Medical Renal Pathology Flashcards
What are the 4 main functions of the kidney?
- elimination of metabolic waste products
- regulation of fluid / electrolyte balance
- regulation of acid-base balance
- production of hormones
What are the 2 main hormones produced by the kidney?
What are their functions?
Renin:
- involved in fluid balance (RAAS)
Erythropoietin:
- stimulates erythrocyte production
What is the treatment for acute renal failure and the associated mortality?
acute renal failure accounts for 15% of hospital admissions
most patients recover
around 10,000 out of 26,000 annually need dialysis
this has a 50% mortality
What are the treatments for the patients that develop chronic renal failure?
50% will have a transplant at some point
40% will have haemodialysis
10% will have peritoneal dialysis
Approximately how many renal transplants are performed each year?
What are the sources?
2300 transplants per year
28% are living donor renal transplants
most are deceased donor transplants
5000 patients are still on the renal transplant waiting list
How will someone with acute renal failure present?
unwell
rapid rise in creatinine and urea
How would someone with nephrotic syndrome present?
oedema
proteinuria
hypoalbuminaemia
How would someone with acute nephritis (nephritic syndrome) present?
oedema
proteinuria
haematuria
hypertension
renal failure
How would someone with chronic renal failure present?
there would be a slow decline in renal function
What are 2 common presentations of renal disease?
haematuria and proteinuria
What biochemical tests are used to assess renal function?
blood tests:
- urea
- creatinine
urine analysis:
- protein
- blood
- electrolytes
How would a renal biopsy be analysed?
- light microscopy
- immunofluoresence
- electron microscopy
What procedure might a urologist perform in diagnosing a renal impairment?
Why?
cystoscopy
to look for obstruction and haematuria
What would be looked for in renal pathology from a radiological point of view?
- obstruction
- kidney size
- structural abnormalities
What is shown in this image?
the renal cortex
this consists of glomeruli and tubules
What types of cells cover the glomerulus?
How do they play a role in acting as a filter?
podocytes cover the glomerulus
the filter involves podocyte foot processes, endothelial cells and the basement membrane
Label the features of the nephron and the blood flow pathway
What 3 main conditions cause vascular damage that affects the kidneys?
- hypertension
- diabetes
- atheroma e.g. renal artery stenosis
What is vasculitis?
What can it cause in the kidney?
acute / chronic vessel wall inflammation with lumen obliteration
various types affect different calibre vessels
e.g. Wegener’s granulomatosis
What is thrombotic microangiopathy?
How can it affect the kidneys?
thrombi in capillaries / arterioles
endothelial damage by bacterial toxins, drugs, complement or clotting system abnormalities
can lead to haemolytic uraemic syndrome
What are the 3 immunological conditions which can cause basement membrane damage?
- circulating immune complexes deposit in the glomerulus
e. g. SLE, IgA / membranous nephropathy - circulating antigens deposit in the glomerulus
- antibodies to the basement membrane / glomerular components
e. g. goodpasture’s syndrome
What can immunological basement membrane damage lead to?
- complement activation
- neutrophil activation
- reactive oxygen species
- clotting factors
these all cause glomerular damage
What are the 4 non-immunological processes that can cause direct glomerular damage?
- endothelial injury
e. g. vasculitis, HTN, clotting disorders - altered basement membrane
e. g. DM hyperglycaemia - abnormal basement membrane or podocytes due to inherited disease
e. g. Alport disease - Abnormal protein deposition (amyloid) impairs function
e. g. myeloma, RA
How is the degree of renal tubule damage related to renal function?
the degree of renal tubule damage correlates with renal function
what are the ischaemic and toxic causes of tubular damage?
Ischaemic:
- hypotension
- vessel damage
- glomerular damage
These cause reduced perfusion, leading to tubular damage
Toxic:
- direct toxins
- hypersensitivity reactions
- crystal deposits
- abnormal protein deposition
These cause direct tubular damage
What are examples of direct toxins?
- drugs - NSAIDs, antibiotics, ACEi, diuretics
- contrast medium
- organic solvents
- heavy metals
- ethylene glycol
- pesticides
What 3 components can cause reduced blood flow to the kidney?
- damage to glomerulus
- damage to tubule
- damage to blood vessels
What diseases are caused by damage to the glomerulus?
Immunological:
- membranous anti-GBM disease
- IgA nephropathy
- lupus nephritis
- post-infective
Non-immunological:
- minimal change disease
- FSGS
What types of diseases cause damage to blood vessels?
