Renal and Urinary tract Pathology

Question 1

What is the difference between the mesangium and the interstitium of the kidney?

Answer 1

The mesangium is the connective tissue found inside the glomeruli, while the interstitium is the connective tissue where the tubules and glomerulus resides

Question 2

What is meant by tubulointerstitial nephritis?

Answer 2

• It is an inflammatory disease that primarily involves the interstitium and tubules
• If a bacterial infection caused the inflammation, the renal pelvis would be primarily be involved, and thus it is called Pyelonephritis
• If the inflammation was due to a non-bacterial infection, it will be called interstitial nephritis

Question 3

What are the types of tubulointerstitial nephritis?

Answer 3

1) Acute pyelonephritis

2) Chronic pyelonephritis

Question 4

What is the most common way by which bacteria reaches the kidney?

Answer 4

Ascending from the lower urinary tract

• It could also be caused by hematogenous spread

Question 5

What is meant by septicemia?

Answer 5

When we find both bacteria and toxins in the blood

Question 6

What is meant by acute pyelonephritis?

Answer 6

• Suppurative inflammation of the kidney and the renal pelvis
• It is caused by a bacterial infection (usually Gram -ve bacilli “like: E.coli, Proteus, Klebsiella, Pseudomonas”)
• It is associated with a lower UTI

Question 7

How does the bacteria reach the kidney?

Answer 7

• Ascending infection from the lower urinary tract
• Hematogenous spread

Question 8

How does the bacteria ascend from the lower urinary tract?

Answer 8

1) Urethra: Colonization of the urethra usually from the perineum (due to poor hygiene)

2) From the urethra to the urinary bladder:

• Urethral instruments (scopes, catheters, etc)
• More common in females due to:
• Proximity of the urethra to the rectum
• Shorter urethra
• Trauma to urethra during sexual activity
• Hormonal changes (which affect the bacterial adherence)

3) Colonization of the urinary bladder: Usually due to stasis of urine which could be due to:

• Obstructed urine flow (stones)
• Impaired nervous system, which will affect the emptying of the bladder (like in diabetes)

4) Bacteria go to the ureters: due to vesicoureteral reflux, where the bacteria from the contaminated urine ascend up (usually due to congenital abnormalities where the part of the ureter that is embedded into the bladder is short and not oblique)

5) Kidney: Reflux of the urine into the kidney, which will affect the renal pelvis first and thus (acute pyelonephritis)

Question 9

Describe the gross morphology of acute pyelonephritis

Answer 9

Yellowish abscess (most imp), which could be unilateral or bilateral

Question 10

Describe the microscopic morphology of tubulointerstitial nephritis

Answer 10

1) Interstitial neutrophilic infiltration

2) Intratubular aggregates of neutrophils (tubular necrosis)

3) Pus cells

• THE GLOMERULI WILL APPEAR NORMAL
• If there was a cast formed, then the infection is in the kidney if not, then it is down in the urinary tract

Question 11

What are the complications of tubulointerstitial nephritis?

Answer 11

1) Papillary necrosis (in diabetes)

2) Pyonephrosis (accumulation of pus within the renal pelvis, calyces, and ureter

3) Perinephric abscess (when the suppurative infection breaks the renal capsule and spreads in the perinephric tissue)

Question 12

What are the urinary findings in tubulointrstitial nephritis?

Answer 12

1) Pus cells (showing a lot of leukocytes, which could be due to an upper or lower UTI)

2) WBC cats (formed in tubules and thus indicate an upper infection, “acute pyelonephritis”)

Question 13

What is meant by chronic pyelonephritis?

Answer 13

• It is the interstitial inflammation and fibrosis of the renal parenchyma with a grossly visible scar and a deformity of the pelvicalyceal system in patients with a history of UTI
• It is an important cause of end-stage renal disease

Question 14

What are the types of chronic pyelonephritis?

Answer 14

1) Chronic obstructive pyelonephritis

2) Chronic reflux-associated pyelonephritis (reflux neuropathy)

Question 15

What is meant by chronic obstructive pyelonephritis?

Answer 15

• When an obstruction (due to a bladder stone, for example leads to stasis of urine) and thus infection
• It is usually associated with recurrent bouts of inflammation and scarring

Question 16

What is meant by chronic reflux-associated pyelonephritis (reflux neuropathy)?

Answer 16

• Due to congenital vesicoureteral reflux and intrarenal reflux + UTI

Question 17

What is the most common cause of chronic pyelonephritis?

Answer 17

Recurrent UTI, which could be due to chronic obstructive pyelonephritis or chronic reflux-associated pyelonephritis

Question 18

What is the gross morphology of chronic pyelonephritis?

Answer 18

• Fibrosis of the pelvis, as it is chronic
• Thinning of the cortex and medulla
• Blurred cortico-medullary junction
• The cortical surface is not smooth
• It could be unilateral or bilateral, and when it is bilateral, the kidneys are not equally damaged

Question 19

What is the microscopic morphology of chronic pyelonephritis?

