Transcript Renal Vascular and Tubulointerstitial Diseases

Renal Vascular and
Tubulointerstitial Diseases
Copyright, 1996 © Dale Carnegie & Associates, Inc.
Why do we Study renal Pathology?
Few signs and symptoms to many different diseases
Different treatments to different diseases
Some renal diseases recur in transplanted kidneys
Patients can be told of prognosis (renal failure,
dialysis..etc)
Plan
1- We’ll talk about Vascular disease that affect
kidney
 2- We’ll outline some of the most common
tubulointerstitial kidney diseases
 3- This will be followed by the lab with in-depth
exploration of the subject.
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Rule #1: The kidney is a very
important organ
We got two of them while we only need 1/4 to
survive (Big reserve)
 Renal Diseases are seldom fatal due to advances
in Renal dialysis
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Rule #2: The kidney is one unit
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Whatever affects the blood vessels will eventually
affect the glomeruli, tubules and interstitium
Rule #3: The tubules get their blood
supply through the peritubular
capillary plexus and vasa recta
These blood vessels arise from the efferent
arteriole as it leaves the glomeruli
 Any disease affecting glomerular capillaries will
cause tubular ischemia and death.
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Rule #4: The kidney is an “innocent
bystander” in many systemic diseases
Hypertension
 Vasculitis
 Thrombotic
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Rule #5: The kidney can be the victim
of its own function
Filtering circulating antibodies causes capillary
trapping and malfunction
 Filtering large proteins blocks the tubules:
Multiple Myeloma
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Renal Vascular Diseases:
Part of systemic disease (more common)
 Isolated to kidney vasculature (less frequent)

Renal Involvement is common in
most types of systemic diseases
Diseases affecting the vessel lumen (thrombosis,
emboli)
 Diseases affecting vessel walls (vasculitis,
hypertension)
 Diseases affecting the tubular epithelial cells
(Drugs, toxins)
 Diseases affecting the interstitium (inflammation,
infection)
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Systemic diseases affecting the
kidney:
Hypertension
 Hypotension/ bilateral cortical necrosis
 Vasculitis
 Thrombotic diseases/DIC
 Systemic Lupus Erythematosis
 Sickle cell Disease
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Hypertension:
Most common causes of renal failure in older
adults
 Diastolic BP 95 mm Hg or higher

Two types of Hypertension are
recognized:
Benign Hypertension
 Chronic, long-standing, most older adults
 Malignant hypertension
 M>F, Younger age group (40)
 African American
 Diastolic Pressure >115 mm Hg
 Headache, retinopathy, ARF, CRF

Hypertension can either be primary or
secondary:
Primary hypertension is usually idiopathic (no
known cause) in 95% of cases
 Secondary hypertension can be attributed to:
 1- Renal causes: Acute GN, Chronic GN,
Renal artery Stenosis, vasculitis…etc.
 2- Endocrine causes: Adrenocortical
hyperfunction..etc.
 3- Vascular diseases (atherosclerosis)

Pathologic features of Hypertension

Benign Nephrosclerosis
 Affects medium and
small size arteries,
sparing the capillaries
 Microscopically:
arteriolar Hyaline
Sclerosis and
thickening
 Arterial Fibroelastic
intimal hyperplasia

Malignant Nephrosclerosis
 All Blood vessels and
glomerular capillaries
 Microscopically:
Arteriolar Fibrinoid
necrosis, glomerular
capillary necrosis,
Crescent
 Arterial hyperplasia
“onion skinning”
“Grain Leather” (benign/chronic)
“Flea-Bitten” (malignant/acute)
Benign Hypertension
arteriole
Malignant hypertension
Onion-skinning
Benign hypertension
Malignant hypertension
Vasculitis:
Inflammation of the Blood vessels
 Mostly autoimmune diseases
 Circulating antibodies

