Nephrology Flashcards
Membranous Glomerulopathy:
histo (light, IF, special stain, EM)
light micro - diffuse GBM thickening without hypercellularity
if - GRANULAR IgG/C3 deposits along GBM
SILVER stain - SPIKE + DOME pattern (spikes of gbm stick out around domes of deposits)
em - irregular SUBEPITHELIAL immune deposits (btwn gbm and podocyte)
Focal Segmental Glomerulosclerosis:
histo - LM, EM
1 nephrotic syndrome in adults
LM - sclerosis is some (focal) glomeruli in only some parts (segmental) of each affected glomerulus; see OBLITERATED CAPILLARIES with HYALIN DEP.
EM - also podocyte FUSION + EFFACEMENT
Membranoproliferative Glomerulonephritis: histo + causes
thickening of GBM with hypercellularity
assoc. with Hep B or C
Mixed cryoglobulinemia
Ab type, organ changes, assoc. disease
IgM in glomerulus > BM thickening + hypercellularity presents as membranoproliferative GNitis
nephritic syn > hematuria and RBC casts
most common in chronic Hep C
Minimal Change Disease
pathophys
1 nephrotic syndrome in kids; idiopathic or after respiratory infection, immunization or insect sting/bite
T-cell production of a GLOMERULAR PERMEABILITY FACTOR (maybe IL-13) > capillary injury with foot process fusion > loss of negative charge causes selective albuminuria
Chronic Kidney Disease Complications
bones? thyroid?
renal osteodystrophy - hyperphosphatemia and hypocalcemia > either osteopenic high-turnover via high PTH or later PTH resistance with osteomalacia
thyroid - uremia inhibits peripheral T4-T3 conversion with HYPOthyroidism
Most common underlying valvular pathology predisposing to infective endocarditis
mitral prolapse
especially with coexistent regurgitation
platelet + fibrin deposits form spontaneously on valve via disturbed flow + endocardial injury
histo of kidney in renal artery stenosis
decreased tubular epithelial size, patchy inflammation and tubulointerstitial / glomerular fibrosis
Acute Interstitial Nephritis: labs + histo
rash, fever, new drug exposure in last 1-3 wks
high creatinine, BUN, oliguria (AKI); eosinophilia + urinary eosinophils; pyuria, hematuria + WBC casts
histo = interstitial infiltrate + edema
Paroxysmal Nocturnal Hemoglobinuria
pathophys, s/s, main organ involved + how?
mutation of PIGA gene > impaired GPI anchor protein > impaired anchoring of CD55 (DAF) and CD56 (MAC inhibitory protein) > complement-mediated hemolysis
hemolytic anemia
pancytopenia
thrombosis - at atypical sites; hepatic, portal + cerebral vv.
kidney - HEMOSIDEROSIS + thrombosis > CKD
Minimal Change Disease
microscopy
light micro - normal
IF - negative for complement and IgG
EM - podocyte effacement + fusion
IgA Nephropathy
syndrome? microscopy?
nephritic syndrome (hematuria + RBC casts)
light micro - segmental glomerular hypercellularity
IF - globular IgA deposits
EM - deposits in mesangium
PSGN
syndrome? microscopy?
nephritic syndrome 2-4 wks after group A strep
LM - cellular proliferation; neutrophils in capillaries
IF - granular deposits of C3 and IgG along GBM
EM - subEPITHELIAL HUMPS (immune deposits)
Anti-GBM disease
syndrome? microscopy?
nephritic syndrome (RPGN usually)
LM - crescent formation
IF - linear C3 and IgG on GBM
EM - GBM breakage, but no deposits seen
Membranous Nephropathy
syndrome? associations?
nephrotic syndrome
viral hepatitis, solid tumors, lupus
AD Polycystic Kidney Disease
mutation? presentation / cyst location/#?
