14 Pathology of Vascular Tubulointerstitial Disease Flashcards
1
Q
Important aspects of the kidney
- How much kidney we need to survive
- Kidney as a unit
- Blood supply
- Innocent “bystander”
- Kidney can be the victim of its own function
A
- How much kidney we need to survive
- We have 2 kidneys but only need 1/4 of one kidney to survive
- Big functional reserve
- Renal diseases are seldom acutely fatal due to advances in renal dialysis
- We have 2 kidneys but only need 1/4 of one kidney to survive
- Kidney as a unit
- Different components of the kidney act as one unit
- Whatever disease that primarily affects the blood vessels will eventually affect the glomeruli, tubules and interstitium
- Blood supply
- Tubules get their blood supply through the peritubular capillary plexus & vasa recta
- These blood vessels arise from the EffA as it leaves the glomeruli
- Any disease affecting glomerular capillaries will cause tubular ischemia and tubular necrosis (cell death)
- Innocent “bystander”
- Kidney is an innocent “bystander” in many systemic diseases
- Adversely affected by HTN, vasculitis, thrombotic diseases, etc.
- Kidney can be the victim of its own function
- Main function: blood filtration & excretion of waste products
- Filtering circulating antibodies causes capillary trapping & malfunction
- Filtering large proteins will settle in the tubular lumen, blocking it and causing tubular damage and renal malfunction i.e.: Multiple Myeloma
2
Q
Renal vascular diseases
- Present as…
- Renal involvement is common in most types of…
A
- Present as…
- Part of systemic disease (most common)
- Isolated to kidney vasculature (less frequent)
- Renal involvement is common in most types of systemic diseases affecting…
- Vessel lumen: thrombosis, emboli, DIC
- Vessel walls: vasculitis, HTN, HoTN, bilateral cortical necrosis
- Tubular epithelial cells: drugs, toxins
- Interstitium: inflammation, infection
- Other: systemic lupus erythematosis (SLE), sickle cell disease
3
Q
Hypertension
- General
- 2 types
- Benign
- Malignant
- Primary vs. secondary
- Primary
- Secondary
- Pathological features
- Benign nephrosclerosis
- Blood vessels affected
- Microscopically
- Other
- Malignant nephrosclerosis
- Blood vessels affected
- Microscopically
- Other
- Benign nephrosclerosis
A
- General
- Persistent diatsolic BP > 95 mmHg
- Most common cause of renal failure in older pts
- 2 types
- Benign
- Chronic, long-standing
- Aka “silent killer” due to vague symptoms & delayed diagnosis
- Malignant
- Male > female
- Younger age group (~40yo)
- African americans > whites
- Presents w/ severe headache, retinopathy, acute & chronic renal failure
- Diastolic BP > 115 mmHg
- Benign
- Primary vs. secondary
- Primary
- __Idiopathic in 95% of cases
- Secondary
- Renal causes: acute or chronci glomerulonephritis, renal artery stenosis, vasculitis, etc.
- Endocrine causes: adrenocortical hyperfunction, etc.
- Vascular causes: atherosclerosis, renal vascular stenosis, etc.
- Primary
- Pathological features
- Benign nephrosclerosis
- Blood vessels affected: medium & small arteries (not capillaries)
- Microscopically: arteriolar hyaline sclerosis & thickening
- Other: arterial fibroelastic intimal hyperplasia
- Malignant nephrosclerosis
- Blood vessels affected: all (including capillaries)
- Microscopically: arteriolar fibrinoid necrosis, glomerular capillary necrosis, crescent
- Other: arteriolar hyperplasia w/ “onion skinning”
- Benign nephrosclerosis
4
Q
Vasculitis
- General
- Seen mostly in…
- Usually caused by…
- Diagnosed by…
- Polyarteritis nodosa
- General
- Serologic tests
- Wegener’s granulomatosis
- General
- Serologic tests
A
- General
- Inflammation of blood vessel walls
- Usually systemic: affects most blood vessels of the body, including blood vessels in kidneys
- Seen mostly in…
- Autoimmune diseases
- Usually caused by…
- Circulating antibodies
- Diagnosed by…
- Visualizing abnormal bood vessles (morphologically)
- Detecting appropriate antibodies int eh pt’s serum (serologically)
- Polyarteritis nodosa
- General
- Affects arcuate & intralobular arteries w/ necrosis
- Acute inflammatory cells (neutrophils) attack the waslls of the arteries & infiltrate the arterial walls on biopsy
- Once the blood vessels are injured, healing occurs w/ aneurysm formation & microinfarcts of the kidney parenchyma
- –> glomerular ischemia, focal segmental sclerosis, & fibrosis
- Other changes seen
- Tubular ischemia & “drop-out”
- Serologic tests
- Detection of antineutrophilc cytoplasm antibodies (P-ANCA) in the pt’s serum (perinuclear pattern)
- General
- Wegener’s granulomatosis
- General
- Granulomatous inflammatoin of blood vessels
- Destruction of bowman’s capsule
- Inflammatory cells (histiocytes + occasional giant cells) invade the blood vessels
- Giant cells are sen around the renal artery
- Serologic tests
- Detection of C-ANCA in the pt’s serum (cytoplasmic pattern)
- General
5
Q
ANCA
- Antigenic targets
- C-ANCA
- P-ANCA
- Clinical associations
- C-ANCA
- P-ANCA
A
- Antigenic targets
- C-ANCA
- Proteinase-3 (Pr-3)
- Bacteiral permeability increasing protein
- Some cytoplasmic patterns (ex. Jo-1 & ribosomal-P)
- P-ANCA
- Myeloperoxidase (MPO)
- Beta-glucuronidase
- Bacterial permeability increasing
- Cathepsin-G, elastase
