RENAL/GENITOURINARY Flashcards
Define Nephrolithiasis
The presence of stones, or calculi, within the urinary system.
What is the most common age to get kidney stones? What percentage of the population will get them?
- Typically occurs in 30-60 year olds
- M>F
- More than 50% lifetime risk of recurrence once you’ve had them
Common: lifetime incidence up to 15%
What are some risk factors for Nephrolithiasis/Kidney stones
high salt intake
male Sex - testosterone - increased oxalate
Stone forming food
Metabolic - Hypercalcaemia, Hyperparathyroidism
Drugs - loop diuretics
What foods can be known to increase the chance of stone formation in Nephrolithiasis?
chocolate, rhubarb, spinach, tea, and most nuts are high in oxalate, and colas are high in phosphate
What are the most common types of kidney stones?
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
What are the two types of calcium stone?
Calcium oxalate (most common)
Calcium phosphate
Calcium Oxalate is the most common stone formation occurring in ~70-80% of cases as calcium
and oxalate are natural chemicals found in lots of foods
What are the colours of the two calcium based stones seen in Nephrolithiasis? How would they appear on x-ray and would they make urine acidic or alkaline?
- Calcium oxalate: most common. Results in a black or dark brown coloured stone that is radio-opaque on an x-ray (shows up as white spot on x-ray). More likely to form in acidic urine.
- Calcium phosphate: dirty white in colour and also radiopaque on an X-ray. More likely to form in alkaline urine.
Other than calcium based kidney stones, what are the other 3 types of kidney stones?
- Uric Acid (red brown colour, not visible on xray (make up 5-10% of stones)
- Struvite, from bacteria (associated with infection) - forms dirty white stones, visible on xray (2-10%)
- Cystine - yellow/light pink coloured (1%)
What causes kidney stones?
Kidney stones form when your urine contains more crystal-forming substances — such as calcium, oxalate and uric acid — than the fluid in your urine can dilute. 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.
What are some risk factors that can cause calcium renal stones?
Risk factors
Low urine volume
Hypercalciuria
Primary hyperparathyroidism
Renal tubular acidosis
Hyperoxaluria
What causes struvite stones to form?
Struvite - Bacteria release urase -
which causes ammonia to form - ammonia makes urine more alkaline, leading to jagged crystals called Staghorns forming
What is the cause of the pain associated with kidney stones?
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
Where are the 3 most common sites where kidney stones can commonly lodge?
• Pelviureteric junction/ureteropelvic junction – where the renal pelvis connects to the ureter
• Pelvic brim – where the ureter crosses over the pelvic brim and the bifurcation of the common iliac
arteries
• Vesicoureteric junction/ureterovesicular junction – where the ureter connects to the urinary
bladder
Kidney stones of
What are the signs of kidney stones?
Flank/ renal angle tenderness
Left and right lumbar region pain
Fever (if sepsis)
What are some symptoms of kidney stones?
-
Acute, severe flank pain (renal colic)
- Classically ‘loin to groin’ pain
- Pain lasts minutes to hours and occurs in spasms (with intervals of no pain or dull ache)
- Fluctuating in severity as the stone moves and settles
-
Nausea and vomiting
Pain is not relieved - Urinary urgency or frequency
- Haematuria: microsopic or macroscopic
Flank/ renal angle tenderness
Left and right lumbar region pain
Fever (if sepsis)
What are some first-line investigations for renal stones?
What is the first line imaging
Urine dipstick can show blood, leukocytes, nitrates
FBC check kidney function and calcium levels
X-ray can show calcium based stones but not uric
Negative pregnancy test
XRAY IS FIRST LINE IMAGING FOR RENAL STONES
What is the gold standard test for renal stones?
Non contrast CT scan of kidney, ureters and bladder (CT KUB) .
Should be performed within 14 hours of admission
^^For non pregnant adult
Renal ultrasound for pregnant adult or child
May use ultrasound if radiation needs to be avoided
Name some differentials for Nephrolithiasis
- Ruptured abdominal aortic aneurysm
- Appendicitis
- Ectopic pregnancy
- Ovarian cyst
- Bowel obstruction
-
Diverticulitis
Gastroenteritis
Pyelonephritis
What is the conservative management for Nephrolithiasis?
- Watchful waiting: stones <5mm should pass spontaneously and followed up in clinic
- Medical expulsive therapy (MET):Alpha-blocker, e.g.tamsulosin, for ureteric stones 5-10mm to help passage. Not indicated for renal stones. - *it helps relax muscles in the ureter, and can increase the flow of urine
What is the acute management of Nephrolithiasis, to help symptoms?
- IV fluids and anti-emetics
-
Analgesia: an NSAID by any route is considered first-line; - IV DICLOFENAC
- IV paracetamol is used if NSAIDs are contraindicated or ineffective
- Antibiotics: if infection is present
Name some surgical methods used in treating Nephrolithiasis.
Extracorporeal shockwave lithotripsy (ESWL)
Ureteroscopy (URS):
Percutaneous nephrolithotomy (PCNL):
What is the first line surgical treatment for both ureteric and kidney stones, size 5 - 10mm? Outline what happens in it
Extracorporeal shock wave lithotripsy (ESWL): utilises high energy ultrasound waves to break the stone into tiny fragments;
uncomfortable, requires analgesia and can cause organ injury. Contraindicated in pregnancy due to risk to the foetus (perform URS instead)
if stones are <5mm, then watchful waiting
What is the second line surgical treatment for both ureteric and kidney stones? Outline what happens in it
Ureteroscopy (URS): pass a ureteroscope through the urethra and bladder up to the ureter (retrograde) and retrieve the stone or fragment it with intracorporeal lithotripsy
What is the third line treatment for Nephrolithiasis, seen in large Kidney stones? (not used for ureteric stones)
Percutaneous nephrolithotomy (PCNL): accessing the renal collecting system percutaneously via a surgical incision in the back for intracorporeal lithotripsy or stone fragmentation
(not used for ureteric stones)
Outline some advice given for people with recurrent stones.
- Increase oral fluids
- Reduce dietary salt intake
- Reduce intake of oxalate-rich foods for calcium stones (e.g. spinach, nuts, rhubarb, tea)
- Reduce intake of urate- rich foods for uric acid stones (e.g. kidney, liver, sardines)
- Limit dietary protein
What medications can be used to reduce the risk of renal stone formation?
Potassium citrate, Thiazide diuretics (e.g., indapamide) in patients with calcium oxalate stones and raised urinary calcium
What is acute kidney injury?
