Pathogens of the Liver

Escherichia Coli Gram -, rod-shaped bacteria of family Enterobacteriaceae Facultative anaerobe with peritrichous flagella Part of natural flora of human intestine (harmless strains) Most causative pathogen of bacterial infections Extraintestinal infection caused by relocation of E. coli from its natural flora to places on or in the macroorganism where proliferation is favorable E. Coli and the Liver- Pyogenic Liver Abscesses Bacteria enter the liver from the gastrointestinal tract via the portal vein, lymphatic drainage of the gut, or the biliary tract Infection of the liver can lead to pyogenic liver abscesses pus-filled areas While over 50% of liver abscesses are polymicrobic, E. coli is the most common bacterium involved The most common cause of abscesses is biliary obstruction, a blockage of any of the ducts that carry bile from liver to the gallbladder and small intestine When bile flow is obstructed, it is easier for the bacteria to colonize Abscess formation is caused by the host defense strategy once bacteria enter the liver Innate immune response: Phagocytes are attracted to the components of the bacterial cell wall creates a chemoattractant gradient that is followed by the phagocytes These macrophages and granulocytes release proinflammatory cytokines IL-1, IL6, and TNF-E hepatic inflammation Abscesses are solitary or multiple lesions filled with dense purulent material lined by fibrous capsules with edges surrounded by epithelioid macrophages, neutrophils, lymphocytes, and eosonophils Symptoms: fever, abdominal pain (usually localized in the upper right quadrant), anorexia, weight loss, confusion, hepatomegaly (liver enlargement), and jaundice from a build-up of bile waste products Treatment: Antibiotics, but with attention to the resistance patterns of E. coli because it is resistant to many of the antibiotics used to treat gram + bacterial infections (should use ones with anaerobic coverage like ampicillin, sulbactam or cefoxitin), and catheter drainage of the abscess

