Ch. 18 7-9 (Dobson) Flashcards
This is the standard therapy for many liver diseases. It is indicated for severe acute or chronic liver disease where the limits of medical therapy have been reached. If successful, it results in prolonged survival and improves quality of life of recipients.
Liver transplantation
39,718 transplants were performed in 2019, a new record high for the seventh consecutive year. Each day, about ______ people receive organs.
80
Rejection is a process in which ________ and _______ produced against graft antigens react against and destroy tissue grafts, and the major antigenic differences between a donor and recipient that result in rejection of transplants are differences in ______ alleles.
T lymphocytes
Antibodies
HLA
Following transplantation, the recipient’s T cells recognize donor HLA antigen from the graft (allogeneic antigens) by two pathways. These are…
1) Graft antigens are presented directly to recipient T cells by graft APCs
OR
2) Graft antigens are picked up by host APCs, processed (like any other foreign antigen), and presented to host T cells
The frequency of T cells that can recognize the foreign antigens in a graft is much higher than the frequency of T cells specific for any microbe. For this reason, immune responses to allografts are stronger than responses to pathogens. These strong reactions can destroy grafts rapidly, so their control requires powerful…
Immunosuppressive agents
After liver transplant, recipient T cells are activated directly (acute rejection) or indirectly (chronic rejection), and proliferation of T cells and activation of effector cells by ________ occur.
CD4+ T cells
_________ and effector cells infiltrate and injure the graft developing rejection signs. Depending on the cytokine environment, activated CD4+ T cells can transform into graft-destructive or graft-tolerance phenotypes which balance the immune response.
CD8+ T cells
CD4+ T cells can also activate B cells, which can develop a further Ab-mediated response against antigens in the graft and generate _______.
AMR (Ab-mediated rejection)
Liver damage is predominantly a ________ reaction after bone marrow transplantation, but a ________ in liver transplantation.
GVH (Graft-versus-Host)
HVG (Host-versus-Graft)
(ACUTE/CHRONIC) rejection is mediated by T cells and Abs that are activated by alloantigens in the graft. It occurs within days or weeks after transplantation and is the principal cause of early graft failure. It may also appear suddenly much later after transplantation if immunosuppression is tapered or terminated.
Acute
In acute cellular rejection, ________ may directly destroy graft cells, or ________ secrete cytokines and induce inflammation, which damages the graft. They may also act against graft vessels, leading to vascular damage.
CD8+ CTLs
CD4+ T cells
In acute AMR (Ab-mediated rejection), Abs bind to vascular endothelium and activate complement via the classical pathway. The resultant inflammation and endothelial damage leads to ischemic changes in the liver parenchyma. This includes destruction of bile ducts resulting in the…
Vanishing bile duct syndrome
Chronic rejection is an indolent form of graft damage that occurs over months or years, leading to progressive loss of graft function. Chronic rejection manifests as interstitial _______ and gradual narrowing of graft blood vessels (graft arteriosclerosis).
Fibrosis
In chronic rejection, the culprits are believed to be T cells that react against graft alloantigens and secrete cytokines, which stimulate the proliferation and activities of ________ and _______ _______ _______ cells in the graft.
Fibroblasts
Vascular smooth muscle
Chronic rejection has resultant inflammation and endothelial damage that leads to ischemic changes in the liver parenchyma. This includes destruction of bile ducts resulting in the…
Vanishing bile duct syndrome
***Also occurs in acute rejection!
The _______ is a common site of complication stemming from transplantation for bone marrow, kidney, and other solid organs. Common themes are toxic or immunologically mediated _______ damage, opportunistic infections related to immune suppression, post transplant lymphoproliferative processes, or recurrent primary disease.
Liver
Liver
Some forms of hepatic disease may be exacerbated by…
Pregnancy
This is the most common cause of jaundice in pregnancy.
Viral hepatitis
While these women require careful clinical management, pregnancy does not specifically alter the course of viral hepatitis, with the exception of _______ infection. For unknown reasons, this runs a more severe course and has a fatality rate approaching 20% in pregnant patients.
HEV
The liver may also be secondarily involved by other infections during pregnancy. These include hepatitis caused by ______, a rare cause of ALF in pregnancy, and liver abscess caused by ________ ________, an organism that thrives in placental tissue, from where it may seed the liver.
HSV
Listeria monocytogenes
In a very small subgroup of pregnant women (0.1%), more serious hepatic complications develop. These disorders include…
- Preeclampsia and Eclampsia
- Acute Fatty Liver of pregnancy
- Intrahepatic Cholestasis of pregnancy
***In extreme cases, eclampsia and acute fatty liver of pregnancy may be fatal!
This occurs in 10% of pregnancies and is characterized by maternal HTN, proteinuria, peripheral edema, and coagulation abnormalities.
Preeclampsia and eclampsia
Subclinical hepatic disease may be the primary manifestation of preeclampsia, as part of a syndrome called the HELLP syndrome. What does this stand for?
H = Hemolysis E = Elevated; L = Liver enzymes L = Low; P = Platelets
In addition to the HELLP syndrome of preeclampsia, when ________ and ________ occur, the condition is called eclampsia and may be life-threatening.
Hyperreflexia
Convulsions