Acute Kidney injury - Deterioration in renal function, rise in serum creatine and urea,
…Due to a rapid decline in GFR ==> Leads to failure to maintain fluid/electrolyte homeostasis
Decrease in function <3 months
According to Kidney Disease: Improving Global Outcomes’ (KDIGO) What are the 3 criteria used in diagnosing an AKI?
one of the following parameters:
- An increase in serum creatinine by ≥ 26.5 micromol/L within 48 hours
- An increase in serum creatinine to ≥ 1.5 times baseline within 7 days
- Urine output < 0.5 mL/kg/hr for six hours
What are the different types of causes that can lead to an AKI? Define them
Pre-renal – reduced blood flow to kidney leading to a falling GFR
Renal – kidney can’t filter blood properly, cells damaged so reabsorption/secretion impaired
Post-renal – anything that can cause blockage of kidney reducing outflow
Causes of AKI - give examples of Pre Renal causes of an AKI
Reduced blood flow to kidney leading to a falling GFR
Shock, + Hypovolaemia (fluid loss) - this could be due to burns, sepsis, acute haemorrhage trauma or bleeding, anaphylaxis
Decompensated Liver disease- Hepatorenal syndrome
GI losses – diarrhoea and vomiting
CV – severe HF, arrhythmias
Renal artery/vein thrombosis/stenosis
Renal hypoperfusion – NSAIDs, ACE-I, ARBs
Hepatorenal syndrome - how can liver cirrhosis lead to renal failure?
Liver cirrhosis leads to portal hypertension
In response to this, portal blood vessels dilate, stretched by large amounts of blood pooling there.
This leads to a loss of blood volume elsewhere, including kidneys.
Leads to hypotension in the kidney and activation of the RAAS. This causes renal vasoconstriction, which combined with low circulation volume leads to starvation of blood to the kidney
Hepatorenal syndrome is fatal within a week or so unless liver transplant is performed
Causes of AKI - give examples of intrarenal causes of an AKI
Acute tubular necrosis – tubule damage following prolonged ischaemia (often following pre-renal AKI)
Nephrotoxic drugs
Glomerulonephritis
Acute interstitial nephritis
Infection
Vasculitis – e.g. in SLE, affects renal arteries, arterioles and glomerular capillaries
Malignant hypertension
What drugs can be nephrotoxic and are known to cause intra renal disease?
NSAIDs – inhibits COX which causes excess vasoconstriction of afferent arteriole
Aminoglycosides - eg gentamicin – 10-15% incidence of ATN
ACE-I/ARBs – results in dilated efferent arterioles decreasing GFR
Methotrexate
Gentamicin
DAMN = (diuretics, ACEi/ ARBs, metformin, NSAIDs)
How can NSAIDs be nephrotoxic, and lead to AKI?
NSAIDs reduce prostoglandin production
* prostoglandins cause vasodilation of the afferent arteriole hence their inhibition causes vasoconstriction
of the afferent arterioles
* this cases reduced perfusion and hence reduced eGFR
Causes of AKI - give examples of postrenal causes of an AKI
Anything that can cause blockage of kidney reducing outflow
Benign Prostate Hyperplasia
Kidney stones in kidney, ureters, bladder, urethra
Cancer
Ovarian, colon, bladder cancer pushing on ureters or urethra
Blood clot
What are some risk factors for getting an AKI
Age - >75 years
Diabetes Mellitus
HF
Sepsis
Peripheral vascular disease
Family history
Drugs
Poor fluid intake/fluid loss
What are some general symptoms of an AKI
Early stages often asymptomatic
Oliguria – decreased urine output
Anuria
Dehydration
Nausea and vomiting
Confusion
Fever (sepsis)
Uraemia – weakness, tremor, fatigue, nausea, vomiting, mental confusion, seizures and coma
Breathlessness – combination of anaemia and pulmonary oedema secondary to volume overload
What are some symptoms of AKI?
Think about the causes! - Pre, Intra, Post etc
IT DEPENDS ON THE CAUSE/TYPE OF AKI
Pre Renal:
Thirst
Cool extremities
Dizziness, Confusion
Signs of fluid loss: excessive sweating, vomiting, diarrhoea and polyuria
- Dyspnoea
- Raised JVP
Intrinsic renal
- Vascular: arterial hypertension; peripheral oedema
Nephritic syndrome: haematuria;
-
Post-renal
- Urinary stones: loin-to-groin pain, haematuria, nausea and vomiting.
- Prostatic issues: dysuria, frequency, terminal dribbling, hesitancy
General symptoms:
Tachycardia
peripheral oedema Hypertension
Poor tissue turgor
Postural hypotension (dehydration)
Fluid overload + ↑JVP, pulmonary oedema (CXR),
What are 3 useful first line investigations for investigating an AKI?
Urine dipstick - may see RBCs, WBCs, cellular casts, proteinuria, positive nitrite – all of these may suggest glomerulonephritis
Bloods – acutely elevated serum creatinine, high serum potassium, metabolic acidosis. LFTs will be deranged in hepatorenal syndrome
Renal ultrasound – for obstruction
Gives assessment of renal size – very small indicates CKD
What other investigations could you do for an AKI?
Monitor urine output
Non-contrast CT KUB
KUB XR
Urine and blood cultures to exclude infection
Autoantibodies – Anti-GBM, ANCA
What are the stages of an AKI?
Can be classed as either
Stage 1 - Creatine rise 1.5-2 fold from baseline, and or <0.5ml/kg/hr urine output for more than 6 hours
Stage 2 - Creatine rise 2-3 fold from baseline, and or <0.5ml/kg/hr urine output for more than 12 hours
Stage 2 - Creatine rise >3 fold from baseline, and or <0.3ml/kg/hr urine output for more than 24 hours
Hyperkalaemia is a complication of AKI, and can lead to a cardiac arrest. How can you manage hyperkalaemia?
3 THINGS -
- IV stat of Calcium Gluconate - Stabilisation of the myocardium
- Variable rate insulin with dextrose infusion - to increase cellular uptake of potassium = Reduction of serum potassium
- oral calcium resonium - Reduction of total body potassium - treat underlying cause
What is the first line management for an AKI?
Treat underlying cause
- Regular monitoring: fluids, urine output, daily weights, baseline creatinine, serial U&Es
- Cease nephrotoxic drugs
- Hypovolaemia: IV fluids
- Hypervolaemic: fluid restriction and diuretics e.g. furosemide
- Obstruction: catheter insertion; surgery to relieve obstruction
TREAT COMPLICATIONS - Hyperkalaemia, pulmonary oedema, uraemia, acidaemia - Bicarbonate
What would you also consider for management in severe AKI?
Dialysis – removal of toxic products in body for patients with failed kidneys.
refer to critical care, get specialist involved!!
Use of a vasopressor, ie Noradrenaline
Consider the need for an inotrope (e.g., dobutamine) to optimise cardiac output if kidney hypoperfusion is caused by impaired cardiac function due to poor left ventricular systolic function
What are some complications of an AKI?
- Hyperkalaemia: when the individual is oliguric, potassium isn’t effectively removed from the blood. – can lead to Cardiac arrest
- Fluid overload
- Metabolic acidosis
-
Uraemia
- Uraemic complications: e.g. encephalopathy, pericarditis
RHABDOMYOLYSIS
What is a useful mnemonic for AKI assessment and management?
