lecture 11 - autoimmune kidney diseases Flashcards
how much of cardiac output does the kidney receive?
25%
what is the filtration fraction (plasma that filters into the nephron)?
20%
what can’t get through the filtration barrier?
red blood cells and serum albumin
what does it mean if you see red blood cells in the urine?
something wrong with the normal physiology of the filtration barrier
what is chronic kidney disease?
structural or functional abnormalities of the kidney with or without decreased GFR
what are the markers for kidney disease?
abnormalities in the composition of blood or urine
how long do you need to have kidney disease before it can be chronic?
more than or equal to 3 months
what can be used to tests for kidney disease?
a dipstick urinalysis
how many stages of chronic kidney disease are there?
5
what is the eGFR like in stage 5 of kidney disease?
less than 15
what are some examples of autoimmune kidney diseases?
Membranoproliferative Glomerulus (MPGN), Atypical haemolytic uraemic syndrome (aHUS), SLE - lupus nephritis, IgA nephropathy and Goodpastures syndrome
what is the most common autoimmune kidney disease?
IgA nephropathy
what is the MPGN pathophysiology?
get proliferations which eat up the space in the glomerulus which means can’t get the function
how can proliferations eat up the space in the glomerulus?
immune activators, chemokines and cytokines
what would you see in MPGN?
dense deposits disease - electron dense glomerulus
how do you diagnose MPGN?
by doing a kidney biopsy
what would you see from the biopsy of MPGN?
hypercellularity, thickening of the glomerular basement membrane and proliferation
what are classical pathways activated by?
they are activated by antibodies
What is the lectin pathway involved in?
It is involved with dealing with apoptotic and damaged cells
What does the activation of lectin and classical pathway lead to?
The C3 activation which passes the alternative pathway which acts on the right side of the complement pathway and acts on the amplification route
What regulators are important in stoping the activation complement?
Factor H and DAF
What is the membrane attack complex important for?
It is important in MPGN
What type of anaphylatoxins can activate the complement system?
C5a and C3a
What do C3a and C5a interact with?
Molecules that lead to vasodilation and vasoconstriction - modulating the blood flow into the kidney
Where are C3 and C4 made?
They are made mostly in the liver - the kidney generates about 20% of the total levels of the complement in the blood
What is one of the most abundant proteins?
C3 - has the potential to cause damage
What works together to inactivate C3?
Factor H and factor I
What does CR1 do?
It is a really important natural regulator the regulates the complement, lectin and the alternative pathways on the cell surface, endothelial cells and the podocytes
What protect against C3?
MCP and DAF they are ubiquitous
What prevents MAC?
CD59
What does the C4 binding protein do?
Stops the lectin and the classical pathway
What are complement regulators involved in?
In the removal of immune complexes, the liver is a major source of clearance
What organ do you want to get rid of immune complexes?
The kidney
What allows the removal of immune complexes?
CR1 - complement receptor 1, it is expressed at high levels of erythrocytes and allows immune complexes to bind and be carried to the liver
What is another type of cell that is important in complement and waste disposal?
Apoptotic cells - they self compact and maintain of all of the DNA and important mitochondrial antigens
What are anaphyltoxins important for?
Bone regeneration
What system is importantly for self tissue renwal?
The complement system
What can C3a signalling help?
Can help dampen down the response
What is C3 glomerulopathy (C3G)?
It is a new name for the spectrum of disorders with glomerular pathology associated with C3 desposition
What is the dominant thing you see in C3 glomerulopathy?
The dysregulation of the alternative pathway in the kidney and deposition of C3 on the glomerular endothelial cells and the mesangial
Where was Factor H deficiency discovered?
In pigs - led to the finding that 1 or 2 people had this. The loss of Factor H leads to dense deposit disease of C3G
What does C3 nephritic factor (C3NeF) do?
It stabilises the C3 convertase and stops it from being broken down by the regulators like Factor H and I - will lead to CB3 action
What has recently been identified?
Anti-Fb - don’t know where they come from
What do anti factor H do?
Interact with regulators and stops the alternative pathway from being over active
What is the haemolytic uraemic syndrome (HUS) triad known as? - biomarkers for HUS
Acute renal failure, thrombocytopenia, microangiopathic hemolytic anemia
What are the triad of HUS caused by?
Shiga toxin producing E.Coli e.g. food poisoning - it is an acute disease
Who does HUS affect?
Infants and young children it has a relatively good prognosis
What does shiga toxin bind to?
GABA3 in the glomerular endothelial cells and activate the cells.
What happens when GABA3 cells in endothelial cells are activated?
They turn inflamed and allow thrombosis. The coagulation system interacts with the complement where clots form - takes out the kidney very quickly
Where does secondary HUS come from?
Clinical or autoimmune disorders even cancer - which can lead to TMA in the kidney
What is Atypical HUS?
It’s a genetic form and leads to TMA
What makes the process go from non thrombotic to thrombotic?
P-Selectin - resulting in TMA
What gene is frequently mutated in aHUS?
CFH - 40% familiar mutations, 25% sporadic
What is taken away to get aHUS?
Factor H, you end up with lysis and deposits of MAC
What is systemic lupus Erythematosus?
A chronic inflammatory systemic autoimmune disease, characterised by polyclonal B-cell activation and abnormal autoantibodies
What does lupus patients not have?
C1Q
What happens in wound healing if you deposit collagen and fibronectin?
Kidney will become unfunctional
What is IgA nephropathy?
An immune complex disease - it has genetic disorder, starts seeing natural antibodies as foreign
what are the 4 stages of wound healing?
haemostasis - clot formation, inflammation, proliferation, regeneration
