Renal Flashcards
Potter Sequence (Syndrome)
Oligohydramnios (too little amniotic fluid) leads to compression of developing fetus leading to limb deformities, facial anomalies (low-set ears and retrognathia), compression of chest and lack of amniotic fluid aspiration into fetal lungs.
This leads to pulmonary hypoplasia (cause of death)
Causes ARPKD, obstructive uropathy (posterior urethral valves), bilateral renal agensis.
Babies who can’t P in utero develop Potter Sequence
P = Pulmonary hypoplasia O = Oligohydramnios (trigger) T = Twisted Face T = Twisted Skin E = Extremity defects R = Renal failure (in utero)
Kidney embryo
1) Pronephros - week 4; then degenerates
2) Mesonephros - functions as interim kidney for 1st trimester; later contributes to male genital system
3) Metanephros - permanent; first appears in 5th week of gestation; nephrogenesis continues through 32-36 weeks of gestation.
- Ureteric Bud - derived from caudal end of mesonephric duct; gives rise to ureter, pelvises, calyces, collecting duct; fully canalized by 10th week
- Metanephric mesenchyme - ureteric bud interacts with this tissue; interaction induces differentiation and formation of glomerulus through to distal convoluted tubule (DCT)
- Aberrant interaction btw these 2 tissues may result in several congenital malformations of the kidney
4) Ureteropelvic junction - last to canalize. Most common site of obstruction (hydronephrosis) in fetus.
Horseshoe kidney
Inferior poles of both kidneys fuse. As they ascend from pelvis during fetal development, horseshoe kidneys get trapped under inferior mesenteric artery and remain low in the abdomen.
Kidneys function normally.
Associated with ureteropelvic junction obstruction, hydronephrosis, renal stones, infection, chromosomal aneuploidy syndromes (Edwards, Down, Patau, Turner), and rarely renal cancer.
Multicystic dysplastic kidney
Due to abnormal interaction between ureteric bud and metanephric mesenchyme.
Leads to a nonfunctional kidney consisting of cysts and connective tissue.
If unilateral (most common), generally asymptomatic with compensatory hypertrophy of contralateral kidney.
Often diagnosed prenatally via ultrasound
Duplex collecting system
Bifurcation of ureteric bud before it enters metanephric blastema creates Y-shaped bifid ureter.
Can alternatively occur when 2 ureteric buds reach and interact with metanephric blastema.
Strongly associated with vesicoureteral reflux and/or ureteral obstruction, higher risk of UTIs.
Which kidney is taken from donor before transplant?
Left.
It has a longer renal vein.
Ureters - course
Ureters pass under uterine artery and under ductus deferens (retroperitoneal)
Gyn procedures involving ligation of uterine vessels traveling in cardinal ligament may damage ureter leading to ureteral obstruction or leak.
Fluid compartments
HIKIN - High K intracellularly
60-40-20 rule (% of body weight for avg person):
60% total body water
40% ICF
20% ECF
Plasma volume measured by radiolabeled albumin
Extracellular volume measured by inulin
Osmolality = 285-295 mOsm/kg H2O
Normal fluid volumes
Normal person is 70kg (70L)
.6 (70) = 42L of total body water
.4 (70) = 28L of non water mass
Of the 42L water mass - 1/3 is extracellular, 2/3 is intracellular
OR 20% of overall = ECF, 40% of overall = ICF
.33 (42) or .2 (70) = 14 L ECF
.67 (42) or .4 (70) = 28 L ICF
Extracellular = Interstitial fluid + plasma
Intracellular includes RBC volume
Blood volume is about 6 L. Of these 6L, 45% is hematocrit (RBC). .45 (6) = 2.8 L of RBC (intracellular) and 3.2 L is plasma (extracellular)
Glomerular filtration barrier
Responsible for filtration of plasma according to size and net charge.
Composed of:
1) Fenestrated capillary endothelium (size barrier)
2) Fused basement membrane with heparan sulfate (negative charge barrier)
3) Epithelial layer consisting of podocyte foot processes
Charge barrier is lost in nephrotic syndrome leading to albuminuria, hypoproteinemia, generalized edema, hyperlipidemia
Renal Clearance
Cx = UxV/Px = volume of plasma from which the substance is completely cleared per unit time.
Cx = Clearance of X (mL/min) Ux = Urine concentration of X (mg/mL) Px = Plasma concentration of X (mg/mL) V = urine flow rate (mL/min)
Cx
Net tubular reabsorption of X
Cx > GFR
Net tubular secretion of X
Cx = GFR
No net secretion or reabsorption
Glomerular Filtration Rate
Inulin clearance can be used to calculated GFR bc it is freely filtered and is neither reabsorbed nor secreted
UV/P for inulin:
GFR = (U inulin)V/(P inulin) = C inulin
GFR = Kf [(Pgc - Pbs) - (pi gc - pi bs)]
gc = glomerular capillary
bs = bowman space
Pi bs normally = 0
Normal GFR = 100 mL/min
Creatinine clearance is an approximate measure of GFR. Slightly overestimates GFR bc creatinine is moderately secreted by renal tubules.
