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
Hepatic involvement in preeclampsia may show modest to severe elevation of serum aminotransferases and mild elevation of serum bilirubin. Hepatic dysfunction sufficient to cause a _________ signifies advanced and potentially lethal disease. This is why the liver can appear with a black pigment, and it is important to obtain a thorough history to not misdiagnose with ________ ________.
Coagulopathy
Dubin-Johnson Syndrome
While this condition most commonly runs a mild course, women with _______ _______ _______ of pregnancy can progress within days to hepatic failure and death.
Acute Fatty Liver
Women with Acute Fatty Liver of pregnancy will present in the latter half of pregnancy, usually the 3rd trimester. Symptoms are directly attributable to incipient hepatic failure, including…
- Bleeding
- N/V
- Jaundice
- Coma
20-40% of pregnant women with Acute Fatty Liver have presenting symptoms that are coexistent with…
Preeclampsia
What is the primary treatment for acute fatty liver of pregnancy?
Termination of pregnancy (meaning give birth)
This disorder is the onset of pruritus in the second or third trimester, followed in some cases (10-25%) by darkening of the urine, and occasionally light stools and jaundice. Resolves within 2-3 weeks of delivery.
Intrahepatic Cholestasis of Pregnancy
With intrahepatic cholestasis of pregancy, total bilirubin is usually ________ and ALP can be positive or negative. Biopsy will also show canalicular cholestasis. Modest risk of fetal loss.
<5 mg/dL
T/F. Intrahepatic Cholestasis of pregnancy can recur in subsequent pregnancies.
True
(Pearl #1) Liver infarcts are rare due to the dual blood supply of 1/3 Hepatic A. and 2/3 Portal V. The only exception to this is what?
Hepatic A. thrombosis in liver transplant as major bile ducts have only arterial supply.
(Pearl #2) Portal V. occlusion can lead to…
Esophageal varices
(Pearl #3) What is the most common cause of intrahepatic blood flow obstruction?
Cirrhosis
(Pearl #4) What is the most common cause of small portal vein branch obstruction?
Schistosomiasis
(Pearl #5) This is a hepatic disorder often seen in HIV patients.
Obliterative portal venopathy
(Pearl #6) This disorder is caused by sinusoidal dilation and forms “blood lakes” in the liver.
Peliosis hepatis
(Pearl #7) This disorder is caused by Hepatic V. obstruction/thrombosis.
Budd-Chiari Syndrome
(Pearl #8) This disease is caused by Jamaican bush tea, and can occur 3 weeks after stem cell transplant. Also can cause cancer.
Veno-Occlusive disease
(Pearl #9) This can occur due to right-sided heart failure or a terminal event.
Passive congestion
(Pearl #10) For this type of rejection disease, acute can occur in 10-50 days while chronic types are 100+ days.
GVHD
(Pearl #11) For transplant rejection, it can either be acute which is _______, or chronic which is _______.
Cellular
Vascular
(Pearl #12) This is the end-point of passive hepatic congestion due to chronic congestive heart failure.
Cardiac Sclerosis (or cardiac cirrhosis)
(Pearl #13) This is what the liver can appear like due to hypoperfusion and retrograde congestion.
Nutmeg liver
What are the benign hepatic neoplasms discussed?
- Nodular hyperplasias (2)
- Hemangiomas
- Adenomas (3)
What are the malignant hepatic neoplasms discussed?
- Hepatoblastoma
- Hepatocellular carcinoma
- Cholangiocarcinoma
- Angiosarcoma
- Lymphoma
- Metastatic
What are the 2 types of nodular hyperplasias?
Focal Nodular Hyperplasia (FNH)
Nodular Regenerative Hyperplasia (NRH)
This type of benign hyperplasia is an incidental finding in an otherwise normal liver in young to middle age adults. It usually has a single well-demarcated lesion with a central scar, this is highly characteristic. “Map-like pattern”.
Focal Nodular Hyperplasia (FNH)
This type of benign hyperplasia consists of multiple nodules that looks like cirrhosis, but has no fibrous septa.
Nodular Regenerative Hyperplasia (NRH)
Nodular Regenerative Hyperplasia can develop _______ _______, and has associations with HIV and rheumatologic disease.
Portal HTN
This is the most common benign neoplasm of the liver (20%) and occurs more in females than males.
Cavernous hemangioma of liver
This is usually asymptomatic and an incidental discovery, but can present as life threatening intraabdominal emergency from hemorrhage due to subcapsular location. Often mistaken for malignancy.
Cavernous hemangioma of liver
This is a benign neoplasm that typically occurs in young women and is strongly associated with use of oral contraceptives and anabolic steroids.
Hepatocellular Adenoma
Hepatocellular Adenomas have three molecular subtypes that have are each associated with distinct clinicopathologic features and varying risk of transformation into HCC. What are the subtypes?
1) HNF1-a inactivated adenomas
2) Inflammatory adenomas
3) B-Catenin activated adenomas
This type of hepatocellular adenoma accounts for 40-50% of cases, has a strong female predilection, and is associated with minimal risk of transformation to HCC. It is fatty with no atypia.
HNF1-a inactivated adenomas