Glomerulonephritis Flashcards
What is another term for glomerulonephritis?
Intrinsic kidney disease
What is glomerulonephritis?
A group of conditions that cause inflammation of or around the glomeruli in the kidney
What is the role of the glomeruli?
To remove excess fluid electrolytes and waste from the bloodstream and pass them into urine
What is the glomerulus?
A network of capillaries
How does blood enter the glomerulus?
Afferent arteriole
What happens as blood passes through the glomerulus?
Small molecules are filtered across the glomerular membrane into the Bowman’s space
What molecules are not filtered at the glomerulus? Give an example
Molecules which which are too large to filter across the membrane
Albumin
How does unfiltered molecules exit the glomerulus?
Efferent arteriole
What are mesanigial cells?
They are specialised pericytes within the kidney that make up the mesangium (middle) of the glomerulus
What is the primary function of mesangial cells?
To remove trapped residues and aggregated protein from the basement membrane thus keeping the filter free of debris
What is the role of the glomerular filtration barrier?
To ensure that large molecules, such as albumin, are unable to escape from the glomerulus into urine
What are the three layers of the glomerular filtration barrier?
Endothelium (Inner Layer)
Basal Lamina (Middle Layer)
Podocytes (Outer Layer)
Describe the endothelium that makes up the glomerular filtration barrier
It has perforations called fenestrae
What is the function of the endothelium layer of the glomerular filtration barrier?
To restrict the filtration of RBC’s
What is the function of the basal lamina layer of the glomerular filtration barrier?
To restrict the movement of negatively charged molecules across the basement membrane
Describe the podocyte layer of the glomerular filtration barrier
There are foot-like processes projecting from podocytes that interdigitate to form filtration slits
What is the pathophysiological cause of glomerulonephritis?
It occurs when there is damage to the glomerular filtration barrier, resulting in the leakage of RBC’s and albumin
What are the five clinical features of glomerulonephritis? Why?
Haematuria, which is the presence of blood within urine resulting in pink-coloured urine
Proteinuria, which is the presence of more than 1.5g (150mg) of protein within urine per day, resulting in foamy urine
Hypertension, which is high blood pressure
Oedema, which specifically affects the patient’s face, hands, feet and abdomen
Oliguria, which is the defined as a decreased urine output – specifically less than 0.5ml/kg/hour
What are the three types of haematuria?
Visible
Microscopic
Dipstick positive
Why is proteinuria a clinical feature of glomerulonephritis?
This is due to the fact that proteins can pass through the triple filtration barrier and into urine
Why is hypertension a clinical feature of glomerulonephritis?
This is due to the fact that salt and water are retained within blood
Why is oedema a clinical feature of glomerulonephritis?
This is due to the retention of fluid
Why is oliguria a clinical feature of glomerulonephritis?
This is due to the retention of fluid
What is nephritic syndrome?
A group of clinical features which reflect inflammation of the kidney
It doesn’t represent a specific syndrome or underlying cause
Are there set criteria a patient must met in order to have nephritic syndrome?
No, instead the patient just presents with the clinical features of glomeruloneprhtiis
What is a prominent clinical feature of nephritic syndrome?
Proteinuria
What is the pathophysiological cause of nephritic syndrome?
It is caused by the invasion of inflammatory cells into the glomerulus
These inflammatory cells then attack the triple filtration barrier, resulting in the leakage of RBCs and some albumin.
What is a prominent clinical feature of nephrotic syndrome? What is not a prominent clinical feature of nephrotic syndrome?
Haematuria
Proteinuria
What are the four criteria of nephrotic syndrome?
Peripheral Oedema
Proteinuria, which is defined as >3.5g per 24hrs
Hypoalbuminemia, which is defined as serum albumin <35g/L
Hypercholesterolaemia, which is defined blood cholesterol > 200mg/dl
What is the pathophysiological cause of nephrotic syndrome?
It is caused by podocytes and their foot processes separating, thus resulting in leakage of albumin and some RBCs
What are the two main classifications of glomerulonephritis?
Proliferative Glomerulonephritis
Non-Proliferative Glomerulonephritis
What is proliferative glomerulonephritis?
