Renal / Urology - lecture notes/extra info Flashcards
(143 cards)
1
Q
Glomerular structure
A
2
Q
What is the mechanism of glomerular injury in Goodpasture’s disease?
A
Antibody binding to intrinsic glomerular antigens (anti-GBM antibodies)
3
Q
What is the unerlying immune mechanism in post-streptococcal glomerulonephritis?
A
Antibody binding to planted glomerular antigens
4
Q
How does lupus nephritis cause glomerulonephritis?
A
Deposition of circulating antigen-antibody complexes in the glomerulus
5
Q
What is the immune mechanism behind IgA nephropathy?
A
Non-specific deposition of circulating IgA antibodies in the glomerulus
6
Q
What is the mechanism of glomerular injury in systemic vasculitis?
A
“Pauci-immune” capillary inflammation, as seen in ANCA-associated vasculitis (e.g., microscopic polyangiitis, granulomatosis with polyangiitis)
7
Q
Name some indications for renal biopsy
A
- Nephrotic syndrome (adults)
- Renal dysfunction of unknown cause (particularly acute)
- To guide treatment or assess prognosis where diagnosis known
- Dysfunction of transplant kidney
- (Haematuria)
- (Proteinuria)
8
Q
Absolute / Relative contraindications to renal biopsy
A
- Abnormal clotting / thrombocytopenia
- Drugs (aspirin , clopidogrel, warfarin, DOACs etc)
- Uncontrolled hypertension (eg > 170/100)
- Single kidney
- Hydronephrosis
- Urinary tract infection
9
Q
In renal biopsy, what process would be used to assess basic morphology and cellular infiltrate, and what special stain can be used to see collagen more clearly?
A
Light microscopy
10
Q
In renal biopsy, what process would be used to detect immunoglobulin or complement component deposition?
A
Immunostaining (immunofluorescence/immunoperoxidase)
11
Q
In renal biopsy, what process would be used to look at ultrastructural detail, including immune deposits?
A
Electron microscopy
12
Q
Case study:
- 45-year-old man with frothy urine, generalised oedema
- Urine dipstick: 4+ protein
- Investigations: Urine protein excretion (5g/24hrs), Albumin (22)
A
Nephrotic syndrome
- proteinuria
- hypoalbuminaemia
- oedema
13
Q
What is the commonest cause of nephrotic syndrome in children?
A
Minimal change syndrome (> 75%)
14
Q
What are the light microscopy findings in minimal change syndrome?
A
Normal appearances
15
Q
What is seen on electron microscopy in minimal change syndrome?
A
Fusion of podocyte foot processes, a non-specific result of proteinuria
16
Q
How does minimal change syndrome typically respond to treatment?
A
Normally steroid-responsive, but may relapse and require stronger immunosuppression
17
Q
What is the usual cause of minimal change syndrome?
A
Usually idiopathic, but can have underlying causes (eg. Drugs (NSAIDs) and lymphoma)
18
Q
How does focal segmental glomerulosclerosis (FSGS) typically present?
A
Nephrotic syndrome +/- renal impairment
19
Q
Why can FSGS be difficult to diagnose on biopsy?
A
It has patchy (focal) involvement, meaning affected areas may be missed
20
Q
What are the key histological features of FSGS?
A
Segmental sclerotic lesions with C3 and IgM deposition
21
Q
How does FSGS respond to steroids compared to minimal change disease?
A
It is much less steroid-responsive
22
Q
What is the prognosis of FSGS?
A
It may progress to end-stage renal failure and can recur after transplantation
23
Q
Focal segmental glomerulosclerosis can be primary or secondary, what are some secondary causes of FSGS?
A
- Obesity
- IV heroin use
- HIV
- Drugs (e.g., pamidronate)
24
Q
What is the most common cause of nephrotic syndrome in adults?
A
Membranous nephropathy
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What are the key histological features of membranous nephropathy?
"Spikes" on basement membranes and IgG deposition
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What conditions are associated with membranous nephropathy?
