Renal physiology TBL

From Iusmphysiology

Contents 1 Acute kidney injury 1.1 Definition 1.2 Epidemiology 1.3 Pathophysiology 1.3.1 Prerenal AKI 1.3.2 Intrinsic AKI 1.3.2.1 Tubular intrinsic AKI 1.3.2.2 Interstitium intrinsic AKI 1.3.2.3 Vascular intrinsic AK

Acute kidney injury

Definition

• We have renamed acute renal failure (AFR) to acute kidney injury (AKI).
  • We renamed it because of an historic inability to sufficiently define ARF.
• Now we define acute kidney injury (AKI) as "a functional or structural abnormality of the kidney as determined by blood, urine, or tissue tests or imagine studies that manifests with 48 hours".
• We use diagnostics like serum creatinine (normally cleared by the kidney) and urine production to determine the occurrance of AKI (acute kidney injury).
  • Serum creatinine increase by 50% or over 0.3 mg / dL is considered diagnostic for AKI.
  • Reduced urine production resulting in less than 0.5 ml / kg / hr for 6 hours is diagnostic for AKI.
    • Oliguria: "production of an abnormally small amount of urine" per wornet

Epidemiology

• The incidence of AKI (acute kidney injury) depends on the setting:
  • hospital population: 5-7%
  • ICU: 15-40%
  • community: 1%
• The mortality of AKI (acute kidney injury) ranges from 36-86% and depends on:
  • setting ICU > hospital > community
  • age
  • illness acuity
  • severity of injury
• Elevated serum creatinine levels, even with only mild increases, can result in large increases in mortality.

Pathophysiology

• There are many ways that the kidney can be injured:
  • decreased perfusion
  • toxins
  • ischemic or obstructive injury to the tubule
  • inflammation and / or edema of the tubulointerstitium,
  • primary glomerular disease
• We divide the pathophysiology into three, broad, anatomical divisions: prerenal, intrinsic / intrarenal, and post-renal.
  • Prerenal makes up 40-70% of AKI pathophys
  • Intrinsic makes up 25-40% of AKI pathophys
  • Postrenal makes up 5-10% of AKI pathophys
• Intrinsic pathophysiology will be the focus of our inquiries and includes several types of injury:
  • acute glomerulonephritis
  • acute interstitial nephritis
  • tubular cell injury
    • Ischemia and inflammation (sepsis, surgery, hypoperfusion)
    • Toxins (direct or indirect)

Prerenal AKI

• Azotemia: "Azotemia is a medical condition characterized by abnormally high levels of nitrogen-containing compounds, such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds in the blood." per wikipedia
• Azotemia is the most common etiology of prerenal AKI.
• Azotemia can occur when the extracellular compartment undergoes a severe decrease in volume.
• We categorize azotemia into volume-responsive or not depending on whether expanding the extracellular compartment resolves the azotemia.
  • For example, adding saline will expand the extracellular compartment.
• Another major cause of prerenal AKI is medications that work upstream of renal function: angiotensin converting enzyme inhibitors (ACEI’s), angiotensin receptor blockers (ARB’s) and NSAIDs (reduce glomerular

capillary perfusion by reducing prostaglandins such that vasodilation is reduced).

• Prerenal AKI timeline:
  • autoregulatory mechanisms of the kidney attempt to maintain blood flow and GFR (think myogenic and tubuloglomerular feedback),
    • Recall that these serve to change the blood flow in the afferent and efferent glomerular arterioles
  • renal hypoperfusion triggers the hormonal response (think renin, aldosterone, and AVP) which mostly maintains the GFR
  • without interventsion, the pt progressive to significant tubular cell injury due to ischemia (which is then intrinsic AKI).

Intrinsic AKI

• There are many causes of intrinsic AKI, so we classify them by their histological location: tubules, interstitium, vasculature, or glomerulus.

Tubular intrinsic AKI

• Tubular injury often occurs by way of inschemia but may also occur because of specific renal toxins that target tubular cells.
• Tubular injury from ischemia is an extension of prerenal injury and occurs in four distinct stages: initiation, extension, maintenance, and recovery.
• Initiation: tubular cells demonstrate a severe depletion of ATP.
• Extension: microvascular congestion and inflammation occur.
• Maintenance: cells continue to repair, migrate, and proliferate to maintain tubular integrity.
• Recovery: GFR improves as cellular differentiation continues and normal cellular and organ function continues

• Tubular injury causes bleb formation on the apical membrane, loss of brush border, loss of surface membrane proteins, reduced polarity, loss of tight junctions, cell detachment, cast formation in the distal tubule (causing obstruction), and leakage of filtrate back into the interstitium.

• Renal toxins can act directly or indireclty.
  • Direct damage to tubular epithelial cells: aminoglycocides, radiocontrast, and cisplatin (a cancer drug)
  • Indirect damage via decreased blood flow: NSAIDs, cyclosporine, radiocontrast.
    • Cocaine and HGM-CoA reductase inhibitors can cause skeletal muscle damage, releasing heme which acts as a sort of endogenous toxin to tubular cells.
  • Precipitatory injury can occur when solutes or metabolites precipitate becasue of pharma: acyclovir, sulfonamides, ethylene glycol (calcium oxalate metabolite), methotrexate, and multiple myeloma light chains.
    • Patients with comorbidities like diabetes mellitus are far more likely to come down with pharam-induced precipitatory toxin damage.

Interstitium intrinsic AKI

• Injury to the interstitium of the kidney is sometimes called acute interstitial nephritis (AIN).
• Acute interstitial nephritis is characterized by invasion of T cells, monocytes, and macrophages.
  • These patches of inflammation can be diffuse or patchy.
• When chronic, AIN leads to interstitial scarring.
• AIN can be induced by drugs, infections, and auto-immune responses:
  • Drugs: penecillins, cephalosporins, sulfonamides, and NSAIDs.
  • Infections: bacterial and viral infections
  • Autoimmune responses: systemic or localized to the kidneys

Vascular intrinsic AK

• Vascular injury to the renal tissue occurs at the micro or macro vascular level.
• Microvascular damage is usually due to ... HELLP