The Pathophysiology of Acute Kidney Injury (struc) Flashcards
What should we focus on for the final?
Abigail’s case
Peripheral edema slide
Feline lymphoma slide
Take home msg slide
Pls be familiar with and understand the remainder of the lecture material and try to integrate it with ur lymphatic system lecture given a few weeks prior
LO
Review physiology
Define acute kidney injury
Describe causes of acute kidney injury and categorize them
Describe the 4 phases of acute kidney injury
Be familiar with clinical presentation, diagnosis and treatment
One of the kidney functions
Excretion of ? solute (urea, creatinine, minerals and other metabolic garbage) in a volume of water that is not itself required to maintain ?
It is the result of carefully regulated ? filtration, ? reabsorption and tubular ?.
kidney functions include ? production, blood ?, metabolic waste and xenobiotics ?, retrieves needed ? substances (water, flucose, electrolytes, low MW proteins), responds to water, electrolyte and acid-base disturbances, ? (glucose production), ? production associated with systemic blood pressure, ? production and ? metabolism
One of the kidney functions
Excretion of unwanted solute (urea, creatinine, minerals and other metabolic garbage) in a volume of water that is not itself required to maintain homeostasis
It is the result of carefully regulated glomerular filtration, tubular reabsorption and tubular secretion.
kidney functions include urine production, blood filtration, metabolic waste and xenobiotics excretion, retrieves needed metabolic substances (water, flucose, electrolytes, low MW proteins), responds to water, electrolyte and acid-base disturbances, gluconeogenesis (glucose production), hormone production associated with systemic blood pressure, RBC production and calcium metabolism
Acute Kidney Injury
** Abrupt damage to the renal ? resulting in a reduction in ? function reflected by alterations in ? filtration, ? production and ? function
Previously named ‘acute ? failure’
Consequences - Failure of the kidneys to meet the excretory, metabolic and endocrine demand of the body:
Retention of ? wastes that may lead to azotemia
Deranged ? status, ? imbalances and acid-base disorders **
Acute Kidney Injury (AKI)
** Abrupt damage to the renal parenchyma resulting in a reduction in kidney function reflected by alterations in glomerular filtration, urine production and tubular function
Previously named ‘acute renal failure’
Consequences - Failure of the kidneys to meet the excretory, metabolic and endocrine demand of the body:
Retention of uremic wastes that may lead to azotemia
Deranged fluid status, eletrolyte imbalances and acid-base disorders **
Describe causes of AKI and categorize them
AKI
1. ?-renal (hemodynamic)
2. ? renal
3. ? renal
prerenal and postrenal disease can coincide w ? renal injury
Describe causes of AKI and categorize them
AKI
1. pre-renal (hemodynamic)
2. intrinsic renal
3. post renal
prerenal and postrenal disease can coincide w intrinsic renal injury
- pre-renal (hemodynamic)
pathophysiology: insufficient delivery of blood to the kidneys e.g. dehydration, hypovolemia, hypotension, decreased effective circulating volume, trauma, shock, drugs etc. - intrinsic renal
pathophysiology: damage to any section of kidney: glomeruli, tubules, interstitium or vessels -> ischemia, toxins, infectious, immune-mediated, neoplasia etc. - post renal
pathoph..: urine leakage within tissue or urinary obstruction e.g. trauma, calculi, mucous plugs, tumors, blood clots, urethra/ureteral structures
Causes
how to categorize?
- prerenal azotemia (first time/acute onset) is a functional abnormality that is potentially ? depending on the primary cause
- prerenal disease can coincide with ? renal injury
Prognosis associated with prerenal azotemia
- early treatment -> favorable prognosis
- prolonged prerenal azotemia -> ? damage -> intrinsic, ? renal failure
PRE-RENAL
- elevated serum BUN or creatinine concentrations
- oliguria
- high urine specific gravity
- detection of the underlying cause
- rapid correction of azotemia after administration of appropriate therapy to restore renal perfusion
Causes
how to categorize?
- prerenal azotemia (first time/acute onset) is a functional abnormality that is potentially reversible depending on the primary cause
- prerenal disease can coincide with intrinsic renal injury
Prognosis associated with prerenal azotemia
- early treatment -> favorable prognosis
- prolonged prerenal azotemia -> structural damage -> intrinsic, irreverisble renal failure
INTRINSIC RENAL
Total loss of ability to ? and ? urine often develops gradually
A USG between 1.007 to 1.029 in dogs or 1.007 to 1.039 in cats associated with clinical dehydration or azotemia is indicative of intrarenal azotemia
Total inability of the nephrons to concentrate or dilute urine (isosthenuria) results in the formation of urine that is similar to that of ? filtrate (approximately 1.008 to 1.012)
> ? patient, with elevated BUN and ? concentrations and impaired ability to concentrate or dilute urine
Dehydrated patient, with ? BUN and creatinine and impaired ability to concentrate urine.