Incremental reductions in GFR define the stages of chronic kidney disease.
Effective Renal Plasma Flow
eRPF can be estimated using para-aminohippuric acid (PAH) clearance bc it is both filtered and secreted in the proximal collecting tubule, resulting in near 100% excretion of all PAH entering kidney
eRPF = U pah V / P pah = C pah
RBF = RPF / (1 - Hct)
eRPF underestimates true renal plasma flow (RPF) by about 10%
Filtration
Filtration fraction (FF) = GFR/RPF
Normal FF = 20%
Filtered load (mg/min) = GFR (mL/min) x Plasma concentration (mg/mL)
GFR can be estimated with creatinine clearance. RPF is best estimated with PAH clearance.
Changes in glomerular dynamics
1) Afferent arteriole constriction:
Lower GFR, Lower RPF, no change FF (GFR/RPF)
2) Efferent arteriole constriction:
Higher GFR, Lower RPF, Higher FF
3) Higher plasma protein concentration:
Lower GFR, Flat RPF, Lower FF
4) Lower plasma protein concentration:
Higher GFR, Flat RPF, Higher FF
5) Constriction of ureter:
Lower GFR, Flat RPF, Lower FF
Prostaglandin effects on glomerulus
Preferentially dilates afferent arteriole (higher RPF, higher GFR, flat FF)
NSAIDs inhibit this
Angiotensin II effects on glomerulus
Preferentially constricts efferent arteriole (Lower RPF, Higher GFR, Higher FF)
ACE Inhibitors inhibit this
Calculation of reabsorption and secretion rate
Filtered Load = (GFR) (Px)
Excretion rate = (V)(Ux)
Reabsorption = filtered - excreted Secretion = excreted - filtered
Glucose clearance
Glucose at a normal plasma level is completely reabsorbed in PCT by Na/Glucose cotransport
At plasma glucose of 200, glucosuria begins (threshold).
At 375, all transporters are fully saturated (Tm)
Glucosuria is an important clinical clue to diabetes mellitus
Normal pregnancy may decrease ability of PCT to reabsorb glucose and amino acids leading to glucosuria and aminoaciduria.
Amino acid clearance
Na-dependent transporters in PCT reabsorb amino acids
Hartnup Disease
Auto recessive
Deficiency of neutral amino acid (like tryptophan) transporters in proximal renal tubular cells and on enterocytes leads to neutral aminoaciduria and lower absoprtion from the gut.
This lowers tryptophan for conversion to niacin leading to pellagra-like symptoms.
Treat with high protein diet and nicotinic acid
List the Renal Tubular Defects (5)
The kidneys put out FABulous Glittering LiquidS.
FA = Fanconi Syndrome is the 1st defect (PCT) B = Bartter Syndrome is next (Thick Ascending loop) G = Gitelman Syndrome is after Bartter (DCT) L = Liddle Syndrome is last (collecting tubule) S = Syndrome of apparent mineralocorticoid excess (collecting tubule)
Fanconi Syndrome
Generalized reabsorptive defect in PCT
Associated with higher excretion of nearly all amino acids, glucose, Bicarb, Phosphate.
May result in metabolic acidosis (prox renal tubular acidosis)
Causes include:
1) hereditary defects (Wilson disease, tyrosinemia, glycogen storage disease)
2) Ischemia
3) Multiple myeloma
4) Nephrotoxins/drugs (expired tetracyclines, tenofovir), lead poisoning
Bartter Syndrome
Reabsorptive defect in thick ascending loop of Henle.
Autosomal recessive
Affects Na/K/2Cl cotransporter
Results in hypokalemia and metabolic acidosis with hypercalciuria
Gitelman Syndrome
Reabsorptive defect of NaCl in DCT
Auto recessive
Less severe than Bartter. Leads to hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria
Liddle Syndrome
Gain of function mutation leading to higher Na reabsorption in collecting tubules (increased activity of epithelial Na channel)
Auto Dominant
Results in HTN, hypokalemia, metabolic alkalosis, lower aldosterone
Tx = Amiloride
Syndrome of apparent mineralocorticoid excess
Hereditary deficiency of 11B-hydroxysteroid dehydrogenase, which normally converts cortisol into cortisone in mineralocorticoid receptor-containing cells before cortisol can act on the mineralocorticoid receptors
Excess cortisol in these cells from enzyme deficiency leads to increased mineralocorticoid receptor activity.
This leads to HTN, hypokalemia, metabolic alkalosis.
