Renal Tract Flashcards
What is a urinary tract infection?
Infection of bladder (cystitis).
What is the most common pathogen causing UTIs?
E. coli
How does E. coli cause a UTI?
Transurethral ascent of colonic commensals (E. coli)
UTIs are normally uncomplicated and resolve within a few days.
Give some risk factors for uncomplicated UTIs?
- Female
- Sexual activity
- Certain types of birth control; diaphragms, spermicidal agents
- Menopause
- Diabetes mellitus
Why are females more prone to UTIs?
Shorter urethra
Why can menopause predispose to UTIs?
Decline in circulating oestrogens in menopause causes changes in urinary tract that make you more vulnerable to infection (e.g. vaginal atrophy)
UTIs can be complicated. Give some situations that cause a UTI to be complicated
- Pregnancy
- Urinary catheterisation
- Comorbidities e.g. immunosuppression
- Atypical/resistant organisms
- Structural/neurological abnormalities
- 3 months post-renal transplant
What complication can a UTI lead to in pregnancy?
Pre-term delivery and low birthweight
Give some complications of UTIs
- Pyelonephritis
- Urosepsis
- Impaired renal function
What symptoms are typically seen in UTIs?
- Urgency
- Frequency
- Dysuria (pain)
- Suprapubic tenderness
- Foul-smelling urine
- Change in urine appearance
In those with underlying cognitive impairment, typical features of UTIs may be absent. How may they present?
with delirium and reduced functional ability
Aside from an abdo exam, what other exam may be helpful in the context of a potential UTI?
Genital examination if vulvovaginal atrophy or herpes simplex is possible
What is the main sign typically seen in UTIs?
Suprapubic tenderness during palpation
What is the main investigation in UTIs?
Urine dipstick
What would a urine dipstick typically show in UTIs?
Positive for leucocytes and nitrites in most cases
Mid stream urine samples should only be sent in which patient populations in a potential UTI?
- High-risk groups (e.g. pregnancy)
- Men
- Children
- Recurrent UTIs
Typical results of a MSU in a UTI?
+ve for nitrites or leukocytes and RBCs → UTI likely
If the MSU is negative for nitrites, leukocytes and RBCs in the context of a potential UTI, what does this indicate?
UTI less likely
Who is a urine dipstick unreliable in?
- Women >65 y/o
- Catheterised patients
What are the red flags in a UTI?
- Haematuria
- Loin & groin pain
- N&V
- Fever
- Rigors
- Change in mental state
What PMH should you ensure to ask about when assessing a patient with potential UTI
- Possible pregnancy → get test!
- Diabetes mellitus
- Neurological conditions
- Immunosuppression
- Urolithiasis
- Bladder catheterisation
What is the typical treatment for uncomplicated UTIs?
Conservative:
- Fluid intake
- Post-coital voiding
- Analgesia
How should you safety net in the context of a UTI?
Any signs of fever, haematuria, loin pain, N&V, altered mental state → seek medical attention
What is the 1st choice Abx in acute, uncomplicated UTIs?
Nitrofurantoin
What is an alternative to nitrofurantoin in UTIs?
Trimethoprim, amoxicillin, cephalexin
Spectrum of nitrofurantoin?
Active against most organisms that cause uncomplicated UTIs including E. coli (gram-negative) and Staph. saprophyticus (gram-positive)
Is E. coli gram positive or negative?
Negative
Mechanism of nitrofurantoin?
- Metabolised in bacterial cells by nitrofuran reductase
- Its active metabolite damages bacterial DNA and causes cell death (bactericidal)
Which type of bacteria are resistant to nitrofurantoin?
Bacteria with lower nitrofuran reductase activity are resistant to nitrofurantoin (rare for E. coli)
How can nitrofurantoin affect urine colour?
Nitrofurantoin specifically can turn urine dark yellow or brown
Side effects of nitrofurantoin?
- GI upset – nausea, diarrhoea
- Immediate & delayed hypersensitivity reactions
- Nitrofurantoin specifically can turn urine dark yellow or brown
What side effect may occur with the use of nitrofurantoin in neonates?
haemolytic anaemia
Contraindications for nitrofurantoin?
- Pregnancy towards term (avoid in 3rd trimester)
- Babies in first 3 months of life
- Renal impairment → leads to impaired excretion, increased toxicity, and reduced efficacy
- Long term use for chronic UTIs → increases risk of adverse effects (particularly in elderly)
Why is nitrofurantoin contraindicated in renal impairment?
Eliminated via kidneys → leads to impaired excretion, increased toxicity, and reduced efficacy
How should pregnant women with asymptomatic bacteriuria** and/or **suspected/proven UTI be treated?
Treat with antibiotic course (and followed up) → be careful of which trimester!!!
Which trimester is trimethoprim advised against in? Why?
1st → folate antagonist
Which trimester is nitrofurantoin advised against in? Why?
3rd → due to risk of haemolytic anaemia
Antenatal services should be informed if which pathogen is identified in the urine of a pregnant women?
group B streptococcal bacteriuria
What is the key differential of a UTI?
Pyelonephritis (UTI affecting the kidneys)
How would pyelonephritis present that could distinguish it from UTI?
Urinary symptoms +
- Febrile (pyrexia)
- Vomiting
- Loin & groin pain
- Renal angle tenderness
If haematuria persists following the treatment of a UTI, what may this indicate?
Possible underlying malignancy
Bladder cancer can also present with; haematuria, irritation or pain when urinating, dysuria etc
Mechanism of disease in pyelonephritis?