More definitive studies (e.g., ultrasonography, radiography, biopsy, exploratory surgery) to establish the underlying cause
? does not resolve after appropriate therapy (online: azotemia??)
INTRINSIC RENAL
Total loss of ability to concentrate and dilute urine often develops gradually
A USG between 1.007 to 1.029 in dogs or 1.007 to 1.039 in cats associated with clinical dehydration or azotemia is indicative of intrarenal azotemia
Total inability of the nephrons to concentrate or dilute urine (isosthenuria) results in the formation of urine that is similar to that of glomerular filtrate (approximately 1.008 to 1.012)
> hydrated patient, with elevated BUN and creatinine concentrations and impaired ability to concentrate or dilute urine
Dehydrated patient, with increased BUN and creatinine and impaired ability to concentrate urine.
More definitive studies (e.g., ultrasonography, radiography, biopsy, exploratory surgery) to establish the underlying cause
azotemia does not resolve after appropriate therapy (online: azotemia? = FIRST TIME/ACUTE ONSET)
POST RENAL
? of the excretory pathway
- elevated serum BUN and creatinine concentrations
- oliguria or anuria, dysuria and tenesmus
- obstructive ? detected by physical exam
- variable urine specific gravity values
Prognosis is associated with obstructive lesions
- Total obstruction for 3-6 days -> ?
- If obstruction is rapidly removed -> ? prognosis
- Long-term prognosis depends on the ? of the underlying cause
POST RENAL
obstruction of the excretory pathway
- elevated serum BUN and creatinine concentrations
- oliguria or anuria, dysuria and tenesmus
- obstructive leisions detected by physical exam
- variable urine specific gravity values
Prognosis is associated with obstructive lesions
- Total obstruction for 3-6 days -> death
- If obstruction is rapidly removed -> favorable prognosis
- Long-term prognosis depends on the reversibility of the underlying cause
How to categorize?
Combinations of azotemia
Pathogenesis
-> Patient with previously compensated primary renal disease:
1. Kidneys have an impaired ability to ?
2. ? crisis
-> Extrarenal mechanisms that may be associated with ? crises
- Protein by-products, stress states (fever, infection, change of environment), prerenal uremia, nephrotoxic drugs
How to categorize?
Combinations of azotemia
Pathogenesis
-> Patient with previously compensated primary renal disease:
1. Kidneys have an impaired ability to compensate
2. uremic crisis
-> Extrarenal mechanisms that may be associated with uremic crises
- Protein by-products, stress states (fever, infection, change of environment), prerenal uremia, nephrotoxic drugs
How to categorize?
Combinations of azotemia
Diagnosis
- Patients with a previous history of compensated primary renal failure
- Detection of primary extrarenal disease processes & generalized renal disease
- Detection of clinical dehydration associated with azotemia and impaired urine concentration -> a portion of the azotemia is prerenal
- Response to therapy
Prognosis.
- Withhold formulating a prognosis until the magnitude of azotemia is reassessed after correcting the prerenal or postrenal components of azotemia
The 4 phases of AKI
Phase 1 - Initiation
? insult – damage initiation
Phase 2 - ? phase
Localized ischemia, inflammation and cellular injury leading to cell apoptosis or necrosis, causing further damage
Phase 3 - ? phase
Phase 4 - ? phase
? tubules repair and heal i.e., ONLY if the basement membrane of the nephron is intact
The 4 phases of AKI (IEMR)
Phase 1 - Initiation
renal insult – damage initiation
Phase 2 - extension phase
Localized ischemia, inflammation and cellular injury leading to cell apoptosis or necrosis, causing further damage
Phase 3 - maintenance phase
Phase 4 - recovery phase
renal tubules repair and heal i.e., ONLY if the basement membrane of the nephron is intact
Phase 1 - initiation
? insult
- Ischemic, nephrotoxic, obstructive
Direct damage to ? tubular cells and ischemia
Hypoxia -> depletion in ? -> increased cellular ? concentration -> activates proteases and ? -> ROS and free radicals -> cellular ? -> ? reaction
** Nephrons within the renal medulla
(proximal convoluted tubule and the thick ascending loop of Henle)
are particularly vulnerable to ?,
due to decreased ? and increased ? demands compared with the rest of the kidney **
PHASE I initiation
Consequences: loss of apical microvilli & absorptive brush border -> loss of cell polarity
- Abnormal solute and electrolyte handling
- Increased sodium delivery to macula densa in distal tubule
- Tubuloglomerular feedback activated -> vasoconstriction afferent arteriole -> worsened renal ischemia
Integrin dysfunction
