HISTO: Renal pathology Flashcards
What are the major functions of the kidney?
- Excretion of metabolic waste products and foreign chemicals (including drugs)
- Regulation of fluid, electrolyte and acid/base balance
- Regulation of blood pressure - renin
- Regulation of haematocrit - erythropoietin
- Regulation of calcium and bone metabolism – via 1,25 Dihydroxycholecalciferol
Where is the kidney located? What is its size? What % of cardiac output does it receive?
Location: retroperitoneal; T12 to L3 on left; right is lower
Size: Mean length 11cm, normal weight 125-170g (male), 115-155g (female)
Cardiac output: Receive around 20% of cardiac output
What is the basic unit of the kidney and what does it consist of?
- Glomerulus
- Afferent and efferent arterioles
- Tubules
What is the pressure at the glomerulus? How much blood is filtered per min? Which cells are vital in its function?
- High hydrostatic pressure (60mmHg)
- 125 mL/min
Podocytes create charge-dependent (anionic) and size-dependent barrier
What is the function of the proximal convoluted tubule?
- Actively resorbs sodium
- Potassium is also reabsorbed
- Hydrogen exchange to allow carbonate resorption
- Co-transport of amino acids, phosphate, glucose
What is the function of the Loop of Henle?
- Descending / thin ascending limb permeable to water but not ions or urea;
- Ascending limb actively resorbs sodium and chloride
- Countercurrent multiplier; aligned with vasa recta
What is the function of the distal convoluted tubule?
- Impermeable to water
- Regulates pH via active transport (proton / bicarbonate)
- Regulates sodium, potassium via active transport (aldosterone)
- Regulates calcium (parathyroid hormone, 1,25 dihydroxycholecalciferol
What is the function of the collecting duct?
- Resorbs water (principal cells,ADH)
- Regulates pH (intercalated cells, proton excretion)
Which part of the nephron has these functions?
- actively resorbs sodium
- is a countercurrent multiplier, aligned with vasa recta
- regulates pH
- regulates calcium
- resorbs water
- Sodium active resorption - PCT, LoH (ascending),
- Regulates pH - DCT, CD
- Countercurrent multiplier - LoH
- Calcium regulation - DCT
- Resorbs water- CD (but LoH ascending is permeable to water, whereas DCT is impermeable)
What is RC?
renal corpuscle
What is M? A?
M - Mesangium
A - afferent arteriole
What is labelled FS?
Fenestration between podocytes of the glomerulus
Below:
- Endothelial cells (inside)
- GBM
- Podocytes outside with fenestrations
What are the signs and symptoms of renal disease/
- Haematuria
- Proteinuria
- Uraemia
- Hypertension
- Oliguria / Anuria
- Polyuria
- Oedema
- Colic
List 3 renal ‘syndromes’.
- Acute renal failure/AKI
- nephrotic syndrome
- microscopic haematuria
ie. constellations of symptoms
List 5 genitourinary/kidney malformations.
- Agenesis
- Renal Fusion (e.g. horse-shoe)
- Ectopic Kidney
- Renal Dysplasia
- Pelvi-ureteric Junction Obstruction
- Ureteral Duplication
- Vesicoureteral Reflux
- Posterior urethral Valves
What is the inheritance pattern of polycystic kidney disease? How common is it? What is a common consequence?
AD
1 in 500
Cause 10% of all end-stage renal failure
What genetic mutations are implicated in polycystic kidney disease?
PKD1, PKD2.. etc
What extra-renal manifestations may occur in PKD?
Berry aneurysm
What is an iatrogenic cause of kidney cysts? Are they dangerous?
Cysts commonly develop in patients with end stage renal disease who are on dialysis. These can be multiple, bilateral, cortical and medullary
What type of renal malignancy can occur due to cystic disease of the kidney?
Papillary renal cell carcinoma
7% risk at 10 years
Define acute renal failure/AKI.
Rapid deterioration in renal function (hours, days)
Common, often in the setting of pre-existing disease
What are some causes of acute renal failure? What is the commonest cause?
- Pre-Renal: Failure of perfusion
- Renal: Acute tubular injury, acute glomerulonephritis, thrombotic microangiopathy
- Post-Renal: Obstruction
Acute tubular injury/ATN is most common.
What can cause acute tubular injury?
- Ischaemia
- Toxins (contrast, Hb, myoglobin, ethylene glycol)
- Drugs esp. PG inhibitors like NSAIDs
Describe the pathophysiology of ATN.
- Loss of brush border and degradation of cells
- Apoptosis of epithelial cells and sloughing into the lumen which may cause luminal obstruction
- Cells which survive spread out
- In recovery, there should be proliferation, differentiation and re-polarisation of these cells again.
