1
Q
What are renal stones also known as?
A
Nephrolithiasis
2
Q
What is the epidemiology of kidney stones?
A
- 30-60 year olds
- More common in male
3
Q
What are the risk factors for developing kidney stones?
A
- Dehydration
- Previous kidney stones
- Stone forming foods
- Metabolic
- Systemic disease: Crohn’s disease (calcium oxalate stones)
- Metabolic:hypercalcaemia, hyperparathyroidism, hypercalciuria (calcium stones)
- Loop diuretics
4
Q
What are some stone forming foods?
A
- Chocolate
- Spinach
- Nuts
- Tea
5
Q
What are the most common types of kidney stones?
A
Calcium-based stones they account for 80%. Having a raised serum calcium and low urine output are key risk factors for calcium collecting into a stone
6
Q
What are the two types of calcium stone?
A
- Calcium oxalate (most common) results in a black or dark coloured stone.
- Calcium phosphate- results in a dirty white colour stone
7
Q
What are some other types of kidney stones?
A
- Uric acid: red-brown in colour and not visible under an x-ray.
Risk factors: food high in purines e.g. shellfish, anchovies, red meat or organ meat, as uric acid is a breakdown product of purine - Struvite- produced by bacteria (Proteus mirabilis, Proteus vulgaris, and Morganella morganii) therefore are associated with infection. Forms dirty white stones visible on X-ray.
- Cystine – associated with cystinuria, an autosomal recessive disease form yellow or light pink coloured stones not visible on x-ray
8
Q
What causes kidney stones?
A
When solutes in the urine precipitate out and crystalline. Urine is a combination of solvent and solutes
If solvent is low (dehydration) or there are high levels of solute (hypercalcaemia) then it is more likely a kidney stone will form.
9
Q
What substances can prevent the formation of kidney stones?
A
Magnesium and citrates inhibit crystal growth
10
Q
What causes struvite stones to form?
A
Bacteria release enzyme urase which causes ammonia to form. Ammonia makes urine more alkaline so favours the precipitation of phosphate, magnesium and ammonium.
These form jagged crystals called Staghorns
11
Q
What is the cause of the pain associated with kidney stones?
A
- The peristaltic action of the collecting duct against the stone.
- Pain is worse at the uteropelvic junction and down the ureter pain subsides once stone gets to the bladder
12
Q
What are the signs of kidney stones?
A
- Flank/ renal angle tenderness
- Fever (if sepsis)
13
Q
What are the symptoms of renal stones?
A
- Acute severe flank pain: loin to groin pain that lasts minuets to hours . Fluctuating pain
- Nausea and vomiting
- Haematuria
- reduced urine output
14
Q
What are some first-line investigations for renal stones?
A
- Urine dipstick can show blood
- FBC check kidney function and calcium levels
- X-ray can show calcium based stones but not uric
15
Q
What is the gold standard test for renal stones?
A
- Non contrast CT scan of kidney, ureters and bladder (CT KUB) .
Should be performed within 14 hours of admission
May use ultrasound if radiation needs to be avoided
16
Q
What is the best form of pain relief for renal stones?
A
- NSAIDs are typically used. IM diclofenac is most commonly used. Opiates are typically used as not good
17
Q
What is the conservative/medical treatment for renal stones?
A
- Watchful waiting is usually used in stones less than 5mm, as there is a 50-80% chance they will pass without any interventions. It
- Tamsulosin is an alpha blocker that can be used to help passage of stones not indicated for renal more for ureteric
18
Q
What are the surgical treatments for renal stones?
A
ESWL involves an external machine that generates shock waves and directs them at the stone under x-ray guidance. The shockwaves break the stone into smaller parts to make them easier to pass.
Ureteroscopy and laser lithotripsy:
A camera is inserted via the urethra, bladder and ureter, and the stone is identified. It is then broken up using targeted lasers, making the smaller parts easier to pass.
Percutaneous nephrolithotomy (PCNL):
PCNL is performed in theatres under a general anaesthetic. A nephoscopy (small camera on a stick) is inserted via a small incision at the patient’s back. The scope is inserted through the kidney to assess the ureter. Stones can be broken into smaller pieces and removed. A nephrostomy tube may be left in place after the procedure to help drain the kidney.
19
Q
What is the advice for a patient suffering from recurrent renal stones?
A
- Increase oral fluids
- Reduce salt intake
- Reduce oxalate/urate rich food intake
- Avoid carbonated drinks
- Add lemon juice to waters
20
Q
What medications can be used to reduce the risk of renal stone formation?
A
Potassium citrate in patients with calcium oxalate stones and raised urinary calcium
Thiazide diuretics (e.g., indapamide) in patients with calcium oxalate stones and raised urinary calcium
21
Q
What are the complications of renal stones?
A
- Obstruction and hydronephrosis: acute kidney injury and renal failure
- Urosepsis: an infected, obstructing stone is a urological emergency and requires urgent decompression
22
Q
What is acute kidney injury?
A
A sudden decline in renal function over a few days. It is diagnosed by measuring serum creatinine
23
Q
What is the RIFLE criteria for classifying AKI?
A
- RIF describes the three levels of renal dysfunction and two outcome measures (LE). These criteria are used to indicate the increasing degree of renal damage and have a predictive value for mortality.
R- Risk
I- Injury
F- failure
L-loss
E- end-stage renal disease
24
Q
What is KDIGO?
A
Kidney Disease: Improving Global Outcomes it divides AKI into 3 stages
Stage 1: serum creatinine greater than 26.5 (1.5-1.9 times baseline) with urine output less than 0.5ml for 6-12 hours
Stage 2: serum creatinine 2-2.9 times the baseline and less than 0.5ml/kg for 12 hours
Stage 3: serum creatinine 3 times the baseline and less than 0.3ml/kg of urine for greater than 12 hours
25
What are the NICE criteria for diagnosing an AKI?
Rise in creatinine of ≥ 25 micromol/L in 48 hours
Rise in creatinine of ≥ 50% in 7 days
Urine output of < 0.5ml/kg/hour for > 6 hours
26
What is the pre-renal cause of AKI?
- Hypoperfusion due to hypovolaemia. This causes ischaemia of the the renal parenchyma. Prolonged ischaemia can lead to intrinsic damage
- Heart failure
- Dehydration
- Hypotension
27
What are the intrinsic renal causes of an AKI?
- **Vascular**: can be due to atherosclerotic disease and dissections. Also can be caused by renal artery stenosis
- **Glomerular**: may be primary or secondary. Can lead to nephritic or nephrotic syndrome
- **Tubulo-intestinal**: usually due to acute tubular necrosis or acute interstitial nephritis that can occur secondary to medications (e.g. NSAIDs, ACE inhibitors, PPI’s, penicillin's) and infections.
28
What are the 3 diseases most linked to renal causes of an AKI?
Intrinsic disease in the kidney is leading to reduced filtration of blood. It may be due to:
Glomerulonephritis
Interstitial nephritis
Acute tubular necrosis
29
What is the post renal cause of an AKI?
- Obstruction- due to urinary stones, malignancy or bladder neck obstruction e.g., benign prostate hyperplasia
30
What are the risk factors for developing an AKI?
