Pathophysiology: Urinary Obstruction

Front 1

What locations can urinary tract obstruction occur in?

Back 1

*Anywhere throughout the collecting system including:
1) Intratubular (e.g. crystals precipitating in tubules, as seen in IV Acyclovir).
2) Intraluminal (lesion is within the lumen of collecting system, such as a stone).
3) Intramural (lesion arises from wall of collecting system, such as bladder tumor causing obstruction).
4) Extrinsic compression (process outside the collecting system causes compression such as a pelvic tumor, or prostate enlargement).
5) Functional obstruction (e.g. neurogenic bladder).

Front 2

What is hydronephrosis?

Back 2

*A stone has caused the obstruction here.

Front 3

Most common cause of obstruction in men?

Back 3

*Prostatic enlargement; urethral obstruction.

Front 4

What happens in the early stages of the pathogenesis of urinary obstruction?

Back 4

1) Increased pressure in Bowman’s space (pressure in this space normally near-zero).

2) Diminished filtration across basement membrane because of smaller pressure gradient.

3) Attempted compensation by increasing blood flow to glomerulus to raise intraglomerular pressure and favor filtration.
*Dilation of afferent arteriole.

Front 5

What happens in the middle stages of the pathogenesis of urinary obstruction?

Back 5

*(4-5 hours).

*Reduced GFR from obstruction leads to gradual reduction in renal blood flow:
1) Likely mediated by decreased distal delivery of sodium from reduced GFR.

2) Thromboxane A2 and other factors (angiotensin II, decreased endothelium-derived relaxing factor) contribute to afferent vasoCONSTRICTION, further reducing GFR!

Front 6

What happens in the late stages of the pathogenesis of urinary obstruction?

Back 6

1) Dilation of urinary collecting system.
2) Increased lymphatic drainage.
3) Reduction in GFR.

*Above factors lead to gradual reduction in tubular pressure back toward normal.

Front 7

What happens to tubular function during obstruction?

Back 7

*Decrease in GFR and decrease in delivery of filtrate to distal nephron can lead to confusing laboratory studies:
1) Decreased urine Na concentration (often <20meq/L; but this ISN'T volume depletion).
2) Increased urine osmolality (often >500mosm/kg).

*Due to injury in the distal nephron, handling of K, acid-load and water are impaired:
1) Hyperkalemia appears out of proportion to the severity of kidney injury (may be an altered response to aldosterone).
2) You see acidosis (non-anion gap) from impaired distal acidification of urine.
3) In cases of partial obstruction, response to ADH may be impaired, leading to polyuria and excess H2O losses.

Front 8

What happens to tubular function once a urinary obstruction is corrected?

Back 8

*Tubular function remains impaired for a time even after relief of obstruction!

*“Post-obstructive diuresis”:
1) You see appropriate mobilization of retained fluid.
2) You see osmotic diuresis from excess solute concentrations (e.g. urea).
3) But there is persistently impaired Na and H2O handling.
4) So you need to watch carefully for volume depletion or electrolyte abnormalities (hypokalemia, H2O depletion).

Front 9

What happens to the GFR in urinary obstruction?

Back 9

*GFR in the affected kidney is clearly reduced.

*Overall GFR is usually preserved IF obstruction is UNILATERAL:
1) Remaining kidney increases its filtration (can double) to compensate.
2) Serum laboratory values may be normal or near-normal.

Front 10

What are the Clinical Features of obstruction?
unilateral--
bilateral--

Back 10

1) Unilateral:
*Flank pain or fullness.
*Pain may be colicky and severe, especially if from an obtructing stone.
*Hematuria if stone-related.

2) Bilateral:
*History of difficulty urinating.
*Suprapubic fullness/tenderness.
*Decrease in urine output (notoriously unreliable clue).
*Increase in urine output (if partial obstruction).

Front 11

What are the Lab findings in obstruction?
unilateral--
bilateral--

Back 11

1) Unilateral:
*All labs usually normal (unless patient only has one kidney).

2) Bilateral:
*Elevated BUN, Creatinine.
*Elevated BUN/Cr ratio, decreased urine sodium, high urine osmolality may all MIMIC volume depletion.

Front 12

How do you make the diagnosis of obstruction?
What do you look for on history and PE?
Labs?

Back 12

*History may provide clues (e.g. history of urinary difficulty or flank or pelvic fullness).

*Physical Exam:
1) Flank tenderness.
2) Lower abdominal/pelvic fullness-- bladder can be palpable.
3) Rectal exam (men) to look for enlarged prostate.
4) Pelvic exam (women) to look for pelvic malignancy.

*Laboratory:
*BUN/Cr and urine indices can be misleading.
*Urinalysis findings of blood and/or crystals can be suggestive of stones (blood and crystals) or malignancy (blood).