Low serum aldosterone levels
Can acquire disorder from glycyrrhetic acid (present in licorice), which blocks activity of 11B-hydroxysteroid dehydrogenase
Renin-Angiotensin-Aldosterone System
Triggers:
1) Lower BP (JG Cells)
2) Low Na delivery (Macula Densa Cells)
3) Higher sympathetic tone (B1 receptors)
What happens?
These triggers increase secretion of Renin
Renin converts Angiotensinogen (from liver) to Angiotensin I
AT I is converted to Angiotensin II via ACE (from lungs and kidney). NOTE!!! ACE also breaks down bradykinins
AT II acts at a lot of places:
1) Acts at AT II receptor type 1 on vascular smooth muscle.
- This leads to vasoconstriction leading to increased BP
2) It constricts efferent arterioles of glomerulus.
- This leads to higher FF to preserve renal function (GFR) in low volume states (i.e. when RBF falls)
3) It triggers aldosterone release from adrenal gland.
- This increases Na channel and Na/K pump insertion in principal cells
- Enhances K and H excretion by way of principal cell K channels and alpha-intercalated cell H ATPases
- All this creates a favorable Na gradient for Na and H2O reabsorption
4) Triggers release of ADH from posterior pituitary
- Increases aquaporin insertion in principal cells (these dudes are in the collecting ducts)
- Leads to H2O reabsoprtion
5) Increases PCT Na/H activity
- leads to Na, Bicarb, H2O reabsorption (can permit contraction alkalosis)
6) Stimulates hypothalamus
- stimulates thirst
Angiotensin II
Affects baroreceptor function; limits reflex bradycardia, which would normally accompany its pressor effects. Helps maintain blood volume and blood pressure.
AT II acts at a lot of places:
1) Acts at AT II receptor type 1 on vascular smooth muscle.
- This leads to vasoconstriction leading to increased BP
2) It constricts efferent arterioles of glomerulus.
- This leads to higher FF to preserve renal function (GFR) in low volume states (i.e. when RBF falls)
3) It triggers aldosterone release from adrenal gland.
- This increases Na channel and Na/K pump insertion in principal cells
- Enhances K and H excretion by way of principal cell K channels and alpha-intercalated cell H ATPases
- All this creates a favorable Na gradient for Na and H2O reabsorption
4) Triggers release of ADH from posterior pituitary
- Increases aquaporin insertion in principal cells (these dudes are in the collecting ducts)
- Leads to H2O reabsoprtion
5) Increases PCT Na/H activity
- leads to Na, Bicarb, H2O reabsorption (can permit contraction alkalosis)
6) Stimulates hypothalamus
- stimulates thirst
ANP, BNP
Released from atria (ANP) and ventricles (BNP) in response to an increase in volume
May act as a “check” on renin-angiotensin-aldosterone system
Relaxes vascular smooth muscle via cGMP leading to an increased GFR, and lower renin
ADH
Primarily regulates osmolarity; also responds to low blood volume states
- Increases aquaporin insertion in principal cells (these dudes are in the collecting ducts)
- Leads to H2O reabsoprtion
Aldosterone
Primarily regulates ECF volume and Na content; responds to low blood volume states
- This increases Na channel and Na/K pump insertion in principal cells
- Enhances K and H excretion by way of principal cell K channels and alpha-intercalated cell H ATPases
- All this creates a favorable Na gradient for Na and H2O reabsorption
Juxtaglomerular apparatus
Consists of mesangial cells, JG Cells (modified smooth muscle of afferent arteriole) and the macula densa (NaCl sensor, part of DCT)
JG cells secrete renin in response to decreased renal blood pressure and increased sympathetic tone (B1)
Macula densa cells sense reduced NaCl delivery to DCT leading to adenosine release which causes vasoconstriction.
JGA maintains GFR via renin-angiotensin-aldosterone system
B-Blockers can decrease BP by inhibiting B1-receptors of the JGA leading to decreased renin release
Substances released by the Kidney (Kidney endocrine function)
1) Erythropoietin
2) 1,25-(OH)2D3
3) Renin
4) Prostaglandins
Erythropoietin
Released by interstitial cells in peritubular capillary bed in response to hypoxia
1,25-(OH)2D3
PCT cells convert 25-OH vitamin D to 1,25-(OH)2 Vitamin D (active form)
The enzyme that does this is 1alpha-hydroxylase
This enzyme is inhibited by PTH
Renin
Secreted by JG Cells in response to lower renal arterial pressure and increased renal sympathetic tone (B1 effect)
Prostaglandins
Paracrine secretion vasodilates the afferent arterioles to increase RBF
NSAIDs block renal-protective prostaglandin synthesis leading to constriction of afferent arteriole and lower GFR
This may result in acute renal failure
What causes a shift of K out of cells leading to hyperkalemia?