Inflammatory:
- vasculitis
Endothelial damage:
- hypertension
- thrombotic microangiopathy
Abnormal deposits:
- amyloid
- diabetes
What kind of diseases cause damage to the tubule?
direct toxicity:
- drugs and poisons
- e.g. gentamicin
hypersensitivity:
- drugs e.g. penicillins
abnormal deposits:
- myeloma
inflammatory:
- pyelonephritis
- others e.g. sarcoid
ischaemic:
- shock
- glomerular damage
- vascular disorders
What are the problems with diagnosing renal conditions based on histological appearance?
- more than one disease may look the same
- some diseases have variable histology
- some names are both diseases (when idiopathic) and appearances (when secondary to known cause)
This means that aetiology and pathophysiology may be unclear
What causes nephrotic syndrome?
What are the features and complications?
ALWAYS DUE TO DAMAGE TO GLOMERULUS
features:
- oedema
- proteinuria ( >3g in 24 hrs)
- hypoalbuminaemia
- +/- hypertension
- +/- hyperlipidaemia
complications:
- infection
- thrombosis
What are the 3 most common causes of nephrotic syndrome?
Membranous nephropathy:
- most common
- mostly in adults under 60
- more common in men
- 20-30% progress to end stage renal failure
focal segmental glomerulosclerosis (FSGS):
- more common in males
- usually idiopathic but also genetic, due to HIV or heroin use
minimal change disease:
- normal histology
- equally affects males and females
also caused by diabetes, lupus nephritis and amyloid
What are the most common causes of nephrotic syndrome in children?
- minimal change disease
- focal segmental glomerulosclerosis (FSGS)
- other causes are rare
What are the symptoms of acute nephritis (nephritic sydrome)?
- oedema
- haematuria
- proteinuria
- hypertension
- acute renal failure
What are the 4 most common causes of acute nephritis in adults?
post-infective glomerulonephritis:
- weeks after streptococcal throat infection
IgA nephropathy:
- common primary glomerular disease
- usually in young adults
- 20-50% develop renal failure over 20 years
Vasculitis:
- unwell, fever, rash, myalgia, arthralgia
SLE:
- autoimmune disease
- usually affects young women
What are the most common causes of acute nephritis in children?
- post-infective glomerulonephritis
- IgA nephropathy
Henoch-Schönlein purpura:
- specific IgA nephropathy (systemic vasculitis) often follows throat infection
- usually in boys
- associated with arthralgia, abdominal pain, purpuric rash, proteinuria, haematuria and acute renal failure
Haemolytic-uraemic syndrome:
- typically in children with E. coli 0157 enteritis
- acute nephritis, haemolysis and thrombocytopenia
What is acute renal failure associated with?
What are the 3 categories of causes?
- anuria / oliguria (<400 ml / 24 hours) + raised creatinine and urea
- malaise, fatigue, nausea, vomiting and arrhythmias
causes:
- pre-renal, renal or post-renal
prognosis is usually good if there is no underlying renal disease
short term dialysis may be needed in some patients
What are the pre-renal causes of acute renal failure?
reduced blood flow to the kidney
- severe dehydration
- hypotension (bleed, septic shock, LVF)
What are the post-renal causes of acute renal failure?
urinary tract obstruction
- urinary tract tumours
- pelvic tumour
- calculi
- prostatic enlargement
What are the renal causes of acute renal failure?
damage to the kidney
When can a renal biopsy be useful in acute renal failure?
a renal biopsy is helpfyl in renal causes
a renal biopsy is unhelpful in pre-renal or post-renal causes
What are the most common causes of acute tubular necrosis/injury/damage as part of acute renal failure?
adults:
- vasculitis
- acute interstitial nephritis / tubulointerstitial nephritis
children:
- PIGN
- Henoch-Schönlein purpura
- haemolytic uraemic syndrome
- acute interstitial nephritis
What is tubulointerstitial nephritis?
tubular damage with inflammation
this is usually due to drugs
What are the complications and treatments for acute renal failure?
complications:
- cardiac failure (fluid overload)
- arrhythmias (electrolyte imbalance)
- GI bleeding (multifactorial)
- jaundice (hepatic venous congestion)
- infection - esp. lung and urinary tract
treatment:
- depends on underlying cause
- short term dialysis may be needed
What does it mean if someone has a permanently reduced GFR?
there is a reduced number of functional nephrons
What are the 5 stages of chronic renal failure?
stage 1:
- normal / increased GFR
- > 90 ml / min / 1.73m2
stage 2:
- mild GFR reduction
- 60 - 89 ml/min/1.73m2
stage 3:
- moderate GFR reduction
- 30 - 59 ml / min / 1.73 m2
stage 4:
- severe GFR reduction
- 15 - 29 ml / min / 1.73 m2
stage 5:
- kidney failure
- GFR < 15 or dialysis
Why is a renal biopsy usually unhelpful in established chronic renal failure?
the kidney will show severe scarring with loss of glomeruli and tubules
end-stage renal disease due to any cause is similar
What are the effects of chronic renal failure?
