6. AKI and CKD Flashcards
Acute Kidney Injury
• Loss of renal function, usually measured by a decline in the ____ ( rise in serum creatinine) that develops over a period of hours to days.
• Affects up to 5% hospitalized patients; 10-30% patients in ICU settings
• Often ____
• High mortality- up to 50% in some series
• Creatinine is a byproduct of muscle breakdown ○ Most commonly used indicator of kidney function in GFR • Complete kidney failure and require dialysis > high mortality despite advances in dialysis and critical care ○ Even if full kidney funciton in hospital; still risk of AKD, CKD and high mortality
GFR
reversible
AKI Classification
• Schemes that try to stage AKD • Biggest challenge in studying/reading research; lack of \_\_\_\_ defintion of AKD ○ Develop standardized shcemes; most are based on: § Changes in \_\_\_\_ § Changes in \_\_\_\_ • Not used \_\_\_\_, but in reported literature you'll see it
uniform
serum creatinine
urine output
Beyond creatinine: injury markers
• Changes in serum creatinine level; when it's rising and GFR is dropping > represents fairly advanced stage of kidney injury ○ Identify markers of \_\_\_\_ damage § \_\_\_\_ biomarkers shown to be indicators of early injury § Not ready for use yet, but in the future will be important
early
urinary
Causes of Acute Kidney Injury
• Most important slide she shows • Divides AKD into etiology ○ Prerenal § Situation where AKD due to decreased BF into the kidney (decrease \_\_\_\_ pressure into the kidney) ○ Postrenal § Situation where AKD due to \_\_\_\_ of urinary flow out of the kidney ○ Intrinsic § Direct damage to the various compartments to the renal parenchyma □ Compromised of: small vessels, arterioles, glomeruli and tubules and interstitium ® Pathologic processes that occur anywhere that cause AKD ○ Most common causes of AKD: \_\_\_\_ failure and \_\_\_\_ injury (acute tubular necrosis [intrinsic] due to ischemia or toxins)
perfusion
obstruction
prerenal
direct tubular
Renal Tissue Hypoxia
• Kidney is vascular • Sees 25% of CO • BF distribution within kidney is not even; most of the blood/oxygen is going to the \_\_\_\_ (glomeruli, filtration occurring here) ○ Much higher O2 tension in the cortex than the \_\_\_\_ ○ Tubules still in the medulla; \_\_\_\_ activity occurring here (ATP consumption) § Straight portion of \_\_\_\_; DAL (Na transport occurs) § Very vulnerable to decreased BF § Damage in setting of ATN or renal ischemia • Blood O2 level determined \_\_\_\_ ○ Lights depending on level of deoxy hemoglobin ○ Deeper levels are red/yellow § In \_\_\_\_ portions as opposed to the cortex
cortex medulla metabolic PT MRI medullary
Prerenal Failure- Causes
____ Depletion
- excessive diuresis, hemorrhage, GI losses, transcellular fluid accumulation (ascites, pancreatitis, burns)
Low ____
- cardiomyopathy, MI, pericardial tamponade, pulmonary embolism
Low ____Resistance - sepsis, liver failure
Increased ____
- liver failure, nsaids, calcineurin inhibitors, renal artery stenosis,
renal vein thrombosis
• Very common • Decreased perfusion into the kidneys, following a drop in BP • Septic shock ○ Vasodilation ○ \_\_\_\_
ECF volume cardiac output systemic vascular resistance renal vascular resistance hypotension
AUTOREGULATION
• Kidneys are good at AR • Drops in arterial BP > kidney maintains renal \_\_\_\_ and GFR to an extent ○ Has to do with mediators causing vasocon and vasodil at these aff/eff arteriolar beds that surround the glomerulus • Via AR > maintain renal BF and GFR to a point • But once arterial pressure drop below \_\_\_\_ > AR mechanisms fail > drop in renal BF and drop in GFR > \_\_\_\_ failur
BF
80
prerenal
Pathophysiology
dec RBF
dec flow of filtrate
inc Na reabsorption
dec GFR
inc reabsorption urea > creatinine
inc BUN/creat
• Rapidly \_\_\_\_ if restore renal BF • No damage to the tubules ○ Evidence by looking at urine sodium (will be \_\_\_\_), or a \_\_\_\_ BUN/creat ratio • Reestablish renal BF > raise BP, renal BF, GFR rapidly corrects
reversible
low
high
Postrenal Failure- Causes
• \_\_\_\_ • Urinary tract obstruction from renal pelvis down to the uretetha ○ Top down • Two functioning kidneys; unilateral obstruction > contralateral kidney can \_\_\_\_ > may not lead to AKD because of filtration/GFR in ongoing kidney ○ For AKD in obstruction: need \_\_\_\_ obstruction, or obstruction of a \_\_\_\_ functioning kidney
obstruction
compensate
bilateral
solitary
Postrenal Failure- Obstruction
Hydronephrosis seen on ____
• Renal ultrasound • Classic finding on a US: hydronephrosis ○ Calyxs are \_\_\_\_ and \_\_\_\_ bc of urine ○ Obstructive nephropathy can be rapidly \_\_\_\_ as long as you relieve the obstruction • Enlarge \_\_\_\_ is an e xample
ultrasound black dilated reversible prostate
Chronic Obstruction
• If obstruction goes on for long time > chronic \_\_\_\_ disease ○ Cortical loss of functioning renal \_\_\_\_ • This is with someone with CKD now