What is Acute Tubulo-Interstitial Nephritis? What are the causes of ATIN?
Immune injury to tubules and interstitium
Caused by immune injury but can also be due to infection and drugs such as:
- NSAIDs
- Antibiotics
- Diuretics
- Allopurinol
- Proton Pump Inhibitors
Describe the infiltrate seen in ATIN.
- Heavy interstitial inflammatory infiltrate with tubular injury
- Can see eosinophils, granulomas
What is acute glomerulonephritis? How does it usually present?
AGN = Acute inflammation of glomeruli
Presents with oliguria with urine casts containing erythrocytes and leucocytes
When sufficient to cause AKI, there are almost always _crescents_ (proliferation of cells within Bowman’s space) as shown.
List three types of acute ‘crescentic’ glomerulonephritis.
- Immune Complex Complex Associated Crescentic Glomerulonephritis
- Anti Glomerular Basement Membrane Disease
- Pauci-immune Crescentic Glomerulonephritis (NB: ANCA positive i.e. anti-neutrophil cytoplasm antibodies)
What are the aetiologies of immune complex associated crescentic glomerulonephritis?
- SLE,
- IgA nephropathy
- Post-Infectious Glomerulonephritis
What is anti-GBM disease? What specific antibody is found in anti-GBM disease?
Rare and severe disease caused by Ab directed against the GBM
Ab directed at C-terminal domain of Type IV collagen - may be detected with serology
What is an extra-renal complication of anti-GBM disease?
Lung injury - this occurs because antibodies in anti-GBM may cross-react with alveolar basement membrane leading to pulmonary haemorrhage
What is seen on histology/immunofluorescence in anti-GBM disease?
Linear deposition of IgG demonstrable on glomerular basement membrane
What are the characteristic features of is Pauci-immune crescenteric glomerulonephritis?
Only scanty glomerular immunoglobulin deposits
Usually ANCA-associated - trigger neutrophil activation and glomerular necrosis
Vasculitis elsewhere
What is the patter of Ig glomerular deposition in Pauci-immune crescenteric glomerulonephritis?
scanty glomerular immunoglobulin deposits
What is the pathophysiology of thrombotic microangiopathy? What can happen to RBCs in this condition?
Damage to endothelium in glomeruli, arterioles, arteries leading to thrombosis
Red cells may be damaged by fibrin –> MAHA/ HUS
What are the aetiologies of thrombotic microangiopathy(TMA)?
Divided into diarrhoea and non-diarrhoea associated.
Diarrhoea associated - e.g. E. coli, toxins released that target renal endothelium
Non-Diarrhoea associated
- Hypertension
- Scleroderma
- Antiphospholipid Antibody Syndrome (+/- SLE)
- Defects in regulation of complement
- Drugs (calcineurin inhibitors)
- Radiation
- Deficiency in ADAMTS13
Name the four main diagnostic features of nephrotic syndrome.
Breakdown in selectivity of glomerular filtration barrier leading to protein leak
- Proteinuria (>3.5g/day)
- Hypoalbuminemia
- Oedema
- Hyperlipidaemia
How are the causes of nephrotic syndrome grouped? Give an example of each.
Primary Glomerular Disease, Non-Immune Complex Related =
- Minimal Change Disease
- Focal Segmental Glomerulosclerosis
Primary Renal Disease, Immune Complex Mediated =
- Membranous Glomerulonephritis
Systemic Disease =
- Diabetes mellitus
- Amyloidosis
- SLE
What is the characteristic/diagnostic feature of MCD?
- Glomeruli look normal by light microscopy
- Effacement of foot processes on EM
- More common in children
What is the prognosis with MCD vs FSGN?
MCD = generally responds to immunosuppression
FSGN = less likely to respond to immunosuppression
Define focal segmental glomerulonephritis.
- Focal = means <50% of glomeruli
- Segmental = only part of the glomeruli
- Sclerosis = scarred
Therefore: some partially scarred glomeruli
Where do immune complexes deposit (IgG and C3) in membranous glomerulonephritis?
Associated with immune deposits on outside of glomerular basement membrane i.e. subepithelial
Most common cause of NEPHROTIC syndrome in adults
What is the antibody directed against in primary MGN?
Primary disease –> antibody against phospholipase A2 type M receptor (PLA2R) in 75% of cases
What are some secondary causes of MGN?
Need to exclude possibility of a secondary disease e.g.
- Epithelial malignancy,
- drugs,
- infections,
- SLE
How common is diabetic nephropathy?
True or false: High glucose levels thought to be directly injurious in diabetic nephropathy.
Affects 30-40% of diabetics
True
What are the stages of diabetic nephropathy?