RENAL DR 26
Record baseline creatine
Exclude obstruction
Nephrotoxic drugs - stop
Assess fluid status
Losses - Measure fluid losses, with catherization
Dipstick
Review medications
26 - rise in creatine over 48 hours for AKI diagnosis
Define Chronic kidney disease.
Chronic kidney disease (CKD) describes a progressive deterioration in renal function. These issues develop over at least 3 months.
In which two ways can Chronic kidney disease be classified?
How many stages in each?
By GFR and by the degree of persistent Albuminuria
Goes G1-G5 and A1-A3
CKD classification - outline the stages GFR 1-5 entail?
1 >90 Normal or increased GFR with other evidence of renal damage*
2 60–89 Slight decrease GFR with other evidence of renal damage*
3 A - 45–59, 3 B - 30–44 = Moderate decreased GFR with or without evidence of other renal damage
4 15–29 Severe decreased GFR with or without evidence of renal damage
5 <15 Established renal failure
CKD scoring - What is the A score based on?
TheA scoreis based on thealbumin:creatinine ratio:
- A1 = < 3mg/mmol
- A2 = 3 – 30mg/mmol
- A3 = > 30mg/mmol
What sort of thing can constitute as renal damage, when classifying CKD?
- Albuminuria (ACR > 3 mg/mmol)
- Electrolyte and other abnormalities due to renal dysfunction (e.g. hyperkalaemia)
- Structural abnormalities on imaging
- A history of kidney transplantation
What percentage of the population are thought to suffer with CKD? What is the rise in prevalence thought to be down to?
- 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
Outline the pathophysiology in the adaptations of nephrons that is seen in CKD. (1)
In CKD, The initial failing and scarring of some nephrons leads to an increased filtration on the remaining Functioning, (remnant) nephrons
These remnant nephrons experience hyperfiltration (increased flow per nephron as blood flow remains the same), ==> adapt with glomerular hypertrophy, and reduced arteriolar resistance
Outline the pathophysiology seen in CKD - what does hyperfiltration/glomerular hypertrophy lead to? How can this be detected?
Increased flow, increased pressure and increased shear stress causes a vicious cycle of raised intraglomerular capillary pressure and strain, which accelerates remnant nephron failure
This increased flow and strain may be detected as new/increasing proteinuria
Name some risk factors for being hypovolaemic
Elderly
Ileostomy/colostomy
Short bowel syndrome
Bowel obstruction
Diuretics
Name some risk factors for being hypervolaemic
AKI
Chronic kidney disease
Heart failure
Liver Failure
What are the most common causes of CKD?
Hypertension (second most common)
Diabetes (most common)
how can hypertension lead to CKD?
Walls thicken in order to withstand pressure 🡪 less blood and O2 to kidney 🡪 ischaemic injury to glomerulus
Diminishes ability for nephron to filter blood
How can Diabetes Mellitus lead to CKD?
Excess glucose in blood stick to proteins (particularly affects efferent arteriole making it stiff and narrow
Creates obstruction for blood to leave glomerulus 🡪 hyperfiltration 🡪 supportive mesangial cells secrete more structural matrix increasing size of glomerulus
Glomerulosclerosis 🡪 CKD
When the glomeruli walls become damaged in CKD (due to hypertension for example) what hapens that can lead to further damge of the nephron?
Immune cells (macrophages and foam cells) slip into damaged glomerulus and release TGF-B1 🡪 mesangial cells regress to immature mesangioblast and secrete extracellular matrix 🡪 glomerulosclerosis (hardening and scarring)
Diminishes ability for nephron to filter blood
What are some other causes of CKD?
Systemic disease e.g., Rheumatoid arthritis
Infections (HIV)
SLE
Medications, PPI, ACE inhibitor, NSAIDs, lithium
Toxins (in smoking)
Age-related decline
Glomerulonephritis
Polycystic kidney disease
What are some risk factors for getting CKD?
Diabetes
Hypertension
Age
Gender – M<F
CVD – IHD, PVD
SLE
Renal stones or BPH
Recurrent UTIs
Smoking
LV hypertrophy
Dyslipidaemia
Family history
What are some general symptoms of CKD?
Can be asymptomatic early on
- Nausea
- Anorexia
- Loss of appetite
-
Frothy urine
Malaise,
oliguria, - decreased urine output
haematuria,
nocturia
What are some specific symptoms of CKD, that are due to complications of it?
- Swollen ankles/ oedema
- Increased bleeding: excess urea in the blood makes platelets less likely to stick to each other
Bone disease – osteomalacia, osteoporosis - *Less 1, 25-dihydroxyvitamin D from kidneys = less Serum calcium - more PTH and bone remodelling
Lethargy - due to anaemia
What are some signs of CKD?
- 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
Bilaterally small kidneys on ultrasound
Postural hypotension
Peripheral oedema
Pleural effusions
What are some investigations you should do in CKD?
What would you see?
FBC – shows anaemia, raised creatinine and urea, decreased Ca2+, raised phosphate, PTH, K+ and renin
Estimated glomerular filtration rate (eGFR), checked with U and E blood test
Urinalysis, on dipstick = Haematuria and proteinuria suggest GN
Leukocytes and nitrites suggest infection
Mid-stream urine sent for microscopy and sensitivity
Albumin to creatinine ratio (ACR)
What type of imaging is often done in investigation CKD? What can it show and what does it look for?
Renal ultrasound – excludes obstruction, gives assessment of kidney size (small kidneys favour CKD) and also looks for other abnormalities such as cysts and masses
What would you pick up on examination for CKD? - Not investigation
Pallor/pale skin
Pulmonary/peripheral oedema (anasarca – oedema everywhere)
Hypertension
Pericarditis/pleural effusion
Retinopathy
Palpable kidneys and/or renal bruit (narrowing of renal vessels)
Uraemic smell
What are some first line management for CKD?
Treat underlying cause
Antibiotics for sepsis
Correct volume depletion with fluids
Immunosuppressive agents for vasculitis
Treat hypertension
Give statins
Tight metabolic control in diabetes
Stop nephrotoxic drugs
What lifestyle changes should someone with CKD do?
Diet – Na+ and K+ restriction, supply Vitamin D - need to reduce CKD Mineral bone disease, by REDUCING SERUM PHOSPHATE AND PTH LEVELS
Smoking
Alcohol
Exercise
Outline how you would manage BP in CKD.
What does the first line treatment do regarding the kidneys and CKD?
A – ACE-Inhibitor (e.g. Ramipril) or Angiotensin II receptor blocker e.g. valsartan
B – Beta Blocker e.g. bisoprolol
C – Calcium channel blocker e.g. amlodipine
D – Diuretic e.g. oral Bendroflumethiazide
ACE-Inhibitors – reduce urinary protein
Half urinary protein = half chance of kidney failure and dialysis
First line treatment in patients who are proteinuric and diabetic
What needs to be monitored in CKD as part of management, especially as prescribing treatment of an ACE inhibitor can also cause this?
Serum potassium needs to be monitored as chronic kidney disease and ACE inhibitors, both cause hyperkalaemia.
