YuanPu Zheng MD January 31 2019 httpskidneycarebrooklyncomeducationresources Goals Glomerulus Proximal Tubule Ascending Thick Limb Distal Convoluted Tubule Macula Densa TubuloGlomerular ID: 909245
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Slide1
Renal PathoPhysiology
for Internal Medicine ResidentsYuanPu Zheng, MDJanuary 31, 2019
https://kidneycarebrooklyn.com/education-resources/
Slide2Goals
GlomerulusProximal TubuleAscending Thick LimbDistal Convoluted Tubule, Macula Densa,
TubuloGlomerular
Feedback
Collecting DuctHormonesBlood Pressure, Bone Homeostasis, Erythropoeisis
Protein Handling
Electrolyte Handling
Water Handling, Urea Handling
Acid Base Homeostasis
Exogenous Stuff/Drugs Handling
Slide3Luminal/Apical/Urinary vs. Basolateral/Interstitial
Luminal/Apical/Urinary – where the urine isBasolateral/Interstitial – where all the reabsorbed stuff goes
Slide4Anatomy SlidesPeritubular Capillaries – capillaries formed off the efferent arteriole that reabsorb stuff from the
basolateral side
Slide5Slide6GlomerulusPerforms FiltrationRenal Blood Flow 1L/minRenal Filtration Fraction about 20%
Normal GFR ~180L/day or ~125cc/minOxygenated blood is supplied by the EFFERENT arteriole, which forms the peritubular capillaries
Slide7Proximal TubuleSodium Cotransport to reclaim filtered molecules
Glucose, Amino Acids, PhosphateATP is used to drive the 3Na-2K Antiporter on the basolateral membraneAcid-Base Balance
Slide8Acetazolamide
Slide9Slide10BASE Reabsorption
ACID Excretion
Slide11Thin Limb of HenleThin descending limb is Permeable to water
Thin ascending limb is Permeable to ions
Slide12Slide13Thick Ascending LimbNKCC2 (Na+ K
+ 2Cl- Cotransporter)Medullary Concentration GradientParacellular Transport
Slide14Loop Diuretics
Slide15Slide16Furosemide Stress TestThe 2-hour urine output (UOP) after Furosemide Stress Test (administration of 1-1.5mg/kg furosemide IV) … “was the only biomarker to significantly predict RRT (ROC AUC 0.866+/-0.08; P=0.001)”
Cut-off point was UOP in 2 hours >200ccJ Am Soc
Nephrol
26: 2023–2031, 2015.
Slide17Distal Convoluted TubuleNaCl cotransport
Macula DensaTubuloglomerular Feedback
Slide18Thiazides
Slide19Tubuloglomerlular Feedback
High urine flow in the Macula Densa causes constriction of AA through adenosine
Slide20Tubuloglomerlular Feedback
Low urine flow in the Macula Densa causes vasodilation of AA through prostaglandins
Slide21Collecting DuctPotassium BalanceWater ConservationAcid-Base Balance
Urea Reabsorption
Slide22Aldosterone
Spironolactone/Eplerenone
Amiloride
H
+
Slide23Urea HandlingUrea concentration increases in the Medullary collecting duct as water is reabsorbedUrea PASSIVELY reabsorbed through UT-A1 and UT-A3 (UT-A3 opened by ADH)
Result: 1200mOsm medullary tonicity and high serum BUN
Slide24Urea
Urea
Slide25Endocrine InputAngiotensin IIAldosterone
AntiDiuretic Hormone (ADH, AVP)Atrial Natriuretic Peptide – increases afferent arteriolar vasodilationProstaglandinsParathyroid Hormone
Slide26Endocrine OutputReninErythropoietin1-alpha-hydroxylase
Slide27Renin-Angiotension-Aldosterone Axis
Increased Beta-Sympathetic tone and decrease renal blood flow release Renin (from granular cells in the afferent arteriole)Renin (protease) cleaves Angiotensin I to Angiotension IIAngiotension II constricts the efferent arterioleIncreased efferent arteriolar pressure
increases filtration fraction
RELATIVE INCREASE in GFR
Increased renal vascular resistanceDECREASED Renal Blood FlowIncreases Aldosterone expression in the adrenal cortexIncreases ADH expression
PMID: 29489242
Slide28Audience Questions?
Slide29Questions for the AudienceWhat’s the Cause of the Problem?
