Renal Flashcards
Pronephros
- week 4; then degenerates.
Mesonephros
functions as an interim kidney for 1st trimester; later contributes to male genital system.
Metanephros development time frame:
permanent; first appears in 5th week of gestation; nephrogenesis continues through weeks 32- 36 of gestation.
Ureteric bud
(metanephric diverticulum) derived from the caudal end of the mesonephric duct; gives rise to ureter, pelvises, calyces, collecting ducts;
fully canalized by 10th week (Me-10-nephric diverticulum)
Metanephric mesenchyme
(ie, metanephric blastema) - ureteric bud interacts with this tissue;
interaction induces differentiation and formation of glomerulus through to distal convoluted tubule (DCT)
Ureteropelvic junction
last to canalize - most common site of obstruction (can be detected on prenatal ultrasound as hydronephrosis).
Horseshoe kidney associated with:
C - cancer (renal, rare)
H - hydronephrosis (eg, ureteropelvic junction obstruction)
I - infection
C - chromosomal aneuploidy syndromes (eg, Turner syndrome; trisom ies 13, 18, 21)
S - stones with
Unilateral renal agenesis
Ureteric bud fails to develop and induce differentiation of metanephric mesenchyme - complete absence of kidney and ureter.
Multicystic dysplastic kidney
Ureteric bud fails to induce differentiation of metanephric mesenchyme - nonfunctional kidney consisting of cysts and connective tissue.
Predominantly nonhereditary and usually unilateral; bilateral leads to Potter sequence.
Duplex collecting system
Blastema creates a Y-shaped bifid ureter.
Strongly associated with vesicoureteral reflux and/or ureteral obstruction, inc risk for UTI’s.
Posterior urethral valves
Membrane remnant in the posterior urethra in males;
It can be diagnosed prenatally by hydronephrosis and dilated or thick-walled bladder on ultrasound.
The most common cause of bladder outlet obstruction in male infants.
Renal vasculature
renal artery - segmental artery - interlobar artery - arcuate artery - interlobular artery - afferent arteriole - glomerulus - efferent arteriole - vasa rectal peritubular capillaries - venous outflow.
SI-AI-A
Course of ureter
_______within the _____ part of the ureter prevents urine reflux.
arises from the renal pelvis, travels under gonadal arteries -> over common iliac artery ->under uterine artery/vas deferens
(retroperitoneal).
Muscle fibers within the intramural part of the ureter prevents urine reflux.
Blood supply to ureter:
PR MAGIC VID
• Proximal:
P - Proximal
R - renal arteries
• Middle: M -Middle A - aorta G - gonadal artery I - internal iliac arteries C - common iliac
• Distal:
V - Vesical arteries (superior)
I - internal Iliac
D - Distal
Glomerular filtration barrier
Composed of:
- Fenestrated capillary endothelium (prevents entry of > 100 nm)
- Basement membrane with type IV collagen chains and heparan sulfate
- Visceral epithelial layer consisting of podocyte foot processes (prevents entry of molecules > 50- 60 nm)
Charge barrier- all 3 layers contain (-) charged glycoproteins-prevents (-) molecules entery.
Normal GFR
= 100 mL/min.
Creatinine clearance is an approximate measure of GFR. Slightly overestimates GFR because creatinine is moderately secreted by renal tubules.
Plasma volume =
Plasma volume = TBV x (I - Hct).
eRPF=?
eRPF = uPAH x V/pPAH = cPAH·
eRPF underestimates true renal plasma flow (RPF) slightly.
Renal blood flow (RBF) = ?
% of CO?
Renal blood flow (RBF) = RPF/(l - Hct).
Usually 20 - 25% of cardiac output.
Filtration fraction (FF) = ?
Filtration fraction (FF) = GFR/RPF Normal FF = 20% .
Filtered load (mg/min)= CFR (mL/min) x plasma concentTation (mg/mL).
Filtered load (mg/min) =?
Filtered load (mg/min) = GFR (mL/min) x plasma concentration (mg/mL).