NOTE: do not routinely offer a renin–angiotensin system antagonist in CKD if the pretreatment potassium is > 5 mmol/L.
What specific diabetes medication is often used in CKD, and what does it do? Give an example of them
SGLT -2 inhibitors like dapagliflozin are particularly used in CKD - USED IN PATIENTS WITH HEART FAILURE
As it decreases renal intraglomerular pressure and inhibits the renin-angiotensin-aldosterone system.
What are some complications of CKD?
Cardiovascular - Heart failure
MSK - Metabolic bone disease, lowered Calcium and Raised Phosphate and PTH
Endocrine - Secondary hyperparathyroidism, and tertiary
Haematological - Anaemia - due to low EPO (Normocytic) or low Iron (Microcytic)
Metabolic - Acidosis, Hyperkalaemia, uraemia - Neuropathy, Encephalopathy, pericarditis
How can you treat the complications of renal disease?
Oral sodium bicarbonate to treat metabolic acidosis
Iron supplementation and erythropoietin to treat anaemia
Vitamin D to treat renal bone disease
Dialysis in end stage renal failure
Renal transplant in end stage renal failure
Outline what renal replacement therapy is. It’s used in severe chronic renal failure. what are the two types
Dialysis – the removal or “uraemic toxins” from the blood by diffusion across a semi-permeable membrane towards low concentrations present in dialysis fluid
Haemodialysis
Surgical construction of AV fistula in forearm – join an artery and vein to make large vessel
Peritoneal dialysis – involves infusing a sugary solution into the abdomen which draws off toxins
Water moves across from circulation into PD fluid by diffusion
When would you consider dialysis in a patient with CKD? What is the next line of therapy after dialysis
Symptomatic uraemic including pericarditis or tamponade
Hyperkalaemia not controlled by conservative means
Metabolic acidosis
Fluid overload resistant to diuretics
If this feels, do kidney transplant
What is pyelonephritis?
Upper urinary tract infection: acute inflammation of the renal pelvis (join between kidney and ureter) and parenchyma
Basically inflammation of the kidney
What some risk factors for pyelonephritis? Who does it predominantly affect?
Predominantly affects females under 35 yrs
- Vesico-ureteral reflux (VUR) - (urine refluxing from the bladder to the ureters – usually in children)
- Female sex
- Sexual intercourse
- Indwelling catheter
- Diabetes mellitus
- Pregnancy
- Urinary tract obstruction e.g. calculi (stones)
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
What is the main bacterial cause of Pyelonephritis? What classification is it? Where is it normally found?
Escherichia coli is the most common cause, as with lower urinary tract infections.
E. coli are gram-negative, anaerobic, rod-shaped bacteria that are part of the normal lower intestinal microbiome.
It is found in faeces and can easily spread to the bladder.
What are some other bacterial causes of Pyelonepritis?
Other causes:
Klebsiella pneumoniae (gram-negative anaerobic rod)
Enterococcus
Pseudomonas aeruginosa
Staphylococcus saprophyticus
Candida albicans (fungal)
pathophysiology of Acute pyelonephritis - what is the main way bacteria can cause an upper UTI? What is a big risk factor that can contribute to this?
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 = urine moves back up urinary tract due to a failure in the vesicoureteral orifice
pathophysiology of Acute pyelonephritis - what are some other ways that can lead to bacteria causing an upper UTI?
- Obstruction also leads to urinary stasis, which makes it easier for bacteria to adhere and colonise the urinary tract
- The infection can also occur via haematogenous spread - through the bloodstream, although this is a lot less common.
What are some symptoms of Pyelonephritis?
Fever
Loin to groin pain
Dysuria (painful to piss) and urinary frequency
Haematuria
Nausea vomiting
Cloudy foul smelling urine
What are some signs of Pyelonephritis?
Tender loin on examination
Pain on palpation of renal angle
Symptoms will often be present on both sides as both kidneys are affected
What symptoms of Pyelonephritis can be used to distinguish it from a lower UTI?
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.
Rare to get these in a lower UTI
What are the investigations for Acute pyelonephritis?
-
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
What is the gold standard test for Acute pyelonephritis?
Mid-stream urine MCS- white blood cell in the urine
What are some differentials for acute pyelonephritis?
- Lower UTI
- Cystitis
- Acute prostatitis
- Urethritis
- Chronic pyelonephritis
What is the treatment for Acute pyelonephritis? What 2 main antibiotics are given?
- Broad spectrum antibiotics (e.g. co-amoxiclav) , and Cefalexin for 7 to 10 days
until culture and sensitivities are avaliable
- Hydration
- Other/ adjuncts
- Admission if systemically unwell or complicated
- IV rehydration
- Analgesia
- Antipyretics
What are the complications of Acute pyelonephritis?
Renal abscess
Recurrent infections
Chronic pyelonephritis-
Papillary necrosis
What is chronic pyelonephritis? What can it lead to??
Chronic Pyelonephritis - recurrent infections of kidneys
Can lead to scarring/thinning of parenchyma, and can progress to CKD/End stage renal failure
How can you assess for renal damage in Chronic pyelonephritis? How/why does this test work?
Dimercaptosuccinic acid (DMSA) scan
Involves Injecting radiolabeled DMSA, which builds up in healthy kidney tissue.
When imaged using gamma cameras, it indicates scarring or damage in areas that do not take up the DMSA - can assess for renal damage
Think of the band, the DMAs
What is cystitis?
A lower UTI that involves the bladder
What are the risk factors of cystitis?
Post-menopause the absence of oestrogen increases the risk
Sexual intercourse
Diabetes - hyperglycaemia prevents neutrophils from carrying out their function against an infection
Poor bladder emptying- allows the bacteria to adhere and colonise the bladder
Catheterisation
outline the aetiology of cystitis.
- 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,
Outline the pathophysiology behind cystitis - other than bacterial infection, what can cause it?
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.
Normal physiology - name some mechanisms the urinary tract has to prevent infection in healthy patients.
urine is normally sterile
- 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.
What are the signs and symptoms of cystitis?
Suprapubic tenderness
- Dysuria: discomfort, pain, burning or stinging associated with urination
- Frequency:
- Urgency:
- Changes in urineappearance/consistency:
- A cloudy or pungent odour
- Haematuria
- Nocturia: passing urine more often than usual at night
- Non-specific, generalised clinical features: e.g. delirium, lethargy, reduced appetite
- Delirium and confusion especially common in elderly patients
What is the 1st line investigation for cystitis? What is gold standard?
