40% ICF; 20% ECF
Glomerular giltration barrier
Filters plasma by size and charge. Consists of fenestrated endothelium, fused BM containing heparan sulfate (neg charge barrer), epithelial layer with podocyte foot processes
Formula for renal clearance
C=UV/P=volume of plasma from which substance completely cleared per unit time
U=urine concentration of X
P=plasma concentration of X
V=urine flow rate
Formula for GFR
GRF = clearance of inulin = Uinulin x V/Pinulin
works because inulin neither reabsorbed nor secreted
Filtration fraction
fraction of circulating plasma that gets filtered into the tubules
=GFR/RPF
normal is 20%
Hartnup disease
AR deficiency of neutral amino acid transporters in proximal renal tubular cells and on enterocytes resulting in neutral aminoa cids in urine and decreased absorption from the gut
Results in pellagra like symptoms due to decreased tryptophan converstion to niacin
Function of early PCT
- reabsorbs all glucose and amino acids
- reabsorbs most ions isotonically
- generates and secretes NH3 to buffer secreted H+
- responds to PTH to decreased phosphate reabsorption
- responds to AT II to increase Na+ reabsortipon via Na+/H+ exchange (permits contraction alkalosis)
Function of loop of henle
Thin descending loop:
- passively reabsorbs H2O via medullary hypertonicity
- concentrates urine
Thick ascending loop
- reabsorbs Na+, K+, Cl-
- paracellular reabsorption of Mg++ and Ca++
- impermeable to water - makes urine less concentrated
Function of early DCT
- reabsorbs Na+ and Cl- making urine dilute
- increases Ca++ reabsorption in response to PTH
Function of collecting tubule
- reabsorbs Na+ in exchange for secretion of K+ and H+ (aldo regulated)
- reabsorbs more water in response to ADH
Aldosterone actions
All in collecting tubule
- principles cells: increases apical K+ conductance, increases Na+/K+ pump, increases ENaC channels
- intercalated cells: increases H+ ATPase activity which increases the HCO3-/Cl- exchanger
Fanconi syndrome
Reabsorptive defect in PCT. Increased excretion of amino acids, glucose, bicarb, and phosphate. Can cause metabolic acidosis.
Can be caused by ischemia, multiple myeloma, nephrotoxic drugs, lead poisoning
Bartter syndrome
Reabsorptive defect in thick ascending loop due to effect in Na+/K+/2Cl- co transporter. AR. Hypokalemia and metabolic alkalosis, hypercalciuria.
Gitelman syndrome
Reabsorptive defect of NaCl in DCT. AR. Hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria.
Liddle syndrome
AD gain of funtion mtation that increases Na+ reabsorption in collecting tubules
Syndrome of apparent mineralocorticoid excess
Deficiency of 11beta hydroxysteroid dehydrogenase: excess cortisol increases mineralocorticoid receptor activity leading to HTN, hypokalemia, metabolic alkalosis. Can acquire from licorice which blocks this enzyme.
Actions of angiotensin II (five)
- vasoconstriction
- constricts efferent arteriole to increase filtration fraction and GFR despite low volume
- promotes aldosterone and ADH secretion
- increases Na+/H+ exchange in proximal collecting tubule
- stimulates hypothalamus leading to thirst
Stimuli for angiotensin II release (3)
Decreased BP sensed by JG cells
Decreased distal delivery of Na+ to macula densa cells
Increased sympathetic tone via beta1 receptors
All stimulate renin which leads to activation of angiotensinogen to angiotensin I
Activity of ANP and BNP
Released from atria and ventricles in response to increased volume. Relax vascular smooth muscle to increase GFR and decrease renin (check on RAAS system)
JG apparatus
Consists of mesangial cells, JG cells (modifed afferent arteriole smooth muscle), macula densa (NaCl sensor that is part of DCT)
Secretes renin in response to decreased renal BP and increased sympathetic tone
Prostaglandins in the kidney
Vasodilate afferent arteriole to increase RBF. Block by NSAIDs leads to constriction of afferent and decreased GFR
Things that shift K+ out of cells (six)
Do LABS: digitalis, hyperosmolarity, lysis of cells, acidosis, beta blocker, high blood sugar
things that shift K+ into cells (four)
Hypoosmolarity
Alkalosis
Beta agonists
Insulin
Presentation of hypo and hyperkalemia
Hypo: U waves, flattened waves, arrhythmia, muscle spasm
Hyper: Wide QRS, peaked T waves, arrhythmias, muscle weakness
Presentation of hypo and hypercalcemia
Hypo: tetany, seiqures, QT prolongation
Hyper: “stones, bones groans, thrones, and psychiatric overtones”
- renal stones
- bone pain
- abdominal pain
- increased urinary frequency
- anxiety and altered mental status
Presentation of hypo and hypermagnesemia
Hypo: tetany, torsades, hypokalemia
Hyper: decreased DTRs, lethargy, bradycardia, hypotension, cardiac arrest, hypocalcemia
Winters formula
Predicts respiratory comp for metabolic acidosis
PCO2=1.5[HCO2-] + 8 +/- 2
Renal tubular acidosis presentation
Normal anion gap metabolic acidosis with hypokalemia or hyperkalemia
Causes of RBC casts
glomerulonephritis, malignant HTN
Causes of fatty (oval body) casts
Nephrotic syndrome
causes of granular casts
ATN - muddy brown
causes of waxy casts
end stage renal disease/chronic renal failure
Pathology of post strep GN
Cause of nephritic syndrome. Granular immune complex and complement deposition in subepithelial space
Pathology of RPGN
crescent moon shape deposits
Goodpasture: linear antibody staining
Pathology and cause of diffuse proliferative glomerulonephritis
Causes: SLE, membranoproliferative GN
wire looping, subendothelial granular deposits
Presents with nephritic syndrome
IgA nephropathy
Episodic hematuria with RBC casts. Nephritic syndrome.
