Genitourinary Flashcards

Question

Pathophysiology of AKI

Answer 1

A common link between the aetiology of AKI is a reduction in the glomerular filtration rate (GFR), which may occur secondary to hypoperfusion (pre-renal), renal parenchymal damage (intrinsic renal) or obstruction to urinary flow (post-renal). **Acute tubular necrosis (ATN) pathophysiology:** ATN can be divided into three stages: - **Initiation**: acute decrease in renal perfusion causing a reduced GFR - **Maintenance**: GFR remains low for days or weeks - **Recovery**: GFR recovers, regeneration of tubulointerstitial cells, polyuric phase may occur Acute tubular necrosis (ATN) has many causes, most of which can be thought as 'ischaemic' or 'nephrotoxic' in nature. Ischaemic causes include the causes for pre-renal, Nephrotoxic causes include medications (aminoglycosides, chemotherapies), contrast, myoglobin (in rhabdomyolysis) and multiple myeloma. Failure of adequate renal perfusion results in ischaemia. Ongoing ischaemia causes a pro-inflammatory response with the release of cytokines, oxygen free radicals and activation of leucocytes and coagulation pathways. At this point, if renal perfusion is not restored, the ongoing ischaemia can lead to cellular injury. Tubular cells are particularly susceptible due to their limited blood supply and high metabolic demand. Damaged tubular cells slough off into the lumen as obstructive casts that further hamper the GFR. Following restoration of a normal GFR the kidneys may recover and tubulointerstitial cells regenerate. A polyuric phase often occurs, this is thought to be due to failure of adequate reabsorption by the recovering tubules.

Answer 2

Due to hypovolaemia: - **Reduced capillary refill time** - **Dry mucous membranes** - **Reduced skin turgor** - **Cool extremities** - **Thirst** - **Reduced urine output** - **Dizziness** - **Confusion: in elderly patients** - **Signs of fluid loss: excessive sweating, vomiting, diarrhoea and polyuria** - **Orthostatic hypotension** - **Tachycardia** Due to hypervolaemia: - **Ankle swelling** - **Orthopnoea:** sensation of breathlessness in lying down position - **Paroxysmal nocturnal dyspnoea** - **Dyspnoea** - **Raised JVP** - **Ascites**

Answer 3

- **Vascular:** arterial hypertension; peripheral oedema - **Nephrotic syndrome:** heavy proteinuria; hypoalbuminaemia and oedema - **Nephritic syndrome:** haematuria; proteinuria; oliguria and hypertension - **Tubulo-interstitial disease:** arthralgia, rashes and fever

Answer 4

- **Urinary stones:** loin-to-groin pain, haematuria, nausea and vomiting. - **Prostatic issues:** dysuria, frequency, terminal dribbling, hesitancy - **Obstruction at the bladder neck:** may be associated with a palpable bladder and a tender suprapubic area.

Answer 5

- **Hyperkalaemia:** arrhythmias - **Uraemia:** - Fatigue, weakness, anorexia, nausea and vomiting - Followed by confusion, seizures and coma - May be pruritus and bruising - **Volume overload:** - Oedema - Pulmonary oedema: breathlessness - **Impaired platelet function:** bruising and increased GI bleeding

Answer 6

- **Assess the current fluid status** of the patient, looking for signs of hypo- or hypervolaemia including checking their urine output. - **Review their medical chart l**ooking for any potential nephrotoxic drugs and their fluid status over the last few days (e.g. have they had a positive or negative fluid balance).

Answer 7

- **FBC:** anaemia and very high ESR suggests myeloma or vasculitis as underlying cause - **U&E** - **Blood gas:** check for metabolic acidosis - **Creatine kinase** - **Vasculitis screen** (e.g. ANCA, ANA) - **Clotting** - **Blood film** - **Complement** - **Immunoglobulins** - **Serum electrophoresis** - **Virology** (hepatitis B/C) - **Urinalysis: dipstick and microscopy** - **Urine osmolality and electrolytes checked** - **Leucocytes** and **nitrites** suggest infection - **Protein** and **blood** suggest **acute nephritis** (but can be positive in infection) - **Glucose** suggests diabetes

Answer 8

- **ECG:** to look for hyperkalaemic changes i.e. arrhythmias - **Imaging:** - **Ultrasound:** look for obstructive uropathy and hydronephrosis - **Non-contrast CT:** if there is a high degree of suspicion of urinary stone - **CXR:** looking for signs of overload - **Renal dopplers:** renal vascular assessment - **Magnetic resonance angiography:** renal vascular assessment - **Renal biopsy:** if cause still not known

Answer 9

- **Regular monitoring:** fluids, urine output, daily weights, baseline creatinine, serial U&Es - **Cease nephrotoxic drugs** (e.g. ACEi, NSAIDs, spironolactone) - **Regular prescriptions should be altered** to reflect the change in creatinine clearance - Hypovolaemia: **IV fluids** - Hypervolaemic: **fluid restriction and diuretics e.g. furosemide** - Obstruction: **catheter insertion; surgery to relieve obstruction** - Electrolyte abnormalities e.g. hyperkalaemia: - **Protection of the myocardium:** 10ml of 10% calcium gluconate. - **Reduce extracellular potassium**: aim is to drive potassium into the intracellular compartment. Insulin and beta agonists (e.g. 2.5mg nebulised salbutamol) are given. - **Additional**: stop or adjust potassium-sparing or potassium-containing medications. Resins can reduce potassium absorption but these take hours/days to have effect. - Metabolic acidosis: **sodium bicarbonate or dialysis** - **Treat sepsis according to sepsis 6 guidelines** - **Complications require urgent dialysis**

Answer 10

- **Hyperkalaemia:** when the individual is oliguric, potassium isn’t effectively removed from the blood. - **Fluid overload** - **Metabolic acidosis** - **Uraemia** - **Uraemic complications:** e.g. encephalopathy, pericarditis

Answer 11

RENAL DRS 26 R - Record baseline creatinine E - Exclude obstruction N - Nephrotoxic drugs stopped A - Assess fluid status L - Losses +/- catheterisation D - Dipstick (Blood +/- protein) R - Review meds S - Screen 26 - Creatinine rise for AKI diagnosis

Answer 12

Renal cell carcinoma (RCC) is an adenocarcinoma most commonly arising from the epithelium of the proximal convoluted tubule. It is also known as hypernephroma or Grawitz tumour

Answer 13

- RCC is the most common type of kidney cancer in adults - Highest incidence is in the Czech republic - Peak age between 60 and 70 years of age - M>F

Answer 14

- **Increasing age**: peak age between 60 and 70 years of age - **Male**: 3:2 ratio of men to women - **Black ethnicity** - **Hereditary** e.g. Von Hippel-Lindau - **Smoking** - **Obesity** - **Hypertension** - **Haemodialysis**

Answer 15

**Renal cell carcinomas form from epithelial cells in the proximal convoluted tubule of the kidney, located in the renal cortex.** The most common type of renal cell carcinoma is **clear cell carcinoma.** It is composed of polygonal epithelial cells and are filled with clear cytoplasm full of carbohydrates and lipids. Other subtypes include: Papillary: Second most common and is bilateral in 33% of cases Chromophobe: Large, pale cells and associated with an excellent prognosis Multilocular cystic: Excellent prognosis Renal medullary: Very aggressive and patients are often metastatic at presentation **RCC's have been linked to mutations on the short arm of chromosome 3 (3p)**. One of the main genes involved is the **VHL gene**, which codes for the **von Hippel-Lindau tumor suppressor protein (pVHL)** which is normally expressed in all tissues. Mutations in pVHL can allow IGF-1 pathway to go into overdrive. This causes dysregulated cell growth and it also upregulates specific transcription factors called hypoxia-inducible factors, which in turn help generate more vascular endothelial growth factor (VEGF), as well as VEGF receptor, leading to growth of new blood vessels. This results in tumour formation. **RCCs can arise sporadically or they can be a part of an inherited syndrome:** - Sporadic tumours (due to mutations in VHL gene) are usually solitary tumours in the upper pole of the kidney, and most often happen among older men that smoke. - Inherited syndromes e.g von Hippel-Lindau can also give rise to RCC. In this situation the tumours typically affect younger men and women and often involve both kidneys.

Answer 16

- **Hypertension: risk factor** - **Flank mass** - **Left-sided varicocele** - Left testicular vein drains into the left renal vein; a left RCC can invade the renal vein causing back-pressure and varicocele formation in left testes - Right testicular vein drains **directly** into the IVC, therefore a right RCC does **not** cause a varicocele - **Evidence of metastatic disease** - SOB - Chronic liver disease - Bone pain

Answer 17

- **Asymptomatic:** over 50% of cases are diagnosed incidentally - **Classic triad: haematuria, flank pain, abdominal mass** (seen in 10-15% of patients) - **Constitutional symptoms: e.g. weight loss, fatigue, fever of unknown origin**

Answer 18

- **Urinalysis:** microscopic haematuria or proteinuria - **Bloods:** - **FBC:** anaemia of chronic disease or polycythaemia - **U&Es**: assess for renal dysfunction - **LFTs and coagulation profile**: derangement suggests liver metastasis - **Bone profile**: elevated calcium is a poor prognostic marker and may also suggest bony metastasis - **LDH**: elevated LDH is a poor prognostic marker - **Abdominal ultrasound**: a sensitive initial modality to help identify benign vs. malignant lesions but CT/MRI is needed if RCC is suspected - **CT abdomen/pelvis with contrast**: the definitive test for diagnosis, with 90% sensitivity and 100% specificity in identifying malignancy

Answer 19

- **MRI** - **CT chest:** if initial imaging suggests malignancy, a CT chest is needed to complete staging and assess for pulmonary metastasis - **Bone scan**: if there is evidence of bony metastases, e.g. pain or hypercalcaemia - **Renal biopsy**: there is a risk of tumour seeding to surrounding structures so not generally performed, but may be considered

Answer 20

**TNM** T = tumour size N = lymph node involvement M = metastases

Answer 21

- **Partial nephrectomy:** standard for T1 tumours (i.e. ≤ 7cm) and performed with curative intent - **Radical nephrectomy**: standard for T2-T4 tumours (i.e. > 7cm). Local lymph node dissection and adrenalectomy may be considered if these structures are involved - **Minimally-invasive procedures**: reserved for patients unfit for surgery, e.g. radiofrequency ablation or embolisation

Answer 22

- **Molecular therapy:** Sunitinib and Pazopanib (receptor tyrosine kinase inhibitors) are first-line agents - **Radiotherapy**: some patients are suitable for palliative radiotherapy - **Cytoreductive surgery**: some patients are suitable for a debulking, non-curative nephrectomy as there is evidence for a slight improvement in survival

Answer 23

- **Metastasis:** adrenal, liver, bone, lung, brain - Metastases to lung is common: cannon ball metastases - **Paraneoplastic syndromes:** production of these by RCC can cause certain conditions e.g. - **Erythropoietin** → polycythaemia - **Parathyroid hormone-related peptide (PTHrP)** → hypercalcaemia - **ACTH** → Raises cortisol levels and causes Cushing’s syndrome - **Renin** → affects blood pressure - **Stauffer syndrome**: also known as paraneoplastic nephrogenic hepatomegaly. RCC results in hepatomegaly, cholestasis and cholestatic jaundice, without any localised liver or biliary metastasis!

Answer 24

Overall 5-year survival is near 70%, whilst early-stage disease has an excellent 5-year survival of >90%. Survival from metastatic disease has almost doubled since the introduction of Sunitinib, with an overall 5-year survival between 30 and 50% in patients with pulmonary metastasis

Answer 25

Wilms’ tumour is a specific type of tumour affecting the kidney in children, typically under the age of 5 years.

Answer 26

- Seen age 2-5 years - It is the chief abdominal malignancy in children

Answer 27

- **Family history** - **Congenital syndromes**: Wilms' tumour presents as part of some syndromes e.g. WAGR, Denys-Drash, Beckwith-Wiedemann syndromes and hemihypertrophy

Answer 28

The tumour consists of the blastema (immature kidney mesenchyme), primitive glomeruli and tubules, and stromal cells. Deletion in a number of tumour suppressor genes such as WT1 (30% of cases) and WT2 have been implicated.

Answer 29

- Signs - Abdominal mass - Microscopic haematuria - Hypertension - Symptoms - Abdominal/ flank pain - Haematuria - Lethargy - Fever - Weight loss - Hypertension

Answer 30

- **Urinalysis:** microscopic haematuria - **U&Es:** elevated urea and creatinine, indicating renal dysfunction - **Ultrasound** of the abdomen to visualise the kidneys. - **CT or MRI scan** can be used to stage the tumour. - **Biopsy** to identify the histology is required to make a definitive diagnosis.

Answer 31

Surgical excision of the tumour along with the affected kidney (nephrectomy).

Answer 32

- Adjuncts Depends on the stage of the disease, the histology and whether it has spread. The main options are: - **Adjuvant chemotherapy** - **Adjuvant radiotherapy**

Answer 33

Renal transplantation: usually reserved for patients with advanced, bilateral disease and renal failure

Answer 34

- **Renal failure:** rare but occasionally seen in those with bilateral disease - **Chemotherapy-related complications:** such as bone marrow suppression and neutropenic sepsis

Answer 35

Early stage tumours with favourable histology hold a good chance of cure (up to 90%). Metastatic disease has a poorer prognosis.

Answer 36

- **Urothelial** (most common >90%) - **Non-urothelial** - Squamous cell carcinoma (1-7%) - Adenocarcinoma (2%) - Sarcoma - Small cell

Answer 37

Transitional epithelium lines the renal pelvis, ureter, bladder, and urethra. Transitional cell carcinoma (TCC) most typically arises within the bladder.

Answer 38

- Bladder cancer is the 11th most common cancer in the UK, and the second most common urological cancer - Over 90% of bladder cancers are TCCs - M>F - Most commonly occurs after the age of 40 yrs - Incidence peaks in the 8th decade

Answer 39

- Tumour suppression mutations (p53 or Rb) - Tumour suppression mutation independent

Answer 40

- **Increasing age**: most common in patients aged 50 to 80 years old - **Male** - **Family history** - **Alcohol** - **Extended dwell times**: not emptying bladder for long periods of time - **Carcinogens:** mnemonic PeeSAC - Phenacetin - an old analgesic - Smoking - Alanine - rubber, dye and textile industries - Cyclophosphamide: medication used to treat cancers and autoimmune diseases - **Occupational exposure** - Aromatic amines: rubber, dye and textile industries - Polycyclic aromatic hydrocarbons (e.g. 2-Naphthylamine): aluminium, coal and roofing industries - Painters and hairdressers

Answer 41

The urothelium is a specific type of transitional cell epithelium that lines the inner surface of much of the urinary tract. This tissue is composed of 3–7 cell layers, and it forms a tight barrier which holds urine without allowing toxins to move across the epithelium and back into the body. That barrier function is largely accomplished by large umbrella cells that line the inner or luminal surface of the urothelium. The bladder changes its shape during the course of its regular function - goes from being wrinkled with rugae to being smooth by unfolding its mucosal surface. The umbrella cells can also stretch to expand the bladder. Cancers arise either: - Through a mutation in a tumour suppressor gene (p53 or Rb) causing cells to grow horizontally **(flat)**, and then the cells can invade the deeper bladder tissues - Through **papillary** finger-like extensions growing on outward from the urothelium. These are often non-invasive and have a better prognosis TCCs may occur as solitary or multifocal lesions. They can recur and metastasise. This makes it hard to treat. Theories for recurrence: - **Field effect:** entire urothelial ‘field’ is exposed to a carcinogen and therefore many of the cells are equally susceptible to tumour formation. - **Implantation theory:** tumour cells detach from one location in the bladder, float through the urine, then implant themselves at another location in the bladder. Metastasis: - **Local** → to pelvic structures - **Lymphatic** → to iliac and para-aortic nodes - **Haematogenous** → to liver and lungs

Answer 42

- **Palpable suprapubic mass** in advanced cases - **Anaemia** e.g. pallor, if chronic bleeding present

Answer 43

- **‘Painless’ haematuria**: microscopic or macroscopic - **Dysuria** (pain when urinating) can occur - **Frequency** - Constitutional symptoms e.g. **weight loss**

Answer 44

As per NICE guidelines, refer people for an appointment within 2 weeks if they are: - **Aged 45 and over** and have**:** - Unexplained visible haematuria **without** urinary tract infection, **OR** - Visible haematuria that persists or recurs **after** successful treatment of urinary tract infection, **OR** - **Aged 60 and over** and have: unexplained microscopic haematuria **and** either dysuria **or** a raised WCC on a blood test **Consider** non-urgent referral for bladder cancer in people **aged 60 and over** with recurrent or persistent unexplained urinary tract infections.

Answer 45

- **Urinalysis:** haematuria - **Bloods:** - **FBC:** assess Hb in patients with chronic haematuria - **U&Es**: renal failure may be present if there is significant bladder outflow obstruction - **Bone profile**: hypercalcaemia and raised ALP with bone metastasis - **LFTs and coagulation screen**: deranged in liver metastasis and to rule out coagulopathy - **Flexible cystoscopy and biopsy:** under local anaesthetic to **confirm** the presence of a bladder tumour; gold-standard diagnostic investigation - **Urinary cytology:** identify cancer cells; not routinely performed

Answer 46

- **CT abdomen and pelvis (CTAP)**: assesses for distant metastasis for high-risk patients or suspected muscle-invasive disease on cystoscopy. Low-risk patients with non-muscle invasive disease do **not** need a CTAP (rarely alters management) - **CT urogram:** for imaging the urinary tract and better visualisation of the renal parenchyma - **Pelvic MRI**: often performed for local staging if cystoscopy suggests muscle-invasive disease - **PET CT**: usually performed if there are unclear findings on CT (e.g. lymph nodes of uncertain significance) - **Bone scan**: if suspecting bone metastasis; e.g. if bone pain or hypercalcaemia is present

Answer 47

T1 - Invades sub epithelial connective tissue T2 - Invades superficial (2a) or deep (2b) muscularis propria T3 - Extends to perivesical fat T4 - Invading other organs e.g. uterus or prostate (4a) or pelvic abdominal wall (4b)

Answer 48

**Trans-urethral resection of bladder tumour (TURBT):** rigid cystoscopy under general anaesthetic, with a post-operative dose of **intravesical mitomycin C (chemotherapy).** Further management will depend on the risk as determined by histology - **Low risk:** no further management - **Intermediate risk:** 6 doses of intravesical mitomycin C - **High risk:** intravesical BCG vaccine, or radical cystectomy if very high risk

Answer 49

- **Radical cystectomy** with neoadjuvant chemotherapy; patients will require an ileal conduit (urostomy) - **Radical radiotherapy** with neoadjuvant chemotherapy is an alternative to surgery

Answer 50

- **Chemotherapy:** cisplatin-based chemotherapy is generally offered - **Palliative treatment**: e.g. radiotherapy for bladder symptoms if curative treatment is not an option

Answer 51

- **Obstructive uropathy:** bladder outflow obstruction causing urinary retention - **Metastasis:** bone, lung and liver are most common

Answer 52

Overall 5-year survival is 55%, but for distant metastatic disease, this drops to 5%.

Answer 53

Occurs most commonly in Egypt where bladder cancer is the most common malignancy in males

Answer 54

The urothelium can change shape and take on a flat, pancake-like appearance of squamous cells. This non-cancerous change is called squamous cell metaplasia. If these cells begin to grow unchecked they can turn into a squamous cell carcinoma. These tumours typically pop up in multiple locations, and show extensive keratinization (filled with keratin).