Usually bacteria travelling up from bladder (transurethral ascent of colonic commensals, usually E.coli)
Most common pathogen causes pyelonephritis?
E. coli
If catheter present or abnormal renal tract, what pathogen is more likely to cause pyelonephritis?
E. coli or Pseudomonas aeruginosa
How is a diagnosis of pyelonephritis made?
- UTI symptoms + loin pain/fever
- Culturing urinary pathogen
Main complication of pyelonephritis to worry about?
Sepsis - tachycardia, hypotension, SOB, sweating, rigors, pallor
Risk factors for pyelonephritis?
- Pregnancy
- Diabetes
- Structural renal abnormalities
- Immunocompromised
What is the key differential for pyelonephritis? How can you tell them apart?
Cystitis → key differential (lower UTI)
- Rarely pyrexial
- Rarely loin/flank tenderness
Prognosis of pyelonephritis?
- Usually responds well to antibiotic therapy – time to resolution of symptoms depends largely on initial severity of disease (complete and uncomplicated recovery within days to weeks).
- Prognosis less favourable in older people and those with complicating factors (e.g. immunosuppressed)
What important bedside investigations should you do in pyelonephritis?
- Urine dipstick
- Pregnancy test
Typical results of urine dipstick in pyelonephritis?
typically positive for leucocytes and nitrites
What bloods would you get in pyelonephritis?
- FBC (raised WCC)
- U&Es (check renal function)
- Blood cultures (before Abx)
What other test should you send to lab in pyelonephritis?
Urine MSU for MC&S → obtain sample before starting empirical drug treatment
Immediate management of pyelonephritis?
Admit patient for IV Abx (broad-spectrum penicillin with b-lactamase inhibitor/ a cephalosporin/a quinolone/gentamicin)
Which Abx are used in pyelonephritis?
Broad-spectrum penicillin with b-lactamase inhibitor/ a cephalosporin/a quinolone/gentamicin
Abx of choice in pregnant women with pyelonephritis?
IV cefalexin
Abx of choice in pregnant women with UTI?
Oral nitrofurantoin or cefalexin
Define urolithiasis
Renal tract calculi/renal stones/urolithiasis are hard masses that form in the urinary tract
Pathophysiology of renal stone formation?
Formed due to over-saturation of the urine
How can renal stone formation lead to blockage?
Stones can grow large in size, fill the hollow structures of the kidney or even travel down the ureter
Lodging of the stone in the ureter blocks the flow of urine and may result in pain.
What is the most common type of renal stone?
Calcium based stones (80%)
What are the 4 main types of renal stones?
- Calcium based (80%)
- Struvite (5-10%)
- Uric acid (5-10%
- Cysteine (1%)
What are struvite stones made up of?
Magnesium, ammonium & phosphate
There are two types of calcium based renal stones. What are they? Which is the most common?
Calcium oxalate (most common)
Calcium phosphate (less common)
Which type of renal stone often leads to large, staghorn calculi?
Struvite
Are renal stones more common in men or women?
Men
Are renal stones more common in older or younger generation?
Younger (<65 y/o)
What & of western population do renal stones affect?
2-3% (very common)
What are the major predisposing factors of calcium based renal stones?
- Hypercalcaemia
- Low urine output
- High doses of vitamin D
- High purine/low Na/low K diet
What factors can cause hypercalcaemia that can lead to calcium based renal stones?
- Calcium supplementation
- Hyperparathyroidism
- Cancer (e.g. myeloma, breast or lung cancer)
What is the major predisposing factor to struvite renal stones?
Recurrent upper UTIs
Why do recurrent upper UTIs predispose to struvite stone formation?
Bacteria (UTIs) can hydrolyse the urea in urine to ammonia which can make urine more alkaline, leading to struvite stones
What is the most common organism that causes UTIs that lead to struvite renal stones?
Proteus infection → causes alkalinisation of the urine which leads to staghorn calculi
Uric acid stones often have no predisposing factors. However, which condition can increase the risk?
Gout → due to hyperuricaemia
What type of diet can predispose to uric acid stones?
Diet rich in purine (kidney, liver, anchovies, sardines and spinach), alcohol, gout, CKD → leads to hyperuricaemia
What is the major predisposing factor to cysteine renal stones?
Homocystinuria – an autosomal recessive inherited metabolic disorder which predisposes to recurrent renal stones and UTIs
Give some risk factors for renal stones
- Low fluid intake
- Urinary tract malformations e.g. horseshoe kidney
- UTIs
- Cystinuria (congenital)
- High sodium intake
- 1ary hyperthyroidism
- Hypervitaminosis D
- Sarcoidosis
- Cushing’s syndrome
- Milk-alkali syndrome
What are the 2 major complications of renal stones?
- Obstruction → leading to AKI
- Infection → with obstructive pyelonephritis
Differentials to rule out in potential renal stones (i.e. abdo pain)?
- AAA – rule out in men >65 with flank pain (triad: syncope, hypotension & back pain)
- Ectopic pregnancy (any woman presenting with abdominal pain)
- Pyelonephritis
- MSK pain
- Shingles
- Colitis
- Bowel cancer
- Renal cancer
- Hydronephrosis
- Gallstones
What is the main presenting complaint in symptomatic renal stones?
Renal colic
Describe renal colic
- Unilateral loin to groin pain that can be excruciating (‘worse than childbirth) → patient can’t stop moving
- Colicky (fluctuating in severity) as the stone moves and settles
- Caused by increased peristalsis around the site of obstruction
Give some other signs & symptoms of renal stones
- Haematuria (90% microscopic)
- N&V
- Reduced urine output
- Symptoms of sepsis if infection present e.g. fever, sweats
- Presentation of hypercalcaemia
Does haematuria in renal stones tend to be micro or macroscopic?