- Malignancy → warrants careful history and possible investigations.
- Drugs (e.g., gold, penicillamine, captopril).
- Infections (e.g., hepatitis, malaria)
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What is the prognosis of untreated membranous nephropathy?
Rule of thirds:
- 1/3 improve spontaneously.
- 1/3 remain stable.
- 1/3 develop progressive disease
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How is membranous nephropathy treated?
It may respond to immunosuppression
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How can Mesangiocapillary Glomerulonephritis (MPGN) present clinically?
It can present in multiple ways, including nephrotic or nephritic syndromes
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What are the key histological features of Mesangiocapillary Glomerulonephritis (MPGN)?
- Mesangial proliferation, often lobular.
- Thickened capillary walls with "double contouring" of the basement membrane
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What is seen on immunofluorescence in Mesangiocapillary Glomerulonephritis (MPGN)?
Positive staining, often with C3 deposition
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What conditions are associated with MPGN?
- Infections (e.g., hepatitis, malaria, endocarditis, shunt nephritis)
- Cryoglobulinaemia
- Malignancy
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What is the earliest clinical feature of diabetic nephropathy?
Microalbuminuria (low level proteinuria)
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What does histology in diabetic nephropathy show?
Kimmelstiel-Wilson lesions (nodular glomerulosclerosis)
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How can amyloidosis present clincially?
heavy proteinuria ± nephrotic syndrome ± renal failure
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Pathology of amyloidosis
Deposition of amyloid within multiple organs, including kidneys
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What special stain is used to identify amyloid?
Congo red stain, which shows apple-green birefringence under polarized light
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What is seen on electron microscopy in amyloidosis?
Amyloid fibrils are visible on electron microscopy
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What are the two main types of amyloidosis, and their associations?
- AL amyloidosis – *light chain deposition (e.g., myeloma)*
- AA amyloidosis – *secondary to chronic inflammation (e.g., infection, connective tissue disorders)*
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Case study:
- 24 year old man presents with macroscopic haematuria
- Had developed a sore throat the previous day
- General examination and blood pressure normal
- Settled spontaneously, but persistent microscopic haematuria 4 weeks later
IgA Nephropathy (Berger's disease)
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What is the most common form of glomerulonephritis?
IgA nephropathy (Berger’s disease)
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What is the underlying pathology of IgA nephropathy?
Deposition of circulating IgA in the mesangium, leading to mesangial matrix expansion and mesangial cell proliferation
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What are the different clinical presentations of IgA nephropathy? (3)
- Asymptomatic microscopic haematuria
- Episodic macroscopic haematuria, often triggered by exercise or respiratory tract infection
- Progressive renal impairment, possibly leading to end-stage renal failure
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What conditions are associated with IgA nephropathy?
- Liver disease
- Henoch-Schönlein purpura (IgA vasculitis) – presents with abdominal pain, joint pain, and purpuric rash
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Case study:
- 30 year old man presents feeling unwell
- Sore throat 2 weeks ago
- Ankle swelling and dark urine for the last few days
- Urine dipstick positive for blood
- BP 160/100
- Creatinine 170
Nephritic pattern
- hypertension
- haematuria
- renal impairment
46
When does post-infectious glomerulonephritis typically occur after a Group A Streptococcal infection?
2-3 weeks after a throat or skin infection caused by Group A Streptococcus
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How does post-infectious glomerulonephritis usually present?
As a nephritic illness
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What are the typical C3 and C4 levels in post-infectious glomerulonephritis?
Low C3 and normal C4 due to activation of the alternate complement pathway
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What does this biopsy indicate?
- Neutrophil infiltration, mesangial and epithelial cell proliferation, IgG and C3 deposition, and subepithelial deposits
post-infectious glomerulonephritis
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What is the treatment for post-infectious glomerulonephritis?
Supportive treatment
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What is the underlying pathology of systemic vasculitis and how it can affect kidneys
Inflammation of blood vessels leading to multiorgan involvement
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What antibodies are associated with systemic vasculitis?
