Disorders Flashcards
Bartter’s syndrome
AR: Na wasting
thick ascending loop of Henlee
defect in NaK2Cl transporter
Sx: hypokalemia, elevated renin and aldosterone, hypochloremic metabolic acidosis, increase PGE2, failure to thrive
some: hypomagnesemia, hypercalinuria
neonatal: polyhydramnios (fetal polyuria)
SALT CRAVING, DEAF
mutations: Na/K/2Cl, ROMK, CLCNKA, CLCKB, barttin
Tx: K and Mg if needed, COX inhibitors
Gittleman’s syndrome
AR: Na wasting
DCT
mutation in Na/Cl cotransporter: presents later in life
Sx: hypokalemia, hypochloremic metabolic alkalosis, hypocalciuria
glucosuria
cause: pregnancy, DM, familial renal glucosuria
Sx: thirst, nocturia due to osmotic diuresis
familial renal glucosuria
mutation in SGLT1
renal failure
loss of ability to balance salt and water
edema causes increase work load of heart leading to HF and pulmonary edema + acidemia and hyperkalemia
diabetic nephropathy
MOST COMMON: ESRD
AA, native american, mexican
nephrotic: glomerular capillary wall deposition
pore size increased and charge difference reduced: proteinuria
chronic
Sx: HTN, increased then decreased GFR, microalbuminemia to macro
HE: increase measangial matrix, glomerular collapse, glomerulosclerosis; normal or increased glomeruli initially
risk: increases sig. when 1st relative of Type 1 DM has diabetic nephropathy
type 1: 10 years before develops
type 2: can’t tell how long
Tx: reduce BP and proteinuria; ACEI/ARB
3 types: glomerular, papillary, tubulointerstitial
nephritic syndrome
endothelial cell
inflammation
UA: 1-2+ proteinuria, hematuria, RBC casts, dysmorphic RBC
spot urine protein creatinine ratio: 1
Sx: periorbital swelling, HTN, elevated BUN and Cr, oliguria
sub endothelial or mesangial: post-infectious glomerulonephritis, lupus nephritis, IgA nephropathy
BM: anti-GBM disease
necrotizing injury and inflammation: ANCA
nephrotic syndrome
visceral epithelial cell (podocyte)
noninflammatory
EM: fusion of pedicels (effacement)
UA: 3+ to 4+, greater than 3.5 g/day, greater than 40 mg/hr/m2 in children, proteinuria, fatty cast
spot urine protein creatinine ratio: 10
Sx: pitting edema, hypercholesterolemia
podocyte injury: MCD, FSGS
sub epithelial complexes: membranous nephropathy
capillary wall: amyloidosis, light chain deposition disease, diabetic nephropathy
Tx: ACEI/ARB, tx hyperlipidemia, corticosteroids, Calcineurin inhibitors
proteinuria
presents as foamy urine
due to barrier failure: large pore or loss of charge selectivity or abnormal circulating protein
Diabetes Mellitus
impairment of insulin secretion and peripheral resistance to insulin
Sx: hyperglycemia (thirst, polyuria, weight loss, vision)
microvascular: CAD, cerebrovascular disease, PVD
Macro: nephropathy, neuropathy, retinopathy
increased thickness of BM and damaged capillaries: reduced Kf
macroalbuminuria: more likely to die than develop ESRD
renal complications: pyelonephritis, emphasematous pyelonephritis, type 4 RTA, neurogenic bladder
lower urinary tract obstruction
stones, BPH
increases PBS and decreases GFR
frequent emptying of bladder
decrease PBS and increases GFR
low capillary flow
increases FF and therefore πG increases and GFR decreases
Addison’s
absence of aldosterone
increased urinary excretion of NaCl
Conn’s syndrome
aldosterone secreting tumor
increased Na reabsorption and K secretion: hypokalemia, hypernatremia, hypertension
Liddle syndrome
AD pseudo hyperaldosteonism gain of function of beta or gamma ENac Sx: HTN, low renin and aldosterone, hypokalemia, metabolic alkalosis Tx: salt restriction
metabolic alkalosis
increased pH, PCO2, HCO3
causes: loop/thiazide diuretics, vomiting, antacids, hyperaldosteronism
non-anion gap metabolic acidosis
decrease pH, PCO2, HCO3 causes: HARDASS Hyperalimentation Addison Disease Renal tubular acidosis Diarrhea Acetazolamide Spironolactone Saline infusion mild to mod. renal insufficiency