- Chronic kidney disease
- Heart failure
- Diabetes
- Liver disease
- Older age (above 65 years)
- Cognitive impairment
- Nephrotoxic medications such as NSAIDS and ACE inhibitors
- Use of a contrast medium such as during CT scans
31
What are the signs and symptoms of pre-renal AKI?
- Reduced capillary refill time
- Reduced skin turgor
- Thirst
- Dizziness
- Tachycardia
- Hypotension
- Reduced urine output
32
What are the signs and symptoms of a vascular AKI?
- Arterial hypertension and peripheral oedema
33
What are the signs and symptoms of nephrotic syndrome AKI?
- Heavy proteinuria
- Hypoalbuminemia
- Oedema
34
What are the signs and symptoms of Nephritic syndrome AKI?
- Haematuria
- Proteinuria
- Oliguria
- Hypertension
35
What are the signs and symptoms of Tubulo-intestinal disease AKI?
- Arthralgia (joint pain)
- Rashes
- Fever
36
What is the most useful investigation for investigating an AKI?
**Urinalysis** for protein, blood, leucocytes, nitrites and glucose.
- Leucocytes and nitrites suggest infection
- Protein and blood suggest acute nephritis (but can be positive in infection)
- Glucose suggests diabetes
37
What other investigations might you perform for an AKI?
- Vasculitis screen (e.g. ANCA, ANA)
- Hepatitis screen
- Blood gas
- LFT
38
What is the management for AKI?
- Regular monitoring
- Cease nephrotoxic drugs
- IV fluids for hypovolaemia
- Relieve obstruction
39
What is the major complication of an AKI and how would ypu treat it?
Hyperkalaemia as potassium is not being removed from the blood.
Treat first with calcium gluconate to protect the heart then use insulin and dextrose. Salbutamol can also be used to drive potassium into cells
40
What are some other complications of an AKI?
- Fluid overload which can cause heart failure and oedema
- Metabolic acidosis
- Uraemia can lead to **Encephalopathy** or **Pericarditis**
41
What is the mnemonic for assessment and management of AKI?
RENAL DRS26
R- Record baseline creatinine
E- Exclude obstruction
N- Nephrotoxic drugs stopped
A- Asses fluid status
L- Losses+/-
D- Dipstick
R- review medications
S- Screen
26- Creatinine rise for AKI diagnosis of higher than 26
42
What is chronic kidney disease?
A progressive deterioration in renal function over at least 3 months
43
What are the most common causes of CKD?
- Hypertension (second most common)
- Diabetes (most common)
44
What are some other causes of CKD?
- Systemic disease e.g., Rheumatoid arthritis
- Infections (HIV)
- Medications, PPI, ACE inhibitor, NSAIDs, lithium
- Toxins (in smoking)
- Age-related decline
- Glomerulonephritis
- Polycystic kidney disease
45
How does hypertension cause CKD?
- Walls of arteries thicken in order to withstand higher pressure resulting in a narrow lumen
- This means less blood is delivered to the kidney resulting in ischaemic injury
- This causes the infiltration of immune cells that secrete **TGF-b1**. This growth factor transforms mesangial cells back to more immature stem ell which diminishes their ability to filter the blood
46
How does diabetes cause CKD?
- Excess glucose in the blood starts sticking to proteins (non-enzymatic glycation).
- This particularly affects the efferent arteriole and causes it to get stiff and narrow. This creates an obstruction and makes it difficult for the blood to leave the glomerulus.
- Over many years this process dimishes the nephrons ability to filter blood
47
What are the signs of CKD?
- Hypertension
- Fluid overload
- Uraemic sallow: yellow or pale brown colour of skin
- Uraemic frost: urea crystals can deposit in the skin
- Pallor
- Evidence of underlying cause
48
What are the symptoms of CKD?
- Pruritis
- Loss of appetite
- Nausea
- Oedema
- Muscle cramps
49
What are the investigations for CKD?
- **Estimated GFR**: can be checked using U&E blood test. **Two tests required 3 months apart**
- **Proteinuria**: can be checked using a **urine albumin:creatinine ratio**. A result of greater than 3mg/mmol is significant
- **Haematuria**: can be checked using a **urine dipstick**
- **Renal ultrasound**
50
What can be used to stage CKD?
G score and A score
51
What is the G score?
G score is based of eGFR
G1: eGFR>90
G2: eGFR: 60-89
G3a: eGFR: 45-59
G3b: eGFR: 30-44
G4: eGFR: 15-29
G5: eGFR<15 known as end-stage renal failure
52
What is the A score?
Based off the albumin:creatinine ratio:
A1: <3
A2: 3-30
A3: >30
53
What score would indicate a paitient does not have CKD?
A1 combined with G1 or G2
54
What is the management for CKD?
Slowing the progression of the disease
Optimise diabetic control
Optimise hypertensive control
Treat glomerulonephritis
Reducing the risk of complications
Exercise, maintain a healthy weight and stop smoking
Special dietary advice about phosphate, sodium, potassium and water intake
Offer atorvastatin 20mg for primary prevention of cardiovascular disease
55
What are the complications of CKD?
- Renal bone disease
- Anaemia
- Cardiovascular- hypertension, hypercholesterolemia , heart failure due to fluid overload and anaemia
56
How does CKD cause renal bone disease?
- There is high serum phosphate as there is reduced phosphate excretion. There is also a low amount of active vitamin D as it is activated in the kidneys
- Therefore there is secondary hyperparathyroidism as a result which leads to an increase in osteoclast activity
57
What are the 3 types of renal bone disease?
- Osteomalacia: occurs due to increased turnover of bones without calcium supply
- Osteosclerosis: osteoblasts respond to increase osteoclast activity and make new tissue but it is poorly mineralised due to the lack of calcium
- Osteoporosis
Osteomalacia (softening of bones)
Osteosclerosis (hardening of bones)
Osteoporosis (brittle bones)
58
What is the management of renal bone disease?
- Supplements of active forms of Vit D. (alfacalcidol and calcitriol)
- Low phosphate diet
- Bisphosphonates can be used to treat osteoporosis
59
How does CKD cause anaemia?
- Erythropoietin is used to stimulate the production of RBC. In CKD there is reduced secretion of erythropoietin.
- Anaemia caused by this can be treated by giving exogenous erythropoietin.
**Blood transfusions should be limited as they can sensitise the immune system (“allosensitisation”) so that transplanted organs are more likely to be rejected**
60
What is pyelonephritis?
- Upper urinary tract infection: acute inflammation of the renal pelvis (join between kidney and ureter) and parenchyma
61
What is the epidemiology of Acute pyelonephritis?
- Affects females under 35
- Unusual in men
62
Why are UTI's more common in women?
The urethra is much shorter in women so it makes it easier for bacteria to reach the bladder and kidneys
63
What causes Acute pyelonephritis?
Can be spread via ascending infections or hematogenous spread
Common species include:
- E.coli (most common)
- Klebsiella
- Enterobacter
- Staphylococcus
64
What are the risk factors for Acute pyelonephritis?