1) Digitalis
2) HyperOsmolarity
3) Lysis of cells (crush injury, rhabdomyolysis, cancer)
4) Acidosis
5) B-blocker
6) high blood Sugar (insulin deficiency)
trick = “DO LABS” on patients with hyperkalemia
What causes a shift of K into cells leading to hypokalemia?
1) Hypo-osmolarity
2) Alkalosis
3) B-adrenergic agonist (increases Na/K ATPase)
4) Insulin (Increases Na/K ATPase)
“IN”sulin shifts K “IN”to cells
Angiotensin II - where does it act? what does it do? Part 2
Made in response to lower BP
Causes efferent arteriole constriction leading to increased GFR and increased FF but with compensatory Na reabsoprtion in proximal and distal nephron
Net effect: preservation of renal function (higher FF) in low-volume state with simultaneous Na reabsoprtion (both proximal and distal) to maintain circulating volume
Parathyroid hormone
Secreted in response to:
1) lower plasma Ca
2) high plasma PO4
3) low plasma 1,25-(OH)2D3
Causes/leads to:
1) increased Ca reabsorption (DCT)
2) lower PO4 reabsorption (PCT)
3) higher 1,25-(OH)2D3 production (higher Ca and PO4 absorption from gut via vitamin D)
ANP - part 2
Atrial Natriuretic Peptide - it’s in the name!
Secreted in response to increased atrial pressure.
Causes increased GFR and increased Na filtration WITH NO COMPENSATORY NA REABSORPTION in distal nephron
Net effect: Na loss and volume loss.
Acts at afferent arteriole and DCT
Aldosterone - again part 2
Secreted in response to low blood volume (via AT II) and high plasma K
Causes more K secretion and more H secretion
Acts at collecting duct
ADH - again part 2
Vasopressin
Secreted in response to high plasma osmolarity and low blood volume.
Binds to receptors on principal cells
Causes more aquaporins to increase H2O reabsorption
Acts at collecting duct
Na imbalances
Low:
Nausea and maliase, stupor, coma, seziures
High:
Irritability, stupor, coma
K imbalances
Low:
U waves on ECG, flattened T waves, arrhythmias, muscle spasm
High:
Wide QRS and peaked T waves, arrhythmias, muscle weakness
Ca imbalances
Low:
Tetany, seizures, QT prolonged
High: Stones (renal) Bones (pain) Groans (abdominal pain) Thrones (higher urinary frequency) Psychiatric Overtones (anxiety, altered mental status)
Not necessarily calciuria
Mg imbalances
Low:
Tetany, torsades de pointes, hypokalemia
High:
Lower DTRs, lethargy, bradycardia, hypotension, cardiac arrest, hypocalcemia
PO4 imbalances
Low:
Bone loss, osteomalacia (adults), rickets (children)
High:
Renal stones, metastatic calcifications, hypocalcemia
Acid-Base physiology - Intro
- = primary disturbance
- = compensatory response
1) Metabolic acidosis
- Low pH**
- Low P CO2**
- Low bicarb*
Compensatory response: Hyperventilation (immediate)
2) Metabolic alkalosis
- High pH**
- High P CO2**
- High Bicarb*
Compensatory response: Hypoventilation (immediate)
3) Respiratory acidosis
- Low pH**
- High P CO2*
- High Bicarb**
Compensatory response: Increased renal Bicarb reabsorption (delayed)
4) Respiratory alkalosis
- High pH**
- Low P CO2*
- Low Bicarb**
Compensatory response: Reduced renal bicarb reabsorption (delayed)
Henderson-Hasselbach Equation
pH = 6.1 + log [HCO3] / (0.3 P CO2)
Winters Formula
P CO2 = 1.5 [HCO3] + 8 +/- 2
Predicted respiratory compensation for a simple metabolic acidosis can be calculated with this formula. If measured P CO2 significantly differs from predicted P CO2, then a mixed acid-base disorder is likely present.
Renal tubular acidosis
Disorder of the renal tubules that leads to normal anion gap (hyperchloremic) metabolic acidosis
Presence of casts in urine
Presence of casts indicates that hematuria/pyuria is of glomerular or renal tubular origin.
For example,
Bladder cancer, kidney stones lead to hematuria (no casts)
Acute cystitis leads to pyuria (no casts)
RBC casts
1) Glomerulonephritis
2) Malignant HTN
WBC casts
1) Tubulointerstitial inflammation
2) Acute pyelonephritis
3) Transplant rejection
Fatty casts (“oval fat bodies”)
Nephrotic syndrome
Granular (“muddy brown”) casts
Acute tubular necrosis
Waxy casts
End-stage renal disease/chronic renal failure
Hyaline casts
Nonspecific - can be a normal finding, often seen in concentrated urine samples
Diffuse glomerular disorders
> 50% of glomerulus is involved
Diffuse proliferative glomerulonephritis
Proliferative glomerular disorders
Hypercellular glomeruli
Membranoproliferative glomerulonephritis
Membranous glomerular disorders
Thickening of glomerular basement membrane (GBM)
Membranous nephropathy
Primary glomerular disease
A primary disease of the kidney specifically impacting the glomeruli
Minimal Change Disease
Secondary glomerular disease
A systemic disease or disease of another organ system that also impacts the glomeruli
SLE, diabetic nephropathy
Nephritic Syndrome
Due to GBM disruption.