-
Urine dipstick: nitrite and leukocyte usually positive:
- PositivenitriteORleukocyte,ANDpositive RBCs: UTI islikely
- NegativenitriteANDpositive leukocyte: UTI isequally likelyto other diagnoses
-
Mid-stream urine microscopy, culture and sensitivity (MC&S):
- Gold standard
- The most specific and sensitive test; bacteria, WBCs, +/- RBCs expected
What are the first and second line treatment for non-pregnant women with cystitis/Lower UTI (drug and duration)
and give duration of treatment too
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
What are the first and second line treatment for pregnant women with cystitis/Lower UTI (drug and duration)
First line: Antibiotic course for 7 days - nitrofurantoin
but avoid nitrofuratnoin in third trimester, give a penicllin instead
Second line: Antibiotic course for 7 days - amoxicillin or cefalexin (1st Gen Cephalosporin)
What are the first and second line treatment for men with cystitis/Lower UTI
First line: Trimethoprim 200 mg twice a day for 7 days
Second line - Nitrofurantoin:
If not resolving, consider an alternative diagnosis !
what are some drugs for UTIs that should be avoided in pregnancy and why?
Trimethoprim carries a teratogenic risk in the first trimester as it inhibits folate synthesis.
Although Nitrofurantoin is first line in pregnant women with lower urinary tract infections, it
should be avoided at term as it may cause neonatal haemolysis
What are the complications of UTIs in pregnancy?
Pre-term delivery
Low-birthweight
When criteria would make you refer someone for suspected bladder cancer?
Aged 45 years 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,
Aged 60 years and over and have unexplained non-visible haematuria and either dysuria or a raised white cell count on a blood test.
Consider non-urgent referral for bladder cancer in people aged 60 years and over with recurrent or persistent unexplained urinary tract infection.
What is prostatitis?
A severe infection involving the prostate that may cause significant systemic upset
What are some causes of prostatitis?
E.coli most common
STI’s
Catheter
Disseminated infections- Secondary to a disseminated infection Bacteria like S.aureus may exhibit ‘metastatic’ spread to multiple locations.
Trauma causing nerve damage is a key risk factor for chronic prostatitis
What are some risk factors of prostatitis
STI
UTI
Indwelling catheter
Post-biopsy
Increasing age
Trauma causing nerve damage is a key risk factor for chronic prostatitis
What are some signs of prostatitis
- Tender, hot, swollen prostate(on digital rectal exam)
- Palpable bladder(if urinary retention)
- UTIs, retention, pain, haematospermia, swollen/boggy prostate on DRE
Pyrexia
Rigors
What are some symptoms of Prostatitis?
Systemically unwell
- Perineal, rectal or pelvic pain
- Back pain
Fever
Rigors
Malaise
Painful ejaculation
Voiding LUTS - Lower urinary tract symptoms:
- Straining
- Poor stream
- Incomplete emptying
- Hesitancy
- Post-micturition dribbling
- Dysuria
What are some investigations for Prostatitis?
Digital Rectal Examination - Prostate is tender, Hard from calcification
Urine dipstick – positive for leucocytes and nitrites
MSU microscopy, culture and sensitivity
Blood cultures
STI screen – chlamydia in particular
Trans-urethral ultrasound scan (TRUSS)
What are the antibiotics typically given in prostatitis?
First line- Oral ciprofloxacin or ofloxacin – fluoroquinolones
Second line- Oral levofloxacin or co-trimoxazole
or according to BMJ, piperacillin/tazobactam
What is the further management for prostatitis, that may be needed?
TRUSS (Transrectal Ultrasound) guided abscess drainage, if needed
- If patient presents with sepsis, patient must be treated according to sepsis 6 principles.
- Patients require further urological review after the acute episode is treated to evaluate for pre-disposing structural abnormalities in the urinary tract.
What is chronic prostatitis characterised by? What is the most predominant risk factor?
by > 3 months of urogenital pain, often associated with LUTS or sexual dysfunction.
- Those with underlying urinary tract abnormalities are at greater risk.
- Men with HIV are at risk of a greater breadth of infection.
Outline some management seen in chronic prostatitis.
-
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
Antibiotic course, cause is bacterial.
What is Urethritis? What is more common, Gonococcal or Non - Gonococcal?
Urethral inflammation due to infectious or non-infectious causes
Non-gonococcal urethritis more common than gonococcal
Name some causes of Urethritis?
Gonococcal
Neisseria gonorrhoea
Non-gonococcal
Chlamydia – most common
Mycoplasma genitalium
Trichomonas vaginalis - A flagellate protozoa
Non-infective
Trauma
Urethral stricture
Irritation
Urinary calculi (stones)
What is the most common STI in young people?
Chlamydia
Certain house mate has this
What are the two categories that urethritis infections are divided into?
Gonococcal and non-gonococcal
What is the cause of gonococcal Urethritis?
Neisseria gonorrhea
What are the common causes of NGU?
Chlamydia trachomatis (most common accounts for up to 50%)
Mycoplasma genitalium
What are the risk factors for getting urethritis?
Male to male sex
Unprotected sex
multiple sexual partners
What are the common symptoms of urethritis?
Urethral discharge
Urethral irritation/itching
Dysuria
Penile discomfort
Skin lesions
What are the key investigations to do in suspected urethritis?
Nucleic acid amplification test (NAAT)
Female – self-collected vaginal swab, endo-cervical swab, first void urine
Male – first void urine
High specificity and sensitivity
Microscopy of gram-stained smears of genital secretions
Blood cultures
Urine dipstick – to exclude UTI
Urethral smear
What is the management for chlamydia
What is the duration
1-week oral doxycycline (a tetracycline)
Pregnant – oral erythromycin (14 days) or oral azithromycin
What is the management for Gonnorrhoea?
IM ceftriaxone (3RD GEN cephalosporin)
Partner notification
What are the complications of urethritis
CAN SPREAD = Epididymitis, Prostatitis
Reactive arthritis
Gonococcal conjunctivitis
Periurethral abscess
Urethral stricture or fistula
What is epididymo-Orchitis?
Inflammation of the epididymis (epididymitis) and inflammation of the testicle (orchitis)
What are the common causes of Epididymo-Orchitis in sexually active men?
STIs, eg
Chlamydia trachomatis
Neisseria gonorrhoea
mycoplasma genitalium
What are some bacterial causes of Epidiymo-orchitis in over 35s/ not sexually active men?
Over 35
UTI – KEEPS
Klebsiella
E. Coli – most common
Enterococcus
Pseudomonas
Staphylococcus – coagulase negative
What are some not bacterial causes of epdidymo-orchitis?
Mumps (viral)
Trauma
Elderly – predominantly catheter related
What are some symptoms and signs of epdidymo-orchitis?
Subacute onset of unilateral scrotal pain and swelling
STI Epididymo-orchitis, eg Urethritis, Urethral discharge
Mumps eg - Headache, Fever, Unilateral/bilateral parotid swelling
Tenderness
Sweats/fever
Signs - Tenderness and palpable swelling
Further signs of Epididymo-Orchitis: What is Prehn’s Sign and cremasteric reflex? How can you use these to differentiate between testicular torsion?
Prehn’s sign positive: pain is relieved with lifting the testicle, negative in testicular torsion
Cremasteric reflex preserved- unlike testicular torsion
What are the investigations for Epididymo-Orchitis?
- 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
What is the treatment for enteric (so not STI) organism causes of Epididymo-Orchitis?
Fluoroquinolone e.g., ofloxacin or ciprofloxacin
What is the treatment for STI organism causes of Epididymo-Orchitis?
