Kidney

Cards (59)

  • Principal Roles of the Kidney
    • excretion of metabolic wastes
    • regulation of extracellular fluids
    • electrolyte composition
    • acid-base balance
  • Three demarcated anatomical areas of the kidney
    • Cortex (90%) - biggest
    • Medulla (6-10%)
    • Papilla (1-2%)
  • Functional Units of the Kidneys
    • Nephron
    • Vascular element
    • Glomerulus
    • Tubular element
  • Renal artery supplies blood to the glomerulus
  • Pathway of blood from the Renal Artery to Glomerulus
    Interlobar - arcuate - interlobular arteries - afferent arterioles
  • Both afferent and efferent arterioles control glomerular capillary pressure and glomerular plasma flow rate
  • The glomerulus is a complex, specialized capillary bed composed primarily of endothelial cells
  • The glomerulus is characterized by an attenuated and fenestrated cytoplasm and visceral epithelial cells such as cell body (podocyte), trabeculae and pedicles (foot processes), glomerular basement membrane (GBM)
  • Three discrete segments of the Proximal Tubule
    • S1 - pars convolute
    • S2 - transition between pars convolute and pars recta
    • S3 - pars recta
  • The proximal tubule is the workhorse of the nephron, as it reabsorbs 60-80% of solute and water filtered at the glomerulus
  • The proximal tubule also reabsorbs virtually all the filtered low MW proteins by specific endocytotic protein reabsorption processes
  • Approximately 25% of the filtered Na and K and 20% of the filtered water are reabsorbed by the segments of the Loop of Henle
  • Tubular fluid entering the thin descending limb - iso-osmotic to the renal interstitium
  • Water is freely permeable, and solutes (electrolytes and urea)
  • Thin ascending limb - impermeable to water, electrolytes are reabsorbed by the active Na/K/2Cl cotransport mechanism (Na, K, ATPase)
  • The early distal tubule reabsorbs most of the remaining impermeable to water
  • The late distal tubule, cortical collecting tubule, and medullary collecting duct perform the final regulation and fine-tuning of urinary volume and composition
  • Acute kidney injury (AKI) is characterized by an abrupt decline in GFR with resulting azotemia
  • AKI describes the entire spectrum of the disease and is defined as a complex disorder that comprises multiple causative factors with clinical manifestations ranging from minimal elevation in serum creatinine to anuric renal failure
  • Any decline in GFR is complex and may result from
    • Prerenal factors - renal vasoconstriction, intravascular volume depletion, insufficient caloric output
    • Postrenal factors - ureteral or bladder obstruction
    • Intrarenal factors - glomerulonephritis, tubular cell injury, death and loss resulting in back leak
  • Mechanisms of Chemically-induced AKI

    Prerenal
    1. Diuretics
    2. Angiotensin receptor antagonists
    3. Angiotensin-converting enzyme inhibitors
    4. Antihypertensive agents
  • Mechanisms of Chemically-induced AKI
    Vasoconstriction
    1. NSAIDS
    2. Radiocontrast agents
    3. Cyclosporine
    4. Tacrolimus
    5. Amphoterin B
  • Mechanisms of Chemically-induced AKI
    Crystalluria
    1. Sulfonamides
    2. Methotrexate
    3. Acyclovir
    4. Triamterene
    5. Ethylene glycol
    6. Protease inhibitors
  • Mechanisms of Chemically-induced AKI
    Tubular Toxicity
    1. Aminoglycosides
    2. Cisplatin
    3. Vancomycin
    4. Pentamidine
    5. Radiocontrast agents
    6. Heavy metals
    7. Haloalkane- and Haloalkene - cysteine conjugates
  • Mechanisms of Chemically-induced AKI

    Endothelial Injury
    1. Cyclosporine
    2. Mitomycin C
    3. Tacrolimus
    4. Cocaine
    5. Conjugated estrogens
    6. Quinine
  • Mechanisms of Chemically-induced AKI
    Glomerulopathy
    1. Gold
    2. Penicillamine
    3. NSAIDS
  • Mechanisms of Chemically-induced AKI
    Interstitial Nephritis
    1. Antibiotics
    2. NSAIDS
    3. Diuretics
  • Chronic Kidney Disease (CKD) is the progressive deterioration of the renal function due to long-term exposure to various chemicals such as analgesics, lithium, and cyclosporine
  • In CKD, alterations are maladaptive, and focal glomerulosclerosis eventually develops, which may lead to tubular atrophy and interstitial fibrosis
  • NSAIDs
    Prostaglandin synthesis suppressor --> decreased renal blood flow --> AKI
  • ACEi

    Blocks vasoconstriction --> precipitous decline in filtration pressure + AKI
  • Many nephrotoxicants have their primary effects on discrete segments or regions of the nephron
  • Site-selective injury
    Can be attributed to the following:
    • site-specific differences in blood flow
    • transport and accumulation of chemicals
    • physicochemical properties of the epithelium
    • reactivity of cellular/molecular targets
    • balance of bioactivation/detoxification reactions
    • cellular energetics
    • regenerative/repair mechanisms
  • The glomerulus is the initial site of chemical exposure within the nephron
  • Cyclosporine, Amphotericin B, and Gentamcin
    Impairs glomerular ultrafiltration without significant loss of structural integrity and decrease GFR
  • Amphotericin B
    Decreases GFR by renal vasoconstriction and decreases glomerular capillary ultrafiltration coefficient (Kf)
  • Gentamicin
    Interacts with anionic sites on the endothelial cells which leads to decreased GFR and decreased Kf
  • Cyclosporine
    Renal vasoconstriction and vascular damage, injurious to the glomerular endothelial cell
  • The proximal tubule is the most common site of toxicant-induced renal injury
  • The proximal tubule has a leaky epithelium, favoring the flux of compounds into proximal tubular cells