Front 13

What therapeutic maneuver can you do to help make a diagnosis of obstruction?

Back 13

*Post-void residual:
-Placement of urethral catheter after patient has attempted to void.
-Greater than 100ml retained urine indicates incomplete bladder emptying.

Front 14

In diagnosing obstruction, what imaging can help?

Back 14

1) Intravenous pyelogram:
*RARELY, IF EVER, performed because of risk of contrast-related kidney injury.

2) Ultrasound:
*Looks for hydronephrosis, dilated renal pelvis.
*Can sometimes identify stones.

3) CT scan:
*More precisely determines location of obstruction.
*Particularly useful in patients with stones.

Front 15

Back 15

IVP showing hydronephrosis. These are rarely done because contrast injures the kidneys.

Front 16

Back 16

*Top: Normal ultrasound.
*Bottom: Hydronephrosis.

Front 17

Back 17

CT scan showing stone causing obstruction.

Front 18

How do you treat an obstruction?

How quickly can normal GFR be regained?

Back 18

*Definitive treatment is relief of obstruction.

*Response to therapy depends on duration and severity of obstruction:
-Expect a return of GFR to normal if obstruction relieved WITHIN A FEW DAYS to a week.
-Complete obstruction UNLIKELY to regain much function after 1-2 weeks.
-Partial obstruction MAY respond favorably even after weeks to months.

Front 19

Take home points in treating urinary obstruction:

Back 19

*Timely intervention is necessary to prevent permanent injury.

*Some laboratory features and even clinical signs can be misleading if obstruction is not suspected.

*Tubular function is impaired, even during the initial stages of recovery.

Front 20

How common are kidney stones?

Back 20

*Very common, affecting up to 10% of the population (lifetime risk).
*Accounts for 1/1000 hospitalizations (generally for pain control), many more ER visits.
*Substantial cost, both in surgical/medical therapies and in loss of productivity.
*Severe pain!!

*Incidence:
-Around 10% lifetime (white males).
-Appears to be rising.
-Gender, ethnic, regional, and seasonal variations.

*Recurrence:
-40-50% recur within 5 years.
-Recurrence rate as high as 75% over 25 years.

Front 21

How do stones present?

Back 21

*Renal colic: Severe flank pain, abrupt onset with radiation to groin.

*Gross or microscopic hematuria.

*Nausea/vomiting, occasional ileus (decrease in intestinal motility).

Front 22

What are the Clinical Findings in kidney stones?
What do you look for on PE & Labs?

Back 22

*Exam:
-Mild fever.
-Flank tenderness.

*Lab:
-Hematuria.
-Possibly crystalluria.
-Elevated WBC.
(∆= pyelonephritis)

Front 23

Epidemiologically, stone formation is more likely in someone who fits what profile?

Back 23

*Stone formation more likely in:
-White.
-Male.
-Live in the South.
-Summertime (early winter in women).

Front 24

What's the chemical makeup of kidney stones?

Back 24

Calcium oxalate 75%
Uric acid 10-15%
Struvite 15-20%
Cystine 1%

Front 25

What is the Life Cycle of the Stone?

Back 25

*Supersaturation (for calcium oxalate, this occurs in 50% of adults).

*Nucleation (forms submicroscopic particles): needs to attach to epithelial surface or grow quickly to avoid being flushed out.

*Growth (may take weeks-months-years).

Front 26

What are the natural Inhibitors of stone formation?

Back 26

1) Citrate: Binds calcium in urine to form soluble complex.

2) Magnesium.

3) Macromolecules:
-Nephrocalcin.
-Tamm-Horsfall protein.

Front 27

What are Predisposing anatomic factors to stone formation? 3

Back 27

1) Horseshoe kidney.

2) Medullary sponge kidney (congenital, mostly women): cystic dilation of ducts-- stagnant urine flow.

3) Polycystic kidney disease.

Front 28

Back 28

Calcium oxalate stones. Look like envelopes.

Front 29

What are the 3 causes of calcium oxalate stone formation?

Back 29

*Crystalloid concentration:
1) Hypercalciuria
2) Hyperoxaluria.
3) Low urine volume.

Front 30

What are the 3 "promoters" of calcium oxalate stone formation?

Back 30

1) Hyperuricosuria (Uric acid “seed” crystal can promote calcium oxalate stone).

2) High sodium diet (promotes calcium excretion in urine).

3) Low-carbohydrate (Atkins) diet:
*Presumably from high protein load, increased purine metabolism and uric acid levels, also chronic acidosis and decreased fluid intake.

Front 31

Discuss hypercalciuria as a risk factor for stone formation?

What are the usual causes of hypercalciuria?

Back 31

*Present in 50% of stone formers (5% have primary hyperparathyrodisim).

*Hypercalcemia + hypercalciuria should raise suspicion for primary hyperparathyroidism.