90% microscopic
What is the classic presentation of hypercalaemia?
‘Moans, bones, stones and groans’
This refers to depressed mood, MSK pain, renal stones and abdominal pain
What is the 1st line imaging in renal stones?
Non-contrast CT of kidneys, ureter and bladder (CT KUB)
Who should not be offered at CT KUB in renal stones? What can be offered instead?
Women <40 y/o shouldn’t really get this 1st line due to radiation risk → offer US KUB instead
What bedside investigations can be performed in renal stones?
- Pregnancy test
- Urine dipstick → haematuria, possible infection
- Vital signs
- Glucose
- ECG
- Beside USS (FAST)
What bloods can be taken in renal stones?
- FBC – WCCs & neutrophils likely to be raised
- U&Es – creatinine & urea likely to be raised
- LFTs
- CRP
- Serum calcium
AXR can also be used to look at renal stones. Describe the presentation of
a) calcium based stones
b) uric acid stones
c) struvite stones
d) cysteine stones
a) smooth, opaque, silky
b) not visible (radiolucent)
c) staghorn calculus
d) yellow, semi-opaque
Which type of renal stone is not visible on AXR?
Uric acid (radiolucent)
Which type of renal stone appears yellow on AXR?
Cysteine
What is a staghorn calculus?
This is where the stone forms in the shape of the renal pelvis, giving it a similar appearance to the antlers of a deer stag (the body sits in the renal pelvis with horns extending into the renal calyces).
What is the management in renal stones <5mm with no signs of obstruction?
Watchful waiting → 50-80% chance will pass spontaneously
What lifestyle measures should be advised in renal stones?
- Increase oral fluid intake (2-3 litres per day)
- Reduce dietary salt intake
- Maintain normal calcium intake (low dietary calcium might increase risk of stones)
Which drug is used in medical expulsive therapy in renal stones?
tamsulosin
What is 1st line analgesic in renal stones?
PR diclofenac
Most common surgical intervention in renal stones?
Extracorporeal shock wave lithotripsy (ESWL) → required in stones >10mm or where there is complete obstruction/infection
Which drug can be offered for hypercalciuria in renal stones?
Thiazides
Which drug can be offered for uric acid stones?
Allopurinol or potassium citrate
Define hydronephrosis
Swelling of one or both kidneys as a result of the build-up of urine. Can also be found in unborn babies during US scans (antenatal hydronephrosis).
Give some risk factors for hydronephrosis
- Pregnancy
- Kidney stones
- Enlarged prostate (BPH)
- Narrowing of ureters e.g. injury, infection, surgery
- Neurogenic bladder
- Cancer
- Pelvic organ prolapse
- Vesicoureteral reflex
Why can pregnancy predispose to hydronephrosis?
possibly due to the increased amount of urine the baby produces in the later stages of pregnancy
Why can vesicoureteral reflux lead to hydronephrosis?
the valve that controls the flow of urine between the bladder and ureters does not function properly, allowing urine to flow back up to the kidneys
Complications of hydronephrosis?
- Can increase risk of UTIs
- In severe cases, can lead to scarring of kidneys and kidney failure
Prognosis of antenatal hydronephrosis?
Often resolves on its own and will cause no long-term problems for mother or baby
Symptoms of hydronephrosis?
- Renal/ureteric colic: describes an acute and severe loin pain when a urinary stones obstructs the flow of urine
-
Pain in back or sides:
- Can be sudden and severe or a dull ache
- May be worse after drinking lots of fluids
- Symptoms of a UTI: frequency, dysuria, pain on urinating, fatigue, fever
- Blood in urine
- Urinating less often than you used to or with a weak stream
What is the diagnostic imaging investigation for hydronephrosis?
US
1st line management of hydronephrosis?
drain urine out of kidneys by inserting catheter
THEN treat underlying causes e.g. remove kidney stones
Define AKI
Defined as a rapid (within 7 days) and sustained (>24 hours) deterioration in kidney function resulting in oliguria and a rise in serum urea and creatinine.
Define oliguria
<0.5ml/kg/hour
Is AKI reversible?
yes
What classification system is used in AKI?
KDIGO
What is the diagnostic criteria for an AKI? (urine output, serum creatinine)
- Urine output <0.5ml/kg/hour for 6 hours
- Serum creatinine increase 1.5x baseline over 7 days
- Serum creatinine increase by 0.3mg/dL in 48 hours
What 2 factors are involved in the diagnosis of AKI?
Serum creatinine & urine output
What defines stage 1 AKI?
Creatinine rise of 1.5x compared to baseline or urine output <0.5ml/kg/hour for 6 hours
What define stage 2 AKI?
Creatinine rise of 2x compared to baseline or urine output <0.5ml/kg/hour for 12 hours
What define stage 3 AKI?
Creatinine rise of 3x compared to baseline or urine output <0.3ml/kg/hour for 24 hours (or anuria for 12 hours) or serum creatinine >354umol/dl
Pathophysiology behind AKI?
AKI can occur when there is a sudden decrease in glomerular filtration rate (GFR):
- GFR is maintained by sufficient blood flow into the kidneys, functioning nephrons and a clear pathway for outflow of urine from the kidney
- At the glomerular level, GFR is dependent on a pressure gradient between the incoming blood at the afferent capillaries and the pressure in Bowman’s space
Give some risk factors for AKI
- CKD
- Diabetes (with CKD)
- Heart failure
- Renal transplant
- Age >75
- Hypovolaemia (e.g. sepsis)
- Contrast administration
- History of AKI
- Solitary kidney
- Oliguria (<0.5ml/kg/hour)
- Liver disease
- Neurological or cognitive impairment or disability (also may mean limited access to fluids if reliance on carer)
- Drugs e.g. NSAIDs
- Symptoms or history of urological obstruction, or conditions that may lead to obstruction
NSAIDs can be implicated in multiple causes of renal impairment so their use should be restricted in patients at risk of AKI. How can they cause pre-renal AKI?