Empirical: ceftriaxone and doxycycline
Basically the treatment for Gonorrhoea
What are some complications of epididymo-orchitits?
- 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
When is a UTI deemed as non complicated? What treatment would you give in a non complicated UTI,
Uncomplicated – non-pregnant females
Not necessary to send MSU and treat empirically
3 days
If MSU sent – adjust antibiotics accordingly
Adjunctive advice
Increase fluid intake
Void pre-post intercourse
Hygiene
name some groups of people where you would see complicated UTIs
Pregnant females
Males
Catheterised patients
Children
Recurrent/persistent infection
Immunocompromised
Nosocomial infection
Structural abnormality
Urosepsis
Associated urinary tract disease
What is Glomerulonephritis?
Glomerulonephritis refers to groups of parenchymal kidney diseases that all result in the inflammation of glomeruli and nephrons
How can Glomerulonephritis be classified?
Nephrotic syndrome – protein leaks due to inflammation of podocytes
Acute GN (nephritic syndrome) – blood vessels inflamed 🡪 blood leaks out
Rapidly progressive GN – features of acute nephritis, focal necrosis and rapidly progressing renal failure
Normal physiology - what are the 3 components of renal capillaries? What holds it all together?
Histologically, capillaries have 3 components:
Epithelium – composed of podocytes which only makes contact with GBM via foot processes
Glomerular BM
Fenestrated endothelium – lining of capillaries
Mesangial cells holding it all together
What is Nephritic syndrome, and what is it caused by?
Nephritic syndrome or acute nephritic syndrome refers to a group of symptoms, not a diagnosis.
These symptoms are caused inflammation that damages the glomerular basement membrane, can be due to a number of different causes.
What are the general clinical manifestations seen in nephritic syndrome?
- Haematuria
- Proteinuria
- Arterial hypertension
- Peripheral and peri-orbital oedema - swelling around eyes
- Decreased urine output
What is IgA Nephropathy? What is it define by
is defined by the presence of 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. - sounds like he was a barrel of laughs
For IgA nephropathy, What would you see on
a) Light Microscopy
b) Electron Microscopy
c) immunofluorescence
- On light microscopy: see mesangial proliferation.
- On electron microscopy: immune complexes are seen in the mesangium.
- On immunofluorescence: IgA immune complexes in the mesangium
What disease is IgA Nephropathy similar to, and how so? How can you tell it apart?
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.
Therefore on Light/electron microscopy and immunofluorescence, you would see the same things.
What is the management for IgA Nepropathy?
- 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
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
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 - Anti DNAase B - specifically
These immune complexes travel to the glomerulus through the blood and deposit in the glomerular basement membrane.
How does streptococcus lead to inflammation, and where abouts in the basement membrane do the immune complexes deposit?
- 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.
other investigations can you do for Post streptococcal Glomerulonephritis - What would you see on imaging from a biopsy?
(light, electron, immunofluorescence)
-
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”.
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!
Briefly outline the pathophysiology of Lupus
Cells have faulty DNA, and when these faulty cells undergo apoptosis, these are released and become nuclear antigens
immune cells recognise them as forgein and create antinuclear antibodies that bind to them.
These can travel in the blood and get stuck in lungs, joint, skin, CNS, Heart Kidneys etc
How does SLE cause glomerulonephritis? Where are is the most common site of deposition?
It is a type III hypersensitivity reaction where immune complexes are deposited in various places including kidney
Most common site of deposition is in the subendothelial space of the glomerular basement membrane
Can also be in the Bowerman’s space, Basement membrane, and in Mesangial cells.
What are the pathological manifestations or SLE GN? Is it Nephrotic or Nephritic?
Depends on where the deposits are. This will determine the problems it causes the kidney - Can be either Nephrotic or Nephritic
What are the symptoms of SLE glomerulonephritis?
Haematuria
Proteinuria
Hypertension
Oedema
Lethargy
Musculoskeletal pain and butterfly rash
What is the gold standard investigation for SLE glomerulonephritis?
What would you see?
-
Renal biopsy: gold-standardinvestigation.
- 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.
What is Goodpasture’s disease/syndrome? What is it also known as?
Goodpasture’s disease, also known as anti-glomerular basement membrane antibody (anti-GBM) disease, is an important cause of pulmonary-renal syndrome
Outline the pathophysiology behind Goodpastures - What antibodies bind to what in collagen? What does this do?
n Goodpasture syndrome, autoantibodies bind to a specific part of the α3 chain that is usually hidden deep within the folded triple helix of Type IV collagen. (makes the basement membrane if you can remember phase 1)
This is a type II hypersensitivity reaction - autoantibodies, usually IgG but rarely IgM or IgA, bind to the the α3 chain, and activate the complement system
Pathophysiology of Goodpastures - what does an activated compliment system lead to?
C1 is now activated, starts engages C2 through C9.
The activated (cleaved) fragments C3a, C4a, and C5a act as chemotactic agents and attract other cells e.g. neutrophils.
These cells cause the formation and release of free oxygen radicals
Leads to damage the basement membrane as well as the nearby endothelium and the underlying organ itself.
Normal physiology - what do the podocytes do?
Normally, podocytes wrap around the glomerular capillaries and maintain the filtration barrier -
preventing large molecular weight proteins from entering the urine, by ACTING AS A CHARGE BARRIER
outline the pathophysiology behind minimal change disease. What is affected?
caused byT-cells in the blood, that release cytokines-glomerular-permeability factor, that specifically damages the foot processes of the podocytes, making them flatten out - a process called effacement.
Damaged foot processes lose their negatively charged coat, eventually allowing negatively charged molecules,
MOST COMMONLY SEEN IN CHILDREN
What do you see in the urine of someone with minimal change disease?
- 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.
What would you see on imaging for 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.
Outline what membraneous Neuropathy is
Thickening of glomerular capillary wall. IgG, complement deposit in sub epithelial surface causing leaky glomerulus.
What specific antigens do you see in Membranous Nephropathy?
What can you do regarding this
One major antigen that’s been identified is the phospholipase A2 receptor or PLA2R
Therefore, in patients in which MN is suspected, can do a serum IgG PLA2R antibody test in order to test for MN
What would you see on Microscopy/Histology for Membranous nephropathy? What kind of pattern do you see?
light microscopy, = Thickened GMB, due to IgG complex deposition
On electron microscopy, there’s flattening of the podocyte foot processes and subpodocyte/subepithelial deposits of immune complexes
See Spike and Dome pattern
What is Focal segmental glomerulosclerosis?
a disease in which scar tissue develops in sections of the glomeruli, the small parts of the kidneys that filter waste from the blood.
its name describes how nephrons with this disease appear histologically.
What are the causes of
a) Primary Focal segmental glomerulosclerosis
b) Secondary Focal segmental glomerulosclerosis?
a) Primary is idiopathic
b) Secondary is down to other conditions, history of heroin abuse, HIV infection, Sickle Cell Anaemia
What would you see under an electron microscope for Focal segmental glomerulosclerosis?