Polyangiitis
Affects Arcuate and Intralobular arteries with
necrosis
 Healing with aneurysm and microinfarcts
 Glomerular ischemia, focal segmental sclerosis,
fibrosis
 Tubular ischemia and “drop-out”
 P-ANCA positive (perinuclear pattern)

Wegener’s Granulomatosis
Another form of systemic vasculitis
 Granuloma and destruction of Bowman’s capsule
 Histiocytic infiltrate/ occasional giant cells
 Giant cells around renal artery
 C-ANCA positive (cytoplasmic pattern)

Polyarteritis
Wegener’s
Thrombotic Diseases that affect the
kidney:
DIC
 Thrombotic Thrombocytopenic Purpura (TTP)
 Hemolytic Uremic Symdrome (HUS)

Thrombotic diseases (clinical)
Thrombocytopenia, anemia
 Neurological symptom (stroke)
 HUS seen in E. Coli poisoning, metastatic Breast
Cancer, Drugs, Oral contraceptives
 Therapy: Plasmapheresis

Thrombotic diseases (Pathology)
Arteriolar and capillary microthrombi
 Endothelial cell injury
 Ischemia and collapse of the glomeruli
 Secondary tubular changes

Medium-size Artery thrombosis
Glomerular Capillary thrombosis
Renal infarcts
Emboli from Mural thrombi of left heart
 Vegetative endocarditis and aortic aneurysms
 Clinically silent and discovered during surgery or
autopsy

Renal Infarcts (Pathology)
Grossly: Wedge-shaped, usually multiple,
bilateral
 Recent infarcts are yellow-white and ringed by
hyperemia
 Old infarcts are fibrous scars, loss of cortical
architecture

Old infarct, wedge-shaped, fibrosis
Summary #1:
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Vascular diseases can be due to systemic or local problems
They can be due to 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
Tubulo-interstitial diseases:
Cluster of abnormalities that, early on, affects the
renal tubules and the interstitium
 Spares the glomeruli and the blood vessels
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TIDs can be divided into the
following categories:
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Ischemic: Acute renal failure, hypotension, blood
loss, shock
Infections: Acute and Chronic pyelonephritis,
viruses, parasites
Toxins: Drugs, analgesics, heavy metals (lead…)
Metabolic: Urate, nephrocalcinosis, Oxalate
Neoplasms: Multiple Myeloma
Immunologic reaction: Transplant rejection
Acute Tubular Necrosis:
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ATN is the destruction of tubular epithelial cells. It
usually affects the proximal convoluted tubules
Is a major cause of acute renal failure.
It is important to remember that ATN is reversible with
full recovery of renal function.
It can be:
 1- Ischemic, preceded by hypotensive episode and is
usually focal with large skip areas
 2- Nephrotoxic due to ingestion, injection or inhalation
of toxins
Acute Tubular Necrosis
(Coagulative)
Regeneration (healing)
Tubulointerstitial Nephritis Due to
drugs:
1- Acute reaction is usually due to an allergic
reaction.
 2- Chronic damage is proportionately and
directly related to the amount and duration of the
exposure to the drug