NSAIDs block prostaglandin mediated vasodilation of the afferent arteriole, which limits the kidney’s ability to regulate local blood flow.
How can NSAIDs cause intra-renal AKI?
NSAIDs can cause acute interstitial nephritis (AIN)
How can NSAIDs cause post-renal AKI?
Long term NSAID use can cause renal papillary necrosis where the medullary papilla sloughs off, causing obstruction to urine flow
What can the causes of AKI be divided into?
- Pre-renal
- Intra-renal
- Post-renal
How does pre-renal AKI occur?
Occurs when there is reduced perfusion to the kidney which reduces the filtration of blood.
Is pre, intra or post-renal AKI most common?
Pre-renal (55%)
What are the major causes of pre-renal AKI?
- Dehydration
- Shock - hypovolaemic, cardiogenic, distributive
- Hypotension
- Renovascular disease e.g. renal artery stenosis
- Heart failure
How does intra-renal AKI occur?
Occurs when there is intrinsic disease (structural/functional) in the kidney, leading to reduced filtration of blood.
This may occur independently or as a transformation of pre-renal AKI.
What are the main causes of intra-renal AKI?
- Acute tubular necrosis (ATN)
- Acute interstitial nephritis (AIN)
- Glomerulonephritis
- Renal vessels - haemolytic uraemia syndrome
What is the most common cause of intra-renal AKI?
Acute tubular necrosis
How does post-renal AKI occur?
Associated with obstruction to outflow or urine from kidney, causing back-pressure into the kidney and reduced kidney function. This is called obstructive uropathy.
What are the major causes of post-renal AKI?
Obstruction can be caused by:
- Ureters: nephrolithiasis (renal stones), retroperitoneal fibrosis
- Bladder: bladder cancer
- Prostate: benign prostate hyperplasia (BPH), prostate cancer
- Urethra: urethral stricture
- External: retroperitoneal mass, ovarian tumours
Obstruction at what level can cause a post-renal AKI in both kideys?
Obstruction at or distal to the level of the bladder can cause a post-renal AKI in both kidneys
Unless there is a solitary kidney, a unilateral obstruction may NOT cause post-renal AKI as the unaffected kidney may be able to compensate.
What are the major complications of AKI?
- Hyperkalaemia
- Fluid overload → pulmonary oedema, pleural effusion, peripheral oedema
- CKD
- Metabolic acidosis
- Uraemia
- Death
How does AKI lead to hyperkalaemia?
Injury involves the late distal nephron and extends into the collecting duct, causing direct injury of cells responsible for K+ secretion
Complications of uraemia caused by AKI?
Can lead to encephalopathy or pericarditis
The KDIGO system confirms an AKI with any of which criteria present?
- Urine output <0.5ml/kg/hour for 6 hours
- Serum creatinine increase 1.5x baseline over 7 days
- Serum creatinine increase by 0.3mg/dL in 48 hours
Why can AKI be challenging to recognise?
AKI can be challenging to recognise as it is often asymptomatic or can present with non-specific symptoms e.g. fatigue, nausea and confusion (can often be mistaken as symptoms of the underlying condition that is causing AKI e.g. sepsis).
Give some signs seen in AKI
- Oliguria or anuria
- Signs of hypovolaemia → dry mucous membranes, reduced skin turgor, tachycardia, hypotension
- Signs of volume overload → hypertension, pulmonary oedema, peripheral oedema, elevated jugular venous pulse
- Signs of uraemia → uraemic encephalopathy (e.g. astrexis, confusion, seizures)
- Signs of post-renal obstruction → palpable or tender distended bladder (urinary retention)
What bedside investigations can be done in AKI?
- Vital signs
- Urinalysis
- 12-lead ECG
What may leucocytes and nitrites in urinalysis suggest in AKI?
infection
What may protein and blood in urinalysis suggest in AKI?
acute nephritis (but can be positive in infection)
What may glucose in urinalysis suggest in AKI?
Diabetes
Purpose of 12-lead ECG in AKI?
look for hyperkalaemia or pericarditis
What bloods would you get in AKI?
- FBC: anaemia, leukocytopenia, thrombocytopenia
- U&Es: creatinine, blood urea nitrogen (BUN), calcium, phosphate, potassium, sodium
- LFTs: serum albumin
- VBG: assess for acidaemia
- ABG: hypoxia (oedema), acidosis, potassium
1st line of imaging in AKI?
US kidneys ureter bladder (US KUB)
Why is a US KUB helpful in AKI?
- Kidney size
- Hydronephrosis
- Post-renal obstruction
- Renal lesions
Why may a CT KUB be useful in AKI?
Post-renal obstruction, renal calculi
Why may a CXR be useful in AKI?
pulmonary oedema
How you should approach an acutely unwell patient with suspected AKI?
DR ABCDE
AKI can be associated with pulmonary oedema (found in B of RRAPID). What can be given to help this?
- Sit patient up and give high flow oxygen
- Give IV furosemide and diamorphine
Typical ABG findings in pulmonary oedema?
