1/30 Tubulointerstitial Disease - Kapoian Flashcards Preview

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Flashcards in 1/30 Tubulointerstitial Disease - Kapoian Deck (32)
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1
Q

kidney compartments

A
  • glomerular
  • vascular
  • tubular
  • interstitial
2
Q

two types of nephrons and difference

A
  1. cortical nephron - shorter
  2. juxtamedullary nephron - longer
3
Q

anatomy of tubular membrane

3 components and their functions

A
  1. 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
  2. luminal/apical membrane
    • contains channels/transporters: allow solutes to pass b/w intracellular space and tubular lumen
  3. basolateral membrane
    • contains: Na/K ATPase, hormone receptors, solute channels/transporters
4
Q

tubular segment terminology

what is included in…

  • prox tubule
  • intermed tubule
  • distal tubule
  • collecting duct system
A

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

5
Q

thick asc limb of LoH

A
  • 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!
6
Q

distal nephron cell types

A
  1. dist convoluted tubule cell
  2. connecting tubule cell
  3. principal cell (collecting duct cell)
  4. intercalated cell (alpha and beta)
7
Q

distal convoluted tubule

begin/end

fx

“diuretic resistance”

A

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
8
Q

connecting tubule

A

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
9
Q

collecting duct

two cell types

A
  1. principal cells
  • aka “collecting duct cell”
  • contributes to net Na reabs via Na channels
  • primary site of K secretion
  • contains ADH and aldosterone receptors
  1. 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

10
Q

diet-induced variations in urinary sodium excretion

hi Na vs lo Na

what cell type affected, what effect?

A

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

11
Q

alpha intercalated cells

A
  • Apical membrane
  • resp for Acid secretion
  • responds to Aldosterone
12
Q

beta intercalated cells

A
  • proton pump on Basolateral membrane
  • responsible for Bicarbonate (Base) secretion

opposite polarity of alpha cells!

13
Q

mechanisms of tubulointerstitial injury:

glomerular injury

A

loss of permselectivity (proteins enter capsule) → lysosomal degradation of urinary proteins ensues

  • complement activation
  • Fe dep tubular injury
  • ROS
  • cytokine release
14
Q

mechs of TI injury:

immunologic processes

A
  • mononuclear cell infiltrate correlates with fx decline
  • altered antigenicity of kidney
  • renal tubule can act as APC
  • can involve humoral or cell mediated response
15
Q

mechs of TI injury:

alterations in tubular metabolism

A

kidney has high rate of O consumption

disease state cause surviving nephrons to display:

  • incr oxygen consumption
  • incr ammoniagenesis
  • incr production of ROS
16
Q

mechs of TI injury:

alteration in intrarenal dynamics

A
  • incr wall tension
  • incr urinary flow rate
17
Q

mechs of TI injury:

diabetes

A

hyperglycemia induces:

  • protein glycation and polyol production
  • GBM releases cytokines, gammaIFN, TNFalpha
  • production of collagen type I and IV
  • production of fibronectin and laminin
18
Q

mechs of TI injury:

crystalline deposition

A
  • 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
19
Q

mechs of TI injury:

nephron obstruction

A
  • intratubular casts in CKD
  • obstruction → chemotactic lipid
  • infl infiltrate releases cytokines and ROS
  • Tamm-Horsfall protein → neutrophil activiation and degranulation + activates complement
20
Q

clinical clues re: TI disease

A
  • mild-mod proteinuria
  • little-no hematuria
  • sterile pyuria (eosinophils)
  • amino aciduria (prox tubule)
  • renal hyperkalemia
  • metabolic acidosis
21
Q

Fanconi syndrome

A

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

22
Q

autosomal dom polysystic kidney disease

A

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
23
Q

acute tubular necrosis

A

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
24
Q

allergic interstitial nephritis

A

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

25
Q

role of infections

A

infection can cause kidney disease via:

  • reactive change to systemic infection
  • direct parenchymal invation (ex. pyelonephritis)

scarlet fever, betahemolytic strep, diphtheria

lesions occur early in course of inf

  • can be focal or diffuse (more edema than infiltrate)
  • infiltrate forms a circular band around vessels in corticomedullary region
26
Q

pyelonephritis

A

most common cause: bacterial infection

  • focal lesion usually ltd to single pyramid
  • wedge shaped lesion with apex doward medulla

infected areas are well demarcated from adj tissue

infl foci arranged radially

27
Q

role of drugs

A

most common cause of acute tubulointerstitial nephritis

best characterized:

  • methicillin → rxn to beta lactam ring
  • rifampin → cell mediated rxn, also see circ antibodies
  • trimethoprim-sulfamethoxasol → produces acute TI nephritis via accumulation of toxic metabolites
  • NSAIDs → altered renal hemodynamics due to reduced intrarenal PGE2 and PGI2
    • PGE2/PGI2 incr Na excretion and renin release
    • PGE2 decr Na reabs in LoH
    • also inhibits ADH

results in HSN rxn

  • rare, not dose-related
  • assoc with fever, skin rash, arthralgia, eosinophilia, eosinophiluria
  • recurs with reexposure to drug
28
Q

medullary sponge kidney

A

common, benign disorder

malformations of terminal collecting ducts in pericalyceal region of pyramids

assoc with small and large medullary cysts (generally diffuse and bilat, but do not involve cortex)

  • most pts asymptomatic, but may have hematuria, UTI, kidney stones
  • some incomplete distal TRA, some mild concentrating defect
  • good long term prognosis
29
Q

sickle cell nephropathy

A

renal sequellae of sickle cell disease due to sickling in vasa recta

concentrating defect, hematuria, paillary rencrosis and renal infarction

hyperkalemia common due to impaired K secretion in collecting tubule

proteinuria → progressive renal dysfx with typical finding of focal glomerulosclerosis

30
Q

multiple myeloma

A

almost half of pts will have renal insuff

monoclonal light chain tox produces most of it

cast nephropathy when light chains bind to Tamm-Horsfall mucoprotein

  • amyloidosis typically assoc with lambda light chains → stains + for Congo Red
  • light chain deposition disease assoc with kapa light chains

plasma cell infiltration into kidney rarely impairs renal fx

31
Q

GPA

granulomatosis with polyangiitis

(formerly Wegeners)

A
  • presistent rhinorrhea
  • purulent/bloody nasal discharge
  • oral/nasal ulcers, sinus pain
  • polyarthralgias, myalgials
  • less common: upper airway symptoms

90% ANCA+

kidneys?

usually presents as acute glomerulonephritis w hematuria, proteinuria, red cell casts seen on urine microscopy

32
Q

lead poisoning

A
  • abd colic
  • extensor muscle weakness
  • encephalopathy
  • short term memory impairment
  • decr libido
  • HTN
  • gout
  • microcytic anemia
  • basophilic stippling on periph smear

kidney?

acute lead nephropathy: Fanconi’s syndrome

  • prox tubule resorptive defect
  • aminoaciduria, glycosuria, phsphaturia
  • can reverse with chelation

chronic lead nephropathy: slowly progressive TI nephritis after prolonged lead exp

  • chelation not v helpful
    *