1/30 Tubulointerstitial Disease - Kapoian

Question 1

kidney compartments

Answer 1

• glomerular
• vascular
• tubular
• interstitial

Question 2

two types of nephrons and difference

Answer 2

1. cortical nephron - shorter
2. juxtamedullary nephron - longer

Question 3

anatomy of tubular membrane

3 components and their functions

Answer 3

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

Question 4

tubular segment terminology

what is included in…

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

Answer 4

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

Question 5

thick asc limb of LoH

Answer 5

• 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!

Question 6

distal nephron cell types

Answer 6

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

Question 7

distal convoluted tubule

begin/end

fx

“diuretic resistance”

Answer 7

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

Question 8

connecting tubule

Answer 8

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

Question 9

collecting duct

two cell types

Answer 9

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

2. 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

Question 10

diet-induced variations in urinary sodium excretion

hi Na vs lo Na

what cell type affected, what effect?

Answer 10

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

Question 11

alpha intercalated cells

Answer 11

• Apical membrane
• resp for Acid secretion
• responds to Aldosterone

Question 12

beta intercalated cells

Answer 12

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

opposite polarity of alpha cells!

Question 13

mechanisms of tubulointerstitial injury:

glomerular injury

Answer 13

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

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

Question 14

mechs of TI injury:

immunologic processes

Answer 14

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

Question 15

mechs of TI injury:

alterations in tubular metabolism

Answer 15

kidney has high rate of O consumption

disease state cause surviving nephrons to display:

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

Question 16

mechs of TI injury:

alteration in intrarenal dynamics

Answer 16

• incr wall tension
• incr urinary flow rate

Question 17

mechs of TI injury:

diabetes

Answer 17

hyperglycemia induces:

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

Question 18

mechs of TI injury:

crystalline deposition

Answer 18

• 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

Question 19

mechs of TI injury:

nephron obstruction

Answer 19

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

Question 20

clinical clues re: TI disease

Answer 20

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

Question 21

Fanconi syndrome

Answer 21

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

Question 22

autosomal dom polysystic kidney disease

Answer 22

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

Question 23

acute tubular necrosis

Answer 23

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

Question 24

allergic interstitial nephritis

Answer 24

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

Question 25

role of infections

Answer 25

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

Question 26

pyelonephritis

Answer 26

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

Question 27

role of drugs

Answer 27

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

Question 28

medullary sponge kidney

Answer 28

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

Question 29

sickle cell nephropathy

Answer 29

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

Question 30

multiple myeloma

Answer 30

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

Question 31

GPA

granulomatosis with polyangiitis

(formerly Wegeners)

Answer 31

• 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

Question 32

lead poisoning

Answer 32

• 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
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