Basic Anatomy and Physiology of the Renal Corpuscle
The renal corpuscle includes the glomerulus, surrounding cells and the bowman’s capsule. The glomerulus is a tuft of capillaries enclosed in the Bowman’s capsule. The Bowman’s capsule is one end of the nephron. The blood reaches the capillaries via the afferent arteriole and leaves the glomerulus via the efferent arteriole which is smaller in diameter. The glomerulus is the first place where filtration occurs. Surrounding cells include mesangial cells, podocytes and juxtaglomerlar apparatus. Mesangial cells secrete the extracellular matrix and regulate glomerular filtration. The podocytes are involved in glomerular filtration. The juxtaglomerular apparatus is involved in the renin-angiotension-aldosterone system which regulates the flow of blood through glomerulus.
The two images below illustrate the different parts of the renal corpuscule.
Figure 1 – A diagram to illustrate the different parts of the renal corpuscle. This Image was made by Michał Komorniczak and can be accessed from: http://en.wikipedia.org/wiki/File:Renal_corpuscle.svg.
Figure 2 – A diagram to illustrate the filtration barrier. This Image was made by Michał Komorniczak and can be accessed from: http://en.wikipedia.org/wiki/File:Filtration_barrier.svg
Glomerulonephritis is a term that refers to a group of conditions in which the glomerulus is damaged. It is one of the main causes of end stage renal failure and there are 2 broad groups of glomerulonephritis; primary and secondary. Primary glomerulonephritis is when the condition is limited to the kidney whereas secondary glomerulonephritis is when the glomerular disease is secondary to systemic disease.
Athough glomerulonephritis refers to damage of the glomerulus, there are specific terms used to describe how much of each glomuerlus is involved and also how many.
- Focal disease – only some of the glomeruli are damaged.
- Diffuse disease – all of the glomeruli are damaged
- Segmental disease- only part of the glomerulus itself is damaged.
- Global disease - the disease affects the entire glomerulus.
Glomerulonephritis can present in a number of ways, in particular, nephrotic syndrome, nephritic syndrome, chronic renal failure and hypertension. The investigations carried out for suspected glomerulonephritis are quite similar regardless of the type –
- Check BP
- Protein/creatinine ratio
- FBC, U+Es, LFTs, Lipid Profile,
- Some special tests may also be required to confirm the diagnosis
- Autoantibodies and hepatitis screen
- Renal Biopsy
This article will go through the abnormalities you may see in the investigations for the specific types of glomerulonephritis. Any specific tests that are necessary for that condition are also discussed.
In general, the treatment of glomerulonephritis usually involves steroids, however, other immunosuppressive drugs such as cyclophosphomide may be needed if patients are unreponsive. Other medications are given according to other symptoms or signs the patient may have. These include ACE inhibitors (to lower blood pressure), diuretics (if patient has oedema), and statins (if the patient has high cholesterol).
Nephrotic or Nephritic Syndrome?
Glomerulonephritis usually presents as either nephrotic syndrome or nephritic sydrome. The two diagrams below explain these terms and please refer to the individual articles on these syndromes for more detail.
The flowchart below divides glomerulonephritis according to their clinical presetantion of either nephrotic syndrome or nephritic syndrome.
Overview of the Different Diseases affecting the Glomerulus
The table below summarises and compares the important points regarding the different types of Glomerulonephritis (GN).
Minimal Change Nephropathy
Minimal Change Nephropathy is the most common cause of nephrotic syndrome in children. The peak age of presentation is between 2 and 8 years. It has been associated with atopy, leukaemia and Hodgkins lymphoma. There is usually a history of recent viral infection. Light microscopy is normal and immunofluorescence is usually negative which is why it is called minimal change. However, on electron microscopy there is widespread fusion of the epithelial podocyte foot processes.
Minimal change nephropathy does not usually lead to chronic renal failure as it is usually responds to steroids and therefore prognosis is good :- 1/3 of the patients will have just one episode, 1/3 of patients have occasional relapses and 1/3 have frequent relapses.
Focal Segmental Glomerulosclerosis (FSGS)
FSGS accounts for 15% of nephrotic syndrome in adults and can be classified into primary and secondary. Primary FSGS is idiopathic and secondary is due to an acquired underlying condition e.g. SLE. Some of the risk factors include obesity, HIV infection, afro-carribean race, positive family history and lithium treatment.