PKD-1 or PKD-2 mutation > tubular cell proliferation + fluid secretion
cysts at ANY point in nephron; <5% nephrons affected
microscopic cysts at birth enlarge over decades, compress parenchyma > atrophy + fibrosis
mostly asymptomatic; flank pain, hematuria + hypertension; end-stage kidney by age 70
liver cysts and cerebral aneurysms
AR Polycystic Kidney Disease
differentiation from AD?
bilateral flank masses at birth or during 1st year (AD occurs later)
cysts in DCT or collecting duct (AD is anywhere in nephron)
US at birth shows large kidneys + cysts are visible if > 1 cm
Multicystic Dysplastic Kidney
kidney appearance/abnormalities?
multiple cysts of varying size; absence of pelvocaliceal system
ureteral or ureteropelvic atresia
affected kidney is nonfunctional; may be bilateral > Potter sequence
abdominal US of fetus / newborn for dx
Potter syndrome
renal abnormalities in fetus (ARPKD, bilateral renal agenesis, etc.) cause oligohydramnios
results in: pulmonary hypoplasia Potter facies (flat nose, recessed chin, epicanthal folds, low ears) limb defects CV abnormalities
Paraneoplastic syndromes in renal cell carcinoma
Hypercalcemia - via parathyroid hormone-related peptide (or prostaglandin overproduction > resorption)
Erythrocytosis - ectopic EPO
(Hepatic dysfunction - unrelated to liver mets)
Specific risk factors for BLADDER and RENAL cancers
renal - smoking, obesity, hypertension; toxin exposure (HEAVY METALS, PETROLEUM)
bladder - smoking, OCCUPATIONAL EXPOSURES (rubber, plastics, aromatic amine dyes, textiles, leather) SCHISTOSOMA haematobium and CYCLOPHOSPHAMIDE
Kidney injury in rhabdomyolysis
mechanism? labs?
Heme pigment release from myoglobin degradation in glomeruli > direct cytotoxicity + vasoconstriction > ACUTE TUBULAR NECROSIS
high CK
myoglobinuria = UA pos for blood, neg for RBCs
AKI - high BUN + creatinine
high K / P / Urate, low Ca
Renal Cell Carcinoma
cell origin + histo? gross appearance?
from PROXIMAL TUBULE cells of cortex; cuboidal/polygonal cells with abundant clear cytoplasm + “chicken wire” vasculature
spherical mass; renal vein invasion common; GOLDEN-YELLOW tissue (high lipids) with NECROSIS + hemorrhage
Renal Cell Carcinoma
presentation + paraneoplasia? risks?
hematuria, flank pain + palpable mass
polycythemia (EPO) or hypercalcemia (PTHrP)
smoking, hypertension + obesity
toxins (heavy metals, petroleum)
mostly in pts 60-70
Renal Oncocytoma
cell origin? gross morpho?
rare COLLECTING DUCT cell tumor
homogenous brown tumor with CENTRAL STELLATE SCAR visible on imaging
PSGN immunofluorescence:
Deposition pattern + location? Molecules deposited?
Subepithelial granular deposits
deposits of IgG, IgMandC3b
Lupus Nephritis
Mechanism? Most common histo pattern?
T3 HS rxn - deposits can be mesangial, subendothelial, and/or subepithelial
Diffuse proliferative glomerulonephritis is #1 type
proteinuria + RBC casts
Calcium Oxalate stones
how to prevent? 2 ways
- Thiazides - increase calcium reabsorption from tubular fluid
- Urine ALKALIZATION - via POTASSIUM CITRATE (also prevents uric acid stones)
(Acetazolamide also alkalinizes urine, but metabolic acidosis result > Ca and Pi mobilization from bone > actually increases Ca stone risk)
Stages of acute tubular necrosis
Initiation - 24-36 hrs
Maintenance - 1-3 weeks
Recovery - months
First stage of ATN
timing, causes (2 categories)
24-36 hours
- Ischemia - hemorrhage, MI, shock, sepsis
- Cytotoxins - contrast, aminoglycosides, myoglobin
Second stage to ATN
timing, presentation
1-3 weeks
Oliguric failure - low GFR, low urine, volume overload
high creat/BUN, high K, metabolic acidosis
Third stage of ATN
timing, presentation, complications
months
Gradual urine output increase > diuresis
Continued tubular impairment causes ELECTROLYTE WASTING (K, Mg, P, Ca)
Maintenance (2nd) stage of ATN
tubular function parameters (3)
low osmolality (<350 mOsm/kg) high sodium (> 30 mEq/l) high fractional excretion of sodium (>1%)
Water Deprivation Testing Method + Results
normal pt?
