Glomerular disease Flashcards
What are the 3 different cell types of the glomerulus?
Lining - endothelial cells
Outside contains podocytes
Mesangial cells
What is the role of the endothelial cells?
Specialised
Gaps allow water and molecules to passs through
Sit on the basement membrane
What is the role of the podocytes?
Form filtration barrier
Prevent large molecules from entering the filtrate
What is the role of the mesangial cells?
Hold down the capillary loop
Prevent the capillary loop from moving
What is glomerulonephritis?
Inflammation to the glomerulus
Leads to rapid deterioration of renal function
What are the symptoms of glomerulonephritis?
Different symptoms which depend on the part of the glomerulus affected and the effectors involved
What are the two types of glomerulonephritis?
Nephrotic syndrome
Nephritic syndrome
Which diseases cause glomerulonephritis?
Different infections
Can be caused by
Systemic infections - SLE
Kidney-specific infections - IgA disease
What is nephrotic syndrome?
Epithelial patterns of injury to the glomerulus
Large concentration of proteins leak out
What are the symptoms of nephrotic syndrome?
Oedema
Hypoalbuminunemia
Proteinuria - 3.5 g/day
What is nephritic syndrome?
Endothelial pattern of injury to the glomerulus
Global damage to the glomerulus
What are the symptoms of nephritic syndrome?
Blood and protein leakage to the urine
Salt and water retention - reduction to the urine formed
Hypertension and high blood pressure
What is another name for low volume of urine formed?
Oliguria
How does a urine dipstick test for glomerular disease?
It’s an early pointer to renal inflammation
Can be used to tell how functional the glomerular filtration barrier is
Normal - little protein and RBC escapes the tight filtration barrier
Abnormal - high concentration of albumin and low mass proteins
What is another way to test for glumorular disease?
Microscope urine to see if blood cells have been released into it
What is the most common cause of glomerulonephritis?
Post-infectious glomerulonephritis
Immune complexes deposit in the kidneys
Antigens and antibodies accumulate in the glomerulus and
Complement activation
Which features of the immune complexes affect the disease features?
Location
Size
Charge
What type of GN happens if antibodies get stuck in the podocytes?
Neprhotic syndrome
Proteins leak out
What type of GN happens if antibodies get stuck under endothelial cells?
Nephritic syndrome
Stimulates WBC in capillary loop - activates WBC and causes damage by release of their contents
How do autoantibodies cause GN?
Autoantibodies are dysfunctional and make antibodies towards self proteins
Antigen-antibody complex is presented to WBC
This triggers complement cascade
Immune complexes travel around the circulation and get stuck in compartments
Kidney is susceptible to blockages as it filters a large amount of blood
Deposition of immune complexes leads to glomerular disease
Where may antigens come from?
Foreign antigens - infection
Endogenous antigens - autoimmunity
Formed in-situ - anti-glomerular basement
Formed in circulation - SLE
What mechanism prevents autoimmunity?
Tolerance
Prevents T cells from reacting to self antigens
How does the body normally get rid of dead or dying cells?
Under normal circumstances the body gets rid of dead and dying cells via apoptosis
Phagocytes ingest and clear them, recycling their contents
What process leads to autoimmunity?
Defects in handling apoptosis in dead or dying cells leads to presentation of self-antigens to the immune system
Apoptotic cells undergo necrosis and contents of the cells are presented to the IS
If chromatin and DNA are in sufficient quantity, an immune response is triggered
What type of GN does mesangial injury induce?
Nephritic syndrome
What type of GN does endothelial injury induce?
Nephritic syndrome
What type of GN does epithelial injury induce?
Nephrotic syndrome
Pathogenesis of lupus
Intracellular contents released when apoptosis goes wrong
DNA, nucleoproteins and cytoplasmic ribonuclear proteins are released
These are expressed on the CSM during apoptosis - antigens form against these
How many antibodies must accumulate for lupus to develop?
2 or 3
What type of GN is present in lupus?
Mesangial injury
Endothelial injury
Epithelial injury
Both nephrotic and nephritic syndrome is present
How does lupus lead to GN?
Deposition of antibodies underneath the podocytes and blood vessel wall
Both nephrotic and nephritic syndrome
Treatments for GN in lupus patients
Remove the antibodies
Remove the infection
Suppress antibodies from being made
What is Goodpasture’s disease?
Autoimmune disease
Caused by circulating anti glomerular basement membrane antibodies
What conditions develop in Goodpasture’s disease?
Acute GN
Pulmonary alveolar haemorrhage
What are the treatments of Goodpasture’s disease?
Glucocorticoids
Cyclophosphamide - suppresses leukocytes
Plasma exchange - remove abnormal antibodies from the circulation
Which side effects arise from the treamtents of Goodpasture’s disease?
Infections
Malignancies - cataracts and melanoma
Metabolic complications
Drug toxicities - bone disease (glucocorticoids), bladder tumour (cyclophosphamide) and avascular necrosis
What are the side effects of glucocorticoids?
Bone disease
What are the side effects of cyclophosphamide?
Bladder tumour