Answer 55

Typically arise due to chronic inflammation: - Recurrent UTIs - Long-standing kidney stones - Infection with schistosoma haematobium - a type of flatworm. They cause chronic inflammation in the badder wall by burrowing in bladder veins and reproducing.

Answer 56

- Usually solitary, and derive from glandular tissue, so they can often produce a lot of mucin. - Adenocarcinomas are the main form of bladder tumors in patients with bladder exstrophy (the bladder protrudes through a birth defect in the abdominal wall and partially or completely sits outside of the body). - Adenocarcinomas can also develop in response to Schistosoma haematobium infections - Adenocarcinomas of the urachus are quite similar to bladder adenocarcinomas. - The urachus is the fibrous tissue sitting at the dome of the bladder which serves as the remnant of the allantois, the canal that allows urine to flow from the fetal bladder into the amniotic sac. - Frequently metastasise

Answer 57

- **Bladder irritation** - **Haematuria** - **Mucusuria** - in adenocarcinomas due to mucus production - **Mucusuria + abdominal pain** - in urachal adenocarcinomas

Answer 58

- **Transurethral resection** - **Radical cystectomy** - Urachal adenocarcinomas management: **bladder dome, urachal ligament, and umbilicus are all generally removed.**

Answer 59

It is thought that squamous cell cancer is associated with a poorer prognosis in comparison to adenocarcinoma

Answer 60

The prostate is a small gland that sits under the bladder and in front of the rectum. The urethra which is the tube through which urine leaves the bladder, goes through the prostate before reaching the penis. This part of the urethra is called the prostatic urethra. The prostate is covered by a capsule of tough connective tissue and smooth muscle. Beneath this layer, it can be divided into a few zones - **The peripheral zone:** the outermost posterior section, is the largest of the zone and contain about 70% of the prostate’s glandular tissue. - **Central zone:** contains about 25% of the glandular tissue as well as the ejaculatory ducts that join with the prostatic urethra. - **Transitional zone:** contains around 5% of the glandular tissue as well as a portion of the prostatic urethra. Each of the tiny glands that make up the prostate is surrounded by a basement membrane made largely of collagen. Sitting within the basement membrane, is a ring of cube-shaped basal cells as well as a few neuroendocrine cells interspersed throughout. Finally, there’s an inner ring of luminal columnar cells. Luminal cells secrete substances into the prostatic fluid, that make it slightly alkaline that give it nutrients which nourish the sperm and help it survive in the acidic environment of the vagina. During an ejaculation, sperm leave the testes, travel through the vas deferens, into the ejaculatory ducts, and travel through the prostatic urethra. Smooth muscles in the prostate contract and push the prostatic fluid into the urethra where it joins the sperm as well as the semen. The luminal cells also produce prostate specific antigen, or PSA, which helps to liquefy the gel-like semen after ejaculation, thereby freeing the sperm to swim. The basal cells and luminal cells of the prostate rely on stimulation from androgens for survival. This includes testosterone, which is produced by the testicles, androstenedione and dehydroepiandrosterone which are produced by the adrenal glands, and dihydrotestosterone, which is made by the prostate itself. Without these androgens, the normal prostate cells, particularly the luminal cells, cannot survive, and undergo apoptosis or programmed cell death.

Answer 61

Prostate cancers most commonly refer to prostate adenocarcinomas but other prostate cancers include transitional cell carcinoma arising from cells in the transitional zone, and small cell prostate cancer arising from neuroendocrine cells.

Answer 62

- Prostate cancer is the most common cancer in males in the UK - It is associated with an 84% overall survival rate - Common in Afro-Caribbean

Answer 63

- **Increasing age:** highest rates amongst men aged 75 to 79 years - **Family history**: 5-10% have a strong family history - **Afro-Caribbean ethnicity** - **Being tall** - **Obesity and high-fat diet** - **Use of anabolic steroids** - **Cadmium exposure:** found in cigarettes, batteries and those working in the welding industry - **BRCA1 and BRCA2** have been linked to prostate cancer

Answer 64

Adenocarcinomas are the most common type of prostate cancer, and these most commonly arise from the peripheral zone of the prostate. They most often results from a genetic mutation in a luminal cell, but can also be a basal cell, and it results in that cell dividing uncontrollably forming a tumour. Early on, prostate cancer cells depend heavily on androgens for survival, but eventually, the cancer cells mutate and find a way to keep multiplying without relying on androgens. If the cancer becomes metastatic, it most commonly spreads to the bones, like the vertebrae or pelvis, resulting in hip or lower back pain. Spread normally occurs along the capsular surface of the prostate, metastasising via the lymphatics and blood.

Answer 65

- **Asymmetrical, hard, nodular prostate with loss of median sulcus** on digital rectal examination - **Urinary retention** - Presents with lower abdominal pain and tenderness, inability to urinate and a palpable bladder - **Palpable lymphadenopathy:** indicates metastatic disease

Answer 66

- **Frequency** - **Hesitancy** - **Terminal dribbling** - **Nocturia** - **Haematuria or haematospermia** - **Dysuria** - **Constitutional symptoms: e.g. weight loss, fatigue** - **Bone pain**: e.g. lumbar back pain: suggests metastatic disease

Answer 67

- **Prostate-specific antigen (PSA)** - Often increased in patients with prostate cancer - Also raised with increasing age and BPH - **Bone profile**: hypercalcaemia and raised ALP suggests bone metastasis - **Liver profile**: assess for liver metastasis - **U&Es**: assess renal function to assess for renal failure secondary to obstruction - **Multiparametric MRI**: **first line for suspected localised cancer** - Previously, **transrectal ultrasound (TRUS)-guided needle biopsy** was the gold-standard diagnostic investigation - **Multiparametric MRI is now first-line** for suspected localised cancer. Reported on using Likert score: 1. **Clinically significant cancer highly unlikely to be present** 2. **Clinically significant cancer is unlikely to be present** 3. **Chance of clinically significant cancer is equivocal** 4. **Clinically significant cancer is likely to be present** 5. **Clinically significant cancer is highly likely to be present** - **Multiparametric MRI-influenced prostate biopsy:** offered to patients with a Likert score of 3 or greater

Answer 68

- **CT abdomen and pelvis / MRI**: usually performed as part of staging - **Bone scan**: if symptoms, e.g. bone pain, or PSA trends are indicative of metastasis then an isotope bone scan must be performed

Answer 69

**Used to grade prostate neoplasms following biopsy giving an overall score ranging from 2 - 10** - The **most prevalent** histological pattern is graded form 1-5, with grade 5 being the **least** differentiated - The **second most prevalent** histological pattern is graded in the same way, and the two scores are added together - Grade 1: Well differentiated cancer. - Grade 2: Moderately differentiated cancer. - Grade 3: Moderately differentiated cancer. - Grade 4: Poorly differentiated cancer. - Grade 5: Anaplastic (poorly differentiated) cancer. - **Used alongside PSA and clinical-stage to assign overall risk** associated with localised cancer

Answer 70

- **Benign prostatic hyperplasia** - **Chronic prostatitis**

Answer 71

**Option 1: Active surveillance or observation** - Active surveillance is preferred in low-risk disease - Observation is a less intense form of monitoring if elderly people with estimated survival <10 years (multiple co-morbidities) **Option 2: Radical prostatectomy** - Removal of the prostate, seminal vesicles, ampulla, and vas deferens, +/- pelvic lymph node dissection; often performed robotically - Commonly performed **Option 3: Radical radiotherapy or brachytherapy +/- anti-androgen therapy** - Radiotherapy is usually delivered over 7-8 weeks - Brachytherapy involves placing radioactive seeds into the prostate to continuously deliver radiotherapy - Hormonal therapy as testosterone helps growth of tumour = anti-androgen e.g. flutamide, or LHRH agonists

Answer 72

**Option 1: Radical prostatectomy** - Pelvic lymph node dissection is more frequently considered in comparison to low-intermediate risk cases; often performed robotically **Option 2: Radical radiotherapy with anti-androgen therapy** **Option 3: Radical radiotherapy with brachytherapy** - Can also be used in intermediate-risk cases **Option 4: Docetaxel chemotherapy with anti-androgen therapy** - Chemotherapy must not be used alone - Also used to treat metastatic cancer - Docetaxel is an anti-microtubule agent that block cell proliferation

Answer 73

- Treated with docetaxel chemotherapy **and** **anti-androgen therapy** - **Bilateral orchidectomy (removal of testes to cause androgen deprivation)** should be offered as an alternative to LHRH agonists

Answer 74

**Cancer-related:** - **Urinary retention** - **Metastasis:** most commonly to bone **Procedure or treatment-related:** - **TRUS biopsy**: haematuria and rectal bleeding, pain, sepsis (1%) - **Surgery:** urinary incontinence, erectile dysfunction (common) - **Radiotherapy**: proctitis, cystitis, colorectal cancer, bladder cancer - **Hormone therapy**: gynaecomastia, hot flushes - **Surgery, radiotherapy or hormones**: erectile dysfunction

Answer 75

Early-stage disease has a fantastic prognosis, with an overall 5-year survival rate of approximately 100% for localised prostate cancer. Metastatic disease is associated with a 5-year survival rate of approximately 30%. In patients conservatively managed (e.g. active surveillance), the Gleason score is the most reliable predictor of death from prostate cancer

Answer 76

- Located in scrotum - Covered by tunica albuginea - Each testis lobule is separated by septa, and within the lobule there are seminiferous tubules where sperm is synthesised - Seminiferous tubules: thick epithelial cells surrounding lumen. The wall is made of germ cells (spermatogonia- which give rise to male gametes) and sertoli cells (supportive cells that provide nutrients to sperm and also form blood-testis barrier) - Outside the tubules there are capillaries and leydig cells (produces testosterone)

Answer 77

- Germ cells are undifferentiated cells which have the potential to differentiate - Some germ cells remain as undifferentiated cells (in the testicles/ovaries) and go on to form sperm and eggs

Answer 78

Testicular cancer is the most common malignancy in young males and usually presents with a firm, painless testicular lump. Testicular cancer can be divided into **germ cell tumours,** which are by far the most common comprising 95% of cases, **non-germ cell tumours** (sex-cord stromal tumours), and **lymphomas**

Answer 79

- Most common malignancy in young males - Testicular cancer is the 18th most common cancer in males in the UK - Often presents between 15 and 35 years old

Answer 80

- **Young males:** seminoma > 35 years; non-seminoma < 35 years - **Caucasian** - **Family history** - **Infertility**: 3-fold increased risk - **Cryptorchidism:** highest risk in abdominal and bilateral undescended testes - **Intersex conditions**: e.g. Klinefelter’s syndrome (extra X chromosome = small undeveloped testicles) - **In-utero exposure to pesticides or synthetic sex hormones** - **Mumps orchitis:** pain and swelling in testicles after mumps - **Testicular atrophy:** often following trauma

Answer 81

Germ cell tumours: >95%, arise from haploid germ cells which partake in spermatogenesis. - **Seminoma:** most common and best prognosis. Made of germ cells that multiply without differentiation - **Embryonal carcinoma:** aggressive and metastasises early. Made from germ cells that turn into embryonic pluripotent stem cells - **Teratoma:** composed of tissue from different germinal layers e.g. teeth, common in children. Can contain all types of tissues! - **Yolk-sac tumour:** common in children and aggressive. Made from germ cells that differentiate into yolk sac tissue - **Choriocarcinoma:** rare but most aggressive. Made out of germ cells that differentiate into syncytiotrophoblasts and cytotrophoblasts (cells that help form placenta) Non-germ cell tumours: arise from diploid sex-cord stroma cells - **Leydig cell tumours:** androgen secreting. Testosterone causes premature puberty. Excess oestrogen can cause delayed puberty and feminisation - **Sertoli cell tumour:** usually clinically silent and benign Lymphoma - **Non-hodgkin lymphoma** (most common)

Answer 82

- **Firm non-tender testicular mass** - Does not transilluminate - Hydrocele (swelling in scrotum) may be present - **Supraclavicular lymphadenopathy**

Answer 83

- **Painless testicular lump** - **Sometimes sharp or dull testicular pain and lower abdominal pain** - Symptoms related to raised β-hCG - **Hyperthyroidism** occurs as the alpha subunit of β-hCG mimics TSH - **Gynaecomastia** - **Loss of libido** - **Erectile dysfunction** - **Testicle atrophy** - **Bone pain:** indicates skeletal metastasis - **Breathlessness, cough or haemoptysis:** indicates lung metastasis - **Back pain:** indicative of lymph node metastasis

Answer 84

- **Ultrasound testicular doppler:** first-line and diagnostic in over 90% of cases - **Tumour markers:** β-hCG, AFP, and LDH must be measured prior to surgery. LDH is raised non specifically in most testicular cancers Seminoma - Occasionally b-hCG Embryonal carcinoma - AFP Teratoma - AFP Yolk sac tumour - AFP Choriocarcinoma - b-hCG

Answer 85

- **CT Chest, abdomen, pelvis:** performed as part of staging to assess for metastatic disease - *NOTE: fine-needle aspiration or percutaneous needle biopsy must not be carried out due to the risk of introducing a new pathway by which the cancer can spread*

Answer 86

- **Testicular torsion** - **Hydrocele** - **Epididymal cyst**

Answer 87

- **Radical orchiectomy** - **Post-orchiectomy active surveillance**: for patients with low-risk disease - **Post-orchiectomy radiotherapy or chemotherapy**: radiotherapy is offered in locally-invasive disease, however, carboplatin (chemo) can be used as an alternative

Answer 88

- **Radical orchiectomy:** some patients also undergo retroperitoneal lymph node dissection - **Post-orchiectomy active surveillance**: for patients with low-risk disease - **Post-orchiectomy combination chemotherapy**: for patients with high-risk disease

Answer 89

- **Radical orchiectomy** - **Seminoma:** adjuvant combination chemotherapy or radiotherapy - **Non-seminoma:** combination chemotherapy

Answer 90

Monitoring using tumour markers and imaging post-treatment

Answer 91

- **Metastasis:** lung, liver, bones, brain, lymph nodes - **Treatment-related:** - **Infertility** secondary to orchiectomy/chemotherapy/radiotherapy - **Secondary malignancy** due to radiotherapy - **Pulmonary or renal toxicity** secondary to chemotherapy

Answer 92

Prognosis is excellent as often detected early. Even in metastatic disease, chemotherapy confers response rates up to 90%. The 5-year survival for all testicular cancers is 95%. All patients should be offered sperm-banking prior to intervention.

Answer 93

Chronic kidney disease (CKD) describes a progressive deterioration in renal function. These issues develop over at least 3 months.

Answer 94

As per NICE, the severity of CKD can be graded based on the eGFR, as well as albumin:creatinine ratio (ACR) The **A score** is based on the **a**lbumin:creatinine ratio: - A1 = < 3mg/mmol - A2 = 3 – 30mg/mmol - A3 = > 30mg/mmol *Renal damage may be evidenced by **one or more** of the following: - Albuminuria (ACR > 3 mg/mmol) - Urine sediment abnormalities - Electrolyte and other abnormalities due to renal dysfunction (e.g. hyperkalaemia) - Histological abnormalities - Structural abnormalities on imaging - A history of kidney transplantation

Answer 95

- Over 10% of the general population are thought to suffer from CKD - Rise in prevalence probably due to an ageing population and the rise in chronic diseases such as diabetes and hypertension

Answer 96

Most common: - **Hypertension** - **Diabetes** Rarer causes: - **Systemic disease e.g. SLE; rheumatoid arthritis** - **Infections e.g. HIV** - **Medications e.g. NSAIDs** - **Toxins e.g. in smoking**

Answer 97

- **Increasing age**: renal function naturally declines after 50 years old - **Afro-Caribbean**: associated with an increased risk of CKD and progression to renal failure - **Diabetes mellitus**: the most common cause overall - **Hypertension**: the second most common cause overall - **Autoimmune conditions**: e.g. SLE and other vasculitides - **Glomerulonephritis**: nephrotic and nephritic syndromes - **Congenital abnormalities**: e.g. adult polycystic kidney disease and vesicoureteral reflux - **Nephrotoxic drugs**: e.g. NSAIDs - **Smoking** - **Enlarged prostate**: results in hydronephrosis; causes include BPH and prostate cancer - **Renal artery stenosis**

Answer 98

**Hypertension:** The walls of arteries supplying the kidney begin to thicken in order to withstand the pressure, and this results in a narrow lumen. A narrow lumen means less blood and oxygen gets delivered to the kidney, resulting in ischaemic injury to the nephron’s glomerulus. Immune cells like macrophages and fat-laden macrophages called foam cells slip into the damaged glomerulus and start secreting growth factors like Transforming Growth Factor ß1 (TGF-ß1). These growth factors cause the mesangial cells to regress back to their more immature stem cell state known as mesangioblasts and secrete extracellular structural matrix. This leads to glomerulosclerosis and diminishes the nephron’s ability to filter the blood - over time leading to CKD **Diabetes:** Excess glucose in the blood starts sticking to proteins in the blood — a process called non-enzymatic glycation. This process of glycation particularly affects the efferent arteriole and causes it to get stiff and more narrow - a process called hyaline arteriosclerosis. This creates an obstruction that makes it difficult for blood to leave the glomerulus, and increases pressure within the glomerulus leading to hyperfiltration. In response to this high-pressure state, the supportive mesangial cells secrete more structural matrix expanding the size of the glomerulus. Over many years, this process of glomerulosclerosis diminishes the nephron’s ability to filter the blood and leads to CKD. - Normally urea in the body gets excreted in the urine, but when there’s a decreased glomerular filtration fate, less urea get filtered out, and therefore it accumulates in the blood. - In addition to getting rid of waste, the kidneys play an important role in electrolyte balance e.g. potassium. So CKD can lead to hyperkalaemia - Another key role of the kidneys relates to balancing calcium levels. Normally, the kidney helps to activate vit D which helps to increase absorption of calcium from the diet. In CKD, this is disturbed, leading to hypocalcaemia, which can further lead to secondary hyperparathyroidism. This leads to increased bone resorption resulting in osteodystrophy - Furthermore, the falling GFR leads to more renin secretion by the kidneys, resulting in further hypertension - The kidney also secretes the hormone erythropoietin which stimulates the production of red blood cells from the bone marrow. In chronic kidney disease, erythropoietin levels fall and this leads to lowered production of red blood cells, and ultimately anemia.

