15_HST110 Introduction to Renal Disease I - AKI 2017 Flashcards
What is definition of acute kidney injury (AKI)?
Sudden, often temporary, loss in kidney function (hours to days). An abrupt decrease in renal function
What is the definition of chronic kidney disease (CKD)?
Structural or functional kidney abnormalities with or without decreased GFR for > 3 months
What is the definition of end stage renal disease (ESRD)?
Total and permanent kidney failure
AKI encompasses both (X) injury to the kidney and acute (Y). Etiology of AKI can be from within the kidney or from external stresses to the kidney
X = direct Y = impairment of function
AKI can be defined as any of the following:
Increase in Cr by ≥ (X) mg/dL within 48 hours
Increase in Cr by ≥ 1.5 times the baseline within the prior (Y) days
Urine volume < (Z) mL/kg/hour for 6 hours
X = 0.3 Y = 7 Z = 0.5
What percent of hospital admissions are due to AKI?
5-13%
What percent of ICU patients have AKI?
1-25%
What is the mortality of AKI in ICU patients (in %)?
15-60%
Recovery potential: Animal studies show permanent damage following experimentally-induced AKI, including what 2 conditions?
tubulointerstitial fibrosis
damage to microvasculature
Multiple human studies show an increased risk of (X) and (Z) even after recovery from AKI
X = CKD Y = ESRD
Define Azotemia
Abnormally high levels of nitrogen-containing compounds (e.g., urea, creatinine) in the blood
Define Oliguria
Low urine output
< 400 mL/day but >100 mL/day
Also defined as < 0.5 mL/kg/hour in adults
Define Anuria
Absence of urine
<100 mL/day
What are the 3 causes of AKI, based on location in the urinary system?
1) Prerenal (“before the kidney”)
2) Intrinsic Renal (“inside the kidney”)
3) Postrenal (“After the kidney”)
Postrenal AKI is typically caused by an (X) to urinary flow, occuring at any level of the urinary tract (kidney, ureters, bladder, or urethra)
X = obstruction
Why is all AKI considered postrenal until proven otherwise?
Early diagnosis and prompt correction of obstruction can result in minimal permanent kidney damage
Uncorrected obstruction can lead to irreversible renal failure
~10% of AKI is postrenal. Not most common, but direct intervention is possible so you want to be able to rule it out early on
Name 3 causes of kidney-localized postrenal AKI
Stones
Cancer
Sloughed papilla
Name 8 causes of ureter-localized postrenal AKI
Stones Cancer Sloughed papilla Extrinsic tumors Retroperitoneal fibrosis Infection Blood clot Trauma
Name 4 causes of bladder-localized postrenal AKI
Cancer
Blood clot
Edema/inflammation
Posterior urethral valves
Name 3 causes of urethra-localized postrenal AKI
Prostate enlargement
Stones
Strictures
How does postrenal AKI cause reduction in GFR? Use a formulaic argument
GFR decreases as a result of an increase in P_BS
GFR = Kf * {P_GC - (P_BS + (PI)_GC)]
Obstruction to urinary flow increases tubular pressure throughout the kidney
Increase in tubular pressure is transmitted back to the Bowman’s space and increases the hydrostatic pressure of Bowman’s space
Therefore, the forces favoring filtration will be decreased, and GFR will fall
What abnormal anatomical features are common in a postrenal urinary obstruction?
Distended structures (renal calyces, renal pelvis), stones or other obstruction present, blocked ureter
Under ultrasound, an obstruction results in what condition or appearance in the kidney, characterized by increased water retention?
Hydronephrosis. Dark regions were water is accumulating are evident. Thinning of the cortex is also seen
Under CT, hydronephrosis appears as a (X) mass
X = bulbous, distended
Name 3 treatment options for postrenal AKI in order of increasing severity and ascending location of obstruction
1) Urethra level: Foley catheter
2) Ureter level: Ureteral stent
3) Kidney level (complete bypass): Percutaneous nephrostomy tubes
Prerenal AKI is instigated by a decrease in renal perfucion. Name 2 conditions this can result from
Decreased ECV
Hypotension
Why does prerenal AKI not represent true “kidney injury?”
