Histo: Renal Pathology Flashcards
Outline which kidney pathology affects the glomerulus, tubulues / interstitium and blood vessels
Glomerulus
Nephrotic syndromes
Nephritic syndromes
Tubules and Interstitium
Acute tubular necrosis
Tubulointerstitial nephritis
Blood vessels
Thrombotic microangiopathies (HUS, TTP)
Define nephrotic syndrome
Several renal diseases which cause increased glomerular permeability.
Characterised by triad:
1. proteinuria (>3g/24hrs / “frothy urine”)
2. Hypoalbuminaemia
3. Oedema (peri-ocular in children)
Primary causes of nephrotic syndrome
- Minimal change disease
- Membranous Glomerular Disease
- Focal Segmental Glomerulosclerosis
Secondary causes of nephrotic syndrome
Diabetes
Amyloidosis
Differentiate between the epidemiology of the primary causes of nephrotic syndrome
* Minimal change disease
* Membranous Glomerular Disease
* Focal Segmental Glomerulosclerosis
Differentiate between the aetiological processes behind the primary causes of nephrotic syndrome
* Minimal change disease
* Membranous Glomerular Disease
* Focal Segmental Glomerulosclerosis
Minimal change disease
Idiopathic - possible trigger being recent allergic reaction as associated with eczema and asthma
Membranous Glomerular Disease
Primary = antibodies against phospholipase A2 present in 75% of cases. commonest
Secondary = SLE, infection, drugs, malignancy
FSGs
Primary = idiopathic
Secondary = obesity, HIV, drugs (lithium, heroin), lymphoma
Differentiate between the changes seen on light microscopy between the primary causes of nephrotic syndrome
* Minimal change disease
* Membranous Glomerular Disease
* Focal Segmental Glomerulosclerosis
Differentiate between the changes seen on electron microscopy between the primary causes of nephrotic syndrome
* Minimal change disease
* Membranous Glomerular Disease
* Focal Segmental Glomerulosclerosis
ALL show loss of podocyte foot processes
membranous glomerular disease shows subepithelial deposits described as “spikey”
Differentiate between the changes seen on immunofluroescence between the primary causes of nephrotic syndrome
* Minimal change disease
* Membranous Glomerular Disease
* Focal Segmental Glomerulosclerosis
Outline the response to steroids between between the primary causes of nephrotic syndrome
* Minimal change disease
* Membranous Glomerular Disease
* Focal Segmental Glomerulosclerosis
- Minimal change disease = good
- Membranous Glomerular Disease = poor
- Focal Segmental Glomerulosclerosis = 50% respond
Outline the management of the primary causes of nephrotic syndrome
* Minimal change disease
* Membranous Glomerular Disease
* Focal Segmental Glomerulosclerosis
- Minimal change disease = 1) steroids 2) cyclosporin
- Membranous Glomerular Disease = steroids and ACEi/ARB to control HTN
- Focal Segmental Glomerulosclerosis= steroids and ACEi/ARB to control HTN
Differentiate between the histological findings of the secondary causes of nephrotic syndrome
* Diabetes
* Amyloidosis
What are the 2 common types of Amyloidosis which can lead to nephrotic syndrome
AA Amyloidosis = acut ephase protein amyloidosis, associated with chronic inflammation
AL Amyloidosis = light chain amyloidosis commonly secondary to multiple myeloma
Outline what the trends in the following investigation would be like in nephrotic syndrome
* Urine dip
* Urine PCR
* Serum albumin
* Total cholesterol
* Immunoglobulins
note: renal biopsy is investigation of choice in adults but avoided in children
Urine dip = proteinuria but NO haematuria
Urine PCR = >300mg/mmol
Serum albumin = low
Total cholersterol = high
Immunoglobulins = low
Define nephritic syndrome
What is it characterised by
Disorders involving glomerular inflammation
Characterised by: PHAROH
Proteinuria (less than nephrotic)
Haematuria
Azootemia (high urea and creatinine)
Red cell casts in urine