increased anion gap metabolic acidosis
decrease pH, PCO2, HCO3 causes: MUDPILES Methanol Uremia Diabetic ketoacidosis Propylene glycol Iron tablets or Isoniazid Lactic Acidosis (shock) Ethylene glycol Salicylates (Aspirin) renal failure: decreased NH4 excretion
respiratory acidosis
increase pCO2, HCO3
decrease pH
causes: hypoventilation; hypercapnia: airway obstruction, acute lung disease, chronic lung disease, opioids, sedatives, weak respiratory muscles
Cl: changes inversely and equally to bicarb
respiratory alkalosis
increase pH
decrease pCO2, HCO3
causes: hyperventilation: hysteria, hypoxemia, salicylates (early), tumor, pulmonary embolism
Cl: changes inversely and equally to bicarb
*preganancy: chronic
type 2 renal tubular acidosis
proximal: loss of bicarbonate Faconi FEHCO3: greater than 10% urine pH: less than 5.5 Sx: hypokalemia
type 1 renal tubular acidosis
distal: decreased acid secretion
Sx: hypokalemia, hypercalciuria, stones, failure to thrive
FEHCO3: less than 5%
urine pH: greater than 5.5
type 4 renal tubular acidosis
aldosterone deficiency decreased acid excretion FEHCO3: less than 5-10% urine pH: greater or less than 5.5 Sx: HYPERkalemia
acute respiratory disorders
acidosis: increase pCO2 by 10 results in increase of bicarb by 1
alkalosis: decrease pCO2 by 10 results in decrease of bicarb by 2
* greater change in pH
chronic respiratory disorder
acidosis: increase pCO2 by 10 results in increase of bicarb by 4
alkalosis: decrease pCO2 by 10 results in decrease of bicarb by 5
Cl responsive metabolic alkalosis
urine Cl less than 20 mEq/l (usually less than 10 mEq/l)
Cl resistant metabolic alkalosis
urine Cl greater than 20 mEq/l (usually greater than 50 mEq/l)
hyperkalemia
Sx: weakness, ileum, EKG: peaked T wave; then wide QRS, short QT, long PR; absent P wave; V tach
causes:
1. increase intake
2. decrease renal excretion: renal failure, decreased tubular flow, distal tubular dysfunction, hypoaldosteronism
3. internal redistribution: insulin deficiency, B2 blocker, hypertonicity, acidosis, cell lysis
Tx:
1. stabilize heart: calcium gluconate
2. move K into cell: insulin, albuterol, bicarb
3. move K out of body: diuretics, kayexalate, dialysis
hypokalemia
Sx: weakness, rhabdomyolysis, ileus, HTN, nephrogenic diabetes insipidus, EKG: flat T wave; prominent U wave, depressed ST
chronic: asymptomatic
causes:
1. inadequate K intake
2. external loss: GI, cutaneous, renal
3. internal redistribution: insulin, catecholamine, alkalemia, cell proliferation
Tx: K, K sparing diuretics
hypokalemia normotensive disorders with metabolic alkalosis
loop and thiazide diuretics vomiting nasogastric suction Bartter's syndrome Gitelman's syndrome
hypokalemia normotensive disorders with metabolic acidosis
renal tubular acidosis (1 and 2)
ureteral diversion
hypokalemia hypertensive disorders
hyper-reninemia: renal artery stenosis, renin secreting tumor
primary hyperaldosteronism: Conn’s syndrome, adrenal hyperplasia or tumor, Cushing’s syndrome (glucocorticoids can bind aldosterone receptor)
hyponatremia
Sx: lethargy, hyporefelxia, mental confusion
1. decrease ECFV: diarrhea, vomiting
2. NO CHANGE ECFV: HF, liver failure
renal Na loss: Una greater than 20 mEq/L
extrarenal Na loss: Una less than 20 mEq/L
Tx: isotonic saline infusion (slow)
nocturia
frequent urination during the night
cause: disability to concentrate urine
central diabetes insipidus
Sx: dilute urine cause: lack ADH resting: high Posm, low Uosm WD: increase Posm ADH infusion: normal Posm, increase Uosm
nephrogenic diabetes insipidus
Sx: dilute urine cause: CD do not respond to AVP congenital: x-linked V2 or AQP2 mutation acquired: defect in medullary interstitial tonicity or cAMP, AQP down regulation, pregnancy resting: high Posm, low Uosm, high ADH WD: increase Posm, increase ADH ADH infusion: no change
polydipsia