Inflammatory process. When it involves glomeruli, it leads to hematuria and RBC casts in urine.
Associated with HTN (from salt retention), High BUN, High Creatinine, Oliguria (low urine output), hematuria, RBC casts in urine, azotemia.
Proteinuria often in subnephrotic range (
Nephrotic Syndrome
Massive proteinuria (> 3.5 g/day) with hypoalbuminemia, resulting edema, hyperlipidemia.
Frothy urine with fatty casts.
Due to podocyte damage disrupting glomerular filtration charge barrier.
May be primary (direct sclerosis of podocytes) or secondary (systemic process like diabetes secondarily damages podocytes)
Severe nephritic syndrome may present with nephrotic syndrome features (nephritic-nephrotic syndrome) if damage to GBM is severe enough to damage charge barrier.
Associated with a hypercoagulable state/thromboembolism (it causes the state) due to antithrombin (AT) III loss in urine and a higher risk of infection (due to loss of immunoglobulins in urine and soft tissue compromise by edema)
1) Focal segmental glomerulosclerosis (primary or secondary)
2) Minimal change disease (primary or secondary)
3) Membranous nephropathy (prim or second)
4) Amyloidosis (secondary only)
5) Diabetic glomerulonephropathy (secondary only)
Nephritic-Nephrotic Syndrome
Severe nephritic syndrome with profound GBM damage that damages the glomerular filtration charge barrier.
This leads to nephrotic-range proteinuria (> 3.5 g/day) and concomitant features of nephrotic syndrome. Can occur with any form of nephritic syndrome, but most commonly seen with:
1) Diffuse proliferative glomerulonephritis
2) Membranoprolifereative glomerulonephritis
Acute poststreptococcal glomerulonephritis
A nephritic syndrome
LM - glomeruli enlarged and hypercellular
ImmunoF - (“starry sky”) granular appearance (“lumpy bumpy”) due to IgG, IgM, and C3 deposition along GBM and mesangium
EM - Subepithelial immune complex (IC) humps
Most often seen in children. Occurs about 2 weeks after GAS infection of pharynx OR skin.
Resolves spontaneously
Type 3 hypersensitivity rxn
Presents with peripheral and periorbital edema, cola-colored urine, HTN
High anti-DNase B titers, Low complement levels
Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN)
A nephritic syndrome
LM and IF - crescent moon shape. Crescents consist of fibrin and plasma proteins (C3b) with glomerular parietal cells, monocytes, macrophages
Poor prognosis. Rapidly deteriorating renal function (days - weeks)
Several disease processes may result in this pattern, in particular:
1) Goodpasture Syndrome - Type 2 hypersensitivity; antibodies to GBM and alveolar basement membrane leads to linear Immunofluorescence (IF)
Hematuria/hemoptysis
Tx = emergent plasmapheresis
2) Granulomatosis with polyangiitis (Wegener)
PR3-ANCA/c-ANCA
3) Microscopic polyangiitis
MPO-ANCA/p-ANCA
Diffuse proliferative glomerulonephritis (DPGN)
A nephritic syndrome
Due to SLE or membranoproliferative glomerulonephritis
LM - wire looping of capillaries
EM - subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition
IF - granular
Most common cause of death in SLE (think “wire lupus”)
DPGN and MPGN often present as nephrotic syndrome and nephritic syndrome concurrently.
IgA nephropathy (Berger Disease)
A nephritic syndrome
LM - mesangial proliferation
EM - mesengial IC deposits
IF - IgA based IC deposits in mesangium.
Renal pathology of Henoch-Schonlein purpura
Often presents with renal insufficiency or acute gastroenteritis. Episodic hematuria with RBC casts. Not to be confused with Buerger Disease (thromboangiitis obliterans)
Alport Syndrome
A nephritic syndrome
Mutation in type 4 collagen leads to thinning and splitting of glomerular basement membrane
Most commonly X linked
Eye problems (retinopathy, lens discoloration), glomerulonephritis, sensorineural deafness
“cant see, cant pee, cant hear a buzzing bee”
“Basket-weave” appearance on EM
Membranoproliferative glomerulonephritis (MPGN)
A nephritic syndrome
Type 1 - subendothelial immune complex (IC) deposits with granular IF; “tram track” appearance on PAS stain and H&E stain due to GBM splitting caused by mesangial ingrowth
Type 2 - intramembranous IC deposits; “dense deposits”
MPGN is a nephritic syndrome that often copresents with nephrotic syndrome.