Low PaO2 and low PaCO2
How can C be approached in AKI? (RRAPID)
Assess fluid status as patient may be hypovolaemic/hypotensive
- IV fluid resuscitation in pre-renal AKI
- Urine output in post-renal – catheterise patient where necessary
Give some examples of nephrotoxic drugs
NSAIDs
Antihypertensive drugs
Aminoglycosides e.g. gentamicin
Diuretics
Why are antihypertensives nephrotoxic?
as these reduce filtration pressure
What are the indications for dialysis (AEIOU)?
- Acidosis – severe metabolic acidosis with pH of <7.20)
- Electrolyte imbalance – persistent hyperkalaemia of >7mM
- Intoxication – poisoning
- Oedema – refractory pulmonary oedema
- Uraemia – encephalopathy or pericarditis
What type of AKI does hypovolaemia cause?
Pre-renal
What type of AKI does an enlarged prostate cause?
Post-renal
What type of AKI does a neurogenic bladder cause?
Post-renal
What type of AKI does heart failure cause?
Pre-renal
What type of AKI does sepsis cause?
Pre-renal
What type of AKI does acute tubular necrosis cause?
Intra-renal
Nephrotoxic drugs and the mechanism via which they cause renal damage
In the early stages of AKI, how may serum creatinine appear?
In the early stages of AKI, the reduction in GFR may coexist with a normal serum creatinine.
Define nephrotic syndrome
A clinical syndrome that arises 2ary to increased permeability of serum protein through a damaged basement membrane in the renal glomerulus. This leads to the loss of significant volumes of protein via the kidneys (proteinuria >/=3.5g/day) which results in hypalbuminaemia (serum albumin =30g/L), leading to oedema.
Triad of features associated with nephrotic syndrome?
- ++ Proteinuria (>/= 3.5g/day)
- Hypoalbuminaemia
- Oedema
How does nephrotic syndrome lead to proteinuria?
- Cytokines damage podocytes causing them to fuse together and destroy charge of the glomerular basement membrane
- This allows increased permeability to plasma proteins – this causes a massive protein loss in the urine
How does nephrotic syndrome lead to hypoalbuminaemia?
Proteinuria results in serum albumin levels being reduced beyond the synthetic ability of the liver.
How does nephrotic syndrome lead to oedema?
Hypoalbuminaemia results in less oncotic pressure → this lets fluid leak out into the interstitium
How does nephrotic syndrome lead to hyperlipidaemia?
As an attempt to maintain oncotic pressure, the liver tries to compensate by increased synthesis of lipoproteins – this is the mechanism postulated to cause the hyperlipidaemia (not fully understood)
How does nephrotic syndrome lead to hypercoagulability?
due to urinary losses of antithrombotic proteins and increased synthesis or prothrombotic factors)
What are the potential complications of nephrotic syndrome?
- Infection (due to urinary loss of immunoglobulins)
- VTE (due to urinary loss of antithrombin III)
- Hyperlipidaemia (due to increased hepatic production of lipids to restore the serum oncotic pressure)
What is the most common cause of nephrotic syndrome in adults?
membranous glomerulonephritis
What is the most common cause of nephrotic syndrome in children?
Minimal change disease
Other causes of nephrotic syndrome:
-
Systemic disease:
- Diabetes mellitus → glomerulosclerosis
- SLE → membranous
- Amyloidosis
-
Minimal change glomerulonephritis:
- Associated with URTI
- Treat with steroids
-
Membranous nephropathy:
- Associated with cancers (lung, colon, breast) inflammatory conditions (SLE, thyroid), infections (hepatitis), drugs
-
Focal segmental glomerulosclerosis:
- More common in African-Caribbean population
- Associated with Berger’s disease, sickle cell, HIV
- Biopsy – focal scarring, IgM deposition
- Treat with steroids or cyclophosphamide/ciclosporin
Symptoms of nephrotic syndrome?
- Triad → proteinuria, hypoalbuminaemia & oedema
- Peripheral oedema (more common in adults)
- Facial oedema (more common in children)
- Periorbital oedema
- Frothiness of urine (due to protein)
- Fatigue
- Recurrent infections (due to immune dysfunction)
- Venous or arterial thrombosis (e.g. myocardial infarction, DVT) due to hypercoagulability
Signs seen in nephrotic syndrome?
- Oedema (e.g. peri-orbital, lower limb, ascites)
- Xanthelasma and/or xanthoma (hyperlipidaemia)
- Leukonychia (hypoalbuminemia)
- SOB (with associated chest signs of pleural effusion e.g. stony dullness in lung bases) due to blood clots (hypercoagulability)
1st line investigation in nephrotic syndrome?
Urinalysis
Results of urinalysis in nephrotic syndrome?
- Proteinuria (protein +++)
- Frothy appearance
Describe the albumin creatinine ratio (in urine) in nephrotic syndrome
Raised albumin creatinine ratio
Management of nephrotic syndrome?
High dose steroids (tapered according to response)
Define nephritic syndrome
A condition involving haematuria, mild to moderate proteinuria (<3.5g/L/day), hypertension, oliguria and red cell casts in the urine.
What is the triad of clinical features seen in nephritic syndrome?
Haematuria, oliguria & hypertension
Questions concerning nephritic syndrome often require you to distinguish between post-streptococcal glomerulonephritis and IgA nephropathy. What is the key distinguishing factor between the two?
Post-streptococcal glomerulonephritis typically presents 3-4 weeks after a sore throat infection
IgA nephropathy typically presents 3-4 days after a mild URTI.
Give some examples of conditions that full purely under nephritic syndrome
Post-streptococcal glomerulonephritis
IgA nephropathy/Henoch-Schonlein purpura
Infective endocarditis
Goodpasture’s disease
Vasculitis
Symptoms seen in nephritic syndrome?
