lecture 11 - autoimmune kidney diseases

Question 1

how much of cardiac output does the kidney receive?

Answer 1

25%

Question 2

what is the filtration fraction (plasma that filters into the nephron)?

Answer 2

20%

Question 3

what can’t get through the filtration barrier?

Answer 3

red blood cells and serum albumin

Question 4

what does it mean if you see red blood cells in the urine?

Answer 4

something wrong with the normal physiology of the filtration barrier

Question 5

what is chronic kidney disease?

Answer 5

structural or functional abnormalities of the kidney with or without decreased GFR

Question 6

what are the markers for kidney disease?

Answer 6

abnormalities in the composition of blood or urine

Question 7

how long do you need to have kidney disease before it can be chronic?

Answer 7

more than or equal to 3 months

Question 8

what can be used to tests for kidney disease?

Answer 8

a dipstick urinalysis

Question 9

how many stages of chronic kidney disease are there?

Answer 9

5

Question 10

what is the eGFR like in stage 5 of kidney disease?

Answer 10

less than 15

Question 11

what are some examples of autoimmune kidney diseases?

Answer 11

Membranoproliferative Glomerulus (MPGN), Atypical haemolytic uraemic syndrome (aHUS), SLE - lupus nephritis, IgA nephropathy and Goodpastures syndrome

Question 12

what is the most common autoimmune kidney disease?

Answer 12

IgA nephropathy

Question 13

what is the MPGN pathophysiology?

Answer 13

get proliferations which eat up the space in the glomerulus which means can’t get the function

Question 14

how can proliferations eat up the space in the glomerulus?

Answer 14

immune activators, chemokines and cytokines

Question 15

what would you see in MPGN?

Answer 15

dense deposits disease - electron dense glomerulus

Question 16

how do you diagnose MPGN?

Answer 16

by doing a kidney biopsy

Question 17

what would you see from the biopsy of MPGN?

Answer 17

hypercellularity, thickening of the glomerular basement membrane and proliferation

Question 18

what are classical pathways activated by?

Answer 18

they are activated by antibodies

Question 19

What is the lectin pathway involved in?

Answer 19

It is involved with dealing with apoptotic and damaged cells

Question 20

What does the activation of lectin and classical pathway lead to?

Answer 20

The C3 activation which passes the alternative pathway which acts on the right side of the complement pathway and acts on the amplification route

Question 21

What regulators are important in stoping the activation complement?

Answer 21

Factor H and DAF

Question 22

What is the membrane attack complex important for?

Answer 22

It is important in MPGN

Question 23

What type of anaphylatoxins can activate the complement system?

Answer 23

C5a and C3a

Question 24

What do C3a and C5a interact with?

Answer 24

Molecules that lead to vasodilation and vasoconstriction - modulating the blood flow into the kidney

Question 25

Where are C3 and C4 made?

Answer 25

They are made mostly in the liver - the kidney generates about 20% of the total levels of the complement in the blood

Question 26

What is one of the most abundant proteins?

Answer 26

C3 - has the potential to cause damage

Question 27

What works together to inactivate C3?

Answer 27

Factor H and factor I

Question 28

What does CR1 do?

Answer 28

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

Question 29

What protect against C3?

Answer 29

MCP and DAF they are ubiquitous

Question 30

What prevents MAC?

Answer 30

CD59

Question 31

What does the C4 binding protein do?

Answer 31

Stops the lectin and the classical pathway

Question 32

What are complement regulators involved in?

Answer 32

In the removal of immune complexes, the liver is a major source of clearance

Question 33

What organ do you want to get rid of immune complexes?

Answer 33

The kidney

Question 34

What allows the removal of immune complexes?

Answer 34

CR1 - complement receptor 1, it is expressed at high levels of erythrocytes and allows immune complexes to bind and be carried to the liver

Question 35

What is another type of cell that is important in complement and waste disposal?

Answer 35

Apoptotic cells - they self compact and maintain of all of the DNA and important mitochondrial antigens

Question 36

What are anaphyltoxins important for?

Answer 36

Bone regeneration

Question 37

What system is importantly for self tissue renwal?

Answer 37

The complement system

Question 38

What can C3a signalling help?

Answer 38

Can help dampen down the response

Question 39

What is C3 glomerulopathy (C3G)?

Answer 39

It is a new name for the spectrum of disorders with glomerular pathology associated with C3 desposition

Question 40

What is the dominant thing you see in C3 glomerulopathy?

Answer 40

The dysregulation of the alternative pathway in the kidney and deposition of C3 on the glomerular endothelial cells and the mesangial

Question 41

Where was Factor H deficiency discovered?

Answer 41

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

Question 42

What does C3 nephritic factor (C3NeF) do?

Answer 42

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

Question 43

What has recently been identified?

Answer 43

Anti-Fb - don’t know where they come from

Question 44

What do anti factor H do?

Answer 44

Interact with regulators and stops the alternative pathway from being over active

Question 45

What is the haemolytic uraemic syndrome (HUS) triad known as? - biomarkers for HUS

Answer 45

Acute renal failure, thrombocytopenia, microangiopathic hemolytic anemia

Question 46

What are the triad of HUS caused by?

Answer 46

Shiga toxin producing E.Coli e.g. food poisoning - it is an acute disease

Question 47

Who does HUS affect?

Answer 47

Infants and young children it has a relatively good prognosis

Question 48

What does shiga toxin bind to?

Answer 48

GABA3 in the glomerular endothelial cells and activate the cells.

Question 49

What happens when GABA3 cells in endothelial cells are activated?

Answer 49

They turn inflamed and allow thrombosis. The coagulation system interacts with the complement where clots form - takes out the kidney very quickly

Question 50

Where does secondary HUS come from?

Answer 50

Clinical or autoimmune disorders even cancer - which can lead to TMA in the kidney

Question 51

What is Atypical HUS?

Answer 51

It’s a genetic form and leads to TMA

Question 52

What makes the process go from non thrombotic to thrombotic?

Answer 52

P-Selectin - resulting in TMA

Question 53

What gene is frequently mutated in aHUS?

Answer 53

CFH - 40% familiar mutations, 25% sporadic

Question 54

What is taken away to get aHUS?

Answer 54

Factor H, you end up with lysis and deposits of MAC

Question 55

What is systemic lupus Erythematosus?

Answer 55

A chronic inflammatory systemic autoimmune disease, characterised by polyclonal B-cell activation and abnormal autoantibodies

Question 56

What does lupus patients not have?

Answer 56

C1Q

Question 57

What happens in wound healing if you deposit collagen and fibronectin?

Answer 57

Kidney will become unfunctional

Question 58

What is IgA nephropathy?

Answer 58

An immune complex disease - it has genetic disorder, starts seeing natural antibodies as foreign

Question 59

what are the 4 stages of wound healing?

Answer 59

haemostasis - clot formation, inflammation, proliferation, regeneration