*Other rarer causes: RTA, sarcoidosis.

Front 32

Discuss Hyperoxaluria as a risk factor for stone formation:

What all causes Hyperoxaluria?

Back 32

*Normal excretion is 15-40mg daily.
*If someone has excess excretion, it is a result of either increased synthesis or dietary absorption.

*Increased synthesis in:
1) Congenital disorders (primary hyperoxaluria types 1 and 2).
2) Excess vit C intake enhances oxalate synthesis in some individuals.

*Increased absorption:
-Normally forms an insoluble complex with Ca in the gut.
-Dietary calcium restriction can actually lead to enhanced oxalate absorption.
-High oxalate diets lead to increased absorption.
-Intestinal malabsorption syndromes (requires an intact colon to absorb the oxalate) like Crohn’s disease, ileal bypass can increase absorption,

Front 33

Discuss the role of urine volume in calcium oxalate stone formation:

Back 33

*“Stone clinic effect”: activity of nephrolithiasis appears to diminish during treatment regardless of therapy.

*Saturation of all crystalloids falls with increased urine volume.

*>2L/day urine output is goal, including at night.

Front 34

Describe the treatment of calcium oxalate stones:
-Universally
-In hypercalciuria
-In hyperoxaluria

Back 34

*Universal: Increase fluid intake (>2L per day urine volume).

*Hypercalciuria:
1) Diet (reduce sodium, reduce animal protein, moderate calcium intake).
2) Thiazide diuretics (reduce urinary calcium excretion).
3) Potassium citrate (increase urinary citrate – stone inhibitor).

*Hyperoxaluria:
1) Low oxalate diet (avoid tea, colas, rhubarb, spinach, chocolate).
2) Calcium supplements (to bind dietary oxalate).

Front 35

Back 35

Uric Acid stones.

Front 36

Discuss uric acid stones:

How do we treat them?

Back 36

*Radiolucent (do not appear on regular X-rays).

*Apart from uric acid stones, also predisposes to calcium stones (may serve as nidus for stone formation).

*Much more soluble at higher pH, so urinary alkalinization (pH 6-7) is treatment.

*Gout + kidney stones is indication for allopurinol.

*Can dissolve spontaneously with treatment.

*Treatment also with purine restricted diet (can add allopurinol if production is excessive).

*Do not use Probenecid!!! (enhances renal excretion of uric acid).

Front 37

Back 37

Infection stones (struvite). "Coffin lid" stones. Cats get these.

Front 38

Discuss Infection stones:
When do we see these?
How do we treat these?

Back 38

*Struvite (Magnesium ammonium phosphate) or apatite (calcium phosphate).

*Forms during infection with urease positive bacteria (Proteus or Providencia). The stones themselves become infected.

*Urine pH is elevated to 8 (urea cleaved to ammonia).

*Difficult to clear.

*Antibiotics first, usually followed by stone removal (may need combination percutaneous and ESWL approach).

*All stone fragments need to come out, or the patient may require chronic suppressive antibiotics.

Front 39

Discuss Cystine stones:
Who gets these?
How do we treat? 2

Back 39

*Rare associated with inherited disorder (COAL) with reduced tubular absorption of cystine, ornithine, arginine, lysine.

*Very poorly soluble (250mg/L) so requires high urine volumes.

*If concentration too high, can use pharmacotherapy with penicillamine or tiopronin.

Front 40

Back 40

Cystine stones

Front 41

What drugs may cause cystine stones? 3

Back 41

*Indinavir, sulfadiazine, triamterene.
*Shown: Indinavir crystals.

Front 42

What's the workup for stones?

Back 42

1) First stone--> Stone analysis, U/A, calcium, phosphate, uric acid, BUN/Cr.

2) Imaging to make sure only one stone.

Front 43

Back 43

*Enormous struvite stone. Surgery indicated.

Front 44

What's the workup for someone who is having recurrent stones?

Back 44

*24h collection of calcium, phosphate, oxalate, citrate, uric acid, creatinine, volume, pH, urea nitrogen, sodium, magnesium.

*Gives you all the variables of stone formation.

Front 45

Who needs a urologist for stones?

Back 45

*90% of stones pass spontaneously.

*Ureteral stones <4mm likely to pass within a year (70%).

*>8mm unlikely to pass (<10%).

Front 46

What are the Indications for removal of a stone? 3

Back 46

*Complete obstruction needs relief in 2 weeks to prevent permanent renal injury.

*Partial obstruction in 4-6 weeks.

*Fever (emergency decompression with stent or percutaneous nephrostomy, remove stone after infection clears).

Front 47

Take home points regarding stones:

Back 47

*Nearly everyone has risk factors for stone formation.

*Stones frequently recur.

*Increasing fluid intake is appropriate management for all types of stones.

*Larger stones, or stones causing obstruction require surgical removal.