- Sexual intercourse
- Catheter
- Diabetes
- Pregnancy
- Renal stones
65
Describe the pathophysiology of Acute pyelonephritis?
- Most often caused by ascending infection. Bacteria will start by colonising the urethra and bladder and make their way up to the kidney
- Risk of lower UTI transferring to an upper UTI is increased by **vesicoureteral reflux** where urine is allowed to move back up the urinary tract due to a failure in the vesicoureteral orifice
66
What are the signs of Acute pyelonephritis?
- Tender loin on examination
- Pain on palpation of renal angle
Symptoms will often be present on both sides as both kidneys are affected
67
What are the symptoms of Acute pyelonephritis?
- Fever
- Loin to groin pain
- Dysuria (painful to piss) and urinary frequency
- Haematuria
- Cloudy foul smelling urine
68
What can help to distinguish Acute pyelonephritis from a lower tract UTI?
- Fever
- Loin/back pain
- Nausea/vomiting
- Renal angle tenderness
69
What are the investigations for Acute pyelonephritis?
- Nitrites as gram negative bacteria such as E.coli and Klebsiella breakdown nitrates into nitrites
- Leukocyte esterase on urine dipstick indicates an infection
Nitrites are better indication. But leukocyte esterase plus haematuria indicates infection
70
What is the gold standard test for Acute pyelonephritis?
- Mid-stream urine MCS- white blood cell in the urine
71
What is the treatment for Acute pyelonephritis?
- **Broad spectrum antibiotics (e.g. co-amoxiclav)** until culture and sensitivities are available
- **Hydration**
72
What are the complications of Acute pyelonephritis?
- Renal abscess
- Recurrent infections
- Chronic pyelonephritis- which can leads to the scaring of renal tissue which can lead to AKI and CKD
- Papillary necrosis
73
What is cystitis?
A lower UTI that involves the bladder
74
What are the risk factors of cystitis?
- Post-menopause the absence of oestrogen increases the risk
- Sexual intercourse
- Diabetes
- Poor bladder emptying- allows the bacteria to adhere and colonise the bladder
75
What are the causes of cystitis?
- 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.
76
What are the signs of cystitis?
Suprapubic tenderness
77
What are the symptoms of cystitis?
- Dysuria
- Frequency
- Urgency
- Nocturia
- changes in appearance
- Suprapubic discomfort
78
What is the gold standard test for cystitis?
- **Mid-stream urine microscopy, culture and sensitivity (MC&S)**:
- The most specific and sensitive test; bacteria, WBCs, +/- RBCs expected
79
What are the treatments for non-pregnant women with cystitis/Lower UTI
Treatment may be delayed if symptoms are mild
- First line would be 3 days of **nitrofurantoin avoided in patients with CKD** or **trimethoprim**
- Second line Antibiotic course for 3 days -**pivmacillinam or fosfomycin single-dose sachet**
80
What are the treatments for pregnant women/catheter related/men with cystitis/Lower UTI?
- **First line:** Antibiotic course for 7 days - nitrofurantoin avoid in third trimester. Trimethoprim is avoided in first trimester as it increases the risk of neural tube defects
- **Second line:** Antibiotic course for 7 days - amoxicillin or cefalexin
81
What are the complications of UTIs in pFregnancy?
- **Pre-term delivery**
- **Low-birthweight**
82
What is prostatitis?
A severe infection involving the prostate that may cause significant systemic upset
83
What are some causes of prostatitis?
- E.coli most common
- STI's
- Catheter
- Disseminated infections- secondary to S.aureus due to metastatic spread
84
What are the signs of prostatitis?
- Tender, hot swollen prostate (on digital rectal exam)
- Palpable bladder
- Tachycardia
- Pyrexia
85
What are the symptoms of prostatitis?
- Dysuria
- Frequency and retention
- Straining
- Back pain
- Fever
- Perineal, rectal or pelvic pain
86
What are the investigations for prostatitis?
- Digital rectal exam
- Urine dipstick
- MSU, semen and blood culture
87
What is the treatment for prostatitis?
First line- Oral ciprofloxacin or ofloxacin
Second line- Oral levofloxacin or co-trimoxazole
88
What are the complications of prostatitis?
- **Acute urinary retention**
- **Epididymitis**
- **Chronic prostatitis**
- **Prostatic abscess**
89
How would you classify chronic prostatitis?
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)
90
What is Urethritis?
Urethral inflammation due to infectious or non-infectious causes. It is primarily a sexually acquired disease!
91
What is the most common STI in young people?
Chlamydia (louis has this)
this is slander and i do not stand for it
92
What are the two categories that urethritis infections are divided into?
Gonococcal and non-gonococcal
93
What is the cause of gonococcal Urethritis?
Neisseria gonorrhea
94
What are the common causes of NGU?
- Chlamydia trachomatis (most common accounts for up to 50%)
- Mycoplasma genitalium
95
What are some rare causes of NGU?
- Trichomonas vaginalis
- Yeasts
- Herpes simplex virus
- Adenovirus
- Other bacteria such as streptococci, mycobacteria, or anaerobes.
96
What are some non-infective causes of urethritis?
- Trauma
- Irritation
- Urinary calculi (in english we call these kidney stones why use silly words)
97
What are the risk factors for getting urethritis?
- Male to male sex
- Unprotected sex
- multiple sexual partners
98
What are the common symptoms of urethritis?
- Urethral discharge
- Urethral irritation/itching
- Dysuria
- Penile discomfort
- Skin lesions
99
What are the investigations for urethritis?
- Nucleic acid amplification test
- Microscopy of gram-stained smears of genital secretions
- Culture of urethral discharge
- Urine dipstick to rule out UTI
100
What is the management for chlamydia?
- Oral **azithromycin** or oral **doxycycline**
- If pregnant give erythromycin
101
What is the management for gonorrhoea?
- IM ceftriaxone with oral azithromycin
Also partner notification and contact tracing
102
What are the complications of urethritis
- **Reactive arthritis**
- **Gonococcal conjunctivitis**
- **Periurethral abscess**
- **Urethral stricture or fistula**
- **Epididymitis**
- **Prostatitis**
- **Penile lymphangitis**
103
What is epididymo-Orchitis?
Inflammation of the epididymis (epididymitis) and inflammation of the testicle (orchitis)
104
What are the common causes of Epididymo-Orchitis in sexually active men?
STIs e.g., Chlamydia trachomatis, Neisseria Gonorrhoea and mycoplasma genitalium
105
What are the common causes of Epididymo-Orchitis in older patitents?
- E.coli and proteus sp.
- Can also be caused by TB and viral infections such as mumps
106
What are the signs of Epididymo-Orchitis?
- Tenderness and palpable swelling
- **Prehn's sign positive**: pain is relieved with lifting the testicle, negative in testicular torsion
- **Cremasteric reflex preserved**- unlike testicular torsion
107
What are the symptoms of Epididymo-Orchitis?
- **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**
108
What are the investigations for Epididymo-Orchitis?
- Urinalysis
- Nucleic acid amplification test (NAAT)
- Swab of urethral secretions
109
What is the treatment for enteric organism causes of Epididymo-Orchitis?
- Fluoroquinolone e.g., ofloxacin or ciprofloxacin
110
What are the complications of Epididymo-Orchitis?