Answer 99

- **Hypertension** - **Fluid overload** - **Uraemic sallow:** a yellow or pale brown colour of skin - **Uraemic frost:** urea crystals can deposit in the skin - **Pallor:** due to anaemia - **Evidence of underlying cause:** e.g. butterfly rash in lupus

Answer 100

- **Lethargy** - **Pruritis** - **Muscle cramps** - **Nausea** - **Anorexia** - **Loss of appetite** - **Frothy urine** - **Swollen ankles/ oedema** - **Increased bleeding:** excess urea in the blood makes platelets less likely to stick to each other

Answer 101

- Primary investigations - **Urine dip:** screen for proteinuria and haematuria - **Urine albumin:creatinine ratio (ACR):** a ratio of >3 mg/mmol is clinically significant proteinuria. This test is now **preferred** over other tests such as protein:creatinine ratio or 24-hour urinary collection - **U&Es:** serum creatinine can be used to calculate eGFR and quantify the severity of CKD; patients may also develop electrolyte disturbances such as hyperkalaemia - **FBC:** normocytic normochromic anaemia secondary to reduced erythropoietin production; usually apparent when GFR is < 35 ml/min - **Bone profile and PTH:** patients are at risk of hypocalcemia, hyperphosphatemia, and secondary or tertiary hyperparathyroidism - **Renal ultrasound:** can be used to investigate patients with accelerated CKD, haematuria, family history of polycystic kidney disease or evidence of obstruction. In CKD, there is bilateral kidney atrophy

Answer 102

- **CT KUB:** if suspecting an obstructive cause then CT imaging can be conducted - **Renal biopsy:** if suspecting an underlying intrarenal cause such as a nephrotic or nephritic syndrome - **Investigate the underlying cause**: for example, request autoantibodies and inflammatory markers if suspecting SLE

Answer 103

- **Lifestyle:** - Smoking cessation, exercise, drinking alcohol in moderation - Avoid nephrotoxic medications; e.g. NSAIDs - Dietary advice: low salt and potassium diets, with fluid restriction if there is evidence of overload - **Cause related management e.g.** - Optimise diabetic control - Optimise hypertensive control - Treat glomerulonephritis - **Renal replacement therapy:** - Typically performed when eGFR is in single digits or there are signs of uraemia - Dialysis is usually commenced first, followed by renal transplantation if the patient is eligible

Answer 104

- **Cardiovascular** - Cardiovascular disease is the leading cause of death in CKD - Hypertension - Hypercholesterolaemia - Heart failure: due to fluid overload and anaemia - **Musculoskeletal** - CKD-metabolic bone disease - **Endocrine** - Secondary hyperparathyroidism - Tertiary hyperparathyroidism occurs after a prolonged period of secondary hyperparathyroidism - **Haematological** - Anaemia: usually normocytic and normochromic and is multifactorial; predominantly due to low EPO, but also reduced erythropoiesis due to uraemia, reduced iron absorption and anorexia due to uraemia - **Metabolic** - Uraemia (leading to peripheral neuropathy, encephalopathy and pericarditis) - Hyperkalaemia - Metabolic acidosis

Answer 105

If the underlying cause of renal impairment is not effectively managed, CKD will ultimately result in end-stage renal failure. However, patients with CKD often die of cardiovascular disease prior to reaching end-stage renal failure. This emphasises the need to monitor and optimise cardiovascular risk factors through smoking cessation, strict diabetes control, statin therapy, and antihypertensives.

Answer 106

1. **Reduced 1-alpha hydroxylase** **activity** in the kidney: leads to **reduced vitamin D** activation 2. **Reduced renal excretion of phosphate**: leads to **hyperphosphataemia**; excess phosphate stimulates bone resorption resulting in osteomalacia Ultimately, CKD results in **hypocalcaemia**. Due to low calcium, high phosphate and low vitamin D levels, **secondary hyperparathyroidism** occurs, resulting in further bone resorption. CKD-MBD may manifest as: - **Osteomalacia**: due to low vitamin D - **Osteitis fibrosa cystica**: hyperparathyroid bone disease - **Osteoporosis** - **Osteosclerosis** - **Adynamic bone disease**: due to a reduction in osteoblast and osteoclast activity

Answer 107

CKD-MBD is sometimes referred to as the ‘silent crippler’ because symptoms usually do not occur until the patient has been on dialysis for several years. - **Bone and joint pain** - **Bone deformation** - **Bone fractures** - **Reduce mobility**

Answer 108

**Bone profile, parathyroid hormone (PTH) and vitamin D levels:** - Assessing for **hypocalcemia**, **hyperphosphatemia**, **secondary or tertiary hyperparathyroidism,** and **low vitamin D** - Should be measured in all patients with an eGFR < 30 ml/min/1.73 m2

Answer 109

The aim in managing CKD-MBD is to reduce serum phosphate and PTH levels. - **Reducing dietary phosphate** is usually **first-line**; foods that are high in phosphate include meats, poultry, fish, nuts, beans and dairy products. - **Vitamin D replacement:** - In early-stage CKD where 1-alpha hydroxylase is still functioning, **cholecalciferol** can be commenced if vitamin D deficient - In later stage disease, **alfacalcidol** or **calcitriol** are used as they are already 1-alpha-hydroxylated and therefore bypass kidney metabolism **Phosphate binders:** used in late-stage disease to reduce phosphate - **Calcium-based binders**: calcium acetate is the first-line phosphate binder to control serum phosphate; can result in vascular calcification and hypercalcaemia - **Non-calcium-based binders**: usually considered if calcium-based binders are ineffective; e.g. sevelamer, lanthanum, aluminium - **Sevelamer**: binds to dietary phosphate to reduce absorption; also reduces uric acid and improves hypercholesterolaemia in CKD **Bisphosphonates:** - Offer bisphosphonates, if indicated, for the prevention and treatment of osteoporosis in people with an eGFR < 30 ml/min/1.73 m2 **Parathyroidectomy:** - Indicated in tertiary hyperparathyroidism

Answer 110

- **Cardiovascular complications** - CKD is an independent risk factor for cardiovascular disease and is associated with hypertension, hypercholesterolaemia and heart failure. - **Management:** **Hypertension:** - **ACE inhibitor (ACEi)**: first-line anti-hypertensive in CKD with proteinuria (raised ACR); e.g. ramipril - ACEi are renoprotective as they reduce filtration pressure and therefore minimise proteinuria - ACEi can cause a small rise in creatinine and reduction in eGFR but should only be stopped if **creatinine** **rises** by ****more than **30%** or **eGFR** **falls** by more than **25%**; if this occurs, investigate for other causes e.g. NSAID use - If ACR is **not** raised, the standard NICE management of hypertension guidelines should be followed - **Target BP**: 140/90 mmHg, or 130/80 mmHg if coexisting diabetes - **Furosemide**: may be beneficial as an anti-hypertensive when GFR is < 45 ml/min as it lowers serum potassium, but should be paused if at risk of dehydration, e.g. infection **Hypercholesterolaemia:** - **Statin:** NICE advises that **all** patients should be commenced on atorvastatin 20mg for both primary and secondary prevention of cardiovascular disease **Secondary prevention:** - Patients are able to continue their secondary prevention antiplatelet agents but they should be aware of the increased risk of bleeding

Answer 111

- **Anaemia** - Usually normocytic and normochromic and is multifactorial; predominantly due to low EPO, but also reduced erythropoiesis due to uraemia, reduced iron absorption and anorexia due to uraemia - **Management:** - **Target Hb**: 10-12 g/dl - **Iron replacement:** commence iron replacement, either orally or intravenously, prior to commencing ESAs; particularly important in patients on haemodialysis - **Erythropoiesis stimulating agents (ESAs):** e.g. erythropoietin (EPO) or darbepoetin

Answer 112

The prostate is a small gland that sits under the bladder and in front of the rectum. The urethra which is the tube through which urine leaves the bladder, goes through the prostate before reaching the penis. This part of the urethra is called the prostatic urethra. The prostate is covered by a capsule of tough connective tissue and smooth muscle. Beneath this layer, it can be divided into a few zones - **The peripheral zone:** the outermost posterior section, is the largest of the zone and contain about 70% of the prostate’s glandular tissue. - **Central zone:** contains about 25% of the glandular tissue as well as the ejaculatory ducts that join with the prostatic urethra. - **Transitional zone:** contains around 5% of the glandular tissue as well as a portion of the prostatic urethra. Each of the tiny glands that make up the prostate is surrounded by a basement membrane made largely of collagen. Sitting within the basement membrane, is a ring of cube-shaped basal cells as well as a few neuroendocrine cells interspersed throughout. Finally, there’s an inner ring of luminal columnar cells. Luminal cells secrete substances into the prostatic fluid, that make it slightly alkaline that give it nutrients which nourish the sperm and help it survive in the acidic environment of the vagina. During an ejaculation, sperm leave the testes, travel through the vas deferens, into the ejaculatory ducts, and travel through the prostatic urethra. Smooth muscles in the prostate contract and push the prostatic fluid into the urethra where it joins the sperm as well as the semen. The luminal cells also produce prostate specific antigen, or PSA, which helps to liquefy the gel-like semen after ejaculation, thereby freeing the sperm to swim.

Answer 113

Increase in the size of the prostate without malignancy. This causes bladder outlet obstruction and lower urinary tract symptoms.

Answer 114

- More common in the elderly - In men aged 51-60, the prevalence of BPH is 50%, whilst 30% have symptoms. In men above the age of 80, the prevalence is 80% - More common in Afro-Caribbean men; black > white > asian

Answer 115

- **Increasing age:** particularly >50 years old - **Family history** - **Ethnicity:** more common in Afro-Caribbean men; black > white > asian - **Diabetes** - **Obesity:** due to increased circulating oestrogens

Answer 116

The basal cells and luminal cells of the prostate rely on stimulation from androgens for survival. This includes testosterone, which is produced by the testicles, and dihydrotestosterone, which is produced in the prostate itself. DHT is produced by 5α-reductase which converts testosterone into the more potent dihydrotestosterone. Androgens bind to androgen receptors in the cell and prevent apoptosis allowing the prostate to continue to grow. BPH involves hyperplasia of both glandular epithelial cells and stromal (connective tissue) cells. Anatomically, the median and lateral lobes are usually enlarged. With age the levels of testosterone drop but the levels of DHT increase as 5α-reductase activity increases. The entire prostate gland enlarges uniformly and small hyperplastic nodules can form within it. Typically, hyperplastic nodules will form in the inner portions of the gland, specifically around the prostatic urethra, called the periurethral zone. When these nodules or the prostate tissue itself compresses the prostatic urethra, it becomes more difficult for urine to pass though. The urine builds up and causes the bladder to dilate. In response, the smooth muscle walls of the bladder will contract harder, and this leads to bladder hypertrophy. The stagnation of urine in the bladder also promotes bacterial growth, and can lead to urinary tract infections.

Answer 117

Digital rectal examination findings - **Smooth, enlarged, and non-tender** **Lower abdominal tenderness and palpable bladder** - Indicates acute urinary retention - Perform bladder scan - Requires urgent catheterisation

Answer 118

- **Lower urinary tract symptoms** (LUTS) - **Voiding**: hesitancy, weak stream, straining and dysuria, incomplete emptying, terminal dribbling - **Storage**: urgency, frequency, nocturia (due to feeling of incomplete emptying), urgency incontinence - **Oliguria:** if complete obstruction - **Lower abdominal pain and inability to urinate** - Indicates acute urinary retention

Answer 119

- **Urinalysis:** the presence of pyuria suggests infection - **Prostate-specific antigen (PSA):** predicts prostate volume, progression and may suggest cancer if significantly raised; BPH can also raise PSA - **U&Es:** renal failure if significant obstruction - **International Prostate Symptom Score (I-PSS):** a 7-symptom questionnaire with an additional **bother score** to predict progression and outcome

Answer 120

- **Transrectal ultrasound:** can estimate prostate size and weight which is useful in guiding surgical management - **Renal tract ultrasound:** if acute urinary retention is suspected, will help identify hydronephrosis (swelling of kidney due to backflow of pressure) - **Flow rate**: non-invasive test, suggests obstructive cause if rate <20ml/second - **Urodynamics:** invasive and measures bladder pressures and muscle activity. Reserved for men aged <50 years, or elderly patients with equivocal flow rate - **Flexible cystoscopy**: not recommended unless symptoms are associated with haematuria, or bladder calculi are suspected

Answer 121

- **Prostatitis** - **Prostate cancer** - **UTI** - **Bladder cancer**

Answer 122

- **Reassurance and watchful waiting** - **Conservative management:** reduce caffeine and fluid intake, healthy diet regimens, exercise, medication review, bladder retraining - *In certain circumstances a long-term catheter, with changes every 3 months, may be used.*

Answer 123

- **α-1 antagonists** e.g. tamsulosin. Considered first-line for symptomatic relief (effective in 70%) - Inhibits the action of noradrenaline and relaxes the smooth muscle in the prostate and bladder neck allowing urine to pass. - Side effects: postural hypotension, dizziness, dry mouth, depression - **5-α reductase inhibitors** e.g. finasteride. - Inhibits DHT formation to reduce prostate size, thus slowing progression (unlike α-blockers). Takes up to 6 months to work! - Side effects: reduced libido, erectile dysfunction, reduced ejaculate volume, gynaecomastia - **Combination therapy:** second-line management is a combination of the above.

Answer 124

**Prostate <30 g**: - **Transurethral incision of the prostate (TUIP):** one or two cuts in the small grooves of the bladder neck to open the urinary channel and allow urine to pass through more easily. **Prostate 30-80g:** - **Transurethral resection of the prostate (TURP):** accessing the prostate through the urethra and “shaving” off prostate tissue from inside using diathermy (heat) - **Holmium laser enucleation of the prostate (HoLEP):** prostate tissue is removed using an electrical current **Prostate >80g:** - **Transurethral electrovaporisation of the prostate (TUVP):** prostate tissue is removed using a laser - **Open prostatectomy** via abdominal or perineal incision Surgery: R - Reccurrent or refractory urinary retention U - Recurrent UTI's S - Bladder stone H - Haematuria refractory to medical therapy E - Elevated creatinine due to bladder outflow obstruction S - Symptom deterioration despite maximal medical therapy

Answer 125

**Urological:** - **Acute urinary retention** - **Urinary tract infections** - **Renal dysfunction**: due to obstructive uropathy - **Haematuria** - **Bladder stones:** secondary to urinary stasis **Procedure-related**: - **Retrograde ejaculation**: commonest complication - **Erectile dysfunction** - **Strictures** - **Incontinence** - **TURP syndrome**: a life-threatening triad of fluid overload, dilutional hyponatraemia and neurotoxicity due to systemic absorption of irrigation fluids during TURP procedure

Answer 126

Prognosis is good for the majority of patients with BPH and most experience at least a moderate improvement in symptoms. Medical therapy itself has its complications, such as reduced libido and reduced erectile function, which should be monitored and discussed with the patient. Clinical progression will occur in approximately 20% of patients, whilst combination medical therapy results in a 66% reduction in progression

Answer 127

Upper urinary tract infection: acute inflammation of the renal pelvis (join between kidney and ureter) and parenchyma

Answer 128

- Predominantly affects females under 35 yrs - Unusual in men - Associated with significant sepsis and systemic upset

Answer 129

Can be via ascending infections or haematogenous spread. Common species include: - **E.coli (most common)** - **Klebsiella** - **Proteus species** - **Enterobacter species** - **Staphylococcus species**

Answer 130

- **Vesico-ureteral reflux (VUR)** - **Female sex** - **Sexual intercourse** - **Indwelling catheter** - **Diabetes mellitus** - **Pregnancy** - **Urinary tract obstruction e.g. calculi (stones)**

Answer 131

- Acute pyelonephritis is most often caused by **ascending infection**: bacteria start by colonising the urethra and bladder - causing a lower urinary tract infections - and make their way up the ureters and kidney. One major factor that increases the risk of an upper UTI from a lower UTI spreading upward is vesico-ureteral reflux, which is where urine is allowed to move backward up the urinary tract which can happen if the vesicoureteral orifice fails. The vesicoureteral orifice is the one-way valve that allows urine to flow from each ureter into the bladder, but not in the reverse direction. This can be the result of a primary congenital defect or it can be caused by bladder outlet obstruction, which increases pressure in the bladder and distorts the valve. - Obstruction also leads to urinary stasis, which makes it easier for bacteria to adhere and colonise the [](https://www.osmosis.org/learn/Renal_system_anatomy_and_physiology)urinary tract - The infection can also occur via **haematogenous spread** - through the bloodstream, although this is a lot less common. Usually pyelonephritis from haematogenous spread is a consequence of septicemia or bacteremia as well as infective endocarditis. - Acute pyelonephritis most often unilateral. - When bacteria mount an attack they usually start by adhering to the renal epithelium of the tubules, which triggers an inflammatory response. Chemokines attract neutrophils to the renal interstitium; but typically the glomeruli and vessels are spared. As neutrophils infiltrate and die off, they make their way through the [](https://www.osmosis.org/learn/Renal_system_anatomy_and_physiology)urinary tract and are peed out. Patients also can present with increased white blood cells in their blood, called leukocytosis, and as a result of the inflammatory immune response, patients can also develop fevers, chills, nausea and vomiting, as well as flank pain at the costovertebral angle. These systemic symptoms are what often distinguish acute pyelonephritis from a lower urinary tract infection.

Answer 132

- **Tender loin** on examination - **Pain on bimanual palpation of the renal angle (over kidney)**

Answer 133

- **High fever and rigors** - **Loin to groin pain** - **Dysuria and urinary frequency** - **Haematuria** - **Other non-specific symptoms (e.g. nausea and vomiting)**

Answer 134

- **Urine dipstick** - Blood - Protein - Leukocyte esterase (produced by neutrophils) - Nitrite (gram negative organisms metabolise nitrates in the urine to nitrites) - Foul smelling urine - **Bloods:** - Elevated WCC - CRP and ESR may be raised in acute infection - **Imaging** - CT scan can help confirm the diagnosis - Ultrasound scans are useful in children to confirm diagnosis and investigate long term damage after recovery - Dimercaptosuccinic acid (DMSA) scans involves injecting radiolabelled DMSA, which builds up in the kidneys and when imaged using gamma cameras gives an indication of renal scarring. This is used in recurrent pyelonephritis to assess the damage.

Answer 135

- **Mid-stream urine MCS:** white blood cell in the urine. Sometimes white blood cell cast - white blood cells and surrounding inflammatory protein debris is “casted” into the shape of the tubule, which is then peed out.

Answer 136

- **Lower UTI** - **Cystitis** - **Acute prostatitis** - **Urethritis** - **Chronic pyelonephritis**

Answer 137

- 1st line - **Broad spectrum antibiotics (e.g. co-amoxiclav)** until culture and sensitivities are avaliable - **Hydration** - Other/ adjuncts - **Admission** if systemically unwell or complicated - **IV rehydration** - **Analgesia** - **Antipyretics** - **Surgery to drain** abscesses or relieve calculi that are causing infection

Answer 138

- **Renal abscess** - Recurrent infections: can be the case in people that have an anatomic problem that allows bacteria to easily cause infections, this can lead to - **Chronic pyelonephritis** - **Papillary necrosis:** death of the renal papillae tissue. Has a much worse prognosis because it can affect the kidney’s overall ability to function.

Answer 139

Upper urinary tract infection: chronic inflammation of the renal pelvis (join between kidney and ureter) and parenchyma

Answer 140

- **Vesico-ureteral reflux** - **Chronic obstruction** - Kidney stones - Congenital malformations e.g. of the posterior urethral valve - BPH - Cervical carcinoma

Answer 141

- An episode of acute pyelonephritis often clears up without much complication. Certain people are predisposed to having recurring bouts of acute pyelonephritis, which eventually leads to chronic pyelonephritis and permanent scarring of the renal tissue. The main risk factor for this is vesico-ureteral reflux. - Chronic obstruction is another risk factor for chronic pyelonephritis. Obstructions in the urinary tract causes urinary stasis which makes it easier for bacteria to adhere to and colonise the tissue, making lower UTIs more likely and therefore upper UTIs more likely. - Obstruction can be bilateral or unilateral - Recurrent episodes of inflammation eventually leads the renal interstitium to undergo fibrosis and scarring, and the tubules atrophy. These changes are generally found on the upper and lower poles of the kidney. - A rare type of chronic pyelonephritis is called xanthogranulomatous pyelonephritis, which happens when an infected kidney stone causes chronic obstruction. The combination of infection and the increased pressure creates granulomatous tissue, which is full of foamy or fat-laden macrophages and can easily be confused for a kidney tumour on imaging.

