Tubulointerstitial Disease Flashcards
What are some of the key features of this kidney?
• is it normal or abnormal?
In cross section, this normal adult kidney demonstrates the lighter outer cortex and the darker medulla, with the renal pyramids into which the collecting ducts coalesce and drain into the calyces and central pelvis.
What are the two leading findings in diseases affecting the tubules and interstitium?
Inflammation
Ischemic or toxic changes
What are the common causes of inflammation in Tubulointerstitial disease?
- Acute Pyelonephritis
- Chronic Pyelonephritis
- Drug Induced Interstitial Nephritis
What causes ischemic or toxic changes in tubulointerstitial diseases?
• Acute Tubular Injury
Acute Pyelonephritis
• What is it?
• What is the most common cause?
• What condition is acute pyelonephritis often associated with?
What is it?
• a common suppurative inflammation of the kidney and the renal pelvis, is caused by bacterial infection
Associated Diseases:
• majority of cases of pyelonephritis are associated with infection of the lower urinary track
E. Coli - most common cause (females often get UTIs to kidney faster due to short urethra)
Besides E. Coli, what other bacteria are associated with Pyelonephritis?
- Proteus
- Klebsiella
- Enterobacter
- Pseudomonas
What is the most common route of infection for Acute Pyelonephritis?
• most common causes for infection to move via this route?
• Other causes?
Ascending Infection - from lower urinary to upper urinary
Causes (VASOD)
• Vesicouteral Reflux
• Anatomy
• Stasis
• Obstruction (BPH, uterine prolapse)
• Diabetes
Other causes: Hematongenous Spread (far less common, but associated with septicemia and INFECTIVE Endocarditis)
What Key histological features are seen here?
• why could this NOT be an acetamenophen overdose?
- Neutrophils are present so inflammation is ACUTE
- Cells can be seen sloughing into the tubules creating WBC Casts
- No EOS. so its not an allergic rxn to medication
What abnormailites are seen here?
• what is the most likely cause?
Extremely Dialated Ureter with Kidney Stones
• this is indicative of vesicouteral reflux
What is this?
• what is the most likely process and etiologic agent that led to this?
Acute Pyelonephritis
• E. coli that ascends the ureter as a result of Vesicouterine Reflux is the most common cause of this
What has happened to this kidney?
Pustules causes by Acute Pyelonephrosis have combined into a large pus pocket
• Females are most likely to get this for anatomical Reasons
What 3 key histological features are you looking for in ACUTE PYELONEPHROSIS?
• what would be seen an uninalysis?
• if this were allowed to progress, what gross changes would you see in the kidney parenchyma?
3 Key Histological Features:
• NORMAL GLOMERULI
• Inflammatory Infiltrate into the Interstitium
• Abscess formation
Urinalysis:
• WBC casts
Gross Changes:
• Papillary Necrosis
T or F: this image is consistent with Acute Pyelonephritis.
True, you can see abscesses, interstitial infiltrate, and spared glomeruli
A 73 year old man presents with WBC casts in the urine and the following CT is obtained. (GFR normal).
• most likely dx?
Probably Acute Pyelonephritis from BPH
T or F: this image is indicative of Chronic Pyelonephritis
FALSE, this is actue pyelonephritis
What would you see on H and E if this were caused by a drug?
these are WBC casts, if this were drug induced then you would see eos on H and E
If glomeruli are typically spared in Acute Pyelonephritis, then why is GFR reduced as the disease progresses?
Reduced GFR is the result of WBC’s (PUS) clogging up the renal tubules
What pathology is shown here?
• what are some causes?
Papillary Necrosis = COAGULATIVE NECROSIS (b.c its pyogenic)
What is shown here?
• Key Histological Featurs?
• Pale Cells in the center of the Papilla indicated nuclear fallout which means this is acute papillary necrosis likely caused by: Sickle cell, Obstructive Pyelonephritis, Diabetes melatis, or Analgesic Abuse
Describe what is see here?
• likely cause?