- Musculoskeletal: reactive arthritis
- Infective: disseminated infection secondary to gonorrhoea
111
What are the complications of Epididymo-Orchitis?
- Musculoskeletal: reactive arthritis
- Infective: disseminated infection secondary to gonorrhoea
- Infertility
- Urological: epidydimal obstruction and scarring secondary to poorly treated infection
112
What is nephritic syndrome?
- Nephritic syndrome or acute nephritic syndrome refers to a group of symptoms, not a diagnosis.
- They fit a clinical picture of having inflammation of their kidney and it does not represent a specific diagnosis or give the underlying cause. -
113
What are the features of nephritic syndrome?
Haematuria
Oliguria
Proteinuria
Fluid retention
114
What is Nephrotic syndrome?
Refers to a group of symptoms without specifying the underlying cause. Therefore, nephrotic syndrome is not a disease, but is a way of saying “the patient has these symptoms”
115
What criteria must a patient fulfil to be diagnosed with nephrotic syndrome?
- Peripheral oedema
- Proteinuria
- Serum albumin less than 25g/L
- Hypercholesterolemia
116
What is IgA nephropathy?
Defined by the presence of dominant or co-dominant mesangial IgA immune deposits, often accompanied by C3 and IgG. Also called Berger's disease (poor guy had the name taken away from him for this boring one)
nephritic syndrome condition
117
What is the most common age to be diagnosed with IgA nephropathy?
80% diagnosed between 16 and 35 and more common in Asian population
118
What causes IgA nephropathy?
- Occurs when abnormal IgA antibodies are produced by the body usually after a respiratory or GI tract infection
- This causes the body to recognise them as foreign producing IgG antibodies to target them. This immune complexes travel in the blood stream and get trapped in the kidneys
119
How do IgA-IgG complexes damage the kidneys?
- They are deposited in the mesangium (tissue surrounding the Bowman's capsule).
- This activates the complement pathway leading to the release of cytokines and macrophages which damage the glomerulus
120
What are the signs of IgA nephropathy?
- Haematuria
- Oedema due to proteinuria
- Cervical lymphadenopathy suggests recent URTI as trigger
- Hypertension
121
What are the symptoms of IgA nephropathy?
- **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 trigge
122
What are the initial investigations for IgA nephropathy?
U&Es and urine dipstick
C3 and C4- C4 will be normal where as C3 might be low
123
What is the diagnostic test for IgA nephropathy?
**Renal biopsy**
- **On light microscopy**: **see mesangial proliferation**.
- **On immunofluorescence:** IgA immune complexes in the mesangium
- **On electron microscopy**: immune complexes are seen in the mesangium.
124
What is a differential for IgA nephropathy?
- **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.
- Management
125
What is the management for IgA nephropathy?
- ACE inhibitor for BP
- Corticosteroids
- Statins
- Omega-3 fatty acids
126
What are the complications of IgA nephropathy?
- **Hypertension:** due to damage to the glomerulus and its filtering function
- **Acute kidney injury**
- **Chronic kidney disease (CKD)**
- **Rapidly progressive glomerulonephritis (RPGN)**
127
What is Post-streptococcal glomerulonephritis?
Post-streptococcal glomerulonephritis (PSGN) is usually an immunologically-mediated delayed consequence of pharyngitis or skin infections caused by **streptococcus pyogenes**
Most frequently seen in children
128
How does streptococcus cause glomerulonephritis?
- Some strep A strains carry the M-protein virulence factor which initiates a type III hypersensitivity reaction. IgG and IgM antibodies form immune complexes
- These immune complexes get deposited on the basement membrane of the glomerulus which initiates an inflammatory response
129
What are the signs of PSGN?
- Haematuria
- Recent strep infection
130
What are the initial investigations for PSGN?
- **Bloods:** low levels of C3 and CH50
- **Positive streptozyme test** confirms recent group A streptococcal infection
131
What else can be investigated in PSGN?
- **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”.
132
What is the treatment for PSGN?
Furosemide
Antibiotics
133
What is the prognosis for PSGN?
PSGN usually resolves on its own in children.
In adults, it can sometimes lead to renal failure.
Age affects prognosis!
134
What is diffuse proliferative glomerulonephritis?
Diffuse proliferative glomerulonephritis is the most common form of lupus nephritis.
135
What are the risk factors for lupus nephritis?
systemic lupus erythematosus - SLE
- **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
136
How does SLE cause glomerulonephritis?
- Lupus is an autoimmune condition that affects multiple organs. It is a type III hypersensitivity reaction where immune complexes are deposited in various parts of the body
- Most common site of deposition is in the **subendothelial space** of the glomerular basement membrane
137
What are the symptoms of SLE glomerulonephritis?
- Haematuria
- Proteinuria
- Hypertension
- Oedema
- Lethargy
- **Musculoskeletal pain and butterfly rash**
138
What are the initial investigations for SLE glomerulonephritis?
- **Urinalysis:** haematuria and proteinuria
- **U&Es:** reduced eGFR as renal failure progresses
- **Renal USS:** exclude structural pathology
139
What is the gold standard investigation for SLE glomerulonephritis?
Renal biopsy
- 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
140
What is the management for SLE glomerulonephritis?
- Lifestyle stop smoking and exercise more
Pharmacological
**Corticosteroids**
**Immunosuppressants** e.g., azathioprine mercaptopurine and cyclophosphamide
**Hydroxychloroquine**
141
What is Goodpasture's disease/syndrome?
Goodpasture’s disease, also known as anti-glomerular basement membrane antibody (anti-GBM) disease, is an important cause of pulmonary-renal syndrome (Goodpasture’s syndrome).Pulmonary-renal syndrome consists of glomerulonephritis and pulmonary haemorrhage.
142
What causes Goodpasture's?
- It is caused by antibodies to the alpha-3 chain of type IV collagen (makes the basement membrane if you can remember phase 1) . - thanks tom x
- Alpha-3 subtype only affects basement membrane of a few tissues particularly **Alveoli** and the **glomeruli**
143
What are the genes linked to Goodpasture's?
HLA-DRB1 or DR4
144
What are the key diagnostic factors for Goodpasture's?
- Reduced urine output
- Haemoptysis (pulmonary haemorrhage)
- Oedema
145
What tests would you perform for Goodpasture's?
- Renal function tests
- GOLD STANDARD- renal biopsy
- anti-glomerular basement membrane (anti-GBM) antibody titre
- ANCA test (50% of patients will have these antibodies as well)
146
What is the treatment for Goodpasture's?
- Oral corticosteroid
- Plasmapheresis to remove the anti-GBM antibodies
- Cyclophosphamide
147
What is nephrotic syndrome ?
It occurs when the basement membrane in the glomerulus becomes highly permeable to protein allowing them to leak from the blood into the urine.
148
What age is nephrotic syndrome most common?
2-5
149
What is the classic triad of nephrotic syndrome?
Low serum albumin
High urine protein count
Oedema
150
What are the 3 other features of nephrotic syndrome?
