Week 6: Acute Kidney Injury Flashcards
Define the pre-renal etiology of AKI
Prerenal AKI or inadequate perfusion is the most common reason for AKI (Renal artery is pre-renal). Poor perfusion can result from hypovolemia, reduced cardiac output, renal vasomodulation/shunting and systemic vasodilation. During the early phases of hypoperfusion, protective autoregulatory mechanisms maintain GFR at a relatively constant level through afferent arteriolar dilation and efferent arteriolar vasoconstriction (mediated by angiotensin II). The GFR eventually declines because of the decrease in glomerular filtration pressure. failure to restore blood volume or blood pressure and oxygen delivery can cause ischemic cell injury and acute tubular necrosis or acute interstitial necrosis, a more severe form of AKI.
Define the intrarenal etiology of AKI
Intrarenal (intrinsic) AKI can result from vascular, microvascular, glomerular, and tubulointerstitial causes. the most commonly seen cause of intrarenal AKI it ATN (Acute Tubular Necrosis). Ischemic ATN most often occurs after surgery but also is associated with prerenal causes such as sepsis, obstetric complications, and severe hemorrhagic trauma or severe burns. Whereas nephrotoxic ATN is usually caused by exposure to radiocontrast media or nephrotoxic medications (e.g., aminoglycosides, NSAIDs, ACEi, ARBs, and antibiotics).
Can also be caused by:
* acute glomerulonephritis (inflammation of the glomerulus)
* vascular disease (issues with vessels in the kidneys)
* allograft rejection
* interstitial disease
Important points to consider:
- hypoperfusion is pre-renal but can cause intra-renal ATN
- oliguria (urine output less than 30ml/hr) is common, but anuria is rare
Define the post-renal etiology of AKI
Postrenal AKI is rare and is usually caused by an obstruction within the urinary tract that affects the kidneys bilaterally (e.g., bladder outlet obstruction, ureteral obstruction, or renal pelvis obstruction). A pattern of several hours of anuria with flank pain followed by polyuria is a characteristic finding. The obstruction causes an increase in intraluminal hydrostatic pressure upstream from the site of obstruction with gradual decrease in GFR.
What is Chronic Kidney Disease and how does it manifest?
CKD is the progressive and irreversible loss of renal function indicated by a decline in GFR to below 60mL/min/1.73m2 for 3 months or more with implications for health. It is associated with systemic diseases, such as diabetes mellitus (most significant risk factor), hypertension, and systemic lupus erythematosus. CKD also is associated with intrinsic kidney diseases, such as AKI, chronic glomerulonephritis, chronic pyelonephritis, obstructive uropathies, or vascular disorders. Clinical manifestations do not occur until renal function declines to less than 25% of normal function.
Discuss the diagnostics for AKI
The hallmark features of AKI are increased SCr, reduced GFR, and decreased urine output. A diagnostic challenge is to differentiate prerenal AKI from ATN.
Pre-renal: associated with history of blood volume depletion or other causes of poor kidney perfusion (e.g., shock, heart failure, renal artery thrombi)
Intrinsic: exposure to nephrotoxins and infection
Postrenal: associated with obstructive uropathies (e.g., enlarged prostate or stones)
Other diagnostic indicators:
- ratios of BUN to plasma creatinine concentration and fractional excretion of sodium (the ratio of filtered sodium to excreted sodium)
- Cystatin C: serum protein, concentration can serve as a measure of GFR and may be useful in detecting early GFR changes
- serial measurements of plasma creatinine concentration provide an index of renal function during the recovery phase (only occur if glomerular filtration is lost and 24hrs +day)
Discuss the diagnostic stages for CKD
Stage 1: Normal kidney function; normal or high GFR (>90mL/min). Usually no signs or symptoms, although hypertension is common.
Stage 2: Mild kidney damage; mild reduction in GFR (60-89mL/min). Subtle hypertension and increasing creatinine and urea levels.
Stage 3: Moderate kidney damage; GFR 30-59 mL/min. Mild symptoms, as above.
Stage 4: Severe kidney damage; GFR 15-29 mL/min. Moderate symptoms as above; erythropoietin deficiency anemia, hyperphosphatemia, increased triglycerides, metabolic acidosis, hyperkalemia, salt/water retention
Stage 5: End-stage kidney disease; established kidney failure, GFR <15mL/min. Symptoms are severe, as above.