- Lactoferrin
- Lysozyme
- C-ANCA
- Clinical associations
- C-ANCA
- Wegener’s granulomatosis
- Other small-vessel vasculitides
- Ulcerative colitis (uncommon)
- Drug rxns like propylthiouracil (rare)
- P-ANCA
- Microscopic polyarteritis
- Idiopathic crescentic necrotising glomerulonephritis
- Other small-vessel vasculitides
- Drug rxns like propylthiouracil (rare)
- C-ANCA
6
Q
Thrombotic diseases that affect the kidney
- Systemic diseases that affect the kidney
- Thrombotic diseases present w/…
- Therapy of thrombotic diseases
- Pathology of thrombotic diseases
A
- Systemic diseases that affect the kidney
- Disseminated intravascular coagulation (DIC)
- Usually a complication of septicemia
- Thrombotic thrombocytopenic purpura (TTP)
- Hemolytic uremic syndrome (HUS)
- Seen in E. Coli poisoning, metastatic breast cancer, drugs, & oral contraceptives
- Disseminated intravascular coagulation (DIC)
- Thrombotic diseases present w/…
- Thrombocytopenia
- Anemia
- Neurological symptoms (ex. stroke)
- Therapy of thrombotic diseases
- Plasmapheresis
- Mostly supportive & symptomatic
- Pathology of thrombotic diseases
- Arteriolar & cpaillary microthrombi w/ endothelial cel linjury
- Ichemia & collapse of the glomeruli –> secondary tubular changes
7
Q
Renal infarcts
- General
- Main cause
- Other causes
- Clinically, renal infarcts are…
- Pathologically, renal infarcts are…
- Grossly
- Recent infarcts
- Old infarcts
A
- General
- Most common abnormalities in the kidney
- Main cause
- Dislodging of the mural thrombi of the left heart
- Other causes
- Vegetative endocarditis
- Aortic aneurysms
- Clinically, renal infarcts are…
- Silent
- Discovered during surgery or autopsy
- Pathologically, renal infarcts are…
- Grossly: wedge-shaped, multiple, & bilateral
- Recent infacts: yellow-white & ringed by hyperemia
- Old infarcts: fibrous cars w/ loss of cortical architecture
8
Q
Acute tubular necrosis (ATN)
- ATN
- 2 types
- Ischemic
- General
- Tubular damage
- Nephrotoxic
- General
- Tubular damage
- Ischemic
A
- ATN
- Destruction of tubular epithelial cells
- Usually affects the PTs
- Major cause of acute renal failure
- Reversible w/ full recovery of renal function
- 2 types
- Ischemic
- Preceded by HoTN episode
- Tubular damage is focal w/ large skip areas of normal tubules
- Nephrotoxic
- Due to ingestion, injection, or inhalation of toxins
- Tubular damage is diffuce & mainly affects metabolically acitve PTs
- Ischemic
9
Q
Tubulo-interstitial diseases
- General
- Categories
- Tubulointerstitial nephritis due to drugs
- General
- Acute damage
- Chronic damage
A
- General
- Cluster of abnormalities that early on affects the renal tubules & interstitium
- Spares the glomeruli & the blood vessels
- Categories
- Ischemic: acute renal failure, HoTN, acute blood loss, shock
- Infections: acute & chronic pyelonephritis, viral & parasitic infections
- Toxins: drugs, analgesics, heavy metals (ex. lead)
- Metabolic diseases: urate accumulation, nephrocalcinosis, oxalate within the renal parenchyma
- Neoplasms: ex. multiple myeloma where monoclonal gamma globulins from the blood are filtered through the glomeruli & deposited as casts within the butular lumen –> tubular cell damage
- Immunologic rxn: ex. rejection of transplanted kidney
- Tubulointerstitial nephritis due to drugs
- General
- Acute or chronic inflammatory cells accumualte within renal parenchyma
- –> interstitial inflammation & tubular damage
- Acute damage
- Usually due to an allergic rxn
- Hallmark inflammatory cell: eosinophil (+ others)
- Chronic damage
- Proportionately & directly related to the amt & duration of drug exposure
- General
10
Q
Acute drug-induced interstitial nephritis
- Due to…
- Examples
- Appearance
- Presentation
- Pathological findings
- Immunofluorescent studies reveal…
A
- Due to…
- Hypersensitivity to a emdication
- Examples
- Sulfonamides
- Synthetic Penicillins
- Diuretics (Thiazides, Furosemide)
- Nonsteroidal anti-inflammatory medication (Phenylbutazone)
- Zantac (Cimetidine)
- Appearance
- 2-40 days after exposure to drugs (avg 15 days)
- Presentation
- Fever
- Peripheral blood eosinophilia
- Hematuria
- Proteinuria
- Itchy skin rash (25%)
- Serum IgE levels (all cases)
- Pathological findings
- Interstitial edema
- Eosinophilic & neutrophilic inflammatory infiltrate
- Less common: mononuclear inflammatory cells (ex. lymphocytes, histiocytes)
- Certain drugs cause granulomatous infiltrate w/ giant celsl (ex. methicillin, thiazides)
- Immunofluorescent studies reveal…
- Linear IgG & complements along tubular basement membrane
11
Q
Chronic interstitial nephritis
- General
- Chronic analgesic nephritis
- Pyelonephritis
A
- General
- Advanced stages of tubulointerstitial diseases
- Renal damage due to…
- Drugs –> chronic analgesic nephritis
- Chronic infections –> pyelonephritis or inflammation of renal parenchyma
12
Q
Chronic interstitial nephritis:
Chronic analgesic nephritis
- General
- Appearance
- Due to…
- Clinical presentation
- Seroius late complication
- Radoigraphic findings
- Pathological findings
- Microscopic findings
A
- General
- Renal damage due to drugs
- Women > men
- Appearance
- After prolonged itnake of analgesics like Aspirin, caffeine, Acetaminophen, Codeine, Phenacetin, etc.