ANCA (Anti-Neutrophil Cytoplasmic Antibodies)
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What does a biopsy show in systemic vasculitis?
Focal necrotising glomerulonephritis, with or without crescents, but it is pauci-immune
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How may systemic vasculitis respond to treatment?
It may respond to therapy if treated early, including immunosuppression and possibly plasma exchange
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What is the underlying cause of Goodpasture's disease?
Antibodies to type IV collagen, specifically targeting the glomerular and alveolar basement membranes
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What are the common presenting symptoms of Goodpasture's disease?
Acute kidney injury and/or pulmonary haemorrhage
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What does a biopsy show in Goodpasture's disease?
Focal necrotising glomerulonephritis, with or without crescents, but with linear antibody deposition
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How may Goodpasture's disease respond to treatment?
It may respond to therapy if treated early, including immunosuppression and possibly plasma exchange
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What is the clinical presentation of rapidly progressive glomerulonephritis (crescentic nephritis)?
Nephritic illness with rapidly deteriorating renal function
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What does a renal biopsy show in rapidly progressive glomerulonephritis?
An acute inflammatory process with crescent formation, which involves cellular proliferation in Bowman’s space.
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Why is early diagnosis crucial in rapidly progressive glomerulonephritis?
It requires rapid diagnosis due to the potential for rapid renal deterioration
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What histological changes can occur in lupus nephritis? (WHO classification - 6 categories)
- I
- II
- III
- IV
- V
- VI
I: Normal glomeruli (including minimal change)
II: Mesangial disease
III: Focal proliferation (< 50%)
IV: Diffuse proliferation (> 50%)
V: Membranous nephropathy
VI: Advanced sclerosis
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Is there always a correlation between clinical presentation and histology in lupus nephritis?
Often, there is poor correlation between clinical presentation and histology
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What is vital for diagnosing lupus nephritis?
A renal biopsy is vital for diagnosing lupus nephritis
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Urine proteins (3)
- Albumin
- Low molecular weight proteins - beta-2 microglobulin, polypeptides, RBP
- Secreted proteins
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Physiology of Nephron
2 sets of capillary networks
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Glomerular filtration barrier
A normal functioning filtration barrier keeps most of the protein in the blood
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How does proteinuria usually present, and how does heavy proteinuria present?
- usually asymptomatic - *incidental detection on urine dipstick*
- Heavy proteinuria --> frothy urine, peripheral oedema
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Features of a urine dipstick + what protein is measured?
- fresh non-centrifuged morning sample
- sterile universal container
- dipstick in container and wipe clean
- results read promptly
.
- Measures albumin concentration via a colorimetric reaction between albumin and tetrabromophenol blue producing different shades of green according to the concentration of albumin
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Advantages and disadvantages of urine dipstick test
- Adv: simple bedside test in multiple settings, rapid diagnosis, cheap
- Disadv: operator dependent, semi-quantitative and insensitive to low-level proteinuria, does not detect non-albumin proteinuria
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Ways of detecting proteinuria
- Urine dipstick
- Urine protein-creatinine ratio and urine albumin-creatinine ratio - *spot urine sample*
- 24hr urine protein collection - *not used that often and can be inaccurate (results vary on hydration lvls of pt - eg. dehydrated --> more protein)
72
What is important to think about and manage in a patient with proteinuria and if it progresses (proteinuria becomes worse) + what is the "nephrotic range"?
- Blood pressure - *consider BP management*
.
"Nephrotic range" - *proteinuria + oedema and hypoalbuminaemia = nephrotic syndrome*
- ACR > 250
- PCR > 300
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Describe the process behind glomerular proteinuria
Disruption in the glomerular filtration barrier
- Loss of structural integrity (podocytes, basement membrane, endothelial cells) can result in excess protein filtration
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Describe the process behind tubular proteinuria + some causes
Caused by effects of absorption/secretion within the renal tubules
- various inflammatory conditions can cause tubular proteinuria
.