Slide30Oliguric AKIHypovolemia
Urinary ObstructionLoss of GFR
Slide31Oliguric HypernatremiaFree Water Deficit
Slide32Polyuric HypernatremiaDiabetes Insipidus
Loop DiureticsNephrotoxins causing DI – Lithium, Amphotericin, etc…
Slide33Hyponatremia with Low BPIncreased free water intake(appropriately) high ADH state
Far less common – cerebral salt wasting
Slide34Hyponatremia on DiureticTHIAZIDEfree water intake + Thiazide direct ADH action
free water intake + Hypovolemia
Slide35Hypernatremia on DiureticLOOP DiureticImpaired renal concentrating ability
Causing inappropriately high urinary water loss
Slide36LOOP DIURETIC
LOOP DIURETIC
Slide37Hypokalemia on DiureticsDirect inhibition of potassium reabsorptionIncreased distal sodium delivery causes increased urinary potassium loss in the collecting duct
Aldosterone required to make ENaC available
Slide38Hypomagnesemia on DrugsPantoprazole
Impaired GI magnesium absorptionCalcineurin InhibitorsRenal Magnesium wasting
Slide39Hypomagnesemia after ATN
Impaired Tubular function leads to impaired paracellular magnesium reabsorption
Slide40Hypokalemia in the setting of Hypomagnesemia
Loss of magnesium cofactor, which is required to close ROMK channel and stop urinary potassium excretion
PMID: 21030597
Slide41Hyperkalemia on Potassium Sparing DiureticsImpaired potassium excretion through ROMK
K-sparing diuretics inhibits ENaC either directly or indirectly
Slide42Case: Serum bicarbonate is 40#1 - Get a blood gasFirst thing to check on Exam?
Hypotensive – Pt admitted to Buckley 5 for heart failure exacerbation
Slide43Diuretic Induced AlkalosisLoss of Chloride out of proportion to Loss of Bicarbonate
Slide44Hypertensive with Metabolic Alkalosis
High Aldosterone State or ENaC activityPrimary hyperaldosteronismHigh renin activity (
renovascular
disease,
reninoma)Mineralcorticoid Excess, Exogenous steroid use, etc.Liddle Syndrome
Slide45Audience Questions?
Slide46Renal Injury – What part of the Nephron is hurt?Primary site of Injury - please
Slide47AcyclovirTubular obstruction from crystallization of acyclovir crystals
Slide48AKI on CisplatinDirect tubular toxicity – Proximal Tubule
Slide49AKI on GentamicinDirect proximal tubular toxicity
PMID: 10223907
Slide50Tenofivir, AmphotericinTubular Toxicity
RTA
Slide51Vancomycin
Tubular ToxicityOxidative injury
Slide52High serum free Light Chains
Depends on the specific light chainTubular obstruction, cast nephropathy, light chain is proinflammatory and nephrotoxicMonoclonal ImmunoDeposition DiseaseAmyloidosis
Slide53Myeloma and Fanconi Syndrome
Proximal RTAGlucosuria, Amino Aciduria, Phosphaturia
Slide54AKI after Iodinated ContrastPrerenalReduced GFR because of afferent arteriolar vasoconstriction
Tubular toxicity, oxidative stress
Slide55AKI after NSAIDsPrerenalRenal arteriolar vasoconstriction
Inhibition of prostaglandin synthesis
Slide56AKI on ACE-I or ARBPrerenalReduced GFR because of efferent arteriolar vasodilation
Slide57MethotrexateTubular ToxicityPrerenal
Slide58AKI from HypercalcemiaTrue Volume Depletion causing Prerenal Azotemia
CaSR in thick ascending limbs inhibits NKCC2
Slide59Calcineurin InhibitorsPrerenal, dose/level dependentTubular toxicity
TMAHypomagnesemiaCJASN February 2009, 4 (2) 481-508
Slide60Lupus Nephritis (Class III or IV)Proliferative GN
Slide61ANCA VasculitisNecrotizing GN
Slide62Questions?
Slide63Goals
GlomerulusProximal TubuleAscending Thick LimbDistal Convoluted Tubule, Macula Densa,
TubuloGlomerular
Feedback
Collecting DuctHormonesBlood Pressure, Bone Homeostasis, Erythropoeisis
Protein Handling
Electrolyte Handling
Water Handling, Urea Handling
Acid Base Homeostasis
Exogenous Stuff/Drugs Handling
Slide64References
Cecil Textbook of Medicine: Chapter 117. Structure and Function of the KidneysHarrison's 18th Edition: Chapter 277. Cellular and Molecular Biology of the KidneyBRS Physiology 4th Ed Costanzo 2006Brenner and Rectors The Kidney, 12th
Edition
Pubmed
Articles (PMID)
https://kidneycarebrooklyn.com/education-resources/