Answer 19

1) Interstitium: fibrosis and chronic inflammation

2) Atrophy of the tubules

3) Dilation of the tubules and they get filled with eosinophilic material (thyroidization)

Question 20

What is meant by acute kidney injury?

Answer 20

• AKA: Acute tubular necrosis (as this is the most common cause of AKI), Acute tubular injury (ATI)
• It is the acute decline in renal function (a reversible acute BUN and serum creatinine)
• If prerenal ARF is treated in time, the symptoms are usually reversible
• If prerenal AKI is not treated soon or adequately, it can lead to ATN.

Question 21

What are the causes of acute kidney injury?

Answer 21

1) Prerenal (impaired perfusion):

• Hemorrhage
• Shock
• Hypovolemia
• Cardiac failure
• Sepsis
• Vascular occlusion

2) Renal:

• Glomerulonephritis
• Drugs
• Toxins
• Prolonged hypotension
• Inflammatory diseases
• Infection
• Inflammatory diseases

3) Post-renal:

• Urinary calculi
• Benign prostatic enlargement
• Carvical cancer
• Urethral strictures/valves
• Retroperitoneal fibrosis

Question 22

In which part of the nephron is ATI most common and why?

Answer 22

• It affects the proximal convoluted tubule mainly as they are sensitive to hypoxia (ischemic ATI) and Toxins (Nephrotoxic ATI), due to its 1. High intracellular concentrations of molecules (both secreted and re-absorbed), 2. Its high exposure to concentrations of the luminal solutes, 3. It has a high rate of oxygen consumption

Question 23

Describe the pathogenesis of acute tubular injury

Answer 23

• We have an apical surface and a basolateral surface
• On the apical surface we have glucose and sodium symporter, which takes any sodium or glucose that goes to the urine
• On the basolateral membrane we have a sodium-potassium antiporter where it takes the sodium into the blood and the potassium into the lumen
• When ischemia occurs, the sodium-potassium pump moves to the apical surface, leading to:
• Hyponatremia
  1. Increased secretion of sodium

2. Reduced reabsorption of sodium
3. The macula densa will sense the high sodium concentration and will send impulses to vasoconstrict the afferent arteriole (tubuloglomerular feedback as it interpreted the increased sodium as a high GFR) this will increase the ischemia
4. Ischemic cells will recruit and cause further inflammation (as they express cytokines and adhesion molecules), causing the cells to detach and go into the lumen (which will cause oliguria due to obstruction of the lumen by the casts)

Question 24

Summarize the pathogenesis of acute tubular injury

Answer 24

• Toxic injury

1) Toxic injury

2) Tubular injury

3a) Tubular backleak

• Decreased urine output

3b) Sloughed cells lead to obstruction

• Decreased urine output (oliguria)
• Decreased GFR

3c) Interstitial inflammation (due to the expression of cytokines and adhesion molecules which will recruit leukocytes)

• Decreased GFR
• Ischemia

1) Ischemia

2) Vasoconstriction

• Tubular injury (same cycle as above)
• Decreased GFR

Question 25

Describe the morphology of acute tubular injury

Answer 25

- Evidence of tubular injury: 1. Flattening of the tubular epithelial cells (from columnar to cuboidal) 2. Blebbing of the brush border (no microvilli) 3. Vaculization and necrosis of the cells (due to the inhibition of the sodium-potassium pump) 4. Detachment of the cells from the underlying basement membrane into the lumen 5. Proteinaceous casts in the tubular lumen 6. Edema and inflammatory infiltrate of the interstitium

Question 26

What are the differences in the morphology between ischemic ATI and Nephrotoxic ATI?

Answer 26

- Ischemia ATI: 1. The lesions are in the proximal tubule and the ascending thick limbs 2. Focal tubular epithelial necrosis with large skip areas in between 3. Rupture of the tubular basement membrane - You can think to yourself Ischemia is a rude karen that keeps INTERRUPTING you while speaking and eventually you burst into anger. (skip or interrupted areas and rupture in the membrane) - Nephrotoxic ATI: 1. Lesion in proximal tubule 2. No skip areas 3. No rupture of the tubular basement membrane -For toxins take it as if they come for everyone, they do NOT skip anyone so you are NOT alive to be angry and burst into anger. (NO skip areas, NO rupture, and as mentioned in the slides in the proximal tubules on the other hand ischemia can also include ascending thick limbs)

Question 27

What are the clinical features of acute tubular injury?

Answer 27

1) Oliguria 2) Increased plasma BUN, and creatinine 3) Hyperkalemia 4) Metabolic acidosis 5) Hyponatremia

Question 28

What are the urine findings of acute tubular injury?

Answer 28

1) Sodium excretion in urine will increase (distinguishes it from prerenal ARF) 2) Muddy brown casts (necrotic epithelial cells in urine)

Question 29

How to diagnose acute tubular injury?