Chronic cystitis
• Hypertrophy with trabeculation of the wall
• Or thin and distended from urine retention (Less Common)
Enlarged Prostate can be seen here. BPH has caused chronic cystitis
A 65-year-old woman had experienced increasing malaise with nocturia and polyuria for the past year. Her blood pressure was 170/95. Urinalysis showed 1+ proteinuria. Serum BUN and creatinine were elevated. Her chart indicates a history of multiple UTIs. She developed worsening renal failure and died of pneumonia. What is the BEST diagnosis?
• what appearance would you expect to see in her Renal Cortex? Medulla?
Chronic Pyelonephritis - given her hx of multiple UTIs and slow and progressive symptoms of renal failure suggest a chronic rather than acute process
Cortex - glomerulosclerosis will be seen - note that this differs from acute pyelonephritis where glomeruli are spared
Medulla - thyroidization of the tubules is seen in this chronic process
This is Xanthogranulomatous pyelonephritis what are some of the key histological features?
- **Foamy Macrophages
- Plasma Cells surrounding**
What is seen here?
Pylonephritic Abscess (was pus filled before they cut it open)
What is seen here?
Acute Papillary Necrosis
What are the 2 forms of Chronic Pyelonephritis?
• Which is more common?
Chronic obstructive
• Stones
• Posterior urethral valves
• BPH
Chronic reflux
• More common
• Superimposed UTI on congenital reflux and intrarenal reflux
T or F: Chronic Pyelonephritis primarily invovles the Tubules and shows scar formation.
True, it definitley shows scar formation BUT it does NOT involve the tubules, instead it typically involves INTERSTITIUM
This is Chronic Pyelonephritis on Gross inspection.
• what are some of the key features?
- Look at cicumference – you see pitting instead of smooth lobulation that is large rather than the bumpy appearance seen in long standing HTN
- Dip because you get scarring in PELVIS that pulls tissue downward, (pyramid blunted horizontal left and scarring above pulls tissue down)
- Typically occurs on the poles of the kidney
What tissue is typically involved in scarring in chronic pyelonephritis?
• what does this lead to?
• Calyces and Pelvis scar leading to Papillary Blunting
• Calyceal deformities
What are two Key features to look for in H and E of Chronic Pyelonephritis?
• others?
• Uneven Interstitial Fibrosis
• Mixed Interstitial Inflammation
• Glomerulosclerosis
• Thyroidization is seen in the tubules along with thinning of the tubule wall
Note: Picture shown here is of someone who is at the end of end-stage disease notic the uneven fibrosis
Shown in this picture is the Uneven distribution of the
What is the likely cause of the Vessel seen in the center of the thyroidized tubules?
• This vessel shows intimal thickening indicative of Long Standing Benign HTN
What is the most likely cause of this appearance in the renal medulla?
• Describe the Appearance.
Acute Tubulointerstitial Nephritis (TIN) - DRUG INDUCED
• interstitial inflammation, often with abundant EOSINOPHILS
and edema
What are some drugs known to cause Acute Tubulointerstitial Nephritis (TIN)?
•what cell type mediates this inflammation?
- synthetic penicillins (methicillin, ampicillin),
- other synthetic antibiotics (rifampin),
- diuretics (thiazides),
- nonsteroidal anti-inflammatory agents, and
- numerous other drugs (phenindione, cimetidine)
T-cell and IgE mediated
What are the morphological Characteristics of Acute Tubular Necrosis?
• what are the two types?
- Damaged Tubular Epithelial cells
- Granular Casts in urine
2 types:
• Ischemic and Nephrotoxic
What are 3 causes of Ischemic Acute Tubular Injury?
- Deceased Blood Flow
- Mismatched Blood Transfusions
- Hemolytic Crisis
What are 3 causes of toxic acute tubular injury?
- Drugs/Poison
- Contrast
Why is GFR reduction seen in tubular injury that is not associated with ischemia?
Tubules become clogged with cells sloughing off the edges
What features do you expect to see on Gross Pathology of Acute Tubular Necrosis?
• Enlarged (up to 30%)
• Congested Medulla (especially at corticomedullary junction)
• Pale Cortex
What 3 possible cause for the Ischemia that lead to this injury?
• what is seen here?
Coarse Granular Brown Casts due to acute tubular necrosis
Ischemic Causes: Reduced Blood Flow, Hemolytic Reaction, Blood Donor Mismatch
What protein is responsible for the formation of the cast seen here?
