Path - Tubulointerstitial Disease 1 Flashcards by Abteen Moshref

4 types of tubulointerstitial diseases of the kidney

Acute tubular necrosis (ATN)
Pyelonephritis
Interstitial nephritis
Cystic diseases

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What is the relationship between acute tubular necrosis (ATN) and acute kidney injury (AKI)?

ATN is a subset of AKI. It is considered to be the worst cases of AKI. Unknown % of AKI.

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What percentage of AKI is due to ATN?

Unknown percentage because renal biopsies are rarely performed

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What is the relationship between ATN and ischemia?

Ischemic ATN is a subset of ATN, roughly 75% of ATN

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What % of ATN is due to ischemia?

Roughly 75%

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What is the gross pathology of a kidney with ATN?

Enlarged, up to 30% above normal
pale cortex
Congested medulla, especially at corticomedullary junction

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A subset of kidneys with ATN will have what gross pathologic feature? When, how, and why?

Certain subset of ATN may have some cortical hemorrhages

Cortical hemorrhages occur due to uneven disease process. If patient develops thromboemboli or septic emboli.

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What portion(s) of the renal tubule are most vulnerable to acute ischemic necrosis? Why?

Proximal straight tubule
Ascending thick limb of LOH

These two portions are in the outermost medulla at the corticomedullary junction, the area that gets congested with acute tubular necrosis

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Describe normal renal tubule cells?

Cuboidal cells with granular eosinophilic cytoplasm

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Pathology. What is the earliest morphologic change of tubular cell injury?

blebbing of luminal side cell membranes, indicates an early ischemic change

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Pathology. Besides blebbing, what is another sign of early ischemic change in ATN?

Vacuolization of cytoplasm as a result of diffuse edema of tubular cells

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Name the 2 reversible changes that are associated with ATN?

Blebbing and vacuolization, both are reversible.

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What else can cause vacuolization of cytoplasm in tubular cells?

Osmotic diuresis

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Pathology. In ATN, what is the next pathologic change in tubules after they have started blebbing and undergone vacuolization of the cytoplasm?

After blebbing and vacuolization:

tubule cells will start to lose their brush border and begin to flatten out (seen in tubules 1-3)
followed by necrosis & sloughing of epithelial cells (seen in 4)

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Pathology. In ATN, the necrosis and sloughing of tubular cells leads to what?

The tubular cells mix into casts with proteinaceous material (seen in the arrows)

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Buzzword. U/A casts in ATN?

muddy brown granular casts seen in UA

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In ATN, besides coagulative necrosis that occurs in tubular cells, what else can occur? Why does this occur?

Besides coagulative necrosis, tubular cells can undergo apoptosis. Nichols explains this as the tubular cell sees that coagulative necrosis coming and decides to kill themselves before that happens.

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The apoptotic renal tubular epithelial cells are most likely to have decreased cytoplasmic activity of what?

BCL-2

BCL-2 is considered an anti-apoptotic protein; therefore, if you have increased apoptosis, you would have decreased activity of BCL-2

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Pathology. In ATN, what other protein could be found in the tubular lumen, especially in instances of crush injury?

Myoglobin released from muscle cells due to crush injury/trauma can cause rhabdomyolysis.

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If a patient ingests ethylene glycol (antifreeze), what chemical compound will cause ATN?

Calcium oxalate

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In ATN, what feature on microscopy indicates that tubular cells are in recovery phase?

Presence of mitotic figures

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In ATN, how is it considered to be reversible? What symptom will persist until recovery phase has started?

Tubular cells are considered to be stable cells, meaning they can reenter the cell cycle and regenerate. This usually will take 2-3 weeks, thus patient can have continuing oliguria until enough cells have regenerated.

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What is being shown here? What features allow you to know what pathology is occurring?

This is renal cell carcinoma, not ATN.

Clues: No well defined tubules, no glomeruli are visible, no architecture. All these lead you to think cancer vs ATN

Can ATN become a medical emergency? If so, when would this occur?

Yes, if K+ > 7 mmol/L

If patient becomes hyperkalemic in ATN, what immediate treatment should you give?

1. IV calcium gluconate - to antagonize membrane depolarization and protect against cardiac arrhythmias 2. IV Insulin (+glucose) - drives K+ into cells 3. Albuterol - acts on B2 receptors to increase Na/K+ activity 4. Resins, such as kayexalate, to bind K+

What is pyelonephritis?

