Pathophysiology of Acute Kidney Injury (AKI)
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Which of the following statements about DAMPs and PAMPs is true?

  • PAMPs originate from damaged tissues.
  • Neither DAMPs nor PAMPs interact with pattern recognition receptors.
  • DAMPs are released only from pathogens.
  • Both DAMPs and PAMPs act as danger signals to the immune system. (correct)

    • M1 macrophages are associated with anti-inflammatory responses.

    False

    What are the two main phenotypes of macrophages?

    M1 and M2

    DAMPs and PAMPs interact with _____ in the innate immune system to signal an immune response.

    <p>pattern recognition receptors (PRRs)</p> Signup and view all the answers

    Match the macrophage phenotype with its corresponding function:

    <p>M1 = Pro-inflammatory response M2 = Tissue repair and regeneration Activated Macrophages = Removal of damaged particles M-CSF Production = Supports anti-inflammatory activity</p> Signup and view all the answers

    What is a consequence of ischemia leading to ATP depletion?

    <p>Activation of intracellular lipases</p> Signup and view all the answers

    Apoptosis is a chaotic process characterized by the rupture of the plasma cell membrane.

    <p>False</p> Signup and view all the answers

    What type of macrophages are involved in the inflammation during the early phase of acute kidney injury (AKI)?

    <p>M1 macrophages</p> Signup and view all the answers

    Reperfusion leads to the production of ________ species which can cause lipid peroxidation.

    <p>reactive oxygen</p> Signup and view all the answers

    Match the cellular responses to their descriptions in epithelial injury:

    <p>Necrosis = Chaotic process with plasma membrane rupture Apoptosis = Highly regulated and not inflammatory Sublethal injury = Disruption of cytoskeletal network and cell detachment</p> Signup and view all the answers

    Which of the following is NOT a consequence of intracellular lipase activation?

    <p>Increased ATP production</p> Signup and view all the answers

    Systemic inflammation can lead to acute kidney injury (AKI).

    <p>True</p> Signup and view all the answers

    What is the role of M2 macrophages in the context of ischemic injury?

    <p>Anti-inflammatory and facilitate recovery</p> Signup and view all the answers

    What does DAMPs stand for?

    <p>Damage-Associated Molecular Patterns</p> Signup and view all the answers

    Macrophage infiltration is associated with scarring and fibrosis in kidney injuries.

    <p>True</p> Signup and view all the answers

    What is the role of TGFβ in kidney injury?

    <p>It promotes fibrosis and contributes to maladaptive repair.</p> Signup and view all the answers

    The innate immune response is activated during _____ injury.

    <p>acute</p> Signup and view all the answers

    Match the type of macrophage with its function during kidney injury:

    <p>M1 = Pro-inflammatory response M2 = Wound healing response M2 (pro-fibrotic) = Progression to chronic kidney disease Macrophage infiltration = Correlates with scarring and fibrosis</p> Signup and view all the answers

    What cellular response can lead to stress-induced senescence in tubular epithelial cells?

    <p>G2/M cell-cycle arrest</p> Signup and view all the answers

    Macrophages only have a pro-inflammatory role in kidney injury.

    <p>False</p> Signup and view all the answers

    What type of receptors are TLRs and NLRs?

    <p>Pattern recognition receptors</p> Signup and view all the answers

    The _____ response helps clear cellular debris and promotes tissue repair.

    <p>adaptive</p> Signup and view all the answers

    What is the primary consequence of maladaptive repair following kidney injury?

    <p>Progression to chronic kidney disease (CKD)</p> Signup and view all the answers

    What is the primary mortality rate for dogs with acute kidney injury (AKI)?

    <p>39%</p> Signup and view all the answers

    Community-acquired AKI presents with early detection due to frequent monitoring.

    <p>False</p> Signup and view all the answers

    Name one of the syndromes included in the definition of acute kidney injury (AKI) in human medicine.

    <p>Sepsis</p> Signup and view all the answers

    In veterinary medicine, AKI is defined as sudden renal parenchymal injury leading to generalized kidney failure to meet __________ demands.