Answer 142

**Imaging:** - **CT urogram (CTU):** shows the renal calyces become “blunted” or flattened. - **Ultrasound** **Urine MCS** **Histology:** - Some tubules might be dilated and full of colloid (glassy-appearing proteinaceous material) that forms as a result of the chronic inflammation. - Colloid can be shaped like the tubules and therefore form “colloid casts”. This happens to look like thyroid tissue and so this process is sometimes referred to as thyroidization of the kidney. - These colloid casts can get peed out and show up in the urine.

Answer 143

- **Correct the underlying cause of recurrent infection** e.g. surgery to correct congenital structural causes or to remove obstruction like kidney stones - **Dialysis** may be needed - **Nephrectomy** might be needed. - **Antibiotics** may play a role

Answer 144

- Renal abscess - Acute renal failure - Chronic kidney disease

Answer 145

Lower urinary tract infection: inflammation of the bladder

Answer 146

- UTIs are one of the most common conditions presenting in primary care - 50% of women experience cystitis and ⅓ of women have had one episode of cystitis by the age of 24 years - F>M - Can occur in children

Answer 147

- **E.coli** (most common) - **Staphylococcus saprophyticus**: approximately 5–10% of cases - **Proteus mirabilis**: more common in males, associated with renal tract abnormalities, particularly caliculi - **Klebsiella** - **Candida**: a rare cause and usually associated with indwelling catheters, immunosuppression or contamination from the genital tract

Answer 148

- **Female sex**: UTIs are much more common in women as the urethra is much shorter and closer to the anus - **Post-menopause**: the absence of oestrogen is a risk factor for UTIs - **Sexual intercourse** - **Diabetes:** hyperglycaemia prevents neutrophils from carrying out their function against an infection - **Catheterisation** - **Infant boys with foreskin** - **Anything causing urinary stasis** e.g. obstruction due to BPH, cervical carcinoma etc - **Poor bladder emptying** **Risk factors for recurrent UTIs include** - In **young** and **pre-menopausal** women: - Sexual intercourse - A mother with a history of UTI - History of UTI in childhood - In **elderly** and **post-menopausal** women: - History of UTI before menopause - Urinary incontinence - Atrophic vaginitis - Cystocele: prolapsed bladder - Increased post-void urine volume - Catheterisation and reduced functional status in elderly hospitalised women

Answer 149

- An inflamed bladder is usually the result of a bacterial infection, but also can result from fungal infections, chemical irritants, foreign bodies like kidney stones, as well as trauma. - Lower UTIs are almost always caused by an ascending infection, where bacteria typically moves from the rectal area to the urethra and then migrate up the urethra and into the bladder. - On rare occasions, a descending infection can happen as well where bacteria starts in the blood or lymph and then goes to the kidney and makes its way down to the bladder and urethra. - Normally, urine is sterile, meaning bacteria doesn’t live there; the composition of urine, which has a high urea concentration and low pH, helps keep bacteria from setting up camp. The unidirectional flow in the act of urinating also helps to keep bacteria from invading the urethra and bladder. Some bacteria, though, are better surviving in and resisting these conditions, and can stick to and colonise the bladder mucosa. - A risk factor is impaired bladder emptying causing urinary stasis, which means urine tends to sit still, allowing bacteria the chance to adhere and colonise in the bladder.

Answer 150

Suprapubic tenderness

Answer 151

- **Dysuria:** discomfort, pain, burning or stinging associated with urination - **Frequency:** passing urine more often than usual - **Urgency:** a strong desire to urinate, which may result in urinary incontinence - Changes in urine **appearance/consistency**: - **A cloudy or pungent odour** - **Haematuria** - **Nocturia:** passing urine more often than usual at night - **Suprapubic discomfort** - Non-specific, generalised clinical features: e.g. **delirium, lethargy, reduced appetite** - **Delirium and confusion** especially common in elderly patients - **Fever** only be present in children

Answer 152

- **Urine dipstick**: nitrite and leukocyte usually positive: - **Positive** nitrite **OR** leukocyte, **AND** positive RBCs: UTI is **likely** - **Negative** nitrite **AND** positive leukocyte: UTI is **equally likely** to other diagnoses - **Mid-stream urine microscopy, culture and sensitivity (MC&S)**: - Gold standard - The most specific and sensitive test; bacteria, WBCs, +/- RBCs expected

Answer 153

- **Bladder scan / post-void residual volume**: if urinary retention or incomplete bladder emptying is suspected - **Renal tract ultrasound**: consider if symptoms are severe or persistent to assess for an underlying cause, e.g. kidney stone, hydronephrosis or renal abscess - **Cystoscopy**: consider if symptoms are severe or persistent to assess for an underlying cause e.g. bladder stone, tumour or diverticulum - **DMSA (Dimercaptosuccinic Acid) Scan:** assess for damage from recurrent or atypical UTIs. This involves injecting a radioactive material (DMSA) and using a gamma camera to assess how well the material is taken up by the kidneys. Where there are patches of kidney that have not taken up the material, this indicates scarring that may be the result of previous infection. - **Micturating Cystourethrogram (MCUG):** should be used to investigate atypical or recurrent UTIs in children under 6 months. It is used to diagnose vesicoureteral reflux. It involves catheterising the child, injecting contrast into the bladder and taking a series of xray films to determine whether the contrast is refluxing into the ureters.

Answer 154

- **Pyelonephritis** should be suspected in people with fever, loin pain or rigors (systemic symptoms) - **Urethritis:** inflammation of urethra, but not bladder - **Serious illnesses**, e.g. sepsis, should be considered in the presence of **red flags** such as loin pain, rigors, nausea, vomiting, and altered mental state

Answer 155

**Generally, antibiotics and hydration** **Prevention involves good hygiene**

Answer 156

- If symptoms are mild, antibiotics may be delayed - **First line:** Antibiotic course for 3 days - nitrofurantoin or trimethoprim - **Second line:** Antibiotic course for 3 days - nitrofurantoin or pivmacillinam or fosfomycin single-dose sachet - **If micro- or macroscopic haematuria present:** re-test after antibiotic and consider specialist referral for an underlying cause (e.g. bladder cancer) if persistent - **If recurrent:** seek specialist advice to investigate for an underlying cause; if no cause is found then consider antibiotic prophylaxis, and topical oestrogen if postmenopausal

Answer 157

- Both symptomatic UTI and asymptomatic bacteriuria are treated with antibiotics due to the risk of progression to acute pyelonephritis - **First line:** Antibiotic course for 7 days - nitrofurantoin - **Second line:** Antibiotic course for 7 days - amoxicillin or cefalexin

Answer 158

- **Do not** treat **asymptomatic bacteriuria** in catheterised patients - **First-line**: nitrofurantoin or trimethoprim for **7 days** - Check for **blockage** and **consider changing** the catheter if it has been in place for **more than 7 days**

Answer 159

- **First line:** Antibiotic course for 7 days - trimethoprim or nitrofurantoin - **Second line:** Antibiotic course for 7 days - amoxicillin or cefalexin - Consider **urological cancer referral if suspected** e.g. if persistent UTI, haematuria, dysuria, raised WBC

Answer 160

**Ascending infection** is the main complication of a lower UTI, resulting in: - **Pyelonephritis** - **Renal** and **peri-renal abscess** - **Impaired renal functio**n or **renal** **failure** - **Urosepsis** **UTI in pregnancy** is associated with: - **Pre-term delivery** - **Low-birthweight** **Complications in men**: - **Prostatitis**: men with UTI may harbour bacteria within the prostate; >50% of men with recurrent UTI have prostatitis which may lead to complications such as prostatic abscess **Other:** - **Urinary stones:** more likely with *Proteus mirabilis* infection which is associated with stone formation in renal collecting ducts

Answer 161

An **acute, uncomplicated UTI** usually resolves within a **few days** **Recurrence** - 25–35% of women with a UTI have a **recurrent infection** within 3 to 6 months - 44% have recurrence within 12 months **Ascending infection** is the main complication of a UTI, and 75% of people with pyelonephritis will have had UTI previously

Answer 162

A severe infection involving the prostate that may cause significant systemic upset.

Answer 163

- Common in men of all ages - Most common UTI in men < 50 - Usually presents > 35 yrs - Associated with LUTs

Answer 164

- **E.coli** is the most commonly isolated pathogen - **Pseudomonas aeruginosa, Klebsiella, Enterococcus and Proteus** may all be causes. - **Sexually transmitted infections,** Chlamydia trachomatis and Neisseria gonorrhoea, are less commonly isolated. - **Urethral instrumentation e.g. catheter** - rarely, acute bacterial prostatitis may follow instrumentation of the urethra. Multiple pathogens and more uncommon pathogens are more likely to be isolated in these cases. - **Disseminated infections -** acute bacterial prostatitis may also occur secondary to disseminated infection with a distant source. Bacteria like S.aureus may exhibit ‘metastatic’ spread to multiple locations.

Answer 165

- **STI** - **UTI** - **Indwelling catheter** - **Post-biopsy** - **Increasing age**

Answer 166

- **Tender, hot, swollen prostate** (on digital rectal exam) - **Palpable bladder** (if urinary retention) - **Tachycardia** - **Pyrexia**

Answer 167

- **Dysuria** - **Urinary frequency** - **Urinary retention** - **Hesitancy** - **Post-micturition dribbling** - **Straining** - **Perineal, rectal or pelvic pain** - **Back pain** - **Fevers** - **Myalgia** - **Malaise**

Answer 168

- **Digital rectal exam** - **Urine dipstick** - **Bloods** - FBC, U&E, CRP - **Cultures** - Mid-stream urine, semen culture, blood culture - **STI testing,** if suspected - **Imaging** - MRI: allows assessment prostate and for the development of abscess. - Trans-urethral ultrasound scan (TRUSS)

Answer 169

- **Antibiotics:** courses typically 14 days - **First line:** Oral ciprofloxacin or ofloxacin - **Second line:** Oral levofloxacin or co-trimoxazole - **IV antibiotics:** for patients with significant infection under microbiology guidance. - **TRUSS guided abscess drainage**, if needed - If patient presents with sepsis, patient must be treated according to **sepsis 6 principles.** - **Further investigations** - Patients require further urological review after the acute episode is treated to evaluate for pre-disposing structural abnormalities in the urinary tract.

Answer 170

- **Acute urinary retention** - **Epididymitis** - **Chronic prostatitis** - **Prostatic abscess**

Answer 171

Chronic prostatitis is characterised by > 3 months of urogenital pain, often associated with LUTS or sexual dysfunction.

Answer 172

**Chronic prostatitis may be categorised as:** - **Chronic prostatitis/chronic pelvic pain syndrome:** clinical features of chronic prostatitis in the absence of an identifiable bacterial infection. - **Chronic bacterial prostatitis:** relatively uncommon, accounting for around 10% of patients with chronic prostatitis. **NIDDK classification** To understand this classification you need to known about the four glass (or two glass) test: pre- and post- prostatic massage. - **Voided bladder 1 (VB1):** first 10ml of urine passed, represents urethra. - **Voided bladder 2 (VB2):** second 10ml of urine passed, represents bladder. - **Expressed prostatic secretions (EPS):** first 10ml of urine passed, represents urethra. - **Voided bladder 3 (VB3):** first 10ml of urine passed, after EPS. The two glass test, just involving EPS and VB3 is commonly used. **I:** Acute bacterial prostatitis (ABP) **II:** Chronic bacterial prostatitis (CBP) **III:** Chronic pelvic pain syndrome (CPPS) **IIIA:** Inflammatory CPPS (leucocytes in semen/EPS/VB3) **IIIB:** Non-inflammatory CPPS (no leucocytes in semen/EPS/VB3) **IV:** Asymptomatic inflammatory prostatitis (histological prostatitis)

Answer 173

- **Chronic prostatitis/chronic pelvic pain syndrome** Aetiology remains poorly understood Infective and inflammatory triggers may be implicated There are suggestions that some may have a neuropathic component Elevated prostatic pressure Pelvic floor myalgia - **Chronic bacterial prostatitis** May develop following an episode of acute bacterial prostatitis or present more insidiously. The urinary tract is frequently implicated as the source of infection but it may also arise from lymphogenous spread of an infection.

Answer 174

- Those with underlying urinary tract abnormalities are at greater risk. - Men with HIV are at risk of a greater breadth of infection. - Rarely STI’s are the infective agent.

Answer 175

- **Urogenital pain:** often described in the perineum but may also be in the external genitalia, back, lower abdomen or rectal. - **Urinary symptoms** - **Hesitancy** - **Dysuria** - **Frequency** - **Sexual dysfunction** - **Pain on ejaculation** - **Erectile dysfunction** - **Premature ejaculation**

Answer 176

- **Urine dipstick and MSU** - **Expressed prostatic secretions** - **Consider Semen MCS** - **STI screen** (including blood borne viruses) - **Consider PSA** (may be elevated in prostatitis or malignancy) - Consider need for **urological investigation** to identify potential underlying structural abnormalities.

Answer 177

- Chronic prostatitis/chronic pelvic pain syndrome - **Analgesia** - Paracetamol - NSAIDs with PPI cover - **Stool softeners** may offer some relief. - **Referral to pain team specialist** may be needed, particularly if neuropathic pain is considered. - **Alpha-blockers (e.g. Tamsulosin)** may be trialled if significant LUTS are present. - **Referral to urology** if symptoms are severe or persistent, or diagnosis is uncertain

Answer 178

- **Referral to urology** - **Antibiotic course** may be given dependent on the suspected organism. - Length of antibiotics courses vary, discussion with microbiology can help guide management. - **Analgesia** - **Stool softeners** - **Surgical intervention** may be indicated e.g. transurethral resection of the prostate (TURP)

Answer 179

Urethral inflammation due to infectious or non-infectious causes. It is primarily a sexually acquired disease!

Answer 180

- Most common condition diagnosed and treated in men at GUM clinics - Common co-infection with other STDs - Non-gonococcal urethritis is more common than gonococcal urethritis - Chlamydia is the most common STI in young people aged 15-24 yrs

Answer 181

- **Gonococcal:** - Neisseria gonorrhoea - **Non-gonococcal:** - Chlamydia trachomatis - the most common cause - Mycoplasma genitalium - Ureaplasma urealyticum - Trichomonas vaginalis - **Non-infective:** - Trauma - Urethral stricture - Irritation - Urinary calculi

Answer 182

- **Sexually active** - **Multiple sexual partners** - **Unprotected sex** - **Male to male sex** - **Male**

Answer 183

- May be asymptomatic (90-95% with gonorrhoea, 50% of patients with chlamydia) - Dysuria (painful urination) +/- discharge; blood or pus - Urethral pruritus - Urethral pain - Penile discomfort - Inflammation/ oedema - Skin lesions - Systemic symptoms

Answer 184

- **Nucleic acid amplification test (NAAT):** - Female - self collected vaginal swab (best), endocervical swab, first void urine - Male - first void volume - High specificity and sensitivity - **Microscopy of gram-stained smears of genital secretions** - **Blood cultures** - **Urine dipstick -** to exclude UTI - **Urethral smear**

Answer 185

- **UTI** - **Candida balanitis or vaginitis** - **Epididymitis** - **Interstitial cystitis** - **Chronic prostatitis** - **Urethral malignancy** - **Nephrolithiasis**

Answer 186

- Chlamydia: - **Oral azithromycin or oral doxycycline** - **Tests for other STIs** - If pregnant: - **Oral erythromycin or oral azithromycin** - Gonorrhoea: - **IM ceftriaxone with oral azithromycin** - **Partner notification** - **Patient education** - **Contact tracing**

Answer 187

- **Reactive arthritis** - **Gonococcal conjunctivitis** - **Periurethral abscess** - **Urethral stricture or fistula** - **Epididymitis** - **Prostatitis** - **Penile lymphangitis**

Answer 188

Inflammation of the epididymis (coiled tube that stores sperm and transports it from the testes) is referred to as epididymitis, whilst orchitis is inflammation of the testicle. The two can co-exist and is referred to as epididymo-orchitis.

Answer 189

- The most common cause of acute scrotal pain is epididymitis - Most common in male 15-30 yrs olds and those over 60

Answer 190

- **In sexually active males** - Sexually-transmitted infection (STI) organisms are common causes: such as **chlamydia trachomatis, neisseria gonorrhoeae and m*ycoplasma genitalium*** - **In older males** - Non-sexually transmitted infection with enteric pathogens play a larger role, including **E.coli and Proteus sp.** - Other rarer causes exist, including **tuberculous** epididymo-orchitis in endemic areas, as well as **viral infections e.g. mumps.**

Answer 191

- **STI-related:** young, multiple partners, unprotected sex - **Enteric-related:** elderly, bladder outflow obstruction, structural/functional abnormality of urinary tract, instrumentation of urinary tract - **Tuberculosis:** can cause epididymo-orchitis - **Mumps**

Answer 192

- **Tenderness and palpable swelling of the epididymis and testicles** - **Prehn’s sign positive** - Pain relief with lifting the affected testicle - Prehn’s sign is negative in testicular torsion - **Cremasteric reflex preserved (unlike torsion)**

Answer 193

- **Unilateral tender, red, and swollen testicle** - Pain develops over a few days - **Lower urinary tract symptoms e.g. dysuria** - **Urethral discharge: may and or may not be present** - **Urethritis: may or may not be present** - **Pyrexia may or may not be present**

Answer 194

- **Urinalysis:** first void sample is most useful and should be sent for microscopy and culture. - **Nucleic Acid Amplification Test (NAAT):** first void urine sample for NAAT to detect the DNA/RNA of the causative organism - **Swab of urethral secretions**: less sensitive than NAAT ****but must also be performed in symptomatic men

Answer 195

- **STD screening** - **Testicular ultrasound**: if the diagnosis is uncertain - **Surgical exploration**: if torsion cannot be confidently excluded clinically and ultrasound is not available expediently

Answer 196

Testicular torsion

Answer 197

Patients should be treated empirically without waiting for test results. - **First-line for STI:** - **Empirical:** ceftriaxone **and** doxycycline - **Additional management**: no sex until review and partner notification - **Test of cure:** only done in cases where gonorrhoea is confirmed - **First-line for enteric organisms**: - **Empirical:** fluoroquinolone e.g. ofloxacin or ciprofloxacin - **Analgesia** - **Scrotal support,** if needed - **Drainage,** if abscess - **Partner notification:** for patients with a confirmed STI causing epididymo-orchitis

Answer 198

Symptoms should improve after 3 days and be reviewed at 2 weeks. In all patients with a confirmed or suspected STI, ensure adequate partner notification and abstinence. If symptoms persist, consider a testicular ultrasound or urological referral.

Answer 199

- **Musculoskeletal**: reactive arthritis secondary to chlamydia or gonorrhoea - **Infective**: disseminated infection secondary to gonorrhoea - **Reproductive**: male subfertility or infertility - **Urological:** epididymal obstruction and scarring secondary to poorly treated infection

Answer 200

In patients treated expediently with antibiotics, symptoms usually resolve rapidly. However, due to this, many patients are non-compliant with medication leading to poorly treated infections. In these cases, rare complications such as epididymal obstruction, and disseminated disease can occur.

Answer 201

Haemolytic uraemic syndrome (HUS) consists of a triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury (AKI).

Answer 202

- In the developed world, HUS has an incidence of 2 cases per 100,000 people per year - Peak incidence between 6 months and 4 years of age.

Answer 203

- **Primary ‘atypical’ HUS** is rare and is associated with complement dysregulation - **Secondary ‘typical’ HUS** is the commonest type of HUS and is typically triggered by Shiga toxin-producing E.coli 0157:H7 through exposure to undercooked meat. The toxin causes endothelial damage leading to microvascular thrombosis. This process consumes platelets, resulting in thrombocytopenia. These thrombi shear red blood cells, which causes microangiopathic haemolytic anaemia and leads to end-organ damage, particularly renal failure.

