Histopathology - Renal Pathology Flashcards
What two syndromes arise from issues with the glomerulus?
- Neprhotic syndrome
- Nephritic syndrome
What are some primary causes of nephrotic syndrome?
- Minimal change disease
- Membranous glomerular disease
- Focal segmental glomerulosclerosis
What are some secondary causes of nephrotic syndrome?
- DIABETES
- Amyloidosis
- SLE
What are some causes of nephritic syndrome?
- Acute-post infectious (e.g. Post-streptococcal)
- IgA Nephropathy (e.g. Berger Disease)
- Rapidly progressive glomerulonephritis
- Alport’s Syndrome (e.g. Hereditary nephritis)
- Thin Basement Membrane Disease (e.g. Benign Familial Haematuria)
What are some conditions that affect the tubules and interstitium?
- Acute tubular necrosis
- Tubulointerstitial nephritis
What are some conditions that affect the renal blood vessels?
Thrombotic Microangiopathies
- HUS
- TTP
What is the triad of nephrotic syndrome?
- Proteinuria (>3g/24hr) / PCR >300mg/mmol
- Hypoalbuminaemia
- Peripheral oedema
What are other characteristic features of nephrotic syndrome?
- Hyperlipidaemia
- Thrombotic disease (increased cholesterol + clotting tendency)
What are some key words associated with nephrotic syndromes?
- Swelling (classically periorbital in children)
- Frothy urine (due to proteinuria)
- ISSUE WITH PODOCYTES (filtration barrier)
What is the general management for nephrotic syndromes?
Steroids
What is the epidemiology, prognosis + general features of minimal change disease?
Epi:
- Most common in children
- Second peak in elderly
Features:
- Possible trigger = recent allergic Rx
- A/w: eczema, asthma
Px:
- <5% ESRF
What are the investigative findings for minimal change disease?
Light microscopy:
- No change
Electron microscopy:
- Loss of podocyte foot processes
Immunofluorescence:
- No immune deposits
What is the management and response for minimal change disease?
- Steroids
- Cyclosporin
90% response to steroids
What is the epidemiology, prognosis + general features of membranous glomerulonephritis?
Epi:
- Common in adults
Features:
- Primary or secondary
- Secondary causes: SLE, Drugs, Malignancy
- Abs against Phospholipase A2 present in 75%
Px:
- 40% ESRF >2-20yrs
What are the investigative findings of membranous glomerulonephritis?
Light microscopy:
- Diffuse glomerular basement membrane thickening
Electron microscopy:
- Loss of pdocyte food processes
- Subepithelial deposits = spikey
Immunofluorescence:
- Immune complex deposits along entire GBM
What is the management and response of management for membranous glomerulonephritis?
- Steroids
- ACEi/ARB to control BP
Response to steroids = poor
What is the epidemiology, prognosis and general features of focal segmental glomerulosclerosis?
Epi:
- Common in adults
- Common in Afro-Caribbean people
Features:
- Primary or secondary
- Secondary causes: OBESITY, HIV, drugs (lithium, heroin), lymphoma
Px: 50% ESRF in 10yrs
What are the investigative findings of focal segmental glomerulosclerosis?
Light Microscopy:
- Focal + segmental glomerular consolidation + scarring
- Hyalinosis
Electron Microscopy:
- Loss of podocyte foot processes
Immunofluorescence:
- No immune deposits
What is the management and response to management of focal segmental glomerulosclerosis?
- Steroids + ACEi/ARB (to control BP)
- Calcineurinin inhibitors
50% response to steroids
What is seen on renal histology of diabetes?
- Diffuse glomerular basement membrane thickening
- Mesangial matrix nodules (KIMMELSTIEL WILSON NODULES)
What is seen on histology of amyloidosis?
Apple green birefringence with Congo red stain
What are some key points to nephrotic syndrome in diabetic patients?
- Classically found in Asians
- First presents with microalbuminaemia
What are some key features of amyloidosis?
AA (Acute Phase Protein) Amyloidosis:
- A/w: Chronic inflammation (e.g. RA, TB)
AL (Light Chain) Amyloidosis:
- Most common from multiple myeloma
Clinical Features:
- Maroglossia
- Heart Failure
- Hepatomegaly
How is a nephrotic syndrome diagnosed?
Urine Dip:
- Proteinuria
- NO haematuria
Urine PCR:
- >300mg/mmol
Serum Albumin:
- Low
Total cholesterol:
- High
Immunoglobulins:
- Low
What is the diagnostic investigation of choice in an adult with nephrotic syndrome?
Renal biopsy
What is nephritic syndrome?
A manifestation of glomerular inflammation
What is the triad for nephritic syndrome?
- Hypertension
- Haematuria
- Peripheral oedema
What are the characteristic features of nephritic syndrome?