- Deranged lipid profile (high levels) - as the liver increases synthesis in response to low levels of albumin
- High blood pressure
- Hyper-coagulability- due to loss of protein C and S in the urine
151
What are the three presentations of nephrotic syndrome?
- Frothy urine
- Oedema
- Pallor
152
What is minimal change disease?
The most common cause in children causing over 90% of cases in children under 10. In minimal change disease, nephrotic syndrome occurs in isolation, without any clear underlying condition or pathology
153
What would a key presentation of nephrotic syndrome be?
If you spot a 2 – 5 year old child with oedema, proteinuria and low albumin, you may be asked about the underling cause. The answer is likely to be nephrotic syndrome.
154
What would be shown on a kidney biopsy with minimal change disease?
- 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.
155
What is Focal segmental glomerulosclerosis?
It is the most common cause of nephrotic syndrome in individuals of African or Hispanic descent
156
What are some risk factors for Focal segmental glomerulosclerosis?
- HIV
- Heroin abuse
- Infection
- Interferon treatment
157
What will Focal segmental glomerulosclerosis look like on light microscopy?
- 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.
158
What is the management for FSG?
Primary FSG has an inconstant response to corticosteroids and some individuals may progress to CKD
159
What can cause membranous nephropathy?
- 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
160
Describe the pathophysiology of membranous nephropathy?
- Damage is caused by immune complexes. They are called subepithelial deposits because they build up between podocytes and glomerular basement membrane.
- 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.**
161
What will a renal biopsy of membranous nephropathy show?
**On light microscopy**: diffuse capillary and basement membrane thickening caused by immune complex deposition
**On immunofluorescence**: will show immune complexes of IgG and C3
**On electron microscopy**: There will be flattening of the podocyte foot processes and subepithelial deposits. There are expansions of the basement membrane that separate around the immune complexes creating a **spike and dome pattern**
162
What is Membranoproliferative glomerulonephritis?
Three types of MPGN: they all cause proliferation of mesangial and endothelial cells in the glomerulus.
Membranoproliferative glomerulonephritis is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane thickening, activating complement and damaging the glomeruli.
163
What is type 1 MPGN?
Most common subtype accounts for 90% of cases associated with SLE, hepatitis CLL and lymphoma
- Deposits in the subendothelial space
164
What is type 2 MPGN (Dense deposit disease)?
- Due to persistent activation of the alternative pathway.
- Low levels of circulating C3
- Associated with **factor H deficiency and lipodystrophy**
- Deposits in the basement membrane
165
What is type III MPGN?
- **Type III MPGN**: poorly understood
- Characterised by subendothelial and subepithelial deposits
- Associated with **hepatitis B** and **C**
166
What are the risk factors for MPGN?
- Age 75% of people are 8-16
- Infections
- CLL
- Acquired partial lipodystrophy (ADP): APL is a very rare condition characterised by the loss of fat and is particularly associated with type II MPGN
167
Describe the pathophysiology of type 1 MPGN?
It starts one of two ways:
Way 1: through hypersensitivity reaction to Hep A or Hep B antigens. These complexes get deposited in the glomerulus and activate the classical complement pathway.
Way 2: There is inappropriate activation of the alternative pathway due to over activity of C3 convertase which can be caused by a special IgG antibody called **nephritic factor**
Either way there are deposits that end up in the subendothelial space which causes inflammation leading to the thickening of the basement membrane and proliferation of the mesangial cells
168
Describe the pathophysiology of type II MPGN?
- It is caused by nephritic factors which stabilise C3 convertase leading to complement deposits in the basement membrane as opposed to the subendothelial space
- Leads to inflammation of the basement membrane and low levels of circulating C3. Will show **tram track appearance on light microscopy**
169
What are the signs and symptoms of MPGN?
- **Oedema**
- **Oliguria**
- **Haematuria**
- **Hypertension**
- **foamy urine**
- **Pink urine**
170
What are some first line investigations for MPGN?
- U&Es
- Urine dipstick
- - **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
171
What is the gold standard for MPGN and what would it show?
Renal biopsy
- Type 1 subendothelial and mesangial immune deposits resulting in tram-track appearance
- Type 2- Intramembranous dense deposits
172
What is the management for 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
173
What is benign prostate hyperplasia?
Increase in the size of the prostate without malignancy. This causes bladder outlet obstruction and lower urinary tract symptoms.
174
How common is BPH?
Men from 51-60 there is a prevalence of 50% above 80 prevalence is 80%
175
What are the risk factors for BPH?
- Increasing age
- Family history
- Ethnicity more common in black people
- Diabetes
- Obesity due to increasing circulation of oestrogen
176
What causes BPH?
- Basal and luminal cells rely on stimulation from androgens for survival. Such as testosterone (produced by testicles) and dihydrotestosterone (produced by prostate). DHT is produced by 5α-reductase which converts testosterone into the more potent dihydrotestosterone.
- As age increases levels of testosterone drop but levels of DHT increase as there is an increase in 5a-reductase activity
- This will form hyperplastic nodules to form
177
What lobes are usually enlarged the most in BPH?
the median and lateral lobes are usually enlarged. (transitional zone)
178
How can BPH cause symptoms?
- Hyperplastic nodules will form in the inner portions of the gland typically around the urethra
- These nodules will compress the urethra making it more difficult to pas urine. This will mean the smooth muscles of the bladder will have to work harder leading to bladder hypertrophy
- The stagnation of the urine in the bladder also promotes bacterial growth leading to UTIs
179
What are the signs of BPH?
- Digital rectal exam will find smooth, enlarged and non-tender prostate
- Lower abdominal tenderness and palpable bladder:
Indicates acute urinary retention
Perform bladder scan
Requires urgent catheterisation
180
What are the signs of BPH?
- Digital rectal exam will find smooth, enlarged and non-tender prostate
- Lower abdominal tenderness and palpable bladder:
Indicates acute urinary retention
Perform bladder scan
Requires urgent catheterisation
181
What are the symptoms of BPH?
- Voiding: weak stream and incomplete emptying
- Storage: urgency and incontinence
- Oliguria: if complete obstruction
- Lower abdominal pain and inability to urinate
Indicates acute urinary retention
182
What are the investigations for BPH?
- Prostate-specific antigen (PSA): predicts prostate volume, may suggest cancer if significantly raised but BPH can also raise it
- International Prostate Symptom Score (I-PSS): a 7-symptom questionnaire with an additional bother score to predict progression and outcome
183
What are the non-surgical treatments for BPH that has bothersome symptoms?
- α-1 antagonists: Tamsulosin it is considered first-line. It inhibits the action of noradrenaline and relaxes the smooth muscle. Can cause **Postural hypotension, dizziness, dry mouth and depression**
- 5-α reductase inhibitors e.g. finasteride. This will work to reduce the prostate size but can take up to 6 months to work. Can cause: **reduced libido, erectile dysfunction, adn gynaecomastia**
184
What are the the surgical options for BPH and when would they be used?
Prostate<30g
- **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)
Prostate >80g
**Transurethral electrovaporisation of the prostate (TUVP)**: prostate tissue is removed using a laser
**Open prostatectomy** via abdominal or perineal incision
185
What is TURP syndrome?
life-threatening triad of fluid overload, dilutional hyponatraemia and neurotoxicity due to systemic absorption of irrigation fluids during TURP procedure
186
What is the most common form of prostate cancer?