obsessive water drinking Sx: hyponatremia, coma, death cause: loss of medullary hyperosmolarity resting: low Posm, Uosm, ADH WD: normal Posm, Uosm; increase ADH ADH infusion: decrease Posm; increase Uosm
osmotic diuresis
cause: hyperosmotic plasma
resting: high Posm, Uosm
WD: increase Posm, Uosm, ADH
ADH infusion: Posm and Uosm remain high
Goodpasture’s
nephritic with crescentic GN
anti-GBM: antibodies against NC1 domain of alpha3 (IV) chain
young adult, white, men (thicker BM)
IF: linear, IgG, C3
Sx: glomerulonephritis with hematuria and hemoptysis, azotemia, arthritis, anemia
Tx: plasmapheresis
effacement of pedicels
nephrotic syndrome
retraction of foot processes and loss of slit pore diaphragm so that long segments of capillary are invested by cytoplasm of a single podocyte
detachment from BM and BM degradation allow proteins to leak into urinary space
lupus nephritis
subendothelial: immune complex HE: wire loops rapidly progressive IF: FULL HOUSE: IgG, IgM, IgA, C3, C4 Tx: glucocorticoids, cyclophosphamide, mycophenolate mofetil, hydroxychloroquine, aspirin
post-streptococcal glomerulonephritis
nephrotic subendothelial to subepithelial: anti-streptolysin O, anti-DNAse B EM: subepithelial HUMPS HE: endocapillary proliferation, neutrophils IF: IgG, C3 (capillary and mesangium) Sx: tea colored urine (RBCs), recent throat or skin infection (1-6 week), HTN, azotemia LOW C3, normal C4: alternate pathway
metabolic (diabetic) glomerular injury
- hyperglycemia causes non-enzymatic glycosylation of proteins resulting in thickened GBM and AGE (advanced glycation end-products)
- AOPP (advanced oxidation products), renin-angiotensin, TGF-beta, AGE activate NADPH oxidases producing ROS leading to mesangial matrix production, podocyte injure and apoptosis and proteinuria
H&E: hyaline sclerosis; diffuse mesangial sclerosis
hemodynamic glomerular injury
supra-normal glomerular capillary pressures cause GBM thickening, mesangial cell hypertrophy and hyperplasia, and mesangial matrix production
causes hyaline sclerosis of afferent but not efferent arteriole: ischemic atrophy of glomerulus
arterionephrosclerosis
more common in A.A. due to apoL1
HTN leads to globally sclerotic glomeruli
malignant HTN
black males ~40 HTN that causes end organ damage greater than 200/120 mmHg Sx: headache, vomiting, proteinuria, hematuria, scotoma (spots before eyes), renal failure H&E: fibrinoid necrosis of arterioles leading to necrosis of glomeruli onion skin gross: flea-bitten kidney P: can be fatal due to renal disease MEDICAL EMERGENCY
diffuse glomerular disease
involving all or most of the glomeruli
focal glomerular disease
involving some glomeruli but not most
global glomerular disease
involving whole glomerulus
segmental glomerular disease
involving only part of glomerulus
proliferative glomerular disease
increased cell
proliferating native cells but also infiltrating inflammatory cells
membranous glomerular disease
increase GBM without increased cells
membrano-proliferative glomerular disease
increased cells and GBM
EM: TRAM TRACKS
membrano-proliferative glomerular disease
increased cells and GBM
pauci-immune glomerulonephritis
crescent: lymphocytes and monocytes in Bowman’s space
antibodies are present but not visible on immunofluorescence or EM
ANCA
Sx: arthritis, arthralgia, myalgia, fatigue
microscopic polyangiitis
small vessel nephritic: necrotizing injury of vascular and glomerular capillary wall pauci-immune P-ANCA rapidly progressive
Churg-Strauss
small vessel nephritic: necrotizing injury of vascular and glomerular capillary wall pauci-immune P-ANCA rapidly progressive
Granulomatous with polyangiitis (Wegner’s)
small vessel
nephritic: necrotizing injury of vascular and glomerular capillary wall
pauci-immune
C-ANCA
Sx: sinopulmonary renal syndrome, purpura
rapidly progressive