central DI pt?
partial / complete nephrogenic DI?
primary polydipsia?
pt deprived of water for 4 hours with hourly checks of serum + urine osmolality; ADH is administered after several hours
normal - urine starts around 500, raises on its own, and does not raise much more after ADH
central DI - urine starts around 100, doesn’t raise much on its own, and raises sharply after ADH
partial/complete NDI - urine starts around 100 and raises slowly to ~ <500 with little change via ADH (partial) or doesn’t raise at all (complete)
primary polydipsia - urine starts around 100, and raises on its own
Post-Obstructive Diuresis
what is it? when does it happen?
kidneys act to normalize fluid volume + solute levels after urinary obstruction
occurs in a patient who is catheterized after obstruction (as in BPH)
TTP-HUS
pentad
- fever
- neurological sx - progressive lethargy
- renal failure
- anemia
- thrombocytopenia
in setting of antecedent GI illness
Turner syndrome
internal abnormalities (not musculoskeletal) + their consequences
CV - bicuspid aorta or COARCTATION
renal - HORSESHOE kidney
repro - STREAK OVARY, infertility, amenorrhea
AR Polycystic Kidney Disease
mutation?
PKHD1 gene for FIBROCYSTIN (in renal tubules + bile ducts); mutation can be spontaneous too
can cause renal insufficiency, nephromegaly and hypertension
if oligohydramnios occurs > Potter sequence
MCC of kidney stones
IDIOPATHIC HYPERCALCIURIA
with NORMOCALCEMIA (regulation via PTH/Vit D maintains normal serum Ca)
(thought to be via increased GI abs, mobilization, or decreased renal reabsorption)
How is PAH handled in the kidney?
freely filtered AND SECRETED
so it estimates RPF well with the formula…
[urinary PAH] x urine flow rate / [serum PAH]
Unilateral renal artery stenosis
changes in the affected (stenotic) kidney?
Hypoperfusion-related changes…
- CORTICAL THINNING + atrophy - diffusely
- TUBULAR ATROPHY - also diffuse
- GLOMERULAR CROWDING
- JGA ENLARGEMENT - releases high levels of renin
Unilateral renal artery stenosis
changes in the unaffected (nonstenotic) kidney?
Hypertensive nephrosclerosis…
- INTIMAL FIBROPLASIA
- HYALINE ARTERIOLOSCLEROSIS
(In severe cases only…
- “ONION SKINNING” - hyperplastic arteriolosclerosis
- FIBRINOID NECROSIS)
Kidney stones that form in high pH (basic) urine?
and low pH (acidic) urine?
Basic - CaPi and Mg-NH4-Pi (struvite)
Acidic - urate and cystine
where do urate stones precipitate and why?
in the distal tubules and collecting ducts
because PH IS LOWEST HERE and urate precipitates at low pH
Renal Papillary Necrosis
causes (5)
- SICKLE CELL disease/trait - obstruct small vessels
- ANALGESIC NEPHROPATHY - nsaids > decrease PGs and constrict afferent arteriole > ischemia
- DIABETES - neg affects vessels
- PYELONEPHRITIS - interstitial edema compresses vessels
- URINARY OBSTRUCTION - same
Renal Papillary Necrosis
macro + micro appearance
Macro - gray-white or yellow necrosis of papillae; SURFACE SCARS appear as fibrous depressions
Micro -
Renal Papillary Necrosis
s/s
sloughed papillae > TISSUE FLECKS in urine
DARK/BLOODY URINE
ureteral obstruction > colicky FLANK PAIN (may be costovertebral too if due to pyelonephritis)
Horseshoe kidney increases the risk of what?
