Acute Kidney Injury, Tubulointerstitial Nephritis, Vascular Diseases Flashcards
What is the clinical presentation of Acute Tubular Injury?
Reduction in renal function Oliguria Uremia (retention of metabolic waste that is not eliminated) Fluid overload Electrolyte abnormalities Acidosis
Pathogenesis of Acute Tubular Injury
Some tubular injury occurs or there is a disturbance in blood flow
Causes intrarenal vasoconstriction, low GFR, less O2 and nutrient delivery to cells
Toxic injury to tubular cells
What type of Acute Tubular Injury tends to alter the PCT more?
Toxic type
Where is cast formation most commonly seen?
DCT of the nephron
How would you describe the necrosis seen is ischemic Acute Tubular Injury?
Patchy or focal
Seen in PCT, thick ascending limb
How do ischemic tubule cells looks differently from normal?
Basement membrane has many detached cells
High eosinophilia
Thinner epithelial lining because the cells are injured
What will lab tests reveal in Acute Tubular Injury? How is ATI typically diagnosed?
Renal failure
In reality, the diagnosis is usually based on clinical grounds
Prognosis and Treatment of Acute Tubular Injury
Reversible
3 phases: initiation, maintenance, recovery
Provide support, watch for HTN or cardiac failure
Monitor electrolytes
What are some causes of Ischemic ATI?
BP drop
Severe trauma
Acute pancreatitis
What are some causes of toxic ATI?
Drugs (antibiotics)
Contrast dyes
Poisons (heavy metal)
Organic solvents
What are some causes of combined ATI (ischemic + nephrotoxicity)?
Mismatched blood transfusion
Hemolytic crises (hemoglobinurea)
Skeletal muscle injury (myoglobinurea)
Intratubular casts
Describe the pathogenesis of antifreeze poisoning and what you’d see under the microscope.
Calcium oxalate is the toxic compound.
Early stage just affects the tubules, but later you will get an interstitial component too.
Calcium oxalate is very bright under polarized light
Describe mercury nephropathy
See acidophilic intracytoplasmic inclusions
Tubulointerstitial Nephritis
List the 3 major categories
Infectious
Drug induced
Other (metabolic or neoplastic)
What is the major factor in allowing bacteria to grow and travel up to the kidneys?
Urine retention
Anything obstructing the changing the unidirectional flow could facilitate growth of bacteria
Acute Pyelonephritis
What infections are the most common causes?
Gram Negative rods (E coli, Proteus, Klebsiella, Enterobacter)
Fungi or viruses in immunocompromised pts
Acute Pyelonephritis
What are some predisposing factors for infection?
Catheterization/Instrumentation Urinary tract obstruction Stones Tumors Enlarged prostate Vesicoureteral reflux Congenital abnormalities Diabetes Immune suppression/insufficiency
Acute Pyelonephritis
Clinical Presentation
Costovertebral angle pain Fever Malaise Frequency/urgency Urosepsis
What would you see under the microscope in Acute Pyelonephritis?
Suppurative inflammation (many PMNs) and formation of focal abscesses
Acute Pyelonephritis
Prognosis
Good for acute onset
Bad for chronic (renal failure)
Acute Pyelonephritis
Treatment
Antimicrobials against the causative agent
Correct any other predisposing factors
What is papillary necrosis? How does one develop it?
Ischemia of the medullary tip leading to necrosis
Medulla normally receives a small blood supply, so it is susceptible to ischemia
Predisposing factors for Papillary Necrosis
Analgesics Diabetes Sickle cell anemia Obstruction Tuberculosis
Who is likely to get a viral interstitial nephritis?
Immunocompromised patients
Describe the progression of chronic pyelonephritis
Mostly bacterial in origin
Gradual buildup of renal insufficiency
Loss of concentrating ability comes first, then patients may notice polyuria and nocturia
Often associated with chronic obstruction and reflux
What are the microscopic findings of chronic pyelonephritis?
“Thyroidization” of the tubules
Tubule cells become dilated and the flow to them decreases
No PMNs invading, but there are lymphocytes
Xanthogranulomatous Pyelonephritis
What kind of infection is it associated with? What is it commonly mistaken for?
Proteus infection, which could also cause a staghorn calculus
May mimic a tumor
Acute Drug-Induced Interstitial Nephritis
Clinical Presentation
Rash
Acute renal failure
Acute Drug-Induced Interstitial Nephritis
Pathogenesis
IgE and T cell mediated immune reaction to drug, often antibiotics, diuretics, or NSAIDs
Interstitial inflammation, abundant eosinophils and edema
This is NOT dose related. It is a hypersensitivity reaction.
Drugs act as haptens, covalently binding to cells and becoming imunogenic
Acute Drug-Induced Interstitial Nephritis
Prognosis
Good in acute
Renal failure in chronic
Acute Drug-Induced Interstitial Nephritis
Treatment
Stop taking the drug!
What is the mechanism of NSAIDs that may cause acute hypersensitivity interstitial nephritis?
NSAIDs inhibit prostaglandin synthesis
Acute Drug-Induced Interstitial Nephritis due to NSAIDs is very similar to what disease?
MCD
Interstitial nephritis
Foot process effacement
What is the compound in Chinese herbs that may induce tubulointerstitial nephritis?
Aristolochic acid
In Chinese herb induced Acute Interstitial Nephritis, what is seen on renal biopsy?
Interstitial fibrosis with atrophy and loss of tubules
Urate Nephropathy
Pathogenesis of Acute and Chronic forms
Acute - tubular and epithelial uric acid crystal buildup
Chronic - also includes interstitial involvement
Urate Nephropathy
What do you see on H&E stain in the chronic form?
Inflammatory reaction, frequently with giant cells (tophi)
Multiple Myeloma
What is the primary pathological problem?
Plasma cell malignancy creating excess Ig or light chain
The proteins circulate in blood and are filtered through the GBM
Multiple Myeloma
Where do the proteins tend to precipitate? What can this lead to?
Distal tubules
Multiple Myeloma could cause uric acid buildup, hypercalcemia, light chain casts, acute renal failure
Arterionephrosclerosis
What is the pathological problem?
Benign HTN leads to thickening and sclerosis of arterial walls (hyaline arteriosclerosis)
How will Malignant HTN effect the kidneys?
Acute phase will bring fibrinoid necrosis of the renal arteries and arterioles
Cause hyperplastic arteriosclerosis (“onion skin”) and smooth muscle hyperplasia
Will eventually lead to renal failure
What are some issues/symptoms that can be seen from renal artery stenosis?
Pain Livedo reticularis (vascular rash) Renal infarct (white)
What is the basic lesion in all thrombotic microangiopathy diseases?
Endothelial injury
3 basic symptoms of Thrombotic Microangiopathy
Microangiopathic hemolytic anemia
Thrombocytopenia
Renal Failure
What is the typical pathogenesis of HUS in children?
STEC (Shiga toxin producing E coli) infection, often ingested in undercooked ground beef
What is the typical pathogenesis of HUS in adults?
Endothelial injury due to atypical uncontrolled complement activation
What is the typical pathogenesis of TTP?
Excess platelet activation from lack of ADAMTS13 enzyme to get rid of vWF multimers in blood
What will lab tests reveal in Thrombotic Microangiopathy?
Thrombocytopenia
Schistocytes in peripheral blood smears
What is seen on H&E stain in Thrombotic Microangiopathy?
Lots of bright red/pink due to fibrin thrombi
Mesangium is dilated and destroyed in the disease process
What is the treatment for Thrombotic Microangiopathy?
Supportive
Care for underlying disease
May use eculizumab antibodies against complement C5 in atypical HUS