In FSGS, damage to the podocytes occurs which leads to scarring (sclerosis) of part of the glomerulus which can be seen on light microscopy shows focal and segmental glomerular sclerosis. Immunofluorescence shows IgM and C3 in a segmental distribution. Electron Microscopy shows fusion of the epithelial podocyte foot processes.
Prognosis can be poor in patients non responsive to steroids and 40-60% of patients develop end stage renal disease within 10 years of diagnosis.
Membranous Nephropathy can be classified into primary and secondary. In 90% of cases it primary (idiopathic) but can be secondary to SLE, hepatitis and malignancy. It is the most common cause of nephrotic syndrome in adults and it is more common in men.
Light Microscopy shows diffuse thickening of the glomerular basement membrane. Immunofluorescence shows diffuse deposition of IgM and C3.
There is no specific treatment for membranous nephropathy and it progresses to end stage renal failure in around 30-50% of patients.
The cause of IgA nephropathy is unknown but it has been associated with abnormal glycosylation of IgA leading to deposition of IgA. It is more common in men. IgA nephropathy can present in many different ways including nephritic syndrome and chronic renal failure.
Light microscopy shows mesangial cell proliferation and matrix expansion. Immunofluorescence shows IgA and C3 deposition. 15% of patients develop end stage renal failure within 10 years of diagnosis.
Patients with Henoch Schonlein Purpura (HSP) with renal involvement will have a histological picture identical to IgA nephropathy. It affects mainly those under 10 years old and typically presents with a vasculitic purpuric rash over the ankles, buttocks and elbows with abdominal pain in addition to renal disease.
Mesangiocapillary (membranoproliferative) Glomerulonephritis (MCGN)
There are 2 main types of MCGN which are clinically very similar. MCGN can present in different ways including nephrotic syndrome, nephritic syndrome, renal failure and hypertension. MCGN can be caused due to SLE and hepatitis.
Light microscopy shows mesangial expansion, mesangial cell proliferation and also thickening of the glomerular basement membrane. Immunofluorescence shows IgG and C3.
Prognosis is poor as there is no specific treatment. 50% of patients develop end stage renal failure within 10 years of diagnosis and 90% develop end stage renal failure within 20 years.
Diffuse Proliferative Glomerulonephritis (Post infection)
This form of glomerulonephritis is classically caused by a streptococcal infection but can be idiopathic. It is more common in men and the peak incidence is between 2-12 years. Presentation is acute and typically within 2 weeks of strep infection. It most commonly presents as nephritic syndrome.
Light microscopy shows mesangial and endothelial cell proliferation and infiltration of glomerulus with neutrophils and monocytes. Immunofluorescence shows C3 and immunoglobulins. Electron microscopy shows subepithelial deposits.
Treatment includes antibiotics to eradicate any remaining pathogen.
Anti-Glomerular Basement Membrane (GBM) Disease (Goodpasture’s Syndrome)
This is a rare condition and is more common in men, associated with the HLA-DR15 tissue type. Autoantibodies to the basement membrane in glomeruli and alveoli cause inflammation. Anti – GBM disease is called Goodpasture’s syndrome when there is both alveolar and GBM damage. Patients usually present with haemoptysis, cough or breathlessness. Renal symptoms include loin pain and oliguria.
Light microscopy shows focal segmental proliferative glomerulonephritis with crescents. Immunofluorescence shows deposits of antibody along the glomerular basement membrane.
If untreated patients die of pulmonary haemorrhage or renal failure but if treated early most recover and do not relapse.
Treatment includes plasma exchange to remove antibodies and high dose steroids (or cyclophosphamide) to maintain remission and prevent further production of antibodies.
- Barrett K.E, Barman S.M, Boitano S and Brooks H.L. Ganong’s Review of Medical Physiology. 23rd Edition (2010).
- Longmore M, Wilkinson I, Davidson E, Foulkes A and Mafi A. Oxford handbook of clinical medicine. 8th Edition (2010).
- Firth J, Maxwell P. Medical Masterclass – Nephrology 2nd edition (2008)
- Colledge N.R, Walker B.R and Ralston S.H. Davidson’s Principles and Practice of Medicine. 21st Edition (2010)
- PIP and EMIS. Patient.co.uk. Available from:www.patient.co.uk
- Oxbridge Solutions Ltd. General Practice Notebook. Available from: www.gpnotebook.co.uk
- Bmj. BMJ Best Practice. Available from: http://bestpractice.bmj.com.