4 things
- Obstruction - at ureteropelvic junction
- Infection - recurrent
- Stones
- Tumors - Wilms in kids; renal cell in adults
Location of kidneys in adult (vertebral level)
T12-L3
What blocks the ascent of a horseshoe kidney?
Inferior mesenteric artery
How can FILTRATION FRACTION be calculated?
FF = GFR/RPF
fraction of total plasma flow that is filtered thru glomerulus
SLIGHT constriction of the efferent arteriole has what effects on…
RPF
GFR
Filtration fraction
RPF goes down
GFR goes up (via increased hydrostatic pressure)
Filtration fraction goes up
(FF = GFR/RPF)
STRONG constriction of the efferent arteriole has what effects on…
RPF
GFR
RPF goes down
GFR goes down
hydrostatic pressure increases in glomerulus, BUT loss of fluid from glomerular capillaries concentrates plasma proteins and eventually RAISES PLASMA ONCOTIC PRESSURE enough to counteract the hydrostatic pressure
5 renal tubular defects in order from PCT to collecting duct
Fans of Bars Git Lit Syndromatically
Fanconi - PCT Bartter - thick ascending Gitelman - DCT Liddle - CD Syndrome of Apparent Mineralocorticoid Excess - CD
Fanconi syndrome
tubule segment + what is handled improperly?
PCT
generalized REABSORPTION DEFECT
AAs, glucose, bicarb and phosphate are all excreted more (+ everything else absorbed in PCT)
Fanconi syndrome
pathophysio effects (3)
- Metabolic Acidosis - proximal RTA
- Hypophosphatemia
- Osteopenia
Fanconi syndrome
5 categories + examples
- Hereditary - Wilson’s, tyrosinemia, glycogen issues
- Ischemia
- Multiple myeloma
- Drugs/toxins - cisplatin, ifosfamide, expired tetracyclines, tenofovir
- Lead poisoning
Bartter syndrome
tubule segment + what is reabsorbed wrong
effects (3 and all are logical once you know the defect + the drug it resembles)
inheritance?
TAL - affects Na/K/2Cl cotransporter
- Metabolic ALKALOSIS, via…
- HYPOkalemia
- HypercalciURIA - more Ca in urine > less in blood
AR inheritance
looks like chronic loop diuretic use (same transporter affected)
Gitelman syndrome
tubule segment + reabs. defect
effects (4 and all BUT ONE are logical once you know the defect)
inheritance?
DCT - NaCl reabsorption affected
- Metabolic ALKALOSIS, via…
- HYPOkalemia
- HypocalciURIA - less Ca in urine > more in blood
- HypoMAGNESEMIA
AR inheritance
looks like chronic THIAZIDE use, except for hypomagnesemia (less severe than Bartter, just as loops are more effective than thiazides)
Liddle syndrome
tubule + absorption issue?
inheritance?
AD - only of the renal tubule disorders that is AD
(“Liddle is little so he has a Napoleon complex and must be dominant”)
GOF mutation cause INCREASED Na reabs. via the ENaC
Liddle syndrome
effects (4)?
(think of the mutation… its effects are then the OPPOSITE of what drugs?)
differential? tx?