Answer 204

- **Age**: most commonly **< 5 years** but can occur at any age, even in adults - **Exposure to Escherichia coli (STEC) 0157:H7**: particularly due to ingestion of undercooked meat; responsible for 90% of cases in children - **Primary ‘atypical’ HUS**: complement dysregulation associated with familial syndromes - **Secondary ‘typical’ HUS**: E. coli 0157:H7, pneumococcal infection, HIV, and other rare causes such as SLE, drugs (e.g. cyclosporin) and cancer

Answer 205

**Typical HUS = D+ haemolytic syndrome (usually associated with diarrhoea)** - E.coli is the main culprit. It attaches to the intestinal wall and secretes shiga-like toxin - The toxin gets absorbed by intestinal blood vessels and is then picked up by immune cells like eosinophils, basophils and neutrophils - The toxin is carried on the surface of these cells to the site of blood filtration - the glomerular capillaries of the kidney - Endothelial cells lining these glomerular capillaries express a glycolipid receptor called globotriaosylceramide or Gb3-receptor that has an incredibly strong affinity for the shiga-like toxin - Once the toxin binds to the Gb3-receptor, it gets engulfed by the endothelial cell. Here, it stops protein synthesis and also leads to the fragmentation of DNA - leading to apoptosis - This disruption to the endothelial lining is repaired by primary haemostasis - platelet plug formation. So when large numbers of kidney endothelial cells start undergoing apoptosis, lots of tiny blood clots start to form in the kidneys **Atypical HUS = D- haemolytic syndrome (no preceding diarrhoea)** - Damage to the endothelial cells lining glomerular capillaries due to: - Infectious causes that are not associated with diarrhoea - Certain medications - Autoimmune causes - Familial forms related to genetic mutations **Either way, the endothelium is damaged. This leads to micrangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure.** - The excessive platelet plug formation leads to thrombocytopenia as platelets are consumed - Microangiopathy refers to the endothelial damage that occurs in the small blood vessels, and the haemolytic anaemia refers to the fact that the clots that form within these small blood vessels act like boulders in a river, making it difficult for red blood cells to flow through without getting damaged and destroyed. Some red blood cells can get smacked up against a blood clot and break - forming schistocytes which are cell fragments. Ultimately this destruction of red blood cells leads to a decreased number of normal functioning red blood cells in the blood, also known as haemolytic anaemia.

Answer 206

- **Dehydration** - Capillary refill > 2s - Tachycardic/hypotensive - Mottled skin - **Pyrexia** - **Pallor:** due to anaemia

Answer 207

- **Bloody diarrhoea** - **Fever** - **Abdominal pain** - **Vomiting** - **Reduced urine output** - Due to RBC destruction: **weakness, fatigue, lethargy, possibly jaundice** - Due to thrombocytopenia: **easy bruising and purpura (bleeding into skin)**

Answer 208

- **Haemolysis screen:** - **FBC:** anaemia, thrombocytopenia - **Blood film:** schistocytes due to microangiopathic haemolysis; fragmented - **LDH:** raised as haemolysis releases lactate dehydrogenase (LDH) - **Haptoglobin:** decreased as haptoglobin binds free haemoglobin - **Liver function:** haemoglobin is broken down to bilirubin - **Urinalysis:** microscopic haematuria and proteinuria - **U&Es:** raised creatinine and reduced eGFR (AKI), often with associated hyperkalaemia - **Stool culture:** E.coli 0157:H7 - **PCR Shiga toxin**

Answer 209

- **IV fluids:** repleting fluid losses is crucial - **Red cell transfusion:** indicated if significant anaemia or reduced haematocrit - **Dialysis:** indicated if there is refractory acidosis, hyperkalaemia, fluid overload or oliguria

Answer 210

- **Antibiotics:** avoid in HUS due to *E.coli* 0157:H7 as they can exacerbate symptoms. Antibiotics may be used in **non-E. coli** causes, such as streptococcal-induced HUS - **Plasma exchange:** indications are complex but typically used for severe cases of HUS **not** associated with diarrhoea - **Eculizumab**: a C5 inhibitor monoclonal antibody typically used in the treatment of adult **atypical** HUS, with greater efficacy than plasma exchange alone

Answer 211

- **Neurological:** encephalopathy, seizures, and strokes are seen in up to 25% of patients - **Renal:** there is a significant ****risk of renal failure, which may require dialysis

Answer 212

Most cases of HUS due to E.coli 0157:H7 are self-limiting, although it does carry a 3% mortality. Furthermore, up to 70% of people with HUS due to E.coli 0157:H7 develop acute renal failure. Fortunately, up to 85% of these patients eventually recover their renal function. Of the various types, atypical haemolytic-uraemic syndrome usually has the worst prognosis

Answer 213

- Nephritic syndrome is typically caused by inflammation that damages the glomerular basement membrane, leading to haematuria and red blood cell casts in the urine. - Eventually, this damage can lead to renal failure, where the individual can present with oliguria, arterial hypertension due to sodium retention, and peripheral and peri-orbital oedema. - Lab tests show high levels of BUN (blood urea nitrogen) and creatinine and on urinalysis, there’s haematuria, proteinuria and RBC casts in the urine. - A 24-hour protein collection is necessary to quantify how many proteins are lost through urine. Nephritic syndrome can be differentiated from nephrotic syndrome because the proteinuria is generally under 3.5 grams per day, or within the “sub-nephrotic range”. - In order to determine the cause, a careful history and a kidney biopsy can help diagnose the particular disease.

Answer 214

There are many disorders that could cause nephritic syndrome. These can be categorised into three groups: - **Caused by type III hypersensitivity** - Post-streptococcal glomerulonephritis - IgA nephropathy - Diffuse proliferative glomerulonephritis - **Caused by multiple causes** - Membranoproliferative glomerulonephritis - Rapidly progressive glomerulonephritis - **Caused by defect in collagen synthesis** - Alport syndrome

Answer 215

- **Haematuria** - **Proteinuria** - **Arterial hypertension** - **Peripheral and peri-orbital oedema** - **Decreased urine output**

Answer 216

- **Bloods:** increased creatinine and BUN (blood urea nitrogen) - **Urinalysis:** haematuria, red blood cell casts, proteinuria (but less than 3.5g per day) - **Renal biopsy** if necessary

Answer 217

- **Immunosuppression** (e.g. steroids) - **Blood pressure control** by blocking the renin-angiotensin system (i.e. ACE inhibitors or angiotensin-II receptor blockers)

Answer 218

- **Acute kidney injury** - **Chronic kidney disease**

Answer 219

Post-streptococcal glomerulonephritis (PSGN) is usually an immunologically-mediated delayed consequence of pharyngitis or skin infections caused by streptococcus pyogenes

Answer 220

- Most frequently seen in children - Usually develops 1-2 weeks after URTI (upper respiratory tract infection)

Answer 221

May be triggered by pharyngitis or skin infection (usually due to streptococcus pyogenes)

Answer 222

- Some group A streptococci strains carry the M-protein virulence factor, which initiates a type III hypersensitivity reaction: antibodies, often IgG and IgM, form immune complexes with the bacterial antigen. - These immune complexes travel to the glomerulus through the blood and deposit in the glomerular basement membrane. - Most of the time they’re subepithelial: between the podocytes and the basement membrane. - The immune complexes initiate an inflammatory reaction in the glomerulus, which involves activation and deposition of C3 complement, inflammatory cytokines, oxidants, and proteases that damage the podocytes.

Answer 223

- Haematuria - Signs of recent infection will be present

Answer 224

- **Bloods:** low levels of C3 and CH50 - **Positive streptozyme test** confirms recent group A streptococcal infection - **Kidney biopsy:** isn’t always necessary, but can provide specific clues - **On light microscopy:** the glomeruli are enlarged and hypercellular. - **On immunofluorescence:** IgG, IgM and C3 deposits along the glomerular basement membrane and the mesangium, which create a “starry sky” appearance. - **On electron microscopy:** subepithelial deposits which appear as “humps”.

Answer 225

- **Furosemide:** for initial treatment of hypertension - **Antibiotics**

Answer 226

PSGN usually resolves on its own in children. In adults, it can sometimes lead to renal failure. Age affects prognosis!

Answer 227

IgA nephropathy (IgAN) is defined by the presence of dominant or co-dominant mesangial IgA immune deposits, often accompanied by C3 and IgG in association with a mesangial proliferative glomerulonephritis of varying severity. Formerly called Berger’s disease.

Answer 228

- IgA nephropathy remains the most common glomerulonephritis in the developed world. - The estimated incidence is 30-45 per million - 80% of cases are diagnosed between the ages of 16 and 35 - IgA nephropathy is more common in Asian populations than Caucasian populations

Answer 229

- **Adolescents and middle age** - **Male gender** - **Ethnicity**: IgA nephropathy is more common in Asian populations than Caucasian populations - **Preceding URTI or gastroenteritis**: infections of the mucosal tracts act as a trigger for the production of IgA, leading to subsequent deposition - **HIV** - **Family history**: an autosomal dominant familial form of IgA nephropathy exists - **Presence of other autoimmune conditions**: linked to conditions such as HSP, SLE, coeliac disease and alcoholic liver disease

Answer 230

- Occurs when abnormal IgA form in the body and the immune system recognises them as foreign. - Episodes of IgA nephropathy tend to develop following an infection of the mucosal lining, for example following an upper respiratory tract infection (URTI) or, less commonly, gastroenteritis. This is likely due to an increased production of IgA, with subsequent IgG recognition and deposition in the kidneys - In response, the body generates IgG antibodies that target these IgAs, forming immune complexes which travel through the bloodstream and then get trapped in the kidney. - The immune complexes specifically deposit in the mesangium (the tissue in the Bowman’s capsule that offers structural support to the glomerular capillaries). - The IgA-IgG immune complexes activate the alternative complement pathway, leading to the release of pro-inflammatory cytokines and migration of macrophages into the kidney, all of which contributes to glomerular injury. - IgA antibodies are mainly secreted by the mucosal tissues of the respiratory and GI tract, so IgA nephropathy usually accompanies a respiratory or a GI infection.

Answer 231

- **Haematuria** - Macroscopic: particularly in younger patients - Microscopic: particularly in older patients - **Oedema:** due to proteinuria - **Cervical lymphadenopathy:** suggests an URTI as a recent trigger - **Hypertension**

Answer 232

- **Pink, red or “coke” tinged urine (haematuria)** - **Foamy urine (proteinuria)** - **Sore throat:** suggests an URTI as a recent trigger - **Loose stools and abdominal discomfort:** suggests gastroenteritis as a recent trigger

Answer 233

- **Urine dipstick:** blood and protein would be expected - **U&Es:** allows the assessment of baseline renal function, as well as monitoring for deterioration - **C3 and C4 levels:** C4 will be normal as the classical complement pathway is **not** activated by IgA nephropathy. However, C3 can either be low or normal depending on the extent of alternative pathway activation. - **Renal biopsy:** definitive **diagnostic** investigation - **On light microscopy**: see mesangial proliferation. - **On immunofluorescence:** IgA immune complexes in the mesangium - **On electron microscopy**: immune complexes are seen in the mesangium.

Answer 234

IgA vasculitis, also known as Henoch-Schonlein purpura: the difference is IgA nephropathy only affects the kidneys, while IgA vasculitis can cause nephritic or nephrotic syndrome, and also presents with colicky abdominal pain, bloody stool, arthritis, and palpable skin lesions.

Answer 235

- **ACE-inhibitor/ARB:** BP control - **Corticosteroids:** offer a 6-month trial if there is persistent proteinuria despite 3-6 months of an ACE inhibitor or ARB - **Statins:** control of high cholesterol has been shown to slow kidney damage - **Omega-3 fatty acids**: available in dietary fish oil, these supplements reduce glomerular inflammation; offer if there is persistent proteinuria despite 3-6 months of an ACE inhibitor or ARB

Answer 236

- **Hypertension:** due to damage to the glomerulus and its filtering function - **Acute kidney injury** - **Chronic kidney disease (CKD)** - **Rapidly progressive glomerulonephritis (RPGN)** - **Nephrotic syndrome**: uncommon and seen in < 10% of patients due to significant proteinuria as a result of increased glomerular permeability - **Henoch-Schönlein purpura**: ****a small-vessel vasculitis secondary to IgA deposition

Answer 237

Approximately 25% of patients with IgA nephropathy develop end-stage renal disease. Poor prognostic factors include: - **Proteinuria**: a decline in kidney function is associated with raised PCR in a dose-dependent manner - **Hypertension** - **Low eGFR**: there is an increased risk of progression to ESRD if there is a low eGFR on first presentation

Answer 238

Diffuse proliferative glomerulonephritis is the most common form of lupus nephritis.

Answer 239

Often caused by systemic lupus erythematosus

Answer 240

Risk factors for lupus nephritis: - **Middle-aged**: peak age of onset is between 15 and 45 years old - **Female gender**: 12 times more common in females - **African and Afro-Caribbean**: more common and more severe in these patients - **Family history**

Answer 241

- Lupus is an autoimmune condition that affects multiple organs, including the kidneys. - This is an example of type III hypersensitivity reaction where immune complexes are formed and deposited in various parts of the body. - Once they reach the kidney, they initiate an inflammatory reaction that leads to nephritic syndrome. - Lupus nephritis is classified depending on the exact site of these immune complexes and subsequent inflammatory reaction. - With diffuse proliferative glomerulonephritis, diffuse means that more than 50% of the glomeruli in both kidneys are affected. - The most common site of deposition is in the subendothelial space: between the endothelial wall and the glomerular basement membrane.

Answer 242

- **Haematuria** - **Proteinuria** - **Hypertension** - **Oedema** - **Lethargy:** linked to renal impairment - Signs of SLE: **musculoskeletal pain; butterfly rash**

Answer 243

- **Urinalysis:** haematuria and proteinuria - **U&Es:** reduced eGFR as renal failure progresses - **Renal USS:** exclude structural pathology - **Renal biopsy: gold-standard** investigation. - **On light microscopy:** immune complexes create an overall thickening of the capillary wall, which gives a “wire loop” appearance. - **On immunofluorescence:** granular immune complexes. - **On electron microscopy:** sub-endothelial immune complexes.

Answer 244

- **Lifestyle:** stop smoking, exercise and dietary advice - **Pharmacology:** combination therapy is often needed and would be commenced under specialist guidance - **Corticosteroids** - **Immunosuppressive agents:** such as cyclophosphamide or azathioprine - **Hydroxychloroquine** - **Renal replacement therapy:** if eGFR continues to deteriorate, patients may need dialysis or renal transplantation - **ACE inhibitor**: preferred for patients with hypertension and renal disease as ACE inhibitors are renoprotective

Answer 245

Renal failure

Answer 246

Diffuse proliferative disease carries the worst prognosis of the lupus nephritis'

Answer 247

Three types of MPGN: they all cause proliferation of mesangial and endothelial cells in the glomerulus.

Answer 248

Primary MPGN is usually seen in younger patients, whilst secondary MPGN is more common overall.

Answer 249

- **Type I MPGN:** the most common subtype (90% of cases) - Associated with **SLE,** **cryoglobulinaemia**, **hepatitis B** and **C**, **chronic lymphocytic leukaemia** and **lymphoma** - **Type II MPGN:** ‘dense deposit disease’ - Due to persistent activation of the alternative complement pathway secondary to **C3 nephritic factor** (found in 70% of patients), which usually stabilises C3 convertase - Low circulating C3 levels - Associated with **factor H deficiency** and **partial lipodystrophy** - **Type III MPGN**: poorly understood - Characterised by subendothelial and subepithelial deposits - Associated with **hepatitis B** and **C**

Answer 250

- **Age**: 75% of primary (idiopathic) cases are diagnosed in patients aged 8-16 years - **Infections**: hepatitis B, hepatitis C, HIV and endocarditis are all risk factors for developing secondary MPGN due to raised antibodies in the blood - **Chronic lymphocytic leukaemia** **and cryoglobulinaemia** - **Acquired partial lipodystrophy (ADP)**: APL is a very rare condition characterised by the loss of fat and is particularly associated with type II MPGN

Answer 251

**Type 1 MPGN** - Most common form - Can be idiopathic or secondary to Hep B or Hep C infection - Type I MPGN usually starts one of two ways: - Through type III hypersensitivity reaction where there are circulating immune complexes made from antibodies bound to antigens released from hep B or hep C infections Over time, these immune complexes that circulate in the body reach the glomerulus and activate the complement system through the classical pathway, also causing complement deposition. These immune complexes end up in the subendothelium: between the endothelial wall and the glomerular basement membrane. - The second way is not caused by a hypersensitivity reaction, but it involves the inappropriate activation of the alternative pathway of the complement system With this pathway, C3 is converted to C3a and C3b by an enzyme called C3 convertase. Inappropriate activation of this enzyme could be caused by a genetic mutation, or a special IgG autoantibody, called “nephritic factor” or C3NeF. This IgG binds to the C3 convertase, stabilising it and allows it to continue working. This “long-life” C3 convertase keeps on converting C3 to C3a and C3b. This process consumes a lot of C3, so serum C3 levels are low. Since in this situation there’s inappropriate activation of complement, there are no immune complex deposits with the complement deposits. - Either way, in type I MPGN the immune complexes and/or complement deposits end up in the subendothelium. - These immune deposits recruit inflammatory cells to the area, causing inflammation and damaging the glomerulus. - This in turn leads to the thickening of the basement membrane, which also triggers the mesangial cells to proliferate and reach through the thick basement membrane with their cytoplasmic arms. - This process is called mesangial interposition which sometimes causes the basement membrane to split around the mesangial cell, forming a duplication of the basement membrane or “tram-track” appearance on light microscopy. - Because of the immune complexes or complement deposits, the glomeruli also appear granular on immunofluorescence. **Type II MPGN** - Also caused by nephritic factors but does not involve immune complexes. - Now classified as its own separate disease called dense deposit disease. - This nephritic factor stabilises the C3 convertase and allows it to keep on converting C3 to C3a and C3b. - Complement deposits in the basement membrane as opposed to the subendothelium as in type I, which leads to inflammation in the basement membrane, and low circulating levels of C3. - MPGN shows the same tram-track pattern on light microscopy.