Describe the functions of the kidneys
Acid-base balance
Water balance
Electrolyte balance
Toxin elimination
Blood pressure
Erythropoietin
D vitamin
Discuss the importance of renal blood flow
The kidneys are highly vascular organs and usually receive 1000 to 1200mL of blood per minute, or about 20-25% of the cardiac output. With a normal hematocrit of 45% about 600 to 700mL of blood flowing through the kidney per minute is plasma. The filtration of the plasma per unit of time is known as the glomerular filtration rate (GFR) which is directly related to the perfusion pressure of the glomerular capillaries. The GFR is directly related to the RBF, which is regulated by intrinsic autoregulatory mechanisms, by neural regulation, and by hormonal regulation. If the mean arterial pressure decreases or the vascular resistance increases, the RBF declines and urinary output decreases. Normal urinary output is about 30mL/h minimum in adults. In the kidney, the autoregulation of the glomerular blood flow helps keep the GFR fairly constant (approx. 120ml/min) over a range of systemic arterial pressures. This is necessary to maintain the clearance of metabolic wastes and the reabsorption of filtered electrolytes and nutrients.
Discuss the structure and function of the glomerulus
The glomerulus is a tuft of capillaries that loop into the Bowman’s space. The bowman space is continuous with the lumen of the renal tubules. The glomerular filtration membrane filters blood components through three layers. Tonicity within the ducts is isotonic.
Discuss the structure and function of the proximal tubule
The proximal tubule is the first segment of the renal tubule, extending from the Bowman space. The proximal tubule contributes to the reabsorption (we reabsorb what we want to keep!) of:
- Sodium
- Potassium
- Amino Acids
- Bicarbonate
- Phosphate
- Urea
- Water
And the secretion of:
- Hydrogen
- Foreign substances
Tonicity is isotonic
Discuss the structure and function of the Loop of Henle
The proximal tubule, descending towards the medulla, joins the Loop of Henle, which extends into the medulla. The Loop of Henle aids in the concentration of urine where the descending loop (highly permeable to water) is responsible for water reabsorption as sodium diffuses in and the ascending loop (permeable to ions but not water) where sodium is reabsorbed by active transport but water stays in, eventually urine is passed into the distal convoluted tubule. Tonicity can be isotonic, hypertonic, or hypotonic.
Discuss the structure and function of the Distal Tubule
The distal tubule is shorter than the proximal tubule but also has straight and convoluted segments. The distal tubule reabsorbs sodium, water (ADH required), and bicarbonate and secretes:
- Potassium
- Urea
- Hydrogen
- Ammonia
- Some drugs
Before meeting with the collecting duct. Hypotonic
Discuss the structure and function of the Collecting Duct
The collecting duct is a large tubule that descends down the cortex and through the renal pyramids of the inner and outer medullae, draining urine into the minor calyx. Here, water is reabsorbed by active transport and sodium, potassium, hydrogen, and ammonia may be reabsorbed or secreted. Final concentration.
Discuss tests of renal function
Renal Clearance: how much of a substance can be cleared from the blood by the kidneys per given amount of time. The application of this principle permits an indirect measure of the GFR, tubular secretion, reabsorption, and the RBF.
Glomerular Filtration Rate: GFR provides the best estimate of functioning renal tissue and is important for assessing or monitoring kidney damage and drug dosing. Measurement of the GFR requires the use of a substance that does not influence GFR; has a stable plasma concentration; is not protein bound; is freely filtered at the glomerulus; is not secreted, reabsorbed, or metabolized by the tubules; is constantly infused to maintain a stable plasma level; and is easy to measure. The clearance of creatinine, a natural substance produced by muscle and released into the blood at a relatively constant rate, is commonly used as an estimate clinically.
Cystatin C is a stable protein in serum filtered at the glomerulus and metabolized in the tubules. Serum levels of Cystatin C are also a marker for estimating the GFR/
The concentration of urea nitrogen in the blood reflects glomerular filtration and urine-concentrating capacity. Because urea is filtered at the glomerulus, blood urea nitrogen (BUN) levels increase as GFR drops. Urea is reabsorbed by the blood through the permeable tubules, so the BUN value rises in states of dehydration and with acute and chronic renal failure when the passage of fluid through the tubules slows. BUN values also change as a result of altered protein intake and protein catabolism making it a poor measure of GFR.
Urinalysis is a noninvasive and relatively in expensive diagnostic procedure. Includes evaluation of the color, turbidity, protein, pH, specific gravity, sediment, and supernatant.
How does aging impact the kidney?
Vascular diseases and decreased perfusion result in kidney cell necrosis, with less filtering units available as we age.
How is kidney dysfunction classified?
- Acute (under 3 months) or Chronic; reversible or irreversible
- Renal Insufficiency: decline of renal function to approximately 25% of normal or GFR of 25-30ml/min
- Renal Failure: significant loss of renal function; levels of serum creatinine and urea are mildly elevated
- End-stage Renal Failure: less than 10% of renal function remains
Define Uremia
Is a syndrome of renal failure and includes elevated blood urea nitrogen (BUN) and creatinine levels accompanied by fatigue, anorexia, nausea, vomiting, pruritus, and neurologic changes. Uremia represents numerous consequences related to kidney failure, including retention of toxic wastes, deficiency states, electrolyte disorders, and immune activation promotion a pro-inflammatory state.