- Metabolic ALKALOSIS
- Hypokalemia
- Hypertension
- Decreased aldosterone
Diff. from hyperaldosteronism by NEARLY UNDETECTABLE serum aldo levels
Tx with AMILORIDE (blocks ENaC)
Syndrome of Apparent Mineralocorticoid Excess
2 causes + inheritance of 1
- AR disorder of 11B-HYDROXYSTEROID DH - can not convert cortisol to inactive cortisone in cells > has some MC activity
- Licorice consumption - glycyrrhetinic acid inhibits enzyme
Syndrome of Apparent Mineralocorticoid Excess
effects (4 … all very logical)
tx (2)
- Metabolic ALKALOSIS, via…
- Hypokalemia
- Hypertension
- Low serum aldo
- K-sparing diuretics
- Corticosteroids - to decrease endogenous production of cortisol (guess you’d have to give one with low MC activity…)
renal complication in sickle cell disease
papillary necrosis
sickling in low pO2 environment of renal medulla > micro- or macrohematuria + flank pain in SC pt
what complicates abdominal surgery in patients with horseshoe kidney?
anomalous origins of MULTIPLE RENAL ARTERIES to the kidney
cells in what TWO PARTS of the kidney are most susceptible to anoxic injury?
PCT and thick ascending limb
use most ATP (and thus O2) for transport processes
4 causes of renal papillary necrosis
SAAD papa
S - sickle cell
A - acute pyelonephritis
A - analgesics
D - diabetes
Drugs commonly causing ACUTE INTERSTITIAL NEPHRITIS (4 categories and a single drug with mnemonic; plus one extra drug)
5 Ps - drugs act as haptens
Pee (diuretics) Pain free (analgesics) Penicillins + cePhalosporins PPIs rifamPin
also sulfonamides… TMP-SMX for uti
what might cause SECONDARY INTERSTITIAL NEPHRITIS (other conditions, infections)
(5 things)
Mycoplasma + Legionella
Sjogrens
SLE
Sarcoidosis
S/s of interstitial nephritis
PYURIA - primarily EOSINOPHILIC
Azotemia
fever, RASH, HEMATURIA, and costovert tenderness
CAN be asymptomatic!
Other than albumin, what two important proteins can be lost in urine in NEPHROTIC SYNDROME?
hint: 1) hematological, and 2) immunological consequences
1) ANTI-THROMBIN III - increased thrombin activity > hypercoagulability; may cause renal vein thrombosis (flank pain and hematuria) or VARICOCELE if left sided
2) GAMMA GLOBULINS - increases risk of infection with encapsulated bacteria
Main protein lost in minimal change disease
albumin only
“selective albuminuria” via loss of GBM negative charge
tx with steroids
(kidney function usually remains normal throughout course of MCD)
FSGS nephrotic syndrome
causes (2 categories + general pathophys)
- assoc. with IV DRUG USE and resulting VIRUSES (HIV, hepatitis)
- Secondary to diseases that injure glomeruli - DM, vasculitis, HTN, SICKLE
podocyte injury via direct (eg, cytotoxic drugs) or indirect (eg, glomerular hyperfiltration) mechanisms
Clinical differences btwn FSGS and MCD (3)
FSGS has…
- NON-selective proteinuria
- POOR STEROID response
- high rate of development of END-STAGE KIDNEY in 10 years
1st glomerular change in diabetic nephropathy
GBM thickening via NEG
Later glomerular change in diabetic nephropathy
Kimmelstiel-Wilson nodules
round pink deposits of laminated MESANGIAL MATRIX
Intracapillary change in diabetic nephropathy?
considering all 3 changes, what is the other name for diabetic nephropathy that describes the pathological situation?
