L7-AKI PAthology Flashcards
What are the most common findings in biopsies of Acute Renal Failure?
ATN
Glomerulonephritis - crescentic GN microvasculitis
AIN
What is the most common cause of AKI?
Acute Tubular Necrosis from Ischemic injury resulting from hypoperfusion from, for example, aortic aneurysm repair clamping renal arteries for too long
What do you see grossly and histologically in Ischemic ATN?
Grossly - Pale cortex, blood pools in medulla, and pale, edematous kidneys
Histologically:
1) Distal and Proximal tubules look the same (normally PCT are pinker, thicker cells)
2) No inflammation, just edema bw tubules
3) Necrosis / Apoptosis of tubular cells ALONG the whole nephron in **patchy distribution **
4) Hyaline casts as proteins normally excreted in urine coagulate in lumen tubule
How does Ischemic ATN present clinically? How does it resolve clinically?
What do you see histologically in recovery?
Presentation: precipitating events, oligura/anuria, elevated serum Cr and BUN
*URINE SEDIMENT
Clinical Resolution: Initiatially, no urine and then it comes back in this order:
1) Initiating phase - Osmotic ratio of 1 w/ serum
2) Maintenance Phase - where Uosm is suboptimal
3) Recover Phase - finally back to concentrating urine
Histologically: see mitosis and big regenerating cells next to flattened cells from injury
What are the 3 special causes of ATN that cause Diffuse Cortical Necrosis - Whole cortex dies? What’s happening?
Normally, ATN causes patchy death. Here is diffuse and whole cortex dies from loss of blood supply
Causes:
1) obstetric emergency
2) septic shock
3) Extensive surgery
Leads to functional vasospasm of arteries/arterioloes w/ superimposed DIC
Whole cortex Dead and white surrounded by Hyperemic Medulla
What are the different features of Toxic vs Ischemic ATN?
Ischemic ATN is patchy along all tubular segments w/ Skip Areas
Toxic ATN iaffcts PROXIMAL tubules and is more diffuse (WHOLE area of proximal tubule affected)
What are the Exogenous causes and Endogenous causes of Toxic ATN?
Exogenous: Radiocontrast, Poisons, Heavy metals, solvents
Drugs: Aminoglycosides, Cyclosporine, Methotrexate
Endogenous: things w/ in cells that are toxic when released
Hemoglobinuria - hemolytic anemia
Myoglobinuria - Rhabdomyolysis
Uric Acid Crystals
Myeloma
Hypercalcemia
What does the histology of Toxic ATN look like? What features does it show?
Vacuolized cells
Proximal tubules are MASSIVELY necrotic
HB and MB casts within tubules - specific stains to see them
Myoglobic casts - pigmented granular
Hemoglobin casts - pigmented tubular
What is acute interstitial nephritis (AIN)? What causes it?
What do you see in AIN?
see Interstitial Inflammation, Tubular inflammation and damage, Edema
Causes:
**Allergic - NSAIDS, Sulfonamides, Ciprofloxacin
Acute Mediated Allograft Rejection
Infectious - Acute Pyelonephritis
Infiltration - sarcoid/lymphoma
What are the drugs that cause AIN?
What is the clinical presentation of Drug-Induced AIN?
Drugs: Sulfonamides, Synthetic antibiotics, Diuretics, NSAIDs, Miscellaneous (like Cimetidine)
Presentation: delayed after drug exposure (time for Ab to form)
Fever, Eosinophilia, Rash
Hematuria, mild proteinuria, Leukocyturia (eosinophiluria)
Increased BUN
What is the histopathology of drug-induced AIN?
INFLAMMATION!!!!!
PMNs OUTSIDE the tubules (unlike infection)
Thiazide-Induced nephritis can cause interstitial granulomas w/ Giant Cells!!!
*Tubulitis - lymphocytes enter walls of tubule
Infectious AIN- what does it look like histologically? How does it occur?
PMNs are WITHIN the tubules
Bacteria grow in lumen and WBC accumulate around it to eliminate and can form abscesses that start below the surface and grow all the way up to the surface! YIKES!
Can be Hematogenos or Ascending (more common)
What are the clinical features of Acute Pyelonephritis?
Pain at CVA
Fever, Malaise
Dysuria, Frequency, Urgency
Pyruria
Leukocyte casts
What are clinical associations w/ acute pyelonephritis?
What are complications of Acute Pyelonephritis?
Clinical Associations: Urinary obstruction, catheters, vesicuuretal reflux, pregnancy, sex/age, pre-existing renal lesions, DM, immunosuppression
Complcaitions:
1) PApillary Necrosis - Diabetes + Obstruction (hypoperfusion from DM and then cant’ clear bacteria as well)
2) Perinephric Abscess - extension of pus through the renal capsule
Name the vascular processes of kidney damage.
Large vessels: thromboembolism, RAS, dissectoin, renal vein thrombosis
Medium Vessels: Polyarteritis nodosa - vasculitis
Microvascular Processes: Thrombotic microangiopathy, Necrotizing glomerular nephritis
Polyarteritis Nodosa - What is it?
What do you see in it?
Fibrinoid necrosis of vascular wall and infiltration by Acute inflammatory cells
Medium sized vessels
See Fibrin deposits in vessel walls
vessel wall looks like clotted blood + fibrin
Which vascular renal processes do you have to biopsy to make diagnosis?
Microvascular Processes!!!!
(also sometimes Medium Sized vessel vasculitis)
What is Thrombotic Microangiopathy?
What is the pathogenesis?
Presence of Thrombi (aggregated platelets and fibrin) in small arteries, arterioles, and capillaries –> Fibrinoid Necrosis of Arterioles
Pathogenesis: small vessels destroyed, endothelial injury and activation w/ subsequent intravascular thrombosis and distal ischemia
What are the causes of Thrombotic Microangiopathy? In general, what’s the over-arching cause in addition to the specific cause?
OVERALL: Renal failure secondary to platelet or platelet-fibrin thrombi together w/ necrosis and thickening of vessels
Genetic: TTP (ADAMTS13 Vwf protease) and HUS (Factor H, I or membrane cofactor protein deficiency)
Iidiopathic HUS or TTP
Infectious: Bacterial Ecoli O157H7 or Viral HIV
Drug Related- Cyclosporine!!!!!! Clopidogrel, Cistplatin, Gemcitabine, VEGF inhibitors (bevacizumab and sunitinib)
Autoimmune - SLE
Miscellaneous - malignancy, pregnancy, post-BM transplant
What histopathology do you see in Glomerular processes?
Necrotizing glomerulonephritis and crescentic glomerulonephritis
FORM CRESCENTS!!!!!
See crescents and know ARF due to glomerular failure
