Pathology of the Kidney, Ureters and Bladder 2

Question 1

Describe acute presentation of urinary calculi.

Answer 1

Colicky pain (because if stone gets to ureters, peristalsis in ureter, get spasm, colicky pain)

Question 2

Describe chronic presentation of urinary calculi.

Answer 2

Present with secondary infection (massive calculus forming, causing atrophy of renal parenchyma, and because restriction of flow, may get secondary infection), or renal failure, or hematuria (due to bleed caused by damage)

Question 3

Define pyelonephritis.

Answer 3

inflammation of the kidney and its pelvis, caused by a bacterial infection

Question 4

Identify the main possible complications of urinary calculi.

Answer 4

In general, obstructive uropathy, which involves hydronephrosis (The dilation of the pelvis and calyces of one or both kidneys because of the accumulation of urine resulting from obstruction of urine outflow), and may lead to:

• Secondary infection (potentially pyelonephritis) (because massive calculus forming, causing atrophy of renal parenchyma, and because restriction of flow, may get secondary infection) (e.g. pyelonephritis, can be acute or chronic)
• Renal failure (post renal)

Question 5

Are urinary calculi acute or chronic ?

Answer 5

May present as either

Question 6

What are the main composition of urinary calculi ?

Answer 6

Calcium (75%) (oxalate or phosphate)
Uric acid (20%)
Cystine (1%)

Some stones are mixed

Question 7

What are some causes of urinary calculi ?

Answer 7

1) Hypercalcemia
– eg due to sarcoid, Renal tubular acidosis, hyperPTHism

2) Gout

3) Obstruction (associated with infection, which can form the nidus around which the stones form)
– eg vesico-ureteric reflux

4) Genetic component (not necessarily, in some cases)
5) Dehydration (higher concentration of calcium and uric acid in filtrate)

INFECTION (e.g. Proteus species) (in addition to one of these likely), because in spite of supersaturated liquid filtering in kidney (which may contain a lot of calcium), infection may be the nidus around which the stones form.

Question 8

Identify the main forms of bladder disease.

Answer 8

• Inflammation (cystitis, can be but does NOT have to be infective e.g. due to some chemotherapy drugs. Can cause bleeding, i.e. haemorrhagic acute cystitis)
• Infection (bacterial cystitis, e.g. due to prostate obstruction, but more common in females and children)
• Calculi
• Neoplasia

Question 9

Why would calculi form in the bladder rather than in the kidney ?

Answer 9

Due to urine stagnation (chronic retention with high concentration of Calcium and/or urate) + some source of infection forming the nidus around which the stones form

Question 10

Identify the main Urinary Tract Neoplasms.

Answer 10

COMMON
• Bladder – urothelial (transitional cell) carcinoma
• Renal – 4/5 are clear cell carcinoma (ccRCC)

RARER
• Renal carcinomas other than clear cell including transitional cell
• Renal nephroblastoma (Wilms’ Tumour)
• Ureter transitional cell carcinoma
• Renal/bladder sarcoma

Question 11

Describe the main features of Wilm’s Tumours.

Answer 11

WILM’S TUMOR (=NEPHROBLASTOMA)

• Especially affects children (usually <3y)
• WT1 tumour suppressor gene (in order for it
to contribute to cancer, need both copies of the gene to be defective)
• Histology resembles immature or embryonal blastema
• Younger patients have better prognosis (if get tumor v young or in utero, v straightforward genetic pathology whereas in older child, more genetic events, so tumor more complex in terms of molecular pathology)
• Surgery, radio, chemo leads to 90% survival
• Often spontaneous, rarely genetic

Question 12

Describe the main features of RCC.

• Where does it originate ?
• Genetic or sporadic ?
• Risk factors
• Frequent metastases
• 5-year survival rate
• Epidemiology
• Treatment
• Additional information
• Main types

Answer 12

• Originates in ducts, esp PCT
• Mostly sporadic
• Main risk factors: smoking and particularly obesity (also chronic cystic disease and kidney failure)
• Grows along renal vein to ivc (unlike other carcinomas which usually spread through lymphatics)
• Metastasises to lung – “cannonball lesions”
• 50% five year survival – but very stage dependant (If metastasis, 20% 5-year survival whereas if localised, 90%
5-year survival)
• Men > women (probably because more smoking)
• Treatment: Surgery
• Paraneoplastic syndromes (eg pyrexia, increased hormones (eg EPO))

• Commonest type is “clear cell”

• Clear cells, because filled with glycogen, and fat
• Genetic-wise, von Hippel-Lindau Syndrome (VHL gene contributes to sensing mechanism for a cell that is hypoxic so if VHL mutation, tumor thinks adverse hypoxic environment so accumulates glycogen and fats)

• Also, Papillary (second commonest)
– hereditary (autosomal dominant)

• Also, chromophobe

Question 13

Is the incidence of RCC increasing, or decreasing ? Why ?