HE: normal, mesangial proliferative, segmental necrotizing, crescents (fibrin): tubulointerstitial GRANULOMAS
Tx: cyclophosphamide
C-ANCA
cytoplasmic
Anti-proteinase3
P-ANCA
perinuclear
Anti-MPO
IgA nephropathy
nephritic: mesangial
CURRENT infection
Sx: brown/red urine (macroscopic hematuria)
IgA nephropathy
Berger’s Disease
nephritic (variable): mesangial CURRENT infection (1-2 days) galactose deficient IgA1 HE: variable; mesangial expansion IF: IgA EM: mesangial deposits Sx: brown/red urine (macroscopic hematuria)
membranous nephropathy
white male adults 4th-6th decade nephrotic: subepithelial Ab: PLA2, NEP EM: SPIKE and DOME immuno: IgG HE: thick BM 2: Hep. B, syphilis, malaria, gold, penicillamine, captorpril, NSAID; lung, colon, skin cancer; SLE, sickle cell risk for loss of renal function: male, greater than 10g/day proteinuria, HTN, azotemia, tubuointerstitial fibrosis, glomerulosclerosis
causes of iso-osmolar hyponatremia
pseudohyponatremia: severe hyperlipidemia and hyperproteinemia
post-transurethral prostatectomy, posthysteroscopic
causes of hypo-osmolar hypervolemic hyponatremia with decreased ECV
TBW and TBNa increase, TBW more than TBNa
CHF, liver disease, nephrotic syndrome, renal disease
causes of hypo-osmolar hypervolemic hyponatremia with increased ECV
acute and chronic renal failure
causes of hypo-osmolar euvolemic hyponatremia
increase TBW; no change TBNa
causes: SIADH, drugs, glucocorticoid deficiency, hypothyroidism, primary polydipsia, lung disorders, CNS disorders and malignancy, drug induced water retention
causes of hypo-osmolar hypovolemic hyponatremia
decrease ECFand ECV
causes: diuretics, aldosterone deficit, diarrhea, vomiting, bleeding, excessive sweating with high water intake, pancreatitis, bowel obstruction, burns
severe hypokalemia
hypernatremia
Uosm less than 300 mOsm/kg: diabetes insipidus
Uosm greater than 500 mOsm/kg: extra-renal water loss, Na infusion, decrease osmotic diuresis
other: primary hyperaldosteronism, Cushing’s, hypertonic hemodialysis, admin. of Na
tubular injury UA
microscopic hematuria, renal tubular epithelial cells, granular casts, specific gravity 1.010, Uosm 300
acute tubular necrosis (ATN)
non-inflammatory tubular injury
cause: ischemia or toxins (aminoglycosides (PT), contrast, amphotercin B)
proximal straight tubule and TALH
occlusion of tubular lumens with cells and casts
muddy brown granular casts
urine Na greater than 20
FeNa greater than 1
allergic interstitial nephritis (AIN)
inflammatory tubular injury
proliferation of interstitial fibroblast and matrix: TGF-B
UA: pyuria, eosinophiluria
cause: penicillin, cephalosporin, NSAIDS; infections, autoimmune, infection
Sx: fever, rash, joint pain, eosinophils, sterile pyuria
obstructive uropathy
tubular injury and possible RBC
mesangial pattern tubular disease
UA: hematuria, RBC casts without proteinuria
hereditary renal glucosuria
AR: PT
mutation of SGLT2
Cystinuria
AR: PT: amino aciduria
mutation of brush border transporter responsible for reabsorption of cystine, ornithine, lysine, arginine
cystine stones
UA: cystine casts
X-linked hypophosphatemia
mutation of PHEX gene: increased FGF23
Sx: urinary Pi wasting, elevated serum alkaline phosphatase, normal Ca and calcitriol
presents: rickets in children and osteomalacia in adults
autosomal recessive hypophosphatmic Rickets
mutation that leads to increased FGF-23
mutation in Na/Pi IIc transporter
oncogenic hypophosphatemic osteomalacia
aquired
increased production of FGF-23 by tumors (fibromas, angiosarcomas, hemangiopericytomas)
Hartnup disease
defect in neutral amino acid transporter SLC6A19
Sx: failure to thrive, photosensitivity, intermittent ataxia, nystagmus, tremor
vitamin D dependent rickets type 1
mutation of 1 alpha hydroxylase
Sx: hypophosphatemia, rickets
Faconi syndrome
generalized PT dysfunction