Mesangial pfolieration and immune complex deposits in mesangium
Alport syndrome
Causes nephritic syndrome, eye problems, deafness
x-linked mutation in type IV collagen
thinning and splitting of GBM with basket weave appearance on EM
membranoproliferative glomerulonephritis
Causes nephritic and nephrotic syndrome.
Type I: subendothelial complex deposits, tram track appearance due to GBM splitting, may be associated with hep B or C infection
Type II: intramembranous complex deposits, associated with C3 nephritic factor
Two complications of nephrotic syndrome
Hypercoagulable state due to antithrombin III loss in ruine
Increased risk of infection due to loss of Ig in urine
Focal segmental GN
Causes nephrotic syndrome (most common cause in blacks and hispanics)
Segmental scerlosis and halinosis. Focal deposits of IgM and C3. Foot process effacement
Inconsistent response to steroids; may progress to chronic renal disease
Minimal change disease
Causes nephrotic syndrome (most common cause in children). Can be triggered by recent infection or immunization.
Normal LM and IF with foot process effacement on EM
Excellent response to steroids
Membranous nephropathy
Most common cause of nephrotic syndrome in caucasian adults. Nephrotic presentation of SLE
Diffuse capillary and GBM thikening with granular immune complex deposition and spike and dome subepithelial deposits on EM
Poor response to steroids, may progress to chronic disease
Amyloidosis of kidney
Causes nephrotic syndrome (kidney most commonly involved organ)
Apple gree birefringence with congo red stain
Diabetic glomerulonephropathy
Causes nephrotic syndrome
Mesangial expansion and GBM thickening, eosinophilic nodular glomerulosclerosis, glycosylation of GBM
Presentation of kidney stones
Unilateral flank pain, colicky pain radiating to groin, hematuria
Calcium kidney stones
Radiopaque on X-ray. Envelope or dumbbell shaped stones. Calcium phosphate precipitates at increased pH, calcium oxalate at decreased pH.
Can occur with ethylene glycol, vit C abuse, hypocitraturia, malabsorption.
Treated with thiazides, hydration, citrate
Ammonium magnesium phosphate kidney stones
Radiopaque on X-ray. Precipitate at increased pH. Coffin lid urine crystals. Caused by infection with urease pos bugs that hydrolyze urea to ammonia, alkalinizing the urine. Can form staghorn calculi.
Treated by treating the infection and removing the stone surgically
Uric acid crystals
Radiolucent rhomboid or rosettes. Precipitate at decreased pH. Associated with hyperuricemia and increased cell turnover (leukemia)
Treat by alkalinizing the urine and with allopurinol
Cystine kidney stones
Radiolucent hexagonal stones. Precipitate at low pH. Hereditary: associated with loss of function of cystine reabsorption.
Seen in kids, can form staghorn calculi
Treated with alkalanization of urine
Diagnosed with sodium cyanide nitroprusside test
Renal cell carcinoma
Population: Men 50-70, higher risk with smoking and obesity, VHL syndrome
Presentation: Hematuria, palpable mass, secondary polycythemia, flank pain, fever. Can cause paraneoplastic syndrome. Often doesn’t present until metastatic. Spreads by blood to lung and bone when invades renal vein.