- causes --> inflammation, infection, autoimmune
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Describe the process behind overflow proteinuria + causes
Excess production of low-moleculra weight proteins
- too much for glomerulus to adequately filter/tubules to reabsorb
(eg. myeloma)
.
- causes --> myeloma (free light chains), rhabdomyolysis (myoglobin), haemolysis (haemoglobin)
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Describe the process behind post-renal proteinuria + causes
Characterised by inflammation in the urinary tract, after the level of the nephron
.
- causes --> inflammation of lower urinary tract (infection, stones)
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Physiological/Benign proteinuria VS Pathological proteinuria
Physiological/Benign:
- *transient proteinuria secondary to fever, heavy exercise, vasopressor, IV albumin (usually < 1g / day)*
- *Orthostatic proteinuria (usually < 3.5g / day)*
.
Pathological:
- due to disruption of the glomerular filtration barrier
- can be associated with microscopic haematuria
- usually > 1g / day
- Nephrotic range proteinuria (> 3.5g / day) --> *usually glomerular*
78
Name some primary glomerulonephritides
- Minimal change disease
- Primary focal segmental glomerulosclerosis
- idiopathic membranous nephropathy
- IgA nephropathy
- idiopathic membranoproliferative glomerulonephritis (MPGN)
79
Name some secondary glomerulonephritides
- Diabetes mellitus
- Systemic amyloidosis
- Secondary focal segmental glomerulosclerosis - *eg. obesity, hypertension, HIV infection*
- autoimmune disease - *eg. SLE*
- secondary membranous nephropathy - *eg. cancer, drugs*
- membranoproliferative glomerulonephritis - *Hepatitis B or C*
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2 conditions which proteinuria is a risk factor for
- cardiovascular disease
- chronic kidney disease (CKD)
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What tests would you do for a patient with proteinuria?
- Hx and physical examination
- urine dipstick and quantification of proteinuria
- assessment of renal function - serum creatinine and GFR
- renal imaging - USS
- relevant blood tests - *ANA, ANCA, Anti-GBM, serum protein electrophoresis and serum free light chain ratio, Hep B / C serology, Complement (lupus nephritis), Anti-PLA2R*
- Renal biopsy --> diagnostic
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Features of nephrotic syndrome:
- urine protein excretion
- albumin lvls
- other features...
- Urine protein excretion > 3.5g / day (uPCR > 300mg/mmol, uACR > 250mg/mmol)
- Hypoalbuminaemia - *serum albumin < 3g/dL
- Oedema and hyperlipidaemia
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What is the underlying cause of nephrotic syndrome? (location of pathology)
Glomerular disease - *disruption of the glomerular filtration barrier with podocyte effacement*
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Clinical features of nephrotic syndrome
- frothy urine
- peripheral oedema
- pulmonary oedema and pleural effusions
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What are general measures for management of nephrotic syndrome?
General (aim is to address fluid overload):
- low sodium diet and fluid restriction
- diuretics
- renin-angiotensin-aldosterone inhibition and BP control
- statin
- anticoagulation - *reduce clot risk*
86
Why is a renin-angiotensin-aldosterone system (RAAS) inhibitors used in the management of nephrotic syndrome?
- *eg. ACE-i, ARB*
- angiotensin constricts and increases GFR - *constriction of efferent arteriole increases pressure within glomerular capillary bed*
- inhibition of angiotensin dilates efferent arteriole and decreases GFR
- this decreases proteinuria
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Management of diabetic nephropathy
- Glycaemic control, BP control, and RAAS inhibition
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What is the first line radiological investigation for kidney stones (renal calculi)?
Non-contrast CT (except < 25yrs females, due to radiation)
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Basic kidney anatomy
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What is a quick, non-invasive bedside test that can be used to look at the kidneys?
Ultrasound
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Normal kidney USS
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What does this USS kidney show?
Epigenic (brighter) fat --> sign of inflammation
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What does this USS kidney show?