Sx: aminoaciduria, glucosuria, hypophophatemia, hyperchloremic metabolic acidosis, hypokalemia, uricosuria
polyuria, polydipsia, volume depletion, arrhythmia, proteinuria, growth retardation, rickets, renal stones
inherited: cysinosis, lots of others
acquired: tenofovir, multiple myeloma, lots of of others
glucocorticoid-remediable hyperaldosteronism (GRA)
congenital
recombination of 11-B-hydroxysteroid dehydrogenase and aldosterone synthase: promoter that makes cortisol is stuck on gene that produces aldosterone
Sx: low renin HTN, hypokalemia
Tx: glucocorticoids
apparent mineralcorticoid excess (AME)
mutations in kidney isozyme of 11BHSD: increase cortisol in kidney that activates aldosterone receptor
Sx: low renin HTN, hypokalemia
Tx: glucocorticoids
PHA type 1
AD: mutation in mineralocorticoid receptor, childhood
AR: loss of function mutation in ENaC
Sx: hyperkalemia, hypernatremia, HYPOTENSION
Tx: Na, fluids, Kayexalate
mirror image of Liddle
PHA type II
Gordon syndrome
chloride shunt syndrome
mutation: WNK1, WNK4, ser/thr kinase that regulates Na/Cl cotransporter
Sx: hyperkalemia, hyperchloremic metabolic acidosis, HTN, low renin and aldosterone
mirror image of Gitelman
Tx: thiazides
renal tubular acidosis (RTA)
normal anion gap metabolic acidosis
positive urine anion gap
Focal segmental glomerulosclerosis (FSGS)
A.A. nephrotic: subepithelial immune complex non-selective proteinuria EM: podocyte effacement H&E: focal, segmental immuno: neg suPAR, apoL1 Sx: may have HTN, half develop ESRD 2: HIV, parvo, heroin, lithium, pamidronate, partial nephrectomy mutations: alpha-actinin-4, podocin, TRPC6, apoL1
minimal change disease (MCD)
children nephrotic: podocyte injury proteinuria: ALBUMIN EM: foot process EFFACEMENT H&E: normal immuno: neg. 2: Hodkin's, NSAID, IFN-alpha Tx: GLUCOCORTICOIDS
rapidly progressive glomerulonephritis
nephritic
renal failure over days/weeks
features of vasculitis
ex: ANCA vasculitis, lupus nephritis
chronic glomerulonephritis
HTN, renal insufficiency, proteinuria greater than 3 g/day
SHRUNKEN kidneys
ex: diabetic and HTN nephropathy
Alport syndrome (Hereditary nephritis)
GBM
X-linked COL4A5: male
Sx: hematuria, progressive proteinuria, ESRD
assoc.: hearing loss, lens abnormalities, platelet defects, esophageal leiomyomas
HE: focal, segmental or global glomerulosclerosis, interstitial fibrosis, foam cells
EM: BASKETWEAVE, focal effacement of podocytes
IF: neg.
hemolytic uremic syndrome (HUS)
hemolytic anemia, renal dysfunction , thrombocytopenia
ONION SKIN
HE: fibrin and platelets in lumen, fibrin in subintima and media of vessels
E. coli H7:O157 verotoxin
thrombocytpenia purpura (TTP)
FEVER, NEUROLOGIC, PURPURA
hemolytic anemia, renal dysfunction , thrombocytopenia,
ONION SKIN
HE: fibrin and platelets in lumen, fibrin in subintima and media of vessels
ADAMTS13 or autoimmune disorders
membranoproliferative glomeruluonephritis
asymptomatic, acute nephritic, nephrotic, crescentic rapidly progressive glomerulonephritis
subendothelial
EM: TRAM TRACKS
HE: hypercellular glomerulus, increased mesangium
immuno: C3, C4, IgG; monoclonal gammopathy (kappa or lambda)
Sx: HTN, decreased GFR
rheumatoid factor, ANA, LOW C3
immune complex mediated: classical pathway
complement mediated: alternative pathway
type 1 MPGN
most common
HE: mesangial hypercellularity, monocytes
sub endothelial and mesangial
IF: IgG
2: neoplasm, infection, collagen vascular disease
Hep. C; LOW C3 and C4
type 2 MPGN
dense deposit disease in capillary wall deficiency of FACTOR H C3c present partial liphodystrophy: loss of fat upper body; macular deposits in eyes LOW C3
type 3 MPGN
subedothelial and sub epithelial with GBM disruption and lamina dens layering
thin basement membrane
female heterozygote COL4A5: defects in alpha-3 or 4 type IV Sx: hematuria HE: normal IF: negative EM: thin GBM
polyarteritis nodosa
medium vessel: infarcts
ANCA NEG.