Filtered load =?
Filtered load = GFR x Px
Reabsorption rate = ?
Reabsorption rate = filtered - excreted.
Secretion rate = ?
Secretion rate = excreted - filtered.
FeNa = ?
fractional excretion of sodium.
Excretion rate = ?
Excretion rate = V x U
FeNa = equsions
= Na+ excreted/Na+ filtered
= V x U / GFR x PNa
= Pcr x UNa/ Ucr x PNa
Glucose clearance
In adults, at plasma glucose of - 200 mg/dL, glucosuria begins (threshold). At a rate of about 375 mg/min, all transporters are fully saturated (Tm).
Early PCT - % Na+ reabsorbed?
Other notes
65- 80% Na+ reabsorbed.
contains a brush border. Reabsorbs all glucose and amino acids and most HC03-, Na+, Cl-, P04l-, K+, H20, and uric acid. Isotonic absorption.
Generates and secretes NH3, which enables the kidney to secrete more H+
Thin descending loop of Henle - % Na+ reabsorbed?
impermeable to Na+
Thick ascending loop of Henle - % Na+ reabsorbed?
Other notes
10- 20% Na+ reabsorbed.
lumen potential generated by K+ backleak ->paracellular reabsorption of Mg2+ and Ca2+.
Impermeable to H20.
Makes urine less concentrated as it ascends.
Early DCT % Na+ reabsorbed?
Impermeable to H20 - Makes urine fully dilute (hypotonic).
5- 10% Na+ reabsorbed.
Collecting tubule - cells
Principle cells - ENac, K+ channel, Na/K+ ATPase activity -> reabsorbs Na+ in exchange for secreting K+
Alfa intercalated cells - Makes urine Acidic -> H+ secretion
Beta intercalated cells - Makes urine Basic -> HCO3- secretion (HCO3-/CI- exchanger on the apical side), reabsorbs H+.
Collecting tubule - % Na+ reabsorbed?
3- 5% Na+ reabsorbed.
Aldosterone activity in DCT
Aldosterone - mineralocorticoid receptor (mRNA ->protein synthesis)
In Principle cells: inc ENac, K+ channel, Na/K+ ATPase activity.
In Alfa intercalated cells: in H+ATPase -> inc HCO3- /Cl- exchanger.
ADH activity in DCT
acts at V2 receptor - insertion of aquaporin H2O channels on the apical side.
Fanconi syndrome CAUSES
Wilsons MIG has Lead/Platinum Toxin Tyers!
Wilson disease
M - multiple myeloma
I - ischemia
G - glycogen storage disease
Lead/Cisplatin
Nephrotoxins/drugs (eg, ifosfamide)
Tyrosinemia
Liddle syndrome
A gain of function mutation -> inc activity of Na+ channel -> inc Na+ reabsorption in collecting tubules.
Autosomal dominant - Presents similarly to hyperaldosteronism, but aldosterone is nearly undetectable.
Treat with amiloride
Syndrome of
Apparent
Mineralocorticoid
Excess
Hereditary 11 beta -HSD deficiency (converts cortisol to cortisone) -> inc cortisol -> Inc mineralocorticoid receptor activity (cortisone inactive in these receptors.
Autosomal recessive or acquired from glycyrrhetinic acid (present in Licorice)
Treat with K+-sparing diuretics (dec mineralocorticoid effects) or corticosteroids (dec endogenous cortisol production)
Renin secreted by ____ in response to:
Secreted by JG cells in response to:
Dec renal perfusion pressure (detected by renal baroreceptors in afferent arteriole).
Dec NaCl delivery to macula densa cells.
inc renal sympathetic discharge (beta 1 effect).
AT II
Helps maintain blood volume and blood pressure.
Affects baroreceptor function; limits reflex bradycardia, which would normally accompany its pressor effects.