Answer 13

Increasing, because of rise in obesity

Question 14

What is the usual presentation for RCC ?

Answer 14

• Painless haematuria most common presentation
• Main also involve mass, pain, metastases
• Due to paraneoplastic syndrome, may also present with pyrexia, and potentially polycythemia (due to increased EPO)

Question 15

Which of the urinary tract neoplasms can we screen cancer cells in urine for ?

Answer 15

No cancer cells in urine in RCC, because although these originate from PTs, they are not connected to urinary space (but may look for hematuria)

Cancer cells may be present in urine in bladder cancer (may also look for hematuria)

Question 16

Define paraneoplastic syndrome.

Answer 16

Cancer does something that is not a direct result of presence of tumor bulk, it’s because of some functional characteristic

Question 17

Describe the main types of bladder cancer, along with their management, and their risk factors.

Answer 17

Bladder cancer AKA Urothelial Cell AKA Transitional Cell Cancer

-Many different types:

• Papillary carcinoma (these may be only superficially invasive, or not at all so can be removed BUT can progress into muscle invasive form)
• In situ carcinoma (cells look malignant, but superficial and not invasive yet. They may well become invasive)
• Muscle invasive/deeply invasive (can metastasise. High fatality rate. Management is cystectomy)

-Field change, so following cancer removal, each year you have 5% change of recurrence
-Management can either be cystectomy (e.g. muscle invasive), but in many cases that is not necessary. Instead, if cancer is not invasive, careful monitoring +
follow up (if new cancers recur, can catch them early and surgically remove them without having had to remove the bladder).

Question 18

What are the main risk factors for bladder cancer ?

Answer 18

Smoking
Industrial workers (eg aniline dyes, can be metabolised into carinogen which is excreted in urine)

Question 19

Describe the typical presentation of bladder cancer.

Answer 19

Hematuria, with possible dysuria and potentially obstruction

Question 20

Identify the main causes of acute renal failure.

Answer 20

• Pre-renal (no renal circulation)
– Shock, major trauma, aortic aneurysm
• Renal (damage to renal parenchyma)
– Some glomerulo-nephritides, toxic eg drugs, malignant hypertension (=accelerated hyperT with fibrinoid necrosis of vessels), vasculitis, analgesics
• Post-renal
– Bladder outflow obstruction: stone, tumor, either way can result in hydronephrosis, hydroureter

Question 21

Identify the main effects of acute renal failure.

Answer 21

• Potassium high (can be life threatening because can get dysrhythmias)
• Creatinine high (not excreting it)
• Maybe oliguria
• Hypertension
• Lipids in nephrotic syndrome

Question 22

Identify the main causes of chronic renal failure.

Answer 22

• Pre-renal (no renal circulation)
– Atherosclerosis
• Renal (damage to renal parenchyma)
– Glomerulonephritis, diabetes, hypertension, polycystic
• Post-renal
– Bladder outflow obstructive: prostate enlargement, uterine prolapse, urethral strictures, neurological damage such as MS or spina bidifa (can result in hydronephrosis, hydroureter)

Question 23

Identify the main effects of chronic renal failure.

Answer 23

• Potassium high
• Creatinine high
• Maybe oliguria
• Hypertension (kidney also regulates BP so if damaged kidney in chronic renal failure, response in BP to get more blood, so renin released)
• Anaemia (if damage to parenchyma, may stop producing as much EPO so anemia)
• Small kidneys

Question 24

What are the main causes of obstructive uropathy ? What is its consequence ?

