1/30 Tubulointerstitial Disease - Kapoian Flashcards
(32 cards)
kidney compartments
- glomerular
- vascular
- tubular
- interstitial
two types of nephrons and difference
- cortical nephron - shorter
- juxtamedullary nephron - longer
anatomy of tubular membrane
3 components and their functions
-
tight junctions (zona occludens)
- brings adj cells together at luminal surface
- barrier to passive diffusion
- boundary between luminal and basolateral membranes
- helps maintain cell polarity
-
luminal/apical membrane
- contains channels/transporters: allow solutes to pass b/w intracellular space and tubular lumen
-
basolateral membrane
- contains: Na/K ATPase, hormone receptors, solute channels/transporters
tubular segment terminology
what is included in…
- prox tubule
- intermed tubule
- distal tubule
- collecting duct system
proximal tubule: prox convoluted tubule + prox straight tubule
intermed tubule: desc thin limb of Henle + asc thin limb of Henle
distal tubule: thick asc limb of Henle + DCT
collecting duct system: connecting tubule + cortical collecting duct + outer/inner medullary collecting duct
thick asc limb of LoH
- aka “distal straight tubule”
- begin: jx of outer/inner medulla
- end: cortex beyond macula densa
- rich in Ha/K ATPase activity
- active Na-Cl resorption
- production of Tamm-Horsfall mucoprotein
- elemental structure of tubular casts → protein that holds casts together!
distal nephron cell types
- dist convoluted tubule cell
- connecting tubule cell
- principal cell (collecting duct cell)
- intercalated cell (alpha and beta)
distal convoluted tubule
begin/end
fx
“diuretic resistance”
begin: beyond macula densa
end: transitional nephron segment
resorbs 5% of filtered Na-Cl
- resorption proportional to delivery
“diuretic resistance”
- loop diuretics enhance distal Na delivery → enhances distal Na reabs
- if prolonged…distal tubular hypertrophy! even more enhanced Na reabs
connecting tubule
impermeable to water
- active Ca reabs
- responds to PTH and calcitriol
- reabs of Na via Na-Cl cotransporter
- sensitive to thiazides
- secretes K in response to aldosterone
collecting duct
two cell types
- principal cells
- aka “collecting duct cell”
- contributes to net Na reabs via Na channels
- primary site of K secretion
- contains ADH and aldosterone receptors
- intercalated cells
- alpha cell and beta cells (based on polarity)
- high deg of carbonic anhydrase activity
ratio of cell types varies b/w species and segment of collecting duct
diet-induced variations in urinary sodium excretion
hi Na vs lo Na
what cell type affected, what effect?
principal cell
low sodium diet
- enhanced aldosterone release
- incr number of open Na channels
- enhanced Na reabs
high sodium diet = opp of low Na diet
alpha intercalated cells
- Apical membrane
- resp for Acid secretion
- responds to Aldosterone
beta intercalated cells
- proton pump on Basolateral membrane
- responsible for Bicarbonate (Base) secretion
opposite polarity of alpha cells!
mechanisms of tubulointerstitial injury:
glomerular injury
loss of permselectivity (proteins enter capsule) → lysosomal degradation of urinary proteins ensues
- complement activation
- Fe dep tubular injury
- ROS
- cytokine release
mechs of TI injury:
immunologic processes
- mononuclear cell infiltrate correlates with fx decline
- altered antigenicity of kidney
- renal tubule can act as APC
- can involve humoral or cell mediated response
mechs of TI injury:
alterations in tubular metabolism
kidney has high rate of O consumption
disease state cause surviving nephrons to display:
- incr oxygen consumption
- incr ammoniagenesis
- incr production of ROS
mechs of TI injury:
alteration in intrarenal dynamics
- incr wall tension
- incr urinary flow rate
mechs of TI injury:
diabetes
hyperglycemia induces:
- protein glycation and polyol production
- GBM releases cytokines, gammaIFN, TNFalpha
- production of collagen type I and IV
- production of fibronectin and laminin
mechs of TI injury:
crystalline deposition
- high PO4 diet assoc with incr Ca and PO4 deposition
- calcification in tubular lumen, interstitium, epi cells of affected tubules
- oxalate → tubular enlargement
- urate → epithelial cell injury and lysozyme release
mechs of TI injury:
nephron obstruction
- intratubular casts in CKD
- obstruction → chemotactic lipid
- infl infiltrate releases cytokines and ROS
- Tamm-Horsfall protein → neutrophil activiation and degranulation + activates complement
clinical clues re: TI disease
- mild-mod proteinuria
- little-no hematuria
- sterile pyuria (eosinophils)
- amino aciduria (prox tubule)
- renal hyperkalemia
- metabolic acidosis
Fanconi syndrome
prevalence:
- most common in ped pop
- adults, usually assoc with multiple myeloma
generalized proximal tubular dysfx with urinary excretion of:
- glucose → glucouria in presence of normal pl glucose
- a.a.s → aminoaciduria
- PO4
- bicarb → nonAG metabolic adiosis
- other low MW proteins (<50kD)
see: hypokalemia, osteomalacia, malnutrition, volume depletion, failure to thrive
autosomal dom polysystic kidney disease
multisystem disorder (1/400-1000 births)
autodom inheritance
- 85% of affected families: PKD1 gene (chr 16)
- 15% of affected families: PKD2 gene (chr4)
- some have neither
renal manifestations: bilat renal cysts, nephromegaly
- decr concentrating ability
- incr renin production in HTN pts
- preserved epo prod in pts with ESRD
- hematuria/hemorrhage
- acute/chronic pain
- UTI
extrarenal manifestations: hepatic cysts, pancreatic cysts, colonic diverticula, intracranial aneurysms, ovarian/testicular cysts
tx:
- control HTN
- protein restriction (not universally beneficial in slowing progression)
- cyst drainage
- pain mgmt
acute tubular necrosis
either ischemic or nephrotoxic insult → necrotic tubular cells
- recovery after 1-3wk in mild to mod cases (longer in severe)
- ddx: ATN and prerenal azotemia
allergic interstitial nephritis
most often induced by drug tx (but sarcoid, legionella, leptospirosis, streptococcus, viral inf also poss)
- see acute rise in Cr temporally related to drug/
- fever often accomp by rash
- eosinophilia/eosinophiluria in over 75%
- urine sediment with WBC/RBC casts
minimal proteinuria