Answer 29

- FENa>3% - FEna = 100 * (Sodium in urine * creatinine in plasma) / (sodium in plasma * creatinine in urine)

Question 30

What is the gross picture of urinary tract obstruction?

Answer 30

- It depends on the level of obstruction, where it could be - In the kidneys (hydronephrosis, pyonephrosis) - In the ureter (hydroureter, hydronephrosis) - Hydro means the structure was expanded by urine, while pyo means the structure was expanded by pus - These enlargments can lead to pressure atrophy which can cause kidney failure

Question 31

Compare between patients one that had very high calcium oxaloacetate and one with high oxaloacetate but also high RBC and WBC in regards to the prevalence of a stone

Answer 31

Althoug patient one has a higher oxaloacetate we would suspect that he has a stone but In the patient with high RBC and WBC we would suspect an injury which means there is a stone already

Question 32

What is urolithiasis and where can it be formed?

Answer 32

- They are stones that can be formed anywhere in the urinary tract: 1) Nephrolithiasis: Renal stone (found in the collecting system of the kidney) 2) Urolithiasis: Stones formed anywhere but the kidney 3) Primary stones: Stones that are formed in sterile urine (usually in the kidney) 4) Secondary stone: Stones that are formed in infection/obstruction

Question 33

What are the risk factors for developing a stone?

Answer 33

1) Familial predisposition 2) Diet (deficiency of vitamin A) 3) Infection 4) Urinary stasis 5) Changes in urinary pH (alkaline urine is a predisposition to one type of stone, however, acidic urine is a predisposition to more than 3 types of stone) 6) Decreased urinary citrate 7) Altered urinary solutes (like dehydration)

Question 34

What are the types of renal stones?

Answer 34

1) Calcium stone (composed of calcium oxalate/calcium phosphate or a mixture of both) 2) Triple stone/struvite stone (composed of magnesium, ammonium and phosphate + CaPO4) 3) Uric acid stone 4) Cystiene stone

Question 35

What forms the triple stone/sturvite stone?

Answer 35

1) Magnesium 2) Ammonium 3) Phosphate 4) CaPO4

Question 36

What are the causes of calcium stones?

Answer 36

1. Hypercalciuria without hypercalcemia (50%) 2. Hypercalcemia and hypercalciuria like in parathyroidism 3. Hyperuricosuria (hypersecretion of uric acid like in gout) 4. Hyperoxaluria (hyperabsorption of oxalate, occurs in Crohn's disease) 5) Idiopathic

Question 37

Describe the morphology of calcium stones

Answer 37

1. Radiopaduq (white color in X-ray) - Calcium oxalate stone: 2. Irregular in shape 3. Hard 4. Covered with sharp projection 5. Black - Calcium phosphate: 1) Soft 2) Pale

Question 38

What are the causes of struvite/triple stone?

Answer 38

- Composed of magnesium, ammonium, phosphate, CaPO - Infection of the UT by urea-splitting bacteria (like proteus), which converts urea to ammonia which will result in alkaline pH - The struvite stone first of all is the biggest (remember it’s made up of 3 materials) and is the only type of stone that grows in alkaline pH because it is usually after an infection of the proteus bacteria that splits the urea to ammonia making the urine alkaline

Question 39

Describe the morphology of a struvite/triple stone

Answer 39

1. Radiopaque (Whit in X-ray) 2. Solitary 3. Yellow-white 4. Largest stone 5. Sometimes it fills the pelvis and calyces (staghorn calculus)

Question 40

What are the causes of a uric acid/urate stone?

Answer 40

1) Hyperuricemia (gout) 2) Leukemia (malignant cells that keep proliferating and dying, I have high cell turnover, so the contents of the cell get poured out like DNA 🡪 purines 🡪 uric acid. This is especially seen post chemo) 3) Stones formed due to acidic urinary pH

Question 41

What is the morphology of a uric acid/urate stone?

Answer 41

1) Smooth 2) Hard 3) Multiple 4) Shows lamination on a cut section 5) Radiolucent (as calcium is not present, it appears black in X-ray)

Question 42

What is the etiology of a cystine stone?

Answer 42

1) Cystinuria (genetic defects in the renal reabsorption of cysteine or other amino acids) 2) Stone that is formed due to an acid urine

Question 43

Describe the morphology of a cysteine stone

Answer 43

1) Radiopaque 2) Smooth 3) Hard 4) Multiple 5) Yellow and waxy

Question 44

What are the complications of renal stones?

Answer 44

1) Migration leads to pain 2) Infection "pyelonephritis and pyonephrosis" 3) Malignancy "squamous metaplasia and later squamous cell carcinoma" 4) Obstruction "Hydronephrosis"

Question 45

What is the treatment of stones?

Answer 45

The treatment is to make the urine more acidic (for struvite stone) and the same for the others, the pharmacological treatment is to reverse what is happening in the pathology.