A -Aldosterone
C - constriction (Vasoconstriction)
A - ADH
N - Na+/K+ activity
E - Efferent arteriole
ANP, BNP
Released from atria (ANP) and ventricles (BNP) in response to inc volume;
inhibits renin-angiotensin aldosterone system;
relaxes vascular smooth muscle via cGMP -> inc GFR, dec renin.
Dilates afferent arteriole, promotes natriuresis.
ADH
Primarily regulates serum osmolality;
Responds to low blood volume states.
Reabsorption of water in collecting ducts.
Reabsorption of urea in collecting ducts - maintain corticopapillary osmotic gradient.
Aldosterone
Primarily regulates ECF volume and Na+ content;
Response to low blood volume states.
Responds to hyperkalemia by inc K+ excretion.
Erythropoietin
Released by interstitial cells in peritubular capillary bed in response to hypoxia.
kidney disease. Supplementation can cause HTN.
Calciferol (vitamin D) made from:
PCT cells convert 25 -OH vitamin D3 to 1,25-(OH)2 vitamin D3 (calcitriol, active form).
Prostaglandins
Paracrine secretion vasodilates the afferent arterioles to inc RBF.
NSAIDs block renal-protective prostaglandin synthesis -> constriction of the afferent arteriole and dec GFR;
this may result in acute kidney injury in low renal blood flow states.
Dopamine
Secreted by PCT cells, promotes natriuresis.
At low doses - dilates interlobular arteries, afferent arterioles, efferent arterioles -> inc RBF, little or no change in GFR.
At higher doses - it acts as a vasoconstrictor.
SHIFTS K+ OUT Of CELL (CAUSING HYPERKALEMIA)
D - Digitalis (blocks Na+/K+ ATPase)
O - Osmolarity (Hyper)
L - Lysis of cells (eg, crush injury, rhabdomyolysis, tumor lysis syndrome)
A - Acidosis
B - Beta-blocker
S - Sugar (insulin deficiency)
S - Succinylcholine (risk in burns/muscle trauma)
Sodium - Electrolyte disturbances
Low presentation- Nausea, malaise, seizures
High presentation- Irritability
Both presentation- stupor, coma
Potassium - Electrolyte disturbances
High presentation- Wide QRS and peaked T waves on ECG
Both presentation- arrhythmias, muscle weakness
Low presentation - CUTS
C - cramps
U - U waves
T - T wave flattened
S - spasm
Calcium - Electrolyte disturbances
Low presentation- Tetany, seizures, QT prolongation, twitching, spasms (“seizers” in CNS, heart, muscles)
High presentation:
Stones (renal) bones (pain) groans (abdominal pain) thrones (inc urinary frequency) psychiatric overtones (anxiety, altered mental status)
Magnesium - Electrolyte disturbances
Low presentation- Tetany, torsades de pointes, hypokalemia, hypocalcemia (<1.0 mEq/L)
High presentation- DTRs, lethargy, bradycardia, hypotension, cardiac arrest, hypocalcemia (depressed neurons, cardiovascular system)
Both presentation- hypocalcemia
Phosphate - Electrolyte disturbances
Low presentation- Bone loss, osteomalacia (adults), rickets (children)
High presentation- Renal stones, metastatic calcifications, hypocalcemia
Winters formula:
If measured Pco2 > predicted Pco2 -> concomitant respiratory acidosis;
If measured Pco2 < predicted Pco2 -> concomitant respiratory alkalosis;
1.5 x [HCO3-] + 8 +/- 2
Respiratory acidosis causes:
M - muscle weakness O - Opioids O - obstruction D - diseases of the lung (acute/chronic) S - sedatives
High anion gap Metabolic acidosis causes:
M - Methanol (formic acid)
U - Uremia
D - Diabetic ketoacidosis
P - Propylene glycol I - Iron tablets or INH L - Lactic acidosis E - Ethylene glycol (oxalic acid) S - Salicylates (late)
