14 Pathology of Vascular Tubulointerstitial Disease Flashcards Preview

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Flashcards in 14 Pathology of Vascular Tubulointerstitial Disease Deck (21)
1

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

  • 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
  • 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

Renal vascular diseases

  • Present as...
  • Renal involvement is common in most types of...

  • 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

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

  • 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
  • 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.
  • 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"

4

Vasculitis

  • General
  • Seen mostly in...
  • Usually caused by...
  • Diagnosed by...
  • Polyarteritis nodosa
    • General
    • Serologic tests
  • Wegener's granulomatosis
    • General
    • Serologic tests

  • 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)
  • 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)

5

ANCA

  • Antigenic targets
    • C-ANCA
    • P-ANCA
  • Clinical associations
    • C-ANCA
    • P-ANCA

  • 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
  • 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)

6

Thrombotic diseases that affect the kidney

  • Systemic diseases that affect the kidney
  • Thrombotic diseases present w/...
  • Therapy of thrombotic diseases
  • Pathology of thrombotic diseases

  • 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
  • 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

Renal infarcts

  • General
  • Main cause
  • Other causes
  • Clinically, renal infarcts are...
  • Pathologically, renal infarcts are...
    • Grossly
    • Recent infarcts
    • Old infarcts

  • 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

Acute tubular necrosis (ATN)

  • ATN
  • 2 types
    • Ischemic
      • General
      • Tubular damage
    • Nephrotoxic
      • General
      • Tubular damage

  • 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

9

Tubulo-interstitial diseases

  • General
  • Categories
  • Tubulointerstitial nephritis due to drugs
    • General
    • Acute damage
    • Chronic damage

  • 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

10

Acute drug-induced interstitial nephritis

  • Due to...
  • Examples
  • Appearance
  • Presentation
  • Pathological findings
  • Immunofluorescent studies reveal...

  • 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

Chronic interstitial nephritis

  • General
  • Chronic analgesic nephritis
  • Pyelonephritis

  • General
    • Advanced stages of tubulointerstitial diseases
  • Renal damage due to...
    • Drugs --> chronic analgesic nephritis
    • Chronic infections --> pyelonephritis or inflammation of renal parenchyma

12

Chronic interstitial nephritis:
Chronic analgesic nephritis

  • General
  • Appearance
  • Due to...
  • Clinical presentation
  • Seroius late complication
  • Radoigraphic findings
  • Pathological findings
  • Microscopic findings

  • 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

Chronic interstitial nephritis:
Pyelonephritis or inflammation of renal parenchyma

  • Acute
  • Chronic

  • Acute
    • Due to acute episodes of bacterial UTIs
  • Chronic
    • Due to repeated episodes of acute pyelonephritis

14

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

  • 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

Chronic interstitial nephritis:
Pyelonephritis or inflammation of renal parenchyma:
Chronic

  • Due to...
  • Pathological findings
  • Microscopic findings

  • 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

16

Nephrocalcinosis

  • General
  • Causes
  • Clinical presentation
  • Detection
  • Microscopic presentation

  • General
    • Ca depositoin int he kidney --> stone formatoin
  • Causes
    • Hyperparathyroidism --> hypercalcemia
    • Multiple myeloma
    • Vitamin D intoxication
    • Excess milk intake or bone metastasis of solid tumors --> bone resorption & Ca deposition in kidneys
  • Clinical presentation
    • Slowly progressive renal insufficiency
    • Ca stones
    • Pyelonephritis may be present
  • Detection
    • Ca stones are detected radiographically
  • Microscopic presentation
    • Ca deposits within tubular epithelial cells
    • Ca seen in basement membranes of tubules
    • Renal cortex: atrophy + scar formation

17

Renal stones

  • Women vs. men
  • Stones
  • Most common renal stones
  • Infection
  • Uric acid stones
  • Cystine stones
  • Mixed uric acid & Ca stones

  • 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

18

Summary 1

  • Vascular diseases can be due to...
  • Malignant hypertension causes...
  • Vasculitis is due to...
  • Thrombotic diseases (DIC) causes...
  • Renal infarcts are due to...

  • Vascular diseases can be due to
    • Systemic or local problems
    • Inflammation of the vessel walls or occlusion of the vessel lumen
  • Malignant hypertension causes more damage than chronic hypertension
  • Vasculitis is due to circulating auto-immune antibodies
  • Thrombotic diseases (DIC) causes damage by clogging the lumen
  • Renal infarcts are due to occluded vessels & are very common and heal with scar formation

19

Summary 2

  • Tubulointerstitial diseases can be due to...
  • Acute Tubular Necrosis can be due to...
  • Drug-induced interstitial nephritis can be...
  • Chronic drug-induced interstitial nephritis will lead to...

  • Tubulointerstitial diseases can be due to many etiologies including toxins, infection and ischemia
  • Acute Tubular Necrosis can be due to ischemia or toxins and is usually reversible
  • Drug-induced interstitial nephritis can be acute (hypersensitivity) or chronic (oxidative damage)
  • Chronic drug-induced interstitial nephritis will lead to Transitional Cell Carcinoma (Late Complication)

20

Summary 3

  • Pyelonephritis can be...
  • Iatrogenic (instrumentation) may...
  • Obstruction causes...
  • Bacteria are mostly...

  • Pyelonephritis can be acute and chronic, F>M
  • Iatrogenic (instrumentation) may introduce the bacteria
  • Obstruction causes bacteria to multiply (good environment at right temperature)
  • Bacteria are mostly patient’s own colonic bacteria

21

Summary 4

  • If you see Eosinophils...
  • If you see Neutrophils...
  • If you see Lymphocytes...
  • If you see Giant cells...
  • If you see Histiocytes...

  • If you see Eosinophils...Think Hypersensitivity (allergic reaction) or Parasite
  • If you see Neutrophils...Think Acute Bacterial infection
  • If you see Lymphocytes...Think Chronic Bacterial infection or viral infection
  • If you see Giant cells...Think Fungal infection and foreign body reaction
  • If you see Histiocytes...Think necrosis and clean up crew