- Due to…
- Cumulative large doses of 2-3 kg over 3 yrs
- Covalent binding + oxidative damage casued by the drug
- Clinical presentation
- Inability to concentrate urine
- Renal distal tubular acidosis
- Pyuria or pus in the urine (mostly sterile) in 100% of pts
- Serious late complication
- Transitional cell carcinoma of the renal pelvis & ureters
- Radiographic findings
- Absent renal papillae due to papillary necrosis by intravenous pyelogram (IVP) or CT
- Pathological findings
- Normal sized kidneys w/ raised & depressed areas of atrophy over necrotic papillae
- Microscopic findings
- Cortical tubulointerstitial nephritis, necrosis, & calcificaiton w/ sloughing of papillae
- Later: interstitial fibrosis & dilated calyces due to lost papillae
13
Q
Chronic interstitial nephritis:
Pyelonephritis or inflammation of renal parenchyma
- Acute
- Chronic
A
- Acute
- Due to acute episodes of bacterial UTIs
- Chronic
- Due to repeated episodes of acute pyelonephritis
14
Q
Chronic interstitial nephritis:
Pyelonephritis or inflammation of renal parenchyma:
Acute (UTIs)
- Women vs. men
- Infecting organisms
- How bacteria reach the kidney
- Most common organisms
- Predisposing factors
- Other causes
- Microscopic findings
A
- Women vs. men
- Women (15-40yo) : men :: 8 : 1
-
Infecting organisms
- Pt’s own flora
- How bacteria reach the kidney
- Ascending route (more common)
- Blood borne (more dangerous)
- Most common organisms
- Gram negative bacilli
- E. coli (most common)
- Proteus, Klebsiella, Enterobacter, Mycobacteria (less common)
- Predisposing factors
- Diabetes
- Pregnancy
- Urinary tract obstruction (ex. BPH)
- Tumors
- Other causes
- Vesico-ureteric reflux
- Immunosuppression
- Iatrogenic causes (ex. instrumentation from catheters, surgery, etc.)
- Microscopic findings
- Acute inflammatory cells (neutrophils) in interstitium –> tubular damage
- Small microabscesses in interstitium –> perinephric abscesses (painful)
15
Q
Chronic interstitial nephritis:
Pyelonephritis or inflammation of renal parenchyma:
Chronic
- Due to…
- Pathological findings
- Microscopic findings
A
- Due to…
- Recent bacterial infections (ex. vesicoureteral reflux &/or obstructions
- Pathological findings
- Irregular broad scars in a “geographic pattern”
- Microscopic findings
- Thickened & fibrosed calyces & renal pelvis
- Dense lymphocytic infiltrate
- Interstitial fibrosis
- Periglomerular fibrosis
- Focal segmental sclerosis
- Tubular atrophy
17
Q
Renal stones
- Women vs. men
- Stones
- Most common renal stones
- Infection
- Uric acid stones
- Cystine stones
- Mixed uric acid & Ca stones
A
- Women vs. men
- Women > men
- Stones
- Size varies b/n gravel size to large stones
- Dilate the renal pelvis & calyceal system
- Most common renal stones
- Composed of Ca oxalate, phosphate, urates, or a mix
- Infection
- W/ urea-splitting bacteria –> alkaline urine & large calculi (Stag horn)
- Uric acid stones
- Seen in 25% of pts w/ gout
- usually small (<2 cm) & radiolucent
- Cystine stones
- Seen exclusively in children w/ hereditary cystinuria
- Very uncommon
- Mixed uric acid & Ca stones
- Very common
- Present w/ severe colicky pain
- May be present as stones are passing from the kidneys through the ureters into the urinary bladder