It is characterised by increased cellularity of the glomerulus
This is due to the invasion of inflammatory cells
What are the four subclassifications of proliferative glomerulonephritis?
IgA nephropathy
Membranoproliferative Glomerulonephritis
Diffuse Proliferative Glomerulonephritis
Crescentic Glomerulonephritis
Is proliferative glomerulonephritis nephrotic or nephritic?
Nephritic
What is the most common glomeurlonephritis classification?
IgA nephropathy
What are another two terms for IgA nephropathy?
Mesangioproliferative glomerulonephritis
Berger’s disease
What is IgA nephropathy?
It is characterised by a mesangial deposition of IgA immune complexes
In which patient group does IgA nephropathy tend to present in?
Male patients
Between the ages of 20 – 30 years old
What are the three risk factors of IgA nephropathy?
Alcoholic cirrhosis
Coeliac disease
Hence Schonlein purpura
How does mesangioproliferative gloumerulonephritis tend to present?
Macroscopic haematuria
Following an upper respiratory tract infection
How are the two features of IgA nephropathy on histological examination?
Mesangial hypercellularity
Positive immunofluorescence for IgA & C3
What is the conservative management of IgA nephropathy?
No treatment
Follow up to check renal function
When do we recommend conservative management of IgA nephropahty?
In cases of isolated haematuria, with no proteinuria and a normal GFR
What are the two pharmacological management options of IgA nephropathy?
ACE inhibitors
Corticosteroids
When are ACE inhibitors used to manage IgA nephropathy?
In cases of persistent proteinuria > 500 - 1000mg/day, with a normal or only slightly reduced GFR
When are corticosteroids used to manage IgA nephropathy?
In cases where there is failure to respond to ACE inhibitors or GFR levels are reduced
What are the three differences between IgA nephropathy and post-streptococcal glomerulonephritis?
IgA nephropathy = high complement levels, haematuria, onset of features following infection is 1-2 days
Post-streptococcal glomerulonephritis = low complement levels, proteinuria, onset of features following infection is 1-2 weeks
How do we diagnose mesangioproliferative glomerulonephritis?
The IgA deposits are not filtered into the urine
An elevated level of IgA is only identified within blood
What is membranoproliferative glomerulonephritis ?
It is characterised by an increased number of cells within the glomerular basement layer of the glomeruli
What is another term for diffuse proliferative glomerulonephritis?
Post infectious glomerulonephritis
What is diffuse proliferative glomerulonephritis?
A severe form in which proliferative changes occur in more than 50% of the glomeruli
In which patient group does diffuse proliferative glomerulonephritis tend to present in?
Younger patients
One to three weeks after an infection of the throat or skin, such as tonsilitis or impetigo
What organism tends to cause diffuse proliferative glomerulonephritis?
Lancefield group A streptococci
Why do infections cause diffuse proliferative glomerulonephritis?
In order to fight the infection, the body produces extra antibodies that can eventually settle in the glomeruli, causing inflammation and thus glomerulonephritis
What is crescentic glomerulonephritis?
It is characterised by the formation of glomerular crescents within the glomeruli
This crescent is formed as a result of cellular proliferation and macrophage influx within the Bowman’s space
What are the two subclassifications of crescentic glomerulonephritis?
ANCA-Associated Glomerulonephritis
Anti-GBM Nephritis
What is ANCA associated glomerulonephritis?
It is a condition in which ANCA vasculitis of the lungs starts to affect the kidneys
How do ANCA antibodies cause ANCA associated glomerulonephritis?
ANCA antibodies are directed against two neutrophilic enzymes – proteinase 3 and myeloperoxidase.
Therefore, when inflammation occurs and neutrophils infiltrate the glomerulus, a high production of ANCA antibodies occurs which then causes tissue damage within the kidney.
What is another name for anti-GMB nephritis?
Goodpasture’s syndrome
What is anti-GMB nephritis?
It is a condition in which anti-GMB antibodies attack the basement membranes of the glomerulus and lung
What are the four clinical features of anti-GMB nephritis?
Acute kidney failure
Proteinuria
Haematuria
Haemoptysis
What is non-proliferative glomerulonephritis?
It is characterised by the appearance of a normal glomerulus
What are the four subclassifications of non-proliferative glomerulonephritis?