LM shows SCLEROSIS causing OBLITERATED CAPILLARIES with HYALINE
“Nodular Glomerulosclerosis” - GBM thickening first, then K-W mesangial nodules with sclerotic capillary changes
(foot processes are also effaced, as in all nephrotic syndromes)
Membranous Glomerulopathy
causes (4 categories, examples)
labs
- causes: idiopathic, or…
1. infection - viral HEPATITIS b/c or SYPHILIS
2. tumors - lung, colon, breast, prostate
3. SLE - although lupus usually nephritic
4. drugs - PENICILLAMINE or NSAIDs
ANTI-PLA2R antibody (highly specific + correlates to disease activity)
Tx and progression of membranous glomerulopathy
Tx - steroids can slow progression
abt 40% progress to ES kidney in 2-20 yrs
Renal amyloidosis microscopy (stains + polarized light)
first sign
later sign
first - focal amyloid deposits in MESANGIUM
later - amyloid obliterates capillaries
eventually, entire architecture of glomerulus is ruined
Congo red - amyloid is pink
Polarized - apple green birefringence
5 causes/subtypes of nephrotic syndrome
- AMYLOID NEPHROPATHY - Congo red and polarized light
- DIABETIC NEPHROPATHY - nodular glomerulosclerosis; k-w nodules
- MINIMAL CHANGE DISEASE - em signs only
- FSGS - via iv drugs/viruses, or dm/htn/vasculitis, sickle
- MEMBRANOUS NEPHROPATHY - via sle/drugs/hepatitis/syphilis/tumors
Most specific sign for pyelonephritis in setting of other UTI sx
white blood cell casts
What 2 parts of the nephron are most susceptible to hypoxic-ischemic injury?
STRAIGHT segment of proximal tubule (medulla)
Thick AL of Henle loop (medulla)
Anion gap calculation
AG = Na - (Cl + HCO3)
What is a normal anion gap value?
8-12 mEq/l
What causes normal anion gap metabolic acidosis?
acronym? (7 words)
HARDASS
- Hyperalimentation - eating too much
- Addison disease
- Renal tubular acidosis
- Diarrhea
- Acetazolamide
- Spironolactone
- Saline infusion
What causes INCREASED anion gap metabolic acidosis?
acronym? (8)
MUDPILES
- Methanol - formic acid metabolite
- Uremia
- Diabetic Ketoacidosis
- Propylene glycol
- Iron or Isoniazid
- Lactic acidosis
- Ethylene glycol - oxalic acid
- Salicylates
1 early childhood renal malignancy
cell / tissue type?
gene / chromosome?
presentation?
Nephroblastoma - Wilms tumor
- embryonic glomerular structures
- WT1 or WT2 suppressor LOF on chr. 11
- LARGE, palpable, UNILATERAL flank mass +/- hematuria
3 syndromes that include Wilms tumor
- WAGR - aniridia, genitourinary malf., retardation
- DENYS-DRASH - diffuse mesangial sclerosis + dysgenesis of gonads
- BECKWITH-WIEDEMANN - macroglossia, organomegaly, “hemihyperplasia” (WT2 mut.)
What is WAGR complex?
it’s an acronym for all the s/s!
- Wilms tumor
- Aniridia - no iris
- Genitourinary malformations
- Retardation
all due to WT1 deletion
What is DENYS-DRASH SYNDROME?
the name hints at 2 of the 3 issues
- Wilms tumor - via WT1 mutation
- gonadal Dysgenesis
- Diffuse mesangial sclerosis - early-onset nephrosis
(Dysgenesis + Diffuse sclerosis in Denys-Drash)
What is Beckwith-Wiedemann syndrome?
the 2nd part of the name hints at 3 of the 4 issues
- Wilms tumor - via WT2 mutation
- Macroglossia
- Organomegaly
- Hemihyperplasia
(think “Wide”-man with his big tongue, organs and… hemi?)
Cystinuria
inheritance?
crystal shape?
AR
hexagon
Cystinuria
defective protein?
malabsorbed molecules?
high-affin, sodium-independent DIBASIC AA TRANSPORTER in pct and intestine
COLA - Cystine, Ornithine, Lysine, Arginine (but all but cystine are soluble and don’t form stones)
Cystinuria
dx (2, one simple one fancy) ?
tx?
high URINARY CYSTINE
SODIUM CYANIDE-NITROPRUSSIDE test - cyanide added to pee > converts cystine to cysteine > nitroprusside added and reacts with -sh grp causing RED-PURPLE color = positive
urinary ALKALINIZATION (eg, acetazolamide or sodium bicarb)
Description of myeloma casts
WAXY and LAMINATED