Normal anion gap Metabolic acidosis causes:
C - chloremia(hyper) H - hyperalimentation A - Addison disease R - Renal tubular acidosis D - Diarrhea
A - Acetazolamide
S - Spironolactone
S - Saline infusion
Respiratory alkalosis causes:
Hyperventilation:
P - Pulmonary embolism A - Anxiety T - Tumor H - Hypoxemia S - Salicylates (early)
Metabolic alkalosis
H+ loss (loss of gastric acid):
Vomiting
Antacid use
HCO3- excess (Kidneys):
Loop diuretics
Hyperaldosteronism
Renal tubular acidosis -
Urine pH/Serum K+
Proximal <5.5 pH< Distal
Both have low K+
Type 4 has high K+ and variable pH
Distal renal tubular acidosis (type 1)
DEFECT
Inability of alfa-intercalated cells to secrete H+ - no new HCO3- is generated -> metabolic acidosis
Proximal renal tubular acidosis (type 2)
DEFECT
PCT defect HCO3- reabsorption -> inc excretion of HCO3- in urine -> metabolic acidosis
Urine can be acidified by alfa-intercalated cells in collecting duct, but not enough to overcome the increased excretion of HCO3- -> metabolic acidosis
Hyperkalemic tubular acidosis (type 4)
DEFECT
Hypoaldosteronism or aldosterone resistance;
hyperkalemia -> dec NH3 synthesis in PCT -> dec NH4+ excretion
Distal renal tubular acidosis (type 1) - CAUSES
A - analgesic nephropathy / autoimmune diseases (eg, SLE)
B - Amphotericin B toxicity
C - congenital anomalies (obstruction) of urinary tract
Proximal renal tubular acidosis (type 2) - CAUSES
Mother FuCker: Multiple myeloma, Fanconi syndrome, carbonic anhydrase inhibitors
Hyperkalemic tubular acidosis (type 4) - CAUSES
Dec aldosterone production:
R - Renin (diabetic hyporeninsm)
A - adrenal insufficiency
N - NSAIDs
T - TMP-SMX
O - obstruction
C - cyclosporine
H - heparin
A - ACE inhibitors, ARBs
D - diuretics (K+-sparing)
RBC casts imply
Glomerulonephritis, hypertensive emergency.
WBC casts imply
Tubulointerstitial inflammation, acute pyelonephritis, transplant rejection.
Fatty casts (“oval fat bodies”) imply
Nephrotic syndrome. Associated with “Maltese cross” sign.
Granular casts imply
Acute tubular necrosis (ATN). Often “muddy brown” in appearance.
Waxy casts imply
End-stage renal disease/chronic kidney disease.
Hyaline casts imply
Nonspecific, can be a normal finding. Form via solidification of Tamm- Horsfall mucoprotein (secreted by renal tubular cells).
Renal cell carcinoma - associated with paraneoplastic syndromes and Tx
P - PTHrP
E - Ectopic EPO
A - ACTH
R - Renin
Treatment: surgery/ablation for localized disease. immunotherapy (eg, aldesleukin) or targeted therapy for metastatic disease rarely curative.
Resistant to chemotherapy and radiation therapy.
Cut the PEAR!
Renal cell carcinoma - Pathology
Polygonal dear cells filled with accumulated lipids and carbohydrates. Often golden-yellow a due to inc lipid content.
Originates from PCT -> invades renal vein (may develop varicocele if left-sided) - IVC -> hematogenous spread -> metastasis to lung and bone.
Manifests with hematuria, palpable masses, 2° polycythemia, flank pain, fever, weight loss.
Renal oncocytoma
Benign epithelial cell tumor arising from collecting ducts.
Large eosinophilic cells with abundant mitochondria without perinuclear clearing a (vs chromophobe renal cell carcinoma).
Presents with painless hematuria, flank pain, abdominal mass.
Often resected to exclude malignancy (eg, renal cell carcinoma).