- Haematuria (can be frank of microscopic)
- Oedema (to a lesser extent compared to nephrotic syndrome)
- Reduced urine output
- Uraemic symptoms (e.g. reduced appetite, fatigue, pruritis, nausea)
Signs seen in nephritic syndrome?
- Haematuria (visible or detectable on urinalysis)
- Oedema
- Hypertension
- Oliguria (<300mls/day)
Results of urinalysis in nephritic syndrome?
- Haematuria (blood +++)
- Proteinuria (mild – protein ++)
- Red cell casts – distinguishing feature of nephritic syndrome, form in nephrons and indicate glomerular damage
Define CKD
A reduction in kidney function or structural damage (or both) present for more than 3 months (with associated health implications). CKD is classified based on the underlying cause, GFR and proteinuria category.
What is the KDIGO criteria for the presence of CKD?
- Decreased GFR (<60ml/min/1.73m2) or;
- Markers of kidney damage (albuminuria, electrolyte abnormalities, structural or histological renal abnormalities) present for >3 months
Patient is usually asymptomatic until what stage of CKD?
Stage 4/5
What are the 4 most common causes of CKD?
- Diabetes
- Hypertension
- Chronic glomerulonephritis
- Polycystic kidney disease
How can diabetes lead to CKD?
high glucose levels damages kidneys
How can hypertension lead to CKD?
puts strain on small vessels in kidneys
What infection can lead to CKD?
Streptococcal (post-strep glomerulonephritis)
Give some examples of nephrotoxic drugs
NSAIDs, ACE inhibitors, aminoglycosides, angiotensin II receptor antagonists, bisphosphonates, diuretics, lithium
The complications of CKD can be understood by considering the key functions of the kidney. What are the 5 key functions of the kidney?
- Waste excretion
- Fluid regulation
- Activation of vitamin D
- Erythropoietin production
- Acid-base balance
The impairment of the kidneys ability to regulate fluid balance in CKD leads to what complications?
Fluid overload:
- Hypertension
- Pulmonary/peripheral oedema
How does CKD affect potassium levels? Why?
Causes hyperkalaemia → due to inability of kidneys to remove excess potassium.
The impairment of waste excretion in CKD leads to what 2 major complications?
- Uraemia (as uric acid is filtered through the kidney) → gout?
- Hyperphosphataemia (phosphates are waste products of metabolism)
How does CKD affect the acid-base balance?
Metabolic acidosis due to:
- impaired ammonia excretion
- reduced tubular bicarbonate reabsorption
- insufficient renal bicarbonate production
Why can CKD lead to anaemia?
Kidneys responsible for EPO production
How does CKD affect calcium levels? Why?
Hypocalcaemia due to 2 mechanisms::
- Phosphate not removed from blood, causing hypocalcaemia in blood as more calcium binds to the excess phosphate
- Vitamin D is no longer converted to its active form by the kidneys, causing inadequate calcium absorption from the gut → levels of calcium in the blood falls, triggering the release of PTH
How does CKD affect parathyroid hormone levels? Why?
Levels of calcium in the blood falls, triggering the release of PTH → hypocalcaemia can trigger 2ary hyperparathyroidism
Complications can be remembered by the pneumonic CRF HEALS. What are these?
- C - Cardiovascular disease
- R - Renal osteodystrophy
- F - Fluid (oedema)
- H - Hypertension
- E - Electrolyte disturbance (hyperkalaemia, acidosis)
- A - Anaemia
- L - Leg restlessness
- S - Sensory neuropathy
Why can CKD cause restless legs?
- Anaemia and/or
- Iron deficiency and/or
- Hypocalcaemia
What is the most common cause of death in CKD?
CVS disease
What is renal osteodystrophy? Why is it seen in CKD?
Caused by disturbed vitamin D, calcium, PTH and phosphate metabolism causing abnormalities in bone turnover and mineralisation
Features:
- Reduced bone density (osteoporosis)
- Reduced bone mineralisation (osteomalacia)
- 2ary/3ary hyperparathyroidism
- May get spinal osteosclerosis
Which 2 factors can be used as prognostic indicators in CKD?
- Increasing proteinuria and/or
- Decreasing eGFR
Potential signs of CKD?
- Oedema
- Pallor (due to renal anaemia)
- Cachexia, signs of malnutrition
- Frothy urine (proteinuria)
- Cognitive impairment (language, orientation, attention)
- Tachypnoea (fluid overload, anaemia, co-morbid ischaemic heart disease)
- Palpable distended bladder (obstructive uropathy)
What is a albumin:creatinine ratio?
Also known as microalbumin.
Involves measuring the amount of albumin in the urine. The amount of urine albumin is compared with the quantity of creatinine (waste product in urine).
what does a high urine albumin creatinine ratio mean?
kidney disease → poor prognostic indicator
What bloods should be done in CKD?
- FBC → anaemia?
- U&Es
- eGFR
- Serum creatinine
- Serum calcium → low?
- Serum phosphate → raised?
- PTH tests
What urine tests should be done in CKD?
- Early morning urine sample → urinary albumin:creatinine ratio (ACR)
- Urine dipstick → haematuria
How can anaemia in CKD be managed?
Monthly subcutaneous erythropoietin injections (target Hb 10-12 g/dL)
NOTE → This should NOT be given in the context of iron deficiency anaemia as can worsen symptoms (check ferritin levels)
How common is BPH?