Answer 252

- **Oedema** - **Oliguria** - **Haematuria** - **Hypertension**

Answer 253

- **Foamy urine (proteinuria)** - **Pink, red or ‘coke’ tinged urine (haematuria)**

Answer 254

- **Urine dipstick:** may demonstrate blood or protein - **Urine microscopy and culture:** confirm the presence of blood or protein and exclude urinary tract infection - **U&Es:** assess baseline renal function and monitor for deterioration - **C3 and C4 levels:** all types of MPGN are associated with C3 hypocomplementaemia - **Type 1 MPGN**: activates classical component pathway → possible C4 **depletion** - **Type 2 MPGN**: normal C4 - C4 levels can be used to distinguish between type 1 and type 2 - **Renal biopsy:** for **definitive diagnosis** - **PAS staining on light microscopy** will show mesangial cell proliferation and capillary thickening; **electron microscopy findings** are as follows: - **Type 1**: subendothelial and mesangial immune deposits resulting in a 'tram-track' appearance - **Type 2**: intramembranous immune complex deposits with 'dense deposits' - **Type 3**: similar features to Type 1 with less hypercellularity - **Immunofluorescence** may reveal C3 deposition, glomeruli appear granular

Answer 255

**Primary (idiopathic) MPGN:** - **Oral cyclophosphamide**: offered for all patients with presumed idiopathic MPGN accompanied by nephrotic syndrome **and** declining kidney function - **Oral mycophenolate mofetil (MMF) and oral corticosteroids**: consider in addition to oral cyclophosphamide **Secondary MPGN:** - **Treat the cause**: if a specific cause is identified, such as hepatitis C virus infection, tailored management is required **General:** - **ACE-inhibitor/ARB:** offered to almost all patients with proteinuric chronic kidney disease to reduce the rate of disease progression - **Statin:** all patients with nephrotic syndrome will be evaluated and treated for dyslipidaemia - **Oral warfarin**: the risk of thrombosis increases as serum albumin falls; consider warfarin in patients with a marked reduction in serum albumin and additional risk factors for thrombosis

Answer 256

- **Hypertension:** due to damage to the glomerulus and its filtering function - **Infection susceptibility:** patients on immunosuppressants are at risk of infection, whilst the loss of immunoglobulin and complement in the urine also contributes - **Pro-thrombotic state:** loss of anti-thrombin III in the urine and increased clotting factor synthesis in liver (to compensate for hypoalbuminaemia) causes hypercoagulability - **Hyperlipidaemia:** increased lipid synthesis occurs in the liver to compensate for hypoalbuminaemia - **Hyperthyroidism:** urinary loss of thyroid binding globulin with nephrotic syndrome may cause low total thyroxine levels - **Hypocalcaemia:** urinary loss of albumin (calcium blood transporter) leads to lower circulating levels of calcium - **Acute kidney injury (AKI)**: MPGN can cause AKI, defined by either oliguria or a rise in creatinine - **Chronic kidney disease**: it is uncommon for patients to present immediately with CKD, however 35-60% of patients will progress to ESRD within 10 years - **Rapidly progressive glomerulonephritis**

Answer 257

35-60% of patients with MPGN will progress to ESRD within 10 years. This number rises to 90% after 20 years. The prognosis for type II is poorer than type I due to a poorer response to treatment

Answer 258

Rapidly progressive glomerulonephritis (RPGN), also known as crescenteric glomerulonephritis, is defined as > 50% glomerular crescent formation on histology or a 50% decline in glomerular filtration rate (GFR) within 3 months

Answer 259

- Can be initiated by type II or III hypersensitivity reactions or sometimes, there are no immune complexes at all. - The inflammation in the glomerulus is so severe, that it breaks the glomerular basement membrane and as a result, the kidney function decreases rapidly in a matter of days to weeks. - RPGN can be idiopathic, but when the cause is known, it can be split into three types: - Type I is associated with Goodpasture disease. It is a type II hypersensitivity reaction caused by anti-glomerular basement membrane antibodies that target the α3 chain of collagen type IV, in the GBM and the alveolar basement membrane. Once these autoantibodies, usually IgG, bind to the α3 chain, they activate the complement system, which damages the basement membrane as well as the nearby endothelium and the underlying organ itself. A similar process is also happening in the basement membrane of the lungs, and causes widespread damage to the alveoli, leading to hemoptysis. - Type II RPGN is another type III hypersensitivity reaction Sometimes, with both post-streptococcal glomerulonephritis and diffuse proliferative glomerulonephritis, the, inflammation in the glomerulus is so severe that it causes the GBM to break, leading to RPGN. - Type III RPGN is caused by pauci-immune vasculitis. Pauci-immune means there’s little or no anti-GBM antibodies or immune-complex deposits. The two ANCA-associated vasculitis include granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, and microscopic polyangiitis. - GPA classically affects the blood vessels supplying three organ systems: the upper respiratory tract, the lower respiratory tract and the kidneys. - Microscopic polyangiitis is precipitated by medications, especially antibiotics like penicillin. - The common feature for RPGN is rapid and severe injury that causes the glomerular basement membrane to break. - This allows material circulating in the blood like red blood cells, inflammatory mediators, plasma proteins, and fibrin to pass through into the Bowman space. - Following this flood of material, more monocytes and macrophages enter the Bowman space, as well as parietal epithelial cells. - The presence of all these foreign materials lead to the expansion of the normally-thin epithelial layer of cells into a thick, characteristic crescent-moon shape.

Answer 260

- **Nephritic syndrome**: haematuria with red cell casts, proteinuria, hypertension and oliguria - **Features of the underlying cause**: for example, anti-GBM disease (Goodpasture’s) is associated with haemoptysis, whereas granulomatosis with polyangiitis (Wegener’s) may present with a vasculitis rash or sinusitis - **GPA symptoms:** - Upper respiratory tract symptoms: chronic sinusitis, otitis media, mastoiditis, perforation of the nasal septum - Lower respiratory tract symptoms: haemoptysis - **Goodpasture disease symptoms:** - Lower respiratory tract symptoms - **Microscopic polyangiitis symptoms:** - Presents similar to GPA but upper respiratory tract symptoms are absent

Answer 261

- **On light microscopy:** crescent moon shape in Bowman’s space mostly made up of fibrin. - **Immunofluorescence** patterns vary with type of RPGN: - Goodpasture disease: immunofluorescence pattern will be linear as antibodies bind to collagen of the glomerular basement membrane. - With type II: immune complexes randomly deposit in the subendothelial space, creating a granular pattern. - Pauci-immune vasculits: immunofluorescence won’t show any immunoglobulins or complement deposition. - Pauci-immune vasculitis: **serum ANCAs** are done to check for this - GPA: c-ANCA antibodies are present and the histology would show non-caseating granulomas. - Microscopic polyangiitis: p-ANCA antibodies are present and histology does not show granulomas.

Answer 262

- Steroids and cyclophosphamide - Treatment of Goodpasture disease: - **Plasmapheresis**: to get rid of bad antibodies.

Answer 263

A genetic disease in which there’s a mutation in the gene that codes for type IV collagen.

Answer 264

- Alport’s syndrome is a rare disease that affects 1 in every 5000-10,000 children. - 50% of untreated males develop kidney failure by age 25

Answer 265

85% of cases are caused by mutations in the COL4A5 gene

Answer 266

- **Male gender**: the condition is most commonly X-linked, therefore severe disease is very rare in females - **Family history**

Answer 267

A genetic disease, where there’s a mutation in the gene that codes for type IV collagen. Type IV collagen is important in the structure of the glomerular basement membrane (GBM), as well as the cochlea, retina, and cornea. In the kidney, defects in type IV collagen result in thinning and splitting of the GBM, with subsequent haematuria, proteinuria, and renal failure.

Answer 268

- **Causes hearing loss during late childhood or adolescence** - **May present with retinopathy and lens dislocation** - **May present with learning disability** - **Haematuria** - **Proteinuria: frothy urine** - **Hypertension** - **Oedema** - **Fatigue and dyspnoea**

Answer 269

- **Audiometry:** sensorineural hearing loss (bilateral) - **Urinalysis:** evidence of haematuria and proteinuria - **U&Es:** evidence of renal failure suggested by a raised creatinine and reduced eGFR - **Renal ultrasound:** exclude structural abnormality - **Renal biopsy: gold-standard** diagnostic investigation - **On electron microscopy:** glomerular basement membrane appears irregularly thin in some areas. Also areas where the glomerular basement membrane is thicker and creates a “basket weave” appearance.

Answer 270

- **ACE inhibitor:** renoprotective and used if proteinuria or hypertension is present - **Renal replacement therapy:** dialysis and transplantation may be needed in advanced disease - Consider transplantation early in young patients with declining renal function - Following transplantation, **transplant failure** may occur due to the presence of anti-GBM antibodies, resulting in a clinical picture similar to Goodpasture’s syndrome - **Refer to ophthalmology** - **Refer to audiologist**

Answer 271

Renal failure

Answer 272

The majority of patients will go on to develop chronic kidney disease at an early age. 50% of untreated males develop kidney failure by age 25, which increases to 90% by age 40 and nearly 100% by age 60. Alport syndrome is associated with an increased risk of cardiovascular disease, therefore a regular lipid screen and metabolic panel should be performed

Answer 273

Nephrotic syndrome is defined as the presence of proteinuria, hypoalbuminaemia, and peripheral oedema

Answer 274

Nephrotic syndrome is relatively rare and has an incidence of 3 cases per 100 000 each year in adults

Answer 275

**Primary: due to direct sclerosis of podocytes on the glomerulus** - **Minimal change disease** - The most common cause in **children** - Often benign and excellent response to steroids - May be preceded by upper respiratory tract infection - Associated with Hodgkin lymphoma - **Focal segmental glomerulosclerosis** - The most common cause in **adults** - Associated with HIV, heroin use, sickle cell disease, SLE - **Membranous nephropathy** - The most common cause in the **elderly** - Can be primary or secondary! - Associated with malignancy, hepatitis B, NSAIDs, SLE - **Membranoproliferative glomerulonephritis** - Rarer cause - **Type I**: associated with hepatitis B and C - **Type II**: associated with C3 nephritic factor **Secondary** - **Diabetes** - Glycosylation of vascular basement membrane leads to microalbuminuria - **Amyloidosis** - Seen in systemic amyloidosis e.g. myeloma and chronic inflammatory conditions - **Infections** - e.g. Hep B, Hep C, HIV - **Drugs** - e.g. NSAIDs, gold, penicillamine

Answer 276

Nephrotic syndrome happens when the glomeruli are damaged and they become more permeable, so they start letting plasma proteins pass from the blood to the nephron and then into the urine. This leads to proteinuria, which is when more than 3.5 grams of protein is excreted through the urine per day. One of the proteins lost through urine is albumin and this leads to hypoalbuminemia. This causes peripheral and periorbital edema since there’s less oncotic pressure in the blood vessels and the fluid leaks out. A nephrotic patient could also present with a hypercoagulable state. This is because the patient is also losing antithrombin III proteins which is the body’s anticoagulant. This means that individuals with nephrotic syndrome are prone to thrombotic and thromboembolic complications. Immunoglobulins are another type of proteins lost through urine, which means that there’s a higher risk for infection. Apart from proteins, lipids are also lost through urine, which gives the urine a frothy or foamy appearance. On microscopy, this leads to fatty lipid casts which are hyaline from dead epithelial cells that contained a lot of fat globules. As compensation, the liver will increase lipoprotein synthesis, which results in hyperlipidemia.

Answer 277

Nephrotic syndrome is characterised by a constellation of features: 1. **Proteinuria** (> 3.5 g/day) 2. **Hypoalbuminemia** (< 30 g/L) which leads to oedema 3. **Hyperlipidaemia** as the liver increases synthesis of lipids in response to low albumin 4. **Hypogammaglobulinemia:** due to loss of immunoglobulin in the urine 5. **Hypercoagulability:** due to loss of antithrombin III, and protein C and S in the urine

Answer 278

Triad of: proteinuria, hypoalbuminaemia, oedema

Answer 279

- **Hypertension** - **Proteinuria** - **Limited or absent haematuria (haematuria more commonly found in NEPHRITIC syndrome)**

Answer 280

- **Frothy urine** - **Facial and peripheral oedema** - **Recurrent infections:** due to hypogammaglobulinemia - **Predisposition to venous thromboembolic disease:** due to hypercoagulability

Answer 281

- **Urinalysis:** proteinuria predominates over haematuria; lipid casts - **24-hour urine protein collection:** > 3.5 g protein - **Urine albumin-creatinine ratio (ACR):** raised due to proteinuria - **U&Es:** monitor eGFR and creatinine to assess for renal failure - **LFTs:** hypoalbuminemia < 25 g/L - **Lipid profile:** hypercholesterolaemia and hypertriglyceridemia - **Renal ultrasound:** exclude structural pathology

Answer 282

- **Renal biopsy:** - Light microscopy to assess glomerular damage - Electron microscopy allows further assessment and visualisation of immune complex deposition - **Assess for the underlying cause** e.g. - If suspecting FSGS, you may consider screening for HIV - ANA, double-stranded DNA antibody, C3 and C4 indicates SLE - Hep B/ Hep C surface antigen?

Answer 283

- **Light microscopy**: normal glomeruli on light microscopy - **Electron microscopy (EM)**: effacement of foot processes

Answer 284

- **Light microscopy**: focal and segmental glomerular sclerosis - **EM**: effacement of foot processes

Answer 285

- **Light microscopy**: thick glomerular basement membrane - **EM**: subepithelial immune complex deposition (spike and dome pattern)

Answer 286

- **Type I**: subendothelial immune complex deposition on EM - **Type II**: intramembranous immune complex deposition on EM

Answer 287

Light microscopy: mesangial sclerosis and Kimmelstiel-Wilson nodules

Answer 288

Light microscopy: apple-green birefringence under polarised microscopy with Congo red stain

Answer 289

- **Low salt, protein and fat diet** - **Improve cardiovascular risk factors**

Answer 290

- **Minimal change disease:** very responsive to steroids, with a 90% response rate - **FSGS:** response to steroids is variable, with up to 50% achieving remission - **Ciclosporin** may be used in steroid-resistant case - **Membranous nephropathy:** corticosteroids are combined with an immunosuppressant; **cyclophosphamide** is the first-line immunosuppressant

Answer 291

- **Diuretics:** symptomatic relief of fluid overload - **ACE inhibitor:** used to reduce proteinuria, particularly in FSGS and membranous nephropathy - **Albumin infusions** may be required in severe hypoalbuminaemia - **Prophylatic anticoagulation** e.g. warfarin - **Antibiotic prophylaxis** may be given if needed (depending on cause) - **Vaccinate** against infections

Answer 292

- **Cardiovascular:** hypercholesterolemia and hypertriglyceridemia are associated with nephrotic syndrome, whilst chronic kidney disease (CKD) increases overall cardiovascular risk - **Haematological:** thrombosis, e.g. renal vein thrombosis, due to **loss** of antithrombin III, and protein C and S in the urine, and the concomitant **rise** in fibrinogen - **Infection:** susceptibility to infections due to hypogammaglobulinaemia - **Renal:** progression to CKD

Answer 293

Prognosis is variable depending on the underlying cause. Prognosis is **good in children** with **minimal change disease** as it is very responsive to steroids and is generally not progressive. Over 90% of patients will respond to oral steroids, with the majority having complete remission. **Adult prognosis is more variable**. In FSGS, treatment may achieve partial or complete remission in 50-60% of patients, whilst the remainder develop renal failure within 10 years. Approximately 50% of patients with membranous disease develop renal failure within 10-20 years.

Answer 294

The most common cause of nephrotic syndrome in children.

Answer 295

The cause is most often idiopathic and it can be triggered by a recent infection, recent vaccination, or by an immune stimulus, like a bee sting.

Answer 296

- This disease is caused by T-cells in the blood, releasing cytokines-glomerular-permeability factor, that specifically damages the foot processes of the podocytes, making them flatten out - a process called effacement. - Normally, podocytes wrap around the glomerular capillaries and maintain the filtration barrier - preventing large molecular weight proteins from entering the urine - Damaged foot processes lose their negatively charged coat, eventually allowing negatively charged molecules, like albumin, to slip into the nephron. - Even though albumin goes through, other larger proteins like immunoglobulins don't. - So there's selective proteinuria; in contrast to other causes of nephrotic syndrome which are characterised by non-selective proteinuria.

Answer 297

- On light microscopy, the glomeruli look completely normal. - In some cases, there can be lipids in the proximal tubular cells. - Immunofluorescence is negative. - The only changes are seen on electron microscopy, where there’s effacement of podocyte foot processes.

Answer 298

Idiopathic minimal change disease is the only nephrotic disease that can be consistently treated with corticosteroids.

Answer 299

- The most common cause of nephrotic syndrome in individuals of African or Hispanic descent. - More common in adults

Answer 300

Can be idiopathic, but many patients have a history of heroin abuse, HIV infection, interferon treatment or congenital malformations.

Answer 301

- Pathophysiology not known but there is effacement of podocyte foot processes. - Additionally, there’s also hyalinosis that’s caused by deposition of lipids and proteins in the glomerulus. - Over time, hyalinosis further develops into sclerosis or scar tissue.

Answer 302

- On light microscopy, there’s sclerosis and hyalinosis among the glomeruli. - FSG is segmental - only a part of the glomeruli is affected - and focal - only some of the glomeruli are affected. - Immunofluorescence is often negative, but can sometimes be positive for deposits of C3, C1 or IgM.

Answer 303

Primary FGS has an inconstant response to corticosteroids and some individuals may progress to CKD

Answer 304

- Can be primary - Or secondary to - SLE, drugs e.g. NSAIDs, gold and penicillamine, infections- particularly hep B, hep C or syphillis and solid tumours e.g. colorectal carcinoma

Answer 305

The damage is caused by immune complexes. These immune complexes are called subepithelial deposits because they build up right between the podocytes and the glomerular basement membrane. These subepithelial deposits are thought to activate the complement system, which directly damages both the podocytes as well as mesangial cells. One major antigen that’s been identified is the phospholipase A2 receptor or PLA2R - In the serum of individuals with membranous nephropathy - you can find IgG antibodies against PLA2R.

Answer 306

On light microscopy, there’s diffuse capillary and glomerular basement membrane thickening caused by immune complexes deposition. When the sample is stained with silver methenamine, irregular expansions from the glomerular basement membrane can be seen. Immunofluorescence will show that the immune complexes are granular and mostly made of IgG and C3. On electron microscopy, there’s flattening of the podocyte foot processes and subepithelial deposits of immune complexes. There are thin expansions of the glomerular basement membrane that separate or surround the immune complexes, creating “spike and dome” pattern.

Answer 307

Poor response to corticosteroids and individuals may progress to CKD

Answer 308

- When there’s a lot of glucose in the blood, it can stick to proteins in the blood- this is called non-enzymatic glycation - As glucose can get through the endothelium, this process of glycation can also involve the basement membrane of the efferent arteriole, making it thicken and creating an obstruction that increases the pressure in the glomeruli as it is harder for blood to leave. - Eventually the afferent arteriole dilates, further increasing the pressure. - High pressure in the glomerulus leads to an increase in the GFR - this is called hyperfiltration. - In response to this high-pressure state, the mesangial cells secrete more and more structural matrix expanding the size of the glomerulus. - This matrix deposition and mesangial expansion happen uniformly, or it can result in little nodules within the mesangium called Kimmelstiel-Wilson nodules - which are tiny little balls of protein.

Answer 309

- Amyloids are proteins with an abnormal shape, which makes them stick together and settle in tissues. - Amyloidosis is the name for the disease that develops as a result of the tissue damage from these protein depositions. - The kidneys often get affected by amyloidosis.

Answer 310

**Typical Features** Nephritic - Haematuria, Hypertension, Oedema Nephrotic - Proteinurea, hypoalbuminaemia, oedema, +/- Hypertension **Key causes** Nephritic - Rapdily-progressive GN, IgAN, Alports, Post-strep GN, Difffuse Proliferative GN, Membranoproliferative GN Nephrotic - MCD, Membranous GN, Focal segmental glomerulosclerosis, amyloidosis

Answer 311

Autosomal dominant polycystic kidney disease is a common genetic disorder characterised by multiple renal cysts.