    <p>excretory</p> Signup and view all the answers

    Match the type of AKI with its description:

    <p>Community-acquired AKI = Delayed presentation after initial insult outside of the hospital Hospital-acquired AKI = Early detection through frequent monitoring of renal markers</p> Signup and view all the answers

    Which of the following options is NOT associated with an increase in mortality in AKI?

    <p>Excellent renal function</p> Signup and view all the answers

    Ischemia-reperfusion injury is one of the common mechanisms of kidney injury.

    <p>True</p> Signup and view all the answers

    What is the odds ratio for survival when AKI is present?

    <p>0.2</p> Signup and view all the answers

    Which of the following is a mechanism involved in sepsis-induced acute kidney injury (AKI)?

    <p>Inflammation and microcirculatory dysfunction</p> Signup and view all the answers

    Ischemia-reperfusion injury leads to the production of reactive oxygen species (ROS).

    <p>True</p> Signup and view all the answers

    What type of injury is characterized by altered renal hemodynamics and direct tubular epithelial toxicity?

    <p>Nephrotoxic AKI</p> Signup and view all the answers

    Inflammatory cytokines such as _____ and TNF-a are involved in the ischemia-reperfusion injury cascade.

    <p>IL6</p> Signup and view all the answers

    Match the type of acute kidney injury with its associated characteristic:

    <p>Ischemia-reperfusion injury = Triggers inflammatory cascade Sepsis-induced AKI = Microcirculatory dysfunction Nephrotoxic AKI = Direct tubular toxicity AKI in general = Involves complex interplay of mechanisms</p> Signup and view all the answers

    Which factor is not typically associated with nephrotoxic acute kidney injury?

    <p>Severe systemic infection</p> Signup and view all the answers

    Maladaptive repair after acute kidney injury can lead to chronic kidney disease (CKD).

    <p>True</p> Signup and view all the answers

    Name one potential consequence of the inflammatory cascade triggered by ischemia-reperfusion injury.

    <p>Cell death</p> Signup and view all the answers

    What is the primary cause of pre-renal AKI?

    <p>Renal hypoperfusion</p> Signup and view all the answers

    Intrinsic renal AKI is caused by a response to renal hypoperfusion.

    <p>False</p> Signup and view all the answers

    Name the phase of AKI where uremic effects dominate.

    <p>Maintenance</p> Signup and view all the answers

    The imbalance in __________ delivery to renal tissue can lead to ischemic injury.

    <p>oxygen</p> Signup and view all the answers

    Match the type of AKI with its characteristics:

    <p>Pre-renal AKI = Response to renal hypoperfusion Intrinsic renal AKI = Parenchymal injury Post-renal AKI = Impaired urine flow Maintenance phase = Uremic effects dominate</p> Signup and view all the answers

    Which of the following best describes the term 'adaptive repair' in AKI?

    <p>Is regulated and supports recovery following injury</p> Signup and view all the answers

    DAMPs primarily recruit leukocytes during the late phase of AKI.

    <p>False</p> Signup and view all the answers

    What cellular event occurs due to ATP depletion during ischemia?

    <p>Loss of ionic gradients</p> Signup and view all the answers

    Ischemia can lead to the production of reactive oxygen species (ROS), resulting in __________ damage.

    <p>lipid peroxidation</p> Signup and view all the answers

    Which of the following mediators is released during the early phase of inflammation in AKI?

    <p>M1 macrophages</p> Signup and view all the answers

    The recovery phase of AKI guarantees complete renal function restoration.

    <p>False</p> Signup and view all the answers

    Identify one key characteristic of tubular dysfunction in AKI.

    <p>Intratubular obstruction</p> Signup and view all the answers

    Reperfusion injury is primarily associated with the production of __________ species.

    <p>reactive oxygen</p> Signup and view all the answers

    Match the phenomenon with its description:

    <p>Necrosis = Chaotic and inflammatory cell death Apoptosis = Regulated programmed cell death Sublethal injury = Cellular dysfunction without death Reperfusion injury = Caused by restoration of blood flow</p> Signup and view all the answers

    What is the primary function of M1 macrophages during the first 24-48 hours after injury?