PHAROH
- P: Proteinuria (less than nephrotic)
- H: Haematuria (coke-coloured urine)
- A: Azootemia (high urea + creatinine)
- R: Red Cell Casts (in urine)
- O: Oliguria
- H: Hypertension
What are general features of post-streptococcal glomerulonephritis and what is its cause?
- 1-3wks post-streptococcal throat infection/impetigo
- Usual cause = Strep. pyogenes (Group A strep)
Glomerular damage due to immune complex deposition
What clinical features are seen for post-streptococcal glomerulonephritis?
- Haematuria (red cell casts)
- Proteinuria
- Oedema
- HTN
What are the investigative findings for post-streptococcal glomerulonephritis?
Bloods:
- Increased ASOT Titre
- Decreased C3
Biopsy:
- Light microscope = Increased cellularity of glomeruli
- Fluorescence = Granular deposits of IgG + C3 in GBM
- Electron microscope = Subendothelial humps
What is the management for post-streptococcal glomerulonephritis?
- Supportive
What are the general features of IgA nephropathy, and what is it?
- Commonest GN worldwide
- More common in East/South asian populations
- Presents 1-2 days after URTI
- Presents with frank haematuria
- Can progress to ESRF
Deposition of IgA immune complexes in glomeruli
What are the clinical features of IgA nephropathy?
- Persistent/recurrent frank haematuria
- Asymptomatic microscopic haematuria
- Other Sx of nephritic syndrome not seen
- Can present with vasculitic rash
What are the investigative findings of IgA nephropathy?
Bloods:
- Increased IgA
Biopsy:
- Immunofluorescence = granular deposition of IgA + C3 in mesangium
What is the rule of thirds associated with IgA nephropathy?
- 1/3 = asymptomatic
- 1/3 = develop CKD
- 1/3 = develop progressive CKD requiring dialysis/transplantation
What is the most aggressive form of glomerulonephritis?
Rapidly progressive (crescenteric) GN
What are some general + clinical features of rapidly progressive glomerulonephritis?
- Can cause ESRF in weeks
- Regardless of cause, all types characterised by presence of crescents in glomeruli
- Classification based on immunological findings
Presentation:
- Nephritic syndrome
- Oliguria + renal failure more pronounced
What are crescents?
Proliferation of macrophages + parietal cells in Bowman’s space which pushes glomerulus to one side
What are the different types of rapidly progressive glomerulonephritis?
- Type1 = Anti-GBM antibody (Goodpastures Syndrome)
- Type 2 = Immune complex mediated
- Type 3 = Pauci-immune/ANCA-associated
What is the pathogenesis and some causes of type 1 rapidly progressive glomerulonephritis + which other organs are involved
Path:
- Anti-GBM antibody (against collagen Type IV)
Causes:
- Goodpasture’s syndrome
- HLA-DRB1 association
Organ involvement:
- Lungs = pulmonary haemorrhages
What is seen on microscopy of type 1 rapidly progressive glomerulonephritis?
Light:
- Crescents
Fluorescence:
- Linear deposition of IgG in GBM
What is the pathogenesis and some causes of type 2 rapidly progressive glomerulonephritis + which other organs are involved
Path:
- Immune complex mediated
Causes:
- SLE
- IgA nephropathy
- Post-infectious GN
- HSP
- Alport’s syndrome
Organ involvement:
- Often limited (except in SLE)
What is seen on microscopy of type 2 rapidly progressive glomerulonephritis?
Light:
- Crescents
Fluorescence:
- Granular (lumpy bumpy)
- IgG immune complex deposition on GBM/mesangium
What is the pathogenesis and some causes of type 3 rapidly progressive glomerulonephritis + which other organs are involved
Path:
- Pauci-immune (e.g. lack of anti-GBM/immune complex)
Causes:
- c-ANCA = Wegener’s granulomatosis
- p-ANCA = Microscopic polyangitis
Organ involvement:
- Vasculitis (skin rashes + pulmonary haemorrhages)
What is seen on microscopy of type 3 rapidly progressive glomerulonephritis?
Light:
- Crescents
Fluorescence:
- Lack of/scanty immune complex deposition
What are some features of hereditary nephritis (Alport’s Syndrome)?
- Hereditary glomerular disease caused by mutation in Type IV collagen α 5 chain
- X-LINKED
- Nephritic syndrome + bilateral sensorineural deafness + eye disorders (lens dislocation + cataracts)
- Presents at 5-20yrs with nephritic syndrome progressing to ESRF
What are some features of thin basement membrane disease (benign familial haematuria)?