Answer 312

- Inheritance of the abnormal genes PKD1 or PKD2 is thought to occur in around 1 in 1000 live births. - It accounts for up to 10% of patients with end stage renal disease (ESRD). - ADPKD is generally a condition of adults and rarely presents in childhood. - The estimated median age of developing ESRD is in 6th decade for PKD1 and 8th decade for PKD2. - M>F

Answer 313

- **Due to PKD1 or PKD2 mutations. Autosomal dominant inheritance** - PKD1 encodes protein polycystin-1: involved in cell adhesion through protein-protein, cell-cell, and/or cell-matrix interactions thought to be due to regulation of calcium influx. **PKD1 has a more severe phenotype and is more common** - PKD2 encodes the protein polycystin-2. It is a type of calcium-permeable channel transmembrane proteins, which co-localises with polycystin-1. **PKD2 has a less severe phenotype** - Rarely, a third form has been identified known as **PKD3**, which has been linked to several genes including GANAB

Answer 314

- **PKD1 mutation** - **Large kidneys** - **Recurrent visible haematuria** - **Frequent kidney infections** - **Afro-Caribbean ancestry** - **Hypertension** - **Male gender**

Answer 315

**Mutations** ADPKD is caused by PKD1 and PKD2 mutations PKD1 mutations cause the more severe and earlier onset variety PKD2 mutations causes less severe disease and is also later in onset PKD1 and PKD2 code for the polycystin 1 and polycystin 2 proteins, respectively, which are components of the primary cilium. The primary cilium is an appendage that sticks out from most cells in the body and receives developmentally important signals. In the nephron, as the urinary filtrate flows by and cause the cilium to bend, polycystin 1 and polycystin 2 respond by allowing calcium influx, which activates pathways in the cell that inhibit cell proliferation. If either component is absent, that signal to inhibit growth isn’t received, and so cells proliferate abnormally and start to express proteins that cause water to be transported into the lumen of the cyst, which makes them get larger and larger, compressing the surrounding tissue more and more. This is how cysts develop and grow A person who develops ADPKD would have inherited a single, heterozygous mutation in PKD1 or PKD2. This leaves one functional copy of the gene in every cell, and this produces enough polycystin 1 or polycystin 2 to prevent cyst formation. BUT a random mutation in the remaining good copy of the gene is almost guaranteed to happen in some of the tubular cells as the kidney develops. This ‘second hit’ causes polycystin 1 or 2 to be absent and is what impairs normal signalling through the cilium and leads to cyst formation. **Cyst consequences:** These cysts, which are lined with renal tubular epithelium, fill up with fluid and get larger over time, making the kidneys much larger than normal. The blood vessels that feed neighbouring healthy nephrons can get compressed by growing cysts, which literally starves them of oxygen. Poorly perfused kidneys respond by activating the RAAS system, which facilitates fluid retention and leads to hypertension. Expanding cysts can compress the collecting system, causing urinary stasis, and in some cases this can lead to [](https://www.osmosis.org/learn/Kidney_stones)kidney stones. Additionally, destruction of the normal renal architecture can cause symptoms like flank pain and haematuria. Over time, as enough nephrons are affected, it leads to renal insufficiency and renal failure. **Extra-renal manifestations:** Polycystins are important in the kidney, but are developmentally important in other places of the body, too. Patients can have cysts that are typically benign pop up in the liver, seminal vesicles, and pancreas. The vasculature can also be affected, for example individuals might develop aortic root dilation which can lead to heart failure, and have berry aneurysms of the cerebral arteries, usually in the Circle of Willis. These aneurysms can have a thin wall, allowing them to rupture and develop into a subarachnoid haemorrhage

Answer 316

- **Bilateral flank masses**: due to large polycystic kidneys - **Hypertension**: seen in most patients by 4th decade of life

Answer 317

- **Abdominal, flank or back pain**: due to large size or cyst complications (rupture/infection) - **Haematuria**: typically occurs in association with ruptured cyst - **Dysuria and fever**: suggestive of urinary tract infection or infected cyst - **Renal colic**: nephrolithiasis (i.e. stones) more common - **Constitutional features of chronic kidney disease**: fatigue, weakness, reduced energy - **Polyuria, polydipsia, nocturia**: excess urine due to poor concentrating ability of kidneys (i.e. not responding to anti-diuretic hormone)

Answer 318

- **Polycystic liver disease**: seen in > 80% of patients on MRI imaging. - **Hepatomegaly**: if polycystic liver disease - **Pancreatic cysts**: seen in up to 36% of patients. - **Cerebral aneurysms**: four times higher compared to general population. Rupture most serious complication of ADPKD. - **Cardiac valve disease**: seen in 25-30%. Most commonly mitral valve prolapse and aortic regurgitation. - **Gastrointestinal abnormalities**: diverticulosis and hernias (abdominal/inguinal) occur at higher frequency - **Seminal vesicle cysts and infertility**: vesicle cysts in up to 40% of males. Rarely causes infertility. ADPKD also associated with poor sperm motility.

Answer 319

**Imaging:** - **Ultrasound**: principle investigations, especially in screening - **Renal MRI/CT**: high sensitivity and good for assessing progression (e.g. kidney size). Useful if concern regarding renal cell carcinoma (RCC) - **CT KUB**: if presenting with suspected renal stone - **Cerebral imaging (e.g. MRA)**: screening for cerebral aneurysms

Answer 320

**If positive family history** - **< 30 years**: ≥3 cysts (unilateral or bilateral) - **30-39 years**: ≥3 cysts (unilateral or bilateral) - **40-59 years**: ≥2 cysts in each kidney **If no family history is present, there is no established imaging based criteria**. Generally, a diagnosis can be made in the presence of multiple bilateral renal cysts (e.g. ≥10 and ≥5mm in size) or bilateral renal enlargement with cysts.

Answer 321

- **Screening patients with family history of ADPKD:** usually with ultrasound - **Genetic testing:** usually reserved for atypical cases with no family history - **Bloods** - **Full blood count**: anaemia if CKD or haemorrhagic cysts - **Urea & electrolytes**: assessment of renal function - **Liver function tests**: any hepatic impairment from cysts - **Bone profile**: calcium/phosphate handling in CKD - **CRP**: infected cysts - **Protein:creatinine ratio** (ACR) - **Urinalysis and MC&S**: infection or haemorrhage

Answer 322

- **Multiple benign cysts**: cysts more common as we age - **Localised cystic benign**: unilateral disease - **Acquired renal cystic disease**: may be seen in patients with CKD on dialysis - **Medullary sponge kidney**: congenital disorder of collecting ducts and calyceal system - **Other genetic conditions**: e.g. autosomal recessive polycystic kidney disease, tuberous sclerosis

Answer 323

Management generally targets the symptoms - **General treatment:** - Blood pressure control: ACE inhibitors - Regular follow-up including renal function assessment and ultrasound to look for progression - Maintain adequate hydration (3+ litres/day) unless significant CKD and dietary sodium restriction - Avoid contact sports due to the risk of cyst rupture - Avoid anti-inflammatory medications and anticoagulants - **Treatment for high-risk patients**: vasopressin (V2) receptor antagonists e.g. Tolvaptan can slow the development of cysts and the progression of renal failure - **Managing complications**: - Treat urinary tract infections and infected cysts: antibiotics - Analgesia for abdominal pain or cyst rupture (avoid NSAIDs). - Rarely, cyst decompression and/or nephrectomy may be needed if recurrent infections or pain that significantly impacts on quality of life. - Haematuria managed conservatively where possible. - If concerns, needs work-up for RCC. - **Transplant/ dialysis:** in cases of kidney failure - **Genetic counselling** may be offered

Answer 324

**Monitor patients for disease progression and complications** - Regular ultrasound to monitor the cysts - Regular bloods to monitor renal function - Regular blood pressure to monitor for hypertension - Aneurysm screening - reserved for patients with a personal or family history of intracerebral haemorrhage, patients who require anticoagulation, patients with high-risk occupations or patients needing major surgery

Answer 325

- **Ruptured cyst**: common cause of loin pain, usually self-limiting - **Haemorrhagic cyst**: describes a ruptured cyst with haemorrhage. If occurs into the collecting system can be associated with visible haematuria. Loin pain common as with ruptured cysts. - **Infected cyst**: many occur in relation to rupture. Typical features include fever, pain, dysuria. - **Renal stones** - **Hypertension** - **ESRD** - **Sepsis** - **Cerebral haemorrhage** (e.g. aneurysm rupture) - **Progressive liver disease:** if cystic liver - **Cardiovascular disease**

Answer 326

Autosomal recessive condition in which the kidneys become filled with hundreds of fluid-filled sacs, causing them to be larger than normal and to quit functioning over time.

Answer 327

- ARPKD is rarer and more severe than ADPKD. - Prevalence at 1 in 40,000 - Disease of infancy

Answer 328

PKHD1 mutation on long arm (q) of chromosome 6

Answer 329

Family history

Answer 330

**Mutations** ARPKD happens when someone inherits a mutation on both copies of the PKHD1 gene, which codes for the fibrocystin protein. Fibrocystin/polyductin protein complex (FPC) is responsible for the creation of tubules and the maintenance of healthy epithelial tissue in the kidneys, liver and pancreas. Fibrocystin co-localizes with polycystin 2, where it might be involved in the regulation pathway and calcium signalling described with ADPKD. It is therefore thought that a similar mechanism might cause cyst formation in ARPKD. **ARPKD consequences:** ARPKD cyst formation can lead to renal failure even before birth, which means the foetus has trouble producing urine, and since amniotic fluid comes from foetal urine, foetuses with ARPKD can develop oligohydramnios, or low amniotic fluid. If enough amniotic fluid is missing, it can can cause Potter syndrome: without the amniotic fluid, the uterine walls compress the foetus, which causes physical developmental abnormalities, like club feet, underdeveloped ear cartilage, low set ears, a flat nasal bridge and abnormalities of the skeleton. There is also the development of pulmonary hypoplasia or underdeveloped lungs since the amniotic fluid is important in helping the lungs expand and develop normally. Underdeveloped lungs can cause respiratory insufficiency after birth, which ends up being fatal in a lot of cases of ARPKD. ARPKD also causes congenital hepatic fibrosis, which over time can cause portal hypertension, or compromised blood flow through the portal venous system. Portal hypertension can cause oesophageal varices, upper GI bleeds, haemorrhoids and splenomegaly from blood being shunted through collateral veins. Cholangiocytes (epithelial cells that line the bile ducts) also have primary cilia that express fibrocystin, and so ARPKD can also cause defects in the bile ducts which leads to dilation. Dilated intrahepatic ducts, which can cause cholestasis or poor bile secretion, and dilation of the common bile duct can lead to ascending cholangitis. **General cyst consequences with ADPKD and ARPKD:** These cysts, which are lined with renal tubular epithelium, fill up with fluid and get larger over time, making the kidneys much larger than normal. The blood vessels that feed neighboring healthy nephrons can get compressed by growing cysts, which literally starves them of oxygen. Poorly perfused kidneys respond by activating the RAAS system, which facilitates fluid retention and leads to hypertension. Expanding cysts can compress the collecting system, causing urinary stasis, and in some cases this can lead to [](https://www.osmosis.org/learn/Kidney_stones)kidney stones Additionally, destruction of the normal renal architecture can cause symptoms like flank pain and hematuria, or blood in the urine. Over time, as enough nephrons are affected, it leads to renal insufficiency and renal failure. Patients with ARPKD usually have end-stage renal failure before reaching adulthood.

Answer 331

- **Oligohydramnios**, **pulmonary hypoplasia** and **Potter syndrome** - **Cystic enlargement** of the **renal collecting ducts** - May present with **renal failure at birth** - **Congenital liver fibrosis**

Answer 332

- **Prenatal ultrasound:** may show bilaterally large kidneys with cysts and oligohydramnios - OR **neonatal ultrasound**

Answer 333

- **CT & MRI:** to monitor liver disease - **Genetic testing**

Answer 334

- **ADPKD** - **Acquired cystic kidney disease** - **Benign cysts** - **Tuberous sclerosis** - **Multicystic dysplasia:** one kidney only is made up of cysts. Other kidney is normal - **Medullary sponge kidney:** congenital disorder of collecting ducts and calyceal system - **Hydronephrosis** - **Renal vein thrombosis**

Answer 335

No actual treatment. Management of PKD is usually directed at specific symptoms and organ dysfunction. - Hypertension: treated with **ACE inhibitors** - **Analgesia** for renal colic related to stones or cysts. (Not NSAIDs) - **Antibiotics** for infection. Drainage of infected cysts may be required. - In cases of kidney failure, **dialysis or kidney transplant** are sometimes needed. Patients may require dialysis in first few days of life with ARPKD - **Genetic counselling** for family members

Answer 336

- **Regular ultrasound to monitor the cysts** - **Regular bloods to monitor renal function** - **Regular blood pressure to monitor for hypertension**

Answer 337

- **Liver failure** due to liver fibrosis - **Portal hypertension** leading to oesophageal varices and other complications - **Progressive renal failure** - **Hypertension** due to renal failure - **Chronic lung disease**

Answer 338

The prognosis is poor. Survival depends on very extensive interventions from a number of different specialties both in the neonatal period and throughout life. Around 1/3 will die in the neonatal period. Around 1/3 will survive to adulthood.

Answer 339

**All testicular lumps = cancer until proven otherwise!** **Acute, tender enlargement of testis = testicular torsion until proven otherwise!** 1. *Can you get above it?* 2. *Is it separate from the testis?* 3. *Cystic or solid?* - Cannot get above = inguinoscrotal hernia, hydrocele extending proximally - Separate and cystic = epididymal cyst - Separate and solid = epididymitis, varicocele - Testicular and cystic = hydrocele - Testicular and solid = tumour, haematocele, granuloma, orchitis, gumma (non cancerous growth)

Answer 340

Smooth, extra-testicular, spherical sac of fluid in the head of the epididymis (top of testicle). They are usually harmless.

Answer 341

- **Usually develop in adulthood** (around the age of 40) - **Not uncommon** - **Rare in children**

Answer 342

Contain clear or milky (spermatocele) fluid They lie above and behind the testis

Answer 343

- Signs - **Palpable lump** (often multiple and bilateral) - **Well defined** and will **transluminate** since fluid-filled - Symptoms - Can cause **dragging and soreness** - May be **pain** if cysts are large

Answer 344

Scrotal ultrasound

Answer 345

- **Hydrocele** - **Varicocele**

Answer 346

- **Usually not necessary** - **Removed, if symptomatic**

Answer 347

Hydrocele refers to a collection of serous fluid between the parietal and visceral layers of the tunica vaginalis (membrane covering the testes).

Answer 348

Originally the tunica vaginalis is part of the peritoneal membrane, but during development of the fetus it becomes separated from the peritoneal membrane and remains in the scrotum, partially covering each testicle.

Answer 349

- **Communicating** These occur due to the failure of normal closure of the processus vaginalis. This allows the passage of peritoneal fluid into the tunica vaginalis. Communicating hydroceles are therefore considered congenital though they may present in older children, adolescents and adults. A patent (open) processus vaginalis is common. It is estimated to be present in 80-94% of newborns and 20% of adults. - **Non-communicating (simple)** There is no abnormal connection with the peritoneal cavity as seen in communicating hydroceles. Instead fluid is produced by the mesothelial lining of the tunica vaginalis. They occur when there is an imbalance between fluid production and absorption. Many are idiopathic but identifiable triggers include trauma, infection (e.g. epididymo-orchitis) and testicular torsion. Others: - **Hydrocele of the spermatic cord:** Segmental closure of the processus vaginalis results in an isolated segment of fluid. - **Abdomino-scrotal hydrocele:** Rarely a hydrocele enlarges, propagates up the inguinal canal and develops an abdominal component.

Answer 350

- **Primary hydrocele:** - More common and larger - Usually in younger men - Associated with a patent processus vaginalis, which typically resolves during the 1st year of life - **Secondary hydrocele:** - Rarer and present in older boys and men - Secondary to: - Testis tumour - Trauma - Infection - TB - Testicular torsion - Generalised oedema In adults communicating hydroceles may present for the first time due to increases in intra-abdominal pressure, fluid overload or continuous peritoneal ambulatory dialysis.

Answer 351

- Scrotal swelling (in front and below testicle) - **Smooth** - **Non-reducible** - **Demonstrating transillumination with pen-torch** - **Non-tender** - **Soft and fluctuant (communicating hydrocele)** - **Stays one size (non-communicating hydrocele)** - Communicating hydroceles tend to change size and increase when standing for prolonged periods

Answer 352

Testicular ultrasound

Answer 353

- **Partially descended testes** - **Inguinal hernia** - **Testicular torsion** - **Varicocele** - **Epididymal cyst** - **Haematoma** - **Tumours (rare)**

Answer 354

- May resolve within first year of life - Patients should have ongoing observation to ensure resolution occurs and to identify the development of an inguinal hernia - If surgery is indicated, it is an open repair with high ligation of patent processus vaginalis (for communicating hydroceles)

Answer 355

- Non-communicating hydroceles may have spontaneous repair. - Scrotal support may help adults with symptoms of discomfort. - Late onset communicating hydrocele less likely to resolve - Aspiration of a hydrocele is simple and may give initial relief - Surgical options include: - **Lord’s procedure:** this involves plication (folding) of the sac. - **Jaboulay procedure:** the sac is opened drained, partially excised, everted and sutured behind the testicle.

Answer 356

A varicocele refers to dilated testicular veins within the pampiniform plexus. The vast majority (around 90%) occur on the left side.

Answer 357

- They occur most commonly in adolescent boys and may affect up to 15% of men. - It is strongly associated with infertility, and is seen in around 40% of men presenting with infertility. - Left side most commonly affected

Answer 358

Varicoceles occur due to dilation of the pampiniform plexus in the scrotum. The pampiniform plexus drains via the gonadal (testicular) veins. Anything that leads to increased pressure may cause varicoceles. This may be caused by incompetent or absent valves leading to venous reflux. The majority occur on the left side (around 90%) due to the asymmetrical anatomy. The left gonadal vein is longer and joins the left renal vein at a right angle. The right gonadal vein drains more obliquely, directly into the IVC. Rarely varicoceles can herald a compressive mass or vascular spread of a malignancy. This is classically described in renal cell carcinoma with spread into the left renal vein. **Malignancy:** Varicoceles may be a sign of a renal cancer (or other intra-abdominal cancers). The majority of all varicoceles occur on the left side as the left gonadal vein tends to drain at a sharp angle into the left renal vein and is longer than the right draining into the IVC. The vast majority of varicoceles will not indicate cancer, however tumours that compress venous return (classically left side, but right side may also be affected) can be a cause.

Answer 359

- Signs - **Palpable veins (described as bag of worms)** - **Scrotum may hang lower on side of varicocele** - **Signs of testicular atrophy may be seen on the affected side.** - Symptoms - **Painless testicular swelling** - May reduce on lying and be exacerbated by a Valsalva manoeuvre (slow breathing) - **Some patients develop symptoms: discomfort, pain or a dragging sensation.**

Answer 360

- **Testicular examination:** demonstrates dilated veins (bag of worms) - Examination is conducted both standing and lying. - The size of each testicle should be evaluated. - **Doppler USS** may be used in cases of diagnostic uncertainty and to confirm diagnosis. - **Fertility assessments** may be completed. Semen analysis can be sent alongside FSH and testosterone levels.

Answer 361

- **Sub-clinical:** No clinical abnormality, only detected by Doppler ultrasound. - **Grade I (small):** Only clinically palpable with Valsalva manoeuvre. - **Grade II (moderate):** Palpable without Valsalva manoeuvre. - **Grade III (large):** Varicocele is visible through the scrotal skin, easily palpable.

Answer 362

**Refer any patient who’s varicocele becomes symptomatic.** Urgent referral is advised if: - **It appears suddenly and is painful** - **Does not drain when lying down** - **Solitary right-sided varicocele** Adolescents may be referred if: - **Reduced testicular volume** - **Patient or parental concern** If the testicular swelling is of uncertain origin, the patient should be referred to urology. Men with infertility may also be referred, particularly if Grade II/III disease with abnormal semen parameters.