assoc.: Hep B (and Hep C and Hairy cell leukemia)
Sx: arthralgia, fatigue weight loss, fever, abdominal pain, near, renal, HTN, skin lesions
HE: SEGMENTAL TRANSMURAL NECROTIZING vasculitis
What indicates ANCAs are pathogenic?
activate PMN
increase contact and adhesion with endothelial cells and vasculature structures
adhesion: B-2 integrin, Mac-1, Fc gamma
*endothelial cells are the primary target in small cell vasculitis
thrombotic microangiopathy (TMA)
normal PTT and PT (prolonged in DIC)
HUS, TTP
drugs, SLE, antiphospholipid, complement defects, HIV, cancer
class I lupus nephritis
minimal measngial
RARE
class II lupus nephritis
mesangial proliferative
class III lupus nephritis
focal proliferative
class IV lupus nephritis
diffuse proliferative
MOST COMMON
class V lupus nephritis
membranous
nephrotic
class VI lupus nephritis
advanced sclerosing
scleroderma
females AA
fibrosis and vascular occlusion
mild renal involvement: dysfunction, proteinuria, HTN
renal crisis: accelerated arterial HTN and/or rapidly progressive oliguria renal failure
Risk factors for renal crisis: early diffuse systemic sclerosis, rapidly progressing, anti RNA polymerase Ab, steroids
HE: intimal and medial proliferation arcuate arteries, fibrinoid necrosis and thrombosis
acute kidney injury (AKI or ARF)
less than 1 month
Cr: greater than 0.5 mg/dl
usually asymptomatic
pre-renal ARF
decrease renal blood flow BUN: Cr ratio: greater than 20 urine mOsm: greater than 500 urine Na: less than 25 FeNa less than 1 causes: volume depletion, CHF, shock, hepatorenal syndrome, renal artery stenosis and ACEI/ARB, NSAIDS
intrinsic renal ARF
glomerular: nephrotic and nephritic
tubular: ATN AIN
vasculitis
BUN: Cr ratio: less than 15
urine mOsm: less than 250
urine Na: greater than 20
muddy brown casts
post-renal ARF
obstruction of flow: voiding complaints
Dx: ultrasound
causes: prostate, cancer, neurogenic bladder,
hepatorenal syndrome
pre-renal AKI
cirrhosis: portal HTN leading to vasodilation and therefore decreased ECV and activation of renin
decrease BP with increased ECFV
UA and kidneys: normal; urine Na less than 10
Tx: liver transplant
chronic kidney disease
Sx: voiding complaints, HTN, edema, flank mass
SERIAL labs needed
SMALL kidneys, WAXY cast, PERIPHERAL NEUROPATHY
usually ASYMPTOMATIC, BONE change with hyperparathyroidism
high risk of CVD
Effects:
nervous system: asterixis, intellectual function, encephalopathy
hypoglycemia (decreased insulin degradation and decreased gluconeogenesis)
anemia
anorexia
drug metabolism effects
decreased Vit D: hypocalcemia, increase PTH
hyperphosphatemia
HYPERKALEMIA
metabolic ACIDOSIS NON ANION GAP
K over 7mmol/L
MEDICAL EMERGENCY
Tx: IV calcium gluconate, IV insulin + glucose
autosomal dominant polycystic kidney disease
ADULT
slow growing cysts compress normal tissue and cause ischemic atrophy
HUGE kidneys
polycystin-1 or 2
ciliopathy, defective mechanosensigin of urine flow, dysregulation of cell adhesion
two hit genetics
autosomal recessive polycystic kidney disease
CHILDREN
cysts replace normal tissue in fetus
mutation: fibrocystin
pulmonary hypoplasia and death
nephronophthisis
medullary cystic disease
SMALL kidneys with numerous small cysts at corticomedullary junction and chronic tubulointerstitial nephritis and fibrosis
mutation: cilia components
most common genetic cause of ESRD in CHILDREN
kidney stones
males dysuria, hematuria, restless, writhing in distress, N/V, flank pain CT: sensitive UA, ultrasound, xray Tx: fluids
