L7. Tubular Diseases

Question 1

What leads to tubular hyaline changes

Answer 1

Proteinuria leads to endocytosis of proteins by tubular cells, which form hyaline deposits.

Question 2

What leads to tubular hyperthrophy?

Answer 2

Hyperthrophied tubules are usually next to atrophic tubules. They become hypertrophied to compensate for the lsot ones

Question 3

Define Acute Renal Failure (ARF)

Answer 3

Sudden decrease in glomerular filtration rate (GFR) which presents as increased serum creatinine and BUN

Question 4

How is ARF defined in terms of urine output

Answer 4

• Oliguric (<400ml urine/24hr)
• Anuric (<100ml/24hr)
• Nonoliguric (> 400ml/24hr)

Question 5

Intrinsic ARF –> Site of injury and subclassification

Answer 5

Site of injury: kidney parenchyma

Subclassification

• Tubular
• Interstitial,
• Glomerular
• Vascular

Question 6

How do we distinguish instrinsic RF from pre-renal ARF

Answer 6

Urinalysis (not very clear ask)

• Intrinsic: urinary Na (>40mEq/L) & fractional excretion of Na (>2%)
• Pre-renal: urinary Na (<20mEq/L) & fractional excretion of Na (<1%)

Question 7

Why is acute tubular necrosis considered a misnomer

Answer 7

There is cell injury but no necrosis and ATN is considered a reversible lesion

Question 8

What are the 2 major etilogic patterns of ATN

Answer 8

• Ischemic
• Toxic

Question 9

What are common causes of ischemic ATN

Answer 9

• Surgery –> sp. involving abdominal vasculature
• Hemorrhage
• Burns
• Crush injuries

Question 10

Explain the patterns of tubular damage in ischemic and toxic inkury

Answer 10

• Ischemic: tubular injury is patchy along the nephron, mainly short lengths of the proximal straight tubules and the thick ascending limbs, w/ large skip areas of normal epithelium in btw.
• Toxic injury: involves often the entire lenghth of the proximal tubule with less skip areas. Due to the secretory function of the PCT –> cause damage

Question 11

Explain why we say that renal medulla normally exits on the brink of hypoxia

Answer 11

Oxygen to medulla is delivered by efferent arteriole after passage through glomerulus.

There is an oxygen gradient from the cortex to the medulla.

Cell are bathed w/ PO2< 10-12 mmHg = Almost hypoxic range + highe activity –> risk for hypoxia

Increase delivery of solute to this areas may lead to hypoxia

Question 12

Mitotic figures in tubular epithelium are sign of

Answer 12

ATN in the process of regeneration or recovery

Question 13

Explain the mechanism of altered cell polarity and its consequences

Answer 13

Altered Cell polarity: tigh juntion btw epithelial cells break –> Na/K pump moves to apical membran

Consequences: Na is pumped out into the lumen lost in urine

K is pumped into cell –> accumulation into blood –> cardiac arhythmia

Question 14

Explain teh pathogenesis of decreased glomerular filtration in ATN

Answer 14

• Damage to tubular endothelial cell –> cast which block flow = obstruction and incrs. intratubular pressure –> Decr. GFR
• Due to epithelial lining damage and reveres polarity there is increse lost of Na in urine –> feedsback to macula densa –> vasoconstriction of afferent arteriol and decr. GFR
• increase interstitial pressure due to leakage from the damaged tubule –> affects vessels and decr. GFR

Question 15

Clinical presentation of kidney disease associated w/ plasma cell dyscrasia

Answer 15

• Elderly
• Back pain
• Hypercalcemia
• Proteinuria due to overload leakage of monoclonal free light chains
• Acute renal failure

Question 16

Characteristic pathology of kidney injury in plasma cell dyscracia

Answer 16

• Prominent cast in distal tubules
• Cast surrounded by a giant cell reaction

Question 17

Pathogenesis of kidney disease in plasma cell dyscrasia

Answer 17

Light chain tubular damage –> direct toxicity or cast

Question 18

Common hereditary cystic disorders of the kidney

Answer 18

• Autosomal dominant polycistyc kidney disease
• Autosomal resecive polycystic kidney disease

Question 19

Explain the 2 hit model of cytogenesis in ADPKD

Answer 19

Cyst appear to arise from clonal expansion of single tubular cell that undergoes a somatic mutation = second hit

Question 20

What is the function of polycystin 1 and 2 and how are they afected in ADPKD

Answer 20

Polycystin 1 = plasma membrane protein

Polycystin 2 = cation channel

Together they they mediate machnosensory calcium mobilization

Polycystin pathway down-regulates cell proliferation, maintain epithelial differentiation and promote renal tubular reabsorption

This processes are lost in ADPKD

Question 21

Autosomal recessive PKD - what causes it?

Answer 21

Scattered mutations on PKHD1 (polycystic kidney and hepatic disease1) gene. All pts w/ 2 truncating mutations died after birth