Answer 24

Extrinsic: Tumors (e.g. cervical cancer)

Intrinsic:
• Within the wall - intrinsic tumour e.g. transitional cell carcinoma
• In the lumen - calculi, blood clot etc

Other causes include pregnancy, prostate enlargement, uterine prolapse, urethral strictures, neurological damage (unsure whether these are intrinsic or extrinsic)

Can result in post-renal renal failure

Question 25

Do we have renal failure if only one kidney is affected ?

Answer 25

One kidney may be affected, but if other still working, no renal failure BUT damaged kidney may produce more renin and cause increase in BP, which may damage normal kidney.

Question 26

How does hydronephrosis come about ?

Hydroureter ?

Answer 26

Hydronephrosis occurs when there is bladder outflow obstruction.
Hydroureter as well

Question 27

Does unilateral obstruction of bladder outflow cause renal failure ?

Answer 27

Must be bilateral to cause renal failure

or unilateral if patient has only one kidney

Question 28

Describe the clinical signs of chronic renal failure (potentially even acute?).

Answer 28

• Anamiea (due to renal damage resulting in decrease EPO production)
• Accumulation of nitrogenous waste (urea, ammonia), resulting in pericarditis
• Encephalopathy
• Bone problems: Osteoporosis + Renal Osteodystrophy
• Immunosuppression (so chronic renal failure gives rise to susceptibility to cancer)
• Neuropathy

Question 29

Explain how bone problems occur in chronic renal failure.

Answer 29

Osteoporosis + Renal Osteodystrophy (“a condition due to chronic kidney disease and renal failure, marked by impaired vitamin D metabolism, elevated serum phosphorus levels, low or normal serum calcium levels, and stimulation of parathyroid function”)

Low vitamin D, so problem with calcium metabolism. When calcium levels are too low, PTH released, so hyperparathyroidism may occur. If PTH increases, Calcium increases. Paradoxical because initially damaged bone, release calcium, cause osteoporosis, but end up with increased calcium.

Question 30

How is chronic renal failure managed ?

Answer 30

1) Renal Replacement Therapy:

Dialysis + Diet and Nutrition (e.g. cut down on bananas, since renal failure associated with hyperK+), to make sure the following is undertaken:

• Fluid and electrolyte balance (including Ca++/Phosphate, because renal failure may lead to osteoporosis and hyperPTH)
• Resorption of solutes
• Excretion
• Endocrine
– Renin blood pressure (if any residual parenchyma, renin may be released causing increase in BP, so control that)
– Erythropoietin (so no anemia) (preserve any kidney function for EPO production, and if necessary provide additional EPO)

ALSO immunosuppressed so control that as well (through diet/meds?)

2) Transplantation (potentially)

Question 31

How is acute renal failure managed ?

Answer 31

“Treating cause, treating complications until kidneys recover. In some cases of acute kidney failure, dialysis may only be needed for a short time until the kidneys get better”

Question 32

Identify the main types of dialysis that exist, and summarise how they work. Identify the main cons (and pros) of each method.

Answer 32

1) Haemodialysis (Put blood in through one way, put dialysate fluid in other, and try and exchange out what you don’t want, but have equimolar amounts of what you do want)
CON: Aluminum may accumulate in patients, resulting in bone disease

2) Continuous ambulatory peritoneal dialysis (“Peritoneum surrounding the abdominal cavity is used as a dialyzing membrane for removal of waste products or toxins accumulated as a result of renal failure”)
PRO: Ambulatory, can be done at home
CON:
-Less efficient (if recurrent infections, can get scarring which makes filter less effective)
-Requires a permanent catheter (higher risk of infection)

Question 33

Define dialysate.

Answer 33

Fluid being discarded along with removed toxic substances after they flow back out of the dialyzer.

Question 34

What are the main problems with renal transplantation ?

Answer 34

REJECTION
• Acute cellular rejection 
• Acute antibody mediated rejection
• Acute vascular rejection
-----
• Chronic allograft nephropathy (chronic rejection)

IMMUNOSUPPRESSION
Kidney is immunogenic so requires cross matching, and immunosuppressive therapy, which can lead to:
– risk of infection eg BK virus
– risk of skin cancer eg HPV (which would only cause warts in normal people)
– risk of lymphoma

DEPENDs ON DONOR AVAILABILITY

Question 35

Which kinds of donors may a patient receive a kidney transplant from ?

Answer 35

– Cadaveric, live related, liver unrelated