Acute Drug-induced Interstitial
Nephritis:
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Hypersensitivity to commonly used meds:
 Sulfonamides
 Synthetic Penicillins
 Diuretics (Thiazides, Furosemide)
 Nonsteroidal anti-inflammatory
(Phenylbutazone)
 Zantac (Cimetidine)
Acute Drug-induced Interstitial
Nephritis (Clinical)
2-40 days after exposure to drugs (Average 15
days)
 Fever, eosinophilia, hematuria, proteinuria
 Skin rash in 25% of patients
 Serum Ig E levels high in all cases
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Acute Drug-induced Interstitial
nephritis (Path)
Interstitial edema
 Eosinophils and neutrophils
 Lymphs and histiocytes (less common)
 Methicillin and Thiazides causes granulomas with
Giant cells
 IF: Linear Ig G and Complements along TBM
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Chronic Interstitial Nephritis
Clinicopathologic term used for advanced stages
of tubulointerstitial diseases
 It can be due to:
 Damage due to drugs (Chronic analgesic
nephritis)
 Damage due to infection (Pyelonephritis)
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Chronic Analgesic Nephritis
Excessive intake of analgesics
 Aspirin, caffeine, Acetaminophen, Codeine,
Phenacetin...
 Cumulative large doses (2-3 kg over 3 yrs)
 Women > Men
 Cellular injury: covalent binding & oxidative
damage
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Chronic Analgesic Nephritis
(Clinical)
Inability to concentrate urine
 Renal distal tubular acidosis
 Pyuria (100% of patients)
 Transitional cell carcinoma (late complication)
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Chronic Analgesic Nephritis (Cont.)
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Absent renal papillae due to papillary necrosis (IVP
radiology)
Cortical tubulointerstitial nephritis
Normal size kidneys with raised and depressed areas
(atrophy over necrotic papillae)
Necrosis and calcification with sloughing of papillae
Interstitial fibrosis and dilated calyces due to lost papillae
Pyelonephritis or inflammation of
renal parenchyma
Acute Pyelonephritis is due to acute episodes of
bacterial infection
 Chronic Pyelonephritis due to repeated episodes
of acute pyelonephritis.
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Urinary Tract Infections
Females 15-40 years of age
 F:M ratio 8:1
 Infecting organisms from patient’s own flora
 Bacteria reaches the kidney by:
 Ascending route (more common)
 Blood born (more dangerous)
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Urinary Tract infections:
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Most common organisms:
 Gram negative bacilli (E. Coli is the most
common)
 Proteus, Klebsiella, Enterobacter, Mycobacteria
(T.B)
Predisposing factors for UTI:
Diabetes
 Pregnanct
 Obstruction (BPH, Tumors..)
 Reflux
 Immunosuppression
 Instrumentation (Catheters, surgery...)
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Acute Pyelonephritis (Microscopic)
Neutrophils in the interstitium
 Tubular damage (later)
 Microabscesses in the interstitium
 May lead to perinephric abscesses (Very painful)
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Ascending Acute Pyelonephritis (Neutrophils)
Chronic Pyelonephritis:
Recurrent bacterial infections
 Vesicoureteral Reflux and/or obstructions
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Chronic Pyelonephritis (Path)
Irregular broad scars in a “geographic pattern”
 Calyces and renal pelvis thickened and fibrosed
 Dense lymphocytic infiltrate and interstitial
fibrosis
 Periglomerular fibrosis, focal segmental sclerosis
and tubular atrophy.
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Chronic Pyelonephritis (Mononuclear Cells)
End Stage Chronic Pyelonephritis
Summary #2:
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Tubulointerstitial diseases can be due to many
etiologies including toxins, infection, 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)
Summary # 3:
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
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Summary #4:
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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.
Nephrocalcinosis
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Calcium deposition in the kidney leading to stones
Possible causes:
 Hyperparathyroidism causing hypercalcemia
 Multiple Myeloma
 Vitamin D intoxication
 Excess milk intake (too much of a good thing)
 Bone metastasis
Nephrocalcinosis (clinical)
Slowly progressive renal insufficiency
 Calcium stones
 Pyelonephritis
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Nephrocalcinosis
Ca++ deposits within tubular epithelial cells
 Calcium in basement membranes
 Atrophy of cortical areas and scar
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Renal stones
Men > Women
 Gravel size to large stones
 Stones dilate renal pelvis and calyceal system
 Calcium Oxalate, Phosphate, Urates, mixed
 Urea-splitting bacteria lead to alkaline urine and
large calculi (Stag horn)
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Renal stones (cont.)
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Other types of stones:
 Uric acid stone in 25% of patients with Gout
 Usually small (<2 cm) and radiolucent
 Cystine stones exclusive in children
 hereditary cystinuria
 Uncommon
 Mixed Uric acid and calcium stones
 Common
Small Stone in Renal Pelvis
Staghorn Calculus)
The End!!!