Define Azotemia
Is characterized by increased BUN levels (normal is 8 to 20 mg/dL) and frequently increased SCr levels (normal is 0.7 to 1.4 mg/dL). Renal insufficiency or kidney failure causes azotemia. Both azotemia and uremia indicate an accumulation of nitrogenous waste products.
Uremia is the manifestation of symptoms because of the azotemia!
What is Acute Kidney Injury and how does it manifest?
AKI is a sudden decline in kidney function with a decrease in glomerular filtration caused by a defect in the excretion of water, salts, and nitrogenous waste products, which accumulate in the blood as demonstrated by an elevation in SCr level and a decrease in urine volume. AKI is a complex syndrome that is classified according to semi-anatomical categories (i.e., pre-renal, intrinsic, and post-renal). Staging of AKI is based on serum creatinine levels (increase) and blood urea nitrogen (increase)
Discuss the pathophysiology of AKI
AKI is commonly a result of extracellular volume depletion, decreased renal blood flow OR toxic/inflammatory injury to the kidney. There are three types based on anatomical location.
Define Post-Ischemic ATN
Involves persistent hypotension, hypoperfusion, and hypoxemia resulting in ischemia, decreased energy resources and increase free radials that lead to the activation of inflammatory cells (e.g., neutrophils, macrophages) and complement and cytokines producing further tubular injury. The transport of sodium and other molecules is impaired with damage seen primarily at the proximal tubule. Shedding of the brush border occurs with the appearance of tubular granular casts in the urine. Ischemia necrosis tends to be patchy and may be distributed along any part of the nephron tubules.
Define nephrotoxic ATN
Typically caused by exposure to radiocontrast media or nephrotoxic medications but can also be caused by bacterial toxins, dehydration, advanced age, concurrent renal insufficiency, and diabetes. Nephrotoxic necrosis and tubular cell apoptosis are usually uniform and limited to the proximal tubules. Typically, damage is limited to the proximal tubule because it is responsible for secretion of foreign substances.
Discuss how Oliguria manifests in AKI
Oliguria, or a urine output of <400mL/24 h, occurs in AKI and can be differentiated from prerenal, intrarenal, and ATN. Three mechanisms have been proposed to account for the decrease in urine volume in AKI.
- Alterations in renal blood flow: Efferent arteriolar vasoconstriction may be produced by intrarenal release of angiotensin II or there may be a redistribution of blood flow from the cortex to the medulla. Autoregulation of blood flow may be impaired, resulting in decreased GFR. Microthrombi may obstruct blood flow. Changes in glomerular permeability and decreased GFR also may result from ischemia.
- Tubular obstruction: necrosis of the tubules causes sloughing of cells, cast formation, and obstruction to urine flow. There can be ischemic edema that results in tubular obstruction, which causes a retrograde increase in hydrostatic pressure, and opposes the hydrostatic pressure of glomerular filtration, thus reducing the GFR. Kidney failure can occur within 24hr.
- Tubular back-leak: tubular reabsorption of filtrate is accelerated as a result of increased permeability caused by ischemia and increased tubular pressure from obstruction.
Discuss the clinical manifestations and progression of ATN
The clinical progression of AKI due to ATN, the most common cause of AKI, occurs in four overlapping phases:
- The initiation phase (24-36hrs evolving injury): occurs with the onset of renal hypoperfusion or toxicity resulting in severe cellular ATP depletion leading to acute cell injury and dysfunction. Prevention of injury is possible during this phase and the next phase with therapeutic interventions, but there is a short window of opportunity.
- The extension phase: is initiated by continued hypoxia following the initial ischemic event and an inflammatory response. Cells continue to undergo injury and death with necrosis and apoptosis present in the outer medulla.
- The maintenance/oliguric phase (weeks-months): is the period of established kidney injury and dysfunction after the initiating event has been resolved. Cells undergo repair, migration, apoptosis, and proliferation, which may last from weeks to months with urine output lowest during this phase. During this phase, SCr, BUN, and serum potassium levels increase; metabolic acidosis develops; there is salt and water overload; and urine output is decreased with oliguria.
- The recovery/polyuria phase: is the interval when glomerular function returns but the regenerating tubules cannot yet concentrate the filtrate. diuresis is common during this phase, with a decline in SCr and urea concentrations and an increase in creatinine clearance. As renal function improves, the increase in urine volume (dieresis) is progressive. The tubules are still damaged early in the recovery phase and have not recovered secretion and reabsorption functions. Polyuria can result in excessive loss of sodium, potassium, and water.