Answer 363

- Surgical - **Inguinal / subinguinal approach** - **Retroperitoneal high ligation** - **Microsurgical inguinal** - **Laparoscopy** - Endovascular - **Antegrade sclerotherapy** - **Retrograde sclerotherapy** - **Retrograde embolisation**

Answer 364

- **Testicular mass** - **Hydrocele** - **Inguinal hernia**

Answer 365

- **Testicular atrophy** - **Infertility/ subfertility**

Answer 366

Testicular torsion is a urological emergency caused by twisting of the testicle on its spermatic cord, leading to ischaemia and eventually necrosis. Germ cells are most susceptible to ischaemia. “6 hour window” after onset before damage from ischaemia is irreversible!

Answer 367

- Incidence of 1 in 4000 in males < 25 years of age in the US - Quite common in adolescent boys and young men - Two peaks; one in the neonatal period and one around puberty, with a peak incidence of 13 to 15 years old

Answer 368

- **Young age** - **Bell clapper deformity:** high riding testicle with a horizontal lie - **Cryptorchidism:** undescended testis increase the risk of torsion and would usually present in the first few months of life - **Trauma:** trauma-induced torsion accounts for less than 10% of cases

Answer 369

**Physiology:** - The developing testicle descends through the inguinal canal and is covered in peritoneum as it does so - This layer of peritoneum is known as the tunica vaginalis, which goes on to attach to the scrotum **Pathology:** - Failure of the tunica vaginalis to properly attach to the scrotum results in the ‘bell clapper’ abnormality (a risk factor for testicular torsion) - Normally the testicle is fixed posteriorly to the tunica vaginalis. Bell-clapper deformity is where this fixation is absent. It allows testicle to rotate within tunica and as it rotates it twists the vessels and cuts of its blood supply

Answer 370

- Signs - **Swollen, high-riding and tender testicle: skin may be erythematous** - **Abnormal lie** - Horizontal lie - Rotated so that epididymis is not in normal posterior position - Elevated (retracted) testicle - **Prehn’s negative:** - Pain is **not** relieved on lifting the ipsilateral testicle, unlike in epididymitis - **Absent cremasteric reflex** - Swipe the superior and inner part of the thigh - A normal reflex contracts the cremaster muscle, pulling up the ipsilateral testis - Reflex **almost always absent**

Answer 371

- **Testicular pain** - Usually unilateral, sudden onset and excruciatingly painful - Often triggered by activity - Pain may be severe, intermittent and self-limiting; intermittent pain does **not** rule out torsion - **Nausea and vomiting** secondary to pain is common - **Lower abdominal pain:** referred pain

Answer 372

Imaging should not be considered if testicular torsion is suspected as it will delay surgery! - 1st line **Surgical exploration:** should be performed immediately if there is high clinical suspicion as it allows definitive diagnosis and management. Should be performed within 6 hours to prevent irreversible damage (90% salvageable at 6 hours and 10% salvageable at ≥24 hours) - Other - **Testicular ultrasound**: operator-dependent; ‘whirl-pool’ sign suggests torsion, as does decreased blood flow in the affected testicle on colour doppler - **Urinalysis:** an abnormal result such as the presence of leukocytes and nitrites may suggest an alternative diagnosis, e.g. epididymo-orchitis

Answer 373

- **Epididymo-orchitis/ epididymitis** - **Torsion of the Hydatid of Morgagni (embryonic remnant of the Mullerian duct)** - **Hydrocele** - **Varicocele** - **Testicular cancer**

Answer 374

Bilateral orchiopexy: the affected testicle is untwisted and fixed to the scrotal sac. The contralateral testicle should always be fixed to prevent contralateral torsion

Answer 375

Ipsilateral orchiectomy and contralateral orchiopexy: removal of the affected testis and fixation of the contralateral testis to the scrotal sac to prevent contralateral torsion

Answer 376

Manual detorsion: a temporary measure that should only be performed if surgery is not available within 6 hours. Surgical exploration must be subsequently performed to ensure the viability of the testis

Answer 377

- **Recurrent torsion**: may occur several years after the procedure despite orchiopexy **(rare)** - **Infertility/ subfertility**: torsion for 10-12 hours results in ischaemia and irreversible damage. Orchiectomy results in decreased spermatogenesis - **Pubertal delay:** may occur, particularly if bilateral orchiectomy is performed; hormone replacement may be required

Answer 378

Prognosis depends on the time taken from onset of symptoms to surgical management, with increasing time resulting in testicular ischaemia and infarction. This can result in loss of the testis and reduced fertility. As a general rule, if surgical intervention is performed: - Within **4-6 hours** of symptoms, the testis can be saved in the majority of cases - A delay of **10-12 hours** or more results in irreversible ischaemia and necrosis - The testis is salvageable **<10% of** cases at **≥24 hours**

Answer 379

“Obstructive Uropathy” refers to a problem passing urine that is a result of an obstruction along the urinary tract. Can be partial, complete, unilateral or bilateral. This can be a lower urinary tract issue: bladder and urethra OR a upper urinary tract issue: kidneys and ureter

Answer 380

- **Lower urinary tract** - Benign prostatic hyperplasia (enlarged prostate) - Prostate cancer - Urethra strictures (from scar tissue) - Neurogenic bladder (no neurological signal telling bladder to contract) - Neurological e.g. cauda equina syndrome - **Upper urinary tract** - Kidney stones - Local cancer masses pressing on the ureters - Ureter strictures (scar tissue narrowing tube)

Answer 381

**Luminal:** - Stones - Blood clot - Sloughed papilla - Tumour **Mural:** - Congenital or acquired stricture - Neuromuscular dysfunction - Schistomiasis **Extra-mural:** - Abdominal or pelvic mass/tumour, - Retroperitoneal fibrosis - BPH or prostate cancer - Pregnancy - Inflammation e.g. peritonitis or diverticulitis - Iatrogenic e.g. post-surgery

Answer 382

- Lower urinary tract obstruction - **Acute urinary retention** (unable to pass urine and increasingly full bladder) - **Lower urinary tract symptoms** (e.g. frequency, poor flow, difficulty initiating urination, terminal dribbling, overflow incontinence) - **Suprapubic pain** - **Distended, palpable bladder thats dull to percussion +/- large prostate** - **Acute confusion:** in the elderly - **May be reduced renal function on bloods**

Answer 383

- **Loin to groin / flank pain on affected side** (result of stretching / irritation of ureter and kidney) - **Reduced / no urine output** - **Non-specific symptoms** (e.g. vomiting) - **Reduced renal function on bloods** - **There may be a superimposed infection**

Answer 384

- **Bloods:** - U&Es - Creatinine - will be raised - FBC - PSA - **Urine** - Dipstick - Microscopy, culture & sensitivity - **Ultrasound:** imaging modality of choice - **CT:** if there is hydronephrosis or hydroureter - **Radionuclide imaging:** functional assessment of kidneys

Answer 385

- Lower urinary tract obstruction management - **Urethral catheter** - **Suprapubic catheter:** - *Requires general anaesthetic for insertion* - *Small risk of bowel injury during insertion* - *Less risk of urethral damage and thus UTI than urethral catheter* - *Less likely to be colonised by bacteria than a long term urethral catheter* - *Long term urethral catheter can lead to urethral erosion and damage to the urethral sphincter* - Clot retention: patient requires **catheterisation and bladder washout** - **Treat underlying cause** e.g. Alpha-1 blockers or TURP for prostatic obstruction

Answer 386

**RUSHES** - **R**etention - **U**TI’s - **S**tones - **H**aematuria - **E**levated creatinine due to bladder outflow obstruction - **S**ymptoms deterioration

Answer 387

- Upper urinary tract obstruction management - **Nephrostomy** - artificial opening created between the kidney and the skin which allows for the urinary diversion directly from the upper tract i.e. renal pelvis - **Ureteric stent** - **Alpha-1 antagonist** e.g. tamsulosin (bladder neck smooth muscle relaxer) - improves flow - **5-alpha reductase inhibitor** e.g. finasteride - inhibits conversion of testosterone to potent form and thus reduces prostate size - **Pyeloplasty:** to widen the PUJ (pelvic-utero junction)

Answer 388

- **Acute Kidney Injury** (postrenal AKI) - **Chronic kidney disease** - **Urinary retention** - **Infection** (from pooling of urine and retrograde infection – bacteria tracking back up urinary tract) - **Dilated kidney / ureters / bladder** - **Pain** - **Hyperkalaemia** - **Metabolic acidosis** - **Post-obstructive diuresis:** rapid fluid depletion after obstruction is resolved. Will require fluid replacement - **Sodium- and bicarbonate-losing nephropathy:** after obstruction is resolved, there are high amounts of sodium and bicarbonate lost in the urine that need replacing

Answer 389

Von Hippel Lindau disease is a rare autosomal dominant disorder characterized by a mutation in a tumour suppressor gene which leads to the formation of cysts and benign tumours in various parts of the body like the eye, CNS, kidneys, adrenal glands and pancreas.

Answer 390

- Patients typically develop their first lesion by their 20s - Age of onset varies with lesion type e.g. haemangioblastomas usually occur earlier in life than RCC tumours.

Answer 391

**Physiology:** The VHL gene is a tumour suppressor gene on the short arm of chromosome 3. It codes for proteins that degrades hypoxia-inducible transcription factor (HIF). HIF upregulates genes that code for platelet-derived and vascular endothelial growth factors, both of which promote new blood vessel formation and cell growth. **Pathology:** In VHL disease, this tumour suppressor gene is mutated which increases HIF, PDGF, VEGF, and ultimately the risk of tumour formation. **Acquiring VHL:** It is inherited in an autosomal dominant pattern, meaning that a VHL patient has a 50% chance of passing it on to each kid they have. 20% of VHL patients have a de novo or new mutation, meaning they are the first VHL patient in their family. **Tumour types:** **Haemangioblastoma:** a benign blood vessel tumour occurring in about 60% of VHL patients. In the central nervous system, these can occur in the retina, brain, and spinal cord. **Cystadenomas:** benign cysts and cyst-like tumours. - The most concerning is the endolymphatic sac tumor of the inner ear which can cause deafness. - Cystadenomas can develop in the broad ligament in women, and the epididymis in men, and incidental cysts can occur in the liver, lung, kidney and pancreas in both men and women. **Renal cell carcinoma** **Pancreatic neuroendocrine tumours** **Paragangliomas:** these tumours release cathecholamines e.g. epinephrine and norepinephrine - They are known as pheochromocytomas when occurring in adrenal glands

Answer 392

Depends on lesion: - Refer to RCC for RCC symptoms - Sympathetic symptoms e.g. headaches, sweating, palpitations, hypertension if paragangliomas present - Deafness if cystadenomas in ear - Blindness with haemangioblastomas affecting the eye - Ataxia (loss of balance) if haemangioblastoma is in cerebellum - Headaches, nausea and vomiting if haemangioblastoma blocks flow of CSF

Answer 393

Depends on lesion type e.g. surgical removal for RCC or laser treatment for haemangioblastomas in the eye

Answer 394

Since new lesions can develop repeatedly in the same organs, regular surveillance is crucial for improving quality of life and lifespan.

Answer 395

The number one cause of death in patients with VHL is the development of RCC

Answer 396

- Normally, urine is held in the bladder, which receives urine from two ureters coming down from the kidneys and then that urine leaves the bladder through the urethra. As urine flows from the kidney, through the ureters and into the bladder, the bladder starts to expand into the abdomen. - The bladder is able to expand and contract as it’s wrapped in a muscular layer - the detrusor muscle - and within that, lining the bladder itself is a layer of transitional epithelium containing “umbrella cells”. These umbrella cells physically stretch out as the bladder fills. - When the urine is collecting in the bladder, there are basically two sphincters that are shut, holding the urine in. The first is the internal sphincter muscle, which is made of smooth muscle and is under involuntary control. Typically, that internal sphincter muscle opens up when the bladder is about half full. - The second is the external sphincter muscle, and it’s made of skeletal muscle and is under voluntary control. - When stretch receptors in the bladder wall sense that the bladder is roughly half full, they send impulses to the sacral spinal cord at levels S2 and S3, known as the micturition center, and the brain, specifically two locations in the pons—the pontine storage center and pontine micturition center. - The spinal cord response is part of the micturition reflex. It causes an increase in parasympathetic stimulation and decrease in sympathetic stimulation which makes the detrusor muscle contract and the internal sphincter relax. It also decreases motor nerve stimulation to the external sphincter allowing it to relax as well. - At this point, urination would occur if not for the pons. The pons is the region of the brain that we train to voluntarily control urination. If we want to delay urination, the pontine storage centre overrides the micturition reflex, and when we want to urinate, the pontine micturition centre allows for the micturition reflex to happen. - Once urine has passed through the external sphincter muscle, it exits the body—in women the exit is immediate and in men the urine flows through the penis before it exits.

Answer 397

Urinary incontinence is a problem where the process of urination, also called micturition, happens involuntarily.

Answer 398

- Urge incontinence: **overactive bladder due to uninhibited detrusor muscle** - Stress incontinence**: urine leaks out due to high abdominal pressure** - Mixed incontinence: **combination of stress and urge incontinence** - Overflow incontinence (neurogenic bladder): **bladder doesn't empty completely which leads to eventual leak. Usually due to damage of peripheral nerves or nerves of the brain and spinal cord** - **Sphincter damage:** outlet incompetence Causes (that damage the nerves involved in micturition reflex): - **Diabetes** - **Bladder cancer** - **Parkinson's** - **Multiple sclerosis** - **Prostatectomy** - **Hysterectomy**

Answer 399

- **Increased age** - **Postmenopausal status** - **Obesity** - **Pregnancy** - **Vaginal delivery** - **Prostate surgery** - **Pelvic floor surgery** - **Pelvic organ prolapse** - **Neurological conditions, such as multiple sclerosis** - **Cognitive impairment and dementia**

Answer 400

- **Urge incontinence** - Sudden urge to urinate because of an "overactive bladder", followed immediately by involuntary urination. This is typically due to an uninhibited detrusor muscle that contracts randomly. - Usually associated with urinary tract infections. Inflammation may trigger the detrusor muscle. - **Stress incontinence** - Increased abdominal pressure overwhelms the sphincter muscles and allows urine to leak out. Causes include pregnancy and exertion, like sneezing, coughing, laughing. - **Overflow incontinence** - Caused by an issue with emptying the bladder. This could be due to a blockage in urine flow, e.g. hypertrophic prostate in men which presses on the urethra or an ineffective detrusor muscle (e.g. in diabetes, neurogenic bladder associated with multiple sclerosis, spinal cord injury). Either way, the bladder doesn’t empty properly, and as a result the bladder fills up and overflows with urine which leaks through the sphincters. Examples of some causes: - Diabetes: excess glucose glycates proteins which can damage sensory fibers in bladder wall, pelvic nerve or in dorsal nerve roots. This interferes with initial stretch signal - Multiple sclerosis: myelin sheath of the nerves is affected. This prevents inhibitory signals from the pons, causing detrusor hyperreflexia - Syphilis: leads to tabes dorsalis (inflammation and scarring of dorsal nerve roots) - Herpes: disturbs sensory fibres in dorsal root - Injury to spinal cord: can result in detrusor hyporeflexia (due to no micturition reflex) or hyperreflexia (due to no inhibitory input from the pons) - Acute injury to brain: hyporeflexia followed by hyperreflexia (similar to spinal cord injury) - Chronic injury to brain: e.g. tumour or Parkinson's, results in detrusor hyperreflexia - **Outlet incompetence:** - Can be caused by urethral hypermobility (urethra can’t be kept still by the muscles surrounding it) or intrinsic sphincter deficiency (damage to sphincter muscles, which is often a complication of prostate surgery).

Answer 401

- Urge incontinence: **frequent urination, especially at night** - Stress incontinence: **urinary leakage with pressure applied to the abdomen** - Overflow incontinence: **weak or intermittent stream or hesitancy**

Answer 402

- **A medical history** should distinguish between the types of incontinence. - Assess for modifiable risk factors: - **Caffeine consumption** - **Alcohol consumption** - **Medications** - **Body mass index (BMI)** - Assess the **severity** by asking about: - **Frequency of urination** - **Frequency of incontinence** - **Nighttime urination** - **Use of pads and changes of clothing**

Answer 403

- **Examination** should assess the pelvic tone and examine for: - **Pelvic organ prolapse** - **Atrophic vaginitis** - **Urethral diverticulum** - **Pelvic masses** During the examination, ask the patient to cough and watch for leakage from the urethra - **Bladder diary:** tracking fluid intake and episodes of urination and incontinence over at least three days. - **Urine dipstick testing:** performed to assess for infection, microscopic haematuria and other pathology. - **Post-void residual bladder volume:** measured using a bladder scan to assess for incomplete emptying. - **Urodynamic testing:** used to investigate patients with urge incontinence not responding to first-line medical treatments, difficulties urinating, urinary retention, previous surgery or an unclear diagnosis. It is not always required where the diagnosis is possible based on the history and examination.

Answer 404

A thin catheter is inserted into the bladder, and another into the rectum. These two catheters can measure the pressures in the bladder and rectum for comparison. The bladder is filled with liquid, and various outcome measures are taken: - **Cystometry** measures the detrusor muscle contraction and pressure - **Uroflowmetry** measures the flow rate - **Leak point pressure** is the point at which the bladder pressure results in leakage of urine. The patient is asked to cough, move or jump when the bladder is filled to various capacities. This assesses for stress incontinence. - **Post-void residual bladder volume** tests for incomplete emptying of the bladder - **Video urodynamic testing** involves filling the bladder with contrast and taking xray images as the bladder is emptied. These are only performed where necessary and not a routine part of urodynamic testing.

Answer 405

- **Bladder retraining** (gradually increasing the time between voiding) for at least six weeks is first-line - **Anticholinergic medication**, for example, oxybutynin, tolterodine and solifenacin - **B3 adrenergic agonist: mirabegron** is an alternative to anticholinergic medications - **Invasive procedures** where medical treatment fails More invasive treatments: - **Botulinum toxin type A** injection into the bladder wall - **Percutaneous sacral nerve stimulation** involves implanting a device in the back that stimulates the sacral nerves - **Augmentation cystoplasty** involves using bowel tissue to enlarge the bladder - **Urinary diversion** involves redirecting urinary flow to a urostomy on the abdomen

Answer 406

- **Avoiding caffeine, diuretics and overfilling of the bladder** - **Avoid excessive or restricted fluid intake** - **Weight loss** (if appropriate) - **Supervised pelvic floor exercises** for at least three months before considering surgery - **Pessary** (device that is inserted) may be helpful to some women - **Surgery:** - **Tension-free vaginal tape** (TVT) procedures involve a mesh sling looped under the urethra and up behind the pubic symphysis to the abdominal wall. This supports the urethra, reducing stress incontinence. - **Autologous sling procedures** work similarly to TVT procedures but a strip of fascia from the patient’s abdominal wall is used rather than tape - **Colposuspension** involves stitches connecting the anterior vaginal wall and the pubic symphysis, around the urethra, pulling the vaginal wall forwards and adding support to the urethra - **Intramural urethral bulking** involves injections around the urethra to reduce the diameter and add support - **Artificial urinary sphincter:** pump inserted into the labia that inflates and deflates a cuff around the urethra, allowing women to control their continence manually. - **Duloxetine** is an SNRI antidepressant used second line where surgery is less preferred

Answer 407

Re-establish a clear pathway for urine flow e.g. catheterisation or medications like alpha-blockers, which relax smooth muscle to assist with urination.

Genitourinary Flashcards

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