BPH is the most common prostate problem in men. Almost all men will develop some enlargement of the prostate as they grow older. By age 60, 50% of men will have some signs of BPH; by age 85, 90% of men will have signs of the condition.
Risk factors for BPH?
- Men >50 y/o (hormonal changes):
- Family history
- Diabetes and heart disease (as well as use of beta blockers)
- Lifestyle – obesity increases risk
Effect of BPH on prostate cancer risk?
NO increased risk of developing prostate cancer!
Potential complications of BPH?
- Urinary symptoms (LUTS)
- Bladder, urinary tract or kidney damage
- Urinary retention
- UTIs
- Bladder stones
- Bladder damage
What is the key symptom in BPH?
Lower urinary tract symptoms (LUTS)
What are LUTS?
These can be:
a) storage symptoms
b) voiding symptoms
c) post-micturition symptoms
Give some examples of storage LUTS
urgency, daytime urinary frequency, nocturia, urinary incontinence
Give some examples of voiding LUTS
weak urine stream or stream that stops at starts, difficulty starting urination
Give some examples of post-micturition LUTS
dribbling at end of urination, inability to completely empty bladder
What should be ruled out in those presenting with possible BPH?
Urinary retention
Investigations in BPH?
- DRE to assess prostate for size, constituency, nodules and tenderness → should reveal benign-feeling, enlarged prostate with no obvious nodules
- Urine dipstick for blood, glucose, protein, leucocytes, nitrites → can rule out infection or other conditions
- Serum creatinine & eGFR → can indicate kidney problems
- PSA testing → prostate cancer ??
Lifestyle changes in BPH?
- Less alcohol, caffeine, fizzy drinks
- Exercise
- Limit artificial sweeteners
- Drink less fluids in evening
What is the 1st line pharmacological treatment in BPH?
Alpha blockers (Doxazosin, Tamsulosin)
What is the 2nd line pharmacological treatment in BPH?
5a-reductase inhibitors (e.g. finasteride)
Mechanism of alpha blockers vs 5a-reductase inhibitors in BPH?
Alpha blockers → relax bladder neck muscles and muscle fibres in prostate, making urination easier
5a-reductase inhibitors → shrink prostate by preventing hormonal changes
What hormone is prostate cancer almost always reliant on?
Testosterone
What is the most common type of prostate carcinoma?
Adenocarcinoma
Most common zone that prostate carcinoma is found in?
Peripheral zone
Risk factors for prostate cancer?
- Increasing age
- FH
- BRCA mutation
- Black African or Caribbean origin
- Tall stature
- Anabolic steroids
- Obesity
- Smoking
- Diet (high in animal fats and milk products)
Symptoms/signs in prostate cancer?
- Lower urinary tract symptoms (LUTS) – similar to BPH
- Haematuria
- Erectile dysfunction
- Discomfort in pelvic area
- Symptoms of advanced disease or metastasis:
- Weight loss
- Cauda equina syndrome
- Bone pain
What are the 2 1st line investigations in suspected prostate carcinoma?
- PR exam
- Urine dip
What may a cancerous prostate feel like on a PR exam?
firm or hard, craggy, or irregular, with loss of central sulcus, may be a hard nodule → 2 week wait urgent cancer referral to urology
What blood test can be done in prostate cancer? What are the issues with it?
PSA (prostate specific antigen) → Counselling prior due to poor sensitivity and specificity
1st lin imaging in prostate cancer?
MRI
What scale is used to interpret MRI results of prostate cancer and guide next investigations?
Likert scale
What Likert scale result warrant a prostate biopsy?
Likert 3 or above
What grading system is used for prostate cancer?
Gleason scale
How is the Gleason score calculated?
The Gleason score is made up for two numbers added together for the total score (e.g. 3 + 4 = 7):
- 1st number → grade of most prevalent pattern in biopsy
- 2nd number → grade of 2nd most prevalent pattern in biopsy
Describe 1-5 of the Gleason Score
- 1 – Normal tissue, well differentiated cells that are small and uniform
- 2 – Increased stroma between glands
- 3 – Distinctly infiltrative margins, moderately differentiated cells
- 4 – Irregular masses of neoplastic glands, poorly differentiated
- 5 – Occasional gland formation seen, very poorly differentiated
What staging system is used in prostate cancer?
TNM:
- TX – unable to assess size
- T1 – too small to be felt on examination or seen on scans
- T2 – contained within prostate
- T3 – extends out of prostate
- T4 – spread to nearby organs
Nodes:
- NX – unable to assess nodes
- N0 – no nodal spread
- N1 – spread to lymph nodes
Metastasis:
- M0 – no metastasis
- M1 – metastasis
Main non-hormonal option in the treatment of prostate cancer?
External beam radiotherapy directed at prostate
What is the 1st line hormonal option in the management of prostate cancer?
GnRH analogues/agonists (e.g. Goserelin, Leuprolide)
What class of drugs are Goserelin, Leuprolide?
GnRH analogues/agonists
GnRH agonists can cause a transient rise in testosterone. What drug can be given to counteract this?
Androgen antagonists/anti-androgens (bicalutamide, enzalutamie).
These drugs prevent an increase in disease activity following a transient surge in LH & FSH.
Side effects of hormonal treatment in prostate cancer?
- Decreased libido
- Impotence
- Infertility
- Gynecomastia
- Weight gain
- Osteoporosis
- Diabetes
- IHD
- Anaemia
What is PSA produced by?
The epithelial cells of the prostate produce PSA.
What is PSA?
PSA is a glycoprotein that is secreted in the semen, with a very small amount entering the blood.
Function of PSA?
Its enzymatic activity helps thin the thick semen into a liquid consistency after ejaculation.