calcium stones
most: Ca oxalate; Ca Pi next
calcium oxalate crystals
cause: hypercalcemia, reduced citrate, excess Na
Tx: do NOT restrict dietary Ca, thiazide diuretics, Na restriction,, K citrate
Magnesium ammonium phosphate (Struvite) stone
or
triple phosphate
UTI with urease producing organism (Proteus, Klebsiella)
urine pH greater than 7 (ammonium produced by bacteria)
coffin lid crystal
Tx: infection
uric acid stones
cause: hyperuricemia urine pH less than 5.5 diamond cyrstals RADIOLUCENT Tx: restrict protein, K citrate, allopurinol
cystine stones
decreased PT reabsorption
Tx: penicillamine, K citrate, alkalinize urine
hexagon crystals
CHILDREN
urinary tract obstruction
mechanical: intraluminal, intramural, extrinsic
functional: neurogenic
common locations: ureter crosses iliac vessels, enters bladder, ureterovesical junction
proximal to bladder: one kidney, normal Cr
distal: both kidneys, increased Cr
retroperitoneal fibrosis
can cause urinary tract infection
chronic bilateral partial urinary tract obstruction
polyuria, azotemia, nonunion gap metabolic acidosis, hyperkalemia, RTA
clear cell carcinoma
MOST COMMON
malignant
chromosome 3p: VHL
gross: solitary, yellow, cysts, necrosis, hemorrhage
HE: clear or eosinophilic cytoplasm, vascular
sporadic: translocation or deletion chromosome 3
hereditary: inactivated mutated VHL, hyper-methylation of VHL
risk: dialysis related renal cystic disease
grade indicates survival rate
oncocytoma
benign renal epithelial neoplasm large cells with lots of mitochondria MAHOGANY BROWN with central STELLATE scar may be multiple
renal carcinoma
male, smoker, older, HTN, obesity
tubule epithelial cells
encapsulated, necrosis, hemorrhage (rupture invaded vein, abnormal new vessels)
metastasis: perinephric fat, VENOUS, LUNG, BONE; next: lymph, liver, adrenal, brain
Sx: dull flank pain, hematuria, abdominal mass
papillary carcinoma
malignant
renal parenchymal tumor
bilateral, multifocal
sporadic: trisomy 7, 16, 17, loss Y
activated MET, translocation 1: PRCC oncogenes
hereditary: trisomy 7, activated MET
risk: dialysis related renal cystic disease
chromophobe carcinoma
large pale cells with prominent cell membranes
lower mortality
Hale’s colloidal iron stain
renal pelvis carcinoma
urothelial: transitional cell carcinoma; can get squamous
CENTRAL location
smoker: get in bladder and can get higher in collecting system
Wilm’s tumor (nephroblastoma)
KIDS: 2-5 yrs
embryonal kidney tumor
HE: mixture of cell types: blastemal, stromal, epithelial
ABDOMINAL MASS
WAGR
no iris, genital abnormalities, mental retardation
Wilm’s tumor
deletion of WT1 gene
Denys-Drash
gonadal dysgenesis
Wilm’s tumor
inactivating mutation WT1 gene
Beckwith-Wiedemann
Wilm’s tumor
one sided organomegaly
genetic imprinting doesn’t silence maternal allele that controls IGF2
light chain disease
nephrotic: glomerular capillary wall deposition
MONOCLONAL
precipitation of Ig chains without elongation
MULTIPLE MYELOMA
Sx: proteinuria, renal failure, tubuolinterstitial syndrome, cardiomegaly, hepatomegaly, sicca syndrome, peripheral neuropathy, GI, pulmonary nodules, arthopathy
sickle cell nephropathy
val for glutamate: 6th aa beta global chain
polymerize with low O2 and sickle
early: glomerular hypertrophy, HEMOSIDERIN, focal hemorrhage or necrosis
late: interstitial inflammation, edema, fibrosis, tubular atrophy papillary infarcts
end: FSGS
vaso-occlusive
Sx: pain crises, hemolysis, reticulocytosis, hyperbilirubinemia, elevated lactate dehydrogenase, low haptoglobin