Prostate adenocarcinoma
187
What are 2 other types of prostate cancer?
- Transitional cell carcinoma
- Small cell prostate cancer arising form neuroendocrine cells
188
What are the risk factors for developing prostate cancer?
- Being tall
- Obesity and high fat diet
- Use of steroids
- Cadmium exposure found in cigarettes, batteries and those in welding industry
- BRCA1 and BRCA"
189
Describe the pathophysiology of a prostate adenocarcinoma
- They commonly arise in the **peripheral zone** of the prostate. This is often a result of a mutation in the luminal cells causing an uncontrollably dividing tumour .
- Early on the cancer relies heavily on androgens to survive but can find a way later on in disease to divide without it.
190
Where does prostate cancer usually spread to if it becomes metastatic?
-Spreads to the bines of the vertebrae and pelvis resulting in hip and in back pain
191
What are the signs of prostate cancer?
- Asymmetrical, hard and nodular prostate with the loss of the median sulcus
- Urinary retention
192
What are the symptoms of prostate cancer?
- Frequency
- Dribbling
- Haematuria or haematospermia
- Dysuria
- Bone pain (suggests metastatic disease)
193
What are the primary investigations for prostate cancer?
**Multiparametric MRI** is first-line for suspected localised cancer. Reported on using Likert score:
- **Prostate-specific antigen (PSA)**
- Often increased in patients with prostate cancer
- Also raised with increasing age and BPH
PSA testing is unreliable, with a high rate of false positives (75%) and false negatives (15%).
194
What do the different scores of the Likert scale suggest?
1- very low suspicion
2- low suspicion
3- Equivocal
4- probable cancer
5- Definite cancer
Prostate biopsy offered to those with scores of 3 or greater
195
How is a prosate biopsy performed?
Transrectal ultrasound-guided biopsy (TRUS)
Transperineal biopsy
Prostate biopsy carries a risk of false-negative results if the biopsy misses the cancerous area. Multiple needles are used to take samples from different areas of the prostate. The MRI scan results can guide the biopsy to decide the best target for the needles.
196
What is the Gleason score and what does it mean?
The Gleason grading system is based on the histology from the prostate biopsies. It is specific to prostate cancer and helps to determine what treatment is most appropriate
It is made up of two numbers from the two most prevalent areas of the biopsy and they are graded 1-5. 1 Being well differentiated (good) and 5 being poorly differentiated.
A Gleason score of:
6 is considered low risk
7 is intermediate risk (3 + 4 is lower risk than 4 + 3)
8 or above is deemed to be high risk
197
What is the preferred treatment for a low risk cancer?
Active surveillance or observation
198
What are the treatment options for prostate cancer?
External beam radiotherapy directed at the prostate
Brachytherapy
Hormone therapy
Surgery
199
What is brachytherapy?
Involves the implanting of radioactive seeds into the the prostate delivering continuous targeted radiotherapy.
The radiation can cause inflammation in nearby organs, such as the bladder (cystitis) or rectum (proctitis). Other side effects include erectile dysfunction, incontinence and increased risk of bladder or rectal cancer.
200
What is the hormone therapy used to treat prostate cancer?
- it aims to reduce the levels of testosterone that can stimulate the tumour to grow
Drugs include
**androgen-receptor blockers**-bicalutamide
**GnRH agonists**- such as goserelin (Zoladex) or leuprorelin (Prostap)
**Bilateral orchidectomy**- removal of the testicles
201
What is the prognosis for prostate cancer?
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%.
202
What is the most common form of testicular cancer?
Germ cell tumours
203
What are some other types of testicular cancer?
Non-germ cell (sex-cord stromal)
Lymphomas
204
Describe the epidemiology of testicular cancer
- 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
205
What are the risk factors for developing testicular cancer?
- Caucasian
- Infertility
- Cryptorchidism
- Intersex
- Mumps
- In-utero exposure to pesticides
206
What are the different types of germ cell tumours?
- **Seminoma**:the most common and best prognosis
Non-seminoma
- **Teratoma:** composed of tissue from different germinal layers e.g. teeth, common in children. Can contain all types of tissues! (most common form of non-seminoma)
- **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)
- **Embryonal carcinoma:** aggressive and metastasises early. Made from germ cells that turn into embryonic pluripotent stem cells
207
What are the signs of testicular cancer?
- Painless lump that will be:
Arising from the testicle
Hard
irregular
No transillumination with torch
208
What are the symptoms of testicular cancer?
Sometimes there can be a sharp or dull testicular pain that can be present in the abdomen as well
- 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**
209
What is the first-line investigation for testicular cancer?
Ultrasound testicular doppler diagnostic in over 90% of cases
210
What are the tumour markers for testicular cancer?
Alpha-fetoprotein – may be raised in teratomas (not in pure seminomas)
Beta-hCG – may be raised in both teratomas and seminomas (20%)
Lactate dehydrogenase (LDH) is a very non-specific tumour marker
211
What is the management for testicular cancer?
- Surgery to remove the affected testicle
- Chemotherapy
- Radiotherapy
- Sperm banking in case of infertility
212
What are the side effects of the treatment for testicular cancer?
- Infertility
- Hypogonadism (testosterone replacement needed)
- Peripheral neuropathy
- Hearing loss
213
What are the common sites of metastasis for testicular tumours?
- Lymphatics
- Lungs
- Liver
- Brain
214
What is the most common form of bladder cancer?
Transitional cell carcinoma (urothelial)
215
What are the other types of bladder cancer?
- Squamous cell carcinoma
- Adenocarcinoma
216
What are the risk factors for bladder cancer?
- Extended dwell times: not emptying bladder for long periods of time
- Alanine - rubber, dye and textile industries
- Cyclophosphamide: medication used to treat cancers and autoimmune diseases
- Smoking
- **Aromatic amines**
- **Polycyclic aromatic hydrocarbons (e.g. 2-Naphthylamine)**
- Painters and hairdressers
217
What can cause squamous cell carcinoma and where is it most common?
Schistosomiasis causes squamous cell carcinoma of the bladder in countries with a high prevalence of the infection for example Egypt
218
What are the signs of bladder cancer?
Palpable suprapubic mass
Anaemia
219
What are the symptoms of bladder cancer?
- KEY SYMPTOM **‘Painless’ haematuria**: microscopic or macroscopic
- **Dysuria** (pain when urinating) can occur
- **Frequency**
- Constitutional symptoms e.g. **weight loss**
220
When would you be referred for a 2 week wait in relation to bladder cancer?
- Over 45 with unexplained haematuria
- Over 60 with microscopic haematuria on urine dipstick plus dysuria or raised WCC
The NICE guidelines also recommend considering a non-urgent referral in people over 60 with recurrent unexplained UTIs.
221
What is the diagnostic test for bladder cancer?
- Flexible cystoscopy and biopsy under local anaesthetic to confirm the presence of a tumour
222
What is the treatment for non-muscle invasive bladder cancer?