Light microscopy - SEGMENTAL SCLEROSIS AND HYALINOSIS OF THE GLOMERULUS
Would see effacement of foot processes under electron microscope
How many types of Membranoproliferative glomerularnephritis are there, what is the hallmark seen in them?
There are 3 types, 1 is most common subtype.
they all cause proliferation of mesangial and endothelial cells in the glomerulus.
Briefly outline the pathophysiology behind the triggering of type 1 Membranoproliferative glomerulonephritis, and what goes on to happen
deleted flashcards on type 2 and 3, too much detail
Through type III hypersensitivity reaction where there are circulating immune complexes, from hep B or hep Cinfections, activates compliment pathway
leads to immune complexes and/or complement deposits end up in the subendothelium
Lead to Thickening of basement membrane, triggers mesangial cells to proliferate and reach through basement membrane with cytoplasmic arms - MESANGIAL INTERPOSTION
What is the histological feature to note that is seen in both type 1 and 2 Membrane proliferative glomerular nephritis?
“tram-track” appearance on light microscopy - due to mesangial interposition which sometimes causes the basement membrane to split around the mesangial cell, forming a duplication of the basement membrane
What is the prostate, and where does it sit lie relation to bladder and rectum? What part of the urethra runs through it?
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.
What are the three main zones that the prostate gland can be divided into?
- 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.
Within the glands of the prostate, what do Luminal cells secrete?
They secrete substances into the prostatic fluid, that make it alkaline ot help sperm survive in acidic pH of vagina, as well as nutrients for sperm
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.
Normal physiology - how is dihydrotestosterone made? What does it do to prostate cells?
DHT is produced by 5α-reductase in the prostate which converts testosterone into the more potent dihydrotestosterone.
both DHT and Testosterone bind to androgen receptors in the cell and prevent apoptosis allowing the prostate to continue to grow.
DHT is 10x more potent that Testosterone
Outline the pathophysiology behind Benign prostatic hyperplasia - why does it occur with increasing age? Where in the prostate is most effected?
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.
How can BPH cause symptoms? What symptoms do you see?
These nodules will compress the urethra making it more difficult to pass urine ==> 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
So see
Dribbling
Straining when urinating
Painful urination (Dysuria)
Trouble initiating urination (Hesitancy)
Incomplete urination and more urination at night (Nocturia)
What are the signs of BPH?
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
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.
5-α reductase inhibitors e.g. finasteride. This will work to reduce the prostate size but can take up to 6 months to work.
What are the the surgical options for BPH and when would they be used?
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)
What is the most common form of prostate cancer? Where in the prostate is it found
Prostate adenocarcinoma - ARISE IN THE PERIPHERAL ZONE
name 2 other, less common forms of prostate cancer.
transitional cell carcinoma arising from cells in the transitional zone, and small cell prostate cancer arising from neuroendocrine cells.
What genes have been linked to prostate cancer, as a risk factor?
BRCA1 and BRCA2 have been linked to prostate cancer
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
What scoring system is used in diagnosing prostate cancer?
Gleason score
From biopsy - assigned a score on a scale of 3 to 5 from 2 different locations. Cancer cells that look similar to healthy cells receive a low score. Cancer cells that look less like healthy cells or look more aggressive receive a higher score.
Normal physiology - what 2 cells are found in the lumen of the seminiferous tubules? What do they do?
Germ Cells - differentiate into spermatogonia
Sertoli Cells - provide nutrients to developing sperm
Normal physiology - name two important structures Outside the Lumen of the seminiferous tubules.
Leydig cells - secrete testosterone, that is allowed into the tubule lumen by Sertoli cells, essential for sperm development
Blood Capillaries are outside
What is the most common form of testicular cancer? How many types are there of it?
Germ cell tumours there are 5 types of this
What are some other types of testicular cancer?
Non-germ cell (sex-cord stromal) cancer of either Leydig or Sertoli cells
- Leydig cell tumours: - will lead to excess Testosterone secretion = causes premature puberty. OR, can have Excess oestrogen can cause delayed puberty and feminisation
- Sertoli cell tumour: usually clinically silent and benign
What are some risk factors for testicular cancer?
- 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
What is the most common type of germ cell testicular carcinoma? What do they secrete?
- Seminoma: most common and best prognosis. Made of germ cells that multiply without differentiation
SECRETE PLACENTAL ALKALINE PHOSPHATASE (PLAP) - normally secreted by the placenta
Name some other types of germ cell testicular carcinoma, and what the germ cells differentiate into.
Embryonal carcinoma: aggressive and metastasises early. - **embryonic pluripotent stem cells **
Teratoma: composed of tissue from different germinal layers e.g. teeth, any type of tissue
Yolk-sac tumour: common in children and aggressive. - made from yolk sac tissue
Choriocarcinoma: rare but most aggressive. Made out of germ cells that differentiate into syncytiotrophoblasts and cytotrophoblasts (cells that help form placenta)
What investiagtions would you do for testicular cancer? What is gold standard, and what should you NOT do?
Gold standard - Doppler Ultrasound of testicles
Tumour markers:β-hCG, AFP (alpha-fetoprotein), and LDH (Lactate dehydrogenase) must be measured prior to surgery.
DO NOT DO BIOPSY, CAN PROVIDE AN EXTRA ROUTE FOR POTENTIAL METASTITSES
What are some first line investigations and gold standard investigations one would do for bladder cancer?
- Urinalysis:haematuria
-
Bloods:
- FBC:assess Hb in patients with chronic haematuria
Flexible cystoscopy and biopsy:under local anaesthetic toconfirmthe presence of a bladder tumour; gold-standard diagnostic investigation
What is the management for superficial, non invasive bladder cancer? What medication do you give on the side?
Trans-urethral resection of bladder tumour (TURBT): rigid cystoscopy under general anaesthetic, with a post-operative dose of intravesical mitomycin C (chemotherapy).
- Intermediate risk:6 doses of intravesical mitomycin C
- High risk:intravesical BCG vaccine
What is the management for muscle invasive bladder cancer?
- Radical cystectomywith neoadjuvant chemotherapy; patients will require an ileal conduit (urostomy) -removal of whole bladder, nearby lymph nodes as well as prostate, seminal vesicles/womb, fallopian tubes
- Radical radiotherapywith neoadjuvant chemotherapy is an alternative to surgery
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.
Normal physiology - what does the primary cillium do in the kidneys, specifically?
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.
Why do cysts form in PCKD?
If either PC1 or PC2 gene is absent, no signal that inhibits growth -
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
What genotype changes are there in adulthood in Autosomal dominant Polycystic kidney disease in order to cause symptoms
A person who develops ADPKD would have 1 single, heterozygous mutation in PKD1 or PKD2 and one functional copy of the gene = this one copy 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.
outline pathophysiology behind autosomal recessive PCKD.
when someone inherits a mutation on both copies of the PKHD1 gene, which codes for the fibrocystin protein.