Rate of false positives and false negatives in PSA testing?
PSA testing is unreliable with a high rate of false positives (75%) and false negatives (15%)
Some common causes of a raised PSA?
- Prostate cancer
- Acute urinary retention
- BPH
- Recent ejaculation or prostate stimulation
- PR exam
- UTI
- Prostatitis
- Prostate cancer
- Urethral instrumentation
- Vigorous exercise (notably cycling)
If any of these are present, it would be wise to avoid a PSA test as it would raise the possibility of investigation.
Define hyperkalaemia
Plasma potassium in excess of >/= 5.5 mmol/L
- Mild → 5.5-5.9 mmol/L
- Moderate → 6.0-6.4 mmol/L
- Severe → >6.5 mmol/L
What is the most common cause of hyperkalaemia?
Kidney disease:
- AKI
- CKD
- Hyperkalaemic renal tubular acidosis
Why are the kidneys the most common cause of hyperkalaemia?
Kidneys are responsible for 90% of potassium excretion, with the rest being excreted via the GI tract.
Which medications can result in hyperkalaemia?
- ACEi
- ARBs
- Potassium-sparing diuretics
- NSAIDs/COX2 inhibitors
- Digoxin (in toxicity)
- Trimethoprim
- Beta blockers – selective and non-selective
- Nicorandil
- Heparin – UH and LMWH
- Ciclosporin
- Tacrolimus
- Renin-inhibitors (e.g. aliskiren)
- Potassium supplements
- IV fluids containing potassium when used inappropriately
How can trauma/burns affect potassium?
Tissue damage 2ary to trauma or burns results in the release of significant volumes of potassium from damaged cells
How can DKA affect potassium levels?
In DKA, potassium shifts from intracellular to extracellular space due to lack of insulin, resulting in hyperkalaemia
How does aldosterone affect potassium?
Aldosterone promotes excretion of potassium by the kidneys
How does Addison’s disease affect potassium levels?
- Aldosterone promotes excretion of potassium by the kidneys
- In Addison’s disease, the adrenal glands are unable to produce adequate levels of aldosterone which results in reduced renal excretion of potassium
- Aldosterone causes sodium to be absorbed and potassium to be excreted
ECG signs of hyperkalaemia?
- Tall tented T waves
- Wide QRS complexes
- Prolonged PR interval
- Flattened P waves
- AV block
Why can hyperkalaemia lead to bradycardia?
Due to hyperkalaemia-induced AV block
Bedside tests to do in hyperkalaemia?
- Vital signs
- 12 lead ECG
- Capillary blood glucose → rule out hyperglycaemia (e.g. DKA)
Bloods to do in hyperkalaemia?
- FBC
- U&Es
- Confirm presence of hyperkalaemia and assess other electrolytes
- Assess renal function (kidneys responsible for 90% of potassium excretion)
- ABG → rule out metabolic acidosis (e.g. hyperkalaemic renal tubular acidosis or DKA)
- Serum cortisol → rule out Addison’s disease (low serum cortisol)
- Digoxin level → rule out toxicity (if relevant)
What is management of hyperkalaemia determined by?
the level of potassium and the presence/absence of associated ECG changes
What is the pharmacological management of hyperkalaemia if there are hyperkalaemia associated ECG changes present?
IV calcium gluconate
Purpose of calcium gluconate in hyperkalaemia?
Should help stabilise the myocardium temporarily for 30-60 minutes and reduce risk of fatal arrhythmia
What 2 pharmacological agents can be used in hyperkalaemia to help shift potassium intracellularly?
- Insulin-glucose infusion
- Salbutamol
How can salbutamol help in hyperkalaemia?
Often used as adjuvant therapy for hyperkalaemia as it promotes the movement of potassium into cells and out of serum
How can insulin-glucose infusion help in hyperkalaemia?
- Insulin helps to shift potassium from the extracellular to intracellular compartment
- Glucose helps to maintain capillary blood glucose levels
Mechanism of calcium polystyrene sulfonate resin (Calcium resonium) in hyperkalaemia?
Can be used to remove potassium via the GI tract
What is the most common type of bladder carcinoma?
Transitional Cell Carcinoma
Risk factors for transitional cell carcinoma (bladder)?
- Smoking
- Aromatic amines (rubber, dyes, chemical industry)
- Cyclophosphamide
Risk factors for squamous cell carcinoma (bladder)?
- Schistosomiasis infection
- Long term catheterisation (10+ years)
What type of bladder cancer can schistosomiasis infection predispose you to?
Squamous cell carcinoma
What symptoms is considered bladder cancer until proven otherwise?
Painless haematuria (visible)
What is the most common type of renal carcinoma?
Adenocarcinoma
Which 3 cancers most commonly cause hypercalcaemia?
- Breast
- Lung
- Myeloma
What triad of symptoms does an AAA present with?
Syncope, hypotension and back pain
What is haemolytic uraemic syndrome?
A condition that can occur when the small blood vessels in your kidneys become damaged and inflamed. This damage can cause clots to form in the vessels. The clots clog the filtering system in the kidneys and lead to kidney failure. Can result in:
- the destruction of blood platelets (cells involved in clotting)
- a low red blood cell count (anemia)
- kidney failure due to damage to the tiny blood vessels of the kidneys
Give 3 classes of medications used in the management of prostate cancer
- GnRH analogues (e.g. Goserelin)
- GnRH antagonists (e.g. Degarelix)
- Androgen antagonists (e.g. Bicalutamide, Enzalutamide)
What is the key Abx that causes hyperkalaemia?
Trimethorprim