Transurethral resection of bladder tumour (TURBT) may be used for non-muscle-invasive bladder cancer. The involves removing the bladder tumour during a cystoscopy procedure.
Intravesical chemotherapy (chemotherapy given into the bladder through a catheter) is often used after a TURBT procedure to reduce the risk of recurrence.
223
What is Intravesical Bacillus Calmette-Guérin (BCG) in relation to treatment for bladder cancer?
May be used as a form of immunotherapy,. Giving BCG vaccine (TB) into the bladder is thought to stimulate the immune system to attack the tumour
224
What is the prognosis for bladder cancer?
Overall 5-year survival is 55%, but for distant metastatic disease, this drops to 5%.
225
What is the most common form of kidney cancer?
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
226
What genetic conditions can cause a RCC?
- Linked to mutations on chromosome 3
- VHL gene is most implicated
- Von Hippel-Lindau syndrome can give rise to RCC in younger people
227
What are the symptoms of RCC?
- **Classic triad: haematuria, flank pain, abdominal mass** (seen in 10-15% of patients)
- **Constitutional symptoms: e.g. weight loss, fatigue, fever of unknown origin**
228
What are some signs of RCC?
- Hypertension
- Flank mass
- Left sided varicocele
229
What is the initial investigation for RCC?
- **Abdominal ultrasound**: a sensitive initial modality to help identify benign vs. malignant lesions but CT/MRI is needed if RCC is suspected
230
What is the gold-standard investigation for RCC?
- **CT abdomen/pelvis with contrast**: the definitive test for diagnosis, with 90% sensitivity and 100% specificity in identifying malignancy
231
What is systematic urethral dissection syndrome? (SUDS)
super dangerous willy problem or something
232
What is the molecular therapy used to treat RCC
Sunitinib and pazopanib which are tyrosine kinase inhibitors
233
What is the prognosis for RCC?
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
234
What is a wilm's tumour?
Wilms’ tumour is a specific type of tumour affecting the kidney in children, typically under the age of 5 years. It is the chief abdominal malignancy in children
235
What is polycystic kidney disease?
Polycystic kidney disease is a genetic condition where the kidneys develop multiple fluid-filled cysts. Kidney function is significantly impaired.
There are a number of associated findings outside the kidneys such as **hepatic cysts** and **cerebral aneurysms**.
236
What are the two types of polycystic kidney disease?
Autosomal dominant
Autosomal recessive
237
What are the two gene mutations for autosomal dominant PKD?
- PKD-1 on **chromosome 16*** which accounts of 85% of cases and is associated with a more severe phenotype
- PKD-2 on **chromosome 4**
238
What causes cysts to form in ADPKD?
- Polycystin proteins are not coded for correctly which allow for calcium influx into to cells to inhibit cell proliferation .
- Consequently cells proliferate abnormally and start to express proteins that cause water to be transported into the cyst.
239
What are the consequences of cyst formation in PKD?
- Leads to the enlargement of certain nephrons which starve healthy nephrons of oxygen.
- This results in the activation of RAAS which causes fluid retention and hypertension
- Over time when enough nephrons are affected it will result in renal failure
240
What are the extra-renal consequences of PKD?
- Cerebral aneurysms
- Hepatic, splenic, pancreatic, ovarian and prostatic cysts
- Cardiac valve disease (mitral regurgitation)
- Colonic diverticula
- Aortic root dilatation
241
What are the signs of PKD?
- Bilateral flank masses
- Hypertension
242
What are the symptoms of PKD?
- Abdominal flank or back pain
- Haematuria
- Dysuria
- Renal colic
-- 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)
243
What is are the investigations for PKD?
- **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)
244
What are the ultrasound diagnostic criteria for PKD?
Known 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
245
What is the conservative treatment for PKD?
- Blood pressure control
- Regular follow up
- Maintain adequate hydration
- Avoid NSAIDs and anticoagulants
- Avoid contact sport to prevent cyst rupture
246
What is the treatment for high-risk patients?
Vasopressin receptor antagonists (Tolvaptan) can slow the development of the cysts
247
What is Chlamydia trachomatis?
A gram-negative bacteria. It is an intracellular organism, meaning it enters and replicates within cells before rupturing the cell and spreading to others.
Chlamydia is the most common sexually transmitted infection in the UK and a significant cause of infertility.
248
What is the national Chlamydia screening programme?
Aims to screen every sexually active person under 25 years of age for chlamydia annually or when they change their sexual partner
249
What are the symptoms of Chlamydia in women?
Abnormal vaginal discharge
Pelvic pain
Abnormal vaginal bleeding (intermenstrual or postcoital)
Painful sex (dyspareunia)
Painful urination (dysuria)
250
What are the symptoms of Chlamydia in men?
Urethral discharge or discomfort
Painful urination (dysuria)
Epididymo-orchitis
Reactive arthritis
251
What is the first line treatment of chlamydia?
100mg of **doxycycline** twice a day for 7 days
252
What is a common non-GU symptom of chlamydia?
Chlamydial Conjunctivitis
253
What is Neisseria gonorrhoeae ?
A gram-negative diplococcus bacteria. It infects mucous membranes with a columnar epithelium, such as the endocervix in women, urethra, rectum, conjunctiva and pharynx.
It spreads via contact with mucous secretions from infected areas.
254
What are the symptoms of gonorrhoeae?
Odourless purulent discharge, possibly green or yellow
Dysuria
Pelvic
Testicular swelling and pain
255
What % of people are symptomatic with gonorrhoea?
90% of men and 50% of women are symptomatic.
256
What is the treatment for gonorrhoea?
A single dose of intramuscular ceftriaxone 1g if the sensitivities are NOT known
A single dose of oral ciprofloxacin 500mg if the sensitivities ARE known
257
What is syphilis?
Caused by bacteria called **Treponema pallidum**. This bacteria is a spirochete, a type of spiral-shaped bacteria.
The bacteria gets in through skin or mucous membranes, replicates and then disseminates throughout the body. It is mainly a sexually transmitted infection.
258
What are the different stages of syphilis?
Primary syphilis involves a painless ulcer called a chancre at the original site of infection (usually on the genitals).
Secondary syphilis involves systemic symptoms, particularly of the skin and mucous membranes. These symptoms can resolve after 3 – 12 weeks and the patient can enter the latent stage.
Latent syphilis occurs after the secondary stage of syphilis, where symptoms disappear and the patient becomes asymptomatic despite still being infected.
Tertiary syphilis can occur many years after the initial infection and affect many organs of the body, particularly with the development of gammas and cardiovascular and neurological complications.
Neurosyphilis occurs if the infection involves the central nervous system, presenting with neurological symptom
259
What are the symptoms of primary and secondary syphilis?
Primary syphilis can present with:
A painless genital ulcer (chancre). This tends to resolve over 3 – 8 weeks.
Local lymphadenopathy
Secondary syphilis typically starts after the chancre has healed, with symptoms of:
Maculopapular rash
Condylomata lata (grey wart-like lesions around the genitals and anus)
Low-grade fever
Lymphadenopathy
Alopecia (localised hair loss)
Oral lesions
260
What are the symptoms of neurosyphilis?