By: Jacqueline Tasarz

Pyogenic Abscess in Liver

Life Cycle of HBV Plasmodium Genus of Parasites Plasmodium falciparum, P. vivax, P. ovale, and P. malariae cause malaria P. falciparum=greatest rates of complication and mortality Most important human parasitic infection, with 500 million people affected each year worldwide Transmitted to humans by infected Anopheles mosquito definitive hosts Plasmodium and the Liver Life cycle of the parasite in the liver: When the mosquito bites, sporozoites or the motile infective and sporelike stage of the parasite are injected into the bloodstream Leave the bloodstream within 40 minutes and invade hepatocytes Sporozoites pass through Kupffer cells (specialized macrophages lining sinusoids of liver) before hepatocyte invasion Once in liver, asexual reproduction takes place sporozoite reproduces into schizont which then divides into multiple merozoites Merozoites release into circulation by rupture of the hepatocytes and now invade erythrocytes Some ruptured cells develop into gametocytes which when are ingested by the mosquito eventually mature to sporozoites Immune response: Where malaria is common, most people have some immunity Infection of variant without antibodies in system can cause serious disease, but most people can survive acute infection It is thought that parasite can inhibit innate and adaptive cytokine inflammatory response P. falciparum can reduce the T-cell proliferation response by stopping the Hepatitis B Virus secretion of IL-12 that would illicit NK activation and switching to IL-10 Causes hepatitis B infection- hepatitis means inflammation of production Life Cycle of Malaria the liver Failure of NK response also does not allow for adequate release of cytokines Partially double-stranded DNA virus of family Hepadnaviridae INF- and TNF Inner nucleocapsid composed of DNA, DNA polymerase and Effectors in protection against hepatic malaria: antibodies, cytokines, CTLs and T helper core antigen HBcAg and an outer envelope of the surface cells, and nitric oxide antigen HBsAg embedded in a membranous lipid derived from Symptoms: liver affected to many different degrees the host cell Group A patients: sudden clinical illness, acute renal failure, purple colored spots on skin Synthesizes viral DNA from an RNA template reverse Group B patients: fever, headache, vomiting, elevation of bilirubin transcriptase malarial hepatitis- hepatocellular jaundice Transmission: Exposure to infected blood or bodily fluids Treatment: anti-malarial medications- there is a large variety of them that are used based on resistance and Estimated that 350 million people are infected worldwide where the infection started Hepatitis B Virus and the Liver No vaccine for malaria because of the complicated life cycle prevention of vector bites and use of anti Non-cytopathic virus must be able to evade immune system to malarials persist Can cause acute hepatitis, if subject clears virus from bloodstream with immune response, or chronic infection Liver Immune System (cirrhosis and cancer) The liver is an important contributor to and a common victim of the Acute hepatitis: those with strong immune immunological responses of the body response=more likely to clear but more tissue Plays a major role in metabolism, protein synthesis, detoxification, and damage to due immune response production of biochemical to aid in digestion Occurs between first 1-4 months of infection Supports almost every organ in the body vital for survival Viral persistence depends on viral factors and on host immune Prone to many diseases because of its location and many functions response Meeting point for antigens and leukocytes circulating in the blood: HBV does not enter an exponential phase of replication until 4-5 Via the portal vein, receives almost all the blood from the weeks after infection (before, infects small amount of entire gastrointestinal tract hepatocytes) Prone to pathogens passed on from GI tract After HBV starts to become prominent in the body innate Via hepatic artery, receives blood from systemic circulation immunity In the pathogens explored here, the majority of pathogenesis caused in the Production of type 1 interferon / cytokines are liver is due to its own immune responses triggered by viral replication when cells recognize the presence of double-stranded RNA Abscesses of E. coli infection Damage to liver cells correlates Tissue damage due to defense mechanisms like T-cell activity with presence of DNA in HBV polymerase Granuloma formation in schistosomiasis NK cells activated when recognizing stress In both parasitic infection explored here, the pathogen matures by asexual induced molecules and change in amount of reproduction or sexual reproduction in the liver without this part of the infected cells with MHC I complex on surface cycle, the pathogen would not be able to continue its proliferation Liver Anatomy Adaptive immunity: responses directed towards 3 virus Invasion by the pathogen varies for these organisms, but all still find their antigens way to the liver The surface antigen (HBsAg), the core antigen (HBcAg) and the e antigen (HBeAg) Enjoy your exploration! May contribute to disease pathogenesis T helper cells produce cytokines necessary for Schistosoma Genus of Parasites development of cytotoxic T cells and B-cell Trematodes that cause schistomiasis- low mortality rate but still causes chronic infections of antibody production organs Chronically infected individuals have weaker T Affects more than 200 million people worldwide cell responses 4 species that cause chronic hepatitis and intestinal fibrosis S. mansoni, S. japonicum, S. Interaction of humoral and cellular responses mekongi, and S. intercalatum allows host to control infection Schistosoma and the Liver Symptoms: Life cycle of parasite: Hepatic pathology thought to be caused by the Cercariae (free-swimming larval form) penetrate through the skin and mature large recruitment of antigen-nonspecific T cells into immature worms and their responses After passing first through lungs and heart, the worms migrate to the portal Acute hepatitis: only 30-50% of infected veins of the liver individuals develop symptoms (only 5% go on to Here, sexual reproduction occurs, adult worms reside and lay eggs develop chronic infection) Egg production starts ~1 month after infection Fever, flu-like symptoms, joint Eggs pass from blood vessels into tissues and shed in feces/urine pain, Fatigue, loss of appetite, Hepatic schistomiasis when eggs are trapped by portal venules and disease is caused by host jaundice, nausea, pain in upper immune response granuloma formation causes most of pathology right abdomen Immune response: T helper cells Liver cirrhosis: severe scarring caused by st Th1 type: increased production of INF- , TNF- , and NO leads to cell 1 inflammation can lead to liver dysfunction mediated immunity symptoms of acute infection with confusion and 2nd Th2 type: activated B-call antibody production humoral possibility of coma, portal hypertension, possible Granuloma development after soluble egg molecules react with kidney failure, enlarged spleen or anemia toll-like receptors, dendritic cells and then Th2 type cells Liver cancer: abdominal pain and swelling, Symptoms: Hepatic schistomiasis enlarged liver, weight loss and fever Heavy infection can cause severe portal fibrosis and enlarged fibrotic portal Treatment: Interferons or nucleotide/nucleoside analogues tracts suppress viral reproduction in chronic patients, liver Portal hypertension transplantation, preventable through vaccination- contains Life Cycle of Schistosoma Treatment: dose of Praziquantel anthelmintic HbsAg for which an antibody is established in the bloodstream