Pelvicalyceal dilatation (or hydronephrosis) --> condition where the renal pelvis widens
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Causes:
- Urine retention in the upper urinary tract
- Blockages in the urinary tract
- Reflux of urine from the bladder into the kidneys
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What position should a patient be in when imaging for kidney stones (renal calculi)?
Prone --> ensuring the stones naturally fall to the anterior part of the bladder, helping to differentiate them from stones that might have already passed into the bladder itself
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Axial CT scan
- R kidney enlarged
- kidney stone in proximal ureter causing upstream dilatation
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USS kidney
Stone with acoustic shadowing --> dark area seen on an ultrasound image behind a kidney stone, which is caused by the stone significantly reflecting sound waves, preventing the ultrasound signal from reaching deeper tissues, and appearing as a shadow on the image
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What is a ureteric jet?
a visible stream of urine that enters the bladder from the ureter. It can be seen during an ultrasound
.
- They can help assess ureteral function
- They can help examine the flow of urine
- They can help detect obstructive uropathy
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Nephrocalcinosis --> generalised calcium deposition in the kidney
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Polycystic renal disease
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Cysts in liver
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What level does the renal artery come out at?
L1/L2
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Clinical features of acute and chronic hyponatraemia
(chronic hyponatraemia features are very non-specific)
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Risk of treating hpyonataraemia too quickly
Osmotic demyelination syndrome - central pontine myelinolysis
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B) Administration of furosemide
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Hypovolaemic shock is a reason a patient might need immediate fluid resus, this is where there is inadequate perfusion to tissues. What are the clinical signs of shock?
- Low SBP (<100mmHg)
- Tachycardia (>90bpm)
- Tachypnoea (>20rpm)
- Delayed CRT
- Cool peripheries
-High or deteriorating EWS
- Response to PLR
- Confusion / decreased LOC
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Benefits of renal transplant over dialysis
- provides greater GFR (closer to normal physiological kidney function)
- replaces non-excretory functions - *erythropoietin production, vitamin D metabolism (hydroxylates vit D)*
- freedom from dialysis (but need for immunosuppressive drugs and intensive follow-up
- greater overall survival (following initial post-operative period)
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Transplant rejection:
- Hyperacute
- Acute
- "Chronic"
- Hyperacute - *due to pre-formed anti-donor antibodies in recipient, can cause graft loss within minutes to hrs, avoided by pre-operative cross-match (untreatable)*
- Acute (occurs days onwards) - *T cell or antibody-mediated, usually responds to additional immunosuppression*
- Chronic - *term is now out of favour, often used non-specifically to include
non-immunological causes of chronic damage (does not usually respond to additional immunosuppression)*
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How do T cells bind with antigens
via APC (on MHC complex)
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T cell activation
- signal 1
- signal 2
- signal 3
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Corticosteroids:
- main site of action -->
- side effects
- main site of action --> cell nucleus
.
side effects:
- impaired glucose tolerance
- gastric irritation
- osteoporosis
- thinning of skin
- easy bruising
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Complications of immunosuppressive drugs
Drug-specific side effects
- Calcineurin inhibitor nephrotoxicity
- Diabetes from tacrolimus
- Diabetes / osteoporosis from steroids
- Bone marrow suppression from antiproliferative agents
- Poor wound healing / high lipids from sirolimus
.
Infection
- “Usual” versus opportunistic pathogens
(eg Pneumocystis, Cytomegalovirus, Cryptosporidium)
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Malignancy
- Skin tumours (basal / squamous cell carcinoma)
- Lymphomas (particularly B cell – Epstein Barr Virus-related)
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Anatomy of renal corpuscle (glomerulus + Bowman's capsule)
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Complications of an acute kidney injury (AKI)/rapid decline GFR
- Fluid overload
- buildup of toxins (uraemic toxins)
- K+ buildup --> hyperkalaemia --> cardiac arrhythmias
- lose acid-base balance
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More renal anatomy: Describe the kidney filtering process
1. Blood filtration in the glomerulus
- Each kidney contains nephrons (filtering units)
- Each nephron has a glomerulus (network of capillaries where blood filtration occurs)
- Glomerulus 'sieves' the blood - *small molecules (water, electrolytes, glucose, and waste products) pass through into the Bowman's capsule, while larger molecules (blood cells and proteins) remain in the blood*
- GFR = *amount of filtrate produced per minute, kept at stable value through several feedback mechnaisms*
.