Headache
Altered behaviour
Dementia
Tabes dorsalis (demyelination affecting the spinal cord posterior columns)
Ocular syphilis (affecting the eyes)
Paralysis
Sensory impairment
261
What is the treatment of syphilis?
A single deep intramuscular dose of benzathine benzylpenicillin (penicillin)
262
What is a varicocele?
Dilated testicular veins within the pampiniform plexus. Around 90% of them occur on the left side
263
Describe the epidemiology of varicoceles
- Occurs most commonly in adolescent boys may affects up to 15%
- Seen in around 40% of men with infertility
264
How do varicoceles form?
- They form when there is increased pressure in the testicular veins that drain the pampiniform plexus.
- This may be caused by incompetent valves leading to venous reflux. The majority occur on the left side as the testicular vein drains into the renal vein at a shard angle first before IVC.
265
What can varicoceles be a sign of?
They can be a sign of renal cancer. The majority occur on the left side so if there is a tumour compressing venous return this could be a cause
266
What are the signs of a varicocele?
- Palpable veins
- Scrotum hanging lower
267
What are the symptoms of a varicocele?
- Painless swelling
- Some patients experience **dragging sensation**
268
What are the investigations for a varicocele?
- **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.
269
When would you refer someone with a varicocele?
- Does not drain when lying down
- It appears suddenly and is painful
- Solitary ride-sided
270
How would you grade a varicocele?
- **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.
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What is a testicular torsion?
It is the twisting of the spermatic cord with rotation of the tentacle (was autocorrect but thought it's funny, I'm getting really bored)
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What are the risk factors for a testicular torsion?
- Young age
- Bell clapper deformity (what a great name this is for a deformity of the testicle). It's when the testicle is high riding and it's horizontal
- Cryptorchidism
- Trauma
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What are the signs of a testicular torsion?
- Abnormal lie
- Prehn's negative pain is not relieved on lifting the ipsilateral testicle
- Absent cremasteric reflex
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What are the symptoms of a testicular torsion
- Awful debilitating pain imagine what it would feel like for your testicle to be twisted round and round like a big knot.
- Pain can be intermittent and be brought on by exercise
- Nausea and vomiting
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How would you investigate a testicular torsion?
- Imaging should not be considered if testicular torsion is suspected as it will delay surgery! Think of how much pain the poor man must be in don't wait give him blood back to his testicle
- 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)
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What are the treatment options for a testicular torsion?
- Bilateral orchiopexy if the testicle is viable. This involves untwisting the testicle and fixing it to scrotal sac. Contralateral one should be fixed as well
- Ipsilateral orchiectomy and contralateral orchiopexy if the testicle is not viable : removal of the affected testis and fixation of the contralateral testis to the scrotal sac to prevent contralateral torsion
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What are the complications of a testicular torsion?
- **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
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What is the prognosis for a testicular torsion?
- 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**
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What is a hydrocele?
Hydrocele refers to a collection of serous fluid between the parietal and visceral layers of the tunica vaginalis (membrane covering the testes).
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What is a testicular appendage torsion?
Torsion of the appendix testis is a **twisting of a vestigial appendage that is located along the testicle.** This appendage has no function, yet more than half of all boys are born with one.
It is also known as **Hydatid of Morgagni (embryonic remnant of the Mullerian duct)**
Although this condition poses no threat to health, it can be painful. Usually no treatment other than to manage pain is needed.
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What is a hydrocele?
Hydrocele refers to a collection of serous fluid between the parietal and visceral layers of the tunica vaginalis (membrane covering the testes).
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What is the pathophysiology behind simple and communicating hydrocele?
Simple - overproduction of fluid in the tunica vaginalis
Communicating - processus vaginalis fails to close, allowing peritoneal fluid to communicate freely with the scrotal portion
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What investigations would you do for a hydrocele?
Investigations
Scrotal ultrasound
Serum AFP and HCG to help exclude malignant teratomas or other germ cell tumours
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What management would you do for a hydrocele?
Management
Resolve spontaneously
Many of infancy resolve by 2 years
**Therapeutic aspiration** or surgical removal
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What is a Epidydimal cyst?
Smooth, extra-testicular, spherical sac of fluid in the head of the epididymis (top of testicle). - also known as a *spermatocele*
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What are some symptoms/signs of an epdidymal cyst?
- 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
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What are some investigatons/Differentials/Management of an epididymal cyst?
- Investigations
- **Scrotal ultrasound**
- Differential diagnosis
- **Hydrocele**
- **Varicocele**
- Management
- **Usually not necessary**
- **Removed, if symptomatic**
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Normal physiology - what happens when the bladder is half full with wee?
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 - Pelvis Splanchnic nerves** , known as the micturition center, and the brain, specifically two locations in the pons.
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Normal physiology - activation of the pelvic sphlanic nerves when the bladder is half full leads to what?
**Micturition reflex**
Activation of pelvic splanchnic nerve S2-S4 cause the detrusor muscles to CONTRACT
- When the detrusor muscle contract, the change in bladder shape pulls open the internal urethral sphincter - is **made of smooth muscle**
**Micturition reflex** also decreases motor nerve stimulation to the external sphincter allowing it to relax as well.
At this point, urination should occur, but why don't just wet ourselves every time the bladder is half full?
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Normal physiology - what stops us from urinating every time our bladder is half full, aka what overrides the **Micturition reflex**
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,
it overrides it by activating ***SYMPATHETIC, HYPOGASTIRC NERVES T10 - L2*** , leading to DETROUSER RELAXATION, BLADDER NECK CONTRACTION
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Normal physiology - what stops us from urinating every time our bladder is half full, aka what overrides the **Micturition reflex**
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,
it overrides it by activating ***SYMPATHETIC, HYPOGASTIRC NERVES T10 - L2*** , leading to DETROUSER RELAXATION, BLADDER NECK CONTRACTION
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What are the types of incontinence?
- Urge incontinence:
- Stress incontinence
- Mixed incontinence:
Overflow incontinence (neurogenic bladder):
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What are some disease that can damage the micturition reflex, and can lead to incontinence?
- **Diabetes**
- **Bladder cancer**
- **Parkinson's**
- **Multiple sclerosis**
- **Prostatectomy**
- **Hysterectomy**
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Outline the pathophysiology behind urge incontinence. What things can cause it?
Sudden urge to urinate because of an "overactive bladder", followed immediately by involuntary urination
typically due to an uninhibited detrusor muscle that contracts randomly.
Usually associated with urinary tract infections. Inflammation may trigger the detrusor muscle.
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Outline the pathophysiology behind stress incontinence. What things can cause it?
Increased abdominal pressure overwhelms the sphincter muscles and allows urine to leak out. Causes include pregnancy and exertion, like sneezing, coughing, laughing.
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Outline the pathophysiology behind overflow incontinence. What things can cause it?
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**. ==> Detrusor cant contract properly so the bladder doesn’t empty properly, and as a result the **bladder fills up and overflows with urine** which leaks through the sphincters.
(e.g. in diabetes, neurogenic bladder associated with multiple sclerosis, spinal cord injury)
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What are the clinical manifestations seen with:
a) Urge incontinence
b) Stress Incontinence
c) Overflow incontinence
- 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**