- Rarely causes nephritic syndrome (usually asymptomatic haematuria)
- Diffuse thinning of GBM caused by mutation in Type IV collagen α 4 chain
- AUTOSOMAL DOMINANT
- Prevalence = ~5%
- Incidental Dx with microscopic haematuria
- Excellent prognosis
What are three differentials for asymtomatic haematuria?
- Thin Basement Membrane Disease (Benign Familial Haematuria)
- IgA Nephropathy (Berger Disease)
- Alport Syndrome
What are some clinical differences between IgA Nephropathy + Benign Familial Haematuria?
- IgA = more common in asian population
- IgA = frank haematuria
- IgA = Change in renal function Cr raised
What is acute tubular injury (acute tubular necrosis)?
- Damage to tubular epithelial cells leads to cells being shed + blocking tubules as casts
- Causes reduced flow + increased haemodynamic pressure in nephron
- Leasd to reduced pressure gradient across BM, causing acute renal failure
- Tubular glomerular feedback reduces blood supply to kidney further as a result of AKI
What is the most common cause of acute renal failure?
Acute tubular necrosis
What are the causes of acute tubular necrosis and how do they work?
Hypovolaemia
- Causes pre-renal ARF leading to ischaemia of nephrons
Nephrotoxins:
- Drugs (Aminoglycosides (gentamicin), NSAIDS)
- Radiographic contrast agents
- Myoglobin (secondary to rhabdomyolysis)
- Heavy metals
What is seen on histology for acute tubular necrosis?
Necrosis of short segments of tubules
What is seen on microscopy of urine for acute tubular necrosis?
Muddy brown casts
What is tubulointerstitial nephritis?
A group of renal inflammatory disorders that involve the tubules + interstitium
What are the different conditions that cause tubulointerstitial nephritis?
- Acute pyelonephritis
- Chronic pyelonephritis + reflux nephropathy
- Acute interstitial nephritis
- Chronic interstitial nephritis / Analgesic nephropathy
What is acute pyelonephritis, its causes, how it presents and what is seen on urineanalysis?
- Bacterial infection of the kidney, usually a result of an ascending infection
- Common cause = E. coli
Presentation:
- Fever
- Chills
- Sweats
- Flank pain
- Renal angle tenderness
- Leukocytosis
+/- Frequency, dysuria + haematuria
Urine:
- Leukocytic casts
What is chronic pyelonephritis + reflux nephropathy and its causes?
- Chronic inflammation + scarring of parenchyma caused by recurrent + persistent bacterial infection
Causes:
- Chronic obstruction (posterior urethral valves, renal calculi)
- Urine reflux (= reflux nephropathy)
What is acute interstitial nephritis, its causes how it presents and its histological findings?
- A hypersensitivity reaction
- Causes: usually drugs (Penicillins, NSAIDs, diuretics) (presents days after drug exposure)
Presents:
- Fever
- Skin rash
- Haematuria
- Proteinuria
- Eosinophilia
- Urine = white cell casts = sterile pyuria
Histo:
- Inflammatory infiltrate with tubular injury, eosinophils + granulomas
What are the features and symptoms of chronic interstitial nephritis/analgesic nephropathy?
- Seen in elderly with long-term analgesic consumption (NSAIDs + Paracetamol)
Sx (only in late disease):
- HTN
- Anaemia
- Proteinuria
- Haematuria
What are two types of thrombotic microangiopathies that affect the kidneys?
- HUS
- TTP
What is the epidemiology and characteristics of HUS?
- CHILDREN
Triad:
- MAHA
- Thrombocytopenia
- (progressive) renal failure
What is the epidemiology + characteristics of TTP?
- ADULTS
PENTAD:
- MAHA
- Thrombocytopenia
- Renal failure
- Fever
- Neurological Sx (LOC, decreased vision)
What is the pathophysiology of HUS?
- THROMBI CONFINED TO KIDNEYS
- A/w: E. coli O157:H7 = Gastroenteritis cause
- Endothelial damage
- Thrombosis, platelet consumption + fibrin strand deposition (leads to low plts)
- Destruction of RBCs (leads to schistocytes + low Hb)
What is the pathophysiology of TTP?
- Genetic/acquired deficiency of ADAMTS13
- THROMBI OCCUR THROUGHOUT CIRCULATION (esp. in CNS)
What is ADAMTS13 MoA?
- Usually cleaves vWF (protease)
- Deficiency leads to formation of giant vWF multimers
- Causes platelet aggregation + fibrin deposition
What are the signs and symptoms of a thromboti microangiopathy (HUS + TTP)?
- Low plts = bleeding (petechiae, haematemesis, melena)
- MAHA = pallor + jaundice
What does HUS usually involve?
Renal failure
How are thrombotic microangiopathies (HUS + TTP) diagnosed?