WAGR complex-
Wilms tumor
Aniridia (absence of the iris)
Genitourinary malformations,
Retardation/intellectual disability
(WT1 deletion)
Denys-Drash syndrome-
Wilms tumor
Diffuse mesangial sclerosis (early-onset nephrotic syndrome),
Dysgenesis of gonads (male pseudohermaphroditism)
WT1 mutation
G1MS
Beckwith-Wiedemann syndrome-
(WT2 mutation)
H - Hemihyperplasia
O - Organomegaly
W - Wilms tumor
Much? - Macroglossia
Transitional cell carcinoma associated with?
can occur in renal calyces, renal pelvis, ureters, and bladder
Causes - problems in your Pee SAC:
P - Phenacetin
S - Smoking
A - Aniline dyes
C - Cyclophosphamide.
Squamous cell carcinoma of the bladder
Chronic irritation of urinary bladder -> squamous metaplasia -> dysplasia and squamous cell carcinoma.
Risk factors include Schistosoma haematobium infection (Middle East), chronic cystitis, smoking, chronic nephrolithiasis.
Presents with painless hematuria.
Stress incontinence - Tx
Treatment: pelvic floor muscle strengthening (Kegel) exercises, weight loss, pessaries.
Urgency incontinence - Tx
Treatment: Kegel exercises, bladder training (timed voiding, distraction or relaxation
techniques}, antimuscarinics (eg, Oxybutynin for Overactive bladder).
Overflow incontinence - Tx
catheterization, relieve obstruction (eg, alfa-blockers for BPH).
Stress incontinence - associations
Inc risk with obesity, vaginal delivery, prostate surgery. Positive bladder stress test (directly observed leakage from urethra upon coughing or Valsalva maneuver).
Urgency incontinence - associations
Overactive bladder (detrusor overactivity) - leak with an urge to void immediately. Associated with UTI.
Overflow incontinence - associations
Associated with polyuria (eg, diabetes), bladder outlet obstruction (eg, BPH), neurogenic bladder (eg, MS). Inc post-void residual (urinary retention) on catheterization or ultrasound.
Acute cystitis - Causes:
Causes:
• E coli (most common).
• Staphylococcus saprophyticus- seen in sexually active young women (E coli is still more common in this group).
• Klebsiella.
• Proteus mirabilis-urine has ammonia scent.
Systemic signs (eg, high fever, chills) are usually absent!
Acute pyelonephritis - Pathology
Neutrophils infiltrate renal interstitium.
Affects cortex with relative sparing of glomeruli/vessels.
Presents with WBCs in urine +/- WBC casts. CT would show striated parenchymal enhancement.
Presents with fevers, flank pain (costovertebral angle tenderness), nausea/vomiting, chills.
Complications include: SCAN S - sepsis (urosepsis) C - chronic pyelonephritis A - abscess (perinephric) N - necrosis (papillary)
Treatment: antibiotics.
Chronic pyelonephritis
The result of recurrent or inadequately treated episodes of acute pyelonephritis.
Typically requires predisposition to infection such as vesicoureteral reflux or chronically obstructing kidney stones.
Coarse, asymmetric corticomedullary scarring, blunted calyx.
Tubules can contain eosinophilic casts resembling thyroid tissue (thyroidization of kidney).
Xanthogranulomatous pyelonephritis
rare;
grossly orange nodules that can mimic tumor nodules;
characterized by widespread kidney damage due to granulomatous tissue containing foamy macrophages.
Associated with Proteus infection.
Consequences of renal failure
M - Metabolic Acidosis
U - Uremia
P - Potassium (high)
A - Anemia (Erythropoietin failure)
L - Lipidemia (especially high triglycerides)
O - osteodystrophy
N - Na+/H2O retention (HF, pulmonary edema, hypertension)
G - Growth retardation and developmental delay
Uremia- a clinical syndrome marked by: PP + CNS trouble • Nausea and anorexia • Pericarditis • Asterixis • Encephalopathy • Platelet dysfunction
Acute interstitial nephritis
Also called tubulointerstitial nephritis. Acute interstitial renal inflammation. Pyuria (classically eosinophils) and azotemia occurring after the administration of drugs that act as haptens.