Tamm-Horsfall glycoprotein (normally secreted by tubular epithelium) along with hemoglobin and other plasma proteins
What is seen here?
• what is the next thing you’d want to know about this person’s urine?
• you want to know if they have positive or negative urine cultures
Differentiate the Pattern seen in Ischemic and Nephrotoxic injury in Acute Tubular Injury.
Ischemic:
• More of a segemented (striped effect) on the tubule
Toxic:
• Even toxicity across the length of the tubule
What portion of the tubule is most susceptilbe to ischemic necrosis?
• Proximal Straight Tubule
What is seen here?
• Key histological Features?
ischemic ATI
attenuation of proximal tubular brush borders
blebbing and sloughing of brush borders,
vacuolization of cells
What toxin likely caused this ACUTE Tubular injury?
The tubular vacuolization and tubular dilation here is a result of the toxic effect of ethylene glycol poisoning
Is this chronic or acute tubular injury?
• how do you know?
Acute - because the tubules are completely oblterated and the glomerulus appears fine (it has not had time to become affected)
What key histologic features are seen here in this Acute Tubular Necrosis?
• shown here is a flattened epithelium with necrosis and sloughing - caused by rhabdomyolysis
What was likely responsible for this transplant failure?
• be specific
• BK virus ******KNOW THIS IMAGE********
What does this radiograph of an adult man show?
autosomal dominant polycystic kidney disease
What are the 4 types of cystic kidney disease?
Simple Cysts
Autosomal Dominant (Adult) Polycystic Kidney Disease
Autosomal Recessive (Childhood) Polycystic Kidney Disease
Medullary Diseases with Cysts
What is this?
• How common?
• Clinical Significance?
• likely cause?
Simple Cyst - you can tell by the smooth walls and lack of sepatations, these are COMMON and of NO CLINICAL SIGNIFICANCE
• patients on Dialysis may aquired these cysts
What is the cause of this appearance in the kidney?
Dialysis
Differentiate Cyst Size in Autosomal Dominant and Autosomal Recessive polycistic Kidney Disease.
• Genes affected?
autosomal Dominant:
• Larger Cysts
Gene: PKD-1 or PKD-2 (polycistin 1 and 2)
autosomal recessive:
• smallter cysts
Gene: PKHD-1
What is shown in this image?
AUTOSOMAL DOMINANT polycystic Kidney Disease
What is the Px for Autosomal Recessive Polycistic Kidney Disease?
• Gene product?
Px:
• POOR
Gene:
• Abnormal fibrocystin protein – expressed on cilia of renal tubules and bile ducts (have congenital hepatic fibrosis) – BIG HINT
What aspect of Autosomal recessive polycystic kidney disease has lead to the appearance in the tissue shown here?
Mutation in the PKHD1 (fibrocystin gene) has caused fibrosis in the bile duct in the liver because it codes for cilia in both bile duct and proximal convoluted tubule
What is shown here?
- Congenital or Acquired?
- symptoms?
Medullary Sponge Kidney
• congenital and bilateral but there is no inheritance patten
• May start showing symptoms of hematuria and/or urinary tract infection as young adults
What is Nephronophthisis–medullary cystic disease complex?
- patient popuation?
- Inherited or Acquired?
- what is the molecular defect?
Cystic kidney disease causing cyst formation at medullary border and unlike Polycystic Kidney Disease, it does NOT cause kidney enlargement
Inheritance:
• Autosomal Recessive Inheritance
Gene Product:
• Encodes genes involved in Ciliary Function
What is the inheritance pattern of the disease that causes this gross appearance?
• Key features
Nephronophthisis–medullary cystic disease complex
• Cysts in the medulla WITHOUT kidney enlargement is key
Shown below is the histological appearance of this disease
Nephronophthisis–medullary cystic disease complex - ultrasound
What mutation is associated with this condition?
• Risks?
Horseshoe Kidney
• Trisomy 18
• Ureters may get obstructed
Cast type?
WBC
Cast Type
Epithelial
Cast Type?
RBC
Cast Type?
Mixed
Cast Type?
Granular
Cast Type?
Hyaline