Type 1 may be secondary to Hep B or C infection. May also be idiopathic.
Type 2 is associated with C3 nephritic factor (Stabilizes C3 convertase leading to lower C3 levels in serum)
Focal segmental glomerulosclerosis
A nephrotic syndrome
LM - segmented sclerosis and hyalinosis
IF - nonspecific for focal deposits of IgM, C3, C1
EM - Effacement of foot process similar to minimal change disease
Most common cause of nephrotic syndrome in blacks and Hispanics.
Can be primary (idiopathic) or secondary to other conditions (HIV, sickle cell, heroin abuse, massive obesity, interferon treatment, chronic kidney disease due to congenital malformations)
Primary disease has inconsistent response to steroids. May progress to chronic renal disease
Minimal Change Disease (Lipid Nephrosis)
A nephrotic syndrome
LM - normal glomeruli (lipid may be seen in PCT cells)
IF - negative
EM - effacement (fusion) of foot processes
Most common cause of nephrotic syndrome in children.
Often primary (idiopathic) and may be triggered by recent infection, immunization, immune stimulus.
Rarely, may be secondary to lymphoma (cytokine-mediated damage).
Primary disease has excellent response to corticosteroids
Membranous nephropathy
A nephrotic syndrome
LM - Diffuse capillary and GBM thickening
IF - granular as a result of immune complex deposition. Nephrotic presentation of SLE.
EM - “spike and dome” appearance with subepithelial deposits
Most common cause of primary nephrotic syndrome in white adults.
Can be primary (idiopathic) or secondary to other conditions [antibodies to phospholipase A2 receptor, drugs (NSAIDs and penicillamine), infections (HBV and HCV), SLE, solid tumors]
Primary disease has poor response to steroids. May progress to chronic renal disease.
Amyloidosis
A nephrotic syndrome
LM - Congo red stain shows apple-green birefringence under polarized light.
Kidney is most commonly involved organ (systemic amyloidosis).
Associated with chronic conditions (multiple myeloma, TB, RA)
Diabetic glomerulo-nephropathy
A nephrotic syndrme
LM - mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions)
Nonenzymatic glycosylation of GBM leads to higher permeability and thickening of efferent arterioles. This leads to higher GFR and mesangial expansion.
Kidney stones
Can lead to severe complications, such as hydronephrosis, pyelonephritis.
Presents with unilateral flank tenderness, colicky pain radiating to groin, hematuria.
Treat and prevent by encouraging fluid intake.
Calcium stones
80%
Precipitates at high pH (calcium phosphate)
Precipitates at low pH (calcium oxalate)
XR = radiopaque
Urine crystal = Envelope-or dumbell-shaped calcium oxalate
Oxalate crystals can result from ethylene glycol (antifreeze) ingestion, vitamin C abuse, hypocitraturia, malabsorption (Crohn Disease).
Most common kidney stone presentation: Calcium oxalate stone in patient with hypercalciuria and normocalcemia
Tx = hydration, thiazides, citrate
Ammonium magnesium phosphate stones
15%
Precipitates at high pH
XR = radiopaque
Urine crystal = Coffin Lid
Also known as struvite. Caused by infections with urease (+) bugs - Proteus, Klebsiella, Staph sapro
These bugs hydrolyze urea to ammonia leading to urine alkalinization
Commonly form staghorn calculi
Tx = eradication of underlying infection, surgical removal of stone
Uric acid stones
5%
Precipitates at low pH
XR = radiolucent
Urine crystal = Rhomboid or rosettes
Risk factors: low urine volume, arid climates, acidic pH
Visible on CT and US, but not XR.
Strong association with hyperuricemia (gout)
Often seen in diseases with high cell turnover, like leukemia
Tx = alkalinization of urine, allopurinol
Cystine stones
1 %
Precipitates at low pH
XR = radiolucent
Urine crystal = hexagonal
Hereditary (auto recess) condition in which cysteine-reabsorbing PCT transporter loses function, causing cystinuria.
Cystine is poorly soluble, thus stones form in urine. Mostly seen in children. Can form staghorn calculi.
Sodium cyanide nitroprusside test (+)
SIXtine stones have SIX sides
Tx = alkalinization of urine
Hydronephrosis
Distention/dilation of renal pelvis and calyces
Usually caused by urinary tract obstruction (renal stones, BPH, cervical cancer, injury to ureter)
Other causes include retroperitoneal fibrosis, vesicoureteral reflux
Dilation occurs proximal to site of pathology.
Serum creatinine becomes elevated ONLY if obstruction is bilateral or if patient has only one kidney.
Leads to compression and possible atrophy of renal cortex and medulla
Renal cell carcinoma
Originates from PCT cells going to polygonal clear cells filled with accumulated lipids and carbs.