QRS PPP SSS DM -
D - Diuretics
M -Mycoplasma
Q - Quinolones
R - Rifampin
S - Sulfonamides
P - Pain-free (NSAIDs)
P - Penicillins and cephalosporins
P - Proton pump inhibitors
S - Sjogren syndrome
S - SLE
S - Sarcoidosis
Acute tubular necrosis - stages:
3 stages:
- Inciting event
- Maintenance phase - oliguric, fatal (lasts 1- 3 weeks; risk of hyperKalemia, Metabolic acidosis, Uremia -> “full of KUM”)
- Recovery phase - polyuric; BUN and serum creatinine fall;
risk of hypokalemia and renal wasting of other electrolytes and minerals
Diffuse cortical necrosis
Acute generalized cortical infarction of both kidneys. Likely due to a combination of vasospasm and DIC.
Associated with obstetric catastrophes (eg, abruptio placentae), septic shock.
Renal papillary
necrosis
Sloughing of necrotic renal papillae -> gross hematuria and proteinuria.
May be triggered by recent infection or immune stimulus.
Associated with:
(SAAD papa with papillary necrosis) S - Sickle cell disease or trait A -Analgesics (NSAIDs) D - Diabetes mellitus
Pyelonephritis (Acute)
Acute tubular necrosis - causes
Can be caused by ischemic or nephrotoxic injury:
• ischemic - 2° to l renal blood flow (eg, hypotension, shock, sepsis, hemorrhage, HF). Results in death of tubular cells that may slough into tubular lumen (PCT and thick ascending limb are high ly susceptible to injury).
• Nephrotoxic - 2° to injury resulting from toxic substances. Proximal tubules are particularly susceptible to injury.
L - lead
A - aminoglycosides
M - myoglobinuria (crush injury)/ hemoglobinuria
P - Platinum drugs (cisplatin)
E - ethylene glycol
R - radiocontrast agents
Acute tubular necrosis - causes
Can be caused by ischemic or nephrotoxic injury:
• ischemic - 2° to l renal blood flow (eg, hypotension, shock, sepsis, hemorrhage, HF). Results in death of tubular cells that may slough into tubular lumen (PCT and thick ascending limb are high ly susceptible to injury).
• Nephrotoxic - 2° to injury resulting from toxic substances. Proximal tubules are particularly susceptible to injury.
L - lead
A - aminoglycosides
M - myoglobinuria (crush injury)/ hemoglobinuria
P - Platinum drugs (cisplatin)
E - ethylene glycol
R - radiocontrast agents
Main causes of renal artery stenosis:
- Atherosclerotic plaques- proximal I/3rd of renal artery, usually in older males, smokers.
- Fibromuscular dysplasia - distal 2/3rd of renal artery or segmental branches, usually young or middle-aged females.
Autosomal dominant
polycystic kidney
disease - Associated with
Associated with berry aneurysms, mitral valve prolapse, benign hepatic cysts, diverticulosis.
Presents with flank pain, hematuria, hypertension, urinary infection, progressive renal failure in 50% of individuals.
Treatment: If hypertension or proteinuria develops, treat with ACE inhibitors or ARBs.
Autosomal recessive
polycystic kidney
disease
Cystic dilation of collecting ducts
Often presents in infancy. Associated with congenital hepatic fibrosis. Significant oliguric renal failure in utero can lead to Potter sequence.
Other - systemic hypertension, progressive renal insufficiency, and portal hypertension from congenital hepatic fibrosis.
Autosomal dominant
tubulointerstitial
kidney disease
Medullary cystic kidney disease. Causes tubulointerstitial fibrosis and progressive renal insufficiency with inability to concentrate urine.
Smaller kidneys on ultrasound. Poor prognosis.
Simple vs complex
renal cysts
Simple cysts are filled with ultrafiltrate (anechoic on ultrasound).
Very common and account for the majority of all renal masses. Found incidentally and typically asymptomatic.
Complex cysts, including those that are:
septated
enhanced
have solid components on imaging.
Require follow-up or removal due to the risk of renal cell carcinoma.