- Desquamation into tubular lumen -> obstruction (casts, debris) -> back-leak of filtrate into the peritubular interstitium + increased glomerular pressure -> ↓ GFR
Renal tubular cells unable to support their energy needs -> activation of intracellular mechanisms cause cellular swelling -> further obstruction of renal tubules
Clinically:
Clinical signs often absent
This phase lasts from hours to a few days
During this stage, ? intervention may prevent progression
Phase 1 - initiation
Renal insult
- Ischemic, nephrotoxic, obstructive
Direct damage to renal tubular cells and ischemia
Hypoxia -> depletion in ATP -> increased cellular calcium concentration -> activates proteases and phospholipases -> ROS and free radicals -> cellular damage -> inflammatory reaction
** Nephrons within the renal medulla
(proximal convoluted tubule and the thick ascending loop of Henle)
are particularly vulnerable to ischemia,
due to decreased perfusion and increased energy demands compared with the rest of the kidney **
PHASE I initiation
Consequences: loss of apical microvilli & absorptive brush border -> loss of cell polarity
- Abnormal solute and electrolyte handling
- Increased sodium delivery to macula densa in distal tubule
- Tubuloglomerular feedback activated -> vasoconstriction afferent arteriole -> worsened renal ischemia
Integrin dysfunction
- Desquamation into tubular lumen -> obstruction (casts, debris) -> back-leak of filtrate into the peritubular interstitium + increased glomerular pressure -> ↓ GFR
Renal tubular cells unable to support their energy needs -> activation of intracellular mechanisms cause cellular swelling -> further obstruction of renal tubules
Clinically:
Clinical signs often absent
This phase lasts from hours to a few days
During this stage, early intervention may prevent progression
PHASE 2 - EXTENSION PHASE
Amplification of the initial renal insult by ongoing ? from ischemia and the resulting ? response
Damage to ? capillary endothelial cells -> enhanced vascular reactivity to vasoconstrictive agents and decreased vascular reactivity to vasodilating agents -> exacerbation of ? and ?
Intrinsic cellular protections may ? these programmed events and spare the cell
PHASE 2 - EXTENSION PHASE
Amplification of the initial renal insult by ongoing hypoxia from ischemia and the resulting inflammatory response
Damage to pertubular capillary endothelial cells -> enhanced vascular reactivity to vasoconstrictive agents and decreased vascular reactivity to vasodilating agents -> exacerbation of ischemia and hypoxia
Intrinsic cellular protections may block these programmed events and spare the cell
PHASE 2 - EXTENSION PHASE
Clinically
Changes continues until there is a definable change in renal function such as decreased urine output or azotemia
- This is when ? signs appear!
- Length of time necessary to see changes is variable, depending on the insult’s nature and severity
Routine laboratory tests and clinical examination findings may not detect evidence of AKI
- Lack of baseline renal values
- Non-specific signs such as lethargy, inappetence and abdominal pain
Intervention may not be ? in this phase
PHASE 2 - EXTENSION PHASE
Clinically
Changes continues until there is a definable change in renal function such as decreased urine output or azotemia
- This is when clinical signs appear!
- Length of time necessary to see changes is variable, depending on the insult’s nature and severity
Routine laboratory tests and clinical examination findings may not detect evidence of AKI
- Lack of baseline renal values
- Non-specific signs such as lethargy, inappetence and abdominal pain
Intervention may not be succesful in this phase
PHASE 3 - MAINTENANCE PHASE
In this stage, a critical amount of ? damage has occurred - stabilization of the GFR at its nadir
? continues but renal blood flow returns to normal, leading to cellular repair
Proliferation and migration of renal tubular cells occurs, beginning the process of re-establishing cell ? and tubular integrity
Clinically
1 to 3 weeks (days to weeks, variable)
Stage when AKI is generally ?
Urine output may be increased or decreased and it resembles the ?, with little modification by tubular processes
PHASE 3 - MAINTENANCE PHASE
In this stage, a critical amount of irreversible damage has occurred - stabilization of the GFR at its nadir
apoptosis continues but renal blood flow returns to normal, leading to cellular repair
Proliferation and migration of renal tubular cells occurs, beginning the process of re-establishing cell polarity and tubular integrity
Clinically
1 to 3 weeks (days to weeks, variable)
Stage when AKI is generally detected
Urine output may be increased or decreased and it resembles the ultrafiltrate, with little modification by tubular processes