Pathogenesis: Originates from PCT cells
Chemo and radiation resistant
Renal oncocytoma
Benign epithelial cell tumor. Well circumscribed. Large eosinophilic cells. Presents with painless hematuria, flank pain, abdominal mass
Wilms tumor
Also called nephroblastoma. Most common renal cancer in kids 2-4. Contains embryonic glomerular structures.
Presentation: large, palpable, unilateral flank mass and/or hematuria
Cause: loss of function mutations in WT1 or WT2. Can be part of Beckwith-Wiedemann syndrome or WAGR complex
Beckwith-Wiedemann syndrome
Wilms tumor
Macroglossia
Organomegaly
Hemihypertophy
WAGR complex
Wilms tumor
Aniridia
GU malformation
Mental retardation
Transitional cell carcinoma
Occurs in urinary tract system: renal calyces, renal pelvis, ureters, bladder
Presents with painless hematuria
Risks: phenacetin, smoking, aniline dyes, cyclophosphamide
Squamous cell carcinoma of bladder
Chronic irritation of bladder leads to squamous metaplasia which leads to dysplasia and SCC
Risk factors: Schistosomal haematobium, chronic cystitis, smoking, chronic nephrolithiasis
Presentation: painless hematuria
Chronic pyelonephritis
Recurrent episodes of acute pyelo leads to scarring and blunted calyces with tubules containing eosinophilic casts resembling thyroid tissue
Associated with VU reflux or chronic kidney stones
Drug-induced interstitial nephritis
Pyuria (esp eosinophils) and azotemia 1-2 weeks after certain drugs - diuretics, penicillins, PPIs, sulfonamides, rifampin. Can occur months after starting NSAIDS
May be associated with fever, rash, hematuria, CVA tenderness
Diffuse cortical necrosis
Cortical infart of both kidneys
Presents with abrupt onset anuria, gross hematuria, flank pain
Associated with obstetric catastrphoes, septic shock
Acute tubular necrosis
Most common cause of AKI. Usually resolves spontaneously but can be fatal. Increased FENa.
Granular casts
Causes: ischemia, nephrotoxicity due to drugs, crush injury, hemoglobinuria
Renal papillary necrosis
Sloughing of necrotic renal papillae leading to gross hematuria and proteinuria.
Associated with sickle cell disease, acute pyelonephritis, NSAIDs, diabetes
Consequences of renal failure
MAD HUNGER:
- metabolic acidosis
- dyslipidemia
- hyperkalemia
- uremia: pericarditis and aterixis, encephalopathy, platelet dysfunction, N/V
- Na+ and water retention
- growth retardation/developmental delay
- EPO failure
- renal osteodystrophy
ADPKD
Mutation: PKD1 on chromosome 16 or PKD2 on chromosome 4, AD
Presentation: flank pain, hematuria, HTN, urinary infection, progressive renal failure in young adulthood. Bilateraly enlarged cystic kidneys
Associations: berry aneurysm, mitral valve prolapse, benign hepatic cysts
ARPKD
Mutation: AR mutation
Presentation: Systemic HTN, progressive renal insufficiency, portal HTN and congenital hepatic fibrosis in neonate. Can cause Potter sequence in utero
Medullary cystic disease
Inherited disease. Tubulointerstitial fibrosis and progressive renal insufficiency. Shrunken kidneys on US
ADH and urea
ADH increases water permeability of collecting ducts. Water leaves tubules causing urea concentration within the tubules to increase.
ADH activates urea transporters in medullary collecting duct so that mroe urea is reabsorbed and its clearance is decreased.
This increases urea in the medullary interstitium, increasing medullary osmotic gradient for water reabsorption
Acyclovir renal toxicity
Occurs in 5-10% of those receiving acyclovir IV. Concentration in collecting d;ct exceeds solubility resulting in crystallization and renal tubular damage. Prevented with hdyration
Tuberous sclerosis
AD condition
Cortical tubers and subependymal hamartomas in brain leading to seizures and mental retardation.
Also can see cardiac rhabdomyomas, facial angiofibromas, ash-leaf patches on skin, and renal angiomyolipomas.
Thrombocytopenic thrombotic purpora-hemolytic uremic syndrome
Pentad of fever, neurologic symptoms, renal failure, anemia, thrombocytopenia in setting of GI illness. Causes microvascular thrombosis in brain kidneys and heart and platelet activation in arterioles and capillaries
Myeloma cast nephropathy
Develops due to excess excretion of free light chains (bence Jones proteins). Proteins form casts that cause tubular obstruction and epithelial injury leading to impaired renal function. Biopsy shows glassy casts that stain eosinophilic