Typically starts as microalbuminuria –> proteinuria –> nephrotic syndrome
Nodular Glomerulosclerosis (shown below, left to right)
- Stage 1 – Thickening of basement membrane on EM
- Stage 2 – Increase in mesangial matrix, without nodules
- Stage 3 – Nodular lesions / Kimmelstiel-Wilson
- Stage 4 – Advanced glomerulosclerosis
What is amyloidosis? What structure does it tend to deposit in?
Amyloidosis - Deposition of extracellular proteinaceous material exhibiting β-sheet structure
What are the commonest forms of amyloidosis in the kidney? What condition is each associated with?
Commonest forms in kidney are
- AA - derived from serum amyloid associated protein (SAA), an acute phase protein; patients tend to have a chronic inflammatory state
- AL - derived from Ig light chains; 80% of patients have multiple myeloma
What stain is used in amyloidosis? Describe its appearance under normal light and polarised light.
Congo red
- Normal light – salmon pink appearance*
- Polarised – apple green appearance (birefringence)*
What are two causes of microscopic haematuria?
- Thin basement membranes
- IgA Nephropathy
What are some causes of asymptomatic proteinuria? What investigations would need to be done?
Broad range of glomerular structural abnormalities or immune complex deposition
Diagnosis often requires:
- renal biopsy for histology
- immunohistochemistry
- EM
What is the pathophysiology of thin BM? How is thin defined here? How does it present?
- Hereditary defect in Type IV collagen synthesis
- Basement membrane <250nm thickness
Presentation: haematuria is only consequence in most cases
What genetic condition causes thin basement membranes? What is the prognosis?
Alport’s Syndrome
X-linked dominant - mutations affecting ⍺5 subunit (but forms exist in which mutation affects ⍺3 or ⍺4 subunit)
Prognosis: typically progressive, renal failure in middle age
Other features: deafness, ocular disease
What is the most common glomerulonephritis?
IgA nephropathy
What is the aetiology of IgA nephropathy? What condition can it be associated with?
–> IgA-predominant mesangial immune complex deposition
Aetiology:
- Not well understood in primary form
- Secondary forms observed in liver, bowel and skin disease
- Can be seen with small-vessel vasculitis (Henoch-Schönlein Purpura)
What classification system is used for IgA nephropathy?
Oxford classification (MEST-C)
What are the stages of CKD?
Define end stage renal failure. What stage of CKD is this?
eGFR <15
Stage 5 of CKD
What is the most common cause of CKD requiring RRT? NB: unknown/uncertain in a lot of cases
- Diabetes – 27.5%
- Glomerulonephritis – 14.1%
- Polycystic Kidney Disease – 7.4%
- Pyelonephritis – 6.5%
- Hypertension – 6.8%
- Renal Vascular Disease – 5.9%
- Other / Uncertain – 31.7%
What is the pathophysiology of hypertensive nephropathy?
Not fully understood
Narrowing of arteries and arterioles–> to scarring and ischaemia of glomeruli
HTN in glomeruli –> altered haemodynamic environment, stress and segmental scarring
What are the histological features of hypertensive nephropathy?
Gross: shrunken kidneys with granular cortices
Histopathology may show:
- “nephrosclerosis”
- arteriolar hyalinosis
- arterial intimal thickening
- ischaemic glomerular changes
- segmental and global glomerulosclerosis
How does SLE affect the kidney? Which antibodies are commonly found in the kidney in SLE?
–> deposition of immune complexes
Antibodies directed at a broad range of intracellular and extracellular antigens e.g. anti-nuclear and anti-dsDNA antibodies are typical
What classification system is used for renal SLE?
ISN/RPS Classification
How is renal SLE classified?
- Class 1 – near normal on light microscopy, minimal mesangial disease
- Class 2- mesangial deposits, not past BM
- Class 3- focal (i.e. <50%) disease, subendothelial deposits
- Class 4 – diffuse (>50%) disease, diffuse deposits
- Class 5 – membranous pattern, subepithelial depoists
- Class 6 – advanced sclerosis (>90%)
NB: Patients can move between classes; it is not necessarily progressive.
Which classes of renal SLE are associated with these types of disease:
- Mesangial ?
- Endothelial ?
- Epithelial ?
- Mesangial - class II
- Endothelial - class III and IV
- Epithelial - class V
List 4 ways in which renal SLE can present.
- Acute Renal Failure/AKI
- Nephrotic Syndrome
- Isolated Urinary Abnormality
- Chronic Kidney Disease
1
- LKM 1 and LKM 2 – AI hepatitis and chronic hepatitis respectively*
- Desmoglein 1 and 2 – pemphigus and cardiac disease respectively*
2
1
- Oil Red O – fat detection*
- Sirius Red – scarring and fibrosis detection*
2