    <p>Clear damaged pathogenic particles</p> Signup and view all the answers

    M2 macrophages are primarily responsible for the initial inflammatory response in acute kidney injury.

    <p>False</p> Signup and view all the answers

    What do DAMPs and PAMPs signal to in the immune system?

    <p>innate immune receptors</p> Signup and view all the answers

    The _______ feedback mechanism involves solute delivery to the macula densa.

    <p>tubulo-glomerular</p> Signup and view all the answers

    Match the macrophage type with its role during kidney injury:

    <p>M1 macrophages = Pro-inflammatory response M2 macrophages = Tissue repair Pro-fibrotic M2 = Progression to chronic kidney disease Macrophage infiltration = Scarring and fibrosis</p> Signup and view all the answers

    Which factors are involved in the tubulo-glomerular feedback mechanism?

    <p>Chloride and renin</p> Signup and view all the answers

    Maladaptive repair leads to inflammation, fibrosis, and chronic kidney disease (CKD).

    <p>True</p> Signup and view all the answers

    What is the role of KIM-1 in tubular epithelial cells?

    <p>Macrophage chemotaxis</p> Signup and view all the answers

    M-CSF is produced by _______ after kidney injury.

    <p>proximal tubular cells</p> Signup and view all the answers

    Which cytokines are released by M1 macrophages?

    <p>IL-1, IL-6, IL-12, TNF</p> Signup and view all the answers

    Chronic kidney disease (CKD) primarily develops due to immediate cell death following acute injury.

    <p>False</p> Signup and view all the answers

    Name one consequence of tubule cell stress-induced senescence.

    <p>Maladaptive repair and fibrosis</p> Signup and view all the answers

    The initial response to injury is characterized by the activation of ______ macrophages.

    <p>M1</p> Signup and view all the answers

    Match the macrophage phase with its function:

    <p>M1 macrophage = Acute injury phase M2 macrophage = Wound healing phase Pro-fibrotic M2 = CKD progression phase</p> Signup and view all the answers

    Study Notes

    Pathophysiology of Acute Kidney Injury (AKI)

    • AKI is defined by a rapid increase in serum creatinine, decrease in urine output, or both.
    • AKI is not a single disease, but a collection of syndromes including sepsis, cardiorenal syndrome, and urinary tract obstruction.
    • AKI can be community or hospital acquired.
    • Community acquired AKI is triggered outside the hospital, with a delay in presentation of a few days.
    • Hospital acquired AKI occurs during the period of hospital treatment, and includes frequent monitoring of kidney function markers for early detection.
    • In dogs with septic peritonitis, AKI occurs in 40% of cases and is associated with decreased survival odds.
    • Mortality rate in dogs with AKI is 39%, versus 9% in dogs without AKI.

    Outline: Pathophysiology of AKI

    • Definition: Detailed description of AKI
    • General pathophysiology of injury: Includes ischemia-reperfusion injury, sepsis, and toxic nephrosis as underlying causes.
    • Renal repair: Describes the body's response to repair damage.
    • Specific pathophysiology: A breakdown of specifics regarding different causes of AKI.
      • Ischemia-reperfusion, sepsis, toxic nephrosis

    AKI: Why a new name?

    • Functional definition: Uses functional markers such as GFR (glomerular filtration rate) surrogates (creatinine, cystatin C, SDMA), and USG (urine specific gravity).
    • Lesional definition: Focuses on injury markers such as urine sediment, casts, renal glucosuria, uGGT (urinary gamma glutamyl transferase), and uNAG (urinary N-acetyl-glucosaminidase).

    Pathophysiology - Historical Classification

    • Pre-renal AKI: Physiologic response to renal hypoperfusion, without tubular injury.
    • Intrinsic renal AKI: Parenchymal injury (glomerular, tubular, vascular, interstitial).
    • Post-renal AKI: Impaired flow of urine (obstruction, rupture).