SICKLE cell, Howell- Jolly
amyloidosis
deposition of proteinaceous material in vessels then interstitium
BETA-PLEATED SHEETS
nonproliferative, noninflammatory glomeruopathy
vascular; tubular atrophy and interstitial fibrosis
APPLE GREEN BIREFRINGENCE
CONGO RED
HIV associated nephropathy
progressive azotemia, proteinuria COLLAPSING FSGS with microcystitic tubular dilation, interstitial inflammation, fibrosis Nef and Vpr viral genes ApoL1 Tx: HAART, ACEI/ARB most still develop ESRD
cryoglobulinemia
HEP. C
immune complexes: RF, IgG, HCV RNA, complement of endothelial surfaces
precipitate at 4 degrees
MEMBRANOPROLIFERATIVE
Sx: palpable purpura, arthralgia, MPGN, lymphoma, peripheral neuropathy
MELTZER’s TRIAD
lymphocyte infection leads to IgM secreting clones
AL amyloid
primary older MOST COMMON MONOCLONAL LIGHT chains urine: BENCE-JONES proteins assoc. MULTIPLE MYELOMA; PLASMA CELL DYSCRASIS Sx: weak, weight loss, NEPHROTIC, peripheral neuropathy, large kidneys and insufficiency, GI, heart Tx: melphalan, dexamethosone
AA amyloid
reactive systemic secondary to CHRONIC INFLAMMATION: RA, IBS, ankylosing spondylitis IL-1 and IL-6 Sx: kidney and GI Tx: eprodisate
Abeta2m amyloid
long term hemodialysis
Sx: synovium, joints and tendon sheaths
ATTR amyloid
senile or familial (AA)
transthyretin
HEART and pulmonary blood vessels
Sx: heart failure or arrhythmia
Abeta amyloid
Alzheimer’s
stage 1 diabetic nephropathy
hyperfiltration, increase GFR
increase kidney size
stage 2 diabetic nephropathy
glomeruli show damage and microalbuminuria
stage 3 diabetic nephropathy
albumin excretion rate exceeds 200 mg/min
increase serum BUN and Cr
increase BP in some
stage 4 diabetic nephropathy
GFR decreases less than 75 ml/min proteinuria high BP further increase BUN and Cr 17 years to develop
stage 5 diabetic nephropathy
kidney failure or ESRD
GFR less than 10 ml/min
23 years to develop
diffuse glomerular diabetic nephropathy
early, less sever
MOST COMMON
identical to HTN and aging glomerulopathy
capillary BM thickening and increased mesangial matrix: begins in stalk of glomerular tuft
nodular glomerular diabetic nephropathy
after 10 years DM
superimposed on glomerulopathy
KIMMELSTIEL WILSON nodules and HYALINE sclerosis of efferent and afferent arterioles
papillary diabetic nephropathy
pyelonephritis
papillary necrosis
tubulo-interstitial diabetic nephropathy
tubular basement membrane thickening
interstitial fibrosis
pyelonephritis
infection of kidney: infected tubules
UA: pyuria and bacteruria
acute urethral syndrome
does NOT have significant bacteriuria
cause: chlamydia, bacterial lower UTI
Sx: dysuria
UTI
females (opp. in infants)
intercourse, SPERMICIDE + diaphragm, OBSTRUCTION, trauma, VESICULO-URTERAL REFLUX, intrumentation
pregnancy: progression more likely, higher bacteriuria; need to check for pyelonephritis
ASCENDING infection, hematogenous much less likely
pathogenesis: adhesion (type 1 and P-fimbriae), colonization, invasion, phase variation
complication: sepsis, abscess, chronic renal insufficiency, struvite renal calculi, recurrent infections
What causes increase in UTI with age?
bacteriuria
male: BPH
female: decrease estrogen and vaginal acidity
lower UTI
freq. of urination, dysuria, turbid urine, suprapubic discomfort, hematuria, asymptomatic cystitis
Tx: female 1-3 days, males 1 week
upper UTI
fever, chills, CVAT, asymptomatic pyelonephritis
Tx: 1-6 weeks
asymptomatic bacteriuria
DO NOT TREAT in elderly or others