- Low Hb + plts
- Signs of haemolysis = increased bilirubin + reticulocytes + LDH
- Fragmented RBCs (SCHISTOCYTES) on blood smear (RBCs sheared as they pass through clots)
- Negative Coomb’s test
What is acute renal failure and what sign is observed as a result?
- Acute decline in renal function
- Low urine output
- Rapid loss of renal function
- Manifests as increased serum Cr + Urea
What are the complications of acute renal failure?
- Metabolic acidosis
- Hyperkalaemia
- Fluid overload
- HTN
- Low Ca
- Uraemia
What are the three different types of acute renal failure?
- Pre-renal
- Renal
- Post-renal
What is the most common cause of acute renal failure?
Pre-renal
What is pre-renal acute renal failure and its causes?
- Decrease in flow to kidneys
Causes:
- Renal Hypo-perfusion (hypovolaemia, sepsis, renal artery stenosis, ACEi, CCF, burns, acute pancreatitis)
What are renal causes of acute renal failure and how do they cause renal failure?
- Direct damage to nephrons
- Acute tubular necrosis
- Acute glomerulonephritis
- Thrombotic microangiopathy
What is the second most common cause of AKI?
Post-renal causes of acute renal failure
How do post-renal causes of acute renal failure work, and what are they?
- Physical blockade to outflow
- Obstruction of urine flow
Causes:
- Stones
- Tumours
- Prostate causes (hypertrophy)
- Retroperitoneal fibrosis
What is chronic renal failure and what is it due to?
- Progressive, irreversible loss of renal function
- Characterised by prolonged Sx of uraemia (fatigue, itching, anorexia, confusion)
- Due to progressive damage
What are the commonest causes of chronic renal failure in the UK?
- Diabetes (20%)
- Glomerulonephritis (15%)
- HTN + Vascular Disease (15%)
- Reflux nephropathy (chronic pyelonephritis) (10%)
- PCKD (9%)
- Obstruction
- ATN
How is chronic renal failure measured + staged?
By using GFR
What are the different stages of chronic renal failure and the GFR ranges for each stage?
- Kidney damage with normal renal function = >90
- Mildly impaired = 60-98
- Moderately impaired = 30-59
- A = 45-49
- B = 30-44 - Severely impaired = 15-29
- Renal failure = <15
What is adult polycystic kidney disease?
A part of a heterogenous group of disorders characterised by renal cysts + numeroud systemic extra-renal manifestations
What is the inheritance of polycystic kidney disease?
AUTOSOMAL DOMINANT
- 85% = PKD1 mutations (Chr 16 - encodes polycystin-1)
- 15% = PKD2 mutations (Chr 4 - encode polycystin-2)
What are the pathological features of polycystic kidney disease?
- Large multicystic kidneys with destroyed renal parenchyma, liver cysts (PKD1) + BERRY ANEURYSMS (leads to SAH + HTN)
What are the clinical features of polycystic kidney disease?
MISHAPES:
- M: abdmominal Mass
- I: Infected cysts + Increased BP
- S: Stones
- H: Haematuria
- A: Aneurysms (berry)
- P: Polyuria + nocturia
- E: Extra-renal cysts
- S: Systolic murmur (mitral valve prolapse)
How is PCKD diagnosed and what is the diagnostic criteria?
Via USS of kidneys
- 15-39yrs = 3+ cysts
- 40-59yrs = >2 cysts in each kidney
- >60yrs = 4 cysts in each ovary
What is the mainstay of Tx for PCKD?
RRT (renal replacement therapy)
What is lupus nephritis?
Kidney damage relating to lupus
What is seen on histology of lupus nephritis?
- Immune complex deposition in capillaries = WIRE LOOP CAPILLARIES
- Deposition of immune complexes + complement in GBM (LUMPY, BUMPY GRANULAR FASHION)
What are the six classes of lupus nephritis?
- Minimal meangial disease (near normal on light microscopy)
- Mesangial proliferative disease
- Focal subendothelial deposits
- Diffuse subendothelial deposits
- Subepithelial immune deposits (membranous disease)
- Advanced sclerosis (>90%)
What are the types of renal cell carcinoma?
- Clear cell carcinoma (well differentiated)
- Papillary carcinoma (Commonest in dialysis-associated cystic disease)
- Chromophobe renal carcinoma (pale, eosinophilic cells)
What are the RFs for developing a renal cell carcinoma?
- Smoking
- Obesity
- HTN
- Unopposed oestrogen
- Heavy metals
- CKD
What are the clinical features of a patient with a renal cell carcinoma?
- Costovertebral pain
- Palpable mass
- Haematuria
What is paraneoplastic syndrome?
- Polycythaemia
- Hypercalcaemia
- HTN
- Cushing’s syndrome
- amyloidosis
What is seen on a kidney biopdy of a patient with multiple myeloma?
Amyloid deposition