Minimal Change Disease
Membranous Glomerulonephritis
Focal Segmental Glomerulosclerosis
Diabetic Nephropathy
Is non-proliferative glomerulonephritis nephrotic or nephritic?
Nephrotic
What is minimal change disease?
It is characterised by the presence of minimal damage under a light microscopy
This damage can only be visualised using an electron microscopy – specifically demonstrating shrunken podocytes and effaced foot processes.
In which patient group does minimal change disease tend to affect?
Children
What is a clinical feature of minimal change disease?
Oedema
What is membranous glomerulonephritis?
It is characterised by IgG deposition within between the basal lamina and podocytes within the glomerular basement membrane
This results in a thickened basement membrane, in which new spikes of basal lamina form underneath the podocytes
IgG results in the activation of complement 3 (C3), which attacks the basal lamina thus creating gaps within the basement membrane that albumin can leak through
What is the most common classification of glomerulonephritis?
Membranous glomerulonephritis
What are the causes of membranous glomerulonephritis? Which is most common?
Idiopathic - most common
Malignant
Rheumatoid disorders
Drugs (NSAIDs)
How do we diagnose membranous glomerulonephritis?
We can conduct an immunology screen to look for the presence of anti-phospholipid A2 receptors (PLA2R)
The IgG deposits are not filtered into the urine. An elevated level of IgG is only identified within blood
What is focal segmental glomerulosclerosis?
It is characterised by scarring of less than 50% of glomerulus tissue
What subclassification has a high progression risk into end stage kidney disease?
Focal segmental glomerulosclerosis
What is diabetic nephropathy?
It is characterised by the deposition of glycated molecules in the basal lamina and mesangial matrix
This results in a thickened, leaky glomerular membrane that allows the leakage of albumin and compression of the capillaries supported by the mesangial matrix
What are the deposits in diabetic nephropathy called?
Kimmelsteil-Wilson lesions
How do we screen diabetic patients for diabetic nephropathy?
Albumin: creatinine ratio
U&Es
What are the four investigations used to diagnose glomerulonephritis?
Urine sample
Blood tests
Kidney biopsy
Immunology screen
What five urine sample results indicate glomerulonephritis?
Haemoglobin, which is elevated
WBCs, which is elevated
Proteinuria, which is an elevated albumin level > 30mg/g
Creatinine, which is elevated > 15900umol over 24hrs
Urea, which is elevated > 20g over 24hrs
What seven blood test results indicate glomerulonephritis?
Haemoglobin, which is reduced < 130g/L
Serum Creatinine, which is elevated >120 umol/L (80, 160
Serum Urea, which is elevated > 7mmol/L
Serum Albumin, which is reduced < 35g/L
Cholesterol, which is elevated > 5.5mmol/L
eGFR, which is elevated > 120mL/min/1.73m2
Compliment Component C3, which is reduced
What is a kidney biopsy?
A kidney biopsy involves using a special needle to extract small pieces of kidney tissue for light and electron microscopic examination
How are kidney biopsies used to diagnose glomerulonephritis?
It enables classification of glomerulonephritis
How is an immunology screen used to diagnose glomerulonephritis?
It identifies the presence of associated antibodies, such as ANCA antibodies and anti-GMB antibodies.
How do we conservatively treat glomerulonephritis?
It involves encouraging a low salt diet, as this will improve the patient’s oedema
What are the four pharmacological treatments of glomerulonephritis?
Hypertensive Agents
Statins
Steroids
Loop Diuretics
What two hypertensive agents are used to treat glomerulonephritis?
ACEI
ARBs
What two statins are used to treat glomerulonephritis?
Warfarin
Heparin
What three steroids are used to treat glomerulonephritis?
Prednisolone
Cyclophosphamide
Azathioprine
What are the three complications of glomerulonephritis?
Acute Kidney Failure
Chronic Kidney Disease
Hypertension
How does glomerulonephritis result in acute kidney failure?
This is due to the glomerular damage can result in the rapid accumulation of waste products
How does glomerulonephritis result in hypertension?
This is due to the fact that damage to the kidneys results in a build-up of waste products in the bloodstream, which can raise blood pressure