    General Pathophysiology – The Phases of AKI

    • I - Initiation: Kidney injury initiation.
    • II - Extension: Progression of injury.
    • III - Maintenance: Kidney function maintained in the face of extensive damage.
    • IV - Recovery: Functional recovery with complete return or chronic kidney disease.

    Pathophysiology - Five Characteristics

    • Microvascular imbalance: Imbalance in vasodilatory and vasoconstrictive factors.
    • Tubular dysfunction: Involves obstruction within the tubules.
    • Cell death: Apoptosis and necrosis.
    • Inflammation: Causes of inflammation are explored.
    • Adaptive and maladaptive repair: Body's repair mechanisms in the context of damage.

    Endothelial Injury (Microvascular Events)

    • Dysbalance between vasodilatory and vasoconstrictive mediators.
    • Energy deprivation of endothelium.
    • Increased permeability and edema.
    • Release of cytokines, chemokines, adhesion molecules.

    (Micro-)Vascular Imbalance in AKI

    • Imbalance in vasodilatory/vasoconstrictive factors.
    • Mismatch between oxygen and nutrient delivery.
    • Often regional, not generalized.
    • Kidney not a primary organ.

    Definition of AKI (hum)

    • Fast increase in serum creatinine.
    • Decreased urine output

    Definition of AKI (vet)

    • Spectrum of diseases with sudden onset renal parenchymal injury.
    • Generalized failure of the kidney to meet excretory, metabolic, and endocrine demands of the body.
    • Rapid hemodynamic, filtration, tubulointerstitial, or outflow injury.

    Interstitial Events (Inflammation, Edema)

    • Injury (Ischemia) → ATP depletion.
    • HIF gene upregulation.
    • Generation of ROS.
    • Inflammation and recruitment of leukocytes.

    Inflammation - Central Role for Macrophages

    • Biphasic phenotypes:
      • M1 pro-inflammatory: Active during the first 24-48 hours of injury, triggered by DAMPs/PAMPs to eliminate pathogen particles.
      • M2 anti-inflammatory: Starts after the initial pro-inflammatory phase. Involved in tissue repair.

    Tubulo-Glomerular Feedback

    • Proximal tubular dysfunction → increased solute delivery to the macula densa.
    • Afferent vasoconstriction and decreased SN-GFR.
    • This contributes to oliguria.

    Ischemia-Reperfusion Injury (IRI)

    • IRI triggers an inflammatory cascade.
    • Pro-inflammatory cytokines are activated.
    • Inflammatory molecules are expressed.
    • Leukocyte infiltration and activation.
    • Generation of reactive oxygen species.

    Sepsis-Induced AKI

    • Combination of mechanisms including ischemia-reperfusion injury, microcirculatory dysfunction, inflammation and metabolic reprogramming.

    Kidney predisposed to toxic injury

    • High blood supply.
    • Filtration and tubular concentration
    • Tubular reabsorption

    Take home messages

    • AKI involves a complex interplay of multiple mechanisms in systemic diseases.
    • Inflammation is central, even without infection.

    Kidney Repair

    • Adaptive repair: restores normal cell function and homeostasis; lost epithelial cells are replaced via proliferation.
    • Maladaptive repair: occurs with prolonged or severe injury and results in scarring, inflammation, fibrosis, and CKD progression.

    Epithelial-to-mesenchymal transition

    • Transition from epithelial cells to mesenchymal cells.
    • Occurs in response to inflammation, ischemia and reperfusion.
    • Results in accumulation of fibrotic scar tissue.

    Antifibrotic strategies

    • Therapies targeting the mechanisms causing fibrogenesis.

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    Related Documents

    2024 HD Academy Pathophysiology of AKI PDF

    Description

    This quiz explores the pathophysiology of Acute Kidney Injury (AKI), including its definitions, causes, and implications for both community and hospital-acquired cases. It covers various syndromes related to AKI and the impact on survival rates in affected dogs. Test your knowledge on this critical topic in veterinary medicine.

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