irreversible
parenchyma
AKI- Intrinsic Renal Disease
- glomeruli
- tubules/interstitium
- vessels• Pathophysiologic processes that can cause acute injury due to direct toxicity/inflam/damage to many parts of kidney
• Glomerular nephritis
○ ____
○ Lupus/vasculitis
• Small renal vessel
○ ____
○ Onion skinning
○ AKD in setting of malignant ____
§ Acute vascular injury in setting of high BP
• Tubular interstitial compartment
○ Lots of ____ cells > lymphos
§ Interstitial nephritis
§ Infalm disorder > seen in ____ reaction to medication
○ Acute tubular necrosis
§ Tubules that are injured > see in tubular CS > loss of cells, naked BM, debris, ____ cells into the tubular lumen
inflamed hyperplasia hypertension dark allergic apoptotit/necrotic
Intrinsic Renal Failure- Causes
Acute tubular injury (ATN)
-____: hypovolemic, cardiogenic, septic shock -Toxins: ____, contrast, myoglobin ~35%
Acute glomerulonephritis
- ____, Anti-GBM, ANCA associated diseases
Acute tubulointerstitial nephritis
- ____, intrarenal precipitation (uric acid, light chains)
Acute vascular nephropathy
-____, malignant hypertension, ____, thrombotic microangiopathy
• ATN most \_\_\_\_ cause of intrinsic AKD • Ischemia is the most common • Toxins can cause AKD ○ IV \_\_\_\_ ○ Myoglobin - endogenous toxin § Rhabdo: trauma with muscle crush § MG filtered by kidneys and cause toxic damage
ischemia aminoglycosides immune complex drug reaction vasculitis atheroembolism common contrast
Causes of Ischemic ATN
Generalized or localized reduction in renal BF
- Intravascular volume ____ and hypotension:
GI, renal, and dermal losses, hemorrhage
- congestive ____
- sepsis
- l____ failure
- Renal vascular dz-
renal artery thrombosis/ embolism/cross-clamping
- Medications-
____/ARB, NSAIDS, Calcineurin inhibitors
> > > ischemic ____ renal failure
• Causes of ischemic ATN ○ All same things that cause prerenal failure § Decreased perfusion into the kidneys □ Volume depletion □ HF □ Sepsis □ Liver failure § If insult is prolonged enough > can transition to ischemic damage of kidneys > \_\_\_\_ § Not clear where a patient lies on the \_\_\_\_ of prerenal to ATN
depletion heart failure liver ACEI acute
ATN
spectrum
Ischemic ATN- Pathophysiologic Processes
• Vascular Effects – \_\_\_\_ alterations – \_\_\_\_ cell injury • \_\_\_\_ Cell Injury • \_\_\_\_
hemodynamic
endothelial
epithelial
inflammation
Effects of AKI on arteriolar tone
• Vasculature in kidney that's damaged by prllonged ischemia ○ \_\_\_\_renal vasoconstriction in setting of hypoperfusion ○ IN normal > renal perf decreases > \_\_\_\_ of renal aff arterioles in order to maintain GFR ○ If kidney is ischemic bc of hypotension going on for long time > in setting of dec perf > increase renal \_\_\_\_ (opposite) § Increase \_\_\_\_ in SMC cells > inc sens to vasocontrictors § It perpetuates the problem > the \_\_\_\_
paradoxical dilation vasoconstriction Ca ischemia
Endothelial Injury in Ischemic ATN
• Sludging ○ CS of peritubular capillary and a tubule ○ In the PTC of ischemic kidney > upregulation of \_\_\_\_ molecules > sludging of \_\_\_\_ and RBCs > vascular \_\_\_\_ > perpetuates the\_\_\_\_ that causes further damage in kidney injury
adhesion
neutros
congestion
ischemia
Tubular Effects
• Tubular epithelium is \_\_\_\_ ○ Transporters on basal membrane, and different on the apical > \_\_\_\_ is critical in order for normal transport of all stuff the kidney must transport § Na, Bicarb, protons ○ NaK ATPase is ubiq expressed on \_\_\_\_ membrane ○ Integrins which keep epi on BM (\_\_\_\_membrane) ○ Ischemia reperfusion > disruption of cytoskeleton in cells and all proteins show in places they \_\_\_\_ be ○ Loss of \_\_\_\_ in tubular epithelium > impairment of Na reabsorption > inappropiate \_\_\_\_ (urine rich in Na) in setting of hypotension/prerenal failure ○ Tubule are damaged, cannot hold on Na, and lack of normal transport ○ Bc intergins arent anchoring cells > cells that shed off the BM and some are necrotic > induction of \_\_\_\_ § Some are viable cells that shed into tubular lumen and the ischemic kidney
basolateral basolateral shouldn't polarity wasting apoptosis
ATN
• \_\_\_\_ BM • Cells in \_\_\_\_ • Some tubular epi cells also look \_\_\_\_ ○ \_\_\_\_ phenomenom
naked
lumen
normal
patchy
Urine Sediment in ATN
• Urinalysis with someone with ATN ○ \_\_\_\_ casts ○ Cell debris that is filled in tubular lumens of nephron and excreted into the urine ○ Can see \_\_\_\_ casts (renal tubular \_\_\_\_ cells; intact) that are excreted in form of casts ○ Discrete solitary tubular epi cells into the urine
muddy brown granular
cellular
epi
Inflammation in Ischemic ATN
* Upregulation of \_\_\_\_ in ischemic ATN * Damaged epi release proinfl \_\_\_\_ > recruit inflam cells > cause further cell death
inflam
cytokines
Pathophysiology of Ischemic ATN
CHEKC ME OUT!