No intrinsic abnormality to the renal parenchyma is seen
How can prerenal AKI be corrected?
With restoration of volume and circulatory deficits
Name 5 causes of prerenal AKI due to ECV depletion (with DECREASED ECF)
Blood loss GI losses Renal losses Skin losses Third spacing
Name 3 causes of prerenal AKI due to ECV depletion (with INCREASED ECF)
CHF
Cirrhosis
Nephrotic syndrom
Stenosis of what blood vessel can cause prerenal AKI?
Renal artery
Name 6 drugs that can cause prerenal AKI
NSAIDs ACE inhibitors ARBs Cyclosporine Tacrolimus IV contrast
How does prerenal AKI cause reduction in GFR? Use a formulaic argument
GFR decreases as a result of an decrease in P_GC
GFR = Kf * {P_GC - (P_BS + (PI)_GC)]
Significant reduction in renal perfusion results in a decrease in capillary hydrostatic pressure
What 3 drugs can cause direct afferent vasoconstriction resulting in prerenal AKI?
Cyclosporine
Tacrolimus
IV contrast
NSAIDs inhibit afferent vasodilation, inhibiting the autoregulatory role of (X), leading to prerenal AKI
X = prostaglandins
ACE inhibitors and ARBs block the efferent vasoconstrictive effects of (X), leading to prerenal AKI
X = angiotensin II
Intrinsic Renal AKI can accur at what 4 levels?
Glomerular
Tubular
Interstitial
Vascular
Name 1 example of intrinsic renal AKI at each of its 4 levels
Glomerular: Acute glomerulonephritis
Interstitial: Acute interstitial nephritis
Tubular: Acute tubular necrosis
Vascular: Vasculitis
What is acute tubular necrosis (ATN), one of the most common causes of AKI, characterized by?
Death of tubular epithelial cells
What are the 2 major types of ATN?
Ischemic (prolonged hypoperfusion of tubules)
Nephrotoxic (direct toxic injury to tubules)
Name 5 common causes of ischemic ATN
Major surgery Trauma Severe hypovolemia Sepsis Burns
Name 4 major categories of the common toxic causes of ATN
Antimicrobials (Aminoglycosides, Amphotericin B)
Chemotherapy (Cisplatin, Ifosfamide)
Radiocontrast agents
Heme pigments (Hemolysis, Rhabdomyolysis)
Tubular injuries due to ATN affect the (X) and (Y) the most since both are in the outer medulla (relatively hypoxic)
X = Proximal tubule (pars recta or S3 segment) Y = TAL of LOH
PT is in charge of secretion of toxins. They can accumulate them as well
What is a common morphological change seen in tubular epithelial cells in ATN before necrosis and luminal obstruction set in?
Loss of polarity following ischemia and reperfusion
Under histological evaluation, ATN appears with what striking features?
Dilated, cystic tubules
Loss of brush border
Debris in tubular lumen
How does ATN cause reduction in GFR? Use a formulaic argument
GFR decreases as a result of an increase in P_BS
GFR = Kf * {P_GC - (P_BS + (PI)_GC)]
Occlusion of the tubular lumens by cellular debris and casts and, with hemolysis or rhabdomyolysis, by precipitation of heme pigments
Elevated intraluminal tubular pressure can disrupt epithelial cell tight junctions and cause backleak of tubular fluid into the circulation
What are the 3 phases of ATN and their timeframes?
