lecture 12 (renal) Flashcards
(55 cards)
1
Q
what are the types of kidney transplant?
A
- living donor (LD)
- donor after brain death (DBD)
- donor after cardiac death (DCD) (worst type as blood flow stopped)
- extended criteria donor (ECD)
2
Q
what is liver donor type?
A
- related
- unrelated/altruisic
- pre-emptive
3
Q
what terms come under extended criteria donor?
A
- hypertension (high blood pressure)
- terminal serum creatinine
- death by cerebrovascular accident
4
Q
what are the fixed risk factors for donors?
A
- donor age
- donor sex
- donor vascular disease or other co-morbidity
- cause of death
5
Q
how does gender effect?
A
- differences in sex hormones causes differences in kidneys
- most unsuccessful is from female to male
6
Q
how is kidney disease recognised?
A
- raised creatine in blood
- hameturia in urine
7
Q
what are the two categories of acute allograft rejection?
A
- cellular (ACR)
- antibody mediated (AMR)
8
Q
what is acute cellular rejection?
A
- interstitial infiltration with mononuclear cells
- disruption of tubular basement membrane by infiltrating cells
- tubulitis and intimal arteritis are associated
9
Q
what is antibody mediated rejection?
A
- driven from post immune response (recipient responding to donor- seen as foreign)
- capillary endothelial swelling
- peritubular capillaries
- arteriolar fibrinoid necrosis
- fibrin thrombi in glomerular capillaries
- frank optical necrosis
- donor specific antibody
10
Q
what shows antibody mediated rejection?
A
- cd4 staining on biopsy
11
Q
what is the treatment of failing graft?
A
- early biopsy to rule out glomerular diseases or immune
12
Q
if biopsy said glomerular disease what would be given?
A
- specific treatment
- further research taken place
13
Q
if biopsy said CNI toxicity and nephropathy what is given?
A
- reduced CNIs
- immunosuppression
14
Q
if the biopsy suggests late acute rejection, chronic T cell rejection, antibody mediated rejection what’s given?
A
- increased CNIs
- immunosuppression
15
Q
what does brain death induce?
A
- renal inflammatory response
- cytokines change basic physiology of kidney that enter after brain death
- make kidneys more immunogenic
16
Q
what occurs under normal conditions?
A
- lymphocytes, neutrophils, platelets etc. all floating passed endothelial
- other side has immune cells in tissues
17
Q
what occurs in ischemia (oxygen removed) ?
A
- damage approaching
- early apoptosis and necrosis
- cell membranes changed
- release of damage associated molecular patterns (DAMPs)
18
Q
what occurs in reperfusion?
A
- complement activation
- DAMPs activate resident and circulating cells
- bloodstream flooded back into kidney
- neutrophils on both sides of membrane
- further tissue damage
- production of chemotactic peptides
19
Q
what is the function of complement system in IRI?
A
- sense damage and pathogens
- can cause acute kidney failure if out of control
20
Q
what are cytokines?
A
- produced by immune cells
- interleukin 1 = activates inflammatory cells
- tissue necrosis factor alpha = cell activation, shock
- interleukin 6 = activates lymphocytes
- interferons = antiviral activity
21
Q
what do histamines do?
A
- from mast cells
- mediate allergic responses
22
Q
what does serotonin (5HT) do?
A
- increase vascular permeability
23
Q
what do prostaglandins, thrombaxnes and leukotriene do?
A
- metabolites or arachidonic acid
- important in blood clotting, lower gastric secretions, induce allergic responses
- production inhabited by aspirin and NSAIDs
24
Q
what do kinins do?
A
- eg. bradykinin
- vasodilation
- increases vascular permeability
25
what does the adaptive immune response do?
- creates different B and T cells for specific antibody mediated and cell mediated immunity
26
what does cell mediated immunity (CMI) involve?
- T lymphocytes
- antigen presenting cells
- MHC
- cellular immunity
27
what does antibody mediated immunity involve?
- B lymphocytes
- plasma cells
- antibodies
- humoral immunity
28
what are HLAs?
- human leukocyte antigens (major histocompatibility complex)
- displayed on surface of most our cells
29
where are MHC class II expressed?
- specialised cells like APCs (macrophages, lymphocytes)
- endothelial cells when nactivated
30
what occurs in renal allograft rejection?
- donor dendritic cells fro kidney activate allospecific T cells in spleen
- activated allospecific cells infiltrate donor kidney
- leads to large cellular immune response
31
what antibodies are present in group A?
- anti B
32
what antigens are in red blood cells in group A?
- A antigen
33
what antibodies are in the plasma in group B?
- anti A
34
what antigens are in the red blood cells of group B?
- B antigens
35
what antibodies are in the plasma of group AB?
- none
36
what antibodies are in the red blood cells in group AB?
- A and B antigens
37
what antibodies are in the plasma of group O?
- anti A
- anti B
38
what blood group is the best for transplant?
- group O
- has basic stock surviving after broken down
- both antibodies available in plasma
38
what antigens are in the red blood cells of group O?
- none
39
what is a 100% match needed for?
- bone marrow transplant as giving all immune cells so could lead to attack of recipient
40
why is a lower percentage match acceptable for kidney?
- transferring less cells
- less chance of rejection
41
how are immune cells that are donor specific gotten rid of?
- treat recipient with antibody called rituximab
42
what does rituximab do?
- binds to B cells and deplete them from the body
- reduces number of donor specific antibodies
- allows accommodation where anitobidy cells removed so can adapt immune system
43
what are the issues in transplants?
- maladaptive repair is issue with transplant
- fibrotic scarring reads to loss of nephrons to chronic failure of graft survival
- many transplants required if fibrosis occurs
- immune system plays into maladaptive repair with the rejection
44
what occurs in ENVP?
- dialysis system/organ perfusion system
- oxygenated blood going round (no immune cells or complement)
- given nutrients and oxygen to repair after ischemia
- reducing risk of activating immune system by giving change to recover
- reconditions the organs
45
how are potentially toxic drugs delivered?
- can use dose just on kidney in isolation from patient
- delivering through nanoparticles
46
why does xenotransplantation occur?
- source of potential cells and organs to transplant
- similar structures to humans
- can genetically modify the pigs
47
what is the issue with porcine hormones?
- renin doesnt cleave human angiotensin
47
what are the issues with using pigs?
- shorter life expectancy
- contains porcine hormones
- hyperacute rejection blood group (needed to be removed before in human)
- C activation different in pigs
48
what porcine genes were deleted as they trigger an immune response?
- GGTA1
- CMAH
- GHR
49
what human genes were added?
- DAF & CD46 (regulates complement cascade)
- TBM & EPCR (regulate blood coagulation)
- HO1 (reduces inflammation)
50
how long did the pig kidney survive for in the experiment?
- survived for 74 hours (until end of experiment)
51
what is another way of putting pig kidney in humans?
- trick immune system
- make chimeric immune system (deleting recipients bone marrow to replace with own plus donors)
52
what is acute rejection brought about by?
- innate blood factors
- inflammatory destruction of tissue
53
what is chronic rejection driven by?
- cells
- maladaptive repair mechanisms