2. Tubular reabsorption and secretion
- After initial filtration in glomerulus, the filtered fluid (ultrafiltrate) enters the renal tubule
- The renal tubule selectively reabsorbs valuable substances like water, glucose, amino acids, and electrolytes back into the bloodstream
- Renal tubule also secretes certain substances, such as excess H+ ions and certain drugs, into the tubular fluid to help regulate pH and eliminate waste products
- The fluid that remains in the tubule after reabsorption and secretion is urine
.
3. Urine formation and excretion
- The tubular fluid (now urine) flows into the collecting duct, where further adjustments to water and electrolyte balance can occur
- The urine then flows from the collecting fucts into the ureters (tubes that carry urine from the kidneys to bladder)
- The bladder stores urine until it is excreted from the body through the urethra
114
Pre-renal causes of AKI
- hypovolaemia (can go into hypovolaemic shock + sepsis) - *renal (diuretics, oscmotic), GI (D+V, haemorrhage), third space losses, skin*
- nephrotoxic drugs
- renovascular disease - *renal stenosis*
- left ventricular dysfunction (impaired cardiac function) - *heart failure*
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AKI classification
- Serum Cr ≥ 26.5 micromol/l in 48 hrs
- Serum Cr ≥ 1.5 (base) within last 7 days
- UO < 0.5ml/kg/hr for 6 hrs
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Risk factors for AKI
- Elderly
- Arteriosclerosis (HTN, DM)
- Pre-existing renal disease
- Underlying CVD
- ARB/ACE-i/Anti-hypertensives/Diuretics
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Post-renal obstructive causes of AKI (intrinsic and extrinsic)
Intrinsic:
- Intraluminal (stone, blood clot, papillary necorsis)
- Intramural (bladder tumour, urethral stricture)
.
Extrinsic:
- Prostate --> *malignancy, BPH*
- Pelvic --> *tumour*
- RPF
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What are the 3 protective mechanisms involved in renal autoregulation (ie. to help maintain renal blood flow)?
1. Myogenic reflex - *the intrinsic ability of the afferent arteriole's smooth muscle to contract in response to increased pressure and relax when pressure decreases, thus regulating blood flow to the glomerulus and protecting it from damage*
2. Tubuloglomerular feedback - *regulates GFR by sensing changes in tubular fluid composition at the macula densa (ie. conc. of NaCl in tubular fluid) and adjusting the afferent arteriole's resistance accordingly (eg. when NaCl concentration increases, the macula densa signals the afferent arteriole to constrict)*
3. Renin-Angiotensin system
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Renal (intrinsic) causes of AKI
- ATN (acute tubular necrosis)
- Acute GN (acute glomerulonephritis) - *can be identified on dipstick --> due to glomerular dysfunction --> letting blood/protein into ureter and therefore urine shows this*
- Acute TIN (acute tubulointerstitial nephritis) - *very steroid-responsive*
- Acute vascular - *thrombosis/dissection/stenosis, emboli, vasculitis*
116
Hyperkalaemia ECG changes
- tall tented T waves
- absent p waves
- broad QRSrolonged PR interval
116
Effects of prostaglandins and angiotensin on the afferent and efferent arterioles respectively
- Prostaglandins - *vasodilators that primarily act on afferent arteriole (increasing renal blood flow and GFR)*
- Angiotensin - *angiotensin II is a vasoconstrictor (acts on both afferent and efferent, but more efferent), leading to increased glomerular pressure and maintains GFR under conditions of reduced renal perfusion*
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