Initiation (hours to days)
Maintenance (1-2 weeks)
Recovery (variable)
The “initiation” phase of ATN is characterized by exposure to (X). The injury is evolving but not established. ATN potentially (Y)
X = ischemia or toxin Y = preventable
In the “maintenance” phase of ATN, (X) injury is established. This stage may be prolonged for as long as (Y) months
X = parenchymal Y = 1-12
In the “recovery” phase of ATN, repair and regeneration of tubules is evident. Increase in urine output (“(X)”) and fall in (Y) are typical
X = post-ATN diuresis Y = creatinine
Acute interstitial nephritis (AIN), a common cause of AKI, is characterized by what condition?
Acute inflammation of the interstitium
What is AIN more commonly caused by?
Drugs that cause hypersensitivity-type reactions. Also associated with infections (bacterial, viral, fungal, mycobacterial) and autoimmune disease (SLE, Sjögren’s)
Name 4 common antibiotics associated with AIN
β-lactam antibiotics (penicillins, cephalosporins)
Sulfonamides
Rifampin
Ciprofloxacin
Name 3 non-antibiotic drugs associated with AIN
NSAIDs
Diuretics (furosemide, thiazides)
Proton-pump inhibitors
AIN presents with a rise in (X) 1-2 weeks after exposure to offending drug. Can be as short as (Y) day(s) (if pre-exposed to drug) or as long as months (e.g. (Z))
X = creatinine Y = 1 Z = NSAIDs
What are the 4 classic signs of drug-associated AIN?
Fever (36%)
Arthralgias (45%)
Skin rash (22%)
Eosinophilia (35%)
The classic triad of fever, skin rash, and eosinophilia for AIN is seen in less that what % of patients?
10-15%
Under histolopathological evaluation, AIN presents with what features?
Interstitial infiltration (lymphocytes, eosinophils)
Interstitial edema
Tubulitis
Glomeruli and vessels normal
How does AIN cause reduction in GFR? Use a formulaic argument
GFR decreases as a result of a combined increase in P_BS and a decrease in P_GC
GFR = Kf * {P_GC - (P_BS + (PI)_GC)]
Interstitial inflammation and edema leads to compression of tubules and vasculature
Occlusion of the tubular lumens elevates intraluminal tubular pressure and hydrostatic pressure in
Bowman’s space
Vascular occlusion reduces perfusion and capillary hydrostatic pressure
Treatment of AIN involves discontinuation of the offending drug. Often leads to (X) of AKI. Recovery can take weeks to months
Oral (Y) may have benefit if administered early (<14 days) after diagnosis
X = complete resolution Y = corticosteroids
Define Acute Glomerulonephritis (GN)
Inflammation and proliferation of glomerular tissue
GN can result in damage to what 3 structures?
GBM, mesangium, and capillary endothelium
What 4 conditions is GN characterized by?
Hematuria with or without RBC casts
Proteinuria
Hypertension
Renal impairment
Spectrum of GN ranges from asymptomatic (X) to (Y) syndrome
X = hematuria Y = nephritic
Under histolopathological evaluation, Acute GN (Diffuse proliferative GN) presents with what feature?
Glomerular hypercellularity (lymphocytes and neutrophils)
Name 3 types of vascular acute kidney disease
Benign or malignant hypertensive nephrosclerosis
Systemic vasculitis
Thrombotic microangiopathy (Hemolytic uremic syndrome (HUS), Thrombotic thrombocytopenic purpura (TTP), Scleroderma)
What is the first “Rule of 3’s” related to the categories of AKI?
Postrenal
Prerenal
Intrinsic renal
What is the second “Rule of 3’s” related to noninvasive diagnostic tools?
History and physical exam
Urinalysis with urinary electrolytes
Ultrasound
What is the third “Rule of 3’s” related to the clinical maxims?
AKI is considered obstructive until proven otherwise
Eliminate postrenal and prerenal causes prior to pursuing intrinsic renal causes
Examine a fresh urine specimen whenever possible!
Name examples of important information to acquire in the History and Exam for renal diseases
Time of onset? History of volume depletion? Difficulty voiding? Other symptoms? Medications? Recent events? (Recent eating/drinking habits and events, recent accidents)
Name examples of useful physical exam findings in the History and Exam for renal diseases
Fever?