Oliguria
Hypertension
Outline the main causes of nephritic syndrome
- Post streptococal glomerulonephritis
- IgA nephropathy (Berger’s Disease)
- Rapidly progressive glomerulonephritis
- Hereditary nephritis
- Thin basement membrane disease (benign familial haematuria)
Key features of post streptococcal nephritis
(sx onset, pathophysiology, sx, bloods, biopsy findings, management)
- Occurring 1-3 weeks after strep throat infection or impetigo
- immune complex deposition = damage
- Main symptoms = haematurai, proteinuria, oedema, HTN
- Bloods = ASOT titre elevated, low C3
- Biopsy = increased cellularity of glomeruli (light micro), granular IgG deposits and C3 in GM (immunofluro), subendothelial humps (electric micro)
- Management = supportive
Key features of IgA nephropathy
(epidemiology, pathophysio, symptoms and onset, bloods, biopsy)
- Commonest cause of GN worldwide
- IgA immune complexes in glomeruli
- Presents 1-2 days after URTI with painless frank haematuria (earlier than post-strep!!) - sometimes with vasculitic rash
- Raised IgA in bloods
- Biopsy = granular deposition of igA and C3 in mesangium
How is Rapid progressive (Crescentic) glomerulonephritis different from other causes of nephritic syndrome
Most agressive form of glomerulonephritis - can cause end stage renal failure in weeks
Oliguria and renal failure more common alongisde other features of nephritic syndrome
Crescents in glomeruli on light microscopy (crescents = proliferation of macrophages, parietal cells in bowman’s space)
Differentiate between the 3 different types of Rapidly progressive glomerulonephritis
(pathogenesis, causes, light microscopy, fluroescence microscopy, additional organ involvement)
Key features of hereditary nephritis (Alport’s Syndrome)
- X-linked hereditary glomerular disease caused by mutation in type4 collagen alpha 5 chain
- Nephritic syndrome + sensorineural deafness + eye disorders
- 5-20yrs old
Key features of Thin Basement Membrane Disease (Benign Familial Haematuria)
- Very rarely a cause of nephritic syndrome - normally results in asymptomatic haematuria alone
- Autosomal dominant mutation causing diffuse thinning of GBM due to mutation to type4 collagen
3 main differentials in asymptomatic haematuria
Thin basemenet membrane disease IgA nephropathy
Alprot syndrome
Pathophysiological mechanism of acute tubular injury
Damage to tubular epithelial cells is commonly due to ischaemia
Causes of Acute Tubular Injury
Ischaemia of Nephrons (arising from pre-renal AKI causes)
Nephrotoxins (e..g drugs such as aminoglycosides or NSAIDs, myoglobin, heavy metals, contrast agents)
Histopathological findings consistent with acute tubular injury
necrosis of short segments of tubules showing loss of brush border and loss of tubular cells (necrosis of tubular cells)
Key features of acute interstitial nephritis
(definition, symptoms, histology)
- Hypersensitvity reaction usually to drugs - hence symptoms starting days after drug exposure
- Symptoms = fever, skin rash, haematuria, proteinuria, eosinophilia
- Histology = inflammatory infiltrarte with tubular injury and presence of granulomas and eosinophils
Differentiate between the two types of thrombotic microangiopathies
(HUS, TTP)
Inheritence pattern of Adult Polycystic Kidney Disease and named mutation & chromosome
autosomal dominant - mutation in PKD1 chromosome 16
What is the pathognomic feature of Adult Polycystic Kidney disease
Large multicystic kidneys with destroyed renal parenchyma
Clinical features of adult polycystic kidney disease
note berry aneurysms are common vascular complication to be aware
types of renal cell carcinoma
Waxy Casts in urine suggests what?
Chronic Kidney Disease
Fatty casts in urine suggest what?
Nephrotic syndrome
What protein is deficient in Polycystic Kidney disease
Polycystin 1