Most common in men 50-70 years old. Increased incidence with smoking and obesity.
Manifests clinically with hematuria, palpable mass, secondary polycythemia, flank pain, fever, weight loss.
Invases renal vein then IVC and spreads hematogenously; metastasizes to lung and bone.
Tx = resection if localized disease. Immunotherapy or targeted therapy for advanced/metastatic disease. Resistant to chemotherapy and radiation therapy.
Most common primary renal malignancy
Associated with gene deletion on chromosome 3 (sporadic or inherited as von-Hippel-Lindau syndrome)
RCC = 3 letters = chromosome 3
Associated with paraneoplastic syndromes (ectopic EPO, ACTH, PTHrP)
“Silent” cancer bc commonly presents as a metastatic neoplasm
Renal oncocytoma
Benign epithelial cell tumor
Large eosinophilic cells with abundant mitochondria without perinuclear clearing (vs Chromophobe renal cell carcnoma)
Presents with painless hematuria, flank pain, abdominal mass
Often resected to exclude malignancy (eg RCC)
Wilms Tumor (Nephroblastoma)
Most common renal malignancy of early childhood (age 2-4)
Contains embryonic glomerular structures
Presents with large, palpable, unilateral flank mass and/or hematuria. Loss of function mutations of tumor suppressor genes WT1 or WT2 on chromosome 11.
May be part of Beckwith-Wiedmann syndrome (Wilms tumor + macroglossia + organomegaly + hemihypertrophy)
OR WAGR complex (Wilms + Aniridia + GU malformation + retardation)
Transitional Cell Carcinoma
Most common tumor of urinary tract system (can occur in renal calyces, renal pelvis, ureters, and bladder)
Painless hematuria (no casts) suggests bladder cancer
Associated with problems in your Pee SAC: Phenacetin (an analgesic drug), Smoking, Aniline dyes, and Cyclophosphamide
Squamous cell carcinoma of the bladder
Chronic irritation of urinary bladder leads to squamous metaplasia leading to dysplasia and squamous cell carcinoma
Risk factors include Schistosoma haemotobium infection (middle east), chronic cystitis, smoking, chronic nephrolithiasis
Presents with painless hematuria
Urinary tract infection (acute bacterial cystitis)
Inflammation of urinary bladder
Presents as suprapubic pain, dysuria, urinary frequency, urgency.
Systemic signs (high fever, chills) are usually absent
Risk factors include female gender (short urethra), sexual intercourse (honeymoon cystitis), indwelling catheter, diabetes mellitus, impaired bladder emptying
Causes:
1) E Coli (#1)
2) Staph sapro - seen in sexually active young women (E coli is still more common in this group tho)
3) Klebsiella
4) Proteus - urine has ammonia scent
Lab findings:
(+) leukocyte esterase
(+) nitrites for gram (-) organisms (esp E Coli)
Sterile pyuria and (-) urine cultures suggest urethritis by N. Gonorrhae or Chlamydia
Acute Pyelonephritis
Neutrophils infiltrate renal interstitium. Affects cortex with relative sparing of glomeruli/vessels.
Presents with fevers, flank pain (CVA tenderness)
Causes include ascending UTI (E Coli most common), hematogenous spread to kidney.
Presents with WBCs in urine +/- WBC casts. CT shows striated parenchymal enhancement
Risk factors: Indwelling catheter, urinary tract obstruction, vesicoureteral reflux, diabetes mellitus, pregnancy
Complications include chronic pyelonephritis, renal papillary necrosis, perinephric abscess, urosepsis
Tx = antibiotics
Chronic Pyelonephritis
The result of recurrent episodes of acute pyelonephritis.
Typically requires predisposition to infections 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)
Drug-induced interstitial nephritis (tubulointerstitial nephritis)
Acute interstitial renal inflammation. Pyuria (classically eosinophils) and azotemia occurring after administration of drugs that act as haptens, including hypersensitivity.
