WEEK 3 - Renal Calculi & Prostate Cancer Flashcards
What are the four main types of renal calculi?
- Calcium stones
- Struvite stones
- Uric acid stones
- Cystine stones
Which form of stone is most common?
Calcium stones
What leads to calcium stone formation?
High levels of Ca in blood and urine - may lead to decreased Ca in the body
What are the four causes of Calcium stones?
- Idiopathic
- Intestinal hyperabsorption of calcium
- Hyperparathyroidism
- Bone demineralisation
How do struvite calculi form?
Form in alkaline urine and in the presence of urease-producing bacteria such as Klebsiella or Pseudomonas
Struvite calculi are more common in?
People who frequently have infections - women are more prone to UTIs and so are more prone to having struvite calculi
When do uric acid calculi develop?
In gout and when there is a high concentration of uric acid in urine (genetic disorder of amino acid disorders)
Are uric acid calculi visible on imaging? Why or why not?
NOP
This is because uric acid calculi form in the urinary epithelium
What period of time in the lifespan are cystine calculi most common?
Childhood
Cystine calculi are due to?
Genetic defect in the renal transport of cystine, leads to cystinuria
List some risk factors for renal calculi development
- Being male
- Being old
- Being indigenous Australian
- Having a family history of kidney stones
- Living in tropical, hot weather
What are three factors influencing calculus growth?
- Crystal growth-inhibiting factors
- Crystal particle retention
- Tissue damage from urea-splitting pathogens
Primary manifestation of renal calculi?
Renal colic (pain that comes and goes) due to peristalsis of the ureters in an attempt to remove calculi Pain is also associated with nausea and vomiting
Sign of renal calculi mid ureter?
Flank pain or pain in the groin or lower abdomen
Sign of renal calculi in the lower ureter?
Urinary urgency and incontinence
What is non colicky pain caused by?
Renal calculi distending the renal calyces or renal pelvis
Two tests for diagnosis of renal calculi?
- Urinalysis
2. Intravenous pyelography
Treatment for renal calculi?
- Calculus removal via surgery
- Prevention via increased fluid intake and increased dietary fibre
Risk factors for prostate cancer?
- Age (older than 65)
- Race (African men more susceptible)
- Family Hx (causes 8x increase in risk)
- Hormones (increased [T])
- Diet (high fat intake increases sex hormones and growth factors)
Protective factor against prostate cancer development?
Diet rich in selenium, vitamin E, lycopene.
Delays development of PCa until 75-85 years of age.
What is degree of differentiation and how is it related to cancer?
Degree of differentiation = degree to which cancer cells are developed
- Poorly differentiated cells = more aggressive cancer cells
- Well differentiated = less aggressive cancer cells
Metastasis is most likely to occur in which areas of the body?
- Bone, followed by
- Lung
- Liver
- Pleura
Where is testosterone found and what are its effects?
Found in circulation - primary circulating androgen
Effects = increased muscle tone, increased libido (desirable effects)
Where is DHT found and what are its effects?
Found in the prostate - primary prostatic androgen
Effects - decreased muscle tone, decreased libido, increased acne (undesirable effects)
What enzyme catalyses the reaction forming DHT from T?
T ——–5 alpha reductase——-> DHT
What receptors do T and DHT bind to, and which binds more potently?
Both bind to androgen receptors (ARs), DHT binds more potently
What are the functions of the glandular epithelium and fibromuscular stroma in the prostate?
- Glandular epithelium = produces secretions for sperm
- Fibromuscular stroma = smooth muscle that houses PICs that contract and mix secretions for sperm
Other than DHT, T can also be converted to what hormone via which enzyme?
T can also be converted to oestogen via aromatase
DHT can be converted to which oestrogenic metabolite?
3-beta-diol
What happens to male sex hormones with age that can lead to prostate cancer?
With age - decreased activity of 5-alpha reductase = decreased DHT. Leads to T being converted to oestrogen instead and causes elevated levels of oestrogen and testosterone
Oestrogen and testosterone together are carcinogenic
How do elevated E and T levels together cause cancer?
Via:
- ROS generation
- DNA toxicity
- Stimulation of IGF (insulin-like growth factor)
- Stimulation of TGF-beta (transforming growth factor beta)
What is the first sign of PCa?
Obstruction of the upper urinary tract = slow urinary stream, nocturia, incomplete emptying, urinary frequency
In prostate cancer, what does the prostate feel like upon digital rectal examination?
Nodular and fixed
Signs of late stages of PCa?
- Bone pain (occurs when cancer metastasises in bones)
- Low back pain
- Oedema in the lower extremities (indicative of liver congestion)
- Enlarged lymph nodes and liver
- Mental confusion when cancer spreads to the brain
Tests for prostate cancer screening?
- Transrectal ultrasound
- Digital rectal exam
- Prostate-specific androgen testing
How is prostate cancer confirmed?
Via biopsy ONLY
Outline the three categories of PCa?
- T1 = asymptomatic, may or may not be palpable on DRE
- T2 = palpable on DRE and confined only to the prostate
- T3 = extended beyond the prostate
Which grading system is used to classify prostatic cancer?
The Gleason grading system
What is radical prostasectomy (RP)?
The complete removal of the prostate and seminal vesicles, pelvic lymph nodes may or may not also be removed.
What is a TURP?
Transurethral resection of the prostate - complete removal of the prostate via the urethra
How is metastatic disease treated in prostate cancer?
With androgen ablation or androgen deprivation therapy
What is an orchiectomy?
Surgical removal of the testicles, effective for symptom reduction and extends survival
What do GnRH analogues do?
Block LH and FSH = decrease testosterone production
What do anti-androgens do?
Block testosterone uptake by the prostate
Why is metformin used in treatment for metastatic disease as a result of PCa?
Metformin is used for its antineoplastic properties - eg. prevents cellular proliferation
How is bone pain associated with late-stage PCa treated?
With bisphosphonates (eg. Pamidronate) - inhibit osteoclastic activity