ya
The Repair Phase
• Kidney is good at \_\_\_\_ itself ○ If residual cells left bheind after insult > these viable cells can \_\_\_\_ and reproliferate and repop the tubular epi and regain \_\_\_\_ and function again ○ Can see full \_\_\_\_ in AKD
healing
dedifferentiate
polarity
recovery
Natural History of AKI
• Best case: ○ Full recovery ○ Patient has AKD > GFR recovers ○ \_\_\_\_ for some reason > high risk pop for further events • Red - worst case ○ Complete kidney failure > \_\_\_\_ • Variation in between ○ Someone had recovery but not as good as baseline > now has CKD > following a diff \_\_\_\_ • Or had CKD to begin with, and acute insult > \_\_\_\_ kidney disease
vulnerable
ESRD
trajectory
acute-on-chronic
Approach to the patient with AKI
• History and Physical Exam
– Hx: Events leading to changes in ____ or hemodynamic
status, exposures to ____
– PE: Volume and ____ status, ____, stigmata of emboli, ____ bladder
• Diagnostic Tests
– ____ indices , urinalysis – Radiographic studies
– ____
• Management
• \_\_\_\_ are most important ○ Rash > interstitial \_\_\_\_ due to drug ○ Bladder is full > large prostate and need a catheter
volume medications/toxins cardiovascular rash distended
blood + urine
biopsy
history/physical
nephritis
Urinalysis
- ____
- ____ stick
• Eachpadcontains reagents for a distinct chemical reaction• Most important test for AKD after physical/hisotry > ____
○ Cheap, quick
○ Sample of urine, and typical urinalsysi composed of two parts:
§ Dipstick
□ Tabs impregnated with various ____: tells blood in urine, leukos, blood, etc.
§ Spin the urine and examine what comes out in pellet
□ Look at the ____
□ What it looks like is hekpful: esp in ruling in the ____ renal processes
• Prerenal failure > hypotensive > give bag of IV fluid > GFR improves > urine will be ____ and not a lot of activity
○ Epi cell from skin in urine > not ____
○ Hyaline cast > not indicative of ____
§ Seen in volume depleted individuals
• RBC in urine sediment
○ Typical finding in ____(lupus, vasculitis, goodpasture)
• Cast of inside tubule
○ All have proteins that can form a matrix, start shedding cells > form casts
• Cast filled with WBC
○ Finding in someone with ____ due to a drug allergy
• Typical finding in ATN
○ ____ casts
○ And renal tubular ____ cells
micrscopy
dipstick
urinalysis
chemical
sediment
intrinsic
bland pathogneumoic patholgoy acute glomerular nephritis interstitial nephritis granular epi
Examples of Urine Sediments
Hyaline casts= ____
RBC CASTS + RBCS = ____
Granular casts/tubular epithelial cells= ____
WBC Cast +WBCS = ____
normal/prerenal
GN
ATN
in nephritis
AKI- Diagnostic Tests
- Radiographic Studies= Renal ____
- Biopsy:
Consider when there is concern for ____ disease, tubulointerstitial nephritis, vasculitis, or cause ____
• Not often used • But used in situations where the urinealsysis indicates issues • Local \_\_\_\_, needle, get some tissue etc. • Renal ultrasound ○ Rule out \_\_\_\_
ultrasound glomerular uncertain anesthesia obstruction
AKI- Treatment
- ____
- Support- optimize ____ status, maintain blood pressure, treat infection, provide nutrition, dose drugs appropriately, dialysis if necessary
- Specific therapy?• No ____
○ For ischemic ATN > no specific therapy; prevent from happening
§ Keep people volume replete; prevent hypotension; don’t give kidney toxic ____ or ____ die if already have some degree of kidney failure
○ In setting of ATN > support patient and hope things get better
§ Dialsysis until kidney function recovers
□ Acute dialysis catheter in the ____
□ Used for AKI
prevention volume specific therapy medications IV contrast jugular vein