Nephritis usually occurs 1-2 weeks after certain drugs (diuretics, penicillin derivatives, proton pump inhibitors, sulfonamides, rifampin), but can occur months after starting NSAIDs
Associated with fever, rash, hematuria, and CVA tenderness, but can be asymptomatic
Diffuse cortical necrosis
Acute generalized cortical infarction of both kidneys. Likely due to a combination of vasospasm and DIC
Associated with obstetric catastrophes (abruptio placentae), septic shock
Acute tubular necrosis
Most common cause of acute kidney injury in hospitalized patients. Can be fatal, especially during initial oliguric phase. Increased FENa
Key finding*** = granular (“muddy brown”) casts
3 stages
1) Inciting event
2) Maintenance phase - oliguric; lasts 1-3 weeks; risk of hyperkalemia, metabolic acidosis, uremia
3) Recovery phase - polyuric; BUN and serum creatinine fall; risk of hypokalemia
Can be caused by ischemic or nephrotoxic injury
1) Ischemic - secondary to lower renal blow flow (hypotension, shock, sepsis, hemorrhage, HF). Results in death of tubular cells that may slough into tubular lumen (PCT and thick ascending limb are highly susceptible to injury)
2) Nephrotoxic - secondary to injury resulting from toxic substances (aminoglycosides, radiocontrast agents, lead, cisplatin), crush injury (myoglobinuria), hemoglobinuria. PCT is particularly susceptible to injury
Renal papillary necrosis
Sloughing of necrotic renal papillae leads to gross hematuria and proteinuria. May be triggered by recent infection or immune stimulus. Associated with sickle cell disease or trait, acute pyelonephritis, NSAIDs, diabetes mellitus
SAAD papa with papillary necrosis
S= Sickle Cell disease or trait A = Acute pyelonephritis A = Analgesics (NSAIDs) D = Diabetes mellitus
Acute Kidney Injury (Acute Renal Failure)
Acute kidney injury is defined as an abrupt decline in renal function as measured by increased creatinine and increased BUN
Prerenal azotemia
Due to lower RBF (hypotension)
This leads to lower GFR
Na/H2O and BUN retained by kidney in an attempt to conserve volume. This leads to increased BUN/creatinine ratio (BUN is reabsorbed, creatinine is not) and lower FENa
Intrinsic renal failure
Generally due to acute tubular necrosis (ATN) or ischemia/toxins; less commonly due to acute glomerulonephritis (e.g. RPGN, hemolytic uremic syndrome).
In ATN, patchy necrosis leads to debris obstructing tubule and fluid backflow across necrotic tubule leading to lower GFR.
Urine has epithelial/granular casts
BUN reabsorption is impaired leading to lower BUN/Creatinine ratio.
Postrenal azotemia
Due to outflow obstruction (stones, BPH, neoplasia, congenital anomalies)
Develops only with bilateral obstruction
Acute renal failure table
1) Prerenal
- Urine osmolality > 500
- Urine Na 20
2) Intrinsic Renal
- Urine osmolality 40
- FENa > 2%
- Serum BUN/Cr 40
- FENa > 1% (mild), > 2% (severe)
- Serum BUN/Cr varies
Consequences of renal failure
Inability to make urine and excrete nitrogenous wastes.
Consequences (MAD HUNGER)
MA = Metabolic Acidosis
D = Dyslipidemia (esp high TGs)
H = Hyperkalemia
U = Uremia - clinical syndrome marked by:
High BUN
- Nausea and anorexia
- Pericarditis
- Asterixis
- Encephalopathy
- Platelet dysfunction
N = Na/H2O retention (HF, pulmonary edema, HTN)
G = growth retardation and developmental delay
E = Erythropoietin failure (anemia)
R = Renal osteodystrophy
2 forms of renal failure: acute (ATN) and chronic (HTN, diabetes mellitus, congenital anomalies)
Renal osteodystrophy
Failure of vitamin D hydroxylation, hypocalcemia, and hyperphosphatemia leading to secondary hyperparathyroidism.
Hyperphosphatemia also independently lowers serum Ca by causing tissue calcifications, whereas low 1,25-(OH)2D3 leads to lower intestinal Ca absorption.
Causes subperiosteal thinning of bones
List the Renal cyst disorders
1) ADPKD
2) ARPKD
3) Medullary cystic disease
ADPKD
Formerly adult polycystic kidney disease. Numerous cysts causing bilateral enlarged kidneys ultimately destroy kidney parenchyma. Presents with flank pain, hematuria, HTN, urinary infection, progressive renal failure
Autosomal Dominant (AD for ADPKD)
Mutation in PKD1 (85% of cases, chromosome 16) or PKD2 (15% of cases, chromosome 4).
Death from complications of chronic kidney disease or HTN (caused by higher renin production).
Associated with berry aneurysms, mitral valve prolapse, benign hepatic cysts.
ARPKD
Formerly infantile polycystic kidney disease. Presents in infancy. Auto recessive (AR for ARPKD)
Associated with congenital hepatic fibrosis. Significant oliguric renal failure in utero can lead to Potter Sequence. Concerns beyond neonatal period include systemic HTN, progressive renal insufficiency, and portal HTN from congenital hepatic fibrosis
Medullary cystic disease
Inherited disease causing tubulointerstitial fibrosis and progressive renal insufficiency with inability to concentrate urine.
Medullary cysts usually not visualized; shrunken kidneys on ultrasound
Poor prognosis
Simple vs Complex renal cysts
Simple cysts are filled with ultrafiltrate (anechoic on ultrasound - black). Very common and accounts for majority of all renal masses. Found incidentally and typically asymptomatic.
Complex cysts, including those that are septated, enhanced, or have solid components on imaging require follow-up or removal due to risk of RCC.