Means that cyst formation will lead to renal failure even before birth - no urine produced, and since amniotic fluid comes from foetal urine, - there is no amniotic fluid
Pathophysiology behind autosomal recessive polycystic kidney disease - What can low amniotic fluid of the in the womb do to the foetus?
can cause Potter syndrome: without the amniotic fluid, the uterine walls compress the foetus.
Causes physical developmental abnormalities,
like club feet, underdeveloped ear cartilage, low set ears, a flat nasal bridge and abnormalities of the skeleton congenital portal hypertension
What are some extra renal manifestations seen in Autosomal dominant Polycystic Kidney disease?
-
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
What is the management for PKD?
-
General treatment:
- Blood pressure control: ACE inhibitors
- Regular follow-up including renal function assessment and ultrasound to look for progression
Maintain adequate hydration
Treatment for high-risk patients: vasopressin (V2)receptor antagonists e.g. Tolvaptan
Transplant/ dialysis: in cases of kidney failure
What would someone with secondary syphilis present with?
ypically 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
What would someone with tertiary syphilis present with?
Tertiary syphilis can present with several symptoms depending on the affected organs. Key features to be aware of are:
Gummatous lesions (gummas are granulomatous lesions that can affect the skin, organs and bones)
Aortic aneurysms
Neurosyphilis
Recap - what is the epididymis
The epididymiis a tube that connects a testicle to a vas deferens in the male reproductive system. It is a single, narrow, tightly coiled tube in adult humans, 6-7m long
It serves as an interconnection between the multiple efferent ducts at the rear of a testicle (proximally), and the vas deferens (distally).
If a scrotal mass is separate from the testicle, what could it be if it was
a) Cystic
b) Solid
- Separate and cystic = epididymal cyst
- Separate and solid = epididymitis, varicocele
If a scrotal mass is testicular, what could it be if it was
a) Cystic
b) Solid
- Testicular and cystic = hydrocele
- Testicular and solid = tumour, haematocele, granuloma, orchitis, gumma (non cancerous growth)
What is a varicocele? What is it caused by
Abnormal dilation of testicular veins in the pampiniform venomous plexus, caused by venous reflux
What are some of the causes of a varicocele, that lead to impaired venous draingae?
Angle at which the left testicular vein enters the left renal vein
Increased reflux from compression of renal vein
Lack of effective valves between the testicular and renal veins
Outline the pathophysiology behind varicoceles. Why does it occur more on the left than it does on the right?
The pampiniform plexus drains via the gonadal (testicular) veins. Anything that leads to increased pressure may cause varicoceles.
Impaired venous drainage 🡪 increased venous pressure 🡪 vein dilatation
The left gonadal vein is longer and joins the left renal vein at a right angle, which impair venous drainage, compared to the right gonadal vein that drains more obliquely, directly into the IVC.
What are some signs and symptoms of a varicoceles
- 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)
-
Painless testicular swelling
What is a testicular torsion?
Testicular torsion refers to twisting of the spermatic cord with rotation of the testicle. leading to ischaemia and eventually necrosis.
“6 hour window” after onset before damage from ischaemia is irreversible!
What is the most typical presentation seen for someone with testicular torsion?
- 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
Often triggered by playing sport - ask about this in onset of symptoms
What are some risk factors for getting testicular torsion?
- 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
What is the bell clapper deformity?
Why does it happen
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
What are some signs for testicular torsion?
- 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
absent cremasteric reflex, and prehns sign negative (Prehns is positive in epididymtis)
in testicular torsion, you have absent cremasteric reflex, and prehns sign negative
What is the cremasteric reflex, and what is prehns sign?
-
Absent cremasteric reflex
- Swipe the superior and inner part of the thigh
- A normal reflex contracts the cremaster muscle, pulling up the ipsilateral testis
Reflexalmost always absent
-
Prehn’s negative:
- Pain isnotrelieved on lifting the ipsilateral testicle, unlike in epididymitis
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.
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).
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
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
Normal physiology - what happens when the bladder is half full with wee?
When bladder half full, stimulates stretch receptors in bladder wall
===> Send impulses to the sacral spinal chord, at levels S2 and S3 -
PELVIC SHPLANIC NERVE, these signals then go up to micturition centre in the pons
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 - at sacral micturition centre, Onuf’s Nucleus
- 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?
Normal physiology - what stops us from urinating every time our bladder is half full, aka what overrides the Micturition reflex
At this point we should just wee ourselves every time the bladder is half full, however at this point, the PONTINE STORAGE CENTRE OVERIDES MICURITION RELFEX
It does this by activating SYMPATHETIC, HYPOGASTIRC NERVES T10 - L2, that cause DETROUSER RELAXATION, and BLADDER NECK CONTRACTION
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.
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.
Outline the pathophysiology behind overflow incontinence. What things can cause it?
Due to either - Obstruction due to blockage in urine flow
or
Ineffective detrusor muscle. ==> Detrusor cant contract properly so the bladder doesn’t empty properly
In both cases, leads to urine build up, to the point that the bladder is so full that urine dribbles/leaks out through sphincters
Obstruction - - eg benign prostatic hyperplasia,
Ineffective detrusor = Diabetes (neurogenic bladder) Multiple sclerosis, Spinal chord injury
Hepatorenal syndrome - how can liver cirrhosis lead to renal failure?
Liver cirrhosis leads to portal hypertension
In response to this, portal blood vessels dilate, stretched by large amounts of blood pooling there.
This leads to a loss of blood volume elsewhere, including kidneys.
Leads to hypotension in the kidney and activation of the RAAS. This causes renal vasoconstriction, which combined with low circulation volume leads to starvation of blood to the kidney
Hepatorenal syndrome is fatal within a week or so unless liver transplant is performed.
Outline gfr stages 1-5 for CKD - what is a cool tool you can use to remeber
1 >90 Normal or increased GFR with other evidence of renal damage
2 60–89 Slight decrease GFR with other evidence of renal damage
3 A - 45–59, 3 B - 30–44 = Moderate decreased GFR with or without evidence of other renal damage
4 15–29 Severe decreased GFR with or without evidence of renal damage
5 <15 Established renal failure
GFR clock!!!
How do loop diuretics work? Give an example
act at the ascending limb of the loop of Henle
Reversibly inhibit the Na/K/Cl cotransporter, inhibiting the reabsorption of filtered sodium and chloride ions.
Ergo hypertonicity of the renal medulla, thus inhibiting water reabsorption by the collecting ducts.
eg Furosemide, Torsemide
How do thiazide diuretics work? Where do they act and give an example
Work on the distal convoluted tubule
inhibit reabsorption of sodium and chloride ions, by blocking the thiazide-sensitive Na-Cl symporter.
Inhibits the reabsorption of water, reabsorption of water is also inhibited, as water follows sodium.
Examples include clorothiazide and Bendroflumethiazide.
How do aldosterone antagonist diuretics work? Give an example
binds competitively to the aldosterone receptor (AR) at the aldosterone-dependent sodium-potassium exchange site.
This promotes sodium and water excretion and potassium retention