Infection of the kidneys

Pyelonephritis is usually caused by? Other less common mechanisms?

- Commonly an **ascending bladder infection**; - Other mechanisms: **hematogenous spread to kidney** vesicoureteral reflux and bladder overdistention of contaminated urine Bladder catheterization

What pathogen most commonly causes pyelonephritis due to ascending infection?

E.coli (90%), proteus, Klebsiella species, enterococcus

What pathogen most commonly causes pyelonephritis due to hematogenous infection?

Staphylococcus \> E. coli

Blunted calyces and cortical scarring is more associated with which route of infection in acute pyelonephritis?

Seen in pyelonephritis due to ascending infection

Describe Gross pathology of acute pyelonephritis

Dark red congestion and areas of light tan suppurative (pus forming) inflammation Some with necrosis Some coalesce into abscesses (upper right of picture)

Abscesses in acute pyelonephritis is due to?

Liquefactive necrosis

Microscopic pathology of acute pyelonephritis will show what 2 common findings?

1. Congestion with some mild hemorrhage 2. Diffuse neutrophil infiltration

What is nuclear dust? Describe its relation to acute pyelonephritis

Nuclear dust = nuclear debris from the breakdown of dead cells, especially neutrophils This is common in later abscesses that have been infiltrated by neutrophils

What characteristic feature do later stage abscesses have?

They will have cracks (then holes) in them, as shown in the picture

What complications can arise from acute pyelonephritis

Acute pyelonephritis due to hematogenous infection has what characteristic pathology in kidney?

Will affect individual glomeruli (difference shown in picture)

Chronic pyelonephritis mainly affects what part of kidney (microscopically)?

Primarily interstitial (vs tubular/glomerular seen in acute)

Pathology. Chronic pyelonpehritis makes tubules look more like what? Mechanism of this?

Tubules look more like **thyroid follicles ("thyroidization")**, due to fibrosis and distended tubules

What is the relationship b/t acute interstitial nephritis (AIN) and drug reactions?

Drug reactions = most common cause of AIN, over 75% - However, MOST drug reactions do NOT cause AIN

Edema, lymphocytes, macrophages, neutrophils, and eosinophils are common in what disorder? Of these, which is the least common, but most specific this disorder?

AIN Eosinophils = least common, but **MOST specific**

Analgesic nephropathy is associated with what 2 features?

Chronic interstitial nephritis and papillary necrosis

What is the black arrow pointing at? What disorder is it associated with?

Black arrow = papillary necrosis Seen in analgesic nephropathy

Analgesic nephropathy is most common in? Is this form of nephropathy common?

Elderly females, due to long term combination analgesic use. Has become rare

Autosomal dominant polycystic kidney disease is most common in children or adults?

Adults

What is AD polycystic kidney disease?

Slowly expanding cysts that compress normal tissue, causing ischemic atrophy

List the 2 genetic mutations that are associated with AD polycystic kidney disease? Which is more common? Describe genetic model of this disease?

Polycystin-1 (**85%**) & Polycystin-2 2 hit genetics, just like retinoblastoma

AD polycystic kidney disease makes up what percentage of CKD (chronic kidney disease)?

10%

AD polycystic kidney disease leads to what 3 pathologic features?

1. Ciliopathy (disorder of cilia) 2. Defective mechanosensing of urine flow 3. dysregulation of cell adhesion

Autosomal recessive polycystic kidney disease more common in children or adults?

Children

What is AR polycystic kidney disease? Pathogenesis and prognosis of it?

Numerous small cysts replace normal kidney tissue during fetal life This causes lack of production of amniotic fluid during gestation, causing **pulmonary hypoplasia** Ultimately, **immediate untreatable respiratory failure at birth**

Buzzword. Pulmonary hypoplasia. What is it associated with? What does it mean?

AR polycystic kidney disease Pulmonary hypoplasia due to lack of amniotic fluid production during gestation

What genetic mutation is associated with AR polycystic kidney disease?

Fibrocystin

Nephronophthisis is classified as what type of kidney disease?

Medullary cystic disease complex

What is the most common genetic cause of end stage renal disease in children?

Nephronophthisis

Pathology of nephronophthisis?

Small kidneys with numerous small cysts at the corticomedullary junction

What kidney disease is relatively common and usually innocuous (not harmful)?

Medullary Sponge kidney. Make sure you know the prognostic difference between this and nephronophthisis (medullary cystic disease complex)