- reduced excretion of water / electrolytes - oedema & hypertension
- reduced excretion of toxic metabolites
- reduced production of erythropoietin - anaemia
- renal bone disease (phosphate / calcium)
What chronic conditions can lead to chronic renal failure in adults and children?
adults:
- diabetes
children:
- developmental abnormalities / malformations
adults and children:
- glomerulonephritis
- reflux nephropathy (repeated infections and scarring)
What is meant by isolated proteinuria?
proteinuria BUT less than the nephrotic range
there is no allied haematuria, renal failure or oedema
What are the 2 causes of isolated proteinuria?
benign:
- e.g. postural, related to pyrexia or exercise
renal disease:
- adults - FSGS, DM, SLE
- children - FSGS, HSP
What is meant by isolated haematuria?
Which investigations must be conducted?
haematuria +/- proteinuria with normal renal function
cystoscopy / urological investigations need to exclude malignancy
What are the usual causes of isolated haematuria?
IgA nephropathy
Thin basement membrane disease:
- inherited condition causing abnormally thin glomerular basement membranes
- renal function usually normal
Alport hereditary nephropathy:
- inherited abnormalities of type IV collagen cause abnormal basement membrane
- sometimes with eye and ear problems
- leads to renal failure +/- deafness +/- occular problems
What are the risk factors and complications associated with acute pyelonephritis?
risk factors:
- female (ascending infection)
- instrumentation
- diabetes
- urinary tract structural abnormalities
complications:
- abscess formation
What are the risk factors and complications associated with chronic pyelonephritis?
risk factors:
- urinary tract obstruction /reflux
complications:
- scarring
- chronic renal failure
What actually is pyelonephritis?
inflammation of the kidney, usually due to a bacterial infection
What happens in renal artery stenosis?
What is it usually caused by and what does it lead to?
most commonly due to atheroma and arterial dysplasia
leads to ischaemic injury of the affected kidney
activation of renin-angiotensin-aldosterone system leads to hypertension
loss of renal tissue leads to reduced renal function
What is renal artery stenosis?
narrowing of the arteries that lead to one or both of the kidneys
commonly due to atherosclerosis so can get worse over time
What is shown in this image?
What is the role of mesangial cells?
they maintain the glomerular structure
What is vasculitis?
How can it affect the kidneys?
What kind of disease is it usually part of?
there are various types affecting different calibre vessels
inflammation in glomerular vessels can cause clotting, obliteration of capillary lumena and glomerulus destruction
inflammation of larger renal arterioles can cause tubule hypoxia
it is often part of systemic disease - rash, fever, myalgia, arthralgia, fever, weight loss
What histological signs are seen in vasculitis?
- fibrin indicates thrombosis in glomerulus once capillary lumena are obliterated
- inflammatory cells surround the artery which has damaged walls
How does hypertension affect the renal vessels and kidneys?
it damages the renal vessels through wall thickening and reduction in lumen size
this produces chronic hypoxia - loss of renal tubules and reduced renal function
reduced renal blood flow activates the RAAS, which exacerbates hypertension
What histological signs would be seen in hypertension?
renal arterioles have a thickened wall and small lumen
What is the commonest cause of end-stage renal failure in the developed world?
diabetes
What are the 2 mechanisms of damage to the kidney in diabetes?
two mechanisms of damage are both due to hyperglycaemia
- damaged basement membrane thickens and the glomerulus produces excess extracellular matrix (nodules)
- small vessel damage causes ischaemia and tubular damage
What is myeloma?
How does it affect renal function?
a plasma cell tumour
causes excess antibodies to deposit in the tubules and cause inflammation and fibrosis
renal tubule loss causes irreversible decline in renal function
what are the histological features of myeloma?
- artery walls with immunoglobulin deposits
- fibrosis
- tubules destroyed by Ig deposits
What is membranous nephropathy?
thickened glomerular capillary walls
What are the histological features of FSGS?
mostly normal except for a solid area with loss of capillary lumena
What are the histological features of post-streptococcal GN and IgA nephropathy?
they both show glomeruli with increased cellularity and loss of capillary lumena
What are the histological features of acute tubulointerstitial nephritis?
many lymphocytes / inflammatory cells in between renal tubules
What are the histological features of anti-GBM disease?
crescents represent cells proliferating in Bowman’s capsule in response to any severe glomerular injury
e.g. vasculitis and post-infective glomerulonephritis
What are the histological features of acute tubular necrosis/injury?
loss of nuclei from tubular cells due to cell death
What are the histological features of chronic kidney damage?
interstitial fibrosis and tubular atrophy
shrunken (atrophic) tubules are surrounded by fibrosis
scarring is present in end-stage renal disease