Blood pressure (hypertension? hypotension?)
Volume status?
Other findings (e.g. rashes)?
What is the time frame for appropriate urinalysis?
30-60 minutes after voiding
How does one prevent contamination in specimen acquisition for urinalysis?
Midstream voiding and collection. For women, noting stage of menstrual cycle
Name 6 of the important tests on a urinalysis dipstick
“Leukocyte esterase” detects urinary WBCs
“Nitrate” detects bacteria in the urine
“Protein” detects only albumin in the urine
“pH” reflects degree of acidification of urine
“Blood” detects heme from RBCs or free hemoglobin or myoglobin
“Specific gravity” provides estimate of urine osmolality
Urine sediment is collected and evaluated using what technique?
Centrifugation of urine sample and resuspension for light microscopy review
What are normal values for urine sediment cellular counts?
RBC
WBC
RBC: 0-2/hpf
WBC 0-5/hpf
Name 4 examples of cells found in urine sediment
RBC, WBC, Tubular Epithelial Cells, Squamous Epithelial Cells (skin)
What do dysmorphic RBC look like and what causes this condition?
Blebbed, mishapen cells
Indicates glomerular filtration barrier damage . Deformation of RBC membranes as they squeeze through the podocyte filtration slits or other barriers causes issues with shape and membrane integrity
What is the interpretation of seeing dysmosphic RBCs in a urine sediment?
Acute GN
Infection
Stones
Malignancy
What is the interpretation of seeing WBCs in a urine sediment?
Infection
Acute interstitial nephritis
Acute glomerulonephritis
Contamination
Where do the cylindrical casts seen in the urine sediment form?
Distal tubule and collecting ducts
What is the primary constituent of urine sediment casts?
Tamm-Horsfall protein
What other general classes of substances can be trapped in the tubular lumen during the formation of casts?
Granules and cells
Hyaline casts can be see in most renal diseases and contain only (X)
X = Tamm-Horsfall protein
What non-renal disease-based conditions can result in hyaline casts?
Dehydration, fever, and post-physical exercise
Granular casts are thought to represent filtered proteins trapped in (X) or cellular degeneration (Y)
X = lysosomes (fine) Y = coarse
“Muddy Brown” granular casts are pathognomonic for what condition?
ATN
RBC casts are a marker of bleeding within the (X). The RBCs usually originate from a damaged (Y). This condition can be seen in (Z)
X = renal parenchyma Y = parenchyma Z = acute glomerulonephritis
WBC casts have (X) trapped within a cast matrix and are a marker of intense inflammation within the kidneys. These WBCs can originate from a damaged (Y) or from inflammed (Z)
X = leukocytes Y = glomerulus Z = interstitium
What 2 AKI conditions can WBC casts be seen in?
Acute interstitial nephritis
Acute glumerulonephritis
Fractional excretion of sodium can suggest prerenal or ATN AKI based on the cutoff. What are these values?
FENa < 1% suggests prerenal
FENa >2% suggests ATN
What is the equation for the fractional excretion of sodium using Creatinine to measure GFR?
FENa = Clearance(Na)/Clearance(Cr) = [(U_Na)/(P_Na)]/[U_Cr)/(P_Cr)] Valid only in oliguric AKI low FENa is NOT specific for prerenal AKI
What is the preferred imaging test to evaluate urinary obstruction
Renal ultrasound
What do small kidneys suggest on a renal ultrasound?
Chronic process (damage or lack of use/atrophy)
What does hydronephrosis on renal ultrasound suggest?
Dilation of the collecting system in one or both kidneys consistent with obstruction
What complications of AKI are common?
Water balance: Hard to predict depending on specific site of injury
Sodium/Volume balance: Edema common
Acid-base balance: Metabolic acidosis common
Calcium/Phosphorus Homeostasis: Hyperphosphatemia with low calcium levels